Trifluoromethyl-substituted 2-isoxazolines

Likewise, trifluoromethyl-substituted nitrile imines [172] and nitrile oxides [173,174, 775] have been used to synthesize trifluoromethyl substituted five-membered ring systems of the pyrazole, isomzole, isoxazoline, and 1,2,4-oxadiazole... 

Alternatively, Shibata and coworkers first realized the catalytic enantioselective synthesis of trifluoromethyl-substituted 2-isoxazolines 69 in 2010 by developing a cinchona-alkaloid-catalyzed asymmetric conjugate addition/cyclization/dehydration cascade reaction with hydroxylamines 67 and enones 68 (Scheme 2.19). A wide range of substrates could be employed in this reaction to give the desired cyclized products with excellent enantioselectivities [33]. 

Since heterocycles containing a trifluoromethyl group are representatives of a major structure type in agricultural and medicinal chemistry, Shibata ct al. have developed a novel enantioselective synthesis of trifluoromethyl-substituted 2-isoxazolines 46 on the basis of a domino oxa-Michael-intramolecular hemi-aminahzation-dehydration reaction of hydroxylamine with a range of ( )-trifluoromethylated enone derivatives 47 [81]. This process, which employed N-3,5-bis(trifluoromethyl)benzyl-quinidinium bromide 48 as a chiral phase-transfer catalyst combined with CsOH as a base provided a series of trifluoromethyl-substituted 2-isoxazolines 46 in high yields and enantioselectivities of up to 94% ee (Scheme 37.8). 

Scheme 37.8 Synthesis of trifluoromethyl-substituted 2-isoxazolines through a domino oxa-Michael-intramolecular hemi-aminalization-dehydration reaction.

Shibata and coworkers [135] described the asymmetric phase-transfer catalytic synthesis of trifluoromethyl-substituted 2-isoxazolines 100 by an enantioselective conjugate addition of hydroxylamine to trifluoromethylated enones 99 and subsequent intramolecular formation of the imine, whereas Briere et al. [136] developed a facile method for the straightforward enantioselective synthesis of 3,5-diaryl pyrazoHnes 102 by phase-transfer-catalyzed conjugate addition of N-Boc-hydrazine... 

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