Reusable Manganese Catalyst for Site-Selective Pyridine C-H Arylations and Alkylations.

Herein, we disclose a recyclable, hybrid manganese catalyst for site-selective azine C-H activation by weak amide assistance. The novel, reusable catalyst enabled C3-H arylation and C3-H alkylation with ample scope, and was characterized by detailed transmission electron microscopy analysis.

Insights into Ruthenium(II/IV)-Catalyzed Distal C-H Oxygenation by Weak Coordination.

C-H hydroxylation of aryl acetamides and alkyl phenylacetyl esters was accomplished via challenging distal weak O-coordination by versatile ruthenium(II/IV) catalysis. The ruthenium(II)-catalyzed C-H oxygenation of aryl acetamides proceeded through C-H activation, ruthenium(II/IV) oxidation and reductive elimination, thus providing step-economical access to valuable phenols. The p-cymene-ruthenium(II/IV) manifold was established by detailed experimental and DFT-computational studies.

Electrochemical Access to Aza-Polycyclic Aromatic Hydrocarbons: Rhoda-Electrocatalyzed Domino Alkyne Annulations.

Nitrogen-doped polycyclic aromatic hydrocarbons (aza-PAHs) have found broad applications in material sciences. Herein, a modular electrochemical synthesis of aza-PAHs was developed via a rhodium-catalyzed cascade C-H activation and alkyne annulation. A multifunctional O-methylamidoxime enabled the high chemo- and regioselectivity. The isolation of two key rhodacyclic intermediates made it possible to delineate the exact order of three C-H activation steps. In addition, the metalla-electrocatalyzed multiple C-H transformation is characterized by unique functional group tolerance, including highly reactive iodo and azido groups.

Thiocarbonyl-enabled ferrocene C-H nitrogenation by cobalt(III) catalysis: thermal and mechanochemical.

Versatile C-H amidations of synthetically useful ferrocenes were accomplished by weakly-coordinating thiocarbonyl-assisted cobalt catalysis. Thus, carboxylates enabled ferrocene C-H nitrogenations with dioxazolones, featuring ample substrate scope and robust functional group tolerance. Mechanistic studies provided strong support for a facile organometallic C-H activation manifold.

MnCl2 -Catalyzed C-H Alkylations with Alkyl Halides.

C-H alkylations with challenging ß-hydrogen-containing alkyl halides were accomplished with sustainable MnCl2 as the catalyst under phosphine-ligand-free conditions. The proximity-induced benzamide C-H activation occurred with ample substrate scope through rate-determining C-H metalation, also setting the stage for manganese-catalyzed oxidative C-H methylations.

Stereospecific Construction of Contiguous Quaternary All-Carbon Centers by Oxidative Ring Contraction.

Oxidative ring contraction of cyclic α-formyl ketones was facilitated by the action of H2 O2 under operationally simple and environmentally benign reaction conditions. The process was highly regioselective and enables stereospecific construction of contiguous quaternary all-carbon centers from stereodefined all-substituted all-cyclic ketones. The asymmetric syntheses of (+)-cuparene and (+)-tochuinyl acetate were also successively achieved by taking advantage of this novel protocol.

Synthesis of naked amino-pyrroloindoline via direct aminocyclization of tryptamine.

The first direct access to unprotected amino-pyrroloindoline via aminocyclization of tryptamine and tryptophan has been described. A variety of structurally diverse amino-pyrroloindolines are furnished by the use of O-(2,4-dinitrophenyl)hydroxylamine (DPH) as the nitrogen source in the presence of catalytic Rh2(esp)2.

Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery.

Lipid nanoparticles (LNPs) are the commonly used delivery tools for messenger RNA (mRNA) therapy and play an indispensable role in the success of COVID-19 mRNA vaccines. Ionizable cationic lipids are the most important component in LNPs. Herein, we developed a series of new ionizable lipids featuring bioreducible disulfide bonds, and constructed a library of lipids derived from dimercaprol. LNPs prepared from these ionizable lipids could be stored at 4 °C for a long term and are non-toxic toward HepG2 and 293T cells. In vivo experiments demonstrated that the best C4S18A formulations, which embody linoleoyl tails, show strong firefly luciferase (Fluc) mRNA expression in the liver and spleen via intravenous (IV) injection, or at the local injection site via intramuscular injection (IM). The newly designed ionizable lipids can be potentially safe and high-efficiency nanomaterials for mRNA therapy.

Development of an LNP-Encapsulated mRNA-RBD Vaccine against SARS-CoV-2 and Its Variants.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is undoubtedly the most challenging pandemic in the current century and remains a global health emergency. As the number of COVID-19 cases in the world is on the rise and variants continue to emerge, there is an urgent need for vaccines. Among all immunization approaches, mRNA vaccines have demonstrated more promising results in response to this challenge. Herein, we designed an mRNA-based vaccine encoding the receptor-binding domain (RBD) of SARS-CoV-2 encapsulated in lipid nanoparticles (LNPs). Intramuscular (i.m.) administration of the mRNA-RBD vaccine elicited broad-spectrum neutralizing antibodies and cellular responses against not only the wild-type SARS-CoV-2 virus but also Delta and Omicron variants. These results indicated that two doses of mRNA-RBD immunization conferred a strong immune response in mice against the wild-type SARS-CoV-2, while the booster dose provided a sufficient immunity against SARS-CoV-2 and its variants. Taken together, the three-dose regimen strategy of the mRNA-RBD vaccine proposed in the present study appears to be a promising reference for the development of mRNA vaccines targeting SARS-CoV-2 variants.

Rhodaelectro-catalyzed chemo-divergent C-H activations with alkylidenecyclopropanes for selective cyclopropylations.

Herein, we report on selectivity control in C-H activations with alkylidenecyclopropanes (ACPs) for the chemo-selective assembly of cyclopropanes or dienes. Thus, unprecedented rhodaelectro-catalyzed C-H activations were realized with diversely decorated ACPs with a wide substrate scope and electricity as the sole oxidant.

MnCl2-Catalyzed C-H Alkylation on Azine Heterocycles.

Low-valent manganese-catalyzed C-H alkylation of pyridine derivatives with both primary and challenging secondary alkyl halides was established by amide assistance. The strategy provided expedient access to alkylated pyridines with wide functional group tolerance and ample scope through weak chelation. Mechanistic studies provided strong support for a rate-determining C-H activation and a SET-type C-X scission.

Tri-Substituted Triazole-Enabled C-H Activation of Benzyl and Aryl Amines by Iron Catalysis.

The design of trisubstituted triazoles set the stage for proximity-induced iron-catalyzed C-H activation of benzyl and aryl amines with ample scope. Thereby, C-H alkylations and C-H arylations proved viable with high levels of chemo and positional selectivities by means of racemization-free iron catalysis with the reusable triazole being removed in a traceless fashion.

Enantioselective Bromo-oxycyclization of Silanol.

Relying on the nucleophilicity of silanol for building up silicon-incorporated scaffold with an enantiopure tetrasubstituted carbon center remains elusive. In this report, asymmetric bromo-oxycyclization of olefinic silanol by using chiral anionic phase-transfer catalyst is described. This protocol provided a facile entry to a wide arrangement of enantiopure benzoxasilole in moderate to excellent enantioselectivities depending on the unique reactivity of bromine/N-benzyl-DABCO complex.

Chiral ion-pair organocatalyst promotes highly enantioselective 3-exo iodo-cycloetherification of allyl alcohols.

By designing a novel chiral ion-pair organocatalyst composed of chiral phosphate and DABCO-derived quaternary ammonium, highly enantioselective 3-exo iodo-cycloetherification of allyl alcohols was achieved using NIS as a halogen source. Based on this reaction, one-pot asymmetric 3-exo iodo-cycloetherification/Wagner-Meerwein rearrangement of allyl alcohols en route to enantioenriched 2-iodomethyl-2-aryl cycloalkanones was subsequently developed. Due to the participation of adjacent iodine, the Wagner-Meerwein rearrangement of 2-iodomethyl-2-aryl epoxide proceeds with unusual retention of stereoconfiguration.