Efficient synthesis of α-amino-vinylphosphine oxides from alkyl nitriles via manganese-catalyzed phosphinoenamination.

A protocol for the synthesis of α-amino-vinylphosphine oxides by phosphinoenamination reaction between alkyl nitriles and phosphine oxides was developed. The combination of Mn(OAc)2 as a Lewis acid and guanidine as a Lewis base was found to be an efficient catalytic system for this reaction. A series of alkyl nitriles and phosphine oxides are compatible with this conversion, furnishing the desired products in up to 95% yield under mild conditions. Furthermore, this method demonstrates the capability of gram-scale synthesis.

Nickel-Catalyzed 1,1-Dihydrophosphinylation of Nitriles with Phosphine Oxides.

Treatment of phosphine oxides with nitriles usually furnishes 1,2-dihydrophosphinylation products. Herein, we developed a nickel-catalyzed 1,1-dihydrophosphinylation of nitriles with phosphine oxides to access primary amines. This reaction proceeded smoothly under very mild conditions. A series of nitriles and phosphine oxides were compatible with this conversion, and the desired products were obtained in moderate to good yields.

Conversions of aryl carboxylic acids into aryl nitriles using multiple types of Cu-mediated decarboxylative cyanation under aerobic conditions.

Here, we used malononitrile or AMBN as a cyanating agent to develop efficient and practical protocols for Cu-mediated decarboxylative cyanations, under aerobic conditions, of aryl carboxylic acids bearing nitro and methoxyl substituents at the ortho position as well as of heteroaromatic carboxylic acids. These protocols involved economical methods to synthesize value-added aryl nitriles from simple and inexpensive raw materials. Further diversification of the 2-nitrobenzonitrile product was performed to highlight the practicality of the protocols.

Inexpensive NaX (X = I, Br, Cl) as a halogen donor in the practical Ag/Cu-mediated decarboxylative halogenation of aryl carboxylic acids under aerobic conditions.

Versatile and practical Ag/Cu-mediated decarboxylative halogenation between readily available aryl carboxylic acids and abundant NaX (X = I, Br, Cl) has been achieved under aerobic conditions in moderate to good yields. The halodecarboxylation is shown to be an effective strategy for S-containing heteroaromatic carboxylic acid and benzoic acids with nitro, chloro and methoxyl substituents at the ortho position. A gram-scale reaction and a three-step procedure to synthesize iniparib have been performed to evaluate the practicality of this protocol. A preliminary mechanistic investigation indicates that Cu plays a vital role and a radical pathway is involved in the transformation.

Decarboxylative Halogenation and Cyanation of Electron-Deficient Aryl Carboxylic Acids via Cu Mediator as Well as Electron-Rich Ones through Pd Catalyst under Aerobic Conditions.

Simple strategies for decarboxylative functionalizations of electron-deficient benzoic acids via using Cu(I) as promoter and electron-rich ones by employing Pd(II) as catalyst under aerobic conditions have been established, which lead to smooth synthesis of aryl halides (-I, Br, and Cl) through the decarboxylative functionalization of benzoic acids with readily available halogen sources CuX (X = I, Br, Cl), and easy preparation of benzonitriles from decarboxylative cyanation of aryl carboxylic acids with nontoxic and low-cost K4Fe(CN)6 under an oxygen atmosphere for the first time.

Cu(II)-mediated phenol oxygenation: chemical evidence implicates a unique role of the enzyme active site in promoting the chemically difficult tyrosine monooxygenation in TPQ cofactor biogenesis of copper amine oxidases.

Cu(II)-mediated autoxidations of 4-tert-butylphenol under various conditions was studied, the data confirmed imidazole is the best ligand to promote phenol oxygenation. The same reaction of 2,4-di-tert-butylphenol proceeded much more quickly to lead nearly exclusively to oxidative coupling rather than oxygenation under high pressure O2. These results suggested that Cu(II)-catalyzed phenol autoxidation by activating O2 and phenol in terms of a phenoxy radical (ArO)-Cu(II)-superoxide ternary complex, whereas selectivity between oxygenation and coupling depends mainly on the electronic structure of ArO. It is appeared that CuAOs could achieve stoichiometric tyrosine monooxygenation by modulating the redox potential of Cu(II) and stabilizing the ternary complex through protein conformational adjustment.

Visible-light-induced C(sp3)-C(sp3) bond formation via radical/radical cross-coupling.

Radical/radical cross-coupling remains challenging due to diffusion control issues. Herein, we report a visible-light-induced radical/radical cross-coupling reaction of quaternary ammonium salts and Hantzschs via C-N and C-C bond cleavage. The current synthetic approach furnishes 1,2-diphenylethanes in moderate to good yields and provides a method for the construction of the C(sp3)-C(sp3) bond.

An Electrochemical Method for Deborylative Hydroxylation of Arylboronic Acids under Metal-free Conditions.

An electrochemical method for the synthesis of (poly)phenols via deborylative hydroxylation of arylborons has been well established under metal-free conditions, whose practicability and advantage has been highlighted by the preparation of drug molecules and preformation of scalable transformation. Mechanistic studies have demonstrated that superoxide anion radical was involved in the conversion followed by the reaction with arylboronic acid substrate.

Bromide ion promoted practical synthesis of phosphinothioates of sulfinic acid derivatives and H-phosphine oxides.

A feasible method for the synthesis of phosphinothioates from sulfinic acid derivatives and phosphine oxides is described. This reaction can be carried out in an open flask at room temperature and in an aqueous medium. The scope of the sulfinic acid derivatives is extensive, with a wide range of sulfinate esters, sulfinic acids, and sodium sulfinates compatible with these conditions, with good to excellent yields of phosphinothioates. In addition, a gram-scale synthesis with this reaction is achieved. A mechanism of this procedure was proposed.

Selective C-C bond cleavage of amides fused to 8-aminoquinoline controlled by a catalyst and an oxidant.

Herein, copper-catalyzed direct C-C bond cleavage of amides fused to 8-aminoquinoline as a directing group to form urea in the presence of amines and dioxygen is reported. Compared to the previous C-H aminations of amides via C-H activation, this reaction presents a catalyst and oxidant controlled C-C bond cleavage strategy that enables amidation through a radical process. CuBr/Ag2CO3/O2 shows the best catalytic result at 150 °C. A series of aryl and alkyl amides were compatible with this transformation. Notably, this method provided access to cyclohexanone, one of the most important industrial materials. The pathway of this reaction was investigated.

Pd-Catalyzed Decarboxylative Ortho-Halogenation of Aryl Carboxylic Acids with Sodium Halide NaX Using Carboxyl as a Traceless Directing Group.

A highly regioselective Pd-catalyzed carboxyl directed decarboxylative ortho-C-H halogenation of cheap o-nitrobenzoic acids with NaX (X = I, Br) under aerobic conditions has been established. The utility of the method has been demonstrated by the gram-scale reaction and derivatization of the product. Experimental results have confirmed Pd and Bi played critical roles in the transformation and indicated the transformation might proceed via 2-halo-6-nitrobenzoic acid derivative intermediate.

Pd-catalyzed dearboxylative Heck coupling with dioxygen as the terminal oxidant.

Pd-catalyzed decarboxylative Heck coupling of aromatic carboxylic acids with various olefins is developed using O(2) as the terminal oxidant. Enhancement of O(2) pressure leads to improving reaction turnover in this transformation and allows significantly reducing catalyst loading for efficient conversion of electron-rich benzoic acids. A Pd catalyst supported by a carbene ligand enables using electron-deficient benzoic acids as coupling partners.

Pd-catalyzed decarboxylative arylation of silyl enol ester sp3 ß-C-H bond under aerobic conditions.

Pd-catalyzed aerobic oxidative coupling of various benzoic acids with silyl enol esters proceeds via a combination of decarboxylation with sp(3) ß-C-H bond activation to give Heck-type products. Mechanistic studies reveal this coupling involves in situ generation of olefin from aerobic oxidation of silyl enolate, followed by decarboxylative Heck coupling.