The first enantioselective synthesis of (S)-5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine: a key intermediate for the preparation of SIB-1508Y

The first enantioselective synthesis of (S)-5-bromo-3-(1-methyl-2-pyrrodidi nyl)pyridine is described via intramolecular hydroboration-cycloalkylation of an azido-olefin intermediate. The chiral homoallylic alcohol was efficie ntly synthesized by enantioselective reduction of the corresponding ketone using (+)-diisopinocamphenylchloroborane as the key reaction. The total syn thesis of (S)-SIB-1508Y was achieved with an enantiomeric excess (e.e.) of 94% in ten steps and in 18% overall yield from the commercially available 5 -bromo-3-pyridinecarboxylic acid. (C) 2001 Elsevier Science Ltd. Ali rights reserved.