Regio- and Chemoselective Access to Dihydrothiophenes and Thiophenes via Halogenation/Intramolecular C(sp2)-H Thienation of α-Allyl Dithioesters at Room Temperature.

An operationally simple, practical, and efficient cascade approach employing α-allyl dithioesters and NBS/NIS has been achieved to access a series of dihydrothiophenes and thiophenes containing diverse functional groups of different electronic and steric natures in good to excellent yields at room temperature in open air. The reaction proceeds via the electrophilic addition of a halogen source (NBS/NIS) to an allylic double bond, followed by intramolecular regio- and chemoselective S-cyclization. This protocol avoids potential toxicity and tedious work-up conditions, and features easy synthesis from readily available starting materials under catalyst-free conditions. Furthermore, 4,5-dihydrothiophenes were aromatized to thiophenes by treatment with KOH in DMF at room temperature. A probable mechanism for the formation of dihydrothiophenes and thiophenes from α-allyl dithioesters has been suggested. Notably, a large-scale experiment and the transformations of products indicated the potential utility of this reaction compared to competing processes for the synthesis of 4,5-dihydrothiophenes and thiophenes.

Electrochemical Synthesis of 1,2,3-Thiadiazoles from α-Phenylhydrazones.

We have developed an electrochemical approach for the synthesis of fully substituted 1,2,3-thiadiazoles from α-phenylhydrazones at room temperature, which is very challenging and complementary to the conventional thermal reactions. The key step involves anodic oxidation of phenylhydrazone derivatives at a constant current followed by N,S-heterocyclization. The protocol is remarkable in that it is free of a base and free of an external oxidant and can be converted to a gram scale for postsynthetic drug development with functional thiadiazoles. Most importantly, the electrochemical transformation reflected efficient electro-oxidation with an operationally friendly easy procedure with ample functional molecules. Cyclic voltammograms support the mechanism of this electro-oxidative cyclization process.

Flow chemistry-enabled studies of rhodium-catalyzed hydroformylation reactions.

We present an automated microscale flow chemistry platform for rapid performance evaluation of continuous and discrete reaction parameters in homogeneous hydroformylation reactions. We demonstrate the versatility of the developed microfluidic platform through a systematic study of the effects of a library of phosphine-based ligands on catalytic activity and regioselectivity.

Ruthenium(II)-Catalyzed C-H Oxygenations of Reusable Sulfoximine Benzamides.

C-H oxygenations of synthetically meaningful sulfoximine benzamides were accomplished by a versatile ruthenium catalysis regime. The ruthenium(II) catalyst was characterized by excellent mono- and chemoselectivity as well as positional selectivity via facile base-assisted intramolecular electrophilic substitution-type (BIES) C-H activation. The synthetic utility of the approach was reflected by high functional group tolerance and sulfoximine removal in a traceless fashion.

Ruthenium(II)-Catalyzed Decarboxylative C-H Activation: Versatile Routes to meta-Alkenylated Arenes.

Ruthenium(II) bis(carboxylate)s proved highly effective for two decarboxylative C-H alkenylation strategies. The decarboxylation proceeded efficiently at rather low temperatures. The unique versatility of the decarboxylative ruthenium(II) catalysis is reflected in the oxidative olefinations with alkenes as well as the redox-neutral hydroarylations of alkynes.

Ruthenium Oxidase Catalysis for Site-Selective C-H Alkenylations with Ambient O2 as the Sole Oxidant.

Ruthenium(II) oxidase catalysis by direct dioxygen-coupled turnover enabled step-economical oxidative C-H alkenylation reactions at ambient pressure. Versatile ruthenium(II) biscarboxylate catalysts displayed ample substrate scope and proved applicable to weakly coordinating and removable directing groups. The twofold C-H functionalization strategy was characterized by exceedingly mild reaction conditions as well as excellent positional selectivity.

Ruthenium(II)-catalyzed C-H acyloxylation of phenols with removable auxiliary.

Intermolecular C-H acyloxylations of phenols with removable directing groups were accomplished with a versatile ruthenium catalyst. Specifically, a cationic ruthenium(II) complex, formed in situ, enabled the chemoselective C-H oxygenations of a broad range of substrates. The catalyst proved tolerant of synthetically valuable functional groups, and the substrate scope included both (hetero)aromatic and, the more challenging, aliphatic carboxylic acids. The proposed reaction mechanism involves a reversible C-H ruthenation and an oxidatively induced C-O-bond-forming reductive elimination.

In(OTf)3-catalysed one-pot versatile pyrrole synthesis through domino annulation of α-oxoketene-N,S-acetals with nitroolefins.

In(OTf)3-catalyzed robust and sustainable one-pot access to previously unknown and synthetically demanding polysubstituted pyrroles via [3 + 2] annulation of α-oxoketene-N,S-acetals with ß-nitrostyrenes has been achieved under solvent-free conditions. The merit of this domino Michael addition/cyclization sequence is highlighted by its operational simplicity, short reaction time (5-10 min), good to excellent yields, tolerance of a large variety of functional groups, and efficiency of producing two new (C-C and C-N) bonds and one highly functionalized pyrrole ring in a single operation, which make it an ideal alternative to existing methods.

Expedient C-H amidations of heteroaryl arenes catalyzed by versatile ruthenium(II) catalysts.

Heteroaryl-substituted arenes and heteroarenes were efficiently amidated through ruthenium-catalyzed C-H bond functionalizations with a variety of sulfonyl azides. Particularly, cationic ruthenium(II) complexes proved to be most effective and allowed nitrogenations of electron-rich and electron-deficient arenes with ample substrate scope.