Photocatalytic redox-neutral α-C(sp3)-H pyridination of glycine derivatives and N-arylamines with cyanopyridines.

A photo-induced α-C(sp3)-H decyanative pyridination of N-arylglycine derivatives with cyanopyridines was developed. This reaction was performed under organic photocatalytic and redox-neutral conditions via a radical-radical cross-coupling process. Besides, the protocol was also suitable for the C(sp3)-H pyridination of N-aryl tetrahydroisoquinolines as well as benzylamines.

Photo-induced phosphorylation/cyclization of N-homoallyl and N-allyl aldehyde hydrazones to access phosphorylated tetrahydropyridazines and dihydropyrazoles.

A photocatalytic radical carbophosphorylation/cyclization of N-homoallyl aldehyde hydrazones with phosphine oxides was developed under metal-free conditions, achieving phosphorylated tetrahydropyridazines in yields up to 95%. Phosphorylated dihydropyrazoles were also constructed, by reacting N-allyl aldehyde hydrazones with phosphine oxides under the same conditions.

Photocatalytic cyclization of 3-(2-isocyanophenyl)quinazolin-4(3H)-ones for the construction of quinoxalino[2,1-b]quinazolinones.

A new kind of building unit, 3-(2-isocyanophenyl)quinazolin-4(3H)-ones, was designed and synthesized for the construction of novel quinoxalino[2,1-b]quinazolinones. The radical cyclization of 3-(2-isocyanophenyl)quinazolin-4(3H)-ones with ethers afforded ether-substituted tetracyclic quinoxalino[2,1-b]quinazolinones under photocatalytic and metal-free conditions. In the process, the isocyano accepts a carbon radical to give an imidoyl radical, which adds to the electron-deficient CN bond in quinazolin-4(3H)-one.

Photocatalytic Carbosulfonylation/Cyclization of N-Homoallyl and N-Allyl Aldehyde Hydrazones toward Sulfonylated Tetrahydropyridazines and Dihydropyrazoles.

N'-Benzylidene-N-homoallylacetohydrazides were designed and synthesized as novel skeletons for the construction of functionalized tetrahydropyridazines. A series of aryl- and alkylsulfonylated tetrahydropyridazines were obtained in yields of up to 94% employing sulfonyl chlorides as the sulfonyl radical sources under visible-light irradiation. Besides, sulfonylated dihydropyrazoles were also produced from N-allyl-N'-benzylideneacetohydrazides. Mechanistic investigations indicated that both energy transfer and single electron transfer processes were involved in accomplishing the radical 6/5-endo-trig cyclization to the C═N bond.

Photocatalytic chemo-, regio- & stereoselective olefinic ß-C-H decarboxylative alkylation of enamides with diacyl peroxides.

A decarboxylative alkylation of enamides with alkyl diacyl peroxides induced by visible-light is described. The chemo-, regio- and stereoselective olefinic ß-C-H alkylation generates a series of primary- and secondary alkylated enamides in yields up to 95%. This transformation bears the advantages of operational simplicity, good functional group compatibility and mild conditions.

Metal-Free Photoinduced Hydrocyclization of Unactivated Alkenes toward Ring-Fused Quinazolin-4(3H)-ones via Intermolecular Hydrogen Atom Transfer.

A visible-light-induced hydrocyclization of unactivated alkenes was developed using 3CzClIPN as the photocatalyst to generate substituted α-methyldeoxyvasicinones and α-methylmackinazolinones in moderate to good yields. An intermolecular hydrogen atom transfer with THF as the hydrogen source was involved. Mechanism studies indicated that the intramolecular addition of the in situ formed aminal radical to the unactivated alkene generated the polycyclic quinazolinone.

Substituent-Controlled Regioselective Photoinduced Cyclization of N-Allylbenzamides with N-Sulfonylaminopyridinium Salts.

The annulation reactions of N-allylbenzamides with N-sulfonylaminopyridinium salts were developed under metal-free photoinduced mild conditions. Substituent-controlled sulfonaminoarylation and sulfonaminooxylation of benzamides were realized: N-allylbenzamides lead to benzosultams, while N-(2-phenylallyl)benzamides give sulfonamidylated oxazoline derivatives. Control experiments indicated that those reactions undergo a radical pathway with arylsulfonamidyl radicals as the intermediates. The aryl C-H bond functionalization in arylsulfonamidyl was involved for the first time to give benzosultams.

Recent advances in C-H functionalization of 2H-indazoles.

2H-Indazoles are one class of the most important nitrogen-containing heterocyclic compounds. The 2H-indazole motif is widely present in bioactive natural products and drug molecules that exhibit distinctive bioactivities. Therefore, much attention has been paid to access diverse 2H-indazole derivatives. Among them, the late-stage functionalization of 2H-indazoles via C-H activation is recognized as an efficient approach for increasing the complexity and diversity of 2H-indazole derivatives. In this review, we summarized recent achievements in the late-stage functionalization of 2H-indazoles, including the C3-functionalization of 2H-indazoles through transition metal-catalyzed C-H activation or a radical pathway, transition metal-catalyzed ortho C2'-H functionalization of 2H-indazoles and remote C-H functionalization at the benzene ring in 2H-indazoles.

Metal-free polychloromethyl radical-initiated cyclization of unactivated N-allylindoles towards pyrrolo[1,2-a]indoles.

A metal-free polychloromethyl radical-initiated cyclization of unactivated alkenes was developed using CH2Cl2 and CHCl3 as the di- and trichloromethyl radical sources. Variously substituted N-allyl-indoles were successfully transformed into the corresponding C2-(di- and trichloromethyl) pyrrolo[1,2-a]indoles in moderate to good yields. This reaction has a broad substrate scope and good functional group tolerance. Dibromomethylated products can also be obtained using CH2Br2 under standard conditions.

Three-component synthesis of arylsulfonyl-substituted indolo[2,1-a]isoquinolinones and benzimidazo-[2,1-a]isoquinolin-6(5H)-ones by SO2 insertion and radical cascade cyclization.

An efficient arylsulfonylation/cyclization of 2-aryl-N-methacryloyl indoles with potassium metabisulfite and aryldiazonium tetrafluoroborates was developed. A series of variously substituted arylsulfonyl indolo[2,1-a]isoquinolin-6(5H)-ones were formed in moderate to good yields via utilization of the nature abundant inorganic salt potassium metabisulfite as a SO2 surrogate. Additionally, this three-component protocol can also be employed for the synthesis of arylsulfonyl-substituted benzimidazo-[2,1-a]isoquinolin-6(5H)-ones.

Rhodium-catalyzed C-H activation/cyclization of aryl sulfoximines with iodonium ylides towards polycyclic 1,2-benzothiazines.

The synthesis of 1,2-benzothiazine derivatives through rhodium-catalyzed C-H activation/cyclization of S-aryl sulfoximines with iodonium ylides was developed for the first time. In this report, C-H and N-H bond functionalization was realized towards a series of tricyclic and tetracyclic sulfoximine derivatives with moderate to excellent yields under simple reaction conditions.

Recent advances in rhodium-catalyzed C(sp2)-H (hetero)arylation.

Arylation is a common behaviour in organic synthesis for the construction of complex structures, especially the biaryls. Among those reported arylation procedures, transition-metal-catalyzed direct C(sp2)-H arylation has been rapidly developed in recent decades and has become a reliable alternative to traditional cross-coupling procedures using organometallic reagents. Great achievements in rhodium-catalyzed C(sp2)-H arylation have been witnessed during the last decade. Aryl halides, simple arenes, aryl boronic acids, arylsilanes, aryl aldehyde, aryl carboxylic acid, diazides, etc. were successfully utilized as arylating reagents under rhodium-catalyzed conditions. In this review, recent achievements in rhodium-catalyzed arylations through C(sp2)-H bond activation were summarized together with the mechanism discussions.

Diacyl peroxides: practical reagents as aryl and alkyl radical sources.

Diacyl peroxides, which can be easily synthesized from corresponding carboxylic acids, are commonly utilized as radical initiators and one electron oxidants. Under thermal, transition-metal catalysis or irradiation conditions the cleavage of relatively weak O-O bonds would occur followed by CO2 extrusion to generate the corresponding aryl or alkyl radicals. Thus, diacyl peroxides can be employed as ideal arylating and alkylating reagents in organic synthesis, including C-H/N-H arylation/alkylation, aryl/alkyl radical addition to unsaturated bonds, hetero arylation/alkylation, eliminative arylation/alkylation, perfluoroalkylation etc. Moreover, these arylation/alkylation protocols have been successfully utilized in the synthesis and late-stage functionalization of natural products as well as bioactive molecules. In this review, recent advances on arylation and alkylation using diacyl peroxides as aryl and alkyl radical sources are summarized and discussed.

RhIII -Catalyzed C6-Selective Oxidative C-H/C-H Crosscoupling of 2-Pyridones with Thiophenes.

A rhodium(III)-catalyzed C6-selective dehydrogenative cross-coupling of 2-pyridones with thiophenes was developed for the synthesis of 6-thiophenyl pyridin-2(1H)-one derivatives. In this reaction, the excellent site selectivity was controlled by the 2-pyridyl directing group on the nitrogen of the pyridone ring. Control experiments indicated that the N-pyridyl was essential for the transformation. To the best of our knowledge, this procedure is the first successful example of the direct C6 heteroarylation of 2-pyridones with electron-rich thiophene derivatives. 4-Pyridone was also used as substrate to generate the corresponding C2 heteroarylated product. Moreover, this pyridyl directing group was readily removable to generate the biheteroaryl structures with a free N-H group.

DTBP-promoted site-selective α-alkoxyl C-H functionalization of alkyl esters: synthesis of 2-alkyl ester substituted chromanones.

The direct C-H functionalization of ethyl acetates was developed, delivering a variety of 1-(4-oxochroman-2-yl)ethyl acetate derivatives by reacting with chromones. This reaction has a wide substrate scope with excellent site-selective C-H activation at the inactive α-hydrogen of the alkoxyl group instead of the α-hydrogen of the carbonyl group under radical conditions. Compared with other protocols for the α-alkoxyl C-H functionalization of alkyl esters, a distinguishing feature of this reaction is that no metal catalyst was required, with DTBP as the sole oxidant.

Peroxide-mediated synthesis of benzimidazo[2,1-a]isoquinoline-6(5H)-ones via cascade methylation/ethylation and intramolecular cyclization.

A metal-free oxidative radical methylation/arylation of 2-arylbenzoimidazoles with DTBP as the oxidant and methyl radical source was developed. The reaction proceeds through a sequential methyl radical addition/cyclization pathway and affords a series of methyl functionalized benzimidazo[2,1-a]isoquinoline-6(5H)-ones in moderate to good yields. Besides, the ethylation/arylation of 2-arylbenzoimidazoles was also achieved with DTAP.

Rh(iii)-Catalyzed regioselective C4 alkylation of indoles with allylic alcohols: direct access to ß-indolyl ketones.

A Rh(iii)-catalyzed and weak coordination carbonyl guided direct C4 alkylation of indoles with allylic alcohols was developed with excellent regioselectivity. This reaction was conducted under mild conditions, leading to a variety of ß-indolyl ketones with good functional group tolerance in moderate to good yields.

Synthesis of dihydroquinolinones via iridium-catalyzed cascade C-H amidation and intramolecular aza-Michael addition.

An iridium-catalyzed annulation of chalcones with sulfonyl azides via cascade C-H amidation and intramolecular aza-Michael addition was developed, affording a variety of 2-aryl-2,3-dihydro-4-quinolones in moderate to good yields. This reaction features easy operation, readily available starting materials, and the cascade formation of two C-N bonds in one pot.

Rhodium-Catalyzed Site-Selective ortho-C-H Activation: Enone Carbonyl Directed Hydroarylation of Maleimides.

Enone carbonyl directed 1,4-addition of ortho-C-H bond in chalcones to maleimides was developed under the catalysis of Rh(III). This reaction furnished a variety of chalcone-based pharmacologically useful 3-arylated succinimide derivatives in good yields with excellent selectivity.

Metal-free radical cascade chloromethylation of unactivated alkenes: synthesis of polychloro-substituted indolines.

The di- and trichloromethylation of N-allyl anilines was developed under metal-free conditions, leading to a variety of di- and trichloromethylated indolines in moderate to good yields. This procedure used the commercially available chemical feedstocks CH2Cl2, CHCl3 and CCl4 as the di- and trichloromethyl sources.