Novel formation of phenylcyclopropanes from the reaction of β-cyanostyrenes and related compounds with 2-methoxyfuran: experimental and theoretical studies

Abstract

As a diene, 2-methoxyfuran fails to generate a Diels–Alder adduct when it reacts with β-cyanostyrenes (cinnamonitriles). However, in the reaction with β-cyanostyrenes possessing additional electron-withdrawing groups (CN, CO2Et and SO2Ph), it yielded two new phenylcyclopropanes. We have used computational methods to investigate the mechanism and to probe the regioselectivity observed in the rearrangement reactions. We used a B3LYP/6-31G* level density functional calculation to locate the transition states (TS), and to account for the selectivity observed in these reactions, we examined the global electronic index involved. An analysis of the results for the reaction pathways of two adducts (the endo and exo isomers) shows that the reaction takes place via a polar stepwise mechanism. The first step involves a side-on nucleophilic attack by the α-carbon atom of the furan ring on the vinyl carbon of the cyanostyrene to give a zwitterionic intermediate. An intramolecular substitution within the intermediate (IN) gives the cyclopropane ring, together with fission of the furan ring. The potential energy barriers for these reactions had the following values: at the nucleophilic addition step, 14.6 and 13.7 kcal mol−1 for 2b, and 18.4 and 17.8 kcal mol−1 for 2c; at the rearrangement step, 22.3 and 22.8 kcal mol−1 for 2b, and 25.1 and 23.1 kcal mol−1 for 2c. Solvent effects in chloroform stabilized the rearrangement steps by 5–6 kcal mol−1, but the nucleophilic addition step appeared to be slightly affected. From the theoretical results, in the case of 2b, the energy of TS2-endo is lower than that of TS2-exo, so more trans-cyclopropane product from the endo form is formed under kinetic conditions. Conversely, in the case of 2c, the energy of TS2-exo is lower and more of the cis-product is formed. Density functional theory analysis of these reactions is in complete agreement with the experimental results.