Synthesis of 1,1′-Diarylethanes and Related Systems by Displacement of Trichloroacetimidates with Trimethylaluminum

Abstract

Benzylic trichloroacetimidates are readily displaced by trimethylaluminum under Lewis acid promoted conditions to provide the corresponding methyl substitution product. This method is a convenient way to access 1,1'-diarylethanes and related systems, which play a significant role in medicinal chemistry, with a number of systems owing their biological activity to this functionality. Most benzylic substrates undergo ready displacement, with electron deficient systems being the exception. The use of an enantiopure imidate showed significant racemization, implicating the formation of a cationic intermediate.

Ester Formation via Symbiotic Activation Utilizing Trichloroacetimidate Electrophiles

“…The methyl-2,2,2-trichloroacetimidate 10 , ethyl-2,2,2-trichloroacetimidate 11 , t -butyl-2,2,2-trichloroacetimidate 13 , allyl-2,2,2-trichloroacetimidate 14 , and benzyl-2,2,2-trichloroacetimidate 17 used in these studies were purchased from commercial sources. Cyclohexyl-2,2,2-trichloroacetimidate 12 , prenyl-2,2,2-trichloroacetimidate 15 , propargyl-2,2,2-trichloroacetimidate 16 , (2,4,6-trimethylphenyl)­methyl-2,2,2-trichloroacetimidate 18 , (4-methoxyphenyl)­methyl-2,2,2-trichloroacetimidate 20 , (3,4-dimethoxoxyphenyl)­methyl-2,2,2-trichloroacetimidate 22 , (4-nitrophenyl)­methyl-2,2,2-trichloroacetimidate 23 , furfuryl-2,2,2-trichloroacetimidate 24 , 1-phenethyl-2,2,2-trichloroacetimidate 25 , , diphenylmethyl-2,2,2-trichloroacetimidate 26 , , and (2-methoxyphenyl)­phenylmethyl-2,2,2-trichloroacetimidate 29 were synthesized as previously reported.…”

Promoter free allylation of trichloroacetimidates with allyltributylstannanes under thermal conditions to access the common 1,1′-diarylbutyl pharmacophore

“…17 More recently the first displacement of an imidate with an alkylmetal reagent (trimethylaluminum) was reported, although in most cases this also required a Lewis acid promoter to achieve good yields. 18 In this study the direct C–C bond formation of benzylic trichloroacetimidates with a stable carbon nucleophile (allyltributylstannanes) is investigated, with the premise that it will lead to a new method to access 1,1′-diarylbutyl groups under mild conditions.…”