Diastereoselectivity nitrile oxide cycloadditions

The 1,3-DC of nitrile oxides and alkenes leads to the formation of 2-isoxazolines, which are useful building blocks in organic chemistry. While the diastereoselective nitrile oxide cycloadditions have been investigated extensively, the development of enantioselective variants is quite rare. 

The convergence of the nitronate and nitrile oxide cycloadditions has allowed for the direct comparisons of yields and stereoselectivities of the two processes. For intramolecular reactions, the nitronate dipole typically required longer reaction times and/or elevated temperatures (22,98,135), however, the nitronate cycloaddition shows considerably higher diastereoselectivity (Table 2.42). Interestingly, the diastereoselectivity is dependent on the placement of a substituent on the tether. In the case of the silyl nitronate derived from 172, the diastereoselectivity is controlled by the substituent at C(l), while cyclization of the analogous nitrile oxide is governed by the substituent at C(l ) (Scheme 2.10) (124). 

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-isoxazohnes, the application of Lewis acid catalysis to nitrile oxide cycloadditions with 4-chiral 3-(2-aIkenoyl)-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 ffc-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 a,p-unsaturated amides 180-188a have all been used in 1,3-dipolar cycloadditions with nitrile oxides, and some of them represent the most diastereoselective reactions of nitrile oxides. The camphor derivative 180 of Chen and co-workers (294), the sultam 181 of Oppolzer et al. (295), and the two Kemp s acid derived compounds 186 (296) and 187 (297) described by Curran et al. (296) are excellent partners for diastereoselective reactions with nitrile oxides, as very high diastereos-electivities have been observed for all of them. In particular, compound 186 gave, with few exceptions, complete diastereoselection in reactions with a wide range of different nitrile oxides. Good selectivities were also observed when using compounds 183 (298) and 184 (299-301) in nitrile oxide cycloadditions, and they have the advantage that they are more readily available. Curran and co-workers also studied the 1,3-dipolar cycloaddition of 187 with silyl nitronates. However, compared to the reactions of nitrile oxides, lower selectivities of up to 86% de were obtained (302). 

N. P. Peet, E. W. Huber, and R. A. Farr, Diastereoselectivity in the intramolecular nitrone, oxime, and nitrile oxide cycloaddition reactions, Tetrahedron 47 7537 (1991). 

Houk s model has been used to account for diastereoselectivity observed in nitrile oxide cycloadditions with the (a-oxyallyl)silanes (46) (88T3945). The direction and magnitude of asymmetric induction was... 

In the case of the ( )-alkene, the diastereoselectivity parallels that observed in nitrile oxide cycloadditions, since the cis configuration is derived from the inside (C-4)-alkoxy conformation. For the inside alkoxy conformation for the (Z)-alkene, a severe steric interaction of the ester group and a methyl of the isopropylidene group is present, hence the ra i-diastereomer is obtained135. 

In addition to being an efficient chiral controller in a number of stereoselective transformations of chiral acrylates, (i.e. the Diels-Alder reaction, the conjugate reduction, the asymmetric dihydroxylation, and the nitrile oxide cycloaddition ) the bomanesultam (11) has been shown to be an exceptionally efficient chiral auxiliary for stereoselective aldol condensations (eqs eq 3 and eq 4). Depending upon the reaction conditions, A -propionylsultam can produce either the syn or anti aldol product with an excellent diastereoselectivity, Furthermore, good diastereoselectiv-ities are also observed for the corresponding acetate aldol reaction (eq 5), ... 

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