Entropy-controlled selectivity in the vinylation of a cyclic chiral nitrone. An efficient route to enantiopure polyhydroxylated pyrrolidines

A short synthesis of 1,4-dideoxy-1,4-imino-L-arabinitol (LAB1) (4) and of 1 ,4-dideoxy-1,4-imino-D-galactitol (5, two azasugars active as enzymatic inh ibitors, is reported. The key reaction is the addition of vinylmagnesium ch loride to (3S,4S)-3,4-bis(benzyloxy)-3,4-dihydro-2H-pyrrole 1-oxide (3), a nitrone easily available from L-tartaric acid. Unexpectedly, the reaction a ffords the corresponding (2S,3S,4S)-1-hydroxy-2-ethenyl-3,4-bis(benzyloxy)p yrrolidine (9) in very good yield and in 93/7 diastereomeric ratio (dr) ind ependently of the reaction temperature, thus representing a unique case of entropy-controlled reaction in a 100 K interval (from +20 degreesC to -80 d egreesC). The trans intermediate 9 is converted in two steps (reduction, N- protection) into the common intermediate (2S,3S,4S)-1-(benzyloxycarbonyl)-3 ,4-bis(benzyloxy)-2-ethenylpyrrolidine (11). Double bond oxidation followed by reductive debenzylation opens a route to the target pyrrolidine azasuga rs 4 and 5.