Chiral γ-Lactams by Enantioselective Palladium(0)-Catalyzed Cyclopropane Functionalizations.
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 C-H functionalization of an achiral cyclopropane to close the pyrrolidine ring in an enantioselective manner. In contrast to aryl-aryl couplings, palladium(0)-catalyzed C-H 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.
Laboratory of Asymmetric Catalysis and Synthesis, EPFL SB ISIC LCSA, BCH 4305, 1015 Lausanne (Switzerland) http://isic.epfl.ch/lcsa.
Julia
J
Pedroni
Laboratory of Asymmetric Catalysis and Synthesis, EPFL SB ISIC LCSA, BCH 4305, 1015 Lausanne (Switzerland) http://isic.epfl.ch/lcsa. nicolai.cramer@epfl.ch.
Nicolai
N
Cramer
CH activation; asymmetric catalysis; lactams; palladium; small-ring compounds