Multiple Absolute Stereocontrol in Cascade Lactone Formation via Dynamic Kinetic Resolution Driven by the Asymmetric Transfer Hydrogenation of Keto Acids with Oxo-Tethered Ruthenium Catalysts

Taichiro Touge; Kazuhiko Sakaguchi; Nao Tamaki; Hideki Nara; Tohru Yokozawa; Kazuhiko Matsumura; Yoshihito Kayaki

doi:10.1021/jacs.9b07297

Multiple Absolute Stereocontrol in Cascade Lactone Formation via Dynamic Kinetic Resolution Driven by the Asymmetric Transfer Hydrogenation of Keto Acids with Oxo-Tethered Ruthenium Catalysts

J Am Chem Soc. 2019 Oct 16;141(41):16354-16361. doi: 10.1021/jacs.9b07297. Epub 2019 Sep 24.

Authors

Taichiro Touge¹, Kazuhiko Sakaguchi¹, Nao Tamaki¹, Hideki Nara¹, Tohru Yokozawa¹, Kazuhiko Matsumura¹, Yoshihito Kayaki²

Affiliations

¹ Corporate Research & Development Division , Takasago International Corporation , 1-4-11 Nishi-yawata , Hiratsuka City , Kanagawa 254-0073 , Japan.
² Department of Chemical Science and Engineering, School of Materials and Chemical Technology , Tokyo Institute of Technology , O-okayama 2-12-1-E4-1 , Meguro-ku, Tokyo 152-8552 , Japan.

PMID: 31502833
DOI: 10.1021/jacs.9b07297

Abstract

A straightforward asymmetric construction of chiral fused γ- and δ-lactones containing multiple contiguous stereocenters was successfully developed by either (1) the dynamic kinetic resolution-asymmetric transfer hydrogenation (DKR-ATH) reaction using oxo-tethered Ru(II) complexes followed by syn-selective lactonization or (2) the tandem DKR-ATH/lactonization in combination with asymmetric hydrogenation catalyzed by Ru-chiral diphosphine complexes. The expedient protocol is applicable to the enantioselective synthesis of natural wine lactone and a biologically active benzo-fused lactone with an unprecedented level of diastereo- and enantioselectivity.

Publication types

Research Support, Non-U.S. Gov't