Selectivity in 1,3-Dipolar cycloadditions of β-substituted captodative olefins - An experimental and DFT transition state study

Captodative olefins 1-acetylvinyl carboxylates substituted with alkyl groups at the β position, 12, strongly modified the regioselectivity of 1,3-dipolar cycloadditions with respect to the behavior observed for their unsubstituted analogs, 1. When the reaction of 12 was carried out with diphenyl nitrone (7a), the corresponding C-4 disubstituted isoxazolidines were obtained as a mixture or as single stereoisomers, in contrast to the isomeric C-5 disubstituted heterocycles yielded by olefins 1. Nevertheless, olefins 12 reacted with benzonitrile oxide (2a) to give the C-5 acetyl isoxazoles, as observed with dipolarophiles 1. This intricate behavior of the reactions between 1,3-dipoles and β-substituted captodative olefins was rationalized on the basis of DFT calculations [B3LYP/6-31(d)] of the transition states (TSs) for nitrone 7a and olefin 12a. Thus, the observed C-4 and endo regio- and stereoselectivities agreed with the most stable TSs, which are mainly stabilized by dipolar and electrostatic interactions.