Formal [3+2] cycloaddition of vinylcyclopropane azlactones to enals using synergistic catalysis

Abstract

The present study reports the asymmetric cyclization of enals with vinylcyclopropane azlactones efficiently catalyzed by the combination of achiral Pd(0) complexes and chiral secondary amines.

Enantioselective Synthesis of SpirothiazolonesviaCooperative Catalysis

“…Later, in 2016, Michelet and Vitale, [8a] J ø rgensen [8b] and Rios [8c] independently published asymmetric [3+2] cycloaddition between vinyl cyclopropanes and α , β ‐unsaturated aldehydes catalyzed by a combination of chiral secondary amine and palladium complex (Scheme 1a). The process proceeding through the formation of transient zwitterionic π‐allyl palladium intermediates and chiral α , β ‐unsaturated iminium ions was also successfully used for the enantioselective preparation of spirocyclic compounds containing oxindole, benzofuranone, Meldrum's acid, and azlactone motifs [8c,d] . In addition, we recently showed that pyrazolone‐fused dihydrooxepines could be activated with palladium generating similar zwitterionic π‐allyl palladium intermediate and used for the synthesis of spirocyclic pyrazolones in high enantio‐ and diastereoselectivity (Scheme 1b) [9] .…”

“…Compound 7 e was prepared in high yield (79%) without loss of optical purity. Similarly, ester 8 e prepared by Wittig olefination [8d] from 4 e , was achieved with retained enantiopurity. Another studied transformation of the prepared spirocyclic compound 4 e was the opening of thiazolone moiety.…”

Asymmetric Catalytic Reactions of Donor–Acceptor Cyclopropanes

“…In this reaction, the chiral prolinol silylether organocatalyst 19 was used to generate the highly activated α,β‐unsaturated iminium ion dipolarophile, and meanwhile induce the stereoselective formation of the five‐membered ring [39a] . This strategy was further extended to indane‐1,3‐dione‐derived‐, azalactonyl‐, dicyano‐ and cyanoester‐substituted vinylcyclopropanes [39b–e] …”

Recent Advances in Stereoselective Ring Expansion of Spirocyclopropanes: Access to the Spirocyclic Compounds

“…In 2019, the Veselý group reported asymmetric (3 + 2)-annulation of azlactone-based SVCPs 58 with α,β-unsaturated aldehydes 48 for the enantioselective synthesis of functionalized spirocyclic derivatives 59 and 59′ under cooperative catalysis ( Scheme 24 ). 29 After the extensive screening of various organo- and metal catalysts, high enantioselectivity with good conversion of the cycloadduct was attained by merging the chiral secondary amine L4 and the Pd(0) complex as the catalyst. The methodology was tolerated for a wide range of aryl and aliphatic substituents, delivering the desired products.…”