Nickel-Catalyzed Dehydrogenative [4+2]-Cycloaddition Route to Dihydropyridones

Significance

Reported is the synthesis of ­dihydropyridones 3 via a dehydrogenative [4+2] cycloaddition of formamides 1 with alkynes 2 under nickel/AlMe₃ cooperative catalysis. The yields of 3 are usually high (63-99%) except in one case (R^¹ = TMS, 23%). Both aryl EDGs and EWGs are tolerated in 1, although the bulky 1-naphthyl group led to sluggish reactivity (74% yield, 89 h ­reaction time). In general, the smaller substituent (R^¹) in unsymmetrical alkynes is introduced at the α-position of the carbonyl of 3 with moderate to excellent regioselectivity. When enantioenriched (>99% ee) (R,R)-1 was used as substrate, complete retention of the stereochemical information was observed. The use of meso-1 led to the opposite diastereomer 5 in moderate yield. A plausible mechanism is proposed based on deuterium labeling experiments.