The synthesis of diverse functionalized carbohydrate derivatives holds great importance for advancing carbohydrate-based drug development. By integrating an atom-economic multicomponent reaction (MCR) strategy, in this work, we report a visible-light-induced, palladium-catalyzed radical three-component reaction involving glycosyl halides, achieving efficient access to C-alkyl glycosides containing a crotonamide scaffold. Moreover, starting directly from glycosyl hemiacetal, the same MCR transformation was achieved in a convenient, one-pot procedure. Leveraging the highly efficient radical trapping ability of 1,3-butadiene, this approach demonstrates broad substrate compatibility across a diverse range of carbohydrate substrates and various aliphatic amine partners including several approved drug molecules containing amine functional groups.

The development of efficient transfer hydrogenation protocols using inexpensive and nontoxic molecular hydrogen donors is highly desirable for the synthesis of medicinally important piperidine derivatives. This study presents a ruthenium-catalyzed transfer hydrogenation of pyridinium salts using inexpensive ammonium formate as the hydrogen source. The method selectively produces tetrahydropyridine derivatives from 4-substituted pyridiniums and fully reduced piperidines from 3-substituted pyridiniums with high efficiency. Additionally, quinolinium and isoquinolinium salts can be reduced under metal-free conditions using ammonium formate. The procedure is scalable, as demonstrated by a gram-scale reaction, and enables subsequent synthetic transformations.

Oxidative deboronation of boron-containing organic species is of wide interest, particularly because of their applications in synthetic routes and biological settings. Two types of oxidation are important and have been studied computationally, as reported herein: 1) reaction with oxidants HOX (X = leaving group), which are commonly employed to achieve B-to-O exchange in synthetic applications and occur under physiological conditions, and 2) reaction with oxygen in air, which, with triethylborane BEt3, is a well-established radical initiation approach. In the reactions with HOX, the prevalent emphasis on a tetrahedral anionic intermediate and its transformation into oxidized products is generally supported by theory, but changes in mechanism should be expected as conditions are varied, particularly concentration, pH, and solvent. The most extreme such change is the transition to radical reactions, which has implications for the safety of reactions and of species administered in vivo and is particularly likely for borinic acids. For autoxidation, theory does not support initiation by oxygen, but trace ozone in air would be a competent initiator.

We report a metal-free protocol for the synthesis of 1,2-diaryl pyrazol-3-ones through the strategic exploitation of N,N'-diborylated hydrazine reactivity. The transformation employs a 4,4'-bipyridyl-catalyzed system that enables in situ generation of N,N'-diborylated hydrazines from azoarenes and bis(pinacolato)diboron, followed by their unprecedented sequential insertion of carbonyl groups from β-keto esters. Gram-scale synthesis and downstream derivatizations demonstrate the practical utility of this method, while the resulting compounds exhibit promising anti-inflammatory activity. Mechanistic studies, including control experiments and DFT calculations, delineate a sequential pathway in which the diborylated hydrazine intermediate undergoes two distinct carbonyl insertion events via four-membered transition states, ultimately affording the pyrazolone core.

A reaction of thioesters and selenoesters with doubly stabilized carbenes generated from the corresponding diazo reagents under Rh or Cu catalysis affords products resulting from formal carbene insertion into the C(O)-S and C(O)-Se bonds. The generality of this transformation was demonstrated across a total of 37 examples. A complex reaction mechanism was proposed based on both the isolation of a key intermediate and DFT calculations for the overall reaction pathway. The resulting densely functionalized products, containing up to four different activating groups attached to the same carbon atom, can be readily converted into a variety of valuable compounds through selective and robust defunctionalization reactions.

Semistabilized azaallyl anions, generated from N-benzyl ketimines in the NaOtBu/DMSO superbase medium, undergo conditions-controlled formal [3 + 2] or [4 + 3] cyclization with diaryldiynes. Consequently, selective switchable syntheses of triarylsubstituted α-arylated N-vinyl pyrroles (in up to 64% yield) and tetraarylated 2H-azepines (in up to 75% yield) have been developed. The synthetic value of this strategy has been validated by successful gram-scale syntheses of both products.

Molecular skeletons containing fused cyclobutane rings are of significant value in drug discovery as they can increase the fraction of sp3 carbons (Fsp3) and impart conformational rigidity. Herein, we report a visible-light photocatalytic strategy for the intermolecular [2 + 2] cycloaddition of indenes with maleimides, which enables the efficient construction of cyclobutane-fused tetracyclic skeletons. Mechanistic investigations confirm that the reaction proceeds via an energy-transfer (EnT) pathway, wherein the excited-state photosensitizer activates the maleimide, followed by cyclization with indene through a triplet biradical intermediate. This method not only establishes an efficient synthetic route toward cyclobutane-fused polycyclic compounds but also further expands the utility of EnT catalysis.

A visible-light-induced cyclogermylation of 1,6-enynes has been developed for the construction of germanium-containing heterocycles. Utilizing germanes and structurally diverse enynes or dienes as substrates, this protocol employs a synergistic dual catalytic system combining photoredox catalysis with hydrogen atom transfer (HAT). This strategy enables a radical-mediated hydrogermylation/cyclization cascade under mild conditions, featuring high reactivity and a broad substrate scope. Notably, this method not only allows for the synthesis of five-membered carbagermanes but also provides efficient access to nitrogen-containing (e.g., pyrrolidine) and oxygen-containing (e.g., tetrahydrofurans) organogermanium heterocycles in good yields.

Hydrosilylation of β-alkyl- and aryl-substituted styrenes with arylsilanes faces challenges of the lack of an active catalyst, difficulty in controlling regioselectivity, and overcoming side reactions. Herein, we report the hydrosilylation of β-alkyl and aryl styrenes with PhSiH3 by the bridged pincer homodinuclear lanthanide metal complexes, which displayed high activity in the hydrosilylation of internal alkenes with PhSiH3, affording the corresponding products in moderate to high yields with excellent regioselectivity under mild conditions.

Titanocene(III)-mediated opening of allylic epoxides is commonly associated with γ-coupling processes rationalized through allyltitanium intermediates. Herein, we show that the regioselectivity of this process is strongly dependent on the substitution pattern of the allylic epoxide. Minimally substituted allylic epoxides undergo highly selective α-α' homocoupling under Cp2TiCl2/Mn conditions to afford symmetrical homoallylic 1,4-diol derivatives, with no detectable formation of γ-γ' or γ-α' coupling products. The absence of cyclization products in substrates bearing pendant alkenes capable of intramolecular radical trapping, together with the unchanged product distribution observed in the presence of 1-methyl-1,4-cyclohexadiene, is consistent with the involvement of organotitanium intermediates.

In this study, we disclose a Cu(OTf)2-catalyzed regioselective nucleophilic amination of quinones to synthesize 3,5-, 3,6-, and mixed diaminoquinones under air. The regioselectivity, controlled by the catalyst coordination and the steric hindrance of amines, follows different patterns: the reactions with anilines afforded the 3,6-diaminoquinones; the coupling with aliphatic primary amines led to the formation of a mixture of 3,6- and 3,5-isomers; and the use of sterically hindered secondary amines delivered the 3,5-isomers. Furthermore, we found that the synthesized diaminoquinones exhibited stable and strong photocurrent responses, suggesting potential applications in optoelectronic materials.

The purity and chemical integrity of oligonucleotides are critical determinants of safety, efficacy, and reproducibility in RNA therapeutics. Impurities arising from incomplete synthesis, degradation, or side reactions can compromise pharmacological performance and induce off-target or immune responses. For long, structured oligonucleotides such as CRISPR guides, purification can be costly in both resources and yield. To overcome these limitations, we developed a purification method based on a 5'-terminal dioctyloxytrityl (DOT) protecting group. In this purification method, DOT-protected full-length compounds show high-resolution separation from truncated impurities. The DOT group can then be removed under mild, rapid, and scalable conditions. DOT chemistry is analogous to "DMT-ON" approaches that are well-known and widely used in the field, and is fully compatible with existing synthesis workflows, but dramatically improves HPLC purification relative to DMT-ON approaches by providing higher retention and thus better resolution to enable the purification of long, complex, and chemically modified sequences.

Herein, we report the first examples of group-14 metal complexes of 5-monoazaporphyrins. Six-coordinate silicon(IV) and tin(IV) complexes of 10,15,20-triaryl-5-monoazaporphyrins (Ar3MAPMX2; M = Si or Sn, X = F, Cl, OH, or OCOPh) were prepared by metalation of the freebases of Ar3MAP (Ar3MAPH2) with the corresponding metal salts, followed by sequential axial-ligand exchange reactions. Furthermore, N-phenylation and N-ethynylation reactions of Ar3MAPSiF2 with the corresponding iodonium salts afforded 5,10,15,20-tetraaryl-MAP salts and 5-ethynyl-10,15,20-triaryl-MAP salts, respectively. We also established an environmentally benign method for synthesizing Ar3MAPH2 without a column-separation process. The structures, aromaticity, and optical and electrochemical properties of the SiIV and SnIV complexes of the MAP derivatives were investigated using X-ray crystallography, spectroscopic techniques, cyclic voltammetry, and DFT calculations. The SiIV and SnIV centers stabilized the HOMO and LUMO energy levels and weakened the diatropic ring-current effect of their MAP ligands. The positive charge generated by introducing substituents on the meso nitrogen considerably stabilized the frontier orbitals, resulting in a decrease in aromaticity. Time-resolved fluorescence spectroscopy of fluorescent SiIV complexes also provided valuable information on the effects of the meso-nitrogen atom and its substituents on the excited-state dynamics of MAP chromophores.