By employing electrophilic TsSCF as an efficient SCF source, we reported Cu/ (chiral sulfoxide-phosphine ligand)-catalyzed enantioselective nucleophilic substitutions. Under this protocol, α-pyridyl-α-fluoro esters as latent carbon nucleophiles, compounds containing a C-SCF stereocenter along with azacycles and fluorine atoms, were obtained in good yields and enantioselectivities under mild conditions (up to 68% yield, 92% ee).

A convenient and practical method has been developed for synthesizing various -aryl pyrazoles from vinyl sulfoxonium ylides and diazonium salts. When using 1,3-disubstituted vinyl sulfoxonium ylides, the reaction selectively yields 1,3,5-trisubstituted pyrazoles. On the other hand, employing 2,3-disubstituted vinyl sulfoxonium ylides results in the formation of 1,3,4-trisubstituted pyrazoles. The reaction proceeds through the novel aryl diazene-derived vinyl sulfoxonium ylide. Furthermore, this method efficiently produces pyrazoles from aniline derivatives in a one-pot transformation. The reaction takes place under transition metal-free, mild conditions using easily accessible starting materials, making it a practical approach for generating pyrazoles in pharmaceutical chemistry.

The concise and efficient total synthesis of (±)-tetraponerine-2 () and (±)-tetraponerine-4 () was achieved in 9% and 14% overall yield, respectively. The key step included the diastereoselective gold(I)-catalyzed intramolecular dehydrative amination of an allylic alcohol-tethered sulfamide to produce the 1,3-diamine moiety. The resulting olefinic side chain was then elaborated by cross-metathesis and cyclized to a five-membered pyrrolidine or a six-membered piperidine ring by intramolecular Mitsunobu -alkylation. The unique tricyclic core of the (±)-tetraponerines was completed through cyclic sulfamide cleavage followed by aminal formation using 4-bromobutanal. This flexible synthetic strategy allows for the variation of the ring size, C-5 alkyl side chain length, and stereochemistry, which enables the preparation of diverse tetraponerine analogs for biological study.

Chiral diphosphines with a biphenyl bridge and the chirality borne by the phosphorus atoms and not due to the atropoisomery of the biaryl backbone have been scarcely studied. Herein, we report the asymmetric synthesis of the (,)-2,2'-bis(ferrocenylphenylphosphino)biphenyl (BipheP*) ligand and its application in Rh-catalyzed hydrogenation. The synthesis was based on the enantioselective preparation of P-chirogenic ferrocenyl(-bromophenyl)phenylphosphine by the reaction of -phosphine-borane with 1,2-dibromobenzene and its homocoupling into BipheP*. Hydrogenations catalyzed by the Rh/BipheP* complex led to enantioselectivities of ≤96%.

An efficient method for the synthesis of heterodiarylmethanes through the coupling of imidazo[1,2-]pyridines and heteroarenes using indoles employing rongalite as a methylenating reagent has been developed. This regioselective C-H functionalization provides a wide range of heterodiarylmethanes of imidazo[1,2-]pyridines and imidazo[2,1-]thiazole. Here, rongalite plays a crucial role in generating a C1 unit in situ, which triggers the heterodiarylmethylation process. The use of inexpensive rongalite (ca. $0.03/1 g), mild reaction conditions, and gram-scale synthesis are some of the key features of this methodology.

Electrooxidative transformations frequently rely on proton reduction as the terminal electron sink. However, this cathodic counterreaction can be slow in organic solvents and can operate at reducing potentials that are incompatible with catalysts and reagents needed for oxidative reactions. We report aminoborate adducts as redox mediators for proton reduction that operate at mild reducing potentials. This reliable cathodic couple ultimately enables successful oxidative organic transformations, including chlorodeborylation, developed herein, and Cu-catalyzed Chan-Lam coupling, reported previously by our group. Pyridinium borate adducts formed during electrooxidative chlorination of aryl trifluoroborates serve as easily reduced complexes (-1.1 V vs Fc/Fc) to catalyze proton reduction. Reactions that promote the formation of borate adducts result in high yields, operate at low cell potentials, suppress aryl trifluoroborate decomposition, and mitigate electrode passivation. These studies illustrate the utility of Lewis acid-base complexes in cathodic counterreactions and underscore the importance of developing both anodic and cathodic reactions in electrosynthesis.

Visible light-promoted α-aminoalkyl radical-triggered α-aminoalkylation and α-diaminoalkylation of Morita-Baylis-Hillman acetates with -methyl arylamines to synthesize -containing alkyl acrylates and γ,γ-diaminobutyl esters was reported. Photoinduced α-aminoalkylation is carried out with Na-eosin Y as an organophotocatalyst at room temperature under metal- and oxidant-free conditions. In particular, the α-diaminoalkylation is performed via α-aminoalkyl radical addition/elimination followed by a catalyst-controlled selective α-aminoalkyl radical addition strategy in one step under the [Ir(dtbbpy)(bpy))]PF/KF catalytic system. The reaction is highly atom- and step-economic, with high selectivity, furnishing -containing alkyl acrylates and butyl esters in moderate to good yields with wide substrate scope.

An innovative solution that overcomes the long-standing inherently low efficiency in -heterocyclic carbene-catalyzed aerobic oxidation of aldehydes is reported. This solution included the design and synthesis of a novel polymerized catalyst and the utilization of a flow reactor. The unprecedentedly high efficiency achieved via this protocol makes it synthetically applicable. A total turnover number (TON) of 26,300 was achieved based on recycling experiments (runs). The highest TON in a single run could be up to 2475 with a turnover frequency (TOF) of 208 h, far superior to its traditional counterpart, in which a typical TON ranges from 20 to 100 with a TOF of less than 10 h. The catalyst has been recycled over 50 times and is still fully active. The success was attributed to the discovery of hidden reactivity, which was observed for the first time as an autoacceleration in the reaction rate during kinetic investigations. The research also provided concrete evidence supporting the conclusion that radical intermediates played crucial roles in the catalytic cycle by having a determinative impact on the overall reaction rate.

A practical nickel-catalyzed decarboxylative cross-coupling of -hydroxyphthalimide esters with 1,4-diiodobenzene analogues has been developed. Under mild reaction conditions, a series of structurally interesting 1,4-dialkylbenzene analogues have been accessed with good functional group tolerance, which are versatile precursors for organic synthesis and a kind of important unit for bioactive molecules, polymers, and other materials. The synthetic application of this methodology was demonstrated by the synthesis of 3-6-dialkylcarbazole derivatives.

We report herein that three facile rearrangements of epoxy ketones can be employed for the efficient and practical synthesis of cephalotaxine, the parent member of the family of alkaloids. The Meinwald rearrangement of epoxy ketone (90%) was used for the preparation of the dense functional groups in the cyclopentane ring of cephalotaxine. A novel acid-catalyzed umpolung S2' rearrangement and the Wharton transposition reaction of epoxy ketones were also developed to synthesize the Mori intermediate via the key azaspiro allylic alcohols in a stereodivergent manner.

The site-selective functionalization of aromatic compounds via C-H activation has emerged as a popular tool in organic synthesis. In this study, we report a regioselective coupling of maleimide to 2-arylbenzo[]thiazoles in the presence of a rhodium(III) catalyst. Depending upon the nature of the substituent (-group) present in the maleimide substrate, either mono- or bis-1,4-addition products were observed in this methodology. In the case of = aryl, cyclohexyl, and -butyl, mono coupling was observed, whereas substituents, such as methyl, ethyl, benzyl, and methyl thiophene, provided bis coupling as the major products. Similar selectivity was also observed in the case of 2-arylbenzo[]oxazoles.

In this report, a new imidazole- and amide-functionalized pincer-like Cu(II) complex () was synthesized and characterized. By employing and 9-azabicyclo[3.3.1]nonane -Oxyl (ABNOH), a catalytic protocol for alcohol oxidation and the subsequent alcohol oxidation-triggered synthesis of quinolines and pyrazines were explored. Alcohols such as 2-aminoaryl alcohols were also oxidized efficiently. As carbonyls from 2-arylaminobenzyl alcohols and secondary alcohols are synthons for quinolines, we explored their synthesis directly from alcohols. The protocol was quite efficient and completed the reaction in only ∼5-10 h. Combinations such as (a) primary 2-arylaminobenzyl alcohols with secondary alcohols or their ketones and (b) secondary 2-arylaminobenzyl alcohols with secondary alcohols or their ketones were found to be very effective for the synthesis of quinolines. The protocol was also successful for the synthesis of various pyrazines from 1,2-diols and 1,2-diaminobenzenes in 10 h. Mechanistic investigations showed that the generated complex acted as an active catalyst: it activated O and subsequently with the cooperation of 9-azabicyclo[3.3.1]nonane -Oxyl (ABNO) activated the α-CH hydrogen of coordinated alkoxide. Then, Cu(II)/Cu(I) reduction led to the formation of carbonyl compounds, which via successive C-C/C-N coupling reactions resulted in heterocycles in the presence of KOBu and .

The newly discovered cyclo[13]carbon, the first artificially synthesized odd-numbered carbon ring, is an intriguing carbon isomer that provides a valuable subject for studying low-symmetry carbon materials. In this work, we employed first-principles calculations to explore the geometric structure and electronic properties of cyclo[13]carbon through various techniques such as vibrational mode analysis, bond order analysis, spin density analysis, electron localization analysis, electrostatic potential and van der Waals potential analysis, visualization of weak interactions, and energy decomposition analysis. We investigated the interaction characteristics of cyclo[13]carbon with small molecules and examined its dimer formation mechanism and dynamics features using ab initio molecular dynamics. Our study reveals the unique physicochemical properties of this novel carbon ring system. The antiaromaticity of the low-symmetry cyclo[13]carbon sets it apart from previously synthesized even-numbered carbon rings, with van der Waals interactions playing a crucial role in its binding with small molecules and in the formation of C dimers. This research provides theoretical insights that complement experimental observations and theoretical studies, aiding further investigation into the diverse properties of fresh carbon material isomers and promoting the synthesis and application of novel molecular materials in molecular electronics and nanotechnology.

This study presents a method for synthesizing functionalized hydrodibenzofuran derivatives. Using palladium catalysis, -aryl cyclic vinylogous esters undergo dehydrogenative intramolecular arylation at the vinylic carbon. Preliminary kinetic isotope effect studies suggest that the C(aryl)-H bond cleavage may be the rate-determining step.

This study focuses on investigating the use of β-cyclodextrin (β-CyD) derivatives as additives in continuous flow peptide synthesis, with particular emphasis on challenging sequences such as the Jung-Redemann decapeptide and the 42-residue amyloid β polypeptide [Aβ(1-42)]. The efficacy of the OH-free β-CyD and two of its derivatives (Ac-β-CyD and HP-β-CyD) is compared with alternative, state-of-the-art synthetic methods, including the widely used and recently improved pseudoproline monomer technique, e.g., Ser(ΨPro). Our results show that the use of β-CyD as an additive results in a significant (8-19%) increase in the purity of the crude polypeptide compared to that determined by our reference method. The chromatograms determined by LC-MS were deconvoluted to estimate the more precise purity of the crude products, and we found that the improvement is greater when the free OH β-CyD is used and moderate when the acetyl-β-CyD or the 2-hydroxypropyl-β-CyD derivatives are used. We have found that the free CyD gives an improvement comparable to that achieved with the Ser(ΨPro) derivative.

An electrochemical tandem cyclization of enaminones with amidines has been reported for the first time using dibromomethane as an initiating agent in an undivided cell. Following this protocol, a vast variety of polysubstituted 5-acylimidazoles were obtained in moderate to good yields without the use of external oxidants. Mechanistic studies indicate that the bromide anion, electroreductively generated from dibromomethane, acts as a redox mediator to complete the catalytic cycle.

Protein-protein interactions (PPIs) are pivotal in regulating cellular functions and life processes, making them promising therapeutic targets in modern medicine. Despite their potential, developing PPI inhibitors poses significant challenges due to their large and shallow interfaces that complicate ligand binding. This study focuses on mimicking peptide loops as a strategy for PPI inhibition, utilizing synthetic peptide loops for replicating critical binding regions. This work explores turn-inducing elements and highlights the importance of proline in promoting favorable conformations for lactamization, yielding high-purity cyclic peptides. Notably, our one-pot method offers enhanced versatility and represents a robust strategy for efficient and selective macrolactamization, expanding the scope of peptide synthesis methodologies. This approach, validated through the synthesis of AAV capsid-derived loops, offers a robust platform for developing peptide-based therapeutics and highlights the potential of peptide macrocycles in overcoming PPI drug discovery challenges and advancing the development of new therapeutics.

The reversible modulation of acidity using molecular photoswitches enables the remote control of a variety of (bio)chemical processes with light. Herein we investigated the structural features that allow amplifying photoinduced p variation in phenol-diarylethene conjugates, which toggle between low- and high-acidity states by switching the conjugation between the ionizable moiety and electron-withdrawing groups upon photoisomerization. By tuning the structure of these conjugates, high p modulation amplitudes were accomplished that surpass those previously reported.

A catalyst-free photoinduced deconstructive fluorosulfonylation cascade of spiro dihydroquinazolinones with DABSO and NFSI is reported. This protocol features mild reaction conditions, good yields and excellent functional group tolerance, providing a practical approach to the quinazolin-4(1)-one-functionalized aliphatic sulfonyl fluorides. In addition, the ease of gram-scale synthesis and the versatility of the SuFEx exchange highlight the application potential of this protocol.

DFT calculations have been performed to gain insight into the mechanism of hydrocarbonylation of olefins and the origin of regio- and chemoselectivity. It is shown that the most feasible mechanism involves five steps: (i) decomposition of acetic formic anhydride, (ii) hydropalladation of olefins, (iii) CO migratory insertion, (iv) iodide-assisted acetate-formate exchange, and (v) formylation or carboxylation. Importantly, carboxylation proceeds via the decomposition of anhydride, followed by reductive elimination instead of direct hydrolysis of anhydride. For phosphine-ligated palladium catalysis, on one hand, the lower stability of the transition state leading to 1,2-hydropalladation could be attributed to H···H steric hindrance. On the other hand, the high chemoselectivity for the aldehyde is ascribed to increased π back-donation effect and ligand-substrate noncovalent interactions, which stabilize the transition state and hence reduce the energy barrier. For ferrocenyl phosphine-ligated palladium catalysis, significant C-H···π interaction between the substrate and proximal phenyl moiety of the phenylphosphine and π-π interaction between formate and phenyl moiety can facilitate the carboxylation process. This in-depth mechanistic insight can account for reactivity and selectivity at an atomistic level and have implications for designing new generations of palladium catalysts.

A synthetic method was developed for the generation of a quaternary carbon center in carbonyl compounds. This innovative process involved the reaction of α-thiolate lactones and cycloalkanones with two equivalents of arynes in acetonitrile to give α,α-diarylated products in 63-85% yields at 25 °C. The reaction unfolds through an unconventional domino process, encompassing sequential 1,2-elimination, 1,2-nucleophilic addition, 1,4-proton transfer, the second 1,2-nucleophilic addition, interrupted Pummerer rearrangement, intramolecular spirocyclization, and sulfonium ring-opening. The potential of this "single-flask" reaction was systematically investigated and found well-suited to generate diarylated carbonyl compounds, incorporating naphthalene, pyridine, quinoline, or isoquinoline rings adorned with various substituents.