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.