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

1977; Wiley; Volume: 60; Issue: 4 Linguagem: Inglês

10.1002/hlca.19770600417

1522-2675

Andrea Vasella,

Asymmetric Synthesis and Catalysis

Stereoselectivity and Reactivity in the 1,3‐Dipolar Cycloaddition of Chiral N ‐(Alkoxyalkyl)nitrones The 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 (5 S )‐configuration. ‐ Use of the hydroxy‐oxime 65 allows synthesis of optically active isoxazolidines with regeneration of the starting hydroxy‐oxime.