215. On the Mechanism and Selectivity of the Combined C−H Activation/Cope Rearrangement

Authors: Jørn H. Hansen, Timothy M. Gregg, Stephanie R. Ovalles, Yajing Lian, Jochen Autschbach, and Huw M. L. Davies

J. Am. Chem. Soc.,

2011, 133 (13), 5076–5085


The combined C−H activation/Cope rearrangement (CHCR) is an effective C−H functionalization process that has been used for the asymmetric synthesis of natural products and pharmaceutical building blocks. Up until now, a detailed understanding of this process was lacking. Herein, we describe a combination of theoretical and experimental studies that have resulted in a coherent description of the likely mechanism of the reaction. Density functional studies on the reactions of rhodium vinylcarbenoids at allylic C−H sites demonstrate that the CHCR proceeds through a concerted, but highly asynchronous, hydride-transfer/C−C bond-forming event. Even though most of the previously known examples of this process are highly diastereoselective, the calculations demonstrate that other transition-states and stereochemical outcomes might be possible by appropriate modifications of the reagents, and this was confirmed experimentally. The calculations also indicate that there is a potential energy surface bifurcation between CHCR and the competing direct C−H insertion.

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