Enantioselective construction of axially chiral cyclohexylidene scaffolds via Pd-catalyzed asymmetric coupling reaction

Abstract

Axially chiral cyclohexylidenes exhibit unique chirality because of the restricted rotation of the C=C bond. Compared with other axially chiral compounds, they are much less explored, and their efficient construction remains a synthetic challenge. Herein, we report the first palladium-catalyzed asymmetric coupling reaction of aryl iodides with 4-substituted cyclohexanol-derived α-diazocarbonyl compounds to give tetrasubstituted cyclohexylidenes in good yields (up to 92%) with excellent enantioselectivities (up to 96% ee ) under mild conditions. This protocol provides a general access to axially chiral cyclohexylidenes. The utility of this unique scaffold was demonstrated by the carboxylic acid serving as a useful chiral ligand in transition-metal-catalyzed C–H bond activation, which showed great promise as a new type of olefin ligand. • Pd-catalyzed asymmetric cross-coupling reaction • Facile access to enantioenriched axially chiral tetrasubstituted alkenes • Broad scope, good yields, and excellent enantioselectivities • Develop skeleton applications Tetrasubstituted alkenes are important building blocks in many natural products, drugs, and functional materials. Their efficient regio- and stereoselective synthesis poses a significant challenge to synthetic organic chemists due to the crowded nature of the double bonds. The reported palladium/Xu-Phos-catalyzed asymmetric coupling reaction of this method allows the use of readily available simple aryl iodides and 4-substituted cyclohexanol-derived α-diazocarbonyl compounds under mild conditions, furnishing a variety of tetrasubstituted cyclohexylidenes in good yields with excellent enantioselectivities. The utility of this unique scaffold was demonstrated by the carboxylic acid serving as a useful chiral ligand in transition-metal-catalyzed C–H bond activation, which showed great promise as a new type of olefin ligand. The first Pd/Xu-Phos-catalyzed asymmetric coupling reaction of aryl iodides with β -hydroxy α -diazocarbonyl compounds has been established to construct axially chiral cyclohexylidene skeletons (up to 92% yield, up to 96% ee ). This protocol provides easy access to axially chiral cyclohexylidenes, one rarely explored class of the atropisomeric family. The carboxylic acid derivatives could serve as a useful chiral ligand in transition-metal-catalyzed C–H bond activation. The proposed mechanism involves palladium carbene asymmetric migration insertion, β -hydroxyl elimination, and reduction of Pd(II) to Pd(0).