Palladium‐Catalyzed Remote Aryldifluoroalkylation of Alkenyl Aldehydes

Abstract

A palladium-catalyzed three-component reaction between fluoroalkyl bromides, arylboronic acids, and alkenyl aldehydes has been developed and provides facile access to 5-, 6-, or 7-difluoroalkylated ketones under very mild reaction conditions. The resultant products can be smoothly converted into CF -containing tetrahydronaphthalenes by a novel silver-catalyzed intramolecular decarboxylative cyclization of 5-aryl-2,2-difluoropentanoic acids.

Iridium(III)-Catalyzed Difluoroalkylation–Bicyclization of 1,7-Enynes toward Benzo[a]fluoren-5-ones under Visible-Light Photoredox Conditions

“…On the basis of these results and previous reports, [3][4][5][6][7] we have proposed a plausible reaction mechanism for this transformation (Scheme 4). Initially, Ir(III) is transformed into the excited state *Ir(III) species under visible-light irradiation.…”

“…6 Very recently, Zhu's group disclosed the palladium-catalyzed remote aryldifluoroalkylation of alkenyl aldehydes. 7 Despite these significant advances, the catalytic difluoroalkylation of 1,7-enynes toward benzo[a]fluoren-5-ones, to the best of our knowledge, has not been documented yet.…”

Recent Progress in Palladium‐Catalyzed Radical Reactions

“…reported the first palladium‐catalyzed remote aryldifluoroalkylation of akenyl aldehydes 52 with fluoroalkyl bromides 54 and arylboronic acids 53 to synthesize difluoroalkylated ketones 55 (Scheme 17). [20] Various 2‐allyl benzaldehydes 52 were investigated, and the corresponding difluoroalkylated ketones 55 were obtained in moderate to good yields. A series of substrates derived from arylboronic acids 53 and bromodifluoroacetamides 54 were compatible for this transformation.…”

Visible‐Light Photoredox‐Catalyzed Remote Difunctionalizing Carboxylation of Unactivated Alkenes with CO2

“…This process combines radical attack to alkenes, hydrogen atom transfer (HAT) and remote C−H functionalization. In this process, to the best of our knowledge, the newly generated radicals via HAT undergo either single‐electron oxidation to an electrophilic carbocation [9c,d,f,h] or directly couple with reaction partners [9e,g] . Another possibility involving the reduction of the radical intermediate to a carbanion and subsequent nucleophilic attack on an expectant electrophile has never been reported for the remote functionalization of alkenes.…”