Darzens glycidic ester condensation asymmetric

A. Schwartz et al. synthesized several calcium channel blockers of the diltiazem group enantioselectively by using an auxiliary-induced asymmetric Darzens gtycidic ester condensation. The condensation of p-anisaldehyde with an enantiopure a-chloro ester afforded a pair of diastereomeric glycidic esters that possessed significantly different solubility. The major product was crystallized directly from the reaction mixture in 54% yield and in essentially enantiopure form. This major glycidic ester was then converted to diltiazem in a few more steps. 

Early work on the asymmetric Darzens reaction involved the condensation of aromatic aldehydes with phenacyl halides in the presence of a catalytic amount of bovine serum albumin. The reaction gave the corresponding epoxyketone with up to 62% ee.67 Ohkata et al.68 reported the asymmetric Darzens reaction of symmetric and dissymmetric ketones with (-)-8-phenylmenthyl a-chloroacetate as examples of a reagent-controlled asymmetric reaction (Scheme 8-29). When this (-)-8-phenyl menthol derivative was employed as a chiral auxiliary, Darzens reactions of acetone, pentan-3-one, cyclopentanone, cyclohexanone, or benzophenone with 86 in the presence of t-BuOK provided dia-stereomers of (2J ,3J )-glycidic ester 87 with diastereoselectivity ranging from 77% to 96%. 

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