Advanced Synthesis & Catalysis最新文献

A new class of sulfide-based catalysts that enable hydrogen atom transfer (HAT) under visible-light-driven photoredox conditions is reported. Based on the potential of indirect HAT processes, alkyl aryl sulfides that undergo single-electron oxidation to generate radical cations were designed as candidate HAT catalysts. A wide variety of alkyl aryl sulfides exhibit catalytic activity, promoting the CH alkylation of a broad range of substrates, including alcohols, ethers, hydrocarbons, and aldehydes, in the presence of an acridinium photocatalyst. The reactions proceed under mild conditions without additional bases or additives. Mechanistic studies, including fluorescence quenching and deuterium labeling, indicate a pathway involving radical cation intermediates. DFT calculations indicate that the 2-thiazolyl structure on the sulfide enhances the catalyst activity by shifting the HAT from an S-centered pathway to an N-centered pathway. This study establishes sulfides as modular platforms for photoredox-mediated HAT catalysis.

We report a highly efficient protocol for the synthesis of silacycles through oxidative annulation cascade with 1,7-enynes via selective functionalization of Si-H/silyl C(sp³)-H bonds of hydrosilanes. Simple N-aminopyridinium salt acts as hydrogen atom transfer reagents for the in situ generation of sulfamidyl radical under photoredox catalytic condition. Notably, this protocol demonstrates broad substrate scope with shorter reaction time and viable to the late-stage functionalization of natural products and pharmaceuticals.

Engineering Cumene Dioxygenase

The painted design by Fátima Navarro-Cetina and WesWizzArt depicts the cumene dioxygenase-catalyzed hydroxylation of monoterpenes. Engineering of this enzyme (depicted as a figurine) yielded variants exhibiting exceptional regioselective control and product formation across various monoterpenes and monoterpenoids, including α-pinene and limonene (stylized as the stems of pine and lemon trees), producing highly sought-after fragrance compounds (depicted in the branches of the corresponding trees). More information can be found in the Research Article by Bernhard Hauer and co-workers (10.1002/adsc.70323).

The combination of azole compounds, such as 1-methylimidazole and oxiranes (e.g., phenyl glycidyl ether) gives carbenoid reactivity at elevated temperatures. Benzoin condensation was performed with 5 mol% azole and 10 mol% oxirane under air at temperatures of 70°C and above, achieving conversions of up to 85% of benzaldehyde and yields of up to 64% of benzoin. The lower benzoin yield is due to the formation of oxidative benzoin follow-up products under these reaction conditions. A variety of combinations of azole compounds and oxiranes have been shown to catalyze benzoin condensation. Thus, a modular, potentially inexpensive method of generating carbenoid reactivity has been revealed. The proposed mechanism for catalyst formation involves oxirane opening by, for example, 1-methylimidazole, which forms a zwitterionic methylimidazolium adduct with the oxirane. Then, the acidic proton in the 2-position of the imidazolium core is deprotonated by the zwitterion's alkoxide releasing the corresponding N-heterocyclic carbene (NHC). In addition to its primary function, surplus oxirane serves as a scavenger, removing acidic byproducts that are formed from the aldehyde through oxidative NHC catalysis. This property enables benzoin condensation without the exclusion of oxygen. The practical utility of this catalytic system was demonstrated by polymerizing simple bifunctional aldehyde/oxirane monomers—namely, 4-(2-oxiranylmethoxy)-benzaldehyde, 3-(2-oxiranylmethoxy)-benzaldehyde, and vanillin-based 2-methoxy-4-(2-oxiranylmethoxy)-benzaldehyde—using 5 mol% 1-methylimidazole in a solventless manner and without excluding air. The monomers polymerized via both the formyl and the oxirane groups, yielded thermosets with glass transition temperatures above 100°C.

Cyclization reactions are pivotal for constructing cyclic scaffolds in pharmaceuticals, natural products, and functional materials. The emerging electrophotocatalytic cyclization synergistically merges the unique activation modes of photoexcitation with the precise electron-transfer control offered by electrochemistry, mitigating the inherent limitations of standalone photocatalysis and electrocatalysis. Specifically, it overcomes the constrained redox window of photocatalysis and the mass transport issues of electrocatalysis, enabling net-oxidative cyclizations under mild and external oxidant-free conditions with H₂ as the byproduct. This review summarizes recent advances in electrophotocatalytic radical cyclizations, categorized by substrates (alkenes, alkynes, and non-alkene/alkyne scaffolds). Reaction mechanisms, characteristics, scopes, and key innovations are discussed, highlighting the distinctive reactivities and selectivities unlocked by this synergistic approach. The current challenges and future perspectives in this rapidly evolving field are also outlined.

Carbonylation represents a straightforward and powerful strategy for installing carbonyl groups into organic molecules. However, the widespread adoption of carbon monoxide gas in laboratories is hampered by its toxicity, flammability, and smell-less properties. To address these challenges, we developed a new carbon monoxide surrogate, inositol hexaformate (HFI), and demonstrated its utility in the palladium-catalyzed aryloxycarbonylation of aryl bromides with phenols. Notably, HFI efficiently releases six equivalents of carbon monoxide, showing a significant improvement in efficiency over commonly used formate surrogates. This work provides a practical and robust method for conducting carbonylation reactions, which is expected to broaden the accessibility of this important transformation in synthetic chemistry.

Amides and sulfoximines are pivotal structural motifs in pharmaceuticals and agrochemicals; however, sustainable and direct methods for their incorporation remain underdeveloped. Herein, a metal- and additive-free protocol is presented for the efficient synthesis of N-acyl sulfoximines via selective NC bond cleavage of amides, utilizing bench-stable N-acyl saccharin as an acylating agent for NH-sulfoximines. This transformation proceeds under mild conditions using green solvents and exhibits a broad substrate scope encompassing natural products and drug derivatives. Notably, the method is compatible with both batch and continuous-flow platforms, achieving a significant reduction in reaction time from 24 h to 15 min. The process offers high yields, excellent functional group tolerance, and gram-scale scalability. Furthermore, the recovery of recyclable saccharin enhances atom economy and minimizes waste generation.

The selective functionalization of indoles using methanol via borrowing hydrogen (BH) and interrupted borrowing hydrogen (I-BH) pathways offers a sustainable approach to access value-added molecules. Herein, the synthesis of a series of benzimidazole-functionalized cyclometalated (NC)-Ru(II) and (NN)-Ru(II) complexes and their application in the chemodivergent functionalization of indoles with methanol are reported, affording either C3-methylated indoles or bis(indolyl)methanes (BIMs). The product selectivity was governed by the hydricity of the Ru–H species, which was effectively tuned by ligand backbone modification. This varying catalytic behavior of these complexes under consideration toward the selective formation of different products was fairly understood by analyzing their electronic properties based on electrochemical and density functional theory studies. Additionally, the electron-rich (NC)-Ru complex facilitated the α-methylation of phenylacetonitrile under relatively mild conditions. Finally, an array of control experiments and the identification of different intermediates aided in establishing the proposed mechanism.

Enantioselective regiodivergent cascade reactions remain a significant challenge due to the dual requirement of achieving precise control over both regioselectivity and stereoselectivity. Herein, a quinine-derived bifunctional catalyst-driven strategy is presented for constructing the diverse asymmetric polycyclic spiro-pyrazolone scaffolds in a cascade manner. The cascade reaction is initiated by the asymmetric vinylogous Michael addition (VMA) of arylidene pyrazolones to the indandione-derived acceptors, followed by regioselective transformations that lead to structurally diverse products. The divergent reaction outcomes are governed by the interaction between the in situ generated conjugate acid of the catalyst and the anionic intermediate (VMA adduct). These outcomes are further modulated by adjustments in the reaction conditions, particularly the polarity of the solvent. In toluene, the reaction predominantly yields the cage product with excellent regio- and enantioselectivity via a cascade pathway involving asymmetric VMA/acetalization/oxa-Michael/Michael addition. In contrast, in MeCN, the reaction proceeds through an asymmetric VMA/proton transfer/aldol/acetalization, furnishing the fused product. Mechanistic studies reveal that the formation of the fused product involves an unusual and reversible reaction pathway. Specifically, the catalyst-controlled 1,6-conjugate addition of 1,3-indandione to the diene intermediate occurs under optimal conditions. This strategy demonstrates a versatile foundation for asymmetric regiodivergent cascade reactions.

Bismuth (Bi)-based materials have emerged as highly promising catalysts for electrochemical CO₂ reduction (CO₂RR) toward formate production, owing to their high intrinsic catalytic activity and low cost. However, a critical challenge for practical application is the dynamic electrochemical reconstruction of Bi-based catalysts during CO₂RR electrocatalysis, an inherently uncontrollable and indeterminate process that often leads to severe structural degradation of catalysts and a subsequent decay in long-term stability and selectivity. Herein, this review focuses on the development of stabilization strategies to moderate the dynamic reconstruction of Bi-based catalysts. In detail, this review systematically analyzes and summarizes three distinct principal strategies: (1) passive suppression strategy, which preserves high-valent Bi^δ+ species by suppressing reconstruction; (2) proactive direction strategy, which directs a controllable “self-optimization” reconstruction toward desired active species; and (3) circumvention strategy, which circumvents the complex reconstruction process through direct synthesis and modification of metallic Bi catalysts. This review aims to construct a rigorous theoretical framework for the rational design and controllable synthesis of advanced Bi-based catalysts, thereby outlining some potential directions for the future industrial applications.