Visible light-promoted difluoromethylthiolation of cycloalkanols by C-C bond cleavage.

A mild and general methodology for the difluoromethylthiolation of cycloalkanols has been developed by employing N-difluoromethylthiophthalimide as the SCF2H radical source, in combination with an acridinium-derived organo-photosensitizer, under redox-neutral conditions. This reaction protocol demonstrates high efficiency, scalability, and mild reaction conditions, thus presenting a green approach for the rapid synthesis of distal difluoromethylthiolated alkyl ketones that are challenging to be synthesized through alternative means.

The Polarizing Trend of Regional CO2 Emissions in China and Its Implications.

CO2 emissions are unevenly distributed both globally and regionally within nation-states. Given China's entrance into the new stage of economic development, an updated study on the largest CO2 emitter's domestic emission distribution is needed for effective and coordinated global CO2 mitigation planning. We discovered that domestic CO2 emissions in China are increasingly polarized for the 2007-2017 period. Specifically, the domestically exported CO2 emissions from the less developed and more polluting northwest region to the rest of China has drastically increased from 165 Mt in 2007 to 230 Mt in 2017. We attribute the polarizing trend to the simultaneous industrial upgrading of all regions and the persistent disparity in the development and emission decoupling of China's regions. We also noted that CO2 emissions exported from China to the rest of the world has decreased by 41% from 2007 to 2017, with other developing countries filling up the vacancy. As this trend is set to intensify, we intend to send an alarm message to policy makers to devise and initiate actions and avoid the continuation of pollution migration.

Palladium-Catalyzed Regio- and Diastereoselective Olefinic C-H Difluoromethylthiolation at Room Temperature.

Herein, we developed palladium-catalyzed regio- and diastereoselective difluoromethylthiolation of acrylamides to form the Z-isomer product at room temperature. Using 8-aminoquinoline as a directing group, this protocol resulted in a high efficiency under mild reaction conditions and showed good functional group tolerances, which opens a novel synthetic methodology for accessing SCF2H-containing skeletons. Moreover, mechanistic studies were conducted to obtain insights into the reaction mechanism, and post-functionalization of the product reactions was performed.

An Update Mini-Review on the Progress of Azanucleoside Analogues.

The development of structurally novel nucleoside analogues is an active area in medicinal chemistry, since these drugs have proven clinical efficacy for decades. Azanucleosides are nucleoside analogues in which the sugar moieties are composed of nitrogen-containing rings or chains. In recent years, many azanucleosides have demonstrated therapeutic potential. In this short review, we describe recent advancements in azanucleosides, which may translate in a better understanding of the molecular design, biological activity, structure-activity relationship, and their related mechanism of action. The information summarized in this paper should encourage medicinal chemists in their future efforts to create more potent and effective chemotherapeutic agents.

Tracing the Uncertain Chinese Mercury Footprint within the Global Supply Chain Using a Stochastic, Nested Input-Output Model.

A detailed understanding of the mercury footprint at subnational entity levels can facilitate the implementation of the "Minamata Convention on Mercury", especially for China, the largest mercury emitter worldwide. Some provinces of China have more than 100 million people, with economic activities and energy consumption levels comparable to those of smaller G7 countries. We constructed a stochastic, nested multiregion input-output (MRIO) model, which regionalized the China block in the EXIOBASE global-scale MRIO table, to model the mercury footprint associated with global supply chains spanning China's regions and other countries. The results show that Tianjin, Shanghai, and Ningxia had the highest per capita mercury footprint in China, which was comparable to the footprint of Australia and Norway and exceeded the footprint of most other countries. Some developed regions in China (e.g., Guangdong, Jiangsu) had higher mercury final product-based inventories (FBI) and consumption-based inventories (CBI) than production-based inventories (PBI), emphasizing the role of these regions as centers of both consumption and economic control. Uncertainties of Chinese provincial mercury footprint varied from 8% to 34%. Our research also revealed that international and inter-regional final product and intermediate product trades reshape the mercury emissions of Chinese provinces and other countries to a certain extent.

Acceptorless Dehydrogenation of N-Heterocycles by Merging Visible-Light Photoredox Catalysis and Cobalt Catalysis.

Herein, the first acceptorless dehydrogenation of tetrahydroquinolines (THQs), indolines, and other related N-heterocycles, by merging visible-light photoredox catalysis and cobalt catalysis at ambient temperature, is described. The potential applications to organic transformations and hydrogen-storage materials are demonstrated. Primary mechanistic investigations indicate that the catalytic cycle occurs predominantly by an oxidative quenching pathway.

Lipid-conjugated nucleoside monophosphate and monophosphonate prodrugs: A versatile drug delivery paradigm.

Integrating lipid conjugation strategies into the design of nucleoside monophosphate and monophosphonate prodrugs is a well-established approach for discovering potential therapeutics. The unique prodrug design endows nucleoside analogues with strong lipophilicity and structures resembling lysoglycerophospholipids, which improve cellular uptake, oral bioavailability and pharmacological activity. In addition, the metabolic stability, pharmacological activity, pharmacokinetic profiles and biodistribution of lipid prodrugs can be finely optimized by adding biostable caps, incorporating transporter-targeted groups, inserting stimulus-responsive bonds, adjusting chain lengths, and applying proper isosteric replacements. This review summarizes recent advances in the structural features and application fields of lipid-conjugated nucleoside monophosphate and monophosphonate prodrugs. This collection provides deep insights into the increasing repertoire of lipid prodrug development strategies and offers design inspirations for medicinal chemists for the development of novel chemotherapeutic agents.

Base-Mediated α-gem-Difluoroalkenylations of Aldehydes and Ketones.

Herein, we present a base-mediated nucleophilic substitution reaction of α-trifluoromethylstyrenes with simple silyl enol ethers, enabling the efficient synthesis of carbonyl-substituted gem-difluoroalkenes. The merit of this protocol is exhibited by its mild reaction conditions, broad substrate scope, and scalable preparation. Notably, this method demonstrates its applicability for late-stage functionalization of structurally complex molecules. Moreover, we illustrate that the resulting products can serve as valuable precursors for the synthesis of diverse medicinally relevant compounds.

Visible-Light Photoredox-Catalyzed Decarboxylative Alkylation of Heteroarenes Using Carboxylic Acids with Hydrogen Release.

Herein, we have developed visible-light photoredox-catalyzed decarboxylating carboxylic acids for alkylation of heteroarenes under mild conditions. The transformation occurred smoothly without the requirement of stoichiometric oxidants in the presence of 0.3 equiv of base, which benefited from the release of hydrogen (H2) and carbon dioxide (CO2). Various substrates and functional groups were tolerated. Primary mechanistic studies suggest that an oxidative quenching pathway and a reductive quenching pathway are both possible in the catalytic cycle.

Visible-Light Photoredox-Catalyzed Iminyl Radical Formation by N-H Cleavage with Hydrogen Release and Its Application in Synthesis of Isoquinolines.

An unprecedented visible-light photoredox-catalyzed iminyl radical formation by N-H cleavage with H2 release has been developed. Its application in the synthesis of various isoquinolines and related polyaromatics in high atom economy at ambient temperature by applying a photosensitizer, Acr+-Mes ClO4-, and a new cobalt catalyst, Co(dmgH)2(4-CONMe2Py)Cl is reported. Mechanistic investigations indicated that the generated iminyl radical initiates the cascade C-N/C-C bonds formation and the catalytic cycle occurs by a simultaneous oxidative as well as reductive quenching pathway.

Redox-Divergent Hydrogen-Retentive or Hydrogen-Releasing Synthesis of 3,4-Dihydroisoquinolines or Isoquinolines.

A rare Ru-catalyzed highly selective synthesis of 3,4-dihydroisoquinolines or isoquinolines is accomplished via a redox-divergent hydrogen-retentive or hydrogen-releasing fashion. Notably, high cis-selectivity of 3,4-dihydroisoquinolines is achieved. Potential applications are shown by gram-scale reactions and very concise synthesis of N-containing polycyclic aromatic compounds. Primary mechanistic investigations indicate that the sequence of the major pathway involves Ru-catalyzed C-H activation, alkyne insertion, and subsequent 6π-electrocyclization.

Oxidant-free dehydrogenative coupling reactions via hydrogen evolution.

Oxidant-free dehydrogenative coupling reactions: Recently, coupling reactions have followed a novel strategy for the construction of C==C, C==N, C==P, and S==S bonds by dehydrogenation without using any extra oxidant, via H2 evolution. These breakthroughs inspire a new direction in the construction of chemical bonds, towards more sustainable, highly atom-economical, and environmentally benign synthetic methods.

Synthesis of fluorenone derivatives through Pd-catalyzed dehydrogenative cyclization.

Palladium-catalyzed dual C-H functionalization of benzophenones to form fluorenones by oxidative dehydrogenative cyclization is reported. This method provides a concise and effective route toward the synthesis of fluorenone derivatives, which shows outstanding functional group compatibility.

N-Directing group assisted rhodium-catalyzed aryl C-H addition to aryl aldehydes.

Direct aryl C-H addition to aryl aldehydes to produce biaryl methanols was reported via Rh catalysis with an N-containing directing group. The method is highly atom-, step-, and redox-economic. The procedure is robust, reliable, and compatible with water and air.

Straightforward synthesis of phenanthrenes from styrenes and arenes.

Semi-one-pot synthesis of phenanthrenes from styrenes and arenes was developed through cross-dehydrogenative coupling. A sequence of Heck-type coupling and photo-cyclization were involved and a variety of functionalities were tolerated. This method provides an effective and practical protocol towards the synthesis of substituted phenanthrenes.