Palladium(II)-Catalyzed Asymmetric 1,3-Dipolar Cycloaddition of Nitrones to 3-Alkenoyl-1,3-oxazolidin-2-ones

• Published in: Journal of organic chemistry 1999-07, Vol.64 (14), p.5017-5023
• Main Authors: Hori, Kazushige, Kodama, Hidehiko, Ohta, Tetsuo, Furukawa, Isao
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo981483g

Chiral phosphinepalladium(II)-catalyzed asymmetric 1,3-dipolar cycloaddition of nitrones to α,β-unsaturated carboxylic acid derivatives has been investigated. In the presence of a catalytic amount of [Pd(NCMe)2{(S)-tolbinap}](BF4)2 [TolBINAP = 2,2‘-bis(di-p-tolylphosphino)-1,1‘-binaphthyl], the reaction of 3-alkenoyl-1,3-oxazolidin-2-ones as dipolarophiles and N-substituted N-benzylidenenitrones has been successfully performed to give isoxazolidine derivatives in high yields with high enantioselectivities. For example, 3-((2,5-dimethyl-3-phenylisoxazolidin-4-yl)carbonyl)-1,3-oxazolidin-2-one was obtained from the reaction of N-benzylidenemethylamine N-oxide and 3-crotonoyl-1,3-oxazolidin-2-one in 89% yield with 60% endo selectivity and 91% ee of the endo isomer. The cycloaddition of N-benzylidenebenzylamine N-oxide and 3-crotonoyl-1,3-oxazolidin-2-one afforded 3-((2-benzyl-5-methyl-3-phenylisoxazolidin-4-yl)carbonyl)-1,3-oxazolidin-2-one in 94% yield with 93% endo selectivity and 89% ee of the endo isomer. Remarkably, the endo/exo selectivity of the products depended on the N-substituent group of the nitrones. These selectivities were explained using molecular modeling.