Synfacts 2015; 11(10): 1055
DOI: 10.1055/s-0035-1560306
Metal-Catalyzed Asymmetric Synthesis and Stereoselective Reactions
© Georg Thieme Verlag Stuttgart · New York

Chiral γ-Lactams by Enantioselective Cyclopropane Functionalization

Mark Lautens
Thomas Johnson
Pedroni J, Cramer N * École Polytechnique Fédérale de Lausanne, Switzerland
Chiral γ-Lactams by Enantioselective Palladium(0)-Catalyzed Cyclopropane Functionalizations.

Angew. Chem. Int. Ed. 2015;
DOI: 10.1002/anie.201505916.
Further Information

Publication History

Publication Date:
18 September 2015 (online)



Cyclopropanes are important components of many biologically active molecules and they can be found fused to a pyrrolidine ring in certain medicines. The authors present a new approach to this ring system using an enantioselective C–H functionalization of a cyclopropane, enabled by a Pd/TADDOL catalyst. This work constitutes a notable advance in the field of C(sp3)–C(sp3) bond formation by C–H activation.



The reaction shows good functional group tolerance and allows the synthesis of a library of diverse cyclopropane-fused pyrrolidines in high yield and with high enantioselectivity. The substrates can be accessed in a sequence by using a variant of the Kulinkovich reaction. The authors also demonstrate that the catalyst can efficiently activate methyl C–H groups in other substrates.