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

Abstract

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.

4.22 Intermolecular 1,3-Dipolar Cycloadditions of Alkenes, Alkynes, and Allenes

“…13 It was believed that the endo/exo-selectivity of the products depends on the N-substituent group of nitrones 20. With benzyl-substituted nitrone 20a, the reaction resulted in 97/3 endo/exo-selectivity.…”

Asymmetric 1,3-dipolar cycloadditions of acrylamides

“…153,154 Late transition metal complexes such as palladium are advantageous as they do not require strictly anhydrous conditions. Employment of the (S)-TolBINAP ligand in the palladium complex 70 led to an endo:exo ratio of up to 93:7, with excellent enantioselectivity for both isomers (entries 22-24, Table 3).…”

Metal-Assisted Stereocontrol of 1,3-Dipolar Cycloaddition Reactions

“…49 Although the reaction types are quite different to each other, both groups reported in 1994 the first successful catalyzed enantioselective nitrone cycloaddition reactions using both achiral nitrones and alkenes by the aid of enantiopure Lewis acid catalysts. After great leading contributions from Jørgensen's group [50][51][52][53][54][55][56][57][64][65][66][67] as well as other groups including Furukawa, 58,59 Kobayashi, 60 Kanemasa,61 Scheeren, 62,63 and others, 68,69 this field has been developed to a high level of diastereoselectivity, enantioselectivity, and catalytic efficiency. All these reactions have been demonstrated successfully by use of dipolarophiles having chelating auxiliaries.…”