Transition-Metal-Catalyzed C-H Bond Activation for the Formation of C-C Bonds in Complex Molecules.

Site-predictable and chemoselective C-H bond functionalization reactions offer synthetically powerful strategies for the step-economic diversification of both feedstock and fine chemicals. Many transition-metal-catalyzed methods have emerged for the selective activation and functionalization of C-H bonds. However, challenges of regio- and chemoselectivity have emerged with application to highly complex molecules bearing significant functional group density and diversity. As molecular complexity increases within molecular structures the risks of catalyst intolerance and limited applicability grow with the number of functional groups and potentially Lewis basic heteroatoms. Given the abundance of C-H bonds within highly complex and already diversified molecules such as pharmaceuticals, natural products, and materials, design and selection of reaction conditions and tolerant catalysts has proved critical for successful direct functionalization. As such, innovations within transition-metal-catalyzed C-H bond functionalization for the direct formation of carbon-carbon bonds have been discovered and developed to overcome these challenges and limitations. This review highlights progress made for the direct metal-catalyzed C-C bond forming reactions including alkylation, methylation, arylation, and olefination of C-H bonds within complex targets.

Luminescent cis-Bis(bipyridyl)ruthenium(II) Complexes with 1,2-Azolylamidino Ligands: Photophysical, Electrochemical Studies, and Photocatalytic Oxidation of Thioethers.

New 1,2-azolylamidino complexes cis-[Ru(bipy)2(NH═C(R)az*-κ2N,N)](OTf)2 (R = Me, Ph; az* = pz, indz, dmpz) are synthesized via chloride abstraction after a subsequent base-catalyzed coupling of a nitrile with the previously coordinated 1,2-azole. The synthetic procedure allows the easy obtainment of complexes having different electronic and steric 1,2-azoylamidino ligands. All of the compounds have been characterized by 1H, 13C, and 15N NMR and IR spectroscopy and by monocrystal X-ray diffraction. Photophysical studies support their phosphorescence, whereas their electrochemistry reveals reversible RuII/RuIII oxidations between +1.13 and +1.25 V (vs SCE). The complexes have been successfully used as catalysts in the photooxidation of different thioethers, the complex cis-[Ru(bipy)2(NH═C(Me)dmpz-κ2N,N)]2+ showing better catalytic performance in comparison to that of [Ru(bipy)3]2+. Moreover, the significant catalytic performance of the dimethylpyrazolylamidino complex is applied to the preparation of the drug modafinil, which is obtained using ambient oxygen as an oxidant. Finally, mechanistic assays suggest that the oxidation reaction follows a photoredox route via oxygen radical anion formation.

Photocatalytic Water-Soluble Cationic Platinum(II) Complexes Bearing Quinolinate and Phosphine Ligands.

Cationic Pt(II) complexes ([Pt(QO/S)(P∧P)]X), having 8-oxy or 8-thioquinolinate (QO/S) and seven different mono- or bidentate phosphines as ligands, have been synthesized and characterized. The photophysical, stability, and photocatalytic properties of those complexes were studied and compared to that of the parent [Pt(QO/S)(dmso)(Cl)]. The coordination of phosphines induced a red-shift in the absorption energy of the MLCT band, whereas the emission wavelength of the complexes only depended on the nature of the quinolinate ligand. Moreover, the photocatalytic activity of the Pt(II) complexes was evaluated in the oxidation of sulfides using atmospheric oxygen as an oxidant. All the complexes were active photocatalysts for that transformation, with [Pt(QO)(BINAP)]Cl and [Pt(QO)(SEGPHOS)]Cl (BINAP: 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, SEGPHOS: (4,4'-bibenzodioxole)-5,5'-diyldiphosphine) exhibiting high catalytic performance and stability. In addition, the enhanced water solubility of the complexes allowed performance of the photooxidation reaction under environmentally friendly conditions. In particular, the catalyst [Pt(QS)(dppe)]Cl, bearing 8-thioquinolinate and diphenylphosphinoethate (dppe) as ligands, successfully catalyzed the oxidation of a variety of sulfides using water as a solvent.

Catalysis with cycloruthenated complexes.

Cycloruthenated complexes have been studied extensively over the last few decades. Many accounts of their synthesis, characterisation, and catalytic activity in a wide variety of transformations have been reported to date. Compared with their non-cyclometallated analogues, cycloruthenated complexes may display enhanced catalytic activities in known transformations or possess entirely new reactivity. In other instances, these complexes can be chiral, and capable of catalysing stereoselective reactions. In this review, we aim to highlight the catalytic applications of cycloruthenated complexes in organic synthesis, emphasising the recent advancements in this field.

Ruthenium-Catalyzed Monoselective C-H Methylation and d 3-Methylation of Arenes.

Site-selective installation of C-Me bonds remains a powerful and sought-after tool to alter the chemical and pharmacological properties of a molecule. Direct C-H functionalization provides an attractive means of achieving this transformation. Such protocols, however, typically utilize harsh conditions and hazardous methylating agents with poor applicability toward late-stage functionalization. Furthermore, highly monoselective methylation protocols remain scarce. Herein, we report an efficient monoselective, directed ortho-methylation of arenes using N,N,N-trimethylanilinium salts as noncarcinogenic, bench-stable methylating agents. We extend this protocol to d 3-methylation in addition to the late-stage functionalization of pharmaceutically active compounds. Detailed kinetic studies indicate the rate-limiting in situ formation of MeI is integral to the observed reactivity.

Asymmetric [2+2] photocycloaddition via charge transfer complex for the synthesis of tricyclic chiral ethers.

The asymmetric synthesis of chiral polycyclic ethers by an intramolecular [2+2] photocycloaddition is described. This process proceeded through a photocatalytically active iminium ion-based charge transfer (CT) complex under visible light irradiation. In this way a stereocontrolled [2+2] photocycloaddition is enabled leading to tricyclic products with good enantiomeric ratios.

Visible light photocatalytic asymmetric synthesis of pyrrolo[1,2-a]indoles via intermolecular [3+2] cycloaddition.

The intermolecular diastereoselective and enantioselective synthesis of pyrrolo[1,2-a]indoles is developed through a [3+2] cycloaddition between silyl-indole derivatives and α,ß-unsaturated N-acyl oxazolidinones by merging photocatalysis and Lewis acid catalysis.