Olefin metathesis catalysts provide access to molecules that are indispensable to physicians and researchers in the life sciences. A persisting problem, however, is the dearth of chemical transformations that directly generate acyclic Z allylic alcohols, including products that contain a hindered neighbouring substituent or reactive functional units such as a phenol, an aldehyde, or a carboxylic acid. Here we present an electronically modified ruthenium-disulfide catalyst that is effective in generating such high-value compounds by cross-metathesis. The ruthenium complex is prepared from a commercially available precursor and an easily generated air-stable zinc catechothiolate. Transformations typically proceed with 5.0 mole per cent of the complex and an inexpensive reaction partner in 4-8 hours under ambient conditions; products are obtained in up to 80 per cent yield and 98:2 Z:E diastereoselectivity. The use of this catalyst is demonstrated in the synthesis of the naturally occurring anti-tumour agent neopeltolide and in a single-step stereoselective gram-scale conversion of a renewable feedstock (oleic acid) to an anti-fungal agent. In this conversion, the new catalyst promotes cross-metathesis more efficiently than the commonly used dichloro-ruthenium complexes, indicating that its utility may extend beyond Z-selective processes.

Olefin metathesis has made a significant impact on modern organic chemistry, but important shortcomings remain: for example, the lack of efficient processes that can be used to generate acyclic alkenyl halides. Halo-substituted ruthenium carbene complexes decompose rapidly or deliver low activity and/or minimal stereoselectivity, and our understanding of the corresponding high-oxidation-state systems is very limited. In this manuscript, we show that previously unknown halo-substituted molybdenum alkylidene species are exceptionally reactive and are able to participate in high-yielding olefin metathesis reactions that afford acyclic 1,2-disubstituted Z-alkenyl halides. Transformations are promoted by small amounts of an in situ-generated catalyst with unpurified, commercially available and easy-to-handle liquid 1,2-dihaloethene reagents and proceed to high conversion at ambient temperature within four hours. Many alkenyl chlorides, bromides and fluorides can be obtained in up to 91 percent yield and complete Z selectivity. This method can be used to easily synthesize biologically active compounds and to perform the site- and stereoselective fluorination of other organic compounds.

Development of catalyst-controlled stereoselective olefin metathesis processes1 has been a pivotal recent advance in chemistry. Incorporation of appropriate ligands within molybdenum-2, tungsten3 and ruthenium-based complexes4 has made reactivity and selectivity levels that were formerly inaccessible feasible. Here, we show that molybdenum monoaryloxide chloride (MAC) complexes furnish higher energy (Z) isomers of trifluoromethyl-substituted alkenes through cross-metathesis (CM) reactions with commercially available, inexpensive and typically inert Z-1,1,1,4,4,4-hexafluoro-2-butene. Furthermore, otherwise inefficient and non-stereoselective transformations with Z-1,2-dichloro- and 1,2- dibromoethene can be effected with substantially improved efficiency and Z selectivity. Synthesis of representative biologically active molecules and trifluoromethyl analogues of medicinally relevant compounds underscore the importance of the advance. The origins of activity and selectivity levels, which contradict the previously proposed principles5, are elucidated with the aid of DFT calculations.

has seen limited progress owing to their instability in solution and insufficient activation of reactants by single metal sites under ambient conditions. [4,5] Consequently, applications of SACs in organic synthesis were limited to certain hydrogenations, [6,7] oxidations, [8,9] and CC bond formations. [10] Very recently, we have reported the first SAC-catalyzed preparation of pharmaceuticals (Lonidamine etc., and their 15 N-labeled analogues) by selective hydrogenation to E-hydrazones and subsequent cyclization using Pt 1 /CeO 2 catalyst. [11] We have also developed the latestage functionalization of pharmaceuticals (Tamiflu) by chemoselective oxidation of sulfides using Co 1 -in-MoS 2 catalyst. [12] Despite excellent functional group tolerance and synthetic utility in both cases, the scope is limited by the use of complex starting materials (i.e., carboxylic esters mediated α-diazoesters synthesis and multifunctionalized sulfides), and the inaccessibility to synthesize multi-ring system as the reactions mainly involve simple hydrogenation/oxidation. [11,12] Quinolines, a major class of heterocycles, are widely occurring in natural and synthetic products with diverse pharmacological and physical properties. [13,14] Among the many methods to synthesize quinolines, the classical Friedländer condensation of an aromatic 2-amino-substituted carbonyl compound with another substituted carbonyl derivative is one of the simplest The production of high-value chemicals by single-atom catalysis is an attractive proposition for industry owing to its remarkable selectivity. Successful demonstrations to date are mostly based on gas-phase reactions, and reports on liquid-phase catalysis are relatively sparse owing to the insufficient activation of reactants by single-atom catalysts (SACs), as well as, their instability in solution. Here, mechanically strong, hierarchically porous carbon plates are developed for the immobilization of SACs to enhance catalytic activity and stability. The carbon-based SACs exhibit excellent activity and selectivity (≈68%) for the synthesis of substituted quinolines by a three-component oxidative cyclization, affording a wide assortment of quinolines (23 examples) from anilines and acetophenones feedstock in an efficient, atom-economical manner. Particularly, a Cavosonstat derivative can be synthesized through a one-step, Fe 1 -catalyzed cyclization instead of traditional Suzuki coupling. The strategy is also applicable to the deuteration of quinolines at the fourth position, which is challenging by conventional methods. The synthetic utility of the carbon-based SAC, together with its reusability and scalability, renders it promising for industrial scale catalysis.

The identification of chemoselective oxidation process en route to fine chemicals and specialty chemicals is a long‐standing pursuit in chemical synthesis. A vertically structured, cobalt single atom‐intercalated molybdenum disulfide catalyst (Co1‐in‐MoS2) is developed for the chemoselective transformation of sulfides to sulfone derivatives. The single‐atom encapsulation alters the electron structure of catalyst owing to confinement effect and strong metal–substrate interaction, thus enhancing adsorption of sulfides and chemoselective oxidation at the edge sites of MoS2 to achieve excellent yields of up to 99% for 34 examples. The synthetic scopes can be extended to sulfide‐bearing alkenes, alkynes, aldehydes, ketones, boronic esters, and amines derivatives as a toolbox for the synthesis of high‐value, multifunctional sulfones and late‐stage functionalization of pharmaceuticals, e.g., Tamiflu. The synthetic utility of cobalt single atom‐intercalated MoS2, together with its reusability, scalability, and simplified purification process, renders it promising for industrial productions.