Chinese Journal of Chemistry最新文献

Indenophenanthrenes have remained largely overlooked as photocatalysts because their intrinsically high exciton binding energies and low molar absorption coefficients restrict both light-harvesting efficiency and single-electron transfer (SET) capability. In this work, we introduce a twisted indenophenanthrene derivative that overcomes these long-standing limitations through intentional distortion of its π-conjugated framework. The resulting nonplanar geometry enhances light absorption and substantially decreases electron–hole pair binding energy, thereby enabling efficient photoinduced SET for the first time within this molecular family. This structurally engineered chromophore functions as a robust metal-free photoredox catalyst. Its catalytic performance was validated through a prototypical decarboxylative coupling reaction between α-amino acids and electron-deficient alkenes. Under mild visible-light irradiation, the catalyst delivers the desired C–C bond-forming products in high yields across a broad substrate scope. A wide range of natural and synthetic amino acids, as well as diverse alkene acceptors, are well tolerated, demonstrating the generality and versatility of this newly developed catalyst platform. Mechanistic studies comprising radical trapping, fluorescence quenching, Stern–Volmer analysis, and a series of control experiments collectively provide compelling evidence for an oxidative quenching pathway mediated by radical intermediates. Over-all, this study establishes a modular design principle for engineering the photophysical and electrochemical properties of purely organic photocatalysts through geometric twisting. By demonstrating that twisted indenophenanthrenes can mediate challenging redox transformations under mild, metal-free conditions, this work positions them as a promising new class of sustainable organic photoredox catalysts for advanced synthetic applications.

Transition-metal-catalyzed oxidative cross-dehydrogenative coupling (CDC) reactions represent an attractive strategy for the direct construction of C–C and C–X (X = heteroatom) bonds, owing to their inherent atom and step economy. This strategy has been recently extended to the B–H/C–H cross-dehydrogenative coupling of carboranes with arenes. However, such transformations typically either rely on the assistance of directing groups or are restricted to intramolecular processes. Herein, we report a palladium-catalyzed direct cross-dehydrogenative coupling between the B–H bond of carboranes and the C–H bond of (hetero)arenes, which affords B(9)-arylated products of o/m-carboranes in good to excellent yields with a broad substrate scope. Notably, this methodology is not limited to simple benzene rings but also delivers high yields with polycyclic aromatic hydrocarbons, five-membered heterocycles, and benzo-fused five-membered heterocycles. Control experiments reveal that B–H activation occurs preferentially over C–H activation. The high reactivity of carboranes toward Pd(II) and their steric hindrance are the keys to this successful transformation, suppressing the formation of (hetero)arene and carborane homo-coupling products, respectively.

To tackle some shortcomings of the classic Fischer indole synthesis employing aldehydes as starting materials, we report herein a reductive Fischer-type indole synthesis based on carboxylic acids. This method comprises a tandem sequence involving B(C₆F₅)₃-catalyzed hydrosilylation of carboxylic acids with Et₃SiH to generate the corresponding O,O-disilyl acetals, p-TsOH-mediated transamination with arylhydrazines to form hydrazones, and a late-stage Fischer indole cyclization. In this manner, carboxylic acids act as surrogates of aldehydes. Using this one-pot protocol, a series of 3-substituted indoles, including 3,4-, 3,5-, and 3,6-disubstituted indole derivatives have been synthesized. The utility of this protocol is demonstrated by the efficient synthesis of the versatile natural product 3-methylindole, the key intermediate in the commercial production of the antidepressant drug Vilazodone (Viibryd), and the core scaffold of one of the most frequently prescribed agents for the treatment of hypercholesterolemia—all from inexpensive, commercially available carboxylic acids and arylhydrazines. The one-pot reaction tolerates several functional groups such as halogen (F, Cl, Br, I), MeO, CN, and CF₃, which are either key moieties for the development of medicinal and agrochemical agents, or can be used as a handle for the further elaboration of the indole products, as demonstrated by the two-step synthesis of a tetracyclic indole derivative.

D- and L-glycero-L-Heptopyranosyl residues are essential structural motifs in glycans and glycoconjugates, yet they remain challenging to obtain from natural sources. Herein, we disclose an efficient protocol for synthesizing D- and L-glycero-L-heptopyranosyl thioglycosides, which are recognized as powerful glycosyl donors. Our strategy pivots on a C1-to-C5 switch strategy, commencing from readily accessible allyl α-C-glycosides. The key transformations include a DBU-catalyzed anomerization of easily available α-C-glycosylethanals, an imidazolidinone-catalyzed α-oxyamination of the aldehydes to install a chiral hydroxy group with high selectivity, and a decarboxylative transformation of the resulting uronic acids into the target thioglycosides. We found that the efficiency of the anomerization step is significantly influenced by the electronic nature of the protecting groups and the conformation of a sugar ring. Intriguingly, the stereoselectivity of the key oxyamination step was found to be independent of the catalyst's chirality. To demonstrate the practical application of this protocol, we synthesized three distinct thioglycosides, including 6-O-methyl-D-glycero-L-gluco-heptopyranosyl thioglycoside, L-glycero-L-galacto-heptopyranosyl thioglycoside and L-glycero-L-manno-heptopyranosyl thioglycoside from the corresponding allyl α-C-glycosides. The ready access to these glycosyl donors paves the way for synthesizing biologically relevant targets, such as Campylobacter jejuni NCTC11168 capsular oligosaccharides, septacidin/spicamycin-type nucleosides, and their analogues.

Cyclodepsipeptides represent a distinctive family of natural cyclic peptides endowed with diverse and potent biological activities, making them promising scaffolds for drug development and agrochemical applications. Incorporation of N-methylated amino acids further enhances their metabolic stability and oral bioavailability by resisting proteolytic degradation. However, the synthesis of such cyclodepsipeptides, especially those containing multiple sterically hindered N-methylated residues, remains a significant challenge for conventional solid-phase peptide synthesis (SPPS) due to inefficient on-resin acylation, sluggish coupling kinetics, and conformational constraints. Herein, we report the first successful application of a novel solid-phase peptide synthesis (SPPS) strategy based on immobilized ribosome-mimicking molecular reactors (RMMRs) for the efficient synthesis of two representative bioactive cyclodepsipeptides: destruxin B (a hexadepsipeptide with two consecutive N-methylated amino acids) and [2S,3S-Hmp]-aureobasidin L (a nonapeptide featuring four N-methylated amino acids). A crucial approach is the use of pre-assembled depsidipeptide building blocks, which mitigate side reactions associated with on-resin esterification, combined with the RMMR platform that accelerates the coupling of sterically hindered residues via an artificial pseudo-intramolecular acyl-transfer mechanism. The linear precursors were efficiently assembled on Oxyma-C RMMR-HMPA resin with high/moderate crude purities (90% for destruxin B, 45% for [2S,3S-Hmp]-aureobasidin L) and much reduced synthesis times (≈15 h and ≈60 h, respectively). Subsequent solution-phase macrocyclization using HATU/DIPEA yielded the target compounds in satisfactory yields (75% for destruxin B, 50% for [2S,3S-Hmp]-aureobasidin L). This robust and time-economic methodology overcomes key limitations of conventional methods, providing a broadly applicable platform for the synthesis of complex cyclodepsipeptides and facilitating future medicinal chemistry exploration of this valuable class of bioactive molecules.

Organosilicon compounds have garnered significant attention due to their unique physicochemical properties and broad applications in pharmaceuticals, materials science, and synthetic chemistry. The construction of C–Si bonds represents a fundamental challenge in this field, with silylboronates emerging as particularly versatile reagents. Conventional catalytic systems heavily rely on precious transition metals (e.g., Pd, Pt, Au) to activate Si–B bonds through oxidative addition or transmetalation pathways. While effective, these methods suffer from limitations in sustainability, cost, and functional group compatibility. The emergence of photoredox and electrocatalytic approaches has opened new avenues for metal-free Si–B bond activation. These strategies enable controlled generation of silyl radicals under mild conditions through single-electron transfer processes, including anodic oxidation or photoinduced electron transfer. This paradigm shift has facilitated diverse radical silylation transformations, such as hydrosilylation and radical-mediated functionalization. Despite these advancements, the integration of silylboronates with photocatalytic Truce-Smiles rearrangements remains unexplored. Herein, we report a visible-light-promoted tandem silylation reaction that addresses this gap. Using silylboronates as silicon sources, our methodology proceeds via a novel Truce-Smiles rearrangement pathway to efficiently construct two distinct types of silylated products from methacrylamide substrates. The optimized reaction conditions employ a photocatalyst and operate at ambient temperature without stoichiometric oxidants, demonstrating excellent functional group tolerance, broad substrate scope, and scalability. The practical utility of this protocol is further verified through successful late-stage functionalization of complex drug molecules. This work not only provides a general strategy for C–Si bond construction but also underscores the potential of photoredox catalysis in expanding the toolbox for sustainable, metal-free synthetic organic chemistry.