B-ALLYL-10-PHENYL-9-BORABICYCLO[3.3.

2]-DECANE

B-Allyl-10-phenyl-9-borabicyclo[3.3.2]decane
Ph B

Ph B
RL

O RS

RL

O RS B

Ph

Et2O, 78 C

Ph HO NMe2 C6H6, 70 C

(2) TMSN R

Ph

(MW 252.20) [865358-58-3] C18 H25 B InChI = 1/C18H25B/c1-2-14-19-17-12-6-10-16(11-7-13-17) 18(19)15-8-4-3-5-9-15/h2-5,8-9,16-18H,1,6-7,10-14H2 InChIKey = MGNDFWIQIFODEO-UHFFFAOYAC
(asymmetric allylboration of ketones, aldehydes, and ketimines) Alternate Name: B-allyl-10-Ph-9-BBD. Solubility: ether, THF, pentane. Preparative Method: 1 prepared from B-Methoxy-9-BBN, Phenyldiazomethane, and Allylmagnesium Bromide according to the literature procedure. This preparation involves resolution of the enantiomers via a modication of Masamunes protocol,2 which entails the use of enantiopure (1,2)-NMethylpseudoephedrine. Handling, Storage, and Precautions: the crystalline precursor (eq 1)1 is air stable and can be stored indenitely at room temperature. Once generated, the title compound must be stored in the absence of air and moisture.
Table 1

O Ph B

RS OH RL

Yield and ee of allylations1 RL RS Me Et Me Me Me Me H % yield 92 70 80 77 74 70 82 % ee 96 94 87 81 92 99 90

1. 2. 3. 4. 5. 6. 7.

Ph Ph Et CH2 =CH i-Pr t-Bu Ph

Allylation of Carbonyl Compounds. Asymmetric allylation of ketones and aldehydes is accomplished in good yield and with high enantioselectivity using B-allyl-10-Ph-9-BBD. The enantiopure allylborane is generated from its pseudoephedrine complexed 10-Ph-9-BBD precursor (eq 1) by treatment with allylmagnesium bromide. The magnesium salt of the N-methyl pseudoephedrine (NMPE) is efciently recovered for recycling.

As would be expected, the related allylborane B-Methylallyl10-phenyl-9-borabicyclo[3.3.2]decane3 is generated from the common NMPE complexed 10-Ph-9-BBD precursor and is effective for asymmetric allylboration with similar results (eq 3). Ozonolysis of the resulting -methyl homoallylic alcohols provides easy access to asymmetric -hydroxy methyl ketones.3
O

Ph B

Ph Me 1. Et2O, 78 C

Me OH Ph 87% 88% ee

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Ph Ph N O Ph B
AllylMgBr Et2O, 78 C 98%

2. workup

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Once generated, B-allyl-10-Ph-9-BBD provides direct and efcient access to asymmetric tertiary homoallylic alcohols.1 Treatment of methyl and ethyl ketones with the reagent results in formation of the intermediate boronic ester (eq 2). Workup of the boronic ester intermediate with NMPE results in release of the asymmetric alcohol and regeneration of the NMPE complexed 10-Ph-9-BBD precursor (eq 2). Allylboration of acetophenone is reported in 92% yield with high enantioselectivity (Table 1); benzaldehyde is asymmetrically allylated with similar results. Notably, compounds in which the groups on the ketone are very similar in size, for example, methyl ethyl and methyl vinyl ketones, are allylated in reasonable yields and enantioselectivities.

Allylation of TMS Ketimines. Asymmetric synthesis of tertiary amines is undertaken by treatment of N-trimethylsilyl (TMS) ketimines with B-allyl-10-Ph-9-BBD.4 The Rochow protocol5 can be employed to convert a nitrile into a thermally unstable mixture of the anti-N-TMS ketimine and enamine. Heating this mixture maximizes the ratio of the syn-N-TMS-ketimine and enamine to the anti-N-TMS-ketimine. This is important as the allylation proceeds smoothly on the syn-N-TMS-ketimine, but slowly and with low enantioselectivity on the anti-ketimine. The enamine provides access to the syn-N-TMS-ketimine in situ (eq 4).4 Allylboration of the ketimine proceeds rapidly (1 h) at 78 C; workup with NMPE results in recovery of the asymmetric homoallylic amine and the regenerated 10-Ph-9-BBD precursor. Yields for the conversion vary from moderate to good, and the enantiomeric excess is generally high (Table 2).
Avoid Skin Contact with All Reagents

B-ALLYL-10-PHENYL-9-BORABICYCLO[3.3.2]-DECANE
Ph B

TMSHN R

TMS H R N

Ph Ph B N O Ph B

TMS Ph
TMSC CH2MgBr Et2O, 78 C 97%

(4) Me OH TMS N B R Ph R TMS N B Ph R C TMS

RCOMe

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Table 2 Allylation of ketimines6 R 1. 2. 3. 4. 5. 6. 7. Ph 4-MeOPh t-Bu c-Hex 4-ClPh 3-Py 2-thienyl % Yield 75 55 50 66 74 50 80 % ee 92 94 98 70 64 71 60

The propargyl borane efciently converts ketones into the corresponding asymmetric -allenyl tertiary carbinols (eq 6); these reactions proceed with good yields (6295%) and high enantioselectivities (7898% ee). Reaction times vary from 3 to 36 h as ketones with electron-withdrawing R groups tend to react more slowly.7 Related Reagents. B-Allyl-9-borabicyclo[3.3.1]nonane; B-Allyldiisocaranylborane; B-Allyldiisopinocamheylborane; BCrotyldiisopinocampheylborane; (R,R)-2,5-Dimethylborolane; Diisopropyl 2-crotyl-1,3,2-dioxaborolane-4,5-dicarboxylate.

Related 10-Ph-BBD Reagents. Enantiopure B-Allenyl-10phenyl-9-borabicyclo[3.3.2]decane (eq 5) and B-( -Trimethylsilyl-propargyl)-10-phenyl-9-borabicyclo[3.3.2]decane (eq 6) are easily prepared from the NMPE complexed 10-Ph-9-BBD precursor.7 Asymmetric allenylboration of ketones provides access to asymmetric homopropargyl alcohols (eq 5) in high yields (6285 %) and enantioselectivity (6193 % ee). Reaction times range from 3 to 12 h at 78 C.7
Ph C N O Ph B ()-R Me OH
RCOMe C3H3MgBr Et2O, 78 C 84%

1. 2. 3. 4. 5.

Ph B

6. 7.

Canales, E.; Prasad, K. G.; Soderquist, J. A., J. Am. Chem. Soc. 2005, 127, 11572. Short, R. P.; Masamune, S., J. Am. Chem. Soc. 1989, 111, 1892. Roman, J. G.; Soderquist, J. A., J. Org. Chem. 2007, 72, 9772. Canales, E.; Hernandez, E.; Soderquist, J. A., J. Am. Chem. Soc. 2006, 128, 8712. Chan, L.-H.; Rochow, E. G., J. Organomet. Chem. 1967, 9, 231. Canales, E.; Hernandez, E.; Soderquist, J. A., J. Am. Chem. Soc. 2006, 128, 8712. Hernandez, E.; Burgos, C. H.; Alicea, E.; Soderquist, J. A., Org. Lett. 2006, 8, 4089.

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Daniel Grant Burnham Institute for Medical Research, La Jolla, CA, USA

A list of General Abbreviations appears on the front Endpapers