UNUSUAL REGIOSELECTIVITY OF THE DIPOLAR CYCLOADDITION REACTIONS OF NITRILE OXIDES AND TERTIARY CINNAMIDES AND CROTONAMIDES

Benzonitrile oxides undergo 1,3-dipolar cycloaddition reactions with m ethyl cinnamate to produce the 5-phenyl and 4-phenyl regioisomers in a pproximately an 80:20 ratio. However, use of N,N-diethylcinnamide as t he dipolarophile unexpectedly resulted in the formation of the 5-pheny l and 4-phenyl regioisomers in a 23:77 ratio. Studies have shown that this phenomena occurs only for tertiary cinnamides, In addition, it ha s been demonstrated that the phenyl group of tertiary cinnamides is no t essential for the reversal of regioselectivity since crotonamides pr oduce the same results and trends as the cinnamides. However, since ac rylates and acrylamides both produce the 5-carbonyl regioisomers, it c an be concluded that the beta-substituent is playing a key role for th e unexpected results by possibly increasing steric interactions betwee n the dipole and dipolarophile in the transition state. Transition sta te energies were calculated for the regioisomeric cycloadduct pairs de rived from several crotonamides as well as methyl crotonate. These cal culations indicate that steric factors are indeed responsible for the reversal of regioselectivity.