Achiral dipolarophiles, nitrile oxide cycloadditions

Yamamoto and co-workers (135,135-137) recently reported a new method for stereocontrol in nitrile oxide cycloadditions. Metal ion-catalyzed diastereoselective asymmetric reactions using chiral electron-deficient dipolarophiles have remained unreported except for reactions using a-methylene-p-hydroxy esters, which were described in Section 11.2.2.6. Although synthetically very useful and, hence, attractive as an entry to the asymmetric synthesis of 2-isoxazolines, the application of Lewis acid catalysis to nitrile oxide cycloadditions with Achiral 3-(2-alkenoyl)-2-oxazolidinones has been unsuccessful, even when > 1 equiv of Lewis acids are employed. However, as shown in the Scheme 11.37, diastereoselectivities in favor of the ft-cycloadducts are improved (diastereomer ratio = 96 4) when the reactions are performed in dichloromethane in the presence of 1 equiv of MgBr2 at higher than normal concentrations (0.25 vs 0.083 M) (140). The Lewis acid... 

The relative rate constants (fe ) do not account for the fact that approach of the nitrile oxide to the 7i-bond can occur from both olefinic diastereofaces with two regioisomeric modes of reaction (Scheme 6.14). In the case of achiral 1-alkenes, only one regioisomer is formed. With chiral dipolarophiles, preference for one of the two is usually found (diastereodifferentiation). The relative diastereofacial reactivity (fejH) is used to evaluate this effect (121). With ethylene, there are four possibilities of attack (two for each face corresponding to the different regio-isomers), and the of each is set as 0.25. In diastereodifferentiating cycloadditions, such as those with a-chiral alkenes, the major isomer generally results... 

There is no doubt that the field of asymmetric induction occupies a very important place in modem synthetic methodology. Elegant protocols designed to cany out dipolar cycloadditions have been developed and important advances in the theoretical description of these processes have taken place as a consequence (vide infra) Diastereoselective cycloadditions have been carried out between optically active nitrile oxides, nitrones,azomethine ylides and achiral dipolarophiles, and between optically active dipolarophiles and achiral nitrile oxides and achiral nitrones. The products have b n put to good use, either by translating the cycloaddition diastereoselectivity to the construction of useful optically active acyclic intermediates, or in Ae total synthesis of natural products (vide infra) ... 

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