Highly Diastereoselective Alkylation of 1-Benzoyl-2-alkyl-3-(1-methylbenzyl)imidazolidin-4-ones

The synthetic utility of 2-alkyl-substituted 1,3-imidazolidinones for the enantioselective preparation of α-amino acids is now well documented in the literature. Incorporation of a N(3)-phenethyl group in these heterocycles leads to substantial enhancements in the diastereoselectivity of alkylation of the corresponding lithium enolates, so that stereoselectivities in the order of 19:1 to 49:1 are observed for 2-isopropyl and 2-tert-butyl derivatives, respectively. X-ray crystallographic analysis on five N(3)-phenethyl-substituted imidazolidinones provided evidence that the long-distance effect of that chiral moiety is the result of conformational changes provoked by steric interactions between the 2-alkyl and the N(3)-phenethyl groups. No additivity of the stereodirecting effects by the stereogenic centers at C(2) and C(1′) was noticed. Thus, as it could have been anticipated from basic principles, intramolecular combinations of stereogenic centers do not necessarily lead to “matched” and “mismatched” joint stereoinducing effects.