Copper(I)-Catalyzed Oxydifluoroalkylation of Alkenes: A Route to Functionalization of Lactones

Abstract

An efficient copper(I)-catalyzed oxydifluoroalkylation of unsaturated carboxylic acids has been developed under mild reaction conditions. Various α-bromodifluoromethyl substituted heterocycles, esters, amides, and ketones were successfully employed as the CF source. This cost-effective copper(I) catalysis provides expedient access to high valued lactones with ample substrate scope, wide functional group tolerance, and up to 98% yield.

Electrochemical fluoromethylation triggered lactonizations of alkenes under semi-aqueous conditions

“…Lactones constitute useful building blocks in many pharmaceutically relevant molecules 13. In this regard, the construction of unprecedented CF 2 H-containing lactones may be beneficial for medicinal chemistry 14. We have been interested in electrochemical lactonizations; however, only C–O bonds were constructed for these transformations 15,16.…”

Radical Strategy for the Transition-Metal-Catalyzed Synthesis of γ-Lactones: A Review

“…17 Scheme 10 Visible-light photocatalytic or Cu-catalyzed reactions between unsaturated carboxylic acids and bromofluoroalkanes A similar reaction was reported by the Li group in 2018. 18 They used CuOAc as catalyst, dtbbpy as ligand, and K 2 CO 3 as base for the oxydifluoroalkylation of unsaturated carboxylic acids with various -bromodifluoromethylsubstituted heterocycles, esters, amides, and ketones to give highly valued CF 2 -containing lactones in 16-98% yields (Scheme 10). This reaction featured broad substrate scope and wide functional group tolerance.…”

“…O were added into the reaction system, the amount of 18 O in the product was obvi-ously increased, which suggested that the oxygen atom of the newly formed ester group is from H 2 O. In addition, this reaction was completely inhibited when excessive radical inhibitors, including TEMPO and BHT, were added, suggesting a radical pathway.…”

Saturated oxygen and nitrogen heterocycles via oxidative coupling of alkyltrifluoroborates with alkenols, alkenoic acids and protected alkenylamines

“…The exible, convergent synthesis of saturated oxygen and nitrogen heterocycles can be accomplished by the addition of a carbon radical to readily available alkenoic acids, alkenols and alkenyl amines under oxidative conditions (Scheme 1a). [1][2][3][4][5][6][7][8][9][10] The carbon radical source is an important variable in these alkene addition processes. Alkylhalides have been applied, in particular when their metal-catalyzed reduction forms stabilized or semi-stabilized carbon radicals, such as those conjugated with carbonyl groups 11 or that are perhalogenated.…”

“…Alkylhalides have been applied, in particular when their metal-catalyzed reduction forms stabilized or semi-stabilized carbon radicals, such as those conjugated with carbonyl groups 11 or that are perhalogenated. 10 Halosulfonate salts that form radicals by oxidative desulfonation have also been used. 4,5 Hypervalent iodine reagents that decompose in the presence of metal catalysts to generate alkyl radicals have been used in such alkene coupling reactions.…”