Asymmetric Cyclopropanation of β,γ-Unsaturated α-Ketoesters with Stabilized Sulfur Ylides Catalyzed by C₂-Symmetric Ureas

Abstract

A novel organocatalytic asymmetric cyclopropanation of β,γ-unsaturated α-ketoesters with stabilized sulfur ylides using C(2)-symmetric urea as a hydrogen-bond catalyst has been described. This reaction allows an efficient access to 1,2,3-trisubstituted cyclopropane derivatives in moderate to good yields with up to 16:1 dr and 90:10 er under mild reaction conditions. The mechanism study proved that the high stereoinduction originated from the cooperative effect of the hydrogen-bond catalyst.

Catalytic Asymmetric Synthesis of Chiral Dihydrobenzofurans through a Formal [4+1] Annulation Reaction of Sulfur Ylides and In Situ Generated ortho‐Quinone Methides

“…We presume that the exposure of sulfur ylide 2a to multiple‐H‐bonding catalyst III affords complex A . [10a], [10c] Then, complex A binds to o ‐QM 5a , which is generated in situ from TBS‐protected phenol substrate 1a in the presence of CsF,[12c] to give complex B . Possibly, catalyst III governs the orientation of both substrates in this complex by H‐bonding interactions and thus enables the asymmetric Michael addition to provide complex C .…”

“…Recently, we disclosed an asymmetric [4+1] annulation of chiral sulfur ylides, and in situ generated o ‐azaxylylenes to afford chiral indolines in good yields and good enantioselectivities[10d] [Scheme (A), up to 93 % yield, 95.5:4.5 e.r. (enantiomeric ratio)].…”

“…[13d] Herein, for the first time, we have developed the enantioselective synthesis of 2,3‐dihydrobenzofuran through an asymmetric [4+1] annulation reaction of acyl‐substituted sulfur ylides and o ‐QM intermediates [Scheme (B)]. This success is based on a cooperative‐catalysis strategy of multiple‐H‐bonding catalysts, which has been well developed in our previous work on annulation reactions of sulfur ylides with unsaturated keto esters[10a] and nitroolefins. [10c]…”

“…This success is based on a cooperative‐catalysis strategy of multiple‐H‐bonding catalysts, which has been well developed in our previous work on annulation reactions of sulfur ylides with unsaturated keto esters[10a] and nitroolefins. [10c]…”

Recent Advances in Organocatalytic Methods for Asymmetric CC Bond Formation

“…[213] Another very effective method for cyclopropanation reactions was described by Xiao et al The reaction of a-keto esters and aromatic sulfur ylidenes is catalyzed by chiral urea 188 to give moderate to good outcome. [214] In situ generation of ylidenes proved to be more effective for Umpolung reactions as Studer et al were able to demonstrate. In this case the [2+1] cycloaddition is followed by formation of isopropyl esters.…”