Mechanisms of the Nickel- and Cobalt-Catalyzed Reductive Aldol Cyclization’S |
Inthe presence of diethylzinc as a stoichiometric reductant, substoichiometricquantities of an appropriate cobalt source catalyse diastereoselectivereductive aldol coupling reactions of a,b-unsaturated amides with ketones. Theuse of a readily available oxazolidine as a chiral auxiliary imparts highlevels of asymmetric induction in these reactions. Thecobalt-catalysed alkylative aldol cyclisations of unsaturated amides with anappendant ketone were studied using a range of trialkylaluminium reagents.Investigations revealed that Co(acac)2·2H2O acts as an effective precatalystfor this transformation and the reaction provides hydroxylactam productscontaining three contiguous stereocentres with high levels ofdiastereoselection. The substrate scope of the reaction was explored andattempts were made to develop an asymmetric variant of this process. Two plausiblereaction mechanisms have been proposed; the first invokes a allylcobalt speciesas a key intermediate in the reaction mechanism and the second involves aradical-mediated pathway.