PAPER: Catalytic enantioselective inverse-electron demand 1,3-dipolar cycloaddition reactions of nitrones with alkenes

Simonsen, K. B.; Bayón, P.; Hazell, R. G.; Gothelf, K. V.; Jørgensen, K. A.

J. Am. Chem. Soc. 1999, 121, 3845–3853, doi: 10.1021/ja983915a

Center for Metal Catalyzed Reactions, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark


A general reaction protocol for catalytic enantioselective 1,3-dipolar cycloaddition reaction of nitrones, activated by chiral Lewis acids, with electron-rich alkenes has been developed. The nitrones are activated by various chiral 2,2‘-dihydroxy-1,1‘-binaphthyl (BINOL)-AlMe complexes, and it has been found that 3,3‘-diaryl-BINOL-AlMe complexes catalyze a highly regio-, diastereo-, and enantioselective 1,3-dipolar cycloaddition reaction of aromatic nitrones with vinyl ethers, giving the exo-diastereomer of the isoxazolidines with de’s up to >90% and up to 97% ee. The reaction has been investigated under various conditions with different nitrones and vinyl ethers (and alkenes), and a general synthetic procedure is presented. The mechanism for the reaction is discussed on the basis of a linear stereochemical effect of the catalyst, the diastereoselectivity, and absolute stereochemistry of the isoxazolidines formed, and theoretical calculations of the 3,3‘-diphenyl-BINOL-AlMe−nitrone intermediate.

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