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Stereodivergent Synthesis of Arylcyclopropylamines by Sequential CH Borylation and Suzuki–Miyaura Coupling
Author(s) -
Miyamura Shin,
Araki Misaho,
Suzuki Takayoshi,
Yamaguchi Junichiro,
Itami Kenichiro
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201409186
Subject(s) - borylation , epimer , chemistry , iridium , catalysis , medicinal chemistry , stereochemistry , coupling (piping) , combinatorial chemistry , selectivity , organic chemistry , alkyl , materials science , aryl , metallurgy
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 CH borylation of N‐cyclopropylpivalamide proceeds with cis selectivity. The subsequent B‐cyclopropyl Suzuki–Miyaura coupling catalyzed by [PdCl 2 (dppf)]/Ag 2 O 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 O 2 . 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 (N 2 or O 2 ) in the coupling stage.