Highly selective electrochemical hydrogenation of alkynes: Rapid construction of mechanochromic materials

Electrochemical hydrogenation has emerged as an environmentally benign and operationally simple alternative to traditional catalytic reduction of organic compounds. Here, we have disclosed for the first time the electrochemical hydrogenation of alkynes to a library of synthetically important Z-alkenes under mild conditions with great selectivity and efficiency. The deuterium and control experiments of electrochemical hydrogenation suggest that the hydrogen source comes from the solvent, supporting electrolyte, and base. The scanning electron microscopy and x-ray diffraction experiments demonstrate that palladium nanoparticles generated in the electrochemical reaction act as a chemisorbed hydrogen carrier. Moreover, complete reduction of alkynes to saturated alkanes can be achieved through slightly modified conditions. Furthermore, a series of novel mechanofluorochromic materials have been efficiently constructed with this protocol that showed blue-shifted mechanochromism. This discovery represents the first example of cis-olefins-based organic mechanochromic materials

Site-Selective C−H Arylation of Primary Aliphatic Amines Enabled by a Catalytic Transient Directing Group

Transition-metal-catalysed direct C–H bond functionalization of aliphatic amines is of great importance in organic and medicinal chemistry research. Several methods have been developed for the direct sp3 C–H functionalization of secondary and tertiary aliphatic amines, but site-selective functionalization of primary aliphatic amines in remote positions remains a challenge. Here, we report the direct, highly site-selective γ-arylation of primary alkylamines via a palladium-catalysed C–H bond functionalization process on unactivated sp3 carbons. Using glyoxylic acid as an inexpensive, catalytic and transient directing group, a wide array of γ-arylated primary alkylamines were prepared without any protection or deprotection steps. This approach provides straightforward access to important structural motifs in organic and medicinal chemistry without the need for pre-functionalized substrates or stoichiometric directing groups and is demonstrated here in the synthesis of analogues of the immunomodulatory drug fingolimod directly from commercially available 2-amino-2-propylpropane-1,3-diol

Direct Aerobic Carbonylation of C(sp2)-H and C(sp3)-H Bonds through Ni/Cu Synergistic Catalysis with DMF as the CO Source

The direct carbonylation of aromatic sp2 and unactivated sp3 C–H bonds of amides was achieved via nickel/copper catalysis under atmospheric O2 with the assistance of a bidentate directing group. The sp2 C–H functionalization showed high regioselectivity and good functional group compatibility. The sp3 C–H functionalization showed high site-selectivity by favoring the C–H bonds of α-methyl groups over those of the α-methylene, β- or γ-methyl groups. Moreover, this reaction showed a predominant preference for functionalizing the α-methyl over α-phenyl group. Mechanistic studies revealed that nickel/copper synergistic catalysis is involved in this process

Palladium-Catalyzed Site-Selective Fluorination of Unactivated C(sp3)−H Bonds

The transition-metal-catalyzed direct C–H bond fluorination is an attractive synthetic tool toward the preparation of organofluorines. While many methods exist for the direct sp3 C–H functionalization, site-selective fluorination of unactivated sp3 carbons remains a challenge. Direct, highly site-selective and diastereoselective fluorination of aliphatic amides via a palladium-catalyzed bidentate ligand-directed C–H bond functionalization process on unactivated sp3 carbons is reported. With this approach, a wide variety of β-fluorinated amino acid derivatives and aliphatic amides, important motifs in medicinal and agricultural chemistry, were prepared with palladium acetate as the catalyst and Selectfluor as the fluorine source

Palladium-Catalyzed Decarboxylative Alkoxycarbonylation of Potassium Aryltrifluoroborates with Potassium Oxalate Monoesters

Palladium-catalyzed decarboxylative alkoxycarbonylation of potassium aryltrifluoroborates with potassium oxalate monoesters in the presence of potassium persulfate was performed under mild conditions. A number of benzoyl esters with a wide variety of substituents at different positions were efficiently synthesized with this method. Mechanism of the palladium-catalyzed decarboxylative carbonylation of aryltrifluoroborates was studied, and a radical-mediated Pd(II)/Pd(IV) catalytic cycle was proposed

Transient ligand‐enabled transition metal‐catalysed C‐H functionalisation

Transition metal‐catalysed C‐H bond functionalisation is one of the most efficient and powerful strategies in synthetic organic chemistry to derivatize otherwise inert sites of organic molecules for the construction of C‐C and C‐heteroatom bonds. However, additional steps are often required in order to install the directing groups to realize the positional functionalisation of the substrates. These tedious steps run counter to the step‐economical nature of the C‐H activation. In contrast, direct functionalisation of the substrate, utilizing the transient ligands, avoids the unnecessary steps for the prefunctionalisation of the substrates. In this mini review, we will provide a short journey for the major progress made in this field for the C‐H functionalisation on sp2 and sp3 carbon centres with different transient working modes, including the covalent, hydrogen, and ionic bonds

Benzisothiazol‐3‐ones through a Metal‐Free Intramolecular N–S Bond Formation

The highly efficient synthesis of benzoisothiazol‐3‐ones from thiobenzamides has been described with good functional group compatibility and excellent yields. This work represents the first example of selectfluor‐promoted N–S bond formation processes. This method provides a facile approach to access various important bioactive benzoisothiazol‐3‐ones

Cobalt-catalysed site-selective intra- and intermolecular dehydrogenative amination of unactivated sp3 carbons

Cobalt-catalysed sp2 C–H bond functionalization has attracted considerable attention in recent years because of the low cost of cobalt complexes and interesting modes of action in the process. In comparison, much less efforts have been devoted to the sp3 carbons. Here we report the cobalt-catalysed site-selective dehydrogenative cyclization of aliphatic amides via a C–H bond functionalization process on unactivated sp3 carbons with the assistance of a bidentate directing group. This method provides a straightforward synthesis of monocyclic and spiro β- or γ-lactams with good to excellent stereoselectivity and functional group tolerance. In addition, a new procedure has been developed to selectively remove the directing group, which enables the synthesis of free β- or γ-lactam compounds. Furthermore, the first cobalt-catalysed intermolecular dehydrogenative amination of unactivated sp3 carbons is also realized., Functionalizing unactivated carbon–hydrogen bonds is challenging, especially when using non-precious metals and dealing with sp3 hybridized carbons. Here, the authors report an intramolecular cobalt catalysed amination of C–H bonds of sp3 carbons, giving access to β- and γ-lactams

Palladium-catalyzed ligand-promoted site-selective cyanomethylation of unactivated C(sp3)–H bonds with acetonitrile

The direct cyanomethylation of unactivated sp3 C–H bonds of aliphatic amides was achieved via palladium catalysis assisted by a bidentate directing group with good functional group compatibility. This process represents the first example of the direct cross-coupling of sp3 C–H bonds with acetonitrile. Considering the importance of the cyano group in medicinal and synthetic organic chemistry, this reaction will find broad application in chemical research

Co-occurrence of fecal incontinence with constipation or irritable bowel syndrome indicates the need for personalized treatment

Background: This study aimed to compare the prevalence and symptoms of fecal incontinence (FI) in relation to irritable bowel syndrome (IBS-associated FI), constipation (constipation-associated FI), and isolation (isolated FI). Methods: Data were analyzed from 3145 respondents without organic comorbidities known to influence defecation function from the general Chinese population who filled in the online Groningen Defecation and Fecal Continence questionnaire. FI, IBS, and constipation were evaluated with the Rome IV criteria. Key Results: The prevalence of FI was 10.5% (n = 329) in the non-comorbidity group. After multivariable logistic regression analysis, IBS (odds ratio [OR]: 12.55, 95% confidence interval [CI]: 9.06–17.36) and constipation (OR: 4.38, 95% CI: 3.27–5.85) were the most significant factors contributing to FI. Based on this finding, 106/329 (32.2%) had IBS-associated FI, 119/329 (36.2%) had constipation-associated FI, and 104/329 (31.6%) had isolated FI. Among the 329 FI respondents, there was a high prevalence of IBS and constipation-related symptoms, including abdominal pain (81.5%) and abdominal bloating (77.8%) for IBS and straining during defecation (75.4%), incomplete defecation (72.3%), defecation blockage (63.2%), anal pain during defecation (59.3%), and hard stools (24%) for constipation. The patients with IBS-associated FI asked for specialists' help less frequently than those with isolated FI. Interestingly, among the patients with constipation-associated FI, 56.3% used anti-diarrhea medicine. Conclusions and Inferences: The prevalence of IBS-associated FI, constipation-associated FI, and isolated FI is comparably high. It is important to diagnose and target the cause of FI to provide personalized and cause-targeting care instead of treating only the FI symptoms.</p