Metallations and Reactions with Electrophiles of 4-Isopropyl-5,5-diphenyloxazolidin-2-one (DIOZ) with N-Allyl and N-Propargyl Substituents: Chiral Homoenolate Reagents

Abstract

N-Allyl, N-cinnamyl, and N-(3-trimethylsilyl)propargyl derivatives of 4-isopropyl-5,5-diphenyloxazolidin-2-one (DIOZ) are prepared by lithiation of the parent DIOZ (with BuLi in THF) and reaction with the corresponding bromides (Scheme 1). Lithiation in the same solvent, with deprotonation by BuLi on the allylic or propargylic CH2 group at dry-ice temperature, provides colorful solutions, which are either combined with aldehydes or ketones directly or after addition (with or without warming) of (Me2N)3TiCl or (i-PrO)3TiCl. Conditions have thus been elaborated under which all three types of conjugated lithium compounds react in the γ-position with respect to the oxazolidinone N-atom: carbamoyl derivatives of enamines and allenyl amines are formed in yields ranging from 60 to 80% and with diastereoselectivities up to 98% (Schemes 2–5). The C=C bond of the N-hydroxyalkenyl groups has (Z)-configuration (products 5 and 8), the allene chirality axis has (M)-configuration (products 9), and the addition to aldehydes and unsymmetrical ketones has taken place preferentially from the Si face. A mechanistic model is proposed that is compatible with the stereochemical outcome (assuming kinetic control and disregarding the presence of Li and Ti species in the reaction mixture; cf. L, M in Fig. 4). Hydrolysis of the enamine derivatives leads to lactols, oxidizable to γ-lactones, with recovery of the crystalline oxazolidinone, as demonstrated in three cases (Scheme 6). Thus, the application of chiral oxazolidinone auxiliaries (cf. Figs. 1 and 2) has been extended to the overall enantioselective preparation of homoaldols.