Amide-Directed, Rhodium-Catalyzed Regio- and Enantioselective Hydroacylation of Internal Alkenes with Unfunctionalized Aldehydes

Abstract

Despite the current progress achieved in asymmetric hydroacylations, highly enantioselective catalytic addition of unfunctionalized aldehydes to internal alkenes remains an unsolved challenge. Here, using a coordination-assisted strategy, we developed a rhodium-catalyzed regio-and enantioselective addition of unfunctionalized aldehydes to internal alkenes such as enamides and β,γ-unsaturated amides. Valuable α-amino ketones and 1,4dicarbonyl compounds were directly obtained with high enantioselectivity from readily available materials.

Rhodium(I) Catalyzed Hydroacylation Reactions of Alkenyl Compounds

“…Very recently, a rhodium-catalyzed amidedirected hydroacylation of enamides 83 and β,γunsaturated amides 84 with non-chelating aldehydes 51 was achieved by Li and co-workers, and a variety of value-added α-amino ketones 85 and 1,4-dicarbonyl molecules 86 were obtained in a highly regio-and enantioselective fashion (Scheme 15). [61] The combination of a catalytic amount of Rh(COD) 2 OTf and a JoSPO ligand exemplified the general applicability of the asymmetric transformation for accessing these versatile building blocks, which probably could not be readily produced by other means. Remarkably, an allyl amide in company with γ,δ-and δ,ɛ-unsaturated amides can undergo an impressive alkene isomerization À hydroacylation sequence, all leading to the product 86 c regio-and enantioselectively.…”

P-Stereogenic Phosphorus Ligands in Asymmetric Catalysis

“…Very recently, two types of amide-directed Rh-catalyzed regio- and enantioselective hydroacylation of internal alkenes with unfunctionalized aldehydes have been reported (Schemes and ) . Both reactions were most efficiently conducted by the use of JoSPOphos as the chiral ligand containing a P-stereogenic secondary phosphine oxide moiety, delivering valuable α-amino ketones and 1,4-dicarbonyl compounds with high enantiomeric excesses.…”