Synthesis of Chiral Nonracemic α-Difluoromethylthio Compounds with Tetrasubstituted Stereogenic Centers via a Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

Hiroya Kondo; Mayaka Maeno; Kenta Sasaki; Ming Guo; Masaru Hashimoto; Motoo Shiro; Norio Shibata

doi:10.1021/acs.orglett.8b02998

Synthesis of Chiral Nonracemic α-Difluoromethylthio Compounds with Tetrasubstituted Stereogenic Centers via a Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

Org Lett. 2018 Nov 16;20(22):7044-7048. doi: 10.1021/acs.orglett.8b02998. Epub 2018 Nov 8.

Authors

Hiroya Kondo¹, Mayaka Maeno¹, Kenta Sasaki¹, Ming Guo¹, Masaru Hashimoto², Motoo Shiro³, Norio Shibata^{1

4}

Affiliations

¹ Department of Nanopharmaceutical Sciences and Department of Life Science and Applied Chemistry , Nagoya Institute of Technology , Gokiso, Showa-ku, Nagoya 466-8555 , Japan.
² Faculty of Agriculture and Life Science , Hirosaki University , 3-Bunkyo-cho , Hirosaki 036-8561 , Japan.
³ Rigaku Corporation , 3-9-12, Matsubara-cho , Akishima-shi, Tokyo 196-8666 , Japan.
⁴ Institute of Advanced Fluorine-Containing Materials , Zhejiang Normal University , 688 Yingbin Avenue , 321004 Jinhua , China.

PMID: 30407832
DOI: 10.1021/acs.orglett.8b02998

Abstract

The synthesis of chiral, nonracemic difluoromethylthio (SCF₂H) compounds that contain a tetrasubstituted stereogenic center is reported. Racemic α-SCF₂H-β-ketoallylesters 5 were initially prepared by an electrophilic difluoromethylthiolation of β-ketoallylesters 6, followed by a Pd-catalyzed Tsuji decarboxylative asymmetric allylic alkylation (DAAA) to provide a wide variety of chiral, nonracemic α-allyl-α-SCF₂H-ketones (4) with high enantiopurity. This strategy can be extended to the enantioselective synthesis of chiral, nonracemic α-allyl-α-trifluoromethylthio(SCF₃)-ketones (7).

Publication types

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