Synthesis of Spirocyclic Pyrrolidine Compounds via Silver-Catalyzed Asymmetric [3 + 2] Cycloaddition Reaction of Imino Esters with α-Alkylidene Succinimides

Ayana Inoue; Kenya Hosono; Shohei Furuya; Shin-Ichi Fukuzawa

doi:10.1021/acs.joc.3c02456

Synthesis of Spirocyclic Pyrrolidine Compounds via Silver-Catalyzed Asymmetric [3 + 2] Cycloaddition Reaction of Imino Esters with α-Alkylidene Succinimides

J Org Chem. 2024 Jan 19;89(2):1249-1255. doi: 10.1021/acs.joc.3c02456. Epub 2024 Jan 4.

Authors

Ayana Inoue¹, Kenya Hosono¹, Shohei Furuya¹, 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: 38174971
DOI: 10.1021/acs.joc.3c02456

Abstract

In this study, the AgOAc/ThioClickFerrophos (TCF) complex was used to successfully catalyze asymmetric [3 + 2] cycloaddition between glycine imino esters and CO₂Me-appended α-alkylidene succinimides to afford spiropyrrolidines in good yields with high diastereo- and enantioselectivities (up to 95% ee). The silver/TCF afforded endo-(2,5-cis) cycloadducts in contrast to the previous exo'-(2,5-trans) selective reaction with ylidene-2,3-dioxopyrrolidine. A wide variety of imino esters bearing electron-donating and electron-withdrawing groups on the phenyl groups and heteroaryl substrates were utilized in this reaction. The scope of α-alkylidene succinimides was investigated, which revealed that substituents on α-benzylidene derivatives had negligible effect on the product yield and stereoselectivity, and α-alkylidene derivatives could be efficiently used as dipolarophiles.