IMPROVEMENT OF TADDOLATE-TICL2-CATALYZED 1,3-DIPOLAR NITRONE CYCLOADDITION REACTIONS BY SUBSTITUTION OF THE OXAZOLIDINONE AUXILIARY OF THE ALKENE WITH SUCCINIMIDE

A significant improvement of metal-catalyzed asymmetric 1,3-dipolar cy cloaddition reactions of acyclic nitrones with alpha,beta-unsaturated carbonyl compounds is described using succinimide as a new auxiliary f or the alpha,beta-unsaturated carbonyl moiety. In the absence of a cat alyst, N-crotonoylsuccinimide reacts with C,N-diphenylnitrone to give the ende-isoxazolidine, whereas in the presence of 10 mol % TiCl2(i-Pr O)(2) the exo-product is obtained. Four different TiCl2-TADDOLate comp lexes have been tested as catalysts for the 1,3-dipolar cycloaddition reactions, and the most successful catalyst was applied (5 mol%) in a series of reactions between two different alkenoylsuccinimides and thr ee different nitrones. The crude products containing an N-acylsuccinim ide moiety were converted directly into the corresponding carboxamides upon treatment with hydrazine. The 1,3-dipolar cycloaddition reaction s proceed with a high degree of exo-selectivity, often >90% de, which is an improvement compared with previous experiments performed using t he oxazolidinone auxiliary for the alkenoyl moiety. Furthermore, the e nantioselectivities are also improved compared with previous work, and ee up to 73% is obtained, which is the highest ee found for these met al-catalyzed exo-selective 1,3-dipolar cycloaddition reactions. The ee can be improved to >90% by recrystallization. The absolute structure of the 1,8-dipolar cycloaddition adduct is determined on the basis of the X-ray crystal structure of a compound with a known configuration. On the basis of this knowledge of the absolute structure of the produc t the mechanism of the reaction is briefly discussed.