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,Oheterocyclic 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.

Automated summary

An efficient chiral gold(I) complex-catalyzed synthetic method for the regio- and enantioselective nitroso-Diels-Alder (NDA) reaction of 1,6-diyne esters with nitrosobenzenes is described. The reaction provides access to a wide range of 3,5,6,8a-tetrahydro-1H-benzo[c][1,2]oxazines as a single regioisomer with high yields and enantiomeric excess values.