Organocatalytic Asymmetric Synthesis of Trifluoromethyl-substituted Diarylpyrrolines: Enantioselective Conjugate Cyanation of β-Aryl-β-trifluoromethyl-disubstituted Enones

摘要

Trifluoromethylated dihydroazoles (1; Figure 1) are an important class of fluorinated heterocyclic compounds with remarkable biological activities, thus making their synthesis a competitive area in life science industries. Ever since the first discovery of the structurally unique 3,5-diaryl-5- (trifluoromethyl)-2-isoxazoline derivatives 1 (X = O) as pest control agents in 2004, the search for new agrochemicals and veterinary medicines has focused largely on this skeleton. Thus far, more than 20000 compounds have been registered, and several promising drug candidates of type A have been discovered (Figure 1). We recently reported the catalytic asymmetric synthesis of 1 using chiral ammonium salts of cinchona alkaloids to promote a hydroxylamine enone cascade reaction involving a conjugate addition/cyclization/ dehydration sequence.