Dynamic Kinetic Resolution Approach for the Asymmetric Synthesis of Tetrahydrobenzodiazepines Using Transfer Hydrogenation by Chiral Phosphoric Acid

Kosaku Horiguchi; Eri Yamamoto; Kodai Saito; Masahiro Yamanaka; Takahiko Akiyama

doi:10.1002/chem.201601611

Dynamic Kinetic Resolution Approach for the Asymmetric Synthesis of Tetrahydrobenzodiazepines Using Transfer Hydrogenation by Chiral Phosphoric Acid

Chemistry. 2016 Jun 6;22(24):8078-83. doi: 10.1002/chem.201601611. Epub 2016 May 6.

Authors

Kosaku Horiguchi¹, Eri Yamamoto², Kodai Saito^{1

3}, Masahiro Yamanaka², Takahiko Akiyama⁴

Affiliations

¹ Department of Chemistry, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo, 171-8588, Japan.
² Department of Chemistry, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo, 171-8501, Japan.
³ Department of Chemistry, Keio University, Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan.
⁴ Department of Chemistry, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo, 171-8588, Japan. takahiko.akiyama@gakushuin.ac.jp.

PMID: 27150449
DOI: 10.1002/chem.201601611

Abstract

Asymmetric synthesis of tetrahydrobenzodiazepines was achieved by transfer hydrogenation of dihydrobenzodiazepines with benzothiazoline having a hydrogen-bonding donor substituent by means of a newly synthesized chiral phosphoric acid. This method was applicable to various racemic dihydrobenzodiazepines to give the corresponding products in good yields with excellent diastereoselectivities and enantioselectivities taking advantage of the dynamic kinetic resolution. Furthermore, the effect of bulky substituent at 3,3'-position on the catalyst and hydrogen-bonding donor substituent on benzothiazoline was fully elucidated by the theoretical study.

Keywords: dynamic kinetic resolution; heterocycles; hydrogenation; organocatalysis; stereoselective synthesis.

Publication types

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