Kinetic Resolution of Tertiary Alcohols by Chiral DMAP Derivatives: Enantioselective Access to 3-Hydroxy-3-substituted 2-Oxindoles

Hiroki Mandai; Ryuhei Shiomoto; Kazuki Fujii; Koichi Mitsudo; Seiji Suga

doi:10.1021/acs.orglett.0c03956

Kinetic Resolution of Tertiary Alcohols by Chiral DMAP Derivatives: Enantioselective Access to 3-Hydroxy-3-substituted 2-Oxindoles

Org Lett. 2021 Feb 19;23(4):1169-1174. doi: 10.1021/acs.orglett.0c03956. Epub 2020 Dec 28.

Authors

Hiroki Mandai¹, Ryuhei Shiomoto², Kazuki Fujii², Koichi Mitsudo², Seiji Suga²

Affiliations

¹ Department of Pharmacy, Faculty of Pharmacy, Gifu University of Medical Science, 4-3-3 Nijigaoka, Kani, Gifu 509-0293, Japan.
² Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.

PMID: 33371678
DOI: 10.1021/acs.orglett.0c03956

Abstract

We developed an efficient acylative kinetic resolution of 3-hydroxy-3-substituted 2-oxindoles by a chiral DMAP derivative having a 1,1'-binaphthyl with two tert-alcohols units. A wide range of 3-hydroxy-3-substituted oxindoles having various functional groups were efficiently resolved (14 examples, up to s = 60) in the presence of 1 mol % of catalyst within 3-9 h. Multigram-scale reactions (10 g) also proceeded with a high s-factor (s = 43) within 5 h.