Dedicated to Professor J. Plumet on the occasion of his 60th birthdayThe 1,3-dipolar cycloaddition of nitrones to alkenes [1] is an atom-economic method for the construction of isoxazolidines, which are important precursors of, for example, alkaloids, amino acids, b-lactams, and amino sugars.[2] Typically, an electron-deficient alkene is involved, with the interaction between the LUMO of the alkene and the HOMO of the nitrone being the determinant for the relative orientation of the reactants. However, steric factors often counterbalance the electronic preferences, particularly in b-unsubstituted enoyl (acryloyl) systems, and make regiocontrol challenging. [3,4] Additionally, both endo/exo and p-facial selectivity have to be addressed. Although amine activation of enals [5] has emerged as an attractive approach, most methods rely on the use of Lewis acids to activate the enoyl system toward the nitrone counterpart. [3,4,6] However, despite the many applications, success in asymmetric nitrone cycloadditions remains very scarce compared to that reached in the parent DielsAlder cycloaddition and only a limited number of alkene templates such as N-enoyl derivatives of oxazolidinone, [4a-c, 6c-6g] thiazolidinethione, [6a] pyrrolidinone, [6b] and pyrazolidinone, [6h] as well as certain alkylidene malonates [6i] have been employed to fulfill this gap. In metal-catalyzed nitrone cycloadditions, not only are bidentate alkene substrates required but also metal-substrate coordination needs to be notably efficient for optimum selectivity. [7] We report herein that excellent combined levels of regio-, endo/exo-, and enantioselectivity may be achieved by using a'-hydroxy enones as new partners for this reaction.Recent observations from these laboratories in the context of Diels-Alder and conjugate addition reactions have shown the role of a'-hydroxy enones in metal-assisted activation, which likely occurs through formation of 1,4-metal-chelated species as the reactive intermediates.[8] It was argued that such a complexation pattern might be effective in nitrone cycloadditions and hence increase the pool of available templates for this reaction. To evaluate this assumption, initial screening reactions were carried out with the chiral a'-hydroxy enone 1 [9] and nitrone 3 a in the presence of several metal triflates (Scheme 1 and Table 1). Data revealed that Cu(OTf) 2 gave the best results and isoxazolidine 4 a could indeed be obtained in high yield and, most notably, with essentially perfect regio-and diastereoselectivity.Gratifyingly, the chemical efficiency and the high degree of regio-and stereocontrol for this Cu(OTf) 2 -mediated reaction was found to be quite general over the range of nitrones 3 a-k examined (Table 2). Nitrones bearing electronrich, electron-neutral, or electron-poor aryl substituents were tolerated with almost equal efficiency to give isoxazolidines 4 a-k in good yields and with diastereomeric ratios ranging Scheme 1. Regio-and stereocontrolled 1,3-dipolar cycloadditions of nitrones to a'-hydroxy enon...