Chemistry of Tertiary Carbon Center in the Formation of Congested C-O Ether Bonds

Goki Hirata; Kentarou Takeuchi; Yusuke Shimoharai; Michinori Sumimoto; Hazuki Kaizawa; Toshiki Nokami; Takashi Koike; Manabu Abe; Eiji Shirakawa; Takashi Nishikata

doi:10.1002/anie.202010697

Chemistry of Tertiary Carbon Center in the Formation of Congested C-O Ether Bonds

Angew Chem Int Ed Engl. 2021 Feb 19;60(8):4329-4334. doi: 10.1002/anie.202010697. Epub 2020 Dec 22.

Authors

Affiliations

¹ Graduate School of Science and Engineering, Yamaguchi University, 2-16-1 Tokiwadai, Ube, Yamaguchi, 755-8611, Japan.
² Department of Chemistry and Biotechnology, Graduate School of Engineering (Center for Research on Green Sustainable Chemistry, Faculty of Engineering), Tottori University, 4-101 Koyamachominami, Tottori city, Tottori, 680-8552, Japan.
³ Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, R1-27, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa, 226-8503, Japan.
⁴ Department of Chemistry, Graduate School of Science, Hiroshima University, Higashi-Hiroshima, Hiroshima, 739-8526, Japan.
⁵ Department of Applied Chemistry for Environment, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo, 669-1337, Japan.

PMID: 33350568
DOI: 10.1002/anie.202010697

Abstract

Nucleophilic substitutions, including S_N 1 and S_N 2, are classical and reliable reactions, but a serious drawback is their intolerance for both bulky nucleophiles and chiral tertiary alkyl electrophiles for the synthesis of a chiral quaternary carbon center. An S_RN 1 reaction via a radical species is another conventional method used to carry out substitution reactions of bulky nucleophiles and alkyl halides, but chiral tertiary alkyl electrophiles cannot be used. Therefore, a stereospecific nucleophilic substitution reaction using chiral tertiary alkyl electrophiles and bulky nucleophiles has not yet been well studied. In this paper, we describe the reaction of tertiary alkyl alcohols and non-chiral or chiral α-bromocarboxamides as a tertiary alkyl source for the formation of congested ether compounds possessing two different tertiary alkyl groups on the oxygen atom with stereoretention.

Keywords: alkylation; amide; etherification; substitution.