D‐Glucosamine in iron‐catalysed cross‐coupling reactions of Grignards with allylic and vinylic bromides: application to the synthesis of a key sitagliptin precursor |
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| Authors: | Matej Sova Rok Frlan Stanislav Gobec Gaj Stavber Zdenko ?asar |
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| Institution: | 1. Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia;2. Lek Pharmaceuticals d.d., Sandoz Development Center Slovenia, API Development, Organic Synthesis Department, Menge?, Slovenia;3. Sandoz GmbH, Global Portfolio Management API, Kundl, Austria |
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| Abstract: | 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/Et3N 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 (Csp3) or alkenyl (Csp2) bromides were coupled with phenylmagnesium (Csp2) or benzylmagnesium (Csp3) 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. |
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| Keywords: | cross‐coupling iron glucosamine Grignard reagent catalysis |
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