Synthesis of α-trifluoromethylated amides by Eschenmoser–Claisen-type rearrangement of allylic alcohols

A new, mild method to prepare α-trifluoromethylated amides bearing an additional trans-configured double bond in γ-position is described. Treatment at room temperature of fluorinated and non-fluorinated allylic alcohols 1 and 2 with the 1,1,3,3,3-pentafluoropropene–diethylamine adduct (PFPDEA) in the presence of triethylamine as base gave the products of [3,3]-sigmatropic Eschenmoser–Claisen-type rearrangements with good yields and excellent diastereoselectivity due to chair-like conformations of transition states. Starting with enantiomerically enriched allylic alcohols chirality transfer from carbon 3 of the allylic system to carbon 2 of the final α-trifluoromethyl carboxamides was observed. This methodology was applied to both simple and more complex, including terpenic, allylic alcohols and might be developed to an alternative strategy to the well-known electrophilic α-trifluoromethylation of carbonyl compounds.

Graphical abstractA new, mild method to prepare α-trifluoromethylated amides bearing an additional trans-configured double bond in γ-position is described. Treatment at room temperature of fluorinated and non-fluorinated allylic alcohols 1 and 2 with the 1,1,3,3,3-pentafluoropropene-diethylamine adduct (PFPDEA) in the presence of triethylamine as base gave the products of [3,3]-sigmatropic Eschenmoser–Claisen-type rearrangements with good yields and excellent diastereoselectivity due to chair-like conformations of transition states. Starting with enantiomerically enriched allylic alcohols chirality transfer from carbon 3 of the allylic system to carbon 2 of the final α-trifluoromethyl carboxamides was observed. This methodology was applied to both simple and more complex, including terpenic, allylic alcohols and might be developed to an alternative strategy to the well-known electrophilic α-trifluoromethylation of carbonyl compounds.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► One-pot, stereospecific synthesis of α-trifluoromethyl-γ,δ-unsaturated amides by a Eschenmoser–Claisen-type rearrangement. ► Chirality transfer from carbon C-3 of the enantiomerically enriched allylic alcohol to C-2 of the corresponding carboxamide. ► General mechanism of action of the pentafluoropropene-diethylamine adduct towards different alcohols.