Organocatalytic Asymmetric Dimerization of γ‐Hydroxyenones to Acetals and Theoretical Investigations into the Diastereoselection

Abstract

A method for the organocatalytic, highly enantioselective, and moderately diastereoselective dimerization (redox isomerization/acetal formation) of γ‐hydroxyenones is disclosed. The stereogenic acetal products were obtained via hemiacetal intermediates followed by a cyclization reaction. With bifunctional thiourea catalysts, high yields and excellent enantioselectivities were achieved for a variety of acetal products under mild reaction conditions. In addition, detailed DFT calculations were performed to investigate the mechanism of this reaction, and these calculations suggested that the diastereoselectivity was due to a kinetically controlled process.

Unravelling the Development of Non-Covalent Organocatalysis in India

“…Work by Pan’s group revealed a methodology for the highly stereoselective and organocatalytic dimerisation (redox isomerisation/acetal formation) of γ-hydroxy aryl enones 74 catalysed by bifunctional amino thiourea catalyst 1A (Scheme 22 ). 68 It describes a first of its kind catalytic method for asymmetric access to stereogenic acetals 75 with high yields and excellent enantioselectivities. Both the stereoisomers obtained have equal energies but selective trans stabilisation was achieved by the catalyst leading to diastereoselectivity.…”

Chiral Binaphthyl Box-Copper-Catalyzed Enantioselective Tandem Michael–Ketalization Annulations for Optically Active Aryl and Heteroaryl Fused Bicyclicnonanes

“…The structures containing O , O - or O , N - acetal and ketal skeletons are pressent in a range of natural products and pharmaceuticals with a broad spectrum of bioactivities . Considerable efforts have been devoted to the synthesis of this type of compounds bearing O , O - or O , N - acetal and ketal moieties, and a number of convenient approaches have been documented for the synthesis of monocyclic acetals, fused acetals, and spiroketals in recent years. Despite these advancements, however, the synthesis of more complexed methylene bridged bicyclo[3.3.1] nonanes with O , O - and O , N - acetal and ketal skeletons, which are recurring structural moieties in a spectrum of medicinal compounds from plant sources, such as Dinsinin, Dinsininol, Naucleamide E, Larutensine, Dracoflavan C and D, etc.…”

Organocatalytic Asymmetric Synthesis of Bridged Acetals with Spirooxindole Skeleton

“…Thus, considerable efforts have been devoted in recent times for the asymmetric synthesis of these compounds . In fact a number of convenient approaches have been developed for the synthesis of monocyclic acetals, fused acetals and spiroketals . For example, List and Čorić have elegantly developed asymmetric synthesis of spiroacetals using imidophosphoric acid as catalyst .…”