Aldol reactions 2- Oxazolidones, chiral

Acyl-l,3-oxazolidine-2-thiones, chiral (1). Nagao and co-workers1 have prepared the chiral 3-acetyl-l,3-oxazolidine-2-thiones (la and lb) and used them to effect diastereoselective aldol reactions. The two chiral auxiliaries show, as expected, opposite diastereoselectivities, but contrast with the diastereoselectivities observed with chiral 4-alkyl-2-oxazolidones (11, 379-381). This aldol reaction has been used to prepare the chiral azetidinone 4 (equation I) and (-I- )-Prelog-Djerassi lactone. 

Independent work on asymmetric aldol reactions by Evans et al. led to the development of alternative chiral boron enolates that exhibit >100 1 facial selectivity. A pair of chiral N-acyl-2-oxazolidones (35)... 

Evans et al. utilized the chiral oxazolidones to prepare optically pure 3-hydroxy-a-amino acids, - important constituents of peptides and 3-lactams. As shown in Scheme 31, an asymmetric aldol reaction using the boron enolate derived from the V-(a-haloacyl)oxazolidone (68) provides the jyn-3-hydroxy-ot-halocarbonyl derivative (69), which is converted to the ann-3-hydroxy-a-azidocarbonyl derivative (70)... 

As for the characteristic controlling of stereochemistry during aldol reaction, the Evans aldol reaction has been extensively modified through the application of Lewis acids, chiral auxiliaries (e.g., oxazolidone, oxadiazinones, thiazolidinethione " ), chelating metals, etc. 

A "heterocyclic" strategy used an oxazolidone ring as a protected carboxyl (an amide) which also served as a chiral auxiliary. Treatment of 6.127 with a boron triflate, for example, gave boron enolate reagent 6.128 in situ, and it reacted with N-Boc leucinal to form 6.129. Boron enolates have been used in many syntheses as an alternative to lithium or sodium enolate in Aldol reactions.S7 Hydrogcnolysis of the methylthio moiety gave a methylene moiety and treatment of the amide auxiliary with base gave 6.95 (24% overall yield). 

Conventional asymmetric aldol reactions have been performed by using chiral enolates and achiral carbonyl compounds. A chiral boron enolate generated from a chiral oxazolidone derivative (26 and 28), dialkylboron tri-fiate, and diisopropylethylamine reacts stereoselectively with aldehydes to afford the corresponding syn aldol adducts (27 and 29) in good yields with excellent diastereoselectivity (Eqs. (8) and (9)) [12]. The opposite sense of asymmetric induction is achieved by changing the chiral auxiliary. Several other chiral auxiliaries have also been developed for highly diastereoselec-tive synthesis of syn aldol adducts (Eqs. (10)-(13)) [13]. 

ASYMMETRIC ALDOL REACTIONS USING THE OXAZOLIDONE CHIRAL AUXILIARY... 

The creation of chiral oxazolidones with a tetrasubstituted chiral centre has been attributed to memory of chirality by an axially chiral enolate intermediate of the aldol reaction involved (Scheme 16). " ... 

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

Oxazolidones as Chiral Auxiliaries Chiral Auxiliary-Mediated Aldol-Type Reactions... 

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