3-Aryl-isoxazolidines

Aryl or alkyl substituents on the exocyclic double bond steer the regioselec-tivity towards the formation of isoxazolidine-4-spirocyclopropanes 274-276 (Table 22, entries 1-3). A complete reversal of regioselectivity to 277-279 was observed in the reactions of methoxycarbonyl substituted methylenecyclo-... 

As for the regioselectivity of the nitrone cycloaddition to MCP and its alkyl or aryl derivatives, a tendency of the three-membered ring to end up at the 4-position of the final isoxazolidine ring clearly emerges from the experimental findings. This result is particularly noteworthy if compared to regiospecific formation of the 5,5-disubstituted isoxazolidines in the reactions of nitrones, not... 

Cycloaddition of a-aryl-A-phenylnitrones to the C16-C17 n-bond in 16-dehydropregnenolone-3P-acetate (545) involves only the minor rotamer (A-form) of the nitrones. It proceeds regio-, stereo- and Jt-facial-selectively to give steroido[16,17-d]isoxazolidines (546) in high yield (Scheme 2.257), (Table 2.24) (760). Similarly the cycloaddition of a,N -diphenylnitrones proceeds with five-membered heterocyclic enones (761). 

The reactions of nitrones with 165 have been described (277-279). In the approach described by Koskinen and co-workers (279), the bulky nitrone 166 was used in a reaction with 165 to give a 20 1 mixture of 167 and an unidentified diastereomer (Note Opposite enantiomers are shown here). Reactions of less bulky nitrones gave lower selectivities (277,278). Kim et al. (280,281) described reactions of 165 with silyl nitronates (Scheme 12.52). The configuration of the direct isoxazolidine products was not determined. Instead, diastereoselectivities of 66-88% de of 169 were found after elimination of the silyloxy group. The reaction of various nitrile oxides proceeded to give the same isoxazoline products 169 as obtained for nitronates (Scheme 12.52). For the reactions of 165 with various alkyl and aryl nitrile oxides 170, the products 169 were obtained with diastereoselectivities of 62-90% de (282-286). In a theoretical study, it was proposed that the... 

Chiral crotonates derived from S-citronellol, l-(—)-menthol, and 5-solketol undergo 1,3-dipolar cycloaddition with cyclic and acyclic nitrones.66 Asymmetric 1,3-dipolar cycloaddition of optically active trifluoromethylated a, /i-unsaturated aryl sulfones (43) with nitrones yield the corresponding isoxazolidines (44) and (45) with high regio- and... 

A method was proposed [196] for the production of 4-phosphazenyl-2,3-dihydropyrrol-2-ones and 5-phosphazenyl-2-pyridones from p-(N-acylphosphazenyl)enamines of dimethyl acetylenedicarboxylate. The authors of [197] examined the chemoselective cycloaddition of C-aryl-N-phenyl nitrones at the 1,2 double bond of allenylphosphonates, leading to a mixture of adducts possessing pyrrolidine and isoxazolidine structures. 

Chromans possessing a fused isoxazolidine moiety 505 can be accessed via a palladium-catalyzed allene insertion-intramolecular 1,3-dipolar cycloaddition cascade reaction between ( )-fV-(2-hydroxybenzylidene)methanamine oxide, allene, and aryl iodides. This process creates two rings, two stereocentres and a quaternary carbon centre in one-pot (Equation 210) <2002CC1754>. 

A different domino reaction yet involving rather similar steps, i.e. car-bopalladation of an allene and nucleophilic attack of a phenol, was elaborated by the same group and leads to isoxazolidines 138 after intramolecular cycloaddition in the intermediates 137 [81] (Scheme 21). This transformation was performed with several aryl and hetaryl iodides 48 and gave the highest yields with electron-rich aryl iodides while only traces of products were obtained starting from electron-deficient aryl iodides. 

N- A ry I - 3 - (ary lmethy 1 )i soxazol id i nes were prepared from O-homoallylhydroxylamines by a Pd-catalyzed domino A-arylation/carboamination process. Optimized reaction conditions used catalytic amounts of Pd(dba)2 and of the bis(phosphine) ligand Xantphos in the presence of an excess of NaO -Bu as a base in toluene. Generally, the substituted isoxazolidines such as 86 were obtained with complete diastereoselectivity and good yields <07JOC3145>. 

The reduction of isoxazolium salts with metal hydrides is also not entirely predictable, and here the progress of the reaction depends on (i) the reagent, (ii) the solvent, and (Hi) the ring substituents. Generally, isoxazolium salts (119) on reduction with sodium borohydride in aqueous acetonitrile give 4-isoxazolines (120), their borane complexes, 3-isoxazolines (121), isoxazolidines (122), and minor amounts of 3-hydroxypropylamines (123). In some cases, however, particularly if the substituent group at C-3 is aryl and the reaction is carried out in ethanol rather than acetonitrile, the major products are... 

Isoxazolidines can be prepared by cyclization of homoallylic A-hydroxylamines. In fact, 5-(iodomethyl)isoxazolidines were obtained by iodocyclization of O-silylated AT-(but-3-enyl) hydroxylamine derived by allylation of prochiral and chiral nitrones <2002COR695, 2000S759>. For example, ry -510 and anti-% 2 underwent stereospecific iodocyclization to isoxazolidines 3,4-m-4,5-m-511 and 3,4-rra r-4,5- t-513, respectively, by treatment with A-iodosuccinimide (NIS) in CHCI3 at 0°C (Scheme 119) <2005TL3789>. Under the same conditions, aryl-substituted 510 and 513 (R = Ph, 4-MeOC6H4) failed to give the corresponding isoxazolidines. 

Diaryl-substituted isoxazolidines were synthesized in a one-pot reaction starting from aryl halides and 0-homoallyl hydroxylamines through a diastereoselective cascade reaction catalyzed by Pd(0). The choice of the phosphine ligand was shown to affect the product distribution between the isoxazolidine and the Heck-type product. The best results were obtained when 1 mol% of Pd2(DBA)3/P(o-Tol)3 was used (DBA = dibenzylideneacetone). For example, under these conditions, isoxazolidine 520 was obtained in 79% yield together with a minor amount of the Heck coupling adduct 521 (Equation 83) <2006TL927>. 

CsMes)M (i )-l,2-bis(diphenylphosphino)propane (H20)] were found to catalyze the 1,3-dipolar cycloaddition of some acyclic and cyclic nitrones with methacrolein with complete diastereoselectivity and good enantioselec-tivity. Some intermediates involved in the process were isolated and characterized and a catalytic cycle involving [M]-aldehyde, [M]-nitrone, and [M]-adduct species was proposed <2005JA13386>. The reactions of A -phenyl C-aryl nitrones with the electron-poor a-bromoacrolein were effectively catalyzed by Zn(ll) complexes such as 534 and afforded isoxazolidine-4-carboxaldehydes, with high diastereo- and enantioselectivity, that were reduced to the corresponding alcohols (Scheme 123) <2004TL4061>. 

Several 2-aryl- and 2-phenylmethyl-3,5-isoxazolidine-dlones were synthesized and found to be bleaching herbicides with good tolerance by soybeans. The most active member, 2-(2-chlorophenyl)methyl-4,4-dimethyl-3,5-isoxazolidinedione, failed to perform in the field due to its instability in soil. To improve the chemical stability by molecular modifications, a series of 3-isoxazolidinones were prepared and found to be highly active bleaching herbicides with excellent soybean tolerance. Synthesis and structure-activity relationships are discussed. One of the most active compounds,... 

The ring nitrogen of N-unsubstituted, iV-alkyl or A7-aryl substituted isoxazolidines are stable under mild conditions. As strong bases, they form quaternary salts. 

Both N-substituted (alkyl/aryl) and N-unsubstituted isoxazolidines are fairly stable to base under mild conditions. Strong base-promoted ring fission or decomposition results are reported <84JOC282, 84TL5355>. 

Cycloaddition reactions as an approach to nitrogen- and oxygen-containing heterocycles have dominated the literature this year and are the topic of the remainder of this section. The intramolecular cycloaddition of aryl oxaziridines to give fused isoxazolidines (71) proceeds in good yield, presumably via a nitrone intermediate. On the other hand the oxime (72) undergoes an intramolecular cycloaddition to give the isoxazolidine (73) and can either be... 

N-Aryl nitrones were generated by visible light-mediated oxidation of N-substituted Af-aryl hydroxylamines e.g. 89 in the presence of a catalytic amount of an Ir(III) polypyridyl complex and the resulting 90 trapped in situ with suitable dipolarophiles. For example, isoxazolidine 91 was synthesized in high yield and good cf5-stereoselectivity in the presence of an excess of ethyl vinyl ether (140L2872). 

Dongol and Tay [110] have recently made use of an intramolecular amination in the development of a one-pot synthesis of isoxazolidines starting from 0-homoallyl hydrox-ylamines 201 and aryl iodides. After a Mizoroki-Heck reaction, a subsequent C—N... 

The Cu(II)-BOX-complex-catalysed 3 + 2-cycloaddition of nitrones with 2-alkenoyl pyridine A -oxide formed isoxazolidines with high diastereo-and enantio-selectivities. ° Microwave catalysis of the 1,3-dipolar cycloaddition of 0 nitrones with tetraethyl l,l-ethenediylbis(phosphonate) produced isoxazolidine (g) bisphosphonates in the absence of solvents. The intennolecular 1,3-dipolar cycloaddition of dimethyl 2-benzylidenecyclopropane-l,l-dicarboxylate with C-aryl or C-amido nitrones formed spiro(cyclopropane-l,4-isoxazolidine) cycloadducts The 1,3-dipolar cycloaddition of nitrones (52) with vinylidenecyclopropanes (53) produced 4-cyclopropylidine-isoxazolidines (54) in moderate yields (Scheme 16). ... 

Isoxazolidine-fused P-lactams 85 were synthesized through a base-promoted cyclization-cyclopropane ring opening of 4-spirocyclopro-paneisoxazolidines 84 prepared in turn by 1,3-DC of N-aryl C-carbamoylnitrones and 2-arylmethylidenecyclopropanedicarboxylates (13T5173). 

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