Unsaturated aldehydes organocatalytic reduction

Nature makes use of NADH (reduced nicotinamide adenine dinucleotide) as a cofactor for enantioselective biochemical hydrogenations, which are typical hydride-transfer reactions. Dihydropyridines and benzimidazolines derivatives are active hydride donors due to the presence of the nitrogen atom and the ability of the molecule to undergo aromatisation. Organocatalytic enantioselective reductions carried out using hydride donors has been studied, and effective reductions have been achieved with imidazoli-dinone organocatalysts, both with a,p unsaturated aldehydes and ketones. Generally, a stoichiometric quantity of reductant (Hantzsch ester 4) is required for these transformations (Scheme 18.5). 

Yang JW, Fonseca MTH, List B (2004) A Metal-Free Transfer Hydrogenation Organocatalytic Conjugate Reduction of a,P-Unsaturated Aldehydes. Angew Chem Int Ed 43 6660... 

Asian J., 2, 820-827 (h) Rueping, M., Dufour, J., and Schoepke, F.R. (2011) Advances in catalytic metal-free reductions from bio-inspired concepts to application in the organocatalytic synthesis of pharmaceuticals and natural products. Green Chem., 13, 1084—1105 (i) Ebner, C. and Pfaltz, A. (2011) Chiral dihydrobenzo [l,4]oxazines as catalysts for the asymmetric transfer-hydrogenation of a, 3-unsaturated aldehydes. Tetrahedron, 67, 10287-10290. 

Qu and co-workers have developed organocatalytic asymmetric aza-Michael addition reaction of achiral purine bases (486) to a,p-unsaturated aldehydes (487) followed by reduction of aldehyde group to give optically active products (488) in 82 89% yield and up to 99% ee (Scheme 121). They were readily converted to phosphonic acids (489) in high yields and high enantioselectivities. 

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