Precision Deuteration Using Cu-Catalyzed Transfer Hydrodeuteration to Access Small Molecules Deuterated at the Benzylic Position

Samantha E Sloane; Zoua Pa Vang; Genevieve Nelson; Lihan Qi; Reilly E Sonstrom; Isabella Y Alansari; Kiera T Behlow; Brooks H Pate; Sharon R Neufeldt; Joseph R Clark

doi:10.1021/jacsau.3c00053

Precision Deuteration Using Cu-Catalyzed Transfer Hydrodeuteration to Access Small Molecules Deuterated at the Benzylic Position

JACS Au. 2023 May 17;3(6):1583-1589. doi: 10.1021/jacsau.3c00053. eCollection 2023 Jun 26.

Affiliations

¹ Department of Chemistry, Marquette University, Milwaukee, Wisconsin 53233-1881, United States.
² Department of Chemistry & Biochemistry, Montana State University, Bozeman, Montana 59717, United States.
³ BrightSpec Inc., Charlottesville, Virginia 22903, United States.
⁴ Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904-4319, United States.

Abstract

A highly regio- and chemoselective Cu-catalyzed aryl alkyne transfer hydrodeuteration to access a diverse scope of aryl alkanes precisely deuterated at the benzylic position is described. The reaction benefits from a high degree of regiocontrol in the alkyne hydrocupration step, leading to the highest selectivities reported to date for an alkyne transfer hydrodeuteration reaction. Only trace isotopic impurities are formed under this protocol, and analysis of an isolated product by molecular rotational resonance spectroscopy confirms that high isotopic purity products can be generated from readily accessible aryl alkyne substrates.