Facial selectivity nitrile oxide cycloadditions

Regio- and steroselective dipolar cycloadditons of benzonitrile oxide and C -diphenylnitrone to levoglucosenone have been recently reported (47). In both cases, the major product results from the addition of the l,3>dipole to the face of the enone opposite the 1,6-anhydro bridge, with the dipole oxygen becoming attached to the p-carbon of the enone. Facial selectivities of 100 1 were observed in the nitrile oxide cycloaddition). 

Facial selectivity in 1,3-dipolar cycloadditions to cis-3,4-dimethylcyclobutene (73) (Scheme 1.21) was studied. Only phenylglyoxylo- and pyruvonitrile oxides lacked facial selectivities (anti syn = 1 1). All other nitrile oxides formed preferably anti-74. The anti/syn ratio increased from 60 40 (R = P-O2NC6K4) and 65 35 (R = Ph) to 87 13 and 92 8 for bulky ten-Bu and mesityl substituents, respectively. The transition-state structure of the cycloaddition of formonitrile oxide was determined using both HF/6-31G and B3LYP/6-31G methods. The... 

Dihydroisoxazoles can be formed by stereoselective 1,3-dipolar cycloaddition of nitrile oxides, for example, to enantiopure allylic alcohols, and these products can be converted into -amino acids 510 by a characteristic nucleophilic addition to the C=N bond in 509 followed by reductive cleavage of the N—O bond and oxidative cleavage of the diol moiety. The facial selectivity in the nucleophilic addition is dictated by the C(5) substituent (Scheme 109), e.g., <2003JA6846, 2004SL1409, 2005JA5376>. 

Dipolar Cycloadditions with Nitrile Oxides (Alkene-+-Isoxazoline) 1,3-Dipolar cycloaddition reactions of N-acryloyl-a-t-butyltoluene-2,a-sultam (6) with various nitrile oxides give isoxazolines with extremely high C(a)-re rr-facial control (eq 3). The levels of selectivity exceed those obtainable with the 10,2-camphorsultam auxiliary and are comparable to the highest levels reported for such cycloadditions. The corresponding reactions of a-methyltoluene-2,a-sultams are less selective. 

High diastereomeric ratios were observed in the 1,3-dipolar cycloaddition of various nitrile oxides to the optically active alcohol 491 <1999TL4349> and the chiral acryloylhydrazides 492 and 493. For example, benzonitrile oxide afforded the isoxazoline 494 in dr = 99 1 <2000TL1453>. The level of facial selectivity obtained in the same 1,3-dipolar cycloaddition with the chiral 3-acryloyl-2-oxazolidinone 493 was very low (d.r. = 43 57), but in the presence of MgBr2 (1 equiv) the reaction proceeded with high diastereoselectivity to give preferentially the isoxazolidine 495 in d.r. =96 4 <2000TL3131>. 

Curran identified Oppolzer s camphor sultam (cf. 81) [77] as a superb chiral auxiliary for the asymmetric [l,3]-dipolar cycloadditions of nitrile oxides (Scheme 18.17) [78-80]. The resulting cycloadducts were generally obtained with high diastereofacial selectivity (dr 90 10). It was proposed that the observed facial differentiation was the result of attack by the nitrile oxide from the top face of conformer 84. This was suggested to be favored on the basis of electronic and steric effects, a proposition that finds support in an X-ray structural analysis of 81 [78, 80]. Cycloaddition of 81 with the nitrile oxide generated in situ from 80 led to isoxazoline 82 in 89 % yield (dr= 92 8). This product constituted a key intermediate in Curran s total synthesis of 83, a bicyclic ketal isolated from ambrosia beetles [80]. 

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