Cu‐Catalyzed Coupling of Aliphatic Amines with Alkylboronic Esters

Abstract

We report a Cu‐catalyzed oxidative coupling of aliphatic amines with benzylic and aliphatic boronic esters to give high value alkyl amines, products found widely in applications from medicinal chemistry to materials science. This operationally simple reaction, which can be performed on gram scale, runs under mild conditions and exhibits broad functional group tolerance. The terminal oxidant of the reaction is O2 from the air, avoiding the need for additional chemical oxidants. Investigation into the reaction mechanism suggests that the boronic ester is activated by an aminyl radical, formed through oxidation of the amine by the Cu catalyst, to give a key alkyl radical intermediate. To demonstrate its utility and potential for late‐stage functionalization, we showcase the method as the final step in the total synthesis of a TRPV1 antagonist.

Pd-Catalyzed Hydroboration of Vinylarenes with B2pin2

“…Specifically, compound 2w and 2v were efficiently converted into alcohol 3 and 4 under mild oxidative conditions, achieving 90% and 88% yields, respectively. Moreover, the C–B bond in 2o and 2s could be transformed into C–C bond and C–N bonds to 5 and 6 , respectively, through Pd-catalyzed Suzuki coupling with 4-iodotoluene and Cu-catalyzed Chan-Lan coupling with morpholine. Additionally, boronic acid ester 2r could be successfully converted to alkyl olefin in the presence of Grignard reagents after treatment with iodine …”