Carbene‐Catalyzed Enantioselective Aldol Reaction: Post‐Aldol Stereochemistry Control and Formation of Quaternary Stereogenic Centers

Abstract

The dominated approaches for asymmetric aldol reactions have primarily focused on the aldol carbon-carbon bond-forming events. Here we postulate and develop a new catalytic strategy that seeks to modulate the reaction thermodynamics and control the product enantioselectivities via postaldol processes. Specifically, an NHC catalyst is used to activate a masked enolate substrate (vinyl carbonate) to promote the aldol reaction in a non-enantioselective manner. This reversible aldol event is subsequently followed by an enantioselective acylative kinetic resolution that is mediated by the same (chiral) NHC catalyst without introducing any additional substance. This post-aldol process takes care of the enantioselectivity issues and drives the otherwise reversible aldol reaction toward a complete conversion. The acylated aldol products bearing quaternary/tetrasubstituted carbon stereogenic centers are formed in good yields and high optical purities.

Carbene‐Catalyzed Enantioselective Aldol Reaction: Post‐Aldol Stereochemistry Control and Formation of Quaternary Stereogenic Centers

“…The absolute configuration of 3 e was confirmed by X-ray analysis. [19] Introducing a chloride atom or a trifluoromethyl group at the 6-position of isatins did not affect the reaction outcomes, with 3 l and 3 m formed in high yields, excellent diastereo-and enantioselectivities. Isatins bearing a fluoride atom or a methyl unit at the 7-position reacted effectively to give 3 n and 3 o with similar results.…”

Designable assembly of atomically precise Al4O4 cubane supported mesoporous heterometallic architectures

“…The aldol reaction is a basic transformation in creating new carbon–carbon bonds and β-hydroxyl carbonyl compounds. 59 Considering the higher stability and catalytically active sites (unsaturated transition metals) on the Al 4 O 4 support, three representative AlOCs ( AlOC-99 , AlOC-109 and AlOC-112 ) were used as catalysts for the direct aldol reaction of acetone and nitro-substituted aromatic aldehyde in DMSO. The catalytic results are summarized in Table S6 †…”

Progress in Organocatalytic Dearomatization Reactions Catalyzed by N‐Heterocyclic Carbenes

“…Recently, Chi et al reported cleverly designed NHC-catalyzed asymmetric aldol reactions of benzofuran-2-carbonates 102 and oxazole-2-carbonates 103. [53] These reactions involve asymmetric dearomatization of the benzofuran and oxazole moieties and give products 104 in yields up to 98 % with excellent enantioselectivities (up to 99 % er) and diastereoselectivities (up to > 20 : 1 dr). They also successfully explored the reaction of O-acylated azlactones 108 and isatins 109 which demonstrated the generality of this strategy (Scheme 28).…”