Catalytic dehydrogenative cross-coupling: forming carbon-carbon bonds by oxidizing two carbon-hydrogen bonds

Electrochemistry represents one of the most intimate ways of interacting with molecules. This review discusses advances in synthetic organic electrochemistry since 2000. Enabling methods and synthetic applications are analyzed alongside innate advantages as well as future challenges of electroorganic chemistry.

Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

Over the last decade, substantial research has led to the introduction of an impressive number of efficient procedures which allow the selective construction of CC bonds by directly connecting two different CH bonds under oxidative conditions. Common to these methodologies is the generation of the reactive intermediates in situ by activation of both CH bonds. This strategy was introduced by the group of Li as cross-dehydrogenative coupling (CDC) and discloses waste-minimized synthetic alternatives to classic coupling procedures which rely on the use of prefunctionalized starting materials. This Review highlights the recent progress in the field of cross-dehydrogenative C sp 3C formations and provides a comprehensive overview on existing procedures and employed methodologies.

The Cross-Dehydrogenative Coupling of C sp 3H Bonds: A Versatile Strategy for CC Bond Formations

Micromachining technology was used to prepare chemical analysis systems on glass chips (1 centimeter by 2 centimeters or larger) that utilize electroosmotic pumping to drive fluid flow and electrophoretic separation to distinguish sample components. Capillaries 1 to 10 centimeters long etched in the glass (cross section, 10 micrometers by 30 micrometers) allow for capillary electrophoresis-based separations of amino acids with up to 75,000 theoretical plates in about 15 seconds, and separations of about 600 plates can be effected within 4 seconds. Sample treatment steps within a manifold of intersecting capillaries were demonstrated for a simple sample dilution process. Manipulation of the applied voltages controlled the directions of fluid flow within the manifold. The principles demonstrated in this study can be used to develop a miniaturized system for sample handling and separation with no moving parts.

Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip

Enantioselective addition of dialkylzincs to aldehydes promoted by chiral amino alcohols. Mechanism and nonlinear effect

Catalytic asymmetric induction. Highly enantioselective addition of dialkylzincs to aldehydes

Oxygen (O(2)) is a prerequisite for cellular respiration in aerobic organisms but also elicits toxicity. To understand how animals cope with the ambivalent physiological nature of O(2), it is critical to elucidate the molecular mechanisms responsible for O(2) sensing. Here our systematic evaluation of transient receptor potential (TRP) cation channels using reactive disulfides with different redox potentials reveals the capability of TRPA1 to sense O(2). O(2) sensing is based upon disparate processes: whereas prolyl hydroxylases (PHDs) exert O(2)-dependent inhibition on TRPA1 activity in normoxia, direct O(2) action overrides the inhibition via the prominent sensitivity of TRPA1 to cysteine-mediated oxidation in hyperoxia. Unexpectedly, TRPA1 is activated through relief from the same PHD-mediated inhibition in hypoxia. In mice, disruption of the Trpa1 gene abolishes hyperoxia- and hypoxia-induced cationic currents in vagal and sensory neurons and thereby impedes enhancement of in vivo vagal discharges induced by hyperoxia and hypoxia. The results suggest a new O(2)-sensing mechanism mediated by TRPA1.

/pdf/trpa1-underlies-a-sensing-mechanism-for-o2-4ipy0mgu71.pdf

TRPA1 underlies a sensing mechanism for O2

This article provides a brief outline of the state of the art of reactions using microreactors with special emphasis on the enhancement of product selectivity. The efficient micromixing possible with a short diffusion path increases the product selectivity of competitive parallel reactions and competitive consecutive reactions. This concept has been expanded to control of the molecular weight and molecular weight distribution in carbocationic polymerization. The efficient heat transfer, based on high surface to volume ratios, allows precise temperature control and is also effective for the control of highly exothermic reactions, such as free radical polymerization.

Enhancement of Chemical Selectivity by Microreactors

We have developed a method that involves the generation of a “cation pool” using low-temperature electrolysis, and then its reaction with nucleophiles under non-oxidative conditions. This one-pot method solves problems associated with conventional oxidative generation of cations and their in situ reaction with nucleophiles, and provides an efficient method for direct oxidative carbon−carbon bond formation. As an example of this method, generation of cation pools from carbamates by low-temperature electrolysis (−72 °C) and their reactions with carbon nucleophiles such as allylsilanes, enol silyl ethers, and enol acetates were examined and the desired products were obtained in good yields. Aromatic compounds and 1,3-dicarbonyl compounds can also be utilized as carbon nucleophiles. The present method was also applied to combinatorial parallel synthesis using a robotic synthesizer.

Direct Oxidative Carbon−Carbon Bond Formation Using the “Cation Pool” Method. 1. Generation of Iminium Cation Pools and Their Reaction with Carbon Nucleophiles

Seiji Suga

Papers

Enantioselective addition of dialkylzincs to aldehydes promoted by chiral amino alcohols. Mechanism and nonlinear effect

Catalytic asymmetric induction. Highly enantioselective addition of dialkylzincs to aldehydes

TRPA1 underlies a sensing mechanism for O2

Enhancement of Chemical Selectivity by Microreactors

Direct Oxidative Carbon−Carbon Bond Formation Using the “Cation Pool” Method. 1. Generation of Iminium Cation Pools and Their Reaction with Carbon Nucleophiles