Ruthenium(II)-Catalyzed Late-Stage Incorporation of N-Aryl Triazoles and Tetrazoles with Sulfonium Salts via C-H Activation.

The late-stage functionalization of active pharmaceutical ingredients is a key challenge in medicinal chemistry. Furthermore, N-aryl triazoles and tetrazoles are important structural motifs with the potential to boost the activity of diverse drug molecules. Using easily accessible dibenzothiophenium salts for the ruthenium-catalyzed C-H arylation, these scaffolds were introduced into a variety of bioactive compounds. Our methodology uses cost-efficient ruthenium, KOAc as a mild base and gives access to a plethora of highly decorated triazole and tetrazole containing drug derivatives.

Photo-Induced Ruthenium-Catalyzed Double Remote C(sp2 )-H / C(sp3 )-H Functionalizations by Radical Relay.

Distal C(sp2 )-H and C(sp3 )-H functionalizations have recently emerged as step-economical tools for molecular synthesis. However, while the C(sp2 )-C(sp3 ) construction is of fundamental importance, its formation through double remote C(sp2 )-H/C(sp3 )-H activation has proven elusive. By merging the ruthenium-catalyzed meta-C(sp2 )-H functionalization with an aliphatic hydrogen atom transfer (HAT) process, we, herein, describe the catalyzed twofold remote C(sp2 )-H/C(sp3 )-H functionalizations via photo-induced ruthenium-mediated radical relay. Thus, meta-C(sp2 )-H arene bonds and remote C(sp3 )-H alkane bonds were activated by a single catalyst in a single operation. This process was accomplished at room temperature by visible light-notably without exogenous photocatalysts. Experimental and computational theory studies uncovered a manifold comprising ortho-C-H activation, single-electron-transfer (SET), 1,n-HAT (n=5-7) and σ-activation by means of a single ruthenium(II) catalyst.

Photo-Induced Ruthenium-Catalyzed C-H Benzylations and Allylations at Room Temperature.

The ruthenium-catalyzed synthesis of diarylmethane compounds was realized under exceedingly mild photoredox conditions without the use of exogenous photocatalysts. The versatility and robustness of the ruthenium-catalyzed C-H benzylation was reflected by an ample scope, including multifold C-H functionalizations, as well as transformable pyrazoles, imidates and sensitive nucleosides. Mechanistic studies were indicative of a photoactive cyclometalated ruthenium complex, which also enabled versatile C-H allylations.

Synthesis and photochromic behaviour of a series of benzopyrans bearing an N-phenyl-carbazole moiety: photochromism control by the steric effect.

Five new N-phenyl-carbazole benzopyrans bearing different substitutions on one of the phenyl rings at the sp3 carbon have been synthesized. Their molecular structures were investigated by X-ray and NMR analyses and through quantum chemical calculations. The photochromic mechanism under UV irradiation in toluene, consisting of the consecutive formation of transoid-cis (TC) and transoid-trans (TT) isomers, was studied by UV-vis spectral and kinetic analyses. These molecules have been specifically designed to ascertain the possibility of favouring the formation of the less thermodynamically stable TT at the photostationary state, upon exploiting steric hindrance effects on the diene part of the molecule. The spectrokinetic study allowed the estimation of most of the spectrokinetic parameters, such as molar extinction coefficients, quantum yields of UV colouration and visible photobleaching, and the rate constants of the fast and slow thermal bleaching processes. Peculiar effects of substituents with different donor strengths on one phenyl ring located at the 3-position were observed on the spectrokinetic properties.

Photo-Induced Ruthenium-Catalyzed C-H Arylations at Ambient Temperature.

Ambient temperature ruthenium-catalyzed C-H arylations were accomplished by visible light without additional photocatalysts. The robustness of the ruthenium-catalyzed C-H functionalization protocol was reflected by a broad range of sensitive functional groups and synthetically useful pyrazoles, triazoles and sensitive nucleosides and nucleotides, as well as multifold C-H functionalizations. Biscyclometalated ruthenium complexes were identified as the key intermediates in the photoredox ruthenium catalysis by detailed computational and experimental mechanistic analysis. Calculations suggested that the in situ formed photoactive ruthenium species preferably underwent an inner-sphere electron transfer.

Deaminative meta-C-H alkylation by ruthenium(ii) catalysis.

Precise structural modifications of amino acids are of importance to tune biological properties or modify therapeutical capabilities relevant to drug discovery. Herein, we report a ruthenium-catalyzed meta-C-H deaminative alkylation with easily accessible amino acid-derived Katritzky pyridinium salts. Likewise, remote C-H benzylations were accomplished with high levels of chemoselectivity and remarkable functional group tolerance. The meta-C-H activation approach combined with our deaminative strategy represents a rare example of selectively converting C(sp3)-N bonds into C(sp3)-C(sp2) bonds.