N-sulfinyl oxazolidinones

Evans and Colombo35 are developing a different route to enantiomerically pure sulfoxides involving intermediate N-sulfinyl oxazolidinones 5. Reaction of these dia-stereomerically pure species with organometallic reagents gives enantiomerically pure sulfoxides, as illustrated by equation 5 carried out on a multigram scale. 

Moreover, N-sulfinyl oxazolidinones have been shown to be good intermediates for the synthesis of chiral sulfinate esters and sulfinamides with excellent ee. In all cases, the absolute configuration of the sulfoxide obtained is in agreement with the fact that nucleophilic displacement occurs with inversion of configuration at the sulfur center in the starting /V-sulfinyl oxazolidinone. 

In a competition experiment between chiral N-sulfinyl oxazolidinone and Andersen s menthyl sulfinate ester, it has been shown that the former is at least two orders of magnitude more reactive than the latter. This finding is being used to avoid some of the problems involved in sulfinate esters, related to the nature of the alkoxide leaving group in the nucleophilic substitution. 

In a broad program of using chiral oxazolidinones in asymmetric synthesis,100 Evans s group published a paper in 1992 on the synthesis and utilization of fV-sulfinyl oxazolidinones as new sulfinylating agent.87 Two chiral auxiliaries were used in the study oxazolidinones derived from (4R, 5S)-norephedrine 74101 and (45)-phenylalanine 75.102 The corresponding fV-sulfinyl oxazolidinones 77 and 78 were obtained either by sulfmylation of the metallated oxazolidinone or by oxidation of the derived N-sulfenamides (Table 15). 

In the oxidation of the N-sulfenamides 79, the w-chloroperbenzoic acid proved to be the best oxidant, yielding the /V-sulfinyl oxazolidinones 78b-d in good yields (72-96%) as 1.4-2.5 1.0 mixtures of diastereoisomers, which were readily purified by chromatography (Scheme 23). 

Recently, Oppolzer s group reported on the synthesis and use of a new sulfinylating agent,107 the /V-sulfinyl sultam 82, as part of a broad program on the use of the versatile bornane-10,2-sultam 81 in asymmetric synthesis.108 The condensation of p-TolSOCI with 81 in THF, using dimethylaminopyridine (DMAP) as catalyst, gave the /V-(p-tolylsulfinyl)bornane- 10,2-sultam as a 6.2 1 diastereomeric mixture. Crystallization of the mixture from E O/hexane afforded pure 82 in 77% yield. X-ray analysis showed the absolute configuration at the sulfinyl sulfur to be (/ ). The reaction has been shown to be kinetically controlled, in contrast to the results obtained when n-BuLi was used instead of DMAR In the latter case, the reaction was under thermodynamic control, in accord with the result obtained by Evans with iV-sulfinyl oxazolidinone (Scheme 25). 

These N-sulfinyloxazolidinone reagents can be synthesized either by sulfinylation of the metallated oxazolidinone or by sulfoxidation of the N-sulfenimide. The crystalline reagents (15) and (16) are readily purified from their respective minor epimers to high diastereoisomeric purity by chromatography and their reactivity toward nucleophiles is reported to be —100 times greater than that of menthyl sulfinate esters. 

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