Water-Soluble Ligands, Metal Complexes, and Catalysts:

Synergism of Homogeneous and Heterogeneous Catalysis

By Wolfgang A. Herrmann" and Christian W. Kohlpaintner"

Dedicated to Professor Ernst Otto Fischer on ihe occasion ofhis 75th birthday

Rapid developments in the field of catalysis are leading to an increased demand for tailor-made
catalysts. Water-soluble complex catalysts, which are being intensively investigated at the
present time, combine the advantages of homogeneous and heterogeneous catalysis: simple
and complete separation of the product from the catalyst, high activity, and high selectivity.
From the large number of available water-soluble ligands, the appropriate catalysts can be
developed for many reactions. The industrial applications in the fields of hydrogenation and
hydroformylation have already indicated the wide scope of this type of catalyst. In addition,
the annual production of 300 000 tons of butyraldehyde through application of water-soluble
rhodium complexes at Hoechst AG in Oberhausen, Germany, has demonstrated the industrial
importance of the concept of complex-catalyzed reactions in aqueous two-phase systems. The
efficient operation of catalytic processes increasingly requires the loss-free recycling of the
noble metal catalyst, and this can be simply and economically realized in two-phase systems.
Special applications in biochemical problems open up developments in the field of water-
soluble transition metal complexes that far transcend the familiar kinds of homogeneous
catalysis. In the near future, the investigation and application of metal complex catalysts that
are compatible with the physiological, cheap, and environmentally friendly solvent, water, is
likely to become a high priority in catalysis research.

1. Introduction I* *I What are [he advantages of water-soluble catalysts? The

The chemistry of water-soluble ligands and their metal
complexes is presently undergoing very rapid growth. The
special advantages of water-soluble catalysts are being in-
creasingly recognized, as is borne out alone by the number of
publications and patents. Following the introduction to in-
dustry of the valuable Ruhrchemie/RhGne- Poulenc process
in 1984 there was spate of publications, which is still contin-
uing (Fig. 1). Meanwhile, about a dozen research groups
applied for patents, and the number of these now even sur-
passes the number of publications in the open literature.
basic problem of homogeneously catalyzed processes is the
separation of the product phase from the (molecular) cata-
lyst, which is soluble in it. The process stages necessary to
achieve this usually include thermal operations such as distil-
lation, decomposition, transformation, and rectification,
which normally lead to thermal stresses on the catalyst.
These can cause decomposition reactions and progressive
deactivation during the lifetime of the catalyst. Furthermore,
thermal separation processes seldom give quantitative recov-
ery of the catalyst, which causes loss of productivity through
loss of metal.
Product separation is simpler for two-phase systems incor-
porating water-soluble catalysts as shown in Figure 2. The

Fig. 2. General principle of two-phase catalysis in water. The metal complex

0 catalyst (K), which is solubilized by hydrophilic ligands, converts the starting
1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 material (in this case, propene and A- B. such as CO/H,) to the products, which
can be separated from the catalyst (medium) by phase separation. Thorough
Fig. 1. Number (n) of publications annually on water-soluble complex ligands mixing ,f the phases is necessary during the catalyt,c process.
and catalysts (excluding patent applications).

[*] Prof. Dr. W. A. Herrmann

Anorganisch-chemisches Institut der Technischen Universitit Miinchen hydrophilic catalyst, which is insoluble in the organic
Lichtinbergstrasse 4, D-85747 Garching (FRG) product phase, is a n (organometallic) coordination complex,
+
Telefax' Int. code (89)3209-3473
and as such is molecularly well defined like conventional
Dr. C W Kohlpaintner
Hoechst AG. Zentralforschune [Hauotlaboratorium
- \ '~ 1) homogeneous catalysts. It brings about the catalytic reac-
Postfach 800320, D-65926Frankfurt am Main (FRG) tions (e.g., C-C coupling) in the aqueous phase or at the
Telefax: Int. code + (69)33 1320
phase boundary, and is removed from the desired product at
[**I Often used abbreviations: tpp = triphenylphosphane; tppts = trisodium
salt of 3,3',3"-phosphanetriylbenzenesulfonic acid; tppms = sodium salt the end Of the reaction by a simp1ephase separation. Ther-
of 3-diphenylphosphinobenzenesulfonicacid. ma1 separation processes, which can have a detrimental ef-

1524 Q VCH VerlagsgeseNschuf!fl

mbH, 0-6945I Weinheim. 1993 $ IO.OO+ ,2510
oS7~-OX33~93jIl11-1524 Angew. Chem. In!. Ed. Engl. 1993,32, 1524-1544
fect on the active life of the catalyst, are thereby avoided.
Because of the high polarity of the water-soluble catalyst and
its consequent insolubility in the organic phase, the loss rate
is often below the limit of detection.
Rates achievable with two-phase systems are strongly de-
pendent on the polarity of the reacting substrate. For ex-
ample, the rhodium-catalyzed hydroformylation of propene
using the water-soluble complex [HRh(CO)(tppts),] takes
place with the apparent activation energy of a homogeneous
reaction, whereas with I-hexene the rate-determining step
appears to be mass transfer.[] Therefore, although overall
reaction rates are lower than in homogeneous reactions, the
simplicity of the process for separating the product from the
catalyst compensates for this disadvantage.
Another technique, which has been practiced for a long
time without any spectacular success, is to immobilize solid
complex catalysts on solid (stationary) supports. Here, the
continuous loss of the metal (bleeding, leaching) and
low reaction rates are serious disadvantages. However, the
immobilization of a catalyst in a mobile phase, that is, an
aqueous solution immiscible with the product phase, repre-
sents an almost ideal combination of homogeneous and het-
erogeneous reaction processes.
This article reviews current developments in both research
and technology, and indicates the areas where this new class
of catalysts has gained acceptance within only a few years to
become state of the art. The review covers the classifica-
tion of water-soluble ligands and their metal complexes to
catalytic uses in the laboratory and industry, and special
applications in biochemistry.
2. Concept of Two-Phase Catalysis
Under the simplified assumption that all starting materials
E are in solution, three variations of the two-phase process
of homogeneous catalysis can be considered (Fig. 3): In the
simplest case the solubilities of the components E and of the
catalyst K are so different that a perfect phase separation
results (Figs. 2 and 3a). A workup step for the product P
follows, depending on its properties and purity, and as a rule
is a distillation. The technical desirable ideal would be a
catalyst K which formed its own phase in which the compo-
nents E and the products P a r e not in the least soluble (Fig. 2
and 3a). If the product P is partly dissolved in the catalyst
phase, an extraction is necessary according to Figure 3 b, and
is performed with the phase of E (for example, petroleum)
which is completely insoluble in K (for example, water). It is
also possible that a two-phase system forms from an initially
uniform phase during the reaction, because the product P is
insoluble in the original medium of the catalyst (Fig. 3c). A
phase separation in the skimmer enables continuous return
of the catalyst to the reactor. Only when the products P are
partly soluble in the catalytic medium K is a solvent extrac-
tion step (related to a distillative workup) necessary for the
whole contents of the reactor (Fig. 3c).
The concept of two-phase catalysis was first realized in-
dustrially in the SHELL Higher Olefins Process (SHOP)
designed by W. Keim et al.[2a-c1I n this procedure ethylene is
polymerized at 80-120C and 70-140 bar in a polar phase
of 1,4-butanediol that also contains the organonickel cata-
lyst to afford oligomers (mainly linear C,_ ,,-n-olefins).

WoCfgang A . Herrmann was born in 1948 in Kelheim/Donau (Bavaria). After studying chemistry
(Diplom at the Technische Universitut Miinchen) under E.O. Fischer (1971), he obtained his
doctorate on a theme from early organometallic stereochemistry at the Universitat Regensburg
with Henri Brunner (1973). From 1975-1976 he pursued his research interests in the USA at
Penn State University with P.S. Skell, and in 1978 completed his habilitation with a thesis on
Organometallic Syntheses with Diazoalkanes. He was appointed Professor at the Universities
of Regensburg (1979) and full professor in Frankfurt ( 1982). In 1985 he accepted the chair at
the Technische Universitat Miinchen as successor to E.O. Fischer. His area ofresearch is synthet-
ic and catalytic chemistry, mainly in the field of organometallic chemistry. He is author of350
original papers and holder of 30 patents, and has received many honours including the Karl
Winnacker Fellowship { 1979- 1983), the Leibniz Award of the Deutsche Forschungsgemein-
schaft (1986), the GermanlFrench Alexander von Humboldt Award (1988) the Otto Bayer
~

Prize (1990). and the Max-Planck-Forschungspreis (1991). He i s member ofthe Akademie der
Wissenschaften und Literatur zu M a i m (1990) and Honorary Doctor ofthe University of Lyon,
France (1990).

Christian W Kohlpaintner was born in 1963 in SchloJberg, near Rosenheim (Bavaria), and
began his study of chemistry at the Technische Universitat Miinchen in 1984. In October 1989,
he joined the research group of Prof. K A . Herrmann. He completed his Diplom in March 1990
on new water-soluble phosphane ligands and catalysts, and received the Ph.D. students Award
,from Hoechst AG. He completed his Ph.D. thesis in August 1992 following work on the
RuhrchemielRhdne- Poulenc process, the two-phase hydroformylation process which is used on
industrial scale. He then joined Hoechst AG and has worked in the Central Research Department
at Frankfurt since the beginning of this year. He has coauthored 6 papers and holds 7 patents.

A n R r w Cliiw. h i . Ed. EngI. 1993, 32, 1524-1544 1525

 S addition of phthalic acid this reaction yields octylphthalates.
starting
materials S
S tions of these solvents with homogeneous catalysts are
S Phosphanes can be converted into water-soluble deriva-
(C)
Fig 3 Simplified flow didgrdm for two-phdse catalysis d) Product(s) P dre
completely insoluble in the medium thdt contdlns thecdtdlyst C, b) product(s)
P dre soluble i n the medium coiitdining C, c) formation of the second phdse
occurs during cdtdlytic process, cf text
The catalyst is formed from [Ni(3,5-cod),] and
(C,H,),PCH,COOH. The products separate as a second,
transparent liquid phase above the 1,4-butanediol and can
therefore be removed without difficulty. After this simple
catalyst/product separation, catalyst traces are washed out
of the olefin phase in the phase separator. The distillation
fractions of the subsequent purification are either marketed
directly or fed into the next two SHOP catalytic steps of
isomerization and metathesis (cf. Fig. 4). This combination
of homogeneous and heterogeneous catalytic steps now oc-
cupies a key position in olefin chemistry.
C catalysis. Apart from the compound tppts (l),which is used
C + solvent
(reactors] I phaseseperator 1] -
Fig. 4. Simplified flow diagram for the first catalytic stage of the SHELL
higher olefins process [SHOP). The subsequent steps of isomerizdtion and
metathesis are not given in detail.
A process for the oligomerization of butadiene developed
along the lines of this technology, which has been known
since 1968, likewise employs 1,4-butanediol as polar phase.
Thus, Keim et al.[2d* describe the dimerization of 1,3-buta-
diene to 1,3,7-octatriene with Pd/phosphane catalysts in ace-
tonitrile with isooctane as extractant for the product. On
1526
Surprisingly, no further information on the use of highly
polar solvents as the second phase is available in the litera-
ture, although in many cases miscibility gaps exist with satu-
rated hydrocarbons, for example, methanol, acetonitrile, ni-
tromethane, dimethylsulfoxide (DMSO), dimethylformam-
ide (DMF), ethyleneglycol, and sulfolan. Nevertheless, reac-
known, and therefore the influence of the second phase on
the chemical and kinetic characteristics of the catalytic cycle
must be taken into account. This treatise, however, aims to
concentrate on water as catalytic medium.
3. Classes of Water-Soluble Phosphanes
tives by the introduction of polar groups, including sul-
fonate, carboxylate, ammonium, phosphonium, and hy-
droxyl A classification based on these func-
tional groups seems expedient and is shown in Scheme 1.
Other hydrophilic substituents, for example, phosphate
groups, have so far been of little importance.
-S 0 , H -SOYA
-Ri @ -PRJ
-on
Scheme 1. Functional groups in water-soluble phosphanes ( A + = cation)
3.1. Sulfonated Phosphanes
3.1.1. Water-Soluble Phosphanes by Direct Sulfonation
Owing to their diverse coordination chemistry, sulfonated
phosphanes at present constitute the most widely used class
of ligands in water-soluble metal complexes, especially in
in a rhodium catalyst for the production of butyraldehyde on
an industrial scale, the monosulfonated derivative tppms (2)
must be mentioned. Both these compounds (sodium salts)
can be obtained by the sulfonation of triphenylphosphane
with oleum and subsequent neutralization with NaOH. The
technique of sulfonating water-insoluble ligand precursors
can be applied to di- and polydentate, and also chiral phos-
phanes, for example, 3-9 (Scheme 2).[-*] The sulfonate
group mostly occupies the position meta to the phosphorus
atom. Tris(p-fluorophenylfphosphanecan be sulfonated in
the meta position.31 The introduction of a sulfonate group
by reaction with o h m is not limited to arylphosphanes. It
can also be carried out with the tris(w-phenylalky1)-
phosphanes P[(CH,),(C,H,)J, ( n = 1, 2, 3, and 6).[141Here,
the sulfonate groups, as expected, occupy the para and, to a
lesser extent, the ortho positions.
The sulfoxylic derivative of 1,2-bis[di(m-sodium-sulfo-
natophenyl)phosphino]ethane (dppets) is now also available
Angeu. Clwn. Int. Ed. Engl. 1993. 32, 1524-1544

1 2
n'PAr, PAr, PAr,
''4
PAr,
4 5
n
n ed by the example in Equations (2a) and (2b). The water-
7 8
Scheme 2. Water-soluble phosphanes obtained by direct sulfonation with
oleum (Ar = rn-C,H,SO,Na; for 9. Ar = p-C,H,SO,Na).
as a ligand for hydroformylation in the two-phase process
since direct sulfonation of 1,2-bis(diphenylphosphino)-
ethane(dppe) by means of oleum (20% SO,) was successful.
However, the Rh/dppets catalyst is not very active in hydro-
formyIati~n.[~']
Because of the oxidizing effect of oleum, an appreciable
fraction of the phosphane is converted into the phosphane
oxide during the process of sulfonation, which complicates
the purification of water-soluble phosphanes substantially
(Section 4). Complete oxidation affords sulfonated phos-
phane oxides, which can be reduced by trichlorosilane after
conversion to sulfonic esters." The water-soluble ligands
are available after hydrolysis of the ester. The use of this
laborious method is meaningful only for phosphanes that
are very sensitive to oxidation. It is not likely to increase in
importance, however, since we discovered an efficient direct
sulfonation method in which the formation of phosphane
oxide is strongly inhibited."']
3.1.2. Introduction of the Sulfonate Group
during Synthesis of the Aryl Phosphane
Sulfonate groups can be introduced during the course of
phosphane synthesis. For example, as shown in Equa-
tion ( I ), the sodium salt of p-diphenylphosphinobenzenesul-
phonic acid (10) is formed from potassium diphenylphos-
phide and sodium p-chlorobenzenesulfonate.['
Ph,PK + C I e-
S 0 , N a -t -
P h , P e S 0 3 N a
10
Water-soluble phosphanes of the type R, -.P-
(p-C,H,SO,K), (R = C,H,, 2-pyridyl, 3-pyridyl; n = 1-3)
can be obtained by the reaction of potassium p-fluoro-
benzenesulfonate with PH, o r primary or secondary phos-
phanes in the "superbasic" medium DMSO/KOH.[' The
unpleasant properties of PH, have to be mastered here, but
otherwise this is a very powerful, general synthetic method.
Surprisingly hydrolysis-resistant sulfonated phenylphos-
phites have recently been prepared."'] The ammonium salts,
in particular, are more water-stable than triphenylphos-
Angels. Clwin. lnt. Ed. Ennl. 1993, 32, 1524- 1544
phite: whereas P(OC,H,), is decomposed within 3 h, the
hydrolysis of the derivative P[p-OC,H,SO,(NH(i-octyl)~)],
is only complete after 24 h.
3
PAr,
3.1.3. Phosphanes with Peripheral Hydrophilic Functional
Groups
6
Functionalized phosphanes that carry sulfonic acid
groups in one o r more side chains are also known. The class
of substances developed by Whitesides et al.r201is represent-
9 soluble phosphane 15 is obtained by acylation of bis(2-
diphenylphosphinoethy1)amine (11) with the carboxylic
chloride (12) of phthalic anhydride followed by reaction with
sodium taurinate (14). This synthesis principle can be ap-
plied to many functionalized acid chlorides. The opening of
the anhydride 13 by 14 is unspecific, so two constitutional
isomers 15a and 1 5 b are always obtained. The maximum
attainable solubility in water is 0.3 molL-'. Further work
on this class of compounds was carried out by Sinou et a1.[211
The tertiary phosphane (C,H,),PCH,CH,SO,Na was pre-
pared from sodium diphenylphosphide and the sodium salt
of 2-bromoethylsulfonic acid.r221
PPh,
PPh,
I1 12 13
PPh,
\ PPh,
13 14 158.b S0,Na
Another route to water-soluble phosphane ligands
through ring opening of sultones was established by Oehme
et al.[23.241Fell et al. extended this concept to tris-
(pyridyl)phosphanes, which can be prepared in water-solu-
ble form by sulfoalkylation with 1 , 2 - a l k a n e ~ u l t o n e s .This
[~~~
procedure results in zwitterionic sulfobetaines with n = 0, 3,
5, 7, and 11 [Eq. (3)j.
+ KCI ( 1)
3.2. Phosphanes with Quaternized Aminoalkyl and
Aminoaryl Groups
Water-soluble phosphanes can also result from the quater-
nization of the nitrogen atom of aminoalkyl and aminoaryl
1527
phosphanes. However, before the nitrogen atom can be alkyl-
ated, the (more reactive) phosphorus center has to be pro-
tected, either by oxidation o r by coordination to a metal.
Subsequent reduction or decomplexation, respectively,
yields the desired phosphane ligands. The most important
example of this class of substances is amphos (16), first
synthesized by Baird et al.~26-2s1 Toth et al.,[291Peiffer et
al.,[301and Nagel et al.[311were able to extend this synthesis
- -
principle to other phosphanes (Scheme 3).
Ph,P NMez
-
2) CH,I
3) HSiCI,
ph,p
16
NMe
17
Ph,P -Y-NHR;Y- Ph,P -Y-NR;X-
18A 18B
Scheme 3. Aminoalkyl- and aminoarylphosphanes (Y = -CH,CH,-,
-CH(CH,)CH,-, -CH,CH(CH3)CH,- ; R = CH,) made water-soluble by
quaternmation of the N atom.
3.3. Carboxylated Phosphanes
Phosphanes with carboxylic groups were some of the ear-
liest investigated water-soluble phosphanes. The first ex-
ample 19 was prepared by Mann et a1.[321in 1952 through
cyanoethylation of diphenylphosphane with subsequent ni-
trile saponification. The development of the carboxy-
alkylphosphanes (phosphinocarboxylic acids) was carried
out predominantly by the research groups of Rauhut, Issleib,
and P o d l a h o ~ r i . ~
The ~ ~most
- ~ ~important
~ example is the
phosphane analog of ethylenediaminetetraacetic acid
(H4edta).r391It is obtained as an air-stable monohydrate of
the tetrasodium salt (20). A new short review of the catalytic
uses of the carboxyalkylphosphanes was published by Je-
gorov and P o d l a h o ~ a . [ ~ ~ l
19 20
The history of the phosphinobenzoic acids 21 goes back as
far as 1945. Gilman and Brown synthesized meta- andpara-
diphenylphosphinobenzoic acid. Not till 1977 did Lucken-
bach and Lorenzr4 succeed in preparing the ortho isomer.
Further work was done by Schumann et al.,[431and Lindner
P h 2 P g o o H
0
21 22
1528
reviewed the progress.[441A newer report refers to a phos-
phorylated derivative 22 of maIeic
Phosphanorbornadienes with a carboxylic anhydride
+
function can be obtained by [4 21 cycloaddition of 3,4-
dimethylphosphol to maleic anhydride and subsequent re-
arrangement [Eq. (4)].[461 Alkaline hydrolysis yields the
water-soluble carboxylates.
eo
MeoMeI
H
+
0
2)
1)NaOH
A Me&co
Me
C02Na
(4)
3.4. Phosphanes with Hydroxyalkyl and
Polyether Substituents
By varying the length of the polyether chain of substituted
phosphanes, the solubility can be deliberately adjusted.
Bisphosphanes of the type 23 (n = 5 ) are insoluble in water.
For n 2 16 (e.g., n = 42), however, they are extremely sol-
~ b l e . ~ Other
] examples related to 23 are the class of com-
pounds 24 (n = 12. 16, 110) and 25 (n = 18).[48.491The num-
ber n gives the average degree of polycondensation.
Supplementary work was performed by Okano et al.,1501who
were the first to prepare phosphanes 26 substituted by crown
ethers!51. 521
23 24
n
25 26
Investigations into water-soluble hydroxyalkyl-substitut-
ed phosphanes were carried out by Chatt et al. in 3973.1s31
The phosphanes are significantly soluble in water only if
they carry several hydroxyalkyl groups.[541 The water-
soluble, commercially available trisubstituted phosphane
P(CH,OH), is being tested in the form of metal complexes
for catalytic properties in the addition of PH,to formalde-
h ~ d e . Homoleptic
~~] nickel, platinum, and palladium com-
plexes of this phosphane were synthesized, and the
elucidation of the structure of the palladium complex
[Pd{P(CH,OH),), . CH,OH] was carried out by single crys-
tal X-ray structural a n a l y ~ i s . [ ~ ~ l
Finally ethylene glycol derivatives react with sugar diace-
tonides to form monoallyl ethers that can be brominated at
the double bond. Successive reaction with phenyl- and
diphenylphosphanes yields hydrophilic phosphanes exhibit-
ing a sugar function in the side
Angrit. Chern. Inr. Ed. Engl. 1993. 32. 1524 - 1544
3.5. Phosphinoalkylphosphonium Salts
A new class of water-soluble phosphanes, named
"phophos", was opened up in 1991 by Baird et al.1581Mono-
quaternization of bisphosphanes yields phosphinoalkyl-
phosphonium salts [Ph,P(CH,),PMe,]X, where n = 2, 3, 6,
o r 10, and X = NO;, C1-, o r PF,. The synthesis proceeds
according to Equations ( 5 a) and ( 5 b). For increasing chain
X ax + LiPPh, - X
length n, the more reactive bromine (or iodine) derivative
must be used instead of the chloro compound. The halides
are converted into the more stable nitrates and hexafluoro-
phosphates by ion exchange or salt metathesis. The rhodi-
um-catalyzed hydrogenation of 1 -hexene gave the following
activity series: [6]-phophos > [10]-phophos> 131-pho-
phos > [2]-phophos, where the numbers correspond to the
chain length n. The reasons for this particular series remain
unclear. The X-ray structural analytical characterization
of the rhodium complex I (nbd)RhC1([2]-phophos)]PF,
(nbd = norbornadiene) and the attachment of the free lig-
ands to cation exchangers[591underline the rapidly growing
interest in this class of compound.
3.6. Other Ligands
As the present article concentrates on metal complexes
and catalysts whose solubility in water depends on hy-
drophilic phosphane ligands, the following topics are not
considered: phase-transfer reagents, saltlike metal catalysts
such as Pd(OAc), and Pd(edta), metal complexes of sul-
fonated 2,2'-bi~yridine[~'.611 and a l i ~ a r i n , [metal
~ ~ ~ com-
~~]
plexes of sulfonated phenanthroline derivatives,L641water-
soluble porphyrins, and cyclopentadienyl ligands.'651 A
summary is given in Ref. 171.
4. Purification of tppts and its Metal Complexes
Besides their catalytic uses, the characterization of the
water-soluble complexes is of interest. Firstly, their bond
strengths, complex geometry, and coordination properties,
for example, can be compared with those of analogous wa-
ter-insoluble complexes.r831Secondly, well-defined water-
soluble model complexes are essential for the understanding
of the individual steps in the catalytic cycle of two-phase
systems. and in kinetic studies. F o r instance, the Hieber
base reaction could also be successfully applied to
[Co,(CO),(tppts),], the water-soluble pendant of
[Co,(CO),(PPh,),], which is converted into the carbonyl
metalate Na[Co(CO),(tppts)] in aqueous NaOH at
p H > 20.["]
A i t ~ r ~ iCi '.l w i i i . In[. Ed. E n ~ l 1993.
. 32, 1524- 1544
The first synthesis of tppts was carried out some
years after Chatt's first reports on the monosulfonation of
triphenylphosphane (tpp).[681Although it was possible to
obtain the triply sulfonated arsenic compound 28,
triphenylphosphane only gave the monosulfonated tppms
(2). In 1975, E. G. Kuntz of Rh8ne-Poulenc Ind., Lyon, was
able to prepare the sodium salt 1 of tppts according to Equa-
tion (6) by prolonging the reaction time, obtaining it in a
purity adequate for industrial use on repeated precipitation
from methanoliwater mixtures.
PPh, + Ilx 15a)
2 28
27
1
The excellent solubility of tppts in water (about
1100gL-')[691 and its related insolubility in almost all or-
ganic solvents prepared the way for its use in two-phase
catalytic processes on an industrial scale. However, for a
long time there was no access to analytically pure tppts and
its metal complexes, mainly due to problems of separation.
The phosphane oxides produced during sulfonation of tpp
could not be completely removed for chemical reasons
(-SO,H vs. -P=O), and the separation of the various sul-
fonated products also presented problems. Only recently has
it been possible to avoid the oxidation of the phosphane
during sulfonation with oleum." 61 Optimization of tempera-
ture, reaction time, and oleum concentration can also help to
reduce the extent of the oxidation of easily oxidizable phos-
phanes."]
The use of "soap chromatography" for the purification of
water-soluble mono- and bisphosphanes is only useful for
analysis, but not for preparative work.[", 'I1 Alone the poor
availability of an exactly defined ligand complicates the
preparation of analytically pure metal complexes. Diffi-
culties are caused by slight oxidation of the phosphane by
atmospheric oxygen in the aqueous phase. Analytically pure
metal complexes of tppts could therefore not be obtained
with conventional methods of p~rification."~ - 741 The
breakthrough came from a change to the use of gel perme-
ation chromatography, adapted to the solution of this prob-
lem, with cyclodextrane as the stationary phases.[" -"I The
experimental apparatus is shown in Figure 5.['*] This was
used for the first convenient preparation of analytically pure
metal complexes of tppts on laboratory scale. The metal
complexes were obtained by direct synthesis, by ligand ex-
change, and through addition methods in which the water-
soluble phosphane combines with a coordinatively unsatu-
rated complex intermediate without displacing another
ligand. With this purification method over 40 metal com-
plexes of the ligand tppts were prepared analytically pure
and characterized (Fig. 6)."'] Spectroscopic data for tppts
and its oxide have been published.[sz1
1529
inert gas c7 L
Fig. 5. Experimental equipment for gel permeation chromatography for the
purification of inetal complexes of tppts. The eluent water is pumped from the
storage vessel A through the flexible poly(viny1idene fluoride) (Viton.
sition, is similarly performed.[*] Bartik et al. report the
molecular structure of [Co,(CO),(tppt~),].~~]
The steric demand of the tppts ligand is about 20 YOgreater
than that of triphenylphosphane (tpp). The cone angle 0
according to Tolmanr8lis170for tppts (tpp: 8 = 145 and
is the same as that of tricyclohexylphosphane (PCy,, Table
1). This explains the tendency of tppts to form complexes in
which the transition metal has a lower coordination num-
ber.[75.761 Thus, the compound [HRh(tppts),J, unlike
[HRh(tpp),], is The linear relationship be-
tween 31PNMR shifts and the cone angle in [L,PdCl,] com-
plexes has been stressed. For steric reasons, sulfonated
O),

bisphosphane chelate ligands, for example biphenyl deriva-

lsoversinic) tube B, the peristaltic pump D, and the three-way valve C into
the column E, which is filled with the gel. A UVjVIS detector or refractometer tives, can more efficiently differentiate regio- and
F fitted with a recorder G is connected to the exit of the Chromatography stereospecificity if the conformative mobility of the ligand is
column. As many water-soluble metal complexes and ligands absorb UV
strongly. the fractions are sometimes difficult to separate with a UV detector.
limited. This possibility for control of a reaction has so far
In these cases, a refractometer should he used, which. after compensation for hardly been recognized.
water, detects very low amounts of substance. The chromatography is operated
in upside-down mode as this gives the best separation results (no tailing). The
stationary phases used are standard gels from LKB Pharmacia (Sephadex G15, Table 1. Cone angles 8 according to Tolman [8l] of some phosphanes
G25, and G50)and Merck (Fractogel TSK HW-40F). A detailed description of
the equipment and its function has been published [76, 781. Phosphane 9 I1 Phosphane 0 I]
ligand ligand

PH, 87 PPh, 145

An example of the efficiency of gel permeation chro- PF3 104 P(m-Cc.H,F), 145
matography as a diagnostic method is the revision of the P(OMe), 107 PCY 3 170
formula of the complex [Ni(tppt~),],[~~] which should be PMe, 118 P(m-C,H,SO,Na), 170 [a]
P(OiPr), 130 P(o-Tol), 194
formulated as [Ni(tppt~),].[~~]The rhodium complexes, iso- P(CF,), 137 P(2,4,6-Me3C,H,), 212
lated as pure substances, were crucial in the elucidation of
[a] From Darensbourg et al. [80].
degradation steps occurring in the two-phase hydroformyla-
tion of propene catalyzed by Rh-tppts catalysts.[791More
recent investigations show that the purification method is
not only successful for tppts, but is applicable to a wide 5. Hydrogenation with Water-Soluble Catalysts
range of water-soluble ligands and their metal complexes.[21
5.1. Reduction of Achiral Unsaturated Substrates

CI n The reduction of CC- and OC-unsaturated compounds

m Fel C
1111111 was the first application of water-soluble catalyst^.[^^-*^^
Dror has stated that cosolvents are necessary for acceptable
hydrogenation A large number of different cata-
lysts and substrates have been studied (Table 2). The TOFs

Table 2. Hydrogenation of unsaturated compounds with water-soluble cata-

U
lysts [a].
Fig. 6. Central atoms of tppts-metal complexes characterized to date
Catalyst ncai [MI Substrate TOF [b] Ref

i.3x 10-3 cyclohexene 3.1

The X-ray characterization of a tppts-metal complex was 1 . o x 10-5 [cl 25-74
recently carried out by Darensbourg et a1.r801UV irradiation LOX 10-5 kl 164
5 . 0 ~lo- [cl 92-198
of [W(CO),] in methanol, according to Equation (7),caused 2x10-3 hexenes
the labile methanol adduct of the W(CO), intermediate to 3 x lo-- hexenes
8.Ox 10-6 36 [dl 1.6-200
react with solid tppts to give the desired complex 36 P 275
[W(CO),(tppts)]. After complexation of the sodium ions by 2.5 x 10-3 Styrene 14-71
kryptofix-[2.2.1], 29 crystallizes out of the solvent mix- 2.5 x 10-3 1-hexene 20 - 84
1.0~10-3 36 1270
ture THF/methoxyethanol/acetonitrile. Crystallization and 5 . 0 ~lo- 39 [dl <lo640
structural characterization of tpp, sulfonated in the para po- 1 . 5 10-5
~ RCH=CHCHO 100-230
4.8 x 10-5 CH,CH,CHO 320-360
1.0 x 10-4 RCH=CHCHO 13-194
5.0~ lo- RCH=CHCHO 25-1260
6.5 x 10 1-hexene 12-296

[a] p(H,) =1 bar. [b] TOF (rurnover .frequency) defined as mol(pro-

0
S0,Na
duct)mol(catalyst)- h - Note that TON (furnover number) is defined differ-

ently: mol(product) mol(catalyst)- [c] RC(0)COOH and RCH=CHCOOH.
[d] See Section 5.2 for formulas. [el Sodium formate as hydrogen source.
29 (with Ioyptofix [2.2.1]) [f] p(HJ = 20-50 bar.

1530 Angex. G e m . Inl. Ed. Engi. 1993,32, 1524- 1544

(turnover Jrequencies-definition in Table 2) are in general
low, but can be increased by the use of cosolvents such as
methanol or ethanol. The rates are limited mainly by the low
solubility of the unsaturated substrate in the aqueous solu-
tion of the catalyst. However, the question where the reac-
tion takes place-phase boundary, organic phase, or
aqueous phase-has hardly been investigated and is still un-
clear. From the comparison of the catalysis results with
[RuHCl(tpp),] (homogeneous) and [RuHCl(tppms),] (two
phases). Wilkinson concludes that the hydrogenation of un-
saturated substrates in the two-phase system proceeds con-
siderably more slowly. The low rate of hydrogenation is due
to the necessary diffusion of the hydrogen to the alkene/wa-
ter interface. In this way, the isomerization, which is the
substantially slower reaction, can compete with the hydro-
genation. However, the hydrolytic cleavage of water-soluble
ligands, for example by cleavage of the dioxolan ring in
PGE- 17-DIOP (30), does not support the low reaction
as the reduction in reactivity applies to all water-
soluble catalysts.
New work by Rh6ne-Poulenc Ind. with ruthenium and
rhodium tppts complexes shows that hydrogenation in
simple two-phase systems (aqueous/organic) is possible
without cosolvents.Iss.
in the aqueous phase; the phase-transfer problem associated
with catalysts not soluble in water and aqueous formate
solutions does not arise.f921Aromatic aldehydes can be al-
most quantitatively hydrogenated, with the exception of aro-
matic aldehydes bearing in the ortho position substituents
that can coordinate (e.g., 2-hydroxy-I -naphthaldehyde or
2-hydroxybenzaldehyde). On the whole, hydride donors
such as formates in a homogeneous phase constitute an in-
teresting situation that deserves further investigation, even
though other authors1s8.891 are of the opinion that, due to
their basic properties, the carbonates formed from the for-
mates deactivate the catalysts more strongly than hydrogen,
which is not associated with by-products.
5.2. Reduction of Prochiral Substrates
The enantioselective hydrogenation of prochiral sub-
strates has been thoroughly investigated. Here, too, the reac-
tion rates are lower than with homogeneous systems. By
using chiral water-soluble Rh-catalysts, prochiral a-acetami-
doacrylic esters (36; R' = R4 = H; R2 = NHCOCH,;
R3 = H, CH,) and a-acetamidocinnamic esters (34; R' =
H, CH,, Na; R2 = CH,, C,H,) are reduced in up to 92O/' r e
(Table 3) and prochiral imines of the type 37 in 94%
ee.[97,981 However, the optical yields obtainable with the
majority of substrates 34-36 are still unsatisfactory.

Table 3. Enantioselective hydrogenation of prochiral substrates with water-so-

luble catalysts [a].
H
Catalyst ncn, [M] Substrate ee [%I TOF [b] Ref.

Rh/30 1.0 x 10-3 34 11-69 ( R ) 102- 1608

Rh/30 5.0~10-3 35 10-41 (S) 30 -4320
Rhj41 !.OX 10-3 34 34-87 ( R ) 333-500
32 33 17
Rh/41 1.o~ 10-3 3s 16-74 (S) 4-500
42 6 . 0 lo-'
~ 34 87-96 ( S ) 870-960
Rh/30 2 . 0 10-3
~ 34 10-60 ( S I R ) 186- 1608
Rh/30 2.0~10-3 35 28-68 (SIR) 366-4320
Rh/6 1.0 x 10-2 34 72-88 ( R )
One valuable application is the selective reduction of a$- Rh/7 1.ox 10-2 34 12-42 (S)
Rh/4 1.0 x 10-2 34,3s, 37,40 8-65 ( R )
unsaturated aldehydes to unsaturated alcohols according to Rh/6 1.0x 10-2 34 81 -87 ( R )
Equation (8).[sgl Rhj7 1.0 x 10-2 34,35,40 20-44 (5')
Rh/4 2.0~ 10-3 36 15-31 ( R )
Rhj6 2.0 10-3 36 20-61 ( R )
Rh/7 2.0~10-3 36 5-21 (S)
R'
- H,,cat.
RZ L
R'

O H
(81
Rh/17
Rh/32
Rh/33
2.5 x lo-'
2.5 x
2.5 x
34
34
34
40-95 ( R )
8-67 (S)
58-94 ( R )
4-50
4- 100
4-50
Rh/l7 2.5 x lo-' 34 40-79 ( R ) 8- 100
RhI7 5.0 x 10-5 36 10-43 (R/S) 833-2166
A catalyst formed from RuCl,/tppts reduces 3-methyl-2- Rh/4 [cl 2.5 10-4 37 2-96 ( R ) 5-16
Rh/6 2.0 x 10-3 38 6-87 [d] 0.6-1.1
butenal to 3-methyl-2-buten-I -01 ("prenol") with 96 YOselec- Rh/7 2 . 0 1~0 - 3 38 7-40 [d] 0.7-1.1
tivity (R' = R2 = CH,) and 84-99% conversion. Other
CC-unsaturated aldehydes are also efficiently reduced (selec- [a] p(H,) = 1-30 bar. Catalysts prepared from Rh' and Rh"'. [b] For defini-
tion of turnover frequency see Table 2. [c] Mono- and disulfonated derivatives.
tivity 2 97 %). Analogous iridium complexes are less active. [d] de[ %] = diastereomeric excess.
The selectivity of ruthenium is the reverse of that observed
with the Rh-tppts system, as in this case the C-C double
bond in the a-position is reduced. Under 20-40 bar ( 2 - Selectivities are influenced by water content and H, par-
4 MPa) pressure of hydrogen, the selectivity is >95% at tial pressure. If the reduction is carried out in solvent mix-
30-80 "C (conversions are mostly around goo/,). tures (e.g., EtOH/H,O), an increase in water content reduces
Sodium and ammonium formates are also suitable as hy- stereo~eIectivity.[~~~991 Increase in pressure can in extreme
dride donors for the hydrogenation of a$-unsaturated and cases even reverse the
aromatic aldehydes with water-soluble Ru c o m p l e ~ e s .911
[~~~ An explanation for the poor optical yields in aqueous
With [RuCl,(tppms),], both the catalyst and the formate are media is provided by the reaction mechanism. According to

Angtw. Chvm. hi.Ed. Engl. 1993, 32, 1524-1544 1531

 with hydrophilic Rh complexes in solvent mixtures has
/-
=Lo,li
kR2
~4 CO,R~
shown that, with increasing S,, the enantioselectivity
Ig( % S/ % R) decreases linearly. The close relationship be-
tween stereoselectivity and the composition of the alcohol/
34 35 36
water mixture used strongly suggests that the two-phase
hydrogenation takes place in the polar phase and not at the

9 phase boundary.

X- +cH3
N

37 (X = H,OMe. Cl)
60
H

\
0
OR2
Sinou et al. and de Vries et al. have reported another
parameter that influences enanti~selectivity.~. 981 In the re-
duction of prochiral imines 37 with Rh complexes of mono-
or disulfonated (2S,4S)-bdpp [bdpp = 2,4-bis(diphenyl-
phosphino)pentane], the optical yield is greater than 92 YO
for monosulfonated ligdnds and only 2% for disulfonated
ligands! Also, the reaction rate for the monosulfonated
38
phosphane is many times greater. The catalytic activity of
water-soluble phosphanes is apparently tunable by the

c&*,-x
4
u
NHCOCH,
degree of sulfonation. No explanation is yet available, and
the influence of electronic and conformational effects must
still be elucidated. Interestingly, the hydrolysis of imines to
amines and ketones plays a subordinate role, so the imine
39 (X = CI,OC(O)CHJ
40 reduction can proceed chemoselectively.
In the reduction of dehydropeptides 38 with water-soluble
chiral Rh complexes of the chelating phosphanes 4,6, and 7,
Scheme 4, the chiral catalyst forms diastereomeric adducts
the diastereomeric excess (YOde) is strongly dependent on the
with the prochiral substrate, and these then undergo irre-
absolute configuration of the substrate.[031With the tetra-
versible oxidative H, addition. According to Halpern, this
sulfonated bisphosphane [(S,S)-bdpp, 41 a de value of only
step decides the enantioselection.lOl The two possible ad-
10 % can be achieved for a dehydropeptide of an R-configu-
ducts react with hydrogen at rates differing by a factor of
rated amino acid (Ac-A-Phe-(R)-Ala-OCH,), but for the
1000. The existence of the catalyst-substrate adduct in
same peptide with an S-amino acid (Ac-A-Phe-(S)-Ala-
aqueous solution has been proved.[] The energy content of
the dihydrido species I and XI can be influenced by solvation. OCH,), the de value is as high as 72%. However, a higher
diastereomeric excess for S-dehydropeptides is not a general
If the energy difference is very small, only a small enan-
feature, as, for the tetrasulfonated (S,S)-cbd (cbd = cyclo-
tiomeric excess is achievable. Amrani and Sinou have there-
butanediop, 7). exactly the opposite result was obtained
fore postulated a small AE for the solvent water and a con-
(higher de from R-dehydropeptide).
comitant low optical yield.[491
The choice of the reducing agent for the hydrogenation
does not influence the stereoselectivity.[1041Formates of am-
monium, potassium, and sodium give very similar results to
molecular hydrogen. The cation has a small effect, although
it is reported that the highest reaction rates and selectivities
are observed with ammonium formate. This small salt effect
is in contrast with the results of Basset et al., who have
I I

i
t
HZ
I HZ
established a strong dependence of the reduction rate on the
salt c~ncentration.[~. lo] The addition of salts produces

higher activities than in homogeneous systems for the reduc-

I II
Scheme4. Oxidative H, addition (according to Halpern [loll) to dia-
stereomeric catalyst -substrate adducts. Ail complex species are positively
charged.
In a later study, a linear relationship between lg(%S/
% R) and the solvophobicity parameter S, is demonstrat-
ed.[991It indicates the change in the free energy of formation
AG, for the transfer of a hydrocarbon from the gas phase
into a given solvent.[021 Upper and lower limits are S, = 1
(water) and S, = 0 (hexadecane). A series of experiments
tion of propionaldehyde with water-soluble Ru complexes.
The fact that water is not only a solvent, but also has a
chemical effect on reductions in two-phase systems is shown
by the Rh-catalyzed hydrogenation of a-acetamidocinnamic
ester in ethyl acetate/D,O. Depending on the phosphane
ligands used, 75 YOdeuterium is incorporated in the reduced
product.[ I The deuteration takes place selectively accord-
ing to Equation (9) in the a position to the acetamido and
ester function. Multiple deuteration does not occur.
Due to their negatively charged substituents, sulfonated
phosphanes can compete with the unsaturated substrate at
R = H, Ph
= I [ Rh(cod)Clj,l/ligand; EE = CH,CO,C,H,
Cat.

1532 Angew. Chcm. Int. Ed. Engl. 1993, 32, 1524- 1544
the electrophilic metal center. Various research groups have
therefore synthesized cationic water-soluble Rh complexes,
and have investigated their behavior in enantioselective hy-
drogenation. Nagel et al. reported that the cationic complex
42["] shows slightly improved enantioselectivity and is a
factor of over 100 more reactive than a similar catalyst based
on a ligand of type 41.["] The nucleophilic carboxylate and
sulfonate groups of 41 are regarded as being responsible for
the reduction in a ~ t i v i t y . ' ~However,
'] the lack of similarity
in reaction conditions casts doubt on the validity of these
experiments.
PPh,
\
41 42
The substitution pattern of the P-bonded phenyl residue
has little influence on the stereoselectivity. Ligands of the
type 17.32, and 33, which have their hydrophilic groupsparci
to the phosphorus atom, were investigated by Toth et
al.r2". In the hydrogenation of dehydrocinnamic acid
derivatives, the Rh-catalysts based on the cationic bisphos-
phanes show almost the same selectivity as those with sul-
fonated ligdnds. Chiral phosphanes sulfonated in the pczra
position would unequivocally clarify the influence of the
substitution pattern on the stereoselectivity, but these com-
pounds are not yet available. The para isomer of tppts,"*'
which has very recently been prepared and characterized by
X-ray structural analysis, could serve as the starting point
for the synthesis of such bisphosphanes.
The principal advantages of water-soluble catalysts- -ease
of separation of the product from the catalyst and long term
stability have been demonstrated in all investigations. The
aqueous solutions of used catalysts show the same activity
and selectivity on reuse after they have been recovered from
the product phase. The industrial outlook for continuous
hydrogenation processes based on water-soluble catalysts
therefore seems to be full of promise.
6. C-C Coupling with Water-Soluble Catalysts
The reported C C coupling reactions include diene hy-
drodimerization, alkylation of CH-acidic compounds, addi-
tion reactions to the C C double bonds (hydroamination and
hydroformylation), and carbonylation of allylic systems.
6.1. Hydrodimerization
The Kuraray Company in Japan is said to operate a pilot
plant for the hydrodimerization of 1,3-butadiene according
to Scheme 5. in which step (a) is a two-phase system with a
Pd/tppms catalyst. The primary product is then isomerized
-
' 0
cl3
H
OO
-H -0 ' 0
c, (d) GI
Scheme 5. The new Kuraray process for the production of 1.')-nonancdiol by
hydrodimerization of 1.3-hutadiene.
to the C, aldehyde with a copper chromite heterogeneous
catalyst, and the resulting product hydroformylated in a
third process step (c), once again with a two-phase catalyst.
The resulting w,w'-dialdehyde is extracted. probably with
cyclohexane, and hydrogenated over molybdenum-doped
Raney nickel to yield 1.9-nonanediol (step d).'''''
6.2. Alkylation of CH-Acidic Compounds
The telomerization of dienes has been extensively investi-
gated by Rhane-Poulenc Functionalized
1,6-octadienes can be obtained from butadiene or isoprene
and acidic compounds according to Equation (10). A cata-
lyst obtained from PdZf/tppts (1/4) is very effective, while
rhodium and platinum instead of palladium give poor yields.
With optimized process operation. the reaction has a re-
gioselectivity of 95/5 (Y functionality in position 1 or posi-
tion 3 ) .
R = H, Me
Y = MeO, EtO, PhO, HO, MeCOO, Me,N
The telomerization of dienes with N-quaternized
aminophosphanes as the catalyst ligands was recently rein-
vestigated.l3'I When [Pd(OAc),] and 18 (fourfold excess) are
used together, a water-soluble catalyst is obtained that is
more active but less selective than its tppts analog
(TOF = 5-26). The reaction is chemoselective; the yield of
side products (e.g., 1,3,7-octatriene) is insignificant. Recy-
cling and reuse of the catalyst are possible with only little loss
of activity.
The isoprenylation of CH-acidic compounds is a similar
type of reaction." 1 0 - ' 1 2 1 In particular, 1,3-dicarbonyl com-
pounds can be alkylated with Rh-tppts catalysts in two-
phase systems. An example is the isoprenylation of barbi-
turic acid according to Equation (1 1). The two potential
isomers are not always produced. When Pd catalysts are
used, the terminal double bond is shifted to an inner loca-
tion, as in the isomerization of Isofeprazon to Feprazon. The
1533
 be obtained according to Equation (13) (C-C coupling with
0 elimination of the end groups -B(OCH,CH,O) and -Br).
The polymerization process is strongly favored by the solu-
bilities of the monomer, the growing polymer, and the cata-
lyst. Polymerization reactions could therefore open up a new
area of applications for water-soluble metal complexes that
65 % 35 % has so far been virtually ignored. Incidently, water should
also be an excellent solvent for radical processes, because the
O H bond enthalpy is extremely high (120 kcalmol-).[201
activated methylene compound adds remarkably regioselec-
tively, and the attack takes place exclusively at the monosub-
stituted double bond. A twofold alkylation of the 1,3-dicar-
bony1 compound, only possible under drastic conditions, is
not observed if conditions are normal (25 C, 48 h). The ease HOPC \
of recovery and reuse of the catalyst-without loss of activ-
ity-have been convincingly demonstrated.
C C couplings can also be carried out with tppms-contain-
ing Pd catalysts.[31 The compound 43 catalyzes, in yields CO,H

[Pd(tppms),].3 H,O 43
6.3. Addition of Hydrogen Cyanide
which can be greater than 99 YO,the arylation (biphenyl syn-
thesis), acetylation, phosphorylation, and vinylation (Heck The nickel-catalyzed addition of hydrogen cyanide to CC
reaction) of halogenated arenes and heteroarenes: In solu- multiple bonds is reported in a Adipic acid and
tion, a rapid phosphane exchange is observed which pre- methylglutaronitrile are obtained from 3-pentenenitrile ac-
sumably takes place through the intermediacy of a PdL, cording to Equation (14). The linear product is formed pref-
species. However, there is no direct proof of the existence of erentially (> 10/1). In 1990, it was recognized that the correct
a complex containing tetracoordinated palladium. Com- formula of the catalyst [Ni(tppts),] is in fact
pound 43 can be used for diverse functionalities, including [Ni(tppts)J.[]
those in unprotected nucleotides and amino acids. The good
results of the Heck reaction and the cross-coupling of termi-
H
nal alkynes with vinyl and aryl iodides are confirmed in an
independent study. Although the active catalytic species
-2 CN HCN
cat. AcN
H&cN (14) +

was not characterized in this case, it must nevertheless be 43.

Water-soluble Pd compounds catalyze allyl substitutions
according to Equation (12) in yields up to 95%. With ac-
etates and carbonates of cinnamyl alcohol (R = C,H,), the
E enantiomers are selectively formed.
R = H, C,H,, CH,OH: R = CO,C,H,, COCH,
NU = CH(COCH,),, SO,C,H,-p-CH, N(CH,CH,),O (rnorpholino)
The ring opening of 3,4-epoxy-l-butene by ethyl aceto-
acetate to give 2-acetyl-6-hydroxy-4-hexenoic acid proceeds
in greater than 80% yield ( E / Z = 85/15).[51 Ally1 halides
can be directly carbonylated by using water-soluble Pd cata-
lysts. 1 6 , I Under normal C O pressure and in the presence
of sodium hydroxide or alkoxide, the B,y-unsaturated acids
o r esters are obtained. Benzyl chloride can also be carbony-
lated to phenylacetic acid in this way.[*] The yields vary
between 4 and 93 YO,depending on the substrate. With allyl
6.4. Hydroformylation
The 0 x 0 synthesis (hydroformylation), which was dis-
covered by Otto Roelen (1897-1993)[1221 in 1938 at the
Ruhrchemie AG, is one of the most important metal-cata-
lyzed alkene reaction^."^^] World capacity for 0 x 0 products
is about 5.6 million tons per annum (excluding 2-ethyl-
hexanol, the most important product of a subsequent reac-
tion). The importance of water-soluble catalysts in this type
of process may be deduced from the increase in capacity
(Fig. 7)[23-1301 and improvement in the performance
parameters of the catalytic process (Table 4). After the dis-
covery of tppts at Rh6ne-Poulenc Ind. in Lyon in 1975, its
implementation on an industrial scale was developed by the
Ruhrchemie AG (now Hoechst AG) in Oberhausen.
6
106x
t w
5
4

[ t a-1 2
halides, only E isomers are formed. 1
The preparation of poly(para-phenylene) derivatives us- 0 1955 1960 1965 1970 1975 1960 19BS 1990
ing Pd/tppms is currently in progress.[ ] Starting from
1,I -biphenyl-4,4-bis(ethylenedioxyborane)and 4,4-dibro- Fig. 7 . Growth of worldwide 0 x 0 capacities W (in million tons per annum).
The sudden increase i n 1968 coincides with the introduction of the Union
mo-1 ,lf-biphenyl-2,2-dicarbonic acid, the water-soluble Carbide Process (Rh catalysis). U p to that time, hydroformylation was per-
polymer 44 with an average molecular weight of 50 000 can formed with cobalt catalysts only.

1534 Angeu.. Chmz. Int. Ed. Engl. 1993, 32, 1524- 1544
Table 4. Technical parameters of the 0 x 0 synthesis A flow diagram of the process is shown in Figure 8. The
Catalyst Catalyst
separation of the catalyst/product mixture is simply carried
parametei-s [HCo(CO),] [HCo(CO),PRJ [HRh(CO)(PR,),] out in a phase separator, from which the aqueous catalytic
R = n-C,H, R = C,H, R = ni-C,H,SO,Na solution flows back to the reactor, while the organic product
P bar1 200-350 50-100 15-20 10-100
continues to the stripping column. An optimized heat recov-
T"C1 110-180 160-200 85-115 50-130 ery system ensures a favorable overall energy balance for this
n / i w ratio [a] 80/20 88,'12 921X 95.5 [b] modern process.
selectivity medium low high very high
hydrogenation medium high low low
activity

[a] Depending on the position of the formyl group at the terminal or internal C of the 6.4.2. New Catalysts
double bond. a linear ( n ) o r branched (isu) aldehyde arises. The desired products are
linear. [b] Variants with nliso = 99/l are now also known. The development of even better water-soluble phosphanes
for two-phase hydroformylation has become a necessity in
recent years. The international downward pressure on the
6.4.1. RuhrchemielRhGne- Poulenc Process prices of 0 x 0 products, mainly caused by the cheap products
from the "developing countries", prescribes the continuous
The first patents were applied for in September 1982 for improvement of the existing process. For the Ruhrchemie/
the synthesis of aldehydes,['311 the recovery of the rhodi- RhGne-Poulenc process, this implies the synthesis of new,
um," 321 and the production of sufficiently pure sulfonated more active catalysts. To name only two examples, the sul-
phosphanes." 331 In particular, the elegant extraction-reex- fonated phosphanes bisbis (45)and norbos (9) enabled Rh
traction process"33. 1341for the tonnage production of tppts catalysts to be produced with superior properties to those of
paved the way for the industrial operation of two-phase hy- the standard Rh-tppts system (see Fig. 9).['- 143.1441 J umps
droformylation. The patent applications that were published
afterwards describe further improvements: process opti-
mization,['3'- l3'1 recovery of the rhodium catalyst,['38-1401
reactivation of catalyst,[2081synthesis of water-soluble tri-
arylphosphanes,['6. 133, 1341and synthesis of new ligdnds and Ar
9
metal coordination compounds for catalytic two-phase sys- 81\19
tems." 3. 1 4 ' These patent applications cannot be treat-
ed individually in this review, but the fact that there are so
many of them bears out the extent of the research activity in
this fieId.Izo4] 97/3
The Ruhrchemie/Rhbne-PouIenc process went into oper-
ation in 1984. Two plants now produce 300000 tons per an-
num of butyraldehyde. Depending on the quality of the
propene starting material, 99 YOconversion and a crude alde-
A
1
hyde product with a n n/iso ratio (for explanation, see foot-
note to Table 4) of approximately 95/5 is attained. Both the
hydrogenation of the alkene and the formation of condensa-
tion products by aldolization are insignificant. The loss of 1

rhodium in the organic phase, despite the high price of this

nliso = 94/6
metal, is a "quantite negligeable".[145. 1461 Catalysts that
generate selectivities of n/iso 2 99/1 have recently been dis-
covered.
tPPtS bisbis norbos
(1984) (1990) (1992)

P/Rh= 1 0.08 0.16

exhaust gas Fig. 9. Results of catalysis with water-soluble rhodium-phosphane com-
plexes (activity A is shown on a linear scale). Activity A = n(alde-
hyde)n(Rh)-' h - ' , Ar = -C,H,S0,3Na. P/Rh ratios are normalized.

stripping column in activity from 16 to 90 (bisbis) or to 118 (norbos) indicate

the currently attainable activity levels. The n/iso ratios in the
propene hydroformylation reaction fall below 95/5 in the
case of norbos only. The large phosphane excess normally
required in the Rh/tppts system and many other standard
I catalysts (e.g. Rh/tpp) can be reduced by more than an order
- of magnitude without causing problems of long-term stabil-
Fig. 8. Flow diagram of the Ruhrchemie/Rh6ne-Poulenc process for the pro-
duction of n-butyraldehyde. in operation at the Ruhrchemie works of Hoechst ity. Thus, the rhodium-norbos system is the most active
AG (Oberhausen) [146. 1511. M = stirring device. water-soluble hydroformylation catalyst known so far.

Angiw. C / i i , m . Inr. E d EngI. 1993. 32. 1524- 1544 1535

 Losses in selectivity are compensated for by the similar com-
mercial values of 17- and iso-butyraldehyde. Moreover. the
ready accessibility of the norbos systems is attractive, be-
cause they allow a systematic variation of substituents.1Iz1 L J

Phosphane chelating ligands are attracting more attention 48 49

for future industrial use, because the special phosphites of formation of the intermediate 49 (not isolable), a s shown in
Union Carbide show extremely high activities and selectivi- Scheme 7.
'
ties in /ionrogoirous/j, c . n / t r / j . x d h y d r ~ f o r m y l a t i o n . ~ ' ~ ~
However. these ligands are readily hydrolyzed, and therefore
cannot be considered for aqueous systems. which was recent-
ly clearly shown in the case of sulfonated phosphites.I"l The
previously mentioned sulfonated tris(o-phenylalky1)phos-
phanes P[(CH,),,p-C,H,SO,Na], (n = 1-3 and 6)[l4] are
more active in rhodium-catalyzed hydroformylation of 1-
octene at low P/Rh ratios (211) than an analogous Rh-tppts
system. In this case, the highest conversion was observed for
17 = 6. Interestingly, higher P/Rh ratios lead to a decrease in
catalytic
Other than in the two-phase catalysis employing Rh/
d p p e t ~ , [ ~there
' ~ is a successful example of homogeneous
catalysis in which the nonsulfonated parent ligand 1.2-his-
(dipheny1phosphino)ethane (dppe) is used. Substrates like
1.3-butadiene undergo hydroformylation to the CS-alde-
9 Ar, P
co

hyde with 21 T O F of 250.[20'1The analogous Rh/tpp catalyst

has hardly detectable activities under otherwise identical
reaction conditions. An application in aqueous medium by
sulfonation of the tpp ligand right be interesting.

6.4.3. Catalyst Deactivation Mechanisms

Although the standard Rh'hppts system has extremely
good long-term stability, a slight loss of activity occurs after
several years' use. The catalyst deactivation mechanism has
recently been clarified in detail (Scheme 6).178.79. 1'11
hydroformy lation cycle
Scheme 7. Deactivation mechanism of Rh'-tppts catalyst in the Ruhrchemie;
Rh6ne- Poulenc process (framed products have been isolated and charactel-.
]zed: see text and ref. [78.151]).
The cleavage of the P-C bond in the phosphane. which
deactivates the catalyst, is caused by the oxidative addition
of tppts to Rh' with the formation of 49a, a Rh"' species with
a five-coordinate central atom. The cleavage of the P-C

D bond, combined with an aryl rearrangement, was previously

46 47
Scheme 6.
Compound 46, which is strictly only a "precatalyst", dis-
sociates to the active 16e species 47. This is supported by a
high-pressure NMR study by Horvith et al.,[1521which
shows that 46 itself does not take up a further CO molecule
from syngas, even at a pressure of 200 bar (20 MPa). The
active species 47 initiates the hydroformylation cycle. which
is not considered further here. The hydroxo complex 48,
which has been isolated and characterized. is formed in water
under hydroformylation conditions (HJCO) and can be re-
versibly converted into 46.The equilibrium lies almost com-
pletely on the side of 46; accordingly, during hydroformyla-
tion there is no danger of the transformation of 46 into the
catalytically inactive hydroxo complex 48. According to
Equation ( 1 5 ) . carbon monoxide displaces a phosphane lig-
and from 48. The deactivation mechanism starts with the
recognized by Garrou et al. as the origin of the deactivation
of phosphane-modified catalysts." 531 The coordination of a
further molecule of tppts causes the reductive elimination of
bis(me~ct-sulfophenyl)phosphinous acid as the tautomer
48 Ar,POH. Benzenesulfonic acid (ArH) and mrtn-formylben-
zenesulfonic acid (Ar-nz-CHO) are formed from the Rh' in-
termediate compound 49 b under the given reaction condi-
tions (and presence of syngas). Both these compounds have
been detected in "exhausted" catalyst solutions.[781
Species 49c, which is formed by H,addition and product
elimination, combines with propene to form the propyl com-
plex 49d. The later course of the reaction is determined by
this intermediate stage. The insertion of CO would produce
the acyl complex and finally the hydroformylation product
butyraldehyde. The oxidative addition of another tppts lig-
and (- 49e). however, would mean that three products
could arise from this cycle: 1) the phosphane. Ar,PC,H,
(pdspp) by phosphido/propyl coupling; 2) benzenesulfonic
acid (ArH); and 3) n?era-formylbenzenesulfonic acid (Ar-m-
CHO) from the intermediate compound 49 b.
The phosphane pdspp was isolated from used catalyst so-
lutions ("contact" solutions). In an aqueous reaction medi-

1536 Angeir. C I I ~ ?l .~ fEd.

. O ? g / . 1993, 32, 1524- 1544
um, the starting compound of the deactivation mechanism is
then regenerated from 49b under CO/H, pressure. The for-
mation of nzetcr-formylbenzenesulfonic acid in isolable quan-
tities rules out the deactivation of the phosphane by ortho-
metalation: as the formyl group is located at the position
originally occupied by the phosphorus atom, the deactiva-
tion must be started off by an oxidative addition of the tppts
ligand to Rh'. Other workers confirm this observation for
Rh- tpp complexes.['54-1561 The subsequent fate of the re-
ductively eliminated bis(rneta-sulfopheny1)phosphinous acid
Ar,POH is shown in Scheme8. For phosphinous acids,
4
ArZP\
0
OH
c--
+<O> '4
Ar,P,
H
-
-
+C3H,CHO
Ar2P\
4
0
CH(OH)C,H,
K2 K5
Scheme 8 . Formation of the main degradation products K5 and K 2 from bis-
(Ar = n-C,H,SO,Na, < 0 z from H,O).
(~iirra-sulihphenyl)pI~osphinousac~d
R,P(O)H. an equilibrium between the hydroxy species
Ar,POH and the phosphane oxide Ar,P(O)H form is postu-
lated, and in fact (CF,),POH is the only hydroxy tautomer
that has yet been isolated. For all weakly electron-with-
drawing substituents R the phosphinous acid is present as
phosphane oxide. Therefore. the reductive elimination of
Ar,POH is followed by rapid tautomerization to Ar,P(O)H.
This compound reacts with the butyraldehyde in solution to
form K5, and is partially oxidized to phosphinic acid K 2 .
Both products were isolated from catalyst solutions originat-
ing from the plant operation.
6.4.4. Further Concepts in Catalytic Hydroformylation
Other aspects of the use of water-soluble catalysts for
hydroformylation include complexes with cationic lig-
ands,'"". 571 binuclear rhodium-tppts complexes,[158-16']
immobilization of water-soluble Rh complexes on ion ex-
c h a n g e r ~ . " polymers."
~~~ '
64. 6 5 1 cyclodextrins,[' 661 and mi-
cellar two-phase h y d r o f o r m y l a t i ~ n . [ ~ ~ ~
Some Rh' complexes of the cationic ligand amphos 16,
[Ph,PCH2CH,NMe,]+, are efficient hydroformylation cat-
alysts when in aqueous solution or immobilized on strongly
acidic cation exchangers.'", Leaching of rhodium does
not occur; nevertheless, the metal can be recovered by elu-
tion from the ion exchange resin with In contrast,
the cobalt complex [Co(CO),(amphos)],(PF6), suffers from
considerable metal leaching. Moreover, when it is in the
liquidiliquid two-phase system or immobilized on the ion
exchange resin, it is less active, and gives poor nliso ratios.
Recently, immobilization of water-soluble metal com-
plexes on solid supports has been investigated,['63- 1661 for
example, [HRh(CO)(tppts),] on the ion exchange resin
Amberlyst A-26.['631Unlike the SAP catalysts (Section 7),
the catalyst-loaded resin can be prepared with no water con-
tent. Hence. the disadvantageous oxidation of tppts to the
corresponding phosphane oxide by water and Rh"' should
be avoidable. The tppts ligand binds to the carrier by three
sulfonate groups; hence the greater stability of the tppts
system relative to the amphos systems can be explained.
1-Tetradecene, 1-dodecene, and I -octene are hydroformy-
lated at 100C and 70 bar pressure with an n/iso ratio of
2.3-3.4/1. The yield of aldehyde is low (seldom greater than
500/), but the extent of isomerization is high and solvent-
dependent (up to 42%). The thermal instability of the resin
at temperatures above 100 "C limits its use. The surprising
long-term stability of this group of catalysts is more encour-
aging. After multiple use of the resin-supported catalyst,
productivity and selectivity hardly decrease (reduction of
P/Rh ratio). Rhodium leaching has not been found. After 16
cycles (corresponding to T O N = 15 OOO!), the extent of phos-
phane oxidation was 80%, caused by moist and oxygen-con-
taining substrates and solvents. The exceptionally long life-
time of this class of catalysts is promising.
Polymer-fixed Rh catalysts still have a long way to go
before they become industrial materials. Drawbacks are
leaching and thermal instability."671 A polyfstyrenedivinyl-
benzene) copolymer with hydrophilic -CH,P(C,H,SO,H),
groups was investigated in Rh'-catalyzed propene hydro-
~ - With a metal loading of 3.4 wt % Rh
f ~ r m y l a t i o n . [ ' ~1651
and P/Rh = 8.7/1, the conversion rate is 3 x 10' mol(a1de-
hyde) per g(Rh) per min after 4 h at 100 "C and 30 bar. The
selectivity (njiso = 1.2/1) is very low, but this is a promising
opening for asymmetric (= enantioselective) variants of hy-
droformylation (see ref. [206]). Again, catalyst stability is
favorable.
The use of longer chain alkenes in liquid/liquid two-phase
systems is limited by the solubility of the substrate in the
aqueous (catalytic) phase. Cyclodextrins, which have inner
lipophilic cavities and hydrophilic surfaces, offer novel pos-
sibilities. As shown in Figure 10, r-cyclodextrin can bind one
molecule of 1-hexene in its cavity, and thus transfer the
alkene across the phase interface. The specific orientation of
the alkene in the cyclodextrin favors the formation of the
linear aldehyde." 661
H
Fig. 10. Orientation and complexation of alkenes in individual cyclodextrin
molecules
The positive prognostication is not yet fulfilled with
[HRh(CO)(tppms),]. By adding a-cyclodextrin, the aldehyde
yield is reduced from 55 YO(without added dextrin) to 11 O h .
The nliso ratio, 7/3, is unaffected. The authors attribute this
to hydrogen bonds between the hydroxyl groups of the a-cy-
clodextrin and the sulfonate groups of the tppts, which is
said to hinder dissociation of a phosphane ligand and hence
the coordination of the alkene. Nevertheless, modified cy-
clodextrins are expected to become important for the 0 x 0
synthesis, because of their ability to cause steric orientation
of substrates.[1681
1537
 Fell et al. first achieved the micellar two-phase hydro-
formylation of longer chain alkenes by the use of the sulfo-
betaine of tris(2-pyridy1)phosphane (see Eq. (3)).12'] The
properties of these interfacially active compounds (n = 0, 3.
5, 7, 9, and 11) can be tuned. The phosphanes form com-
plexes and promote dissolution. By suitable choice of n, they
acquire surfactant properties, and, above a critical concen-
tration, form micelles. The lipophilic alkenes can be trapped
in the long alkyl groups of the micelles. The active Rh center
is also inside the micelle as a result of the coordination to the
phosphorus atom. For example, tetradecene can be hydro-
formylated, with a 79 YOyield of aldehyde (njiso ratio = 3/1).
The most suitable phosphane has a chain length n of 5. If
n> 5. stable emulsions are formed and phase separation can
become a problem. In no case is rhodium loss observed.
The binuclear rhodium complexes of the type [Rh,(p-
SR),(CO),(tppts),] of Kalck et al. should also be men-
tioned."58-'621 T hey show the usual activity in the hydro-
formylation of I-hexene, but unusually high selectivity
(njiso = 18jl). The hydroformylation can also be carried out
without hydrogen, since the solvent water can function as
the H, source through the water-gas shift reaction:
C O + H,O CO, + H, . 1-Hexene a t p H = 4.8 can be con-
verted into I-heptanol with 75% yield (80C, p ( C 0 ) =
8 bar, P/Rh = 6, 15 h, selectivity 95.8 'YO). The use of water as
a source of hydrogen makes this class of complexes especially
interesting.
7. Supported Aqueous Phase Catalysts
The recent development of "supported aqueous phase cat-
alysts" (SAP 1701began in 1989 with a publica-
tion in By their work on SAP catalysts, Davis et
al. opened the way to hydroformylate very hydrophobic
alkenes such as oleyl alcohol, octene, or dicyclopentadiene
with the water-soluble catalyst [HRh(CO)(tppts),], using the
principle sketched in Figure 11.
Fig. 1 1 . Schematic diagram of a SAP catalyst according to ref. 11691. Working
principle: a thin, aqueous film containing a water-soluble catalyst, for example
[HRh(CO)(tppts),], adheres to silica gel with a high surface area. These cata-
lysts act at the liquidiliquid interface.
7.1. Preparation of S A P Catalysts
To produce SAP catalysts, a granulated, porous support
material with a large inner surface is added to a stirred
1538
aqueous solution of [HRh(CO)(tppts),J and tppts (ligand
excess), and then dried under vacuum. The hydrophilic carri-
ers consist of "controlled-pore glass" (CPG) with a definite
but variable large inner surface (CPG-240, CPG-350). CPG-
240 has a mean pore diameter of 237 A, a pore volume of
0.95 mL g- '( Ifr 4.3 "/o) and a specific surface area of
77.5 m'g-'. After removal of all the solvent, a dry, yellow
powder remains which still contains about 2.9 wt YOwater.
The metal complex is homogeneously distributed on the in-
ner and outer surface of the support. If this catalyst materia1
is treated a t 30 Torr and 30 "C with water vapor, a controlled
amount of water can be added, depending on the contact
time. A comprehensive account of the process is given in
Ref. 11721.
7.2. Hydroformylation and Hydrogenation with SAP
Catalysts
The SAP catalysts were developed for the hydroformyla-
tion of liquid substrates that are completely insoluble in wa-
ter, for example, oleyl alcohol." 7 2 1 In the Ruhrchemie/
Rh6ne-Poulenc process, longer chain alkenes can only be
hydroformylated in the presence of solubilizers, for ex-
ample, tetraalkylammonium salts containing four long-
chain alkyl Oleyl alcohol is converted into the
C,, aldehyde at 100"C, 51 bar, and a CO/H, ratio of Ill, in
96.6 YOyield without any rhodium loss at all. Moreover, after
filtering off the stationary phase, the liquid phase does not
contain rhodium, either as a complex species o r as a colloid.
The water content of the support is important. For example,
the hydroformylation of I-octene is characterized by a re-
duction in activity for a water content of more than 8 wt %.
Also, the n/iso ratio and the system stability are reduced with
increasing water content. It is thought that the resulting
greater mobility of [HRh(CO)(tppts),] promotes decomposi-
tion reactions.
The site of the reaction is well established. On supports
with physically different structures, the activity depends on
the specific surface; that is, the reaction takes place at the
phase boundary. Thus, the results are in agreement with
those of solid [HRh(CO)(tppts),] . nH,O. In its isolated
state, the solid contains up to 16 wt % water-it is in a sense
a "primitive SAP catalyst". In the hydroformylation of 1-
octene in cyclohexane, the results almost match values with
SAP catalysts: 98.7% conversion, nliso = 2.1 -2.9. As the
Rh complex is insoluble in the organic reactants, the reaction
must take place at the solid/liquid interface. This conclusion
is supported by comparative investigations of two-phase sys-
tems and SAP catalysts.[' For classical liquid/liquid sys-
tems, the rate of hydroformylation decreases in the series
I-hexene > 1-octene > 1-decene; with the SAP catalytic
method, these alkenes react at virtually the same rate. Typi-
cally for surface effects, the solubility of the alkene in the
aqueous phase is no longer the rate-determining factor. The
low n/iso ratio of 2.8 in the three cases is due to coordinative-
ly unsaturated complexes such as [HRh(CO),(tppts)], which
are known for their poor regioselectivities."
When the complex [C~,(CO),(tppts),][~~~ is immobilized
on CPG-340 and used for the hydroformylation of I-hexene,
there is only negligible leaching of cobalt into the product
Angew. Chew Inr. Ed. Engl. 1993. 32, 1524-1544
phase.['741 However, in a typical two-phase reaction, the
metal loss is not inconsiderable. A t 190"C, 55 bar (CO/
H, = l / l ) the degree of conversion reaches 68% (njiso22)
after 8 h, depending on the water content. Other publica-
tions describe improved methods of producing SAP cata-
lysts, and the extension of hydroformylation to other unsat-
urated compounds.[' 751
In variations of the SAP catalytic method, platinum/tin
tppts complexes can be obtained." 761 The most active water-
insoluble, homogeneous hydroformylation catalyst based on
platinum is the compound [PtCl(tpp),SnCI,]. Tin(i1) chlo-
ride increases both the reaction rate and the n/iso ratio. How-
ever. due to the sensitivity of the platinum-tin bond to hy-
drolysis, a tppts-modified system cannot be used in water. As
the amount of water on the SAP catalyst (as little as 3 YO)is
required only for the solubilization of the sulfonate groups
of the tppts, the hydrolysis of the metal-metal bond should
be able to be kinetically limited. Therefore, CPG-350 was
impregnated with [PtCl,(tppts),], and treated with a solution
of SnCI, in CH,CI,. The vacuum-dried SAP catalyst con-
tains 1.4 wt% water (TGA data). The high selectivity (n/
is0 = ca. 12/1) compared with the tin-free system [PtCI,-
(tppts),] (njiso = 3/1) indicates a stable Pt.. . CI.. . Sn inter-
action. The reaction rates are low, and decrease further as
the water content increases to 7.4 wt% because the active
species decomposes. Hydrogenation and isomerization are
strikingly dominant. In the SAP catalytic method after
120 h, [PtCl(tppts),SnCI,] at lOO"C, 70 bar (HJCO), and a
P/Rh ratio of 2/1 converts 1-hexene into only 26% heptanal
and 12.7% hexane, but 21.2% 2-hexene and 7.6% 3-hexene
are also formed. However, as no metal loss is observed, this
method of immobilization seems to have some industrial
future if further optimization of the parameters can be
achieved.
With SAP catalysts based on Ru-tppts complexes, the
selective reduction of a,B-unsaturated aldehydes to ally1 al-
cohols can be performed. Thus, a t 100 bar pressure of H2(!),
3-methyl-2-butenal and all-trans-retinal are reduced with al-
most quantitative yield and high selectivity (up to 89%). The
reduction in activity on recycling the catalyst material is due
to successive adsorption of the reactants. Metal loss only
dominates when polar solvents such as methanol are used.
For the first time such a decrease in activity following cata-
lyst recycling has been clearly documented; as a result, the
industrial use of SAP catalysts for this particular reaction is
viewed with It remains to be seen whether
the concept of SAP catalysts meets the high expectations for
it.[1711
7.3. Wacker Oxidation
The Wacker process for long-chain alkenes also requires
solubilizing agents. To compare performance with SAP cata-
lysts, PdCI, and CuCI, ( l / l ) were immobilized o n CPG-240
(1 5 wt YOH,O)." In 3 h, this catalyst converted 1-heptene
at IOO'C, p ( 0 , ) = 4 bar, and a n alkene/Pd ratio of 210/1
into 2-heptanone (oxidation), 2-heptene, and 3-heptene (iso-
merization). In the conventional Wacker process, isomeriza-
tion is insignificant. In the SAP catalytic process, the oxida-
tion of Pdo to P d 2 + is probably very slow, so isomerizations
Angew. Chctn. l t z t . Ed. Engf. 1993. 32, 1524- 1544
a t the stage of the Pd-alkene complex become more signifi-
cant. The reduction in isomerization with increasing 0, par-
tial pressure is consistent with this conclusion and with a
more rapid Cu' oxidation. In spite of the unfavorable
product distribution, SAP catalytic technology has the ad-
vantage that use of corrosive solutions of Cu2 is avoided.
+
The latter problem affects all conventional Wacker pro-
cesses.
To sum up, immobilized water-soluble complex catalysts
extend the concept of two-phase reactions to a new technical
dimension." 791
8. Special Uses of Water-Soluble Ligands
In addition to their main use in catalysis, water-soiubk
ligands have a number of special uses.
8.1. Membrane Modification by Selective
Hydrogenation
The hydrogenation of unsaturated fatty acids is an impor-
tant process, because these compounds form part of the
membrane structures of a wide range of lipid class-
es.[180-ls6] Water-soluble catalysts are very much more suit-
able than their lipophilic derivatives, as no solvent vector
such as T H F o r DMSO is needed for the transport of the
metal complex into the membrane. Furthermore, water-sol-
uble catalysts are easier to remove from the still intact mem-
brane at the end of the reaction, and even the polarity of the
catalyst can be controlled by suitable choice of hgand. The
location of the reaction can be selected by exploiting the
variable extent of penetration into the membrane.
The initial research in this field was carried out by Madden
et al. during 1978-1980."80* 18'] The hydrogenation activity
of the catalyst IRhCl(tppms),] on phosphatidylcholine from
soya lecithin was determined for the vesicles produced by
ultrasound or mechanical perturbation. The water-soluble
metal complex has amphiphilic character due to its sulfonat-
ed phosphane ligands and unsubstituted phenyl groups. This
bipolarity facilitates the transition between the polar
aqueous phase and the lipophilic hydrocarbon phase. Ap-
proximately 85% of the catalyst is either'on o r in the mem-
brane-like moths in the fold of a curtain. The membrane
structure is not destroyed even if 20 molo/' catalyst (based on
phospholipid) is present. All the double bonds can usually be
hydrogenated, even including those deep inside the mem-
brane layer. The catalyst therefore diffuses through the
membrane in a few hours. At the end of the reaction, approx-
imately 70o/' of the metal complex can be recovered from the
membrane by means of ion exchangers.
Further investigations of the hydrogenation of di-
oleylphosphatidylcholine liposomes were published, in
which the hydrogenation activity of the complexes
[RhCl(tppms),] and [RhCl(dpup),] were compared,['821
[dpup = disodium diphenylphosphinoundecylphosphate,
(C,H,),P(CH,), lP( =O)(ONa),]. At 37 "C, 1.2 bar H,, and
p H = 6.9, a cisltruns isomerization (oleic acid to elaidic acid)
takes place before the hydrogenation. The cis isomer is not
hydrogenated, but the trans isomer is. The rate of hydro-
1539
genation is independent of the catalyst concentration. The
kinetics are indicated by the equilibrium in (16). If
the critical micelle concentration is exceeded, the water-sol-
uble catalyst is present as a large reservoir in the form of
micelles. The micelles are in equilibrium with the monomeric
form of the catalyst, whose concentration remains constant
irrespective of the initial amount used. The monomeric Rh
complex diffuses to the membrane and catalyzes hydrogena-
tion there. As the monomer concentration does not change,
the rate of hydrogenation is constant. Equilibrium (16) raises
the question of the self-association of water-soluble metal
complexes for the first time, a subject which is also of interest
in connection with colloids (see Section 9).
The phospholipids located on the outside of the mem-
brane can be hydrogenated with [RhCl(tppms),],[' 831 and
the cholesteryl acids and triacylglycerides located further in-
side the membrane are also reduced, but with decreased ac-
tivity. The hydrogenation of the "inner" compounds that
can nevertheless be observed is explained by the intermin-
gling of the CC unsaturated alkyl chains with the phospho-
lipids bonded to the surface (Fig. 12). The sulfonate groups
of the water-soluble catalyst are oriented at the hydrated
surface of the lipoprotein, while the active rhodium center
penetrates the alkyl chain layer of the phospholipid.
hydrophobic lipids inside
the structure (e.g. triacyl-
glycerides, choiesterin) polypeptidechains
\ with hydrophilicgroups
phospholipids with
polar headgroups
aqueous
medium
+++
Fig. 12. Schematic diagram o f a plasma lipoprotein (from ref. [lX41).
Vigh et al.['85' have compared Ru and Rh catalysts for the
hydrogenation of membranes. Under normal conditions, the
complex [RuCl,(tppms),] is more active than the normally
used catalyst [RhCl(tppms),], which becomes superior to the
Ru analog above 30 "C (Fig. 13).
The hydrogenation of protoplast membranes is also pos-
sible.1'861The fluidity properties of biomembranes are main-
t
A[%] 30
10 d ,-'
-
0 ,-*-:
0 10 20 30 40 50
T["C]
Fig. 13 Comparison of hydrogenation activities A (in "/o hydrogenation) of
[Ru"Cl,(tppms),] (0)and [Rh'Ci(tppms),] (B).
1540
ly determined by the number and position of the cis double
bonds in the unsaturated fatty acids. Many physiological
and biochemical processes are fundamentally linked to the
viscosity of the cell membrane. The homogeneously cata-
lyzed hydrogenation of the cis double bonds of Fatty acids
within an intact membrane by means of a water-soluble
catalyst can therefore contribute to a deeper understanding
of the modification of membrane fluidity. The complex
[ R ~ C I ~ ( t p p m s ) ~has
] [ ~been
' ~ used for this purpose. The cat-
alyst is very selective at 30 "C and 7 bar Hzfor the conversion
of linoleic acid (C18, three double bonds) into less unsaturat-
ed C18 acids (two to zero double bonds). If the extent of
hydrogenation exceeds 30%. a serious loss of living proto-
plasts takes place. Destruction of intact protoplasts can be
avoided by shorter contact times. From kinetic consider-
ations, cell-like defense reactions can work against the con-
tinuing hydrogenation according to the principle of "homeo-
viscous adaptation".
8.2. Light and Membrane Fluidity
Natural liposomes with a single or double layer can be
hydrogenated by using the catalyst system [RuCl,(bpy),]/
[RhCl(tppms),] (bpy = 2.2'-bipyridine)['871 with ascorbate
as a light-induced hydride donor." 881 The combination of
ruthenium and rhodium enables the nascent hydrogen to be
produced in an ascorbate buffer. The light-collecting species
is the complex [RuCl,(bpy),], and hydrogen transfer is per-
formed by [RhCl(tppms),]/ascorbate.
The system is effective for the hydrogenation of ethene
and ethyne and for the hydroformylation of ethene.['871The
in situ generated hydrogen enables hydrogenation even at
0.1 bar partial pressure (TON = 40 for ethene, quantum
yield = 1.8). The pressureless(!) hydroformylation gives
a TON of 3.5 with a quantum yield of 0.1 YOThe mechanism
of the quantum uptake by the Ru" complex (Ru"/Ru'
reduction) and the formation of the active species
[HRu(CO)(tppms),] is formulated in Equations (1 7- 19).
Despite these interesting results, the catalyst system is still
somewhat unstable.
8.3. Regeneration of NAD(P)+ with Water-Soluble
Catalysts
NAD(P)+ cofactors have important applications in bio-
technological processes, for example. the conversion and
storage of solar energy. According to the initial research into
the regeneration of NAD(P)+ cofactors." 891 NAD(P)+ can
be reduced in the presence of the water-soluble rhodium(r1r)
Angcw Climi. Inr. E d E~igl.1993. 32. 1524 1544
~
complex with tris(2,2'-bipyridyl-5-sulfonicacid) both elec-
trochemically and photochemically with IRu(bpy),]' t as a
photosensitizer in aqueous alcoholic solution. However, re-
action of the NAD(P)H and alcohol dehydrogenase with
cyclohexanone yielded cyclohexanol in only small amounts.
Only 46 catalytic cycles were performed in 33 days (based on
the Rh complex). Higher conversions were achieved with
[RhCl(tppms),].['yol NAD(P)+ cofactors are thermally and
photochemically reduced. Formate and ascorbate were used
as hydrogen sources. Kinetic investigations show that the
rate-determining step is cleavage of the C-H bond and sub-
sequent formation of a hydridorhodium species. The reac-
tion follows Michaelis-Menten kinetics with an apparent
'.
activation energy of 20 kcalmol- If the reduction is fol-
lowed by an enzymatic reaction, such as reduction of ac-
etaldehyde to ethanol by horse liver alcohol dehydrogenase,
biologically active NAD(P)H can be produced, but the activ-
ities are inferior to reactions with conventionally regenerated
NAD(P)H. Higher activities cannot be obtained, because the
free ligand tppms produced by photodissociation acts as an
inhibitor towards the metal complex. Reaction rates and
regioselectivities of the reduction of NAD(P)+ are low in
comparison to enzymatic systems. A further problem is the
inhibition of secondary enzymatic reactions by tppms.
9. Water-Soluble Catalysts-Colloids?
In spite of their catalytic potential, colloidal transition
metals have so far attracted little attention. The preparation
of stable water-soluble colloidal metals is comparatively sim-
ple, and their stability has recently been improved with the
aid of sulfonated phosphane ligands such as tppms. Schmid
et al. have carried out truly remarkable work on the prepara-
tion of water-soluble gold colloids (formula [Au,(tppms),],
where r / v = 20/1, relative molecular weight about 40 x lo6,
particle diameter about 18 nm). The material has metallic
properties, and can be repeatedly dissolved in and reprecipi-
tated from water.["'. '921 Bonnemann et al. have shown that
colloidal particles of various metals can be prepared from
solution as a solid substance by stabilization with alkylam-
monium ions, can be stored in a stable condition, and subse-
qently redissolved. These operations leave the catalytic prop-
erties almost '941
no optical induction, from which the existence of a colloidal
"heterogeneous catalyst" is deduced. The same is true if a
Rh"' starting complex is present. The reduction to Rh' (pre-
formation) is associated with the oxidation of the phos-
phane. The catalyst formed shows hydrogenation activity
but is not enantioselective. All these findings support the
view that rhodium colloids, which are stabilized by phos-
phane oxides and are active hydrogenation catalysts, are
present in aqueous systems.
The redox chemistry of the simple system RhCI;3 HzO/
tppts in water was thoroughly investigated by Patin et al.IZ0l1
The formation of an Rh"'-hydroxo complex according to
Equation (20) followed by coordination of a molecule of
tppts according to Equation (21) leads to the reduction of
Rh"' to Rh'. Labeling experiments with H,"0 identified
water as the source of oxygen in the concomitant phosphane
oxidation. In the presence of acids or chloride-containing
salts, the formation of the chloro(hydroxo) complex in
Equation (20) can be suppressed. Accordingly, the addition
RhCI, + H,O' $ [RhCI,(*OH)] + HCI (20)
[Rh"'CI,(*OH)] + P(m-C,H,SO,Na),
1 (21)
{Rh'CI} + 'O=P(m-C,H,SO,Na),
{Rh'Cl) + 3P(rn-C6H,SO,Na), -
[R h'Cl{P(m-C,H,SO,Na),),]
(22)
50
of 0 . 5 HCIO,
~ o r 2~ NaCl solution reduced the extent of
phosphane oxidation from 70% (without addition) to 12%
or 5 0/~.r1991The solvent-stabilized Rh' chloride is coordinat-
ed by free unoxidized tppts, and forms the water-soluble
complex 50 analogous to the Wilkinson compound
[Eq. (22)]. It eliminates a molecule of tppts to form the sol-
vated complex 51, which dimerizes to the stable compound
52 (P = phosphane) [Equation (23)]. This study emphasizes
that the situation for even simple catalyst systems in water is
much more complex than for normal homogeneous catalytic
systems in organic media. The findings further support the
idea of catalytically active colloids. Their role is still poorly
understood, but their potential is obvious." 9 3 , 1941

If the complex [RhCl(tppts),] is prepared by the reaction

of RhC1;3 H,O with tppts in an ethanol/water mixture, the a,,,, .PAr,
rppts \\

hgand tppts is quickly and completely oxidized during the

'
u
Rh" 7 Rh" 7

hydrogenation of an alkene (detected by 3 1 PNMR). This + tppts 4

'
Ar,P 'PAr, Ar,P Solv.
shows that rhodium colloids stabilized by phosphane oxide
50 51
are the active species, as the rhodium remains in solution.
Several publications on this theme have appeared recently,
but they d o not adequately explain the role of rhodium col-
loids in two-phase catalysis.['95
Sinou et al. used the example of alkene hydrogenation to 52
investigate the question of the homogeneous or heteroge-
neous nature of the active catalyst species in two-phase sys-
t e m ~ . [ ' ~ 'Catalysis
] experiments with chiral, water-soluble 10. Perspectives
phosphanes and their oxides clearly showed that Rh' forms
enantioselective homogeneous catalysts with water-soluble Following the technological breakthrough of the
phosphanes. On the other hand, systems containing Rh' and Ruhrchemie/Rhbne -Poulenc process (1984), water-soluble
phosphane oxide show the same hydrogenation activity but catalysts based on coordination complexes and organo-

1541
metallic compounds have promoted the long overdue bridg-
ing of the chasm between homogeneous and heterogeneous
catalysis. The concept of stationary supports (immobi-
lized homogeneous catalysts), which has to date not had
any convincing success, has been overtaken by that of mo-
bile carriers, in which water, the catalyst medium, brings
additional process advantages. Common ground first ap-
peared in 1989 with the development of supported aqueous
phase catalysts (SAP catalysts). The sometimes excellent
compatibility of complex catalysts with water (up to 130 C
process temperature) was not expected even by experts in
catalysis, who need to get accustomed to the idea. To ensure
success, the ligands selected must have very high solubility in
water. Experience suggests that 1 kg L- is a practical guide-
line. However, this criterion is not met by all the ligand
classes usually used in homogeneous catalysis, so synthetic
chemistry is again required. Rh-catalyzed hydroformylation,
the most extensively investigated process, provides convinc-
ing evidence of the advantages of the two-phase aqueous
reaction system. All the phosphane iigands tested so far are
more active and selective in their water-soluble (sulfonated)
forms than in the homogeneously catalyzed process, often by
a very large margin. Water is excellent as a reaction and
catalyst medium on grounds of solubility (for example, dif-
ferential solubility of starting compound and product(s)) or
the thermodynamics of a desired reaction.[2o71These advan-
tages combine ideally with the techniques of separation and
recycling of the noble metal, which are continuously being
perfected. This young interdisciplinary field of modern cata-
lyst research and technology belongs to the future in research
at universities and in Even organometallic
complex catalysts such as the much investigated methyltri-
oxorhenium(vI1) ([CH,ReO,]) are soluble and stable in wa-
ter.[2021
This article results from a joint research project of Hoechst
AG (Werk Ruhrchemie) and the Technische Universitat
Miinchen. Since 1986 this project has followed the new devel-
opments in two-phase hydroformylation and its potential. A s is
typical for this field, the authors came into contact with ihe
subject through practical industrial experience and must thank
their colleagues in Oberhausen for numerous consultations
over several years of collaboration, especially Drs. Bahrmann,
Frohning, Heymanns, Konkol, Kottmann, Lappe, Peters, Rei-
chelt, and Weber. We also acknowledge fruitful cooperation
with former Doctoral students Jiirgen Kulpe (Hoechst A G ) ,
Jiirgen Kellner (Deutsche Shell A G ) , and Herbert Riepl
(Klinge-Stiftung Holding GmbH) in the Munich institute as
well as the present PhD students Rainer Manetsberger. Guido
Albanese, and Rochus Schmid. Special thanks are due to Pro-
fessor Boy Cornils and Professor Klaus Kiihlein (both Hoech-
st A G ) for their hospitality io W A . H . and for numerous scien-
tific discussions.
Received: May 7, 1993 [A922IE]
German version. A n p i , . Chem. 1993. /O5. 1588
Translated by R. G. Leach. Bdsingstoke (UK)
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