Synthesis of Diarylalkanes by Photoreductive 1,2-Diarylation of Alkenes with Aryl Halides and Cyanoaromatics.

We report a visible light-induced photoreductive strategy for three-component diarylation of alkenes with aryl halides and cyanoaromatics. Upon photoredox catalysis and with tertiary alkyl amines as the electron transfer agent, aryl halides selectively undergo halogen atom transfer to generate the aryl radicals and two C(sp2)-C(sp3) bonds between the cabron atoms are created in a radical addition and radical-radical coupling fashion to rapidly assemble diverse functionalized polyarylalkanes with high regio- and chemoselectivity. This method can be applied to broad feedstocks, including terminal alkenes, internal alkenes, aryl iodides, aryl bromides, aryl chlorides, electron-deficient benzonitriles, and isonicotinonitriles.

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.

Intermolecular 1,2-Difunctionalization of Alkenes Enabled by Fluoroamide-Directed Remote Benzyl C(sp3)-H Functionalization.

A copper-catalyzed remote benzylic C-H functionalization strategy enabling 1,2-difunctionalization of alkenes with 2-methylbenzeneamides and nucleophiles, including alcohols, indoles, pyrroles, and the intrinsic amino groups, is reported, which is characterized by its redox-neutral conditions, exquisite site-selectivity, broad substrate scope, and wide utilizations of late-stage modifying bioactive molecules. This reaction proceeds through nitrogen-centered radical generation, hydrogen atom transfer, benzylic radical addition across the alkenes, single-electron oxidation, and carbocation electrophilic course cascades. While using external nucleophiles manipulates three-component alkene alkylalkoxylation and alkyl-heteroarylation with 2-methylbenzeneamides to access dialkyl ethers, 3-alkylindoles, and 3-alkylpyrroles, omitting the external nucleophiles results in two-component alkylamidation ([5+2] annulation) of alkenes with 2-methylbenzeneamides to benzo-[f][1,2]thiazepine 1,1-dioxides.

Iron-Catalyzed Intermolecular 1,2-Difunctionalization of Styrenes and Conjugated Alkenes with Silanes and Nucleophiles.

The first iron-catalyzed 1,2-difunctionalization of styrenes and conjugated alkenes with silanes and either N or C, using an oxidative radical strategy, is described. Employing FeCl2 and di-tert-butyl peroxide allows divergent alkene 1,2-difunctionalizations, including 1,2-aminosilylation, 1,2-arylsilylation, and 1,2-alkylsilylation, which rely on a wide range of nucleophiles, namely, amines, amides, indoles, pyrroles, and 1,3-dicarbonyls, thus providing a powerful platform for producing diverse silicon-containing alkanes.

1,2-Alkylarylation of Styrenes with α-Carbonyl Alkyl Bromides and Indoles Using Visible-Light Catalysis.

A new intermolecular 1,2-alkylarylation of styrenes with α-carbonyl alkyl bromides and indoles using fac-[Ir(ppy)3] as the photoredox catalyst has been developed. The method allows the simultaneous formation of two new carbon-carbon bonds through three component reaction, and represents a new single-electron transfer (SET) strategy for the 1,2-alkylarylation of the styrenes with broad substrate scope and excellent functional group tolerance.

Silver-Mediated Intermolecular 1,2-Alkylarylation of Styrenes with α-Carbonyl Alkyl Bromides and Indoles.

A new iron-facilitated silver-mediated radical 1,2-alkylarylation of styrenes with α-carbonyl alkyl bromides and indoles is described, and two new C-C bonds were generated in a single step through a sequence of intermolecular C(sp(3)-Br functionalization and C(sp(2))-H functionalization across the alkenes. This method provides an efficient access to alkylated indoles with broad substrate scope and excellent selectivity.

Rhodium(III)-Catalyzed [3+2]/[5+2] Annulation of 4-Aryl 1,2,3-Triazoles with Internal Alkynes through Dual C(sp2)-H Functionalization.

A rhodium(III)-catalyzed [3+2]/[5+2] annulation of 4-aryl 1-tosyl-1,2,3-triazoles with internal alkynes is presented. This transformation provides straightforward access to indeno[1,7-cd]azepine architectures through a sequence involving the formation of a rhodium(III) azavinyl carbene, dual C(sp(2))-H functionalization, and [3+2]/[5+2] annulation.

Metal-Free Radical [2+2+1] Carbocyclization of Benzene-Linked 1,n-Enynes: Dual C(sp(3))-H Functionalization Adjacent to a Heteroatom.

A new metal-free oxidative radical [2+2+1] carbocyclization of benzene-linked 1,n-enynes with two C(sp(3))-H bonds adjacent to the same heteroatom is described. This method achieves two C(sp(3))-H oxidative functionalizations and an annulation, thus providing efficient and general access to a variety of fused five-membered carbocyclic hydrocarbons.

Metal-free oxidative ipso-carboacylation of alkynes: synthesis of 3-acylspiro[4,5]trienones from N-arylpropiolamides and aldehydes.

A general and metal-free radical route to synthesis of 3-acylspiro[4,5]trienones is established that utilizes TBHP (tert-butyl hydrogenperoxide) as an oxidation and a reaction partner to trigger the oxidative ipso-carboacylation of N-arylpropiolamides with aldehydes. This method offers a new difunctionalization of alkynes through oxidative cross coupling of the aldehyde C(sp(2))-H bond with an ipso-aromatic carbon.

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.

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.

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.

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.

Photochemical Divergent Ring-Closing Metathesis of 1,7-Enynes: Efficient Synthesis of Spirocyclic Quinolin-2-ones.

A photocatalytic method for the ring-closing 1,7-enyne metathesis using the α-amino radical as an alkene deconstruction auxiliary is present. Preliminary mechanistic studies suggest that intramolecular 1,5-hydrogen atom transfer is the key to the generation and ß-scission of the α-amino radical, while the dearomatization of arenes and ring opening of cyclopropanes are the key to construct spirocyclic quinolin-2-ones. This approach highlights the potential of ring-closing 1,7-enyne metathesis, providing a green, efficient, and step-economical way for the synthesis of spirocyclic quinolin-2-ones.

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.

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.

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.

Decarboxylative C(sp3)-N Cross-Coupling of Diacyl Peroxides with Nitrogen Nucleophiles.

We have disclosed a new radical-mediated decarboxylative C(sp3)-N cross-coupling of diacyl peroxides with nitrogen nucleophiles. The primary and secondary alkyl radicals derived from corresponding diacyl peroxides were generated by copper catalysis or by merging copper catalysis and photoredox catalysis, respectively. Various N-alkyl nitrogen nucleophiles, including indazoles, triazoles, indoles, purine, carbazole, anilines, and sulfonamide, were provided with a broad substrate scope and good functional group tolerance.

Radical-mediated alkoxypolyhaloalkylation of styrenes with polyhaloalkanes and alcohols via C(sp3)-H bond cleavage.

We have developed a new radical-mediated alkoxypolyhaloalkylation of styrenes with polychloroalkanes and alcohols for the facile synthesis of complex polyhaloalkanes. 4-Methoxybenzenediazonium tetrafluoroborate is a good radical initiator for this transformation. This protocol is well applied to the late-stage functionalization of complex molecules, including vitamin E, estrone and cholesterol derivatives.

Indium controlled regioselective 1,4-alkylarylation of 1,3-dienes with α-carbonyl alkyl bromides and N-heterocycles.

We here describe a new, selective indium-promoted silver-mediated intermolecular oxidative 1,4-alkylarylation of 1,3-dienes with α-carbonyl alkyl bromides and N-heterocycles for producing functionalized N-heterocycles, which is characterized by its exquisitely controllable regio-/stereo-selectivity and excellent tolerance of functional groups. Mechanistically, the formation of the carbonyl-coordinated η3-allyl-In complex radical intermediate is the key factor for successfully achieving regio- and stereo-selectivity toward 1,4-difunctionalization and (E)-isomers.