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D ‐Glucosamine in iron‐catalysed cross‐coupling reactions of Grignards with allylic and vinylic bromides: application to the synthesis of a key sitagliptin precursor
Author(s) -
Sova Matej,
Frlan Rok,
Gobec Stanislav,
Stavber Gaj,
Časar Zdenko
Publication year - 2015
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/aoc.3327
Subject(s) - chemistry , reagent , catalysis , allylic rearrangement , glucosamine , ligand (biochemistry) , coupling reaction , medicinal chemistry , organic synthesis , acceptor , organic chemistry , combinatorial chemistry , receptor , physics , condensed matter physics , biochemistry
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.