Isoxazoli dines

IsoxazoIidine-3,3-dicarboxylic acid, 2-methoxy-dimethyl ester reaction with bases, 6, 47 Isoxazolidine-3,5-diones synthesis, 6, 112, 113 Isoxazoli dines conformation, 6, 10 3,5-disubstituted synthesis, 6, 109 oxidation, 6, 45-46 PE spectra, 6, 5 photolysis, 6, 46 pyrolysis, 6, 46 reactions, 6, 45-47 with acetone, 6, 47 with bases, 6, 47 reduction, 6, 45 ring fission, S, 80 spectroscopy, 6, 6 synthesis, 6, 3, 108-112 thermochemistry, 6, 10 Isoxazolidin-3-ol synthesis, 6, 111 Isoxazolidin-5-oI synthesis, 6, 111... 

Whereas there are numerous examples of the application of the products from diastereoselective 1,3-dipolar cycloaddition reaction in synthesis [7, 8], there are only very few examples on the application of the products from metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction in the synthesis of potential target molecules. The reason for this may be due to the fact that most metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction have been carried out on model systems that have not been optimized for further derivatization. One exception of this is the synthesis of a / -lactam by Kobayashi and Kawamura [84]. The isoxazoli-dine endo-21h, which was obtained in 96% ee from the Yb(OTf)3-BINOL-catalyzed... 

Like the nitrone-olefin [3 + 2]-cycloaddition, the nitrone-allene [3 + 21-cycloaddition also takes place regioselectively to furnish methylene-substituted isoxazoli-dine derivatives. The substituents of the 3- and 4-positions of the cycloadducts 72a and 72b are disposed cis in contrast, the reaction of 70 with allenyl sulfone 71c gives rise to the trans-cycloadduct 72c exclusively (Table 12.4). On treatment with base or heating, methyleneisoxazolidines 72 readily rearrange to isoxazo-lines via a 1,3-hydrogen shift. 

The alkenyl nitrone 321 can conceivably undergo two different cycloaddition modes to afford either the bridged bicyclo[2.2.1] adduct 322 or the fused bicyclo[3.2.0] adduct 323. Three examples of fused adducts were reported, each formed with total diastereoselectivity, and on reductive cleavage of the isoxazoli-dine N—O bond (with concomitant N-debenzylation) they afforded the corresponding polysubstituted cyclobutylamines. 

Ukaji and co-workers (379-381) described the first, and so far only, metal-catalyzed asymmetric 1,3-dipolar cycloaddition of nitrile oxides with alkenes. Upon treatment of allyl alcohol with diethylzinc and (7 ,/ )-diisopropyl tartrate followed by the addition of diethylzinc and substimted hydroximoyl chlorides 274, the isoxazoli-dines 275 are formed with enantioselectivities of up to 96% ee (Scheme 12.87). 

In addition to the procedures listed in Table 3.38, further reactions have been used to generate halides upon cleavage. In Section 3.5.2, iodolactonization is presented as a method for the preparation of iodomethyl lactones from resin-bound pentenoic or hexenoic acid derivatives. Closely related to the iodolactonization is the iodine-mediated formation of 2-(iodomethyl)tetrahydrofurans from resin-bound isoxazoli-dines (Entry 9, Table 3.38 for the mechanism, see Figure 15.5). Nitriles can also be prepared by cleavage and simultaneous dehydration of amides RCONH2 from the Rink or Sieber linkers with TFA anhydride (Entry 10, Table 3.38). 

The procedure described illustrates the use of 1,3-dipolar addition7 of nitrones to olefins for the preparation of isoxazoli-dines The preparations of 2,3,5,5-tetraphenylisoxazolidine and ethyl 2,3-diphenyl-5-methylisoxazolidine-4-carboxylate, as described in Notes 9 and 10, respectively, indicate the versatility of the method. 

In 2003, the thermolysis of 3,4-cis ring-fused 5-spirocyclopropane isoxazoli-dines, in the presence of a protic acid (TFA) at 70-110°C, has been reported to yield 3,4-c/s ring-fused azetidin-2-ones with concomitant extrusion of ethylene, in good yields (Scheme 93), [201]. 

Chmielewski and colleagues reported a Bu3SnH-mediated radical-induced isoxazoli-dine-isoxazolidin-5-one transformation (equation 99)778, while Sulsky and coworkers described conformational switching in the synthesis of a spiro[2H-indol]-3(lH)-ones (e.g. 122) by radical cyclization, an example of which is depicted in equation 100787. In this final example, Takekawa and Shishido described the selective cleavage of substituted cyclopropanes via stannane-induced radical fragmentation, an example of which is illustrated in equation 101791. 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

In a recent example the singlet nitrenium ion 155 derived from isoxazoli-dines undergoes rearrangement via aryl migration with the participation of the pentacoordinate intermediate [Eq. (6.152)] ... 

After removal of the solvent, 13-14 g. (82-88%) of the isoxazoli-dine is obtained as an orange oil by high-vacuum distillation at 163-173° (0.003 mm.). Redistillation of this material yields... 

TL4419). The exo adduct 16 is formed in 95% ee from diphenylnitrone and 3-crotonyl-oxozolidin-2-one in the presence of titanium catalysts generated in situ from diisopropyl-titanium dichloride and chiral diols (94JOC5687). Intramolecular cycloaddition of the nitrone 17 yields the bicyclic isoxazoli-dine 18 stereoselectively (94JCS1661). The oxadiazabicyclo[3.3.0]octane 21 is formed when the oxime 19 is heated. The reaction proceeds by an intramolecular 1,3-dipolar... 

On the other hand, Ali and co-workers reported that the anomeric effect dictates the solution conformational behavior of several isoxazoli-dines, which exist in several envelope and half-chair puckered conformations (95SA(A)2279). As evidenced by NMR, nitrogen inversion converts the cis isomer (cis-4) into the trans isomer (trans- ), and the small coupling constants (0-1.5 Hz) between the C5-H proton and the C4r-H protons suggest a dihedral angle near 90°, which indicates that cis- and trans-4 adopt a conformation with a pseudoaxially oriented ethoxy group as a... 

The effect of the addition of Lewis acid upon the stereoselectivity of cycloaddition of chiral nitrones 3a and 34 to electron-rich alkene, with ethyl vinyl ether and the further transformation of so-prepared isoxazoli-dine 36b to new fi-amino acid ester 40, has been also investigated by the same team (Fig. 10). The 1,3-dipolar cycloaddition of nitrone 3a with ethyl vinyl ether imder AlMes and Et2AlCl catalysis proceeded diastereoselectively and finished at - 8 °C over 20 h, providing only two diastereoisomers 35a and 36a in a ratio of 90 10 with erythro-cis 35a predominant, although four diastereoisomers are possible. Indeed, cycloaddition in the absence of any Lewis acids proceeded very slowly with excess of ethyl vinyl ether at room temperature over 14 days to give a mixture of all four diastereoisomers 35-38 with a considerable decrease of the stereoselectivity in a ratio of 59 12 14 15, although erythro-cis 35a was still the major adduct. The 1,3-... 

It was thought this could be achieved by treatment of the alkoxylamine with Yb(OTf)3 first to generate the isoxazoli-dine 30 before addition of the aldehyde (Scheme 10.48). This would most likely result in the Z-oxy-iminium species as the most favored conformation to afford the cw-adduct [43]. The hypothesis was tested and resulted in the successful synthesis of 2,5-cw-pyrrolo-isoxazolidines with excellent yields and diastereoselectivity. An example is shown in Scheme 10.48. 

With few exceptions [125], the 5-substituted isoxazoli-dines are produced selectively from monosubstituted... 

Moon M-E, Park JY, Jeong E-H, Vajpayee V, Kim H, Chi K-W. Regio- and diastereoselective 1,3-dipolar cycloaddition between perfluoro-2-methyl-2-pentene and nitrones a facile approach to partially-fluorinated isoxazoli-dines. Bull. Korean Chem. Soc. 2010 31(6) 1515-1518. 

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