Regioselectivity metal enolate formation

The regioselectivity of enolate formation is governed by the usual factors so that methyl benzyl ketone forms the more stable enolate with sodium metal. This undergoes smooth and rapid conjugate addition to acrylonitrile, which is unsubstituted at the P position and so very reactive. 

Regioselective enolate formation using kinetic deprotonation of an unsymmetri-cal ketone has been discussed in Section 1.1.1. The specihc enolate can react with aldehydes to give the aldol product, initially formed as the metal chelate in aprotic solvents such as THF or EtiO. Thus, 2-pentanone, on deprotonation with lithium diisopropylamide (LDA) and reaction of the enolate with butanal, gave the aldol product 44 in reasonable yield (1.56). 

In alkenyl- and alkynylcarbene complexes the addition of nucleophiles to the carbene carbon competes with the addition to the 3-carbon of the conjugated C-C multiple bond. [17] The regioselectivity of the addition of amines to alkynylcarbene complexes is temperature dependent 1,2-addition is favoured by lower temperatures. [17c] Enolates turned out to be efficient C-nucleophiles for Michael addition reactions to unsaturated metal carbenes. The product distribution may depend on steric factors as shown in Scheme 7 for the addition of different enolates to alkenylcarbene complex 10. The less bulky acetone enolate 11 adds to the carbene carbon protonation of the primary addition product results in demetalation and in the formation of a mixture of isomeric enones 12. In contrast, the more bulky cyclopentanone enolate 13 adds to the less shielded vinylic position. 

Silyl enol ethers as electron-rich olefins are susceptible to one-electron oxidation by metallic oxidants [121-123]. The chemoselectivity in the oxidative transformations is controlled by the redox potentials of the reactants. VO(OEt)Cl2 induces chemose-lective homo- or cross-coupling of silyl enol ethers as shown in Scheme 2.58 to give the 1,4-diketones via regioselective carbon-carbon bond formation [124]. The more highly substituted the silyl enol ethers 68 are, the more readily they are oxidized. The silyl ketene acetals 73 are also readily oxidized and undergo cross-coupling with silyl enol ethers 69 to give the y-keto esters 74 (Scheme 2.59). 

---