Tmuhedmn Vol. SO, No. 44, pp. 127SS-32772. 1994 Copyright 8 1994 Elsevicr Science Ltd Printedin GreatBritain.AU rightsreserved 004ww4 $7.oo+o.00 zyxwvutsr Addition to Activated Imines of Enolates from C hiral iV= Acyloxazolidinones Isaac Abrahams, Majid Motevalli, Andrew J. Robinson and Peter B. Wyatt* DeFamnent of Chemistry. Queen Mary and Westfield College, University of London, Mile End Road, London El 4NS, UK Abstractz The lithium and titanium enolates of N-acyloxazotidinones la-c add in their chelated forms to PhCH=NTs, to give stereoselectively the B-amino acid derivatives 3a-c and 4a-c. The relative configurations of the newly created chiral centres were established by conversion to the !rans (8p-c) or cis (9a. c) fi-lactams. Absolute stereochemistry was assigned by correlation with known compounds 108 and ent-lla, together with an X-ray crystal structure determination on 9a. The use of the lithium enolate of la at -78 ‘C gave only a 1.4~ 1 ratio of anri product 3a to syti product 4a, but this ratio was improved to >5:1 by the use of the chlorotitanium enolate of la at -55 ‘C or below. Similar results were obtained by using the chlorotitanium enolate of lb, but for the chlorotitanium enolate of the N- @henylacetyl)oxazolidinone lc the pqortion of syn product 4c to anri product was significantly greater, consistent with a kinetically controlled reaction involving the si face of the chelated (Z)-enolate and the competing alternative transition states TS3 (reaction on si Ike. of imine) and T!%7 (reaction on re face of imine). Introduction The enantioselective synthesis of P-amino acids and p-lactams is important because these units occur in many antibiotics and alkaloids.1 The main synthetic strategies that have been adopted are: (i) addition of enolate equivalents to imines? (ii) [2+2] cycloadditions of ketenes with imines (Staudinger reaction)3 and (iii) conjugate additions of amines or their metal Sal&8 to a&unsaturated carbonyl compounds. There have been several reports of the use in strategy (i) of enolates bearing a chiral auxiliary.9v1° Evans, in discussing the reactions of chiral enolates with 2-phenylsulfonyl-3_phenyloxaziridine, has written in a footnote that sodium and lithium enolates from N-acyloxazolidinones reacted quantitatively with N- (benzylidene)benzenesulfonamide to give aldol-type adducts. l1 We are unaware of any discussion of the stereochemical outcome of this particular reaction, even though the corresponding additions of such enolates to aldehydes have attracted considerable interest.12-16 Recently Boger and Honda17 described studies involving the addition of tin (II), boron and titanium (IV) enolates of N-acyloxazolidinones to pyridiie-2- carboxaldimines. They found that only the tin enolates gave good yields and that the product distribution was consistent with a preference for reaction vio a transition state wherein the pyridine nitrogen, but not the oxazolidinone carbonyl group, co-ordinated to the metal atom: i.e. the ‘nonchelated’ transition state was the favoured one. Here we describe our studies of the reactions between lithium and titanium enolates of N- acyloxazolidinones and activated benzaldimines: the enolates were found to react in chelated form and to show selectivity between the syn and anri products, 12755