STEREOSELECTIVE REACTION OF AN ENOLATE WITH CHIRAL ALPHA-HALO BORONIC ACID-ESTERS

Reaction of tert-butyl trans-lithiopropionate (6) with (S,S)-diisopropylethanediol (“DIPED”) (1R)-(1-bromopentyl)boronate (9a) yielded semipurified tert-butyl (2S,3S)-3-hydroxy-2-methylheptanoate (11a) (“three”) in a 60:1 ratio to the “erythro” diastereomer. Other threo/erythro ratios included DIPED (1R)-(1-bromo-2-methylpropyl)boronate (9b) to crude 11b, 15:1, DIPED (α-bromobenzyl)boronate (9c) to crude 11c, 8:1; (3S,4S)-2,5-dimethoxy-2,5-dimethyl-3,4-hexanediol (1R)-(1-bromo-pentyl)boronate (9d) to semipurified 11a, 10:1; and pinacol (1-bromopentyl)boronate (5) via 7 to semipurified racemic 11a, >100:1. These reactions are sluggish, and α-bromo boronic acid esters generally give better yields than the corresponding chloro compounds. Less hindered ester enolates appear to undergo Claisen condensation under the reaction conditions, and only the tert-butyl ester proved useful. An efficient synthesis of (3S,4S)-2,5-dimethoxy-2,5-dimethyl-3,4-hexanediol (16) and its use as a chiral director for chain extension of boronic acid esters are described. © 1990, American Chemical Society. All rights reserved.