Theoretical insight into the regioselective formation of pyrazolo[1,4]-oxazepine and -oxazines.

AuCl-, AuCl-, or AuClPEt-catalyzed formation mechanisms of pyrazolo[1,4]oxazepines and the NaH-promoted mechanism of pyrazolo[1,4]oxazines were investigated computationally. The structural properties of the reactants were studied in various solvents and with different functionals. The hybrid functionals B3LYP, M06, M06-2X, PBEPBE, and wB97X-D in density functional theory were used to determine and discuss the energetics of the compounds. The electronic properties of groups (R = H or R ≠ H) attached to the alkyne moiety played an essential role in the corresponding 7-endo-dig cyclization or 6-exo-dig cyclization in the presence of a gold catalyst. The regioselectivities of the products were investigated, and the natural bond orbitals of the reactants were determined. Furthermore, a gold-catalyzed alternative mechanism is suggested for synthesizing pyrazolo[1,4]oxazines using a terminal alkyne (R = H) moiety as substrate.