Pd-Catalyzed Deacylative [4 + 1] Annulation of N-Arylimidoyl Chlorides with ß-Keto Esters Leading to 2-Fluoroalkyl Indoles.

A palladium-catalyzed [4 + 1] annulation of N-arylimidoyl chlorides with ß-keto esters has been developed. In the presence of Pd(OAc)2, PCy3, and K3PO4, a variety of fluoalkyl-containing N-arylimidoyl chlorides smoothly underwent the cascade C-H imidoylation/deacylative Heck-type reactions to afford biologically important 2-fluoroalkyl indoles in moderate to good yields.

Cu-Catalyzed Carbocyclization for General Synthesis of N-Containing Heterocyclics Enabled by BrCF2COOEt as a C1 Source.

A practical and efficient copper-catalyzed carbocyclization of 2-functionalized anilines with ethyl bromodifluoroacetate has been developed. Ethyl bromodifluoroacetate is employed as the C1 source via quadruple cleavage in this transformation. This reaction can afford a variety of N-containing heterocyclics with satisfactory yields and excellent functional group compatibility.

Synthesis of Trifluoromethylated Dibenzoxepines via Palladium-Catalyzed Tandem C-O Bond Formation/C-H Arylation.

A palladium-catalyzed cyclization reaction of phenols with trifluoromethyl-containing ortho-bromo-ß-chlorostyrenes has been developed. In the presence of palladium(II) acetate, tricyclohexylphosphine, and cesium carbonate, a variety of 6-trifluoromethyldibenzo[b,d]oxepines were prepared in moderate to good yields through the tandem O-alkenylation of general phenols and subsequent C-H arylation.

TBAI-Mediated Cyclization and Methylsulfonylation of Propargylic Amides with Dimethyl Sulfite.

A tetramethylammonium iodide (TBAI)-mediated cyclization and methylsulfonylation of propargylic amides enabled by dimethyl sulfite as a SO2 surrogate and methyl source have been developed. The transition metal-free and oxidant-free reaction provides a practical and efficient approach for the selective synthesis of methylsulfonyl oxazoles in moderate to excellent yields with good functional group compatibility.

Ni-Catalyzed Reductive Fluoroalkylacylation of Alkynes for the Steroselective Synthesis of Fluoroalkylated Enones.

A Ni-catalyzed three-component reductive fluoroalkylacylation of alkynes with fluoroalkyl halides and acyl chlorides is presented. This dicarbofunctionalization provides an efficient method for the synthesis of fluoroalkyl-incorporated enones under mild conditions with high yields and excellent regioselectivity and stereoselectivity.

Ni-Catalyzed Reductive Arylalkenylation of Alkynes for the Selective Synthesis of Polysubstituted Naphthalenes.

A Ni-catalyzed reductive arylalkenylation of alkynes with 1-bromo-2-(2-chlorovinyl)arenes in the presence of zinc powder has been developed. This base-free cyclization provides a novel protocol for the selective synthesis of 2-trifluoromethyl naphthalenes and ethyl 2-naphthoates from simple starting materials in moderate to good yields with excellent tolerance of functional groups.

Copper-Catalyzed Selective Defluorinative Sulfuration of Trifluoropropanamides Leading to α-Fluorothioacrylamides.

A practical and efficient method for the synthesis of α-fluorothioacrylamide was developed from selective defluorinative sulfuration of trifluoropropanamides with disulfides. The N-chelation-assisted copper-catalyzed defluorination and sulfurization reactions feature excellent functional group tolerance and incorporation of both sulfur atoms of disulfides into acrylamides.

Enantioselective Three-Component Fluoroalkylarylation of Unactivated Olefins through Nickel-Catalyzed Cross-Electrophile Coupling.

A nickel-catalyzed, enantioselective, three-component fluoroalkylarylation of unactivated alkenes with aryl halides and perfluoroalkyl iodides has been described. This cross-electrophile coupling protocol utilizes a chiral nickel/BiOx system as well as a pendant chelating group to facilitate the challenging three-component, asymmetric difunctionalization of unactivated alkenes, providing direct access to valuable chiral ß-fluoroalkyl arylalkanes with high efficiency and excellent enantioselectivity. The mild conditions allow for a broad substrate scope as well as good functional group toleration.

Selective, Intermolecular Alkylarylation of Alkenes via Photoredox/Nickel Dual Catalysis.

A regioselective, intermolecular 1,2-alkylarylation of alkenes with aryl halides and alkyl oxalates has been developed via photoredox/nickel dual catalysis. This dual-catalytic protocol involves a radical relay process, where radical addition is followed by a nickel-assisted coupling, forging two consecutive C-C bonds in a single operation. The mild and redox-neutral conditions allow for good compatibility in the scope of olefins, (hetero)aryl halides, as well as alkyl oxalates.

A four-component radical cascade trifluoromethylation reaction of alkenes enabled by an electron-donor-acceptor complex.

An efficient four-component radical cascade reaction of alkenes, enabled by an EDA complex between Togni's reagent and Hantzsch ester, has been reported. This operationally simple protocol demonstrates excellent selectivity, which is dominated by the innate polar effect, providing facile access to important δ-CF3 carbonyls under mild conditions. To further demonstrate the wide synthetic utility of this method, a three-step synthesis of CF3-naftidrofuryl has been successfully conducted.

Intermolecular selective carboacylation of alkenes via nickel-catalyzed reductive radical relay.

The development of catalytic carboacylation of simple olefins, which would enable the rapid construction of ketones with high levels of complexity and diversity, is very challenging. To date, the vast majority of alkene carboacylation reactions are typically restricted to single- and two-component methodologies. Here we describe a three-component carboacylation of alkenes via the merger of radical chemistry with nickel catalysis. This reaction manifold utilizes a radical relay strategy involving radical addition to an alkene followed by alkyl radical capture by an acyl-nickel complex to forge two vicinal C-C bonds under mild conditions. Excellent chemoselectivity and regioselectivity have been achieved by utilizing a pendant weakly chelating group. This versatile protocol allows for facile access to a wide range of important ß-fluoroalkyl ketones from simple starting materials.

One-Pot Synthesis of Quinoxalinones via Tandem Nitrosation/Cyclization of N-Aryl Cyanoacetamides.

A new one-pot strategy for the synthesis of quinoxalin-2-ones from the tandem nitrosation/cyclization reaction of N-aryl cyanoacetamides with tert-butyl nitrite has been developed. The dehydrogenative N-incorporation is achieved through a sequence of nitrosation, tautomerization, and cyclization, affording quinoxalin-2-ones in moderate to good yields with good functional group tolerance.

Transition-Metal-Free Conversion of Trifluoropropanamides into Cyanoformamides through C-CF3 Bond Cleavage and Nitrogenation.

A new transition-metal-free transformation of trifluoropropanamides into cyanoformamides through a sequence of C-CF3 bond cleavage and nitrogenation using tert-butyl nitrite as the nitrogen source is described. The method features direct detrifluoromethylation, broad substrate scopes, and excellent selectivity control, representing a new shortcut for constructing the nitrile group involving C-CF3 σ-bond cleavage.

Copper-mediated stereospecific C-H oxidative sulfenylation of terminal alkenes with disulfides.

A copper and iodine-mediated C-H oxidative sulfenylation of olefins with diaryl disulfides has been developed for the stereospecific synthesis of vinyl thioether. With the combination of Cu(OTf)2 and I2, a variety of terminal alkenes underwent oxidative coupling reaction with various diaryl disulfides successfully to afford the corresponding E-vinyl sulfides in moderate to good yields.

FeCl3-promoted carboxamidation and cyclization of aryl isonitriles with formamides toward phenanthridine-6-carboxamides.

An iron-promoted tandem carboxamidation and cyclization between aryl isonitriles and formamides has been developed. The one-pot strategy can be applied to a wide range of 2-isocyanobiphenyls and formamides with excellent functional group tolerance for the synthesis of phenanthridine-6-carboxamides in moderate to excellent yields.