N-heterocyclic carbene-catalyzed atroposelective synthesis of axially chiral 5-aryl 2-pyrones from enals

Axially chiral molecules have been widely used in inorganic, material and medicinal chemistry. Compared with well-established N-heterocyclic carbene (NHC)-catalyzed asymmetric construction of centrally chiral molecules, NHC-catalyzed atroposelective synthesis of axially chiral molecules remains largely underdeveloped. Notably, alkynyl acyl azolium intermediates were commonly used in constructing a heteroaryl ring to furnish axially enantioenriched heteroaryl-aryls. The inherent character of the intermediates often led to react with sterically hindered substrates difficultly. Herein, we have successfully disclosed the atroposelective synthesis of axially chiral heteroaryl-aryls from sterically hindered enols through the use of chiral NHCs as catalysts for highly enantioselective Coates-Claisen rearrangements via catalytically generated alpha,beta-unsaturated acyl azoliums. This approach will enable the concise synthesis of valuable tetra-ortho-substituted 2-pyrones in one step with good yield and chirality control.

Automated summary

Axially chiral molecules are widely used in various fields of chemistry, and the synthesis of axially chiral molecules catalyzed by NHCs remains underdeveloped. In this study, we successfully achieved the atroposelective synthesis of axially chiral heteroaryl-aryls using chiral NHCs as catalysts for highly enantioselective Coates-Claisen rearrangements via catalytically generated alpha, beta-unsaturated acyl azoliums. This approach enables the concise synthesis of tetra-ortho-substituted 2-pyrones with good yield and chirality control.