Iodoarene-directed photoredox ß-C(sp3)-H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer and hydrogen atom transfer.

Site selective functionalization of inert remote C(sp3)-H bonds to increase molecular complexity offers vital potential for chemical synthesis and new drug development, thus it has been attracting ongoing research interest. In particular, typical ß-C(sp3)-H arylation methods using chelation-assisted metal catalysis or metal-catalyzed oxidative/photochemical in situ generated allyl C(sp3)-H bond processes have been well developed. However, radical-mediated direct ß-C(sp3)-H arylation of carbonyls remains elusive. Herein, we describe an iodoarene-directed photoredox ß-C(sp3)-H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer (XAT) and hydrogen atom transfer (HAT). The method involves diethylaminoethyl radical-mediated generation of an aryl radical intermediate via XAT, then directed 1,5-HAT to form the remote alkyl radical intermediate and radical-radical coupling with cyanoarenes, and is applicable to a broad scope of unactivated remote C(sp3)-H bonds like ß-C(sp3)-H bonds of o-iodoaryl-substituted alkanones and α-C(sp3)-H bonds of o-iodoarylamides. Experimental findings are supported by computational studies (DFT calculations), revealing that this method operates via a radical-relay stepwise mechanism involving multiple SET, XAT, 1,5-HAT and radical-radical coupling processes.

Electroreductive Remote Benzylic C(sp3)-H Arylation of Aliphatic Ethers Using Cyanoarenes for the Synthesis of α-(Hetero)aryl Ethers.

An iodoarene-driven electroreductive remote C(sp3)-H arylation of unsymmetrical 1-(o-iodoaryl)alkyl ethers with cyanoarenes for the site selective synthesis of α-(hetero)aryl ethers is developed. With the introduction of cyanoarenes as both aryl sources and electron transfer mediators, this method includes an iodoarene-driven strategy to enable the regiocontrollable formation of two new bonds, one C(sp2)-H bond, and one C(sp2)-C(sp3) bond, in a single reaction step through the sequence of halogen atom transfer (XAT), hydrogen atom transfer (HAT), radical-radical coupling, and decyanation.

Photoredox-Catalyzed Alkylarylation of N-Aryl Bicyclobutyl Amides with α-Carbonyl Alkyl Bromides: Access to 3-Spirocyclobutyl Oxindoles.

A visible-light-induced radical alkylarylation of N-aryl bicyclobutyl amides with α-carbonyl alkyl bromides for the synthesis of functionalized 3-spirocyclobutyl oxindoles is described in which ß-selective radical addition of the alkyl radical to N-aryl bicyclobutyl amides forms a key radical intermediate followed by interception with intrinsic arene functional group. This approach can be applicable to a wide range of α-carbonyl alkyl bromides, including primary, secondary, and tertiary α-bromoalkyl esters, ketones, nitriles, and nitro compounds.

Nickel-Catalyzed Reductive Cross-Coupling of Propargylic Acetates with Chloro(vinyl)silanes: Access to Silylallenes.

Because of their various reactivities, propargyl acetates are refined chemical intermediates that are extensively applied in pharmaceutical synthesis. Currently, reactions between propargyl acetates and chlorosilanes may be the most effective method for synthesizing silylallenes. Nevertheless, owing to the adaptability and selectivity of substrates, transition metal catalysis is difficult to achieve. Herein, nickel-catalyzed reductive cross-coupling reactions between propargyl acetates and substituted vinyl chlorosilanes for the synthesis of tetrasubstituted silylallenes are described. Therein, metallic zinc is a crucial reductant that effectively enables two electrophilic reagents to selectively construct C(sp2)-Si bonds. Additionally, a Ni-catalyzed reductive mechanism involving a radical process is proposed on the basis of deuteration-labeled experiments.

Cobalt-Promoted Photoredox 1,2-Amidoamination of Alkenes with N-Sulfonamidopyridin-1-ium Salts and Free Amines.

A cobalt-promoted photoredox 1,2-amidoamination of alkenes with N-sulfonamidopyridin-1-ium salts and free amines for the synthesis of unsymmetrical vicinal diamines has been developed. The reaction handles N-(sulfonamido)pyridin-1-ium salts as the sulfonamidyl radical precursors and free amines as the nucleophilic terminating reagents to enable the formation of two new C(sp3)-N bonds in a single reaction step and offers a route to selectively producing unsymmetrical vicinal diamines with an exquisite selectivity and a good compatibility of functional groups.

Divergent [2 + n] Heteroannulation of ß-CF3-1,3-enynes with Alkyl Azides via Hydrogen Atom Transfer and Radical Substitution.

A copper-promoted divergent intermolecular [2 + n] heteroannulation of ß-CF3-1,3-enynes with alkyl azides via alkyl radical-driven HAT and radical substitution (C-C bond formation) to form four- to ten-membered saturated N-heterocycles is developed. This method enables the aryl-induced or kinetically controlled site selective functionalization of the remote C(sp3)-H bonds at positions 2, 3, 4, 5, 6, 7, or 8 toward the nitrogen atom through triplet nitrene formation, radical addition across the C═C bond, HAT and radical substitution cascades, and features a broad substrate scope, excellent site selectivity, and facile late-stage derivatization of bioactive molecules. Initial deuterium-labeling and control experiments shed light on the reaction mechanism via nitrene formation and HAT.

Aryldiazonium-Salt-Triggered Carboxylative Azotization of Pyrroles or Indoles with Polyhalomethanes via Halogen-Atom Transfer (XAT).

A halogen-atom-transfer (XAT)-based method for carbonylazotization of pyrroles or indoles with aryldiazonium salts and polyhalomethanes via dual C(sp2)-H bond functionalization is described. Using aryldiazonium salts realizes carbonylation/azotization of pyrroles or indoles via polyhalomethyl-radical-mediated and electrophilic substitution, thus providing a green, efficient, and step-economy approach for synthesis of multifunctional pyrroles or indoles from the easily available substrates. Notably, this strategy relies on the use of aryldiazonium salts to extend the well-established iodine atom transfer to bromine or chlorine atom transfer.

Palladium/Norbornene Cooperative Catalysis Bifunctionalization: Acylation/Cyanation of Aryl Iodides by Cleaving C-CN Bond of Aryl Acyl Nitrile.

A palladium/norbornene catalyzed two-component coupling process involving acylation/cyanation of aryl iodides is reported. In this work, aryl acyl nitrile compounds are cleverly selected to provide both nitrile and acyl sources by palladium-catalyzed cleavage of the C-CN bond as both an electrophilic reagent and a termination reagent. This is the first example of C-CN bond cleavage bifunctionalization of aryl iodides. After a series of important NBE derivatives are screened, the products resulting from the bifunctionalization of aryl iodides are smoothly obtained. This strategy has a wide range of substrates and good functional group compatibility. Moreover, this synthetic protocol demonstrated a good application for the synthesis of diverse O,N,C-substituted isoindolinones.

Visible-Light-Induced Photoredox 1,2-Dialkylation of Styrenes with α-Carbonyl Alkyl Bromides and Pyridin-1-ium Salts.

A visible-light-driven photoredox dialkylation of styrenes with α-carbonyl alkyl bromides and pyridin-1-ium salts for the synthesis of polysubstituted 1,4-dihydropyridines is reported. This reaction enables the formation of two new C(sp3)-C(sp3) bonds in a single reaction step and provides a strategy that employs pyridin-1-ium salts as the functionalized alkylating reagents via dearomatization to directly trap the resulting alkyl radicals from radical addition of alkenes and then terminate the alkene dialkylation.

Electroreductive Carboxylation of Propargylic Acetates with CO2: Access to Tetrasubstituted 2,3-Allenoates.

An electroreductive carboxylation of propargylic alcohols with CO2 and then workup with TMSCHN2 to construct tetrasubstituted 2,3-allenoates is developed. This method allows the incorporation of an external ester group into the resulting allene system through electroreduction, carboxylation, and deacetoxylation cascades. Mechanistically, electricity on/off experiments and cyclic voltammetry analysis support the preferential generation of the CO2 radical anion or the 3-aryl propargylic acetate radical anion based on the electron nature of the aryl rings.

Palladium-Catalyzed ß-C(sp3)-H Arylation of Silyl Prop-1-en-1-ol Ethers with Aryl Halides: Entry to α,ß-Unsaturated Ketones.

A palladium(0)-catalyzed ß-C(sp3)-H arylation of silyl prop-1-en-1-ol ethers with aryl halides for the synthesis of α,ß-unsaturated ketones is presented. In contrast to the reported ß-C(sp3)-H arylation of ketones, the chemoselectivity of this current method relies on the Pd(0) catalytic systems and reaction temperatures: While using the Pd(dba)2/DavePhos/KF system at 80 °C resulted in ß-C(sp3)-H monoarylation to produce ß-monoarylated α,ß-unsaturated ketones, harnessing the Pd(OAc)2/t-Bu XPhos/K2HPO4 system at 110 °C induced ß-C(sp3)-H diarylation to afford ß,ß-diarylated α,ß-unsaturated ketones. The method provides a versatile route that uses readily available ketone-derivatized α-nonsubstituted silyl prop-1-en-1-ol ethers as the alkene sources and is characterized by a good functional group compatibility, a broad substrate scope, and an excellent selectivity.

Cobalt-Promoted Electroreductive Cross-Coupling of Prop-2-yn-1-yl Acetates with Chloro(vinyl)silanes.

An electroreductive cross-coupling of prop-2-yn-1-yl acetates with chloro(vinyl)silanes for producing tetrasubstituted silylallenes is developed. The method enables the formation of a new C─Si bond through the cathodic reduction formation of the silyl radical, radical addition across the C≡C bond, the alkenyl anion intermediate formation, and deacetoxylation and represents a mild, practical route to the synthesis of silylallenes. Mechanistic studies reveal that CoCl2 acts as the mediator to promote the formation of the alkenyl anion intermediate via electron transfer.

Aryldiazonium Salt-Triggered [2 + 2 + 1] Heteroannulation of Indoles by an Arylhydrazone Radical-Relayed 1,5-Hydrogen Atom Transfer.

An unprecedented three-component [2 + 2 + 1] annulation cascade of indoles with aryldiazonium salts and polyhalomethanes or acetone is presented by dual hydrogen atom transfer (HAT) and C-H functionalization. By employing readily accessible aryldiazonium salts as the radical initiators and electrophiles and polyhalomethanes and acetone as the C1 units, this method unprecedentedly constructs a pyrazole ring on an indole ring skeleton through the formation of two C-N bonds and a C-C bond in a single reaction.

Cobalt(III)-Catalyzed Directed C-7 Selective C-H Alkynylation of Indolines with Bromoalkynes.

A cobalt(III)-catalyzed directed C-7 alkynylation of indolines with easily accessible bromoalkynes has been developed. The reaction has a broad substrate scope with excellent yields and represents a powerful route to the synthesis of 7-alkynyl-substituted indolines. In addition, the reaction can be extended to the coupling of N-aryl 7-azaindoles, highlighting the synthetic practicability of the strategy.

Nickel Photocatalyzed Reductive 1,4-Dicarbofunctionalization of 1,3-Enynes with N-Methylamines and Organohalides Enabled by Site-Selective C(sp3)-H Functionalization.

A cooperative nickel and photoredox reductive catalysis for 1,4-dicarbofunctionalization of 1,3-enynes with tertiary N-methylamines and organohalides to produce tetrasubstituted allenes is presented. This method enables the generation of the aminoalkyl C(sp3)-centered radicals by site selective cleavage of the N-methyl C(sp3)-H bonds in tertiary N-methylamines and is extended to alkyl bromides as the electrophilic terminating regents. Mechanistic studies indicate that the reaction involves a radical process and a Ni0/NiI/NiIII catalytic cycle.

Pd-Catalyzed Intermolecular Carbonylative Dearomatization of Arylamines with Propargylic Acetates for Synthesis of Bridged Polycyclic Lactams.

A new palladium-catalyzed multicomponent dearomatization of arylamines with CO and propargylic acetates for the synthesis of bridged polycyclic lactams is described. This method allows double annulation at the ipso and para positions of the amino group to form four new bonds, three C-C bonds and one C-N bond. DFT calculations and experimental studies indicate that the efficient formation of the allenecarboxanilide intermediate is the key step to achieve the dearomative transformation.

Recent Advances in N-O Bond Cleavage of Oximes and Hydroxylamines to Construct N-Heterocycle.

Oximes and hydroxylamines are a very important class of skeletons that not only widely exist in natural products and drug molecules, but also a class of synthon, which have been widely used in industrial production. Due to weak N-O σ bonds of oximes and hydroxylamines, they can be easily transformed into other functional groups by N-O bond cleavage. Therefore, the synthesis of N-heterocycle by using oximes and hydroxylamines as nitrogen sources has attracted wide attention. Recent advances for the synthesis of N-heterocycle through transition-metal-catalyzed and radical-mediated cyclization classified by the type of nitrogen sources and rings are summarized. In this paper, the recent advances in the N-O bond cleavage of oximes and hydroxylamines are reviewed. We hope that this review provides a new perspective on this field, and also provides a reference to develop environmentally friendly and sustainable methods.

Nickel-Catalyzed Radical Heck-Type C(sp3)-C(sp2) Coupling Cascades Enabled by Bromoalkane-Directed 1,4-Aryl Shift: Access to Olefinated Arylalanines.

A bromoalkane-directed radical 1,4-aryl shift strategy for nickel-catalyzed reductive Heck-type C(sp3)-C(sp2) coupling cascades of α-amino-ß-bromocarboxylic acid esters with α-trifluoromethyl alkenes for producing gem-difluorinated arylalanines is presented. The α-aminoalkyl radicals generated from neophyl-type aryl migration function as robust coupling partners to allow for further Giese-type addition with electron-deficient α-trifluoromethyl alkenes and vinyl sulfones, thereby realizing a new radical cascade for the simultaneous installation of an aromatic ring and olefin motif into amino acid backbones.

The transient-chelating-group-controlled stereoselective Rh(i)-catalyzed silylative aminocarbonylation of 2-alkynylanilines: access to (Z)-3-(silylmethylene)indolin-2-ones.

A new method involving mild acryl transient-chelating-group-controlled stereoselective Rh(i)-catalyzed silylative aminocarbonylation of 2-alkynylanilines with CO and silanes is presented for producing (Z)-3-(silylmethylene)indolin-2-ones. Upon using an acryl transient chelating group, 2-alkynylanilines undergo an unprecedented alkyne cis-silylrhodation followed by aminocarbonylation to assemble (Z)-3-(silylmethylene)indolin-2-ones. Mechanistic studies show that acryl transient chelating effects result in the key alkyne cis-silylrhodation process.

Nickel-Catalyzed C-S Reductive Cross-Coupling of Alkyl Halides with Arylthiosilanes toward Alkyl Aryl Thioethers.

A nickel-catalyzed C-S reductive cross-coupling of alkyl halides with arylthiosilanes for producing alkyl aryl thioethers is developed. This reaction is initiated by umpolung transformations of arylthiosilanes followed by C-S reductive cross-coupling with alkyl halides to manage an electrophilic alkyl group onto the electrophilic sulfur atom and then construct a C(sp3)-S bond, and features exquisite chemoselectivity, excellent tolerance of diverse functional groups, and wide applications for late-stage modification of biologically relevant molecules.