Stereochemistry of Cyclic Ketone Alkylation

Enolate reactions involve an early, reactant-like transition state. There is no appreciable bond formation at the transition state hence, the transition state should resemble 

In conformationally rigid systems, steric factors play an important role in determining the facial selectivity of alkylations of enolates. Whereas alkylation of enolate A proceeds via a chairlike transition state, attack of the electrophile on enolate B in an antiparallel manner is subject to a synaxial interaction with the axial Me group. Hence, parallel approach of the electrophile through a twist boat transition state prevails. 

Alkylation of the enolate derived from deprotonation of the lactone shown below occurs nearly exclusively from the face opposite from the r-butyl group.  

Imine anions are superior to the corresponding enolate anions of the parent carbonyl compounds in alkylation reactions because they give only monoalkylated products of predictable regioselectivity. They can be prepared from aldehyde imines as well as from ketone imines by deprotonation with EtMgBr, LDA, or t-BuLiA  

High yields of alkylated aldehydes and ketones are obtained when using primary and even secondary alkyl halides in the presence of HMPA or DMPU. Little rearrangement is observed with allylic halidesA Moreover, the new alkyl group is generally introduced at the less substituted a-carbon, even with a, 3-unsaturated aldehydes or ketones. 

---