D ‐Glucosamine in iron‐catalysed cross‐coupling reactions of Grignards with allylic and vinylic bromides: application to the synthesis of a key sitagliptin precursor

A sustainable D ‐glucosamine ligand is successfully introduced into iron‐catalysed C C cross‐coupling reactions for the first time. The Fe(acac) 2 / D ‐glucosamine·HCl/Et 3 N catalytic system was effective at 5 mol% loading in coupling reactions of Grignard reagents with organic bromides. Moderate to high efficiency was achieved with preserved stereochemistry when allyl (Csp 3 ) or alkenyl (Csp 2 ) bromides were coupled with phenylmagnesium (Csp 2 ) or benzylmagnesium (Csp 3 ) bromides. The catalytic system developed was also successfully applied for the novel and economic preparation of a Michael‐acceptor‐like starting material used in an alternative synthesis of the drug sitagliptin, a known blockbuster for the treatment of type II diabetes mellitus. Copyright © 2015 John Wiley & Sons, Ltd.