Kinetic enolates

Conditions for kinetic control of enolate formation can be applied to the Robinson annulation to control the regiochemistry of the reaction. Entries 5 and 6 of Scheme 2.11 are cases in which the reaction is carried out on a preformed enolate. Kinetic... 

Enolates are selectively formed by treating ketones with a strong base such as lithium diisopropylamide (LDA) [LiN(i-C3H7)2] and tetrahydrofuran (THE) at —78°C, NaH or alkoxide ion. LDA and THE at —78°C give less stable, i.e. less substituted, enolate (kinetic enolate) 3.5 from unsymmetrical ketone 3.4, whereas methoxide (CEisO ) forms the more stable, i.e. more substituted, enolate (thermodynamic enolate) 3.6 from unsymmetrical ketone 3.4. 

A large part of carbonyl chemistry is concerned with enolization. Kinetic deprotonation of ketones suggests the following preference CH3CO >CH2CO >CHCO. On considering the carbanions as acid-base complexes it becomes clear that the primary complex is better stabilized than the secondary one, which is, in turn, more stable than the tertiary complex. 

In some cases, there is a competition within a molecule for closure to rings of different sizes. If the closure is an irreversible reaction such as alkylation of an enolate, kinetic control may allow three-membered ring closure to predominate over five-membered as in Equation 8.17 [27]. The electrophilic carbon closer to the nucleophilic site is found first, in spite of the incorporation of ring strain. With reversible reactions, the thermodynamic product predominates. That is, the low strain five- or six-membered rings whl form to the exclusion of three- or four-membered alternatives (Scheme 8.13). In Claisen and aldol cychzations, five- and six-membered rings are not in competition with each other. Seven-membered rings may sometimes be closed readily without high dilution (Eq. 8.18) [28]. 

---