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Transition-metal-catalyzed Suzuki-Miyaura coupling has significantly advanced C-C bond formation and has been well recognized in organic synthesis, pharmaceuticals, materials science and other fields. In this rapid development, cross coupling without transition metal catalyst is a big challenge in this field, and using widely existing tertiary amines as electrophiles to directly couple with boronic acids has great hurdles yet significant application prospects. Herein, we report an efficient and general deaminative arylation and alkenylation of tertiary amines (propargyl amines, allyl amines and 1H-indol-3-yl methane amines) with ary and alkenylboronic acids enabled by difluorocarbene under transition-metal-free conditions. Preliminary mechanism experiments suggest that in situ formed difluoromethyl quaternary amine salt, nitrogen ylide and tetracoordinate boron species are the key intermediates, the subsequent 1,2-metallate shift and protodeboronation complete the new coupling reaction.

Divergent synthesis for precise constructions of cyclic unsymmetrical diaryl disulfides or diselenides and polythiophenes from CF3 -containing 1,3-enynes and S8 was developed when the ortho group is F, Cl, Br, and NO2 on aromatic rings. Meanwhile, disulfides (diselenides) were also quickly constructed when the ortho group is H. These transformations undergo cascade thiophene construction/selective C3-position thiolation process, featuring simple operations, divergent synthesis, broad substrate scope, readily available starting materials, and valuable products. A novel plausible radical annulation process was proposed and validated by DFT calculations for the first time. A series of derivatizations about the thiophene (TBT) and disulfides were also well-represented.

A new chiral Brønsted acid, generated in situ from a chiral phosphoric acid boron (CPAB) complex and water, was successfully applied to asymmetric indole reduction. This "designer acid catalyst", which is more acidic than TsOH as suggested by DFT calculations, allows the unprecedented direct asymmetric reduction of C2-aryl-substituted N-unprotected indoles and features good to excellent enantioselectivities with broad functional group tolerance. DFT calculations and mechanistic experiments indicates that this reaction undergoes C3-protonation and hydride-transfer processes. Besides, bulky C2-alkyl-substituted N-unprotected indoles are also suitable for this system.

Reported herein is a stereospecific 1,4-metallate rearrangement for single-geometry ketoxime synthesis from oxime chlorides and arylboronic acids. This strategy exhibits broad substrate scope with excellent stereoselectivity under mild reaction conditions. In comparison with the conventional approaches, each configuration of unsymmetric diaryl oximes, as well as the thermodynamically less stable Z isomer of aryl alkyl ketoximes can be selectively and exclusively obtained. The reactivities of unsymmetric diaryl oximes and the Z isomer of aryl alkyl oximes, a class of underexplored molecules, enables efficient access to the corresponding isoquinolines, isoquinoline N-oxides, and amides having a single configuration.

A direct strategy for intramolecular transfer oxygenation of alkynes and cycloisomerization of 2-nitroalkynes to synthesize a wide range of C2-quaternary indolin-3-ones was developed by a copper/diboron system. The desired allylation, benzylation and propargylation products were obtained in moderate to excellent yields with good functional group tolerance. The mechanism study indicated that this protocol involved a radical process.

An efficient and convenient synthesis of valuable disulfanes and benzenesulfonothioates, having a 2-aminofuran framework, has been developed by employing a copper-catalyzed transformation of readily available N-tosylhydrazone-bearing thiocarbamates. This method features an inexpensive metal catalyst, mild reaction conditions, good functional-group tolerance, short reaction times, and delivers valuable and complex products. A copper carbene generated from an N-tosylhydrazone-bearing thiocarbamate is proposed as the key intermediate for the transformation and it triggers the subsequent cascade. Remarkably, the Ts anion released from N-tosylhydrazone further serves as a nucleophile, thus rendering the formation of benzenesulfonothioates under controlled conditions.

A direct and single-step procedure towards substituted pyrimidine and pyridine derivatives via Lewis acid-promoted [3+3] annulation between 3-ethoxycyclobutanones and enamines or amidines is presented. Diverse substituted pyrimidine and pyridine derivatives were obtained in good to high yields with a wide substrate scope.

An original and efficient copper-catalyzed 1,6-hydrodifluoroacetylation of para-quinone methides with difluoroalkyl bromides has been described with bis(pinacolato)diboron (B2pin2) as reductant. In this reaction, a new C(sp3)–CF2 bond is constructed under smart conditions. A broad substrate scope of para-quinone methides (p-QMs) make this protocol very practical and attractive. Preliminary mechanistic studies manifested that a difluoroalkyl radical pathway was involved in this reaction. Also the presence of the diboron reagent was an essential requisite in this transformation.

Cleavage of the carbon–carbon triple bonds of alkynes was achieved, which led to the synthesis of arylnitriles under transition-metal-free conditions. A vast range of terminal alkyne substrates underwent this reaction to provide the corresponding nitriles in moderate to good yields with good functional group tolerance.

A domino Knoevenagel-decarboxylation-alkene difunctionalization sequence has been developed for the conversion of benzaldehydes into β-ketophosphonates, catalyzed by a cooperative Cu/Fe system, whereby C-P and C=O bonds are formed simultaneously in a one-pot reaction. The reaction proceeds in good yields and with a broad substrate scope and environmentally benign conditions.

A copper(I) iodide-catalyzed, highly efficient acylation of benzothiazoles with aryl methyl ketones as carbonyl sources under a nitrogen atmosphere was developed. This is an unprecedented protocol and an extremely efficient method for the selective synthesis of 2-acylbenzothiazoles from commercially available, cheap starting materials with excellent chemoselectivity, good functional group tolerability and high turnover numbers (up to 14,200); also scaling up to 160 mmol without loss of the efficiency is possible. A variety of 2-acylbenzothiazoles was smoothly prepared in good to excellent yields from aryl methyl ketones and benzothiazoles by a one-pot domino protocol of combined sp3 CH oxidation, ring opening, and condensation.

A novel domino palladium-catalyzed nitration of Meyer–Schuster intermediates which were generated in situ from propargylic alcohols was developed, by the use of t-BuONO, leading to α-nitro enones in good to excellent yields at room temperature with a broad functional group tolerance.

A mild, reductive cyclization of ortho-nitrostyrenes affords indoles via in situ generated nitroso arenes.

Cleavage of the carbon–carbon triple bonds of alkynes was achieved, which led to the synthesis of arylnitriles under transition-metal-free conditions. A vast range of terminal alkyne substrates underwent this reaction to provide the corresponding nitriles in moderate to good yields with good functional group tolerance.

An efficient and general method for C(sp2)–H difluoroalkylation of aldehyde derived hydrazones via a CuII/B2pin2-catalyzed reaction between difluoroalkyl bromides and hydrazones was developed. In this reaction, both aromatic and aliphatic difluoroalkylated aldehyde derived hydrazones could be achieved in good to excellent yields. For some heteroaromatic aldehyde derived hydrazones, two fluoroacetates could be introduced onto the final products. A preliminary mechanism study manifested that a difluoroalkyl radical via SET pathway was involved in the reaction. In addition, the catalytic diboron reagent plays an indispensable role in this transformation.

An efficient copper-catalyzed decarboxylative hydroboration of phenylpropiolic acids with bis(pinacolato)diboron was developed, affording β-vinylboronates as the only products in high yields. Extra hydrogen sources such as methanol are not needed in this catalytic system. This reaction could be performed successfully under ligand- and base-free conditions. It demonstrated that phenylpropiolic acids can be employed as alkyne synthons in the hydroboration reaction and exhibited good reactivity and higher selectivity than terminal alkynes.

Catalyzed by a simple copper salt, the reaction of an aryl aldehyde and a terminal alkyne in the presence of piperidine delivers the valuable chalcone products, which were rarely found in previous A3 coupling reactions. This reaction can be applied to a wide range of substrates. Mechanistic studies indicate that this reaction experiences a tandem process containing A3 coupling, copper assisted isomerization of propadienamine to allenylamine and subsequent hydrolysis.

A transition-metal-free synthesis of alkylboronates, utilizing arylacetylenes or vinyl arenes and bis(pinacolato)diboron through tandem borylation and protodeboronation, has been developed. This reaction is efficient, practical and environmentally benign, leading to anti-Markovnikov products with excellent regioselectivity, broad functional group tolerance and excellent yields in both small and gram scales.

A copper-catalyzed hydrofluoroacetylation of arylacetylenes or alkynyl carboxylic acids with bromofluoroacetates was developed. The reaction shows excellent stereoselectivity to afford fluoroacetylated alkenes in good to excellent yields with a broad substrate scope. A preliminary mechanism study suggested that a radical pathway was involved in the reaction and (phenylethynyl)copper might be the key intermediate for the reaction. B2pin2 also plays an indispensable role in this novel hydrofluoroacetylation reaction.

A novel copper-catalyzed chemoselective reduction of a carbon–carbon double or triple bond to a carbon–carbon single bond in α,β-unsaturated ketones is developed. This reaction proceeds under hydrogen gas or stoichiometric metal hydride free conditions. Saturated ketones were obtained in good to excellent yields with a broad substrate scope. Mechanistic studies reveal that the two hydrogen atoms come from H2O in the system. Thus this reaction represents a highly efficient, and remarkably chemoselective strategy.

We report here an unprecedented Fe/Cu synergistically catalyzed deesterificative or deamidative oxyphosphorylation of unsaturated carboxylates or amides with H-phosphonates. The valuable β-ketophosphonates were obtained along with chemoselective cleavage of Csp2–C(CO) or Csp–C(CO) bonds in good yields under oxygen atmosphere with a wide substrate scope.

A copper-catalyzed oxidative direct formation of amides from nonactivated carboxylic acids and azoles with dioxygen as an activating reagent is reported. The azole amides were produced in good to excellent yields with a broad substrate scope. The mechanistic studies reveal that oxygen plays an essential role in the success of the amidation reactions with copper peroxycarboxylate as the key intermediate. Transamidation occurs smoothly between azole amide and a variety of amines.

Chemoselective cleavage of the C(CO)–C(alkyl) bond in aryl ketones leading to azole amides is disclosed with a broad substrate scope. Aryl ketones with a variety of long-chain alkyl groups have been demonstrated to be active substrates and mechanism studies suggested that molecular oxygen serves both as an oxidant and a reactant in this strategy.

A synergistic Cu/Fe-catalyzed aerobic oxyphosphorylation of alkynes or alkynyl carboxylic acids with H-phosphonate is disclosed. The useful β-ketophosphonate products were obtained in good yields under oxygen atmosphere in a novel way. This reaction exhibits a wide substrate scope, and the mechanistic experiments indicate that a radical mechanism forms both C–P and C═O bonds simultaneously. This mechanism contrasts existing aerobic difunctionalization of alkynes.

A metal-, base-, ligand-, and additive-free protocol for the efficient construction of a variety of sulfonamides is developed.

The scalable alkylation of 1,3-dicarbonyl compounds with substituted toluene derivatives or arylmethylbenzene derivatives is described.

The reaction of various aryl and hetarylmethylketones with aliphatic and benzylic alcohols as well as arylethyl alcohol derivatives or even cholesterol to α-ketoesters is described.

A copper(I) iodide-catalyzed, highly efficient acylation of benzothiazoles with aryl methyl ketones as carbonyl sources under a nitrogen atmosphere was developed. This is an unprecedented protocol and an extremely efficient method for the selective synthesis of 2-acylbenzothiazoles from commercially available, cheap starting materials with excellent chemoselectivity, good functional group tolerability and high turnover numbers (up to 14,200); also scaling up to 160 mmol without loss of the efficiency is possible. A variety of 2-acylbenzothiazoles was smoothly prepared in good to excellent yields from aryl methyl ketones and benzothiazoles by a one-pot domino protocol of combined sp3 CH oxidation, ring opening, and condensation.

Other amides such as N,N-diethylformamide, N-formylmorpholine and N-formylpiperidine provide the corresponding products in low yields.

Title compounds, which are important structural units for the preparation of insecticides and multiple-substituted benzene derivatives, are synthesized by a green and practical method starting from readily available materials.

Aromatic aldehydes or ketones from copper catalyzed aerobic oxidative decarboxylation of phenylacetic acids and α-hydroxyphenylacetic acids have been synthesized. This reaction combined decarboxylation, dioxygen activation, and C–H bond oxidation steps in a one-pot protocol with molecular oxygen as the sole terminal oxidant. This reaction represents a novel decarboxylation of an sp3-hybridized carbon and the use of a benzylic carboxylic acid as a source of carbonyl compounds.

A Cu2O-catalyzed aerobic oxidative decarboxylative ammoxidation to primary benzamides from phenylacetic acids and α-hydroxyphenylacetic acids is developed. A variety of primary benzamides could be prepared smoothly, in good to excellent yields, by means of a one-pot domino protocol combining decarboxylation, dioxygen activation, oxidative C-H bond functionalization, and amidation reactions.

A series of 2-substituted benzothiazoles (III) and (V) (28 examples in all) is readily prepared by a KI-catalyzed oxidative arylation of benzothiazoles (I) with corresponding aldehydes (II) and (IV), respectively.

A Cu(II)-catalyzed oxidative decarboxylative synthesis of 2-aryl benzothiazole from phenylacetic acids and α-hydroxyphenylacetic acids has been developed. This reaction proceeds via Cu(II)-catalyze...