title: Stereodivergent synthesis of arylcyclopropylamines by sequential C-H borylation and Suzuki-Miyaura coupling.
abstract: A step-economical and stereodivergent synthesis of privileged 2-arylcyclopropylamines (ACPAs) through a C(sp(3))-H borylation and Suzuki-Miyaura coupling sequence has been developed. The iridium-catalyzed C-H 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.
authors.affiliation: Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602 (Japan).
authors.forename: Shin
authors.initials: S
authors.lastname: Miyamura
authors.forename: Misaho
authors.initials: M
authors.lastname: Araki
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Junichiro
authors.initials: J
authors.lastname: Yamaguchi
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Itami
mesh_terms: D001895:Boron / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D007495:Iridium / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: D003521:Cyclopropanes; D007495:Iridium; D002244:Carbon; D006859:Hydrogen; C067351:cyclopropylamine; D001895:Boron
keywords: CH activation; boron; cross-coupling; iridium; small ring systems