Stereogenic alkylation

The situation changes when chiral ester enolates or chiral amide enolates are alkylated. There, the half-spaces on the two sides of the enolate planes of the substrates are diastereotopic, and alkylating reagents can react from one of the sides selectively (see discussion in Section 3.4.1). Stereogenic alkylations of such enolates therefore may take place diastereo selectively. 

The related 2-/-butyl derivative has also been prepared and used to advantage as a temporary protective group for the stereogenic center of amino acids during alkylations. ... 

The 2-alkyl derivatives have been prepared to protect the stereogenic center of the a-hydroxy acid during alkylations. ... 

With a-alkyl-substituted chiral carbonyl compounds bearing an alkoxy group in the -position, the diastereoselectivity of nucleophilic addition reactions is influenced not only by steric factors, which can be described by the models of Cram and Felkin (see Section 1.3.1.1.), but also by a possible coordination of the nucleophile counterion with the /J-oxygen atom. Thus, coordination of the metal cation with the carbonyl oxygen and the /J-alkoxy substituent leads to a chelated transition state 1 which implies attack of the nucleophile from the least hindered side, opposite to the pseudoequatorial substituent R1. Therefore, the anb-diastereomer 2 should be formed in excess. With respect to the stereogenic center in the a-position, the predominant formation of the anft-diastereomer means that anti-Cram selectivity has occurred. 

Allylmetal reagents which hear alkyl or aryl groups at both termini are stereogenic and usually add aldehydes w ith a high degree of reagent-induced stereoselectivity (Section D.3.3.1.5.1.). Some of these reagents have been prepared in enantiomerically enriched form and used in enantioselective synthesis. Table 4 collects some representative examples. 

The diastereofacial selectivity of Lewis acid promoted reactions of allylsilancs with chiral aldehydes has been thoroughly investigated58. Aldehydes with alkyl substituted a-stereogenic centers react with a mild preference for the formation of Cram products, this preference being enhanced by the use of boron trifluoride-diethyl ether complex as catalyst58. 

Useful Cram selectivity is observed for Lewis acid induced reactions between 3-alkoxyallylstan-nanes and aldehydes with alkyl substituted a-stereogenic centers116. 

While the chemistry of alkyl and allylic sulfoxide anions is similar to that of phosphine oxides, phosphinates and sulfone stabilized anions (Sections 1.5.2.2.1 -2), the situation is further complicated by the additional stereogenic center at sulfur. Therefore in all cases, asymmetric induction may arise from the stereocenter at sulfur. 

The alkylation of an enolate creates a new stereogenic center when the a-substituents are nonidentical. In enantioselective synthesis, it is necessary to control the direction of approach and thus the configuration of the new stereocenter. 

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