Enantio‐ and Diastereoselective Aldol‐Reaction of 2,6‐Dimethylphenyl Propionate Using Titanium‐Carbohydrate Complexes

Abstract

Abstract Chloro(cyclopentadienyl)bis(1,2:5,6‐di‐ O ‐isopropylidene‐α‐ D ‐glucofuranos‐3‐ O ‐yl)titanium ( 1 ) is used for the transmetallation of Li‐enolates obtained from propionyl derivatives. While such Ti‐enolates of ketones and hydrazones appear to be unreactive, the ( E )enolate 13 of 2,6‐dimethylphenyl propionate ( 11 ) adds to the re ‐side of aldehydes, affording various syn ‐aldols 14 with high dia‐ and enantioselectivity (92–97% ds, 91–97% ee, cf . Scheme 2 and Table 1 ). Racemic syn ‐aldols (±)‐ 14 are obtained analogously from the achiral bis(2‐propyloxy)‐Ti‐enolate 15 ( Scheme 2 and Table 2 ). In contrast to the unstable Li‐enolate 10 , the Ti‐enolates 13 and 15 isomerize at −30°, presumably to the thermodynamically more stable ( Z )‐enolates ( Scheme 4 ), While the diastereoselectivity of the achiral enolate 15 is lost upon this equilibration, the chiral ( Z )‐enolate 27 quite unexpectedly affords anti ‐aldols 12 of high optical purity (94–98% ec) and, in most cases, with acceptable‐to‐good diastereoselectivity (82–90% ds). Notable exceptions are branched unsaturated and aromatic aldehydes which form a greater proportion of synepimers of moderate optical purity ( Scheme 5 and Table 3). Consistent with these findings, re‐facial‐and ami ‐selective aldol‐addition is also exhibited by the ( Z )‐configurated Ti‐enolate 22 of N ‐propionyl‐oxazolidi‐none 19 ( Scheme 3 ).