A Stereoselective Access to Dihydroxylated Pyrrolidines by Reductive Ring Contraction of 1,2-Oxazines

Abstract

Protected dihydroxylated 1,2-oxazine derivatives such as RAC- 4 were converted into tetrahydro-1,2-oxazines RAC- 7 by employing BH 3 ·THF for the stereoselective reduction of the C=N bond. Compound 7A underwent a reductive ring contraction on hydrogenation in the presence of palladium on charcoal to provide RAC- 5 in good yield. Enantiopure 1,2-oxazine derivatives 13 and 14 were prepared using (-)-menthol as chiral auxiliary. Their diastereo-selective dihydroxylation and BH 3 ·THF reduction furnished enantiopure tetrahydro-2 H-1,2-oxazine derivatives 17 and 18 in good overall yield. Enantiomers (6 R)- 18 and (6 S)- 18 were transformed into the two enantiomeric hydroxylated pyrrolidine derivatives 5 in moderate yield.