Herein, a metal-free electrochemical dihydroxylation of unactivated alkenes is described. The transformation proceeds smoothly under mild conditions with a broad range of unactivated alkenes, providing valuable and versatile dihydroxylated products in moderate to good yields without the addition of costly transition metals and stoichiometric amounts of chemical oxidants. Moreover, this method can be applied to a range of natural products and pharmaceutical derivatives, further demonstrating its synthetic utility. Mechanistic studies have revealed that iodohydrin and epoxide intermediate are formed during the reaction process.

Organoboron compounds play an irreplaceable role in synthetic chemistry and the related transformations based on the unique reactivity of C-B bond are potentially the most efficient methods for the synthesis of organic molecules. The synthetic importance of multiboron compounds in C-C bond formation and function transformation reactions is growing and the related borations of activated or nonactivated alkenes have been developed recently. However, introducing directly two boron moieties into the terminal sites of alkenes giving 1,1-diborylalkanes in a catalytic fashion has not been explored yet. Here we describe a synthetic strategy of 1,1-diborylalkanes via a Ni-catalyzed 1,1-diboration of readily available terminal alkenes. This methodology shows high level of chemoselectivity and regioselectivity and can be used to convert a large variety of terminal alkenes, such as vinylarenes, aliphatic alkenes and lower alkenes, to 1,1-diborylalkanes.1,1-diborylalkanes are useful building blocks in synthetic chemistry. Here, the authors present a highly chemo- and regioselective Ni-catalyzed reaction for the synthesis of 1,1-diborylalkanes from a wide variety of readily available terminal alkenes.

The control of regioselectivity in Heck-type reaction of unactivated alkenes represents a longstanding challenge due to several detachable hydrogens in β-H elimination step, which generally afford either one specific regioisomer or a mixture. Herein, a copper-catalyzed intermolecular Heck-type reaction of unactivated alkenes and N-fluoro-sulfonamides with divergent regioselectivities is reported. The complete switch of regioselectivity mainly depends on the choice of different additives. Employment of alcohol solvent gives access to vinyl products, while the addition of carboxylate leads to the formation of allylic products. In addition, exclusion of these two promoting factors results in β-lactams via a C-N reductive elimination. This protocol shows a broad substrate scope for both alkenes and structurally diverse N-fluoro-sulfonamides, producing the corresponding products with excellent regio- and stereoselectivities. Further control experiments and DFT calculations provide in-depth insights into the reaction mechanism, highlighting the distinct effect of the additives on a bidentate auxiliary-stabilized Cu(III) intermediate.

Hydrofunctionalization, the direct addition of an X-H (e.g., X=O, N) bond across an alkene, is a desirable strategy to make heterocycles that are important structural components of naturally occurring molecules. Described here is the design and discovery of "donor-acceptor"-type platinum catalysts that are highly effective in both hydroalkoxylation and hydroamination of unactivated alkenes over a broad range of substrates under mild conditions. A number of alkene substitution patterns are accommodated, including tri-substituted, 1,1-disubstituted, (E)-disubstituted, (Z)-disubstituted and even mono-substituted double bonds. Detailed mechanistic investigations suggest a plausible pathway that includes an unexpected dissociation/re-association of the electron-deficient ligand to form an alkene-bound "donor-acceptor"-type intermediate. These mechanistic studies help understand the origins of the high reactivity exhibited by the catalytic system, and provide a foundation for the rational design of chiral catalysts towards asymmetric hydrofunctionalization reactions.

Development of single-atomic-site catalysts with high metal loading is highly desirable but proved to be very challenging. Although utilizing defects on supports to stabilize independent metal atoms has become a powerful method to fabricate single-atomic-site catalysts, little attention has been devoted to cation vacancy defects. Here we report a nickel hydroxide nanoboard with abundant Ni2+ vacancy defects serving as the practical support to achieve a single-atomic-site Pt catalyst (Pt1/Ni(OH)x) containing Pt up to 2.3 wt% just by a simple wet impregnation method. The Ni2+ vacancies are found to have strong stabilizing effect of single-atomic Pt species, which is determined by X-ray absorption spectrometry analyses and density functional theory calculations. This Pt1/Ni(OH)x catalyst shows a high catalytic efficiency in diboration of a variety of alkynes and alkenes, yielding an overall turnover frequency value upon reaction completion for phenylacetylene of ~3000 h-1, which is much higher than other reported heterogeneous catalysts.

Monensin A is a prototypical natural polyether polyketide antibiotic. It acts by binding a metal cation and facilitating its transport across the cell membrane. Biosynthesis of monensin A involves construction of a polyene polyketide backbone, subsequent epoxidation of the alkenes, and, lastly, formation of cyclic ethers via epoxide-opening cyclization. MonCI, a flavin-dependent monooxygenase, is thought to transform all three alkenes in the intermediate polyketide premonensin A into epoxides. Our crystallographic study has revealed that MonCI's exquisite stereocontrol is due to the preorganization of the active site residues which allows only one specific face of the alkene to approach the reactive C(4a)-hydroperoxyflavin moiety. Furthermore, MonCI has an unusually large substrate-binding cavity that can accommodate premonensin A in an extended or folded conformation which allows any of the three alkenes to be placed next to C(4a)-hydroperoxyflavin. MonCI, with its ability to perform multiple epoxidations on the same substrate in a stereospecific manner, demonstrates the extraordinary versatility of the flavin-dependent monooxygenase family of enzymes.

Peptides and peptidomimetics are emerging as an important class of clinic therapeutics. Here we report a peptide-guided method for the functionalization and macrocyclization of bioactive peptidosulfonamides by Pd(II)-catalyzed late-stage C-H activation. In this protocol, peptides act as internal directing groups and enable site-selective olefination of benzylsulfonamides and cyclization of benzosulfonamides to yield benzosultam-peptidomimetics. Our results provide an unusual example of benzosulfonamide cyclization with olefins through a sequential C-H activation, which involves the generation of a reactive palladium-peptide complex. Furthermore, this protocol allows facile self-guided macrocyclization of sulfonamide-containing peptides by intramolecular olefination with acrylates and unactivated alkenes, affording bioactive peptidosulfonamide macrocycles of various sizes. Together, our results highlight the utility of peptides as internal directing groups in facilitating transition metal-catalyzed functionalization of peptidomimetics.

Biomimetic modularization and function-oriented synthesis of structurally diversified natural product-like macrocycles in a step-economical fashion is highly desirable. Inspired by marine furanocembranoids, herein, we synthesize diverse alkenes substituted furan-embedded macrolactams via a modular biomimetic assembly strategy. The success of this assembly is the development of crucial Pd-catalyzed carbene coupling between ene-yne-ketones as donor/donor carbene precursors and unactivated Csp3‒H bonds which represents a great challenge in organic synthesis. Notably, this method not only obviates the use of unstable, explosive, and toxic diazo compounds, but also can be amenable to allenyl ketones carbene precursors. DFT calculations demonstrate that a formal 1,4-Pd shift could be involved in the mechanism. Moreover, the collected furanocembranoids-like macrolactams show significant anti-inflammatory activities against TNF-α, IL-6, and IL-1β and the cytotoxicity is comparable to Dexamethasone.

Halocyclization of alkenes is a powerful bond-forming tool in synthetic organic chemistry and a key step in natural product biosynthesis, but catalyzing halocyclization with high enantioselectivity remains a challenging task. Identifying suitable enzymes that catalyze enantioselective halocyclization of simple olefins would therefore have significant synthetic value. Flavin-dependent halogenases (FDHs) catalyze halogenation of arene and enol(ate) substrates. Herein, we reveal that FDHs engineered to catalyze site-selective aromatic halogenation also catalyze non-native bromolactonization of olefins with high enantioselectivity and near-native catalytic proficiency. Highly selective halocyclization is achieved by characterizing and mitigating the release of HOBr from the FDH active site using a combination of reaction optimization and protein engineering. The structural origins of improvements imparted by mutations responsible for the emergence of halocyclase activity are discussed. This expansion of FDH catalytic activity presages the development of a wide range of biocatalytic halogenation reactions.

Preparation of single atom catalysts (SACs) is of broad interest to materials scientists and chemists but remains a formidable challenge. Herein, we develop an efficient approach to synthesize SACs via a precursor-dilution strategy, in which metalloporphyrin (MTPP) with target metals are co-polymerized with diluents (tetraphenylporphyrin, TPP), followed by pyrolysis to N-doped porous carbon supported SACs (M1/N-C). Twenty-four different SACs, including noble metals and non-noble metals, are successfully prepared. In addition, the synthesis of a series of catalysts with different surface atom densities, bi-metallic sites, and metal aggregation states are achieved. This approach shows remarkable adjustability and generality, providing sufficient freedom to design catalysts at atomic-scale and explore the unique catalytic properties of SACs. As an example, we show that the prepared Pt1/N-C exhibits superior chemoselectivity and regioselectivity in hydrogenation. It only converts terminal alkynes to alkenes while keeping other reducible functional groups such as alkenyl, nitro group, and even internal alkyne intact.

Using a magnetron sputtering approach that allows size-controlled formation of nanoclusters, we have created palladium nanoclusters that combine the features of both heterogeneous and homogeneous catalysts. Here we report the atomic structures and electronic environments of a series of metal nanoclusters in ionic liquids at different stages of formation, leading to the discovery of Pd nanoclusters with a core of ca. 2 nm surrounded by a diffuse dynamic shell of atoms in [C4C1Im][NTf2]. Comparison of the catalytic activity of Pd nanoclusters in alkene cyclopropanation reveals that the atomically dynamic surface is critically important, increasing the activity by a factor of ca. 2 when compared to compact nanoclusters of similar size. Catalyst poisoning tests using mercury and dibenzo[a,e]cyclooctene show that dynamic Pd nanoclusters maintain their catalytic activity, which demonstrate their combined features of homogeneous and heterogeneous catalysts within the same material. Additionally, kinetic studies of cyclopropanation of alkenes mediated by the dynamic Pd nanoclusters reveal an observed catalyst order of 1, underpinning the pseudo-homogeneous character of the dynamic Pd nanoclusters.

Deoxygenation of aldehydes and their tautomers to alkenes and alkanes has implications in refining biomass-derived fuels for use as transportation fuel. Electrochemical deoxygenation in ambient, aqueous solution is also a potential green synthesis strategy for terminal olefins. In this manuscript, direct electrochemical conversion of vinyl alcohol and acetaldehyde on polycrystalline Cu to ethanol, ethylene and ethane; and propenol and propionaldehyde to propanol, propene and propane is reported. Sensitive detection was achieved using a rotating disk electrode coupled with gas chromatography-mass spectrometry. In-situ attenuated total reflection surface-enhanced infrared absorption spectroscopy, and in-situ Raman spectroscopy confirmed the adsorption of the vinyl alcohol. Calculations using canonical and grand-canonical density functional theory and experimental findings suggest that the rate-determining step for ethylene and ethane formation is an electron transfer step to the adsorbed vinyl alcohol. Finally, we extend our conclusions to the enol reaction from higher-order soluble aldehyde and ketone. The products observed from the reduction reaction also sheds insights into plausible reaction pathways of CO2 to C2 and C3 products.