ASYMMETRIC NITROALKENE [4+2] CYCLOADDITIONS - ENANTIOSELECTIVE SYNTHESIS OF 3-SUBSTITUTED AND 3,4-DISUBSTITUTED PYRROLIDINES

2-Substituted 1-nitroalkenes undergo highly diastereoselective, Lewis-acid-promoted, [4 + 2] cycloaddition with chiral vinyl ethers derived from (R)-2,2-diphenylcyclopentanol and (1R,2S)-2-phenylcyclohexanol to afford cyclic nitronates in high yields. The resulting nitronates were reduced with hydrogen at 160 psi in the presence of platinum oxide to afford enantiomerically enriched pyrrolidines (both as the free base and N-protected derivatives) in good yields. A series of 3-substituted pyrrolidines (71-97% ee) were prepared, as well as (3S,4R)-4-methyl-3-phenyl-N-(p-tolylsulfonyl)pyrrolidine (92% ee) and (3S,4S)-3,4-diphenylpyrrolidine (99% ee). The chiral auxiliaries can be recovered in nearly quantitative yields after hydrogenation.