Pd‐Catalyzed Transfer of Difluorocarbene for Three Component Cross‐Coupling^†

Abstract

of main observation and conclusion Outstanding accomplishments have been achieved in the chemistry of difluorocarbene, but transitionmetal-catalyzed transfer of difluorocarbene for coupling remains a challenging task. Herein, we describe a Pd-catalyzed coupling of difluorocarbene with two aryl carbon centers to give difluoromethylenation products, which cannot be obtained by any previous difluorocarbene-transformation method.

Nucleophilic strategies to construct –CF2– linkages using borazine-CF2Ar reagents

“…Within the last several years, transition metal catalysis has become an increasingly popular strategy to install CF 2 R motifs. 21–26 The Zhang group has recently advanced this field by using halodifluoromethyl arenes 27,28 and alkanes 29 as radical/electrophilic partners in conjunction with organonucleophiles to form products with internal –CF 2 – linkages. The Crudden and Baran groups have investigated difluoromethyl aryl and difluoroalkyl sulfones, another class of radical/electrophilic reagents that can be further transformed into ArCF 2 R products.…”

Reductive Catalytic Difluorocarbene Transfer via Palladium Catalysis

“…The reaction exhibited high functional group tolerance. A variety of versatile synthetic handles, including strong base and nucleophile-sensitive moieties, such as ester (5, 20, 21), formyl (16,22), enolizable ketone (17,18), amide (19), and cyano (23), and other functional groups, such as cyclic amine (11), thioether (12), aryl silane (13), and aryl fluoride (15), were compatible with the reaction, providing a good opportunity for further derivatizations. Remarkably, substrates bearing two carbon electrophiles were also competent coupling partners, with aryl bromide as the primary reaction site.…”

“…[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] However, using metal difluorocarbene complexes for catalytic synthesis remains a long-standing challenge because the isolated metal difluorocarbene complexes lack the catalytic activity necessary for difluorocarbene transfer. [13][14][15][16][17][18][19][20][21][22] Recently, we developed a palladium-catalyzed difluorocarbene transfer reaction that can efficiently couple difluorocarbene with proton sources and nucleophiles, including aryl borons [23][24][25] and terminal alkynes [28] (Figure 1d). In this palladium-catalyzed process, a palladium(0) difluorocarbene complex [Pd 0 -(L n )]=CF 2 (A) was found to exhibit strong nucleophilicity.…”

Transition metal-catalyzed reactivity of carbenes with boronic acid derivatives for arylation (alkylation) and beyond

“…As discussed in previous reports, a proton source is required for the difluoromethylation of aryl/vinylboronic acids with difluorocarbene in the presence of a Pd-catalyst. [26][27][28] In 2020, the Xiao group utilized an electrophilic carbon source for a three-component cross-coupling reaction 32 between arylboronic acids, sulfonium salts, and difluorocarbene to synthesize difluoromethylated compounds with arylboronic acids via Pd-catalyzed transfer of difluorocarbene (Scheme 16). First, Ph 2 IOTf was employed as a phenyl cation equivalent, resulting in compound 123 with 40% 19 F-NMR yield.…”