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 theposition, 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.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)