Construction of Polyfunctionalized 2,4-Dioxa-8-azaspiro[5.5]undec-9-enes and 2,4,8-Triazaspiro[5.5]undec-9-enes via a Domino [2+2+2] Cycloaddition Reaction

The three-component reaction of alpha,beta-unsaturated N-arylaldimines, dialkyl but-2-ynedioates, and 2-arylidene Meldrum acids in DCM at room temperature gave mixtures of cis/trans-11-aryl-7-styryl-2,4-dioxa-8-azaspiro[5.5]undec-9-enes in satisfactory yields. The similar three-component reaction with 2-arylidene-N,N'-dimethylbarbituric acids afforded cis-11-phenyl-7-styryl-2,4,8-triazaspiro[5.5]undec-9-enes as major products. On the other hand, the three-component reaction of N-arylaldimines, dialkyl but-2-ynedioates, and 2-arylidene Meldrum acids or 2-arylidene-N,N'-dimethylbarbituric acids afforded cis/trans-isomeric spirocompounds in satisfactory yields with high diastereoselectivity. This domino [2+2+2] cycloaddition reaction proceeded with sequential nucleophilic addition of N-arylaldimine to an electron-deficient alkyne, Michael addition, and annulation process. The stereochemistry of all cis/trans isomeric spirocompounds was clearly elucidated by the determination of 33 single-crystal structures. The diastereoselectivity of the three-component reaction was correlated by DFT calculations.

Automated summary

The three-component reactions involving alpha,beta-unsaturated N-arylaldimines, dialkyl but-2-ynedioates, and specific acids yielded mixtures of spirocompounds with satisfactory yields and high diastereoselectivity. The reaction mechanism was elucidated through sequential nucleophilic addition, Michael addition, and annulation process. The stereochemistry of the products was confirmed by determining single-crystal structures, and the diastereoselectivity was correlated by DFT calculations.