Chiral auxiliary oxazolidone derivative

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. 

The chiral A/ -propionyl-2-oxazolidones (32 and 38) are also useful chiral auxiliaries in the enantioselective a-alkylation of carbonyl compounds, and it is interesting to observe that the sense of chirality transfer in the lithium enolate alkylation is opposite to that observed in the aldol condensation with boron enolates. Thus, whereas the lithium enolate of 37 (see Scheme 9.13) reacts with benzyl bromide to give predominantly the (2/ )-isomer 43a (ratio 43a 43b = 99.2 0.8), the dibutylboron enolate reacts with benzaldehyde to give the (3R, 25) aldol 44a (ratio 44a 44b = 99.7 0.3). The resultant (2R) and (25)-3-phenylpropionic acid derivatives obtained from the hydrolysis of the corresponding oxazolidinones indicated the compounds to be optically pure substances. 

Oxazolidones, chiral, (1) and (2). Evans et al. have prepared these two chiral 2-oxazolidones by reaction of phosgene with (S)-valinol and (IS, 2R)-norephedrine, respectively, and used them as recyclable chiral auxiliaries for carboxylic acids in cnantioselective reactions of the derived imides. 

They also reported the intramolecular version of this asymmetric Diels-Alder reaction [53]. ( , )-Trienecarboximides of type 45 derived from chiral oxazolidones undergo Me2AlCl-catalyzed intramolecular Diels-Alder reactions affording bicyclic compounds 46 with high endo and diastereoselectivity (endolexo = -100 1). The stereochemistry is controlled by the stereogenic center at C4 of the chiral auxiliary (Xc) (Sch. 29). 

In order to overcome the problems associated with acid hydrolysis of amides of prolinol, the Evans research group has investigated the diastereoselectivity of the alkylation of imides derived from chiral 2-oxazolidones. Imide enolates are somewhat less nucleophilic than amide enolates, but they have the advantage that their diastereomeric alkylation products are easily separated and the imide linkage is cleaved with a variety of reagents under mild conditions. As shown in Scheme 64, alkylation of the chelated (Z)-enolate of the propionimide derived from (S)-valinol (135) with benzyl bromide occurred in high chemical yield and with high si-face diastereoselectivity. In addition to oxazolidones, imidazoli-diones have proved to be useful chiral auxiliaries for diastereoselective enolate alkylations. ... 

Substituted 2-oxazolidones 165 are useful chiral auxiliaries for diastereoselective functionalization at the a-carbon of their amide carbonyl group. The a-fluoroaldehydes 166 were prepared by a series of reactions electrophilic fluorination of the corresponding oxazolidinone sodium enolates with AMluorobenzenesulfonimine reductive removal of the auxiliary with LiBH4 and Dess-Martin oxidation. The aldehydes are so unstable for isolation that they are converted with (R)-/ -toluenesulfinamide to /7-toluenesul(inimines 167, which are isol-able and satisfactorily enantio-enriched. Chiral sulfinimine-mediated diastereoselective Strecker cyanation with aluminum cyanide provided cyanides 168 in excellent diastereose-lectivity, which were finally derived to 3-fluoroamino acids 169 (see Scheme 9.37) [63]. 

Asymmetric halogenation of carboxylic acid derivatives has also been achieved by D.A. Evans (refs. 11,12) via chiral N-acyl oxazolidones. For instance, an N-acyl oxazolidone prepared by acylation of the (4S)-benzyl-2-oxazolidone chiral auxiliary derived from (S)-phenylalanine, is converted to its (Z)-dibutyl boron enolate, which is added to a NBS slurry, at low temperature (Fig. 6) ... 

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]. 

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