Thieno isoxazoline

Thieno[2,3-d]isoxazoline, 4,4-dioxo-3-(2,4,6-trimethylphenyl)-3 a,6a-dihydro-synthesis, 6, 998... 

The first example of a [2 + 4] cycloaddition of a thiophene 1-oxide seems to be the formation of a 1 1 mixture of the syn and anti isomers of 3-(2,4,6-trimethylphenyl)-8b-methylbenzo[6]thieno[2,3-mesitonitrile oxide with 3-methyIbenzo[6]thiophene 1-oxide (Scheme 190) (79TL4845). The cycloaddition seems to be regioselective. 

From 3,4-dibromotetrahydrothiophene 1,1-dioxide in the presence of pyridine and mesitonitrile oxide is obtained 4,4-dioxo-3-(2,4,6-trimethylphenyl)-3a,6a-dihydro-thieno[2,3-d]isoxazoline (172). A second equivalent of nitrile oxide leads to the formation of the 2 1 adduct (173). NMR analysis and crystallographic studies show the formation of the adduct where the regioselectivity corresponds to the oxygen atom of the dipoles bonded to the carbon atom /3 to the sulfone group, the endo nature of the addition, and the anti situation of the two rings in the diadduct (173) (81JOC3502). 

Either intramolecular nitrile oxide cycloadditions (INOC) or intramolecular silylnitroate cycloadditions (ISOC) of /3-nitrosulfides 477 gives isomeric thieno[3,4-c]isoxazolines 478 and 479 (Equation 17) <1997SC1865>. 

Ab initio MO calculations on 3-formyl-(5 2-isoxazoline-BF3-complex suggests that s-trans conformation is preferred over s-cis conformation. Nucleophiles attack the stable s-trans conformer from the opposite side of the C-4 substituent, giving the respective anti adducts <93T7637>. The regioselectivity of the 1,3-dipolar cycloadditions of mesitonitrile oxide with benzo[b]thiophene S-oxide and S,S-dioxide yielding only 2,3-dihydrobenzo[b]thieno[2,3-d]isoxazolines, is discussed in terms of frontier MO interactions on the basis of photoelectron spectra and CNDO/S calculations <82JOC2461>. 

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