Carbon-carbon bond formation

O C-C Bond Formation

O Alkylation of enolates, enamines and

hydrazones
O Alkylation of heteroatom stabilized
anions
O C=C Bond Formation
O Claisen rearrangement
O Wittig reaction
O Peterson olefination

Alkylation of enolates
O Enolates:
O -deprotonation of a ketone, aldehyde or ester by

treating with a strong non-nucleophilic base

O The carbonyl group will stabilizes the resulting
negative charge
O Common bases: NaH, EtONa, NaNH2
base

enolate

O Enolate formation
O Acid catalyzed (thermodynamic)
H+
more substituted

O Based induced (thermodynamic or

kinetic)
Base

less substituted

O Regioselective Enolate Formation

O Kinetic enolate deprotonation of the

most accessable proton

O Typical condition: a strong hindered (nonnucleophilic base)

LDA/THF, -78C

Li+

O Themodynamic enolate reversible deprotonation

to give the most stable enolate; more highly substituted
C=C of the enol form
O Typical Condition: RO-M+ in ROH, protic solvent allows
reversible enolate formation

- K+

tBuO-K+, tBuOH

- K+
thermodynamic enolate

kinetic

more substituted alkene

O Alkylation of enolates:
O Primary alkyl halides, alylic and benzylic halides work well
O Secondary halides can be troublesome
O Tertiary halides dont work
O Rate of alkylation is increased in more polar solvents

1. LDA, THF, -78C

2. Me-I

O C-C bond formation using enamines

O Advantages: mono alkylation usually gives product from

kinetic enolization

acid
more stable, kinetic
enamine

less stable, thermodynamic

enamine

O C-C bond formation using hydrazones

O Hydrazones are isoelectronic with ketones
O Hydrazone anions are more reactive than corresponding

ketone or aldehyde enolate

O Drawback: can be difficult to hydrolyze

Me2N.NH 2

LDA/THF

H+, -H2O
E+

E+
hydrolysis

O C-C bond formation using heteroatom stabilized

anions
O Sulfones
LDA/THF

Al(Hg)

O Sulfoxides
LDA/THF

Raney Ni

C=C Bond Formation

O Aldol condensation
O Wittig reaction
O Peterson olefination
O Aldol condensation
O Initially give b-hydroxy ketones which under

certain conditions readily eliminated to give a,bunsaturated carbonyls

LDA, THF, -78C

elimination of H 2O

O Mannich reaction formation of a,b-

unsaturated carbonyls or a-methylene

carbonyls

H2C=O, Me2NH.HCl

O Wittig Reaction
O Reaction of phosphonium ylide with aldehydes

and ketones
Ph3P

strong base

ylide

phosphorane

X-

-Ph3P=O

betaine

oxaphosphetane

O Geometry of olefin
non-stablilized ylide
Z-olefin

stabilized ylide
E-olefin

+ -

E-olefin

O Peterson Olefination

LDA/THF

negative chage stabilized by Si

-Me3SiO

mixture of E and Z alkenes

Show an arrow mechanism for the following reactions.

Ph3P=CHCH2CH3
O

Predict the product(s) or reactant(s) for the following reactions.

O
1. LDA
?
2. CH3CH2I