Trifluoromethyl substituted ketimines

Scheme 1.7 Preparation of trifluoromethyl substituted ketimines via the ethanolate adduct.

Optically active trifluoromethyl-substituted tetrahydroimidazo[l, 5-c] quinazoline derivatives 44 were synthesized by Zhao and coworkers via a diastereo- and enantioselective Mannich-type cyclization cascade reaction of a-aryl isocyanoacetates and trifluoromethyl-substituted cyclic ketimines, using a multihydrogen-bonding donor squaramide/AgOAc cooperative catalytic system in THF at 0°C (Scheme 30) (140L4566). The products were obtained in 76—99% yield with a diastereomeric ratio of greater than 15 1 and 58-98% enantiomeric excess. 

The C6 thiourea 24 has been shown recently to be well suited for the enanti-oselective aza-Henry reaction of rritromethane with ketimines, yielding the products in high yields and ee s (Scheme 6.29) [71]. The reaction was also performed with a nitro-cyclopropane alkane and a trifluoromethyl substituted ketamine, thus forming a precursor for the synthesis of possible anti-HIV drug candidates. 

The only example of an N-sulfonyl ketimine participating in an ene reaction involves the tosyl imine of trifluoroacetone 266 [90] [Eq.(62)]. When heated with a terminal olefin such as allyl benzene (265) in refluxing xylene, imine 266 leads to ene product 267 in moderate yields. However, internal alkenes gave significantly lower yields of ene products. The inefficiency of the ene process with more highly substituted olefins was ascribed to unfavorable steric effects due to the bulky trifluoromethyl groups. Interestingly, with /J-methyl styrene and allyl thiophenyl ether, [2+2]-cycloadducts were detected rather than ene products. 

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