Theoretical Insights into Ester-Directed Reactions between Propiolates with 1,2-Benzisoxazoles by Au(I) Catalyst: [4 + 2]-Annulation versus Michael-Type Products

Au­(I)-catalyzed selective reactions of Et- and tBu-substituted propiolates (1a and 1a′) with 1,2-benzisoxazole­(2a) provide a new strategy for purposefully access to desired bioactive heterocycles. Using DFT calculations, we have systematically investigated the detailed mechanisms and origins of the ester-controlled chemoselectivity. The calculated results indicated that both reactions are initiated by LAu+ π-coordination, N nucleophilic attack, and NTf2–-assisted stepwise H-shift, generating a nitrilium species identified as a common and requisite intermediate, which is significantly different from the experimentally proposed 6-alkoxy-1,3-oxazin-1-ium intermediate. Starting from the nitrilium intermediate, the newly established nucleophilic cyclization, alkene release, and NTf2–-assisted stepwise protodeauration provides [4 + 2]-annulation product P1, while the nitrilum dissociation, O nucleophilic attack, and NTf2–-assisted stepwise protodeauration generates Michael-type product P2. Further explorations showed that tBu-controlled chemoselectivity of P1 over P2 can be attributed to the energy favorable aromaticity of selective-determining nucleophilic cyclization TS. With substitution of tBu by Et group, the reversal of chemoselectivity to P2 formation might be closely related to the presence of extremely unstable Et cation in ethylene release TS leading to P1.