Chiral Silver Complex-Catalyzed Asymmetric Conjugate Addition of 1-Pyrroline-5-Carbonitrile to α-Enones

Haruna Araki; Shohei Furuya; Kazuya Kanemoto; Shin-Ichi Fukuzawa

doi:10.1021/acs.joc.2c02315

Chiral Silver Complex-Catalyzed Asymmetric Conjugate Addition of 1-Pyrroline-5-Carbonitrile to α-Enones

J Org Chem. 2023 Jan 20;88(2):924-932. doi: 10.1021/acs.joc.2c02315. Epub 2023 Jan 10.

Authors

Haruna Araki¹, Shohei Furuya¹, Kazuya Kanemoto¹, Shin-Ichi Fukuzawa¹

Affiliation

¹ Department of Applied Chemistry, Institute of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.

PMID: 36626719
DOI: 10.1021/acs.joc.2c02315

Abstract

The conjugated addition reaction of 1-pyrroline-5-carbonitrile to α-enones was effectively catalyzed by AgF/ThioClickFerrophos (TCF) in diethyl ether in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and nearly single diastereomers of adducts with good enantiomeric excesses (up to 97% ee) were obtained in high yields. The reduction of the nitrile group with H₂/Raney Ni in ethanol successfully transformed the conjugate adduct to the corresponding spirocyclic piperidine (60% yield) as a single stereoisomer.