Synthesis of geminal bis(hydroxymethyl)pyrrolidine and pyrrolizidine imino sugars

Abstract

Reductive alkylation of N-Boc-pyrrolecarboxylate methyl ester 1 under Birch conditions with iodomethyl pivalate and subsequent reduction of the ester moieties provided the symmetric diol 3, a flexible building block for the synthesis of geminally disubstituted pyrrolidine imino sugars. This key intermediate was used for the first known synthesis of a 2,2-bis(hydroxymethyl)pyrrolidine imino sugar. In a similar manner a pyrrolizidine imino sugar was synthesised by oxidation of the deprotected pyrrolidine to the nitrone 10, which was subjected to a highly diastereoselective 1,3-dipolar cycloaddition with an allylic alcohol. Reductive cleavage of the N–O bond and recyclisation yielded the polyhydroxylated pyrrolizidine 13.