Can-Cheng Guo

Pd-catalyzed decarboxylative arylation of thiazole, benzoxazole, and polyfluorobenzene with substituted benzoic acids.

A Pd-catalyzed decarboxylative coupling of thiazoles and benzoxazole with various substituted benzoic acids is developed. The reaction is compatible with both electron-rich and electron-poor benzoic acids. It can also be extended to the synthesis of polyfluoro-substituted biaryls using polyfluorobenzenes as the starting materials.

Transition-Metal-Free Oxidative α-C–H Amination of Ketones via a Radical Mechanism: Mild Synthesis of α-Amino Ketones

A transition-metal-free direct α-C-H amination of ketones has been developed using commercially available ammonium iodide as the catalyst and sodium percarbonate as the co-oxidant. A wide range of ketone ((hetero)aromatic or nonaromatic ketones) and amine (primary/secondary amines, anilines, or amides) substrates undergo cross-coupling to generate synthetically useful α-amino ketones. The mechanistic studies indicated that a radical pathway might be involved in the reaction process. The utility of the method is highlighted through a concise one-step synthesis of the pharmaceutical agent amfepramone.

Copper-Catalyzed Aerobic Decarboxylative Sulfonylation of Cinnamic Acids with Sodium Sulfinates: Stereospecific Synthesis of (E)-Alkenyl Sulfones

A copper-catalyzed aerobic decarboxylative sulfonylation of alkenyl carboxylic acids with sodium sulfinates is developed. This study offers a new and expedient strategy for stereoselective synthesis of (E)-alkenyl sulfones that are widely present in biologically active natural products and therapeutic agents. Moreover, the transformation is proposed to proceed via a radical process and exhibits a broad substrate scope and good functional group tolerance.

A new evidence of the high-valent oxo–metal radical cation intermediate and hydrogen radical abstract mechanism in hydrocarbon hydroxylation catalyzed by metalloporphyrins

Abstract Forty metalloporphyrins with different peripheral substituents (R) on the porphyrin ring, RTPPM III Cl and [RTPPM III ] 2 O (M=Fe, Mn), were synthesized, and were used to catalyze cyclohexane hydroxylation with iodosobenzene under mild conditions. A Hammett relationship, log k = ρσ + c , was shown to exist between the rate constants k of the cyclohexane hydroxylation and Hammett constants σ of substituents on the porphyrin rings. The value of the reaction constant ρ changed from 0.3 to 0.5 for the cyclohexane oxidation catalyzed by metalloporphyrins, and electron-withdrawing groups increased the reaction speeds. This means that the reaction mediator was a radical cation, and that the rate-determining step of the reaction was a radical reaction. These research results provided a new evidence for the high-valent oxo–metal radical cation intermediate and hydrogen radical abstraction mechanism in hydrocarbon hydroxylation catalyzed by metalloporphyrins.

Iron-facilitated oxidative radical decarboxylative cross-coupling between α-oxocarboxylic acids and acrylic acids: an approach to α,β-unsaturated carbonyls.

The first Fe-facilitated decarboxylative cross-coupling reaction between α-oxocarboxylic acids and acrylic acids in aqueous solution has been developed. This transformation is characterized by its wide substrate scope and good functional group compatibility utilizing inexpensive and easily accessible reagents, thus providing an efficient and expeditious approach to an important class of α,β-unsaturated carbonyls frequently found in bioactive compounds. The synthetic potential of the coupled products is also demonstrated in subsequent functionalization reactions. Preliminary mechanism studies suggest that a free radical pathway is involved in this process: the generation of an acyl radical from α-oxocarboxylic acid via the excision of carbon dioxide followed by the addition of an acyl radical to the α-position of the double bond in acrylic acid then delivers the α,β-unsaturated carbonyl adduct through the extrusion of another carbon dioxide.

Investigations on cytotoxicity and anti-inflammatory potency of licofelone derivatives

A series of C5-substituted licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid) derivatives were developed by a parallel synthesis approach and investigated for cytotoxicity against MCF-7 and MDA-MB-231 cells as well as for anti-inflammatory potency in vitro and in vivo. Dependent on the C5-substituent, the compounds showed high selectivity for MCF-7 cells. Especially 2-oxoethyl benzoate derivatives were inactive at the MDA-MB-231 cell line and as active as 5-FU at MCF-7 cells. C5-acetyl (8a), -2-oxoethyl formiate (8e), -2-oxoethyl acetate (8f) and -2-oxoethyl propionate (8g) derivatives showed growth inhibition at both cell lines, comparable with cisplatin. Modifications significantly reduced the inhibitory potency at COX-1 and COX-2 in vitro and in the xylene-induced ear swelling assay in mice. Only compound 8a was equipotent to licofelone, ibuprofen and celecoxibe in vivo.

Phenyliodonium diacetate mediated direct synthesis of benzonitriles from styrenes through oxidative cleavage of C═C bonds.

A metal-free PhI(OAc)2 mediated nitrogenation of alkenes through C═C bond cleavage using inorganic ammonia salt as nitrogen source under mild conditions was developed, affording nitriles in moderate to good yields. The advantages of this reaction are mild reaction conditions, operational simplicity, and use of an ammonium salt as nitrogen source. Based upon experimental observations, a plausible reaction mechanism is proposed.

First industrial-scale biomimetic oxidation of hydrocarbon with air over metalloporphyrins as cytochrome P-450 monooxygenase model and its mechanistic studies

A novel industrial-scale trial for cyclohexane oxidation with air over metalloporphyrins as cytochrome P-450 monooxygenase model was reported. Upon addition of extremely low concentrations (1–5 ppm) of simple cobalt porphyrin to the commercial cyclohexane oxidation system, and decrease of the reaction temperature and pressure about 20 °C and 0.4 MPa respectively, the conversion rate of the cyclohexane oxidation increased from 4.8% to 7.1%, the yield of cyclohexanone raised from 77% to 87%, and a 70,000-ton cyclohexanone equipment set yielded an output of 125,000 tons cyclohexanone. Furthermore, a novel biological-chemical-cycle coupling mechanism was proposed to rationalize the aerobic oxidations of hydrocarbons catalyzed by the metalloporphyrins.

Rational oxidation of cyclohexane to cyclohexanol, cyclohexanone and adipic acid with air over metalloporphyrin and cobalt salt

A systematic study on the effect of a catalyst on the aerobic oxidation of cyclohexane was carried out using cobalt isooctanoate, metalloporphyrin p-ClTPPCo and [p-ClTPPFe]2O as catalysts. The results showed that the metalloporphyrin-catalyzed system performed better than the traditional cobalt salt (Co isooctanoate) in terms of both the reaction conversion and the selectivity of cyclohexanol and cyclohexanone (KA oil). More importantly, we discovered that bisironporphyrin complex, which was traditionally considered to be either non-active or not-so-active for hydrocarbon oxidation, excelled at 155°C, achieving high selectivity for KA oil (80%) and good reaction conversion (13.8%). This result is in sharp contrast to earlier results by others. Meanwhile, the production of adipic acid was also increased and good selectivity of adipic acid among the by-products was also obtained. Our study suggested that [p-ClTPPFe]2O catalyzed aerobic oxidation could be used to produce adipic acid in addition to KA oil. Some mechanistic rationales were proposed to explain the superior performance of the [p-ClTPPFe]2O catalyst based on its unique structural and chemical properties.

Transition-Metal-Free TBAI-Facilitated Addition-Cyclization of N-Methyl-N-arylacrylamides with Arylaldehydes or Benzenesulfonohydrazides: Access to Carbonyl- and Sulfone-Containing N-Methyloxindoles.

A highly efficient addition-cyclization of N-methyl-N-arylacrylamides with arylaldehydes or benzenesulfonohydrazides was developed using a catalytic amount of the quaternary ammonium salt (TBAI) under metal-free conditions, leading to the carbonyl- and sulfone-containing oxindoles. Compared to previous methods, which require excessive amounts of explosive organic peroxides and precious or toxic metal reagents, the present protocol, which gave access to 3,3-disubstituted oxindoles, is a safe and green approach, resulting in the formation of various useful carbonyl- and sulfone-containing oxindoles in yields of 40-94%.