Stereoselektivität und Reaktivität bei der 1,3‐dipolaren Cycloaddition chiraler N‐(Alkoxyalkyl)nitrone

Abstract

Stereoselectivity and Reactivity in the 1,3‐Dipolar Cycloaddition of Chiral N‐(Alkoxyalkyl)nitronesThe stereoselectivity in the reaction of hydroxy‐oxime 1 with acetaldehyde and methyl methacrylate yielding the diastereomeric isoxazolidine‐ribosides 9–12 was determined to be 93%. The predominant adducts 9 and 10 were cleaved to the diastereomeric isoxazolidines 19 and 20, respectively, which upon oxidation gave the same optically active 2‐isoxazoline 21, thus demonstrating the participation in the cycloaddition of both (E/Z)‐isomeric nitrones 13 and 14. Based upon comparison of the optical rotations, the isoxazolidines 7, 8, 19 and 20 and the 2‐isoxazolines 21 and 22 possess the same chirality, found to be R by correlating 7 with (+)‐(S)‐citramalic acid. ‐ Since the hydroxy‐oximes 1 and 36 showed the same stereo‐selectivity in the reaction with formaldehyde and methyl methacrylate, the trityl group of 1 does not influence the stereoselectivity in the cycloaddition. The hydroxyoxime 38 led in the same type of reaction to the isoxazolidines 7, 8, 19 and 20 possessing (S)‐chirality, the stereoselectivity (79–95%) being similar to the one observed with 1 (67–95%). The explanation of this stereoselectivity is based upon a stereoelectronic effect in the transition state of the cycloadditions (kinetic anomeric effect). As predicted, the N‐(alkoxyalkyl)nitrones showed enhanced reactivity in the cycloaddition with unactivated olefins (leading to 47, 48, 50 and 51). The importance of exo vs. endo approach of the dipolarophile was evidenced by reacting 1 with formaldehyde and methyl acrylate giving predominantly 57 with (5S)‐configuration. ‐ Use of the hydroxy‐oxime 65 allows synthesis of optically active isoxazolidines with regeneration of the starting hydroxy‐oxime.