Copper-catalyzed asymmetric hydrogenation of 2-substituted ketones via dynamic kinetic resolution

Olga V. Zatolochnaya; Sonia Rodríguez; Yongda Zhang; Kendricks S. Lao; Sergei Tcyrulnikov; Guisheng Li; Xiao-Jun Wang; Bo Qu; Soumik Biswas; Hari P. R. Mangunuru; Daniel Rivalti; Joshua D. Sieber; Jean-Nicolas Desrosiers; Joyce C. Leung; Nelu Grinberg; Heewon Lee; Nizar Haddad; Nathan K. Yee; Jinhua J. Song; Marisa C. Kozlowski; Chris H. Senanayake

doi:10.1039/C8SC00434J

Copper-catalyzed asymmetric hydrogenation of 2-substituted ketones via dynamic kinetic resolution†

Olga V. Zatolochnaya,

^a Sonia Rodríguez,*^a Yongda Zhang,

*^a Kendricks S. Lao,^a Sergei Tcyrulnikov,^b Guisheng Li,^a Xiao-Jun Wang,^a Bo Qu,

^a Soumik Biswas,^a Hari P. R. Mangunuru,

^a Daniel Rivalti,^a Joshua D. Sieber,

^a Jean-Nicolas Desrosiers,^a Joyce C. Leung,^a Nelu Grinberg,^a Heewon Lee,^a Nizar Haddad,^a Nathan K. Yee,^a Jinhua J. Song,^a Marisa C. Kozlowski*^b and Chris H. Senanayake^a

Author affiliations

* Corresponding authors

^a Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Old Ridgebury Road, Ridgefield, CT 06877, USA
E-mail: yongda.zhang@boehringer-ingelheim.com, sonrodrod@hotmail.com

^b Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA
E-mail: marisa@sas.upenn.edu

Abstract

A new class of tunable heterophosphole dimeric ligands have been designed and synthesized. These ligands have enabled the first examples of Cu-catalyzed hydrogenation of 2-substituted-1-tetralones and related heteroaryl ketones via dynamic kinetic resolution, simultaneously creating two contiguous stereogenic centers with up to >99 : 1 dr and 98 : 2 er. The ligand-Cu complexes were isolated and characterized by single crystal X-ray, and DFT calculations revealed a novel heteroligated dimeric copper hydride transition state.

This article is part of the themed collection: Most popular 2018-2019 main group, inorganic and organometallic chemistry articles

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Copper-catalyzed asymmetric hydrogenation of 2-substituted ketones via dynamic kinetic resolution†

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Copper-catalyzed asymmetric hydrogenation of 2-substituted ketones via dynamic kinetic resolution

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