Highly chemoselective palladium-catalyzed conjugate reduction of .alpha.,.beta.-unsaturated carbonyl compounds with silicon hydrides and zinc chloride cocatalyst

Abstract

A three-component system comprised of a soluble palladium catalyst, hydridosilane, and zinc chloride is capable of efficient conjugate reduction of a,&unsaturated ketones and aldehydes. The optimal set of conditions includes diphenylsilane as the most effective hydride donor, any soluble palladium complex in either the 0 or I1 oxidation state, when it is stabilized by phosphine ligands, and ZnCll as the best Lewis acid cocatalyst. The reaction is very general with respect to a broad range of unsaturated ketones and aldehydes, and it is highly selective for these Michael acceptors, as reduction of a,@-unsaturated carboxylic acid derivatives is very sluggish under these conditions. When dideuteriodiphenylsilane is used to reduce unsaturated ketones, deuterium is stereoselectively introduced at the less-hindered face of the substrate and regioselectively at the 8-position. Conversely, when reductions are carried out in the presence of traces of D20, deuterium incorporation occurs at the a-position. On the basis of deuterium-incorporation experiments and 'H NMR studies, a catalytic cycle is postulated in which the first step involves reversible coordination of the palladium complex to the electron-deficient olefin and oxidative addition of silicon hydride to form a hydridopalladium olefin complex. Migratory insertion of hydride into the coordinated olefin produces an intermediate palladium enolate which, via reductive elimination, collapses back to the Pd(0) complex and a silyl enol ether, which is then hydrolyzed to the saturated ketone. In addition to catalyzing that hydrolysis, ZnC12 facilitates the hydrosilation process. Despite the bewildering variety of reducing agents available for synthetic chemistry, new and ever more selective reductants are in constant demand. Most popular of selective reducing agents are the various metal hydrides, mainly those of boron and alu- minum,' an abundance of which have been designed over the past 4 decades and new derivatives of which are continuously being developed.* However, the hydridic nature of most of these group 13 and other metal hydrides can limit their usefulness, particularly when high chemoselectivity is required.