ASYMMETRIC-SYNTHESIS OF 1-ACYL-3,4-DISUBSTITUTED PYRROLIDINE-2-BORONIC ACID-DERIVATIVES

An analogue of N-acetylkainic acid having a cyano group and a boronic acid group in place of the two carboxyl groups has been synthesized wi th high stereocontrol via a series of chain extensions of pinanediol [ (trityloxy)methyl]boronate with (dihalomethyl)lithium followed by appr opriate nucleophilic substitution of the resulting chloro or bromo bor onic ester. Substituents were introduced in the order isopropenyl, cya nomethyl, and bis(trimethylsilyl)amino. The last of these was converte d to acetamido, the hydroxyl function was unmasked and mesylated, and the pyrrolidine ring was closed. Attempts to carry out further chain e xtension on the boronic ester resulted in low yields, evidently the hi ghly polar amido substituent interferes with the (dichloromethyl)lithi um insertion process. (C) 1998 Elsevier Science Ltd. All rights reserv ed.