Fukuyama reduction explained

The Fukuyama reduction is an organic reaction and an organic reduction in which a thioester is reduced to an aldehyde by a silyl hydride in presence of a catalytic amount of palladium. This reaction was invented in 1990 by Tohru Fukuyama.^[1] In the original scope of the reaction the silyl hydride was triethylsilane and the catalyst palladium on carbon:

Fukuyama reductions are used for the conversion of carboxylic acids (as thioester precursor) to aldehydes which is considered a difficult procedure because of the ease of secondary reduction to an alcohol.

Reaction mechanism

The basic reaction mechanism for this reaction takes place as a catalytic cycle:

• Oxidative addition:

+ Pd^0 -> RC(O)-Pd^-SR

• Transmetallation:

+ R3SiH -> + R3Si-SR

• Reductive elimination:

RC(O)-Pd^-H -> + Pd^0

Scope

In a variation of the Fukuyama reduction the core BODIPY molecule has been synthesized from the SMe-substituted derivative:^[2] Additional reagents are copper(I)-thiophene-2-carboxylate (CuTC), Pd(dba)2 and tri(2-furyl)phosphine

In the related Fukuyama coupling the hydride is replaced by a carbon nucleophile.

Notes and References

1. Facile reduction of ethyl thiol esters to aldehydes: application to a total synthesis of (+)-neothramycin A methyl ether Tohru Fukuyama, Shao Cheng Lin, Leping Li J. Am. Chem. Soc., 1990, 112 (19), pp 7050–7051
2. The Smallest and One of the Brightest. Efficient Preparation and Optical Description of the Parent Borondipyrromethene System. I. J. Arroyo, R. Hu, G. Merino, B. Z. Tang, E. Peña-Cabrera, J. Org. Chem. 2009, ASAP