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

Abstract

1,1'-Diarylbutyl groups are a common pharmacophore found in many biologically active small molecules. To access these systems under mild conditions, the reaction of diarylmethyl trichloroacetimidates with allyltributylstannanes was explored. Simply heating allyltributylstannane with the trichloroacetimidate resulted in substitution of the imidate with an allyl group. Unlike other methods used to access these systems, no strong base, transition metal catalyst, Brønsted acid or Lewis acid promoter was required to affect the transformation. Conversions are best with electron rich benzylic trichloroacetimidate systems, where excellent yields are achieved just by refluxing the reactants together in nitromethane.

Dialkylation of Indoles with Trichloroacetimidates to Access 3,3-Disubstituted Indolenines

“…Our recent studies on promoter free substitution reactions with trichloroacetimidate electrophiles [68,69,70,71,72,73,74] led us to speculate that imidates may be reactive enough to participate in indole dialkylation without the need for a Lewis acid catalyst. Heating 2-methyl indole 14 and allyl trichloroacetimidate 11 in refluxing 1,2-dichloroethane (DCE) for 24 h showed no trace of alkylation product, however, so the use of TMSOTf as the Lewis acid was then investigated (Table 1).…”

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.…”