CuH-Catalyzed Reductive Coupling of Nitroarenes with Phosphine Oxides for the Direct Synthesis of Phosphamides.

A CuH-catalyzed reductive coupling of nitroarenes with phosphine oxides is developed, which produces a series of phosphamides in moderate to excellent yields with good functional group tolerance. Gram-scale synthesis and late-stage modification of nitro-aromatic functional molecule niclosamide are also successfully conducted. The mechanism study shows that the nitro group is transformed after being reduced to nitroso and a nucleophilic addition procedure is involved during the reaction.

Ligand-Free Iron-Catalyzed Construction of C-P Bonds via Phosphorylation of Alcohols: Synthesis of Phosphine Oxides and Phosphine Compounds.

An efficient method for the construction of C-P(V) and C-P(III) bonds via the iron-catalyzed phosphorylation of alcohols under ligand-free conditions is disclosed. This strategy represents a straightforward process to prepare a series of phosphine oxides and phosphine compounds in good to excellent yields from the readily available alcohols and P-H compounds. A plausible mechanism is also proposed. We anticipate that this mode of transforming simple alcohols would apply in chemical synthesis widely.

Highly efficient esterification of carboxylic acids with O-H nucleophiles through acid/iodide cooperative catalysis.

The esterification of carboxylic acids is an important reaction for preparing esters which find wide applications in various research fields. In this manuscript, we report an acid/iodide cooperative catalytic method which enables highly efficient esterification of carboxylic acids with a wide range of equivalent O-H nucleophiles including both alcohols and weak nucleophilic phenols. Under the reaction conditions, both aromatic and aliphatic carboxylic acids including those bearing functional groups work well, furnishing the corresponding esters in good to high yields. Moreover, this reaction is scalable and applicable to the modification of bioactive molecules. These results demonstrate the synthetic value of this new reaction in organic synthesis.

Pd-catalyzed ortho-C-H arylation of free anilines with arylboric acids forming o-amino biaryls.

We report a Pd-catalyzed ortho-C-H arylation of free anilines with arylboric acids. Under the reaction conditions, a wide range of arylboric acids can couple with free anilines to produce the corresponding o-amino biaryls in moderate to good yields with good functional group tolerance. This reaction can be conducted on the gram scale. The products can be easily further functionalized via transformation of the free amino group. These results indicate the potential synthetic value of this new reaction in organic synthesis.

Synthesis and Spectroscopic Characterization of Selected Water-Soluble Ligands Based on 1,10-Phenanthroline Core.

Water-soluble ligands based on a 1,10-phenanthroline core are relatively poorly studied compounds. Developing efficient and convenient syntheses of them would result in new interesting applications because of the importance of 1,10-phenanthrolines. In this manuscript, we describe novel and practical ways to introduce a carboxyl and, for the first time, a phenol and dithiocarboxyl group under mild reaction conditions. This strategy enables highly efficient and practical synthesis of suitable organosulfur compounds with high added value, high chemoselectivity, and a broad substrate range. We present the selective conversion of a hydroxydialdehyde in the form of 10-hydroxybenzo[h]quinoline-7,9-dicarbaldehyde into its derivative, unique hydroxydicarboxylic acid, by an oxidation procedure, giving 10-hydroxybenzo[h]quinoline-7,9-dicarboxylic acid. A similar procedure resulted in the formation of 9-methyl-1,10-phenanthroline-2-carboxylic acid by oxidation of commercially available neocuproine. An alternative method of obtaining 1,10-phenanthroline derivatives possessing carboxylic acid group can be based on the hydrolysis of ester or nitrile groups; however, this synthesis leads to unexpected products. Moreover, we apply Perkin condensation to synthesize a vinyl (or styryl) analog of 1,10-phenanthroline derivatives with phenol function. This reaction also demonstrates a new, simple, and efficient strategy for converting methyl derivatives of 1,10-phenanthroline. We anticipate that the new way of converting methyl will find wide application in chemical synthesis.

Palladium-Catalyzed Decarbonylative Annulation of 2-Arylbenzoic Acids with Internal Alkynes toward Phenanthrenes.

A palladium-catalyzed decarbonylative annulation of 2-arylbenzoic acids with internal alkynes via C(sp2)-H activation has been developed. A series of phenanthrenes were produced in moderate to good yield with good functional group tolerance. The mechanism study indicated that the C(sp2)-H activation should be the rate-determining step during the reaction.

Synthesis of acyl fluorides through deoxyfluorination of carboxylic acids.

A direct deoxyfluorination of carboxylic acids by utilizing inorganic potassium fluoride (KF) as a safe and inexpensive fluoride source has been developed. Both aryl carboxylic acids and cinnamyl carboxylic acids could be efficiently transformed into valuable acyl fluorides in moderate to high yields with good functional group tolerance. A scale-up reaction could be carried out smoothly under solvent-free conditions, which further demonstrated the practicality of this reaction in organic synthesis.

Palladium-catalysed deaminative/decarboxylative cross-coupling of organoammonium salts with carboxylic acids.

A palladium-catalysed carbon-carbon bond-forming reaction via deaminative/decarboxylative cross-coupling of organoammonium salts with carboxylic acids was developed. Under the reaction conditions, polyfluoroaromatic carboxylic acids, propiolic acids and α-cyano benzyl carboxylic acid reacted smoothly with benzyl ammonium salts to produce the corresponding carbon-carbon coupling products in good-to-excellent yields.

Palladium-catalyzed and norbornene-mediated C-H amination and C-O alkenylation of aryl triflates.

The C-H amination and C-O alkenylation of aryl triflates was achieved through Pd/norbornene (NBE) cooperative catalysis. By this strategy, various ortho-alkenyl tertiary anilines including those bearing functional groups were produced in good to excellent yields. This reaction represents a new conversion model for phenoxides. It expands the scope of Catellani-type reactions and the application of phenoxides in organic synthesis.

Palladium-Catalyzed Decarbonylative Cyanation of Carboxylic Acids with TMSCN.

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.

Nickel-Catalyzed Decarbonylative Thioetherification of Carboxylic Acids with Thiols.

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.

Base-promoted direct E-selective olefination of organoammonium salts with sulfones toward stilbenes and conjugated 1,3-dienes.

A base-promoted direct deaminative olefination of organoammonium salts was developed. Only mediated by KOtBu, a series of benzyl and cinnamyl ammonium salts reacted smoothly with sulfones, producing the valuable stilbenes and related 1,3-diene derivatives in good to high yields with good functional group tolerance and excellent E-selectivity. With this developed method, biologically active resveratrol and DMU-212 were also successfully prepared, which further demonstrates the practicality of this reaction.

Highly Chemoselective Transamidation of Unactivated Tertiary Amides by Electrophilic N-C(O) Activation by Amide-to-Acyl Iodide Re-routing.

The challenging transamidation of unactivated tertiary amides has been accomplished via cooperative acid/iodide catalysis. Most crucially, the method provides a novel manifold to re-route the reactivity of unactivated N,N-dialkyl amides through reactive acyl iodide intermediates, thus reverting the classical order of reactivity of carboxylic acid derivatives. This method provides a direct route to amide-to-amide bond interconversion with excellent chemoselectivity using equivalent amounts of amines. The combination of acid and iodide has been identified as the essential factor to activate the amide C-N bond through electrophilic catalytic activation, enabling the production of new desired transamidated products with wide substrate scope of both unactivated amides and amines, including late-stage functionalization of complex APIs (>80 examples). We anticipate that this powerful activation mode of unactivated amide bonds will find broad-ranging applications in chemical synthesis.

Transition-Metal-Free and Base-Promoted Carbon-Heteroatom Bond Formation via C-N Cleavage of Benzyl Ammonium Salts.

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.

Practical Electro-Oxidative Sulfonylation of Phenols with Sodium Arenesulfinates Generating Arylsulfonate Esters.

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.

Palladium-Catalyzed Stereoselective Difunctionalization of Bicyclic Alkenes with Organoammonium Salts and Organoboronic Compounds.

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 ß-borylated products further demonstrated the synthetic value of this new reaction in organic synthesis.

Discovery of an Oxidative System for Radical Generation from Csp3-H Bonds: A Synthesis of Functionalized Oxindoles.

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).

Transition-metal-free and base promoted C-C bond formation via C-N bond cleavage of organoammonium salts.

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.

Controllable Phosphorylation of Thioesters: Selective Synthesis of Aryl and Benzyl Phosphoryl Compounds.

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.

Metal- and radical-free aerobic oxidation of heteroaromatic methanes: an efficient synthesis of heteroaromatic aldehydes.

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.