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Phenol trifluoromesylates were utilized as substrates to synthesize aromatic tertiary amines in moderate to excellent yields through a Catellani-type pathway.

A palladium-catalysed C–C bond-forming reaction via deaminative and decarboxylative cross-coupling of organoammonium salts with a series of carboxylic acids (including polyfluoroaromatic, propiolic and α-cyano benzyl carboxylic acids) was developed.

A base-promoted direct deaminative olefination of organoammonium salts was developed.

A facile and versatile method for generating radicals from Csp3-H bonds under metal-free and organic-peroxide-free conditions was developed. By combining safe persulfate and low-toxic quaternary ammonium salt, a wide variety of Csp3-H compounds including ethers, (hetero)aromatic/aliphatic ketones, alkylbenzenes, alkylheterocycles, cycloalkanes, and haloalkanes were selectively activated to generate the corresponding C-centered radicals, which could be further captured by N-arylacrylamides to deliver the valuable functionalized oxindoles. Good functional group tolerance was demonstrated. The useful polycarbonyl compound and esters were also modified with the strategy. Moreover, the combination can also be applied to the practical coupling between simple haloalkanes and N-hydroxyphthalimide (NHPI).

A palladium-catalyzed difunctionalization of bicyclic alkenes with organoammonium salts and organoboronic compounds was reported. A wide range of functionalized cyclic products, including those bearing functional groups, were produced stereoselectively in good to excellent yields. The gram-scale experiment, one-pot operation, and synthetic application of β-borylated products further demonstrated the synthetic value of this new reaction in organic synthesis.

The direct decarbonylative cyanation of benzoic acids with TMSCN was achieved through palladium catalysis. By this strategy, a wide range of nitriles including those with functional groups was synthesized in good to high yields. Moreover, this reaction applied to modifying bioactive molecules such as adapalene, probenecid, telmisartan, and 3-methylflavone-8-carboxylic acid. These results demonstrate that this new reaction has potential synthetic value in organic synthesis.

A nickel-catalyzed decarbonylative thioetherification of carboxylic acids with thiols was developed. Under the reaction conditions, benzoic acids, cinnamic acids, and benzyl carboxylic acids coupled with various thiols including both aromatic and aliphatic ones produce the corresponding thioethers in up to 99% yields. Moreover, this reaction was applicable to the modification of bioactive molecules such as 3-methylflavone-8-carboxylic acid, probenecid, and flufenamic acid, and the synthesis of acaricide chlorbenside. These results well demonstrated the potential synthetic value of this new reaction in organic synthesis.

A direct decarbonylative Sonogashira coupling of terminal alkynes with carboxylic acids was achieved through palladium catalysis. This reaction did not use overstoichiometric oxidants, thus overcoming the homocoupling issue of terminal alkynes. Under the reaction conditions, a wide range of carboxylic acids including those bioactive ones could couple readily with various terminal alkynes, thus providing a relative general method for preparing internal alkynes.

A facile and general method for constructing carbon-heteroatom (C-P, C-O, C-S, and C-N) bonds via C-N cleavage of benzyl ammonium salts under transition-metal-free conditions was reported. The combination of t-BuOK and 18-crown-6 enabled a wide range of substituted benzyl ammonium salts to couple readily with different kinds of heteroatom nucleophiles, i.e. hydrogen phosphoryl compounds, alcohols, thiols, and amines. Good functional group tolerance was demonstrated. The scale-up reaction and one-pot synthesis were also successfully performed.

The first visible light-induced dioxygenation of α,β-unsaturated amides with N-hydroxy compounds under air was developed with the use of the non-toxic organic dye rose bengal as the photoredox catalyst. This metal-free reaction is highly chemoselective, producing the corresponding β-oxy alcohols rather than the competitive cyclized products through aminooxyarylation. Other aromatic alkenes, dihydrofurans and dienes, were also applicable to this reaction. Compared with the established radical dioxygenation methods to construct β-oxy alcohols, the present photochemical protocol avoids the use of (over)stoichiometric amounts of hazardous/poisonous oxidants, transition metals and additional reducing reagents, yielding the desired dioxygenated products in a safe and eco-friendly fashion. Moreover, the practical application of this methodology is highlighted by a concise two-step synthesis of 1,4-dioxane-2-carboxamides, a framework for building Mcl-1 inhibitors.

The direct C–H arylation and acylation of azoles with carboxylic acids were achieved through Pd/Cu cooperative catalysis. Various biaryls and biaryl ketones were selectively produced in good to high yields from the same substrates. The key factor of high chemoselectivity was the choice of a suitable phosphine ligand: biaryls were generated selectively with dppp as the ligand, while biaryl ketones were obtained with high selectivity using dpph or Ph2PCy as the ligand.

A transition-metal-free and base promoted C-C bond forming reaction of benzyl C(sp3)-H bond with organoammonium salts via C-N bond cleavage has been reported. Benzyl ammonium salts as well as cinnamyl ammonium salt could couple readily with various benzyl C(sp3)-H species, producing the corresponding products in moderate to excellent yields with good functional group tolerance. Late stage chemical manipulation enabled the specific 1,2-diarylethane structure of products transformed into useful olefin compounds via dehydrogenation, which further demonstrated the utility of this reaction.

Herein, we highlight advances in the phosphorylation of readily available carboxylic acids and their derivatives forming synthetically important P(O)–sp3C, P(O)–sp2C, and P(O)–spC bonds, with an emphasis on the results demonstrated since 2010. This review examines the challenges associated with the use of this strategy for the synthesis of organophosphorus compounds and details advances in the design of catalytic systems that suppress these problems thus resulting in notable progress. Mechanistic details are discussed where available.1 Introduction2 Formation of P(O)–sp3C Bonds3 Formation of P(O)–sp2C Bonds4 Formation of P(O)–spC Bonds5 Outlook and Conclusion

A palladium-catalyzed cyclobutanation of aryl sulfonates with strained alkenes has been developed. The methodology is featured to achieve the cleavage of both C–O and C–H bonds of phenol derivative...

The trifluoromethylation of benzoic acids with TMSCF3 was achieved through nucleophilic substitution with the use of anhydrides as an in situ activating reagent. Under the reaction conditions, a wide range of carboxylic acids including the bioactive ones worked well, thus providing a facile and efficient method for preparing aryl trifluoromethyl ketones from the readily available starting materials.

A practical and sustainable synthesis of arylsulfonate esters has been developed through electro-oxidation. This reaction employed the stable and readily available phenols and sodium arenesulfinates as the starting materials and took place under mild reaction conditions without additional oxidants. A wide range of arylsulfonate esters including those bearing functional groups were produced in good to excellent yields. This reaction could also be conducted at a gram scale without a decrease of reaction efficiency. Those results well demonstrated the potential synthetic value of this reaction in organic synthesis.

The controllable phosphorylations of thioesters were developed. When the reaction was catalyzed by a palladium catalyst, aryl or alkenyl phosphoryl compounds were generated through decarbonylative coupling, while the benzyl phosphoryl compounds were produced through deoxygenative coupling when the reaction was carried out in the presence of only a base.

A palladium-catalyzed decarbonylative alkenylation of aromatic carboxylic acids was developed. Under the reaction conditions, various benzoic acids including those bearing functional groups coupled to terminal alkenes, producing the corresponding internal alkenes in good to high yields. Cinnamic acids and bioactive benzoic acids such as 3-methylflavone-8-carboxylic acid, probenecid, adapalin, and febuxostat were also applicable to this reaction, demonstrating the potential synthetic value of this new reaction in organic synthesis.

A palladium-catalyzed N-acylation of tertiary amines by carboxylic acids was achieved through C-N cleavage. This reaction showed a wide substrate scope. Both aromatic and aliphatic acids served well as the acylating reagents and coupled with tertiary amines to produce the corresponding amides in good to excellent yields. With the strategy, bioactive carboxylic acids were also efficiently modified, highlighting the synthetic value of the process in organic synthesis.

A direct phosphorylation of the sp3C-CN bond catalyzed by a nickel catalyst is disclosed. A wide range of primary nitriles readily coupled with secondary phosphine oxides to produce the corresponding phosphorylated products in high yields. As a key step, this new method was applied to the synthesis of anticancer drug Combretastatin-A4, significantly shortening its synthetic path.

Three-component reactions can directly convert three reactants into the desired products in one pot and thus greatly shorten the synthetic path. Recently, transition-metal catalysis has been applied in the difunctionalization of alkenes and remarkable progress has been achieved to facilitate the construction of a wide range of functional molecules with high atom- and step-economic efficiency. This Focus Review highlights recent advances in this field.

An efficient oxidative aminooxyarylation of alkenes under a transition-metal-free condition was described. Under the reaction conditions, N-hydroxyphthalimide (NHPI) reacted readily with N-arylacrylamides to produce cyclic products via a radical C–H functionalization process, achieving both C–O and C–C bonds formation in one pot. This reaction provided a facile access to the valuable aminooxylated oxindoles. The benzylic and α-methylene C(sp3)-H bonds were also aminooxylated under the reaction conditions.

An efficient iodocarbocyclization of alkenes for the synthesis of iodooxindoles has been developed. This reaction proceeds in a chemoselective manner and shows excellent tolerance of various functional groups, including a chemosensitive hydroxymethyl group. Nonmetal inorganic iodine pentoxide was used as both the oxidant and iodine source, making this protocol very practical. On the basis of experimental observations, a plausible electrophilic reaction mechanism was proposed.

A t-BuONa-mediated C-OH/P(O)-H cross dehydration coupling to produce alkylphosphine oxides is developed. This reaction employed readily available alcohols and P(O)-H compounds as the starting materials, providing an efficient alternative method for constructing sp3 C-P bonds. A reasonable reaction path involving dehydration and subsequent regio-selective hydrophosphorylation of the resulting alkenes was proposed.

Trimethyl phosphine was used as an efficient catalyst for the addition of P(O)-H compounds to electron-deficient alkenes. The addition reactions were generally conducted using a catalytic amount of Me3P under mild reaction conditions. Both 1 to 1 and 1 to 2 adducts were obtained.

Alkynes are important raw materials for the generation of a variety of useful organic compounds through the construction of new C C, C H or C X bonds. Although relatively low in thermodynamic reactivity, alkynes can be readily and selectively activated in the presence of functional groups under mild conditions. The activation is done by means of metal or metal-free catalysis through either selective alkyne C C bond or terminal alkyne C H bond reactions. From the standpoint of green chemistry, it is desirable to develop catalytic processes for the transformation of alkynes that have the least impact on our environment. In this mini-review, we summarize the progresses of alkyne transformation to functional substances in the past six years, with emphasis on the results generated in our research group: heterocoupling of terminal alkynes into unsymmetrical 1,3-diynes, selective hydrogenation of alkynes with formic acid or hypophosphorous acid, and functionalization of alkynes by O-, P-, or S-containing molecules. The advantages and disadvantages of these processes and the effects of reaction conditions are systematically described. Moreover, the catalysts adopted for these processes are illustrated and compared. Finally, we make a prediction on the processes that have potential for industrial applications in the near future.

A metal-free and radical-free synthesis of heteroaromatic aldehydes was developed through aerobic oxidation of methyl groups in an I2/DMSO/O2 catalytic system. Under the reaction conditions, various functional groups such as methoxy, aldehyde, ester, nitro, amide, and halo (F, Cl, Br) groups were well tolerated. The bioactive compounds like chlorchinaldin derivative and papaverine were also oxidized to the corresponding aldehydes and ketones. This reaction provided an efficient method for preparing the valuable heteroaromatic aldehydes.

A nickel-catalyzed phosphorylation of aryl triflates with P(O) H compounds is disclosed. This reaction can proceed smoothly under a mild reaction condition, producing the corresponding aryl phosphorus compounds in good to high yields.

Optically active α-hydroxyphosphinates with both C- and P-stereogenic centers are obtained by rhodium- or iridium-catalyzed substrate-directed stereoselective addition of the optically pure H-phosphinates to aldehydes. The reaction most probably proceeds by a transition-metal-catalyzed mechanism with hydridometal complexes as key intermediates in the catalytic cycle.

Efficient Ni-catalyzed direct cross-couplings of benzylic alcohol derivatives with arylacetonitriles via CO activation are described. Various α-benzylated arylacetonitriles including those with functional groups can be prepared under mild reaction conditions.

The nickel-catalyzed α-benzylation of sulfones with readily available benzylic alcohol derivatives was achieved via C–O activation. The transformation was complete in 30 minutes using a simple Ni(COD)2 as a catalyst without any additional ligands. A variety of substituted sulfones including the building block for bioactive compound eletriptan were synthesized by using the strategy.

An efficient Ni-catalyzed synthesis of (E)-olefins using the readily available benzylic alcohol derivatives and arylacetonitriles is described. This transformation should proceed via a tandem process involving nickel-catalyzed cross coupling via C–O activation and subsequent stereoselective E2 elimination.

Efficient copper-catalysed aerobic oxidative esterification of N-heteroaryl methanes with alcohols has been developed. A variety of N-heteroaryl esters including those with functional groups are produced in good to excellent yields under the present reaction conditions.

The first nickel-catalyzed phosphinylation of C–S bonds forming C–P bonds is developed. The reaction can proceed readily with the simple Ni(cod)2 at a loading down to 0.1 mol% at the 10 mmol scale. Various aryl sulfur compounds, i.e. sulfides, sulfoxides and sulfones all couple with P(O)–H compounds to produce the corresponding organophosphorus compounds, which provides an efficient new method for the construction of C–P bonds.

A simple and environmentally benign method was developed for the synthesis of chalcones in high to excellent yields by a phosphorous acid promoted alkyne–aldehyde hydration–condensation in an oil/water two-phase system. The method is the first efficient protocol for the preparation of chalcones that is mediated by a simple Bronsted acid in a two-phase system.

An efficient and highly stereoselective reduction of a gem-dibromocyclopropane to the corresponding monobromocyclopropane under mild reaction conditions was developed using a combination of dimethy...

A palladium-catalyzed alkynylation of aromatic amines with terminal alkynes via in situ formed trimethylammonium salts is developed. Compared with previous system using ammonium salts as starting materials and high loading of pre-prepared NHC-Pd catalyst (10 mol% Pd), this reaction directly employed amines as the coupling partners and the commercially available Pd2(dba)3/PPh2Cy (1 mol% Pd) as the catalyst, greatly simplifying the manipulation and decreasing the cost.

A palladium-catalyzed phosphorylation of benzyl ammonium triflates with P(O)H compounds has been developed. Various benzylphosphorus compounds were produced in good to excellent yields with high functional group tolerance. All the three kinds of hydrogen phosphoryl compounds, i.e. H-phosphonates, H-phosphinates and secondary phosphine oxides, were applicable to this reaction. The successful scale-up experiment and one-pot synthetic operation also well demonstrated its practicality.

A palladium-catalyzed decarbonylative alkynylation of amides via C–N bond activation is developed. Compared with the reported Ni/Cu catalyzed reaction, which only proceeded well with silylacetylenes, this transformation was also applicable to both aromatic and aliphatic terminal alkynes, including those bearing functional groups, and thus provided a general and straightforward access to diverse internal alkynes.

A selective oxidative para-acylation of unprotected anilines with methyl groups in N-heteroarylmethanes was achieved. This transformation proceeds under mild metal-free reaction conditions to produce the corresponding valuable diarylmethanones in good to high yields, featuring high site-selectivity, high functional-group-tolerance, gram-scale synthesis and easy product-derivation. Preliminary mechanistic studies revealed that the present oxidative para-acylation would take place via a Friedel–Crafts-type process of in situ imines and the steric hindrance might be the key issue for the high regio-selectivity.

Under an oxygen atmosphere, the copper-mediated direct C3-cyanation of indole C–H bonds, using cheap and safe DMF as a CN source, took place selectively to produce the corresponding C3-cyanoindoles in good yields. A possible mechanism for this selective cyanation was proposed.

The mechanism of the palladium-catalyzed cross dehydrogenative coupling of P(O)–H compounds with terminal alkynes was studied. Successive ligand-exchange reactions of Pd(OAc)2 with a hydrogen phosphoryl compound and a terminal alkyne take place readily to replace the two acetates on palladium, producing the corresponding (phosphoryl) (alkynyl)palladium complexes, which upon heating decomposed to the corresponding alkynylphosphorus compound. It is also confirmed that in the stoichiometric reactions of the complexes, the configuration at phosphorus is retained. On the basis of these stoichiometric reactions, an efficient synthesis of P-chiral alkynylphosphoryl compounds via palladium-catalyzed stereoselective cross dehydrogenative coupling of P-chiral P(O)–H compounds with terminal alkynes was developed. The key palladium complexes and the stereochemistry of the chiral phosphorus compounds are all unambiguously determined by single-crystal X-ray analysis.

The first copper-catalyzed aerobic oxidative C(aryl)OH bond functionalization of catechols is reported. Under air, at room temperature, in the presence of a copper catalyst, catechols react with amines to produce the corresponding benzoxazoles in high yields. Mechanistic studies suggest that the reaction proceeds via an intriguing competitive oxidation and a synergetic catalysis between catechol and amine.

The Ni-catalyzed direct C-H/C-O cross couplings of benzylic alcohol derivatives with fluorobenzenes and heteroarenes are disclosed. This transformation provides a straightforward and efficient method for the synthesis of these valuable heteroatom-containing compounds.

Iron-catalyzed aerobic oxidative functionalization of sp3 C–H bonds has been developed for the construction of N-heterocycles from easily available carboxylic acid derivatives and o-substituted anilines. This transformation represents a widely applicable protocol to N-heterocycles using biofriendly iron as a catalyst in combination with molecular oxygen or air as the sole oxidant.