Novel formation of isoxazoline N-oxide in addition to Michael adduct from the reaction of β-nitrostyrenes with 2-methoxyfuran -Experimental and theoretical studies

摘要

2-Methoxyfuran reacts with β-nitrostyrenes to give Michael adducts. Interestingly, isoxazoline N-oxides were obtained in the reactions with β-nitrostyrenes possessing additional electron-withdrawing groups [COPh (2f) and CO2Et (2g)]. (Z)-Nitrostyrene (2g) gives trans-isoxazoline (4g) and (E)-nitrostyrene (2f) leads to the cis-form product 4f. We have used theoretical methods to investigate the mechanism and to probe the regio- and stereo-selectivity observed in the rearrangement and the Michael reactions. To account for the selectivity observed in these reactions, we examined the Fu-kui functions and located the transition states (TS) using density functional theory (DFT) calculations at the B3LYP/6-31G* level. The first step involves a nucleophilic attack by the α-carbon atom (C4) of the furan ring on the vinyl C-atom (C5) of the nitrostyrene part to give a zwitterionic intermediate (IN1). Fission of the C-O bond of the furan ring in the intermediate and ring closure via the oxygen atom (endo-O atom) of the nitro group gives the isoxazoline N-oxide. Alternatively, the intermediate (IN1) may be transformed into the Michael adduct by an intramolecular proton transfer mediated by the formation of a four-membered transition-state structure. The potential-energy barriers for these reactions had the following values: 5.1 kcal/mol for 2f and 17.0 kcal/mol for 2g' (CO2Me) at the rearrangement step, and 41-49 kcal/mol for the proton-transfer step. The solvent effect in CHCl3 stabilized the electrophilic attack by 1-14 kcal/mol. DFT analysis of these reactions is in good agreement with the experimental results.