Journal of the American Chemical Society 2008-06-11

Diastereoselective nickel-catalyzed reductive aldol cyclizations using diethylzinc as the stoichiometric reductant: scope and mechanistic insight.

Pekka M Joensuu, Gordon J Murray, Euan A F Fordyce, Thomas Luebbers, Hon Wai Lam

Index: J. Am. Chem. Soc. 130(23) , 7328-38, (2008)

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Abstract

In the presence of diethylzinc as a stoichiometric reductant, Ni(acac) 2 functions as an efficient precatalyst for the reductive aldol cyclization of alpha,beta-unsaturated carbonyl compounds tethered to a ketone electrophile through an amide or an ester linkage. The reactions are tolerant of a wide range of substitution at both alpha,beta-unsaturated carbonyl and ketone components and proceed smoothly to furnish beta-hydroxylactams and beta-hydroxylactones with generally high diastereoselectivities. A series of experiments, including deuterium-labeling studies, was carried out in an attempt to gain some insight into the possible reaction mechanisms that might be operative.