Chiral Gold Complex Catalyzed Cycloisomerization/Regio- and Enantioselective Nitroso-Diels–Alder Reaction of 1,6-Diyne Esters with Nitrosobenzenes

An efficient chiral gold(I) complex-catalyzed synthetic method that enables the cycloisomerization/regio- and enantioselective nitroso-Diels–Alder (NDA) reaction of 1,6-diyne esters with nitrosobenzenes is described. The sequential ring formation protocol offers access to a wide variety of 3,5,6,8a-tetrahydro-1H-benzo[c][1,2]oxazines as a single regioisomer in yields up to 99% and enantiomeric excess values of up to 99%. This is in contrast to the analogous NDA reactions of the cycloisomerized 1,6-diyne ester with nitrosoarenes in the absence of the chiral gold(I) complex catalytic system, which were found to give the N,O-heterocyclic product with the opposite regiochemistry. Experimental and computational studies based on a postulated chiral dinuclear gold species containing two coordinated nitrosoarene molecules that undergoes an asynchronous concerted NDA reaction with the cycloisomerized 1,6-diyne ester provides insight into the observed product regio- and enantioselectivities.