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Chiral γ‐Lactams by Enantioselective Palladium(0)‐Catalyzed Cyclopropane Functionalizations
Author(s) -
Pedroni Julia,
Cramer Nicolai
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201505916
Subject(s) - cyclopropane , cyclopropanation , enantioselective synthesis , palladium , aryl , chemistry , pyrrolidine , catalysis , ring (chemistry) , ligand (biochemistry) , combinatorial chemistry , stereochemistry , organic chemistry , receptor , biochemistry , alkyl
Cyclopropanes fused to pyrrolidines are important structural features found in a number of marketed drugs and development candidates. Typically, their synthesis involves the cyclopropanation of a dihydropyrrole precursor. Reported herein is a complementary approach which employs a palladium(0)‐catalyzed CH functionalization of an achiral cyclopropane to close the pyrrolidine ring in an enantioselective manner. In contrast to aryl–aryl couplings, palladium(0)‐catalyzed CH functionalizations involving the formation of C(sp 3 )C(sp 3 ) bonds of saturated heterocycles are very scarce. The presented strategy yields cyclopropane‐fused γ‐lactams from chloroacetamide substrates. A bulky Taddol phosphonite ligand in combination with adamantane‐1‐carboxylic acid as a cocatalyst provides the γ‐lactams in excellent yields and enantioselectivities.