Organic Chemistry Laboratory, Nagoya University

Shin Miyamura, Misaho Araki, Takayoshi Suzuki, Junichiro Yamaguchi, and Kenichiro Itami

Angew. Chem. Int. Ed. 2014, Early view. DOI: 10.1002/anie.201409186

A step-economical and stereodivergent synthesis of privileged 2-arylcyclopropylamines (ACPAs) through a C(sp³)H borylation and Suzuki–Miyaura coupling sequence has been developed. The iridium-catalyzed CH borylation of N-cyclopropylpivalamide proceeds with cis selectivity. The subsequent B-cyclopropyl Suzuki–Miyaura coupling catalyzed by [PdCl₂(dppf)]/Ag₂O proceeds with retention of configuration at the carbon center bearing the Bpin group, while epimerization at the nitrogen-bound carbon atoms of both the starting materials and products is observed under the reaction conditions. This epimerization is, however, suppressed in the presence of O₂. The present new ACPA synthesis results in not only a significant reduction in the steps required for making ACPA derivatives, but also the ability to access either isomer (cis or trans) by simply changing the atmosphere (N₂ or O₂) in the coupling stage.