A new route to chiral hydroxypyrrolidines from D-erythrose via intramolecular 1,3-cycloaddition

Abstract

2,3-O-Isopropylidene-D-erythrose (1) reacted with ethoxycarbonylmethylene(triphenyl)phosphorane in refluxing benzene to give the E and Z alkene esters (2a) and (2b). The ester (2a) was converted, via the 6-triflate (7a) and 6-azide (3a), into the dihydrotriazole (8) by 1,3-cycloaddition. Ring opening of compound (8) with sodium ethoxide gave the pyrrolidine diazo ester (9) which on hydrogenolysis gave (2R,3S,4R)-ethyl (3,4-isopropylidenedioxypyrrolidin-2-yl)acetate (5). A similar series of reactions from the Z-ester (2b) gave the pyrrolidine ester (6), the 2S-isomer of (5). Thermolysis of the diazo ester (10), the 2S-isomer of (9), gave(Z)-(3S,4R)-ethyl (3,4-isopropylidenedioxypyrrolidin-2-ylidene) acetate (12) which was reduced with sodium cyanoborohydride to give the ester (5). The esters (2a) and (2b) undergo rapid and quantitative cyclisation in the presence of ethoxide ion. Kinetically the β-isomer (18) is preferred [100% from (2b), 86% from (2a)]; at equilibrium the α-isomer (19) is favoured (82%).