Cyclic sulfonium salts are a class of heterocyclic compounds containing a tetravalent sulfur atom.Due to their inherent electronic deficiency,they exhibit excellent thermodynamic stability and high reactivity,and thus play a significant role in organic synthesis.In recent years,the ring-opening reactions of cyclic sulfonium salts have garnered significant atten-tion for their application in the construction of sulfur-containing compounds,particularly through nucleophilic and free radical type ring-opening reactions.These reactions not only provide new approaches for the synthesis of diverse sulfur-containing compounds but also broaden their potential applications in drug development and functional materials.The latest research progress of ring-opening reactions of cyclic sulfonium salts is summarized,focusing on the formation reactions of C-C bond and C-heteroatom bond in nucleophilic and free radical type ring-opening reactions.The substrates scope and reaction mechanisms are discussed in detail,and the potential value of these methodologies in the synthesis of sulfur-containing com-pounds is also discussed.
Over the past decade,photocatalysis has emerged as one of the frontiers in organic chemistry,attracting tremendous interest from the synthetic community.Compared to traditional methods,photocatalytic reactions offer advantages such as mild conditions,high functional group tolerance and unique reactivity and selectivity.As an important area of photocatalysis,the transformation of imines is undergoing continuous advancements.Under photocatalytic conditions,the reactivity of imines is reshaped,allowing them to undergo single-electron reduction to form α-aminoalkyl radicals-a process that can even reverse their polarity,enabling them to act as carbon nucleophiles.N-Heterocycles and amines are among the most prevalent and important organic compounds,which are found in numerous alkaloids and pharmaceutical molecules.Therefore,the conversion of imine compounds to amines under photocatalytic conditions has introduced new methodologies to solve important problems in the synthesis of drugs and related fields,which were hardly achieved by traditional synthetic strategies.This review summarized the research progress on the photocatalytic synthesis of amines from imines viaα-aminoalkyl radicals,with a focus on selectivity and functional group tolerance.
酰胺键广泛存在于小分子、多肽及蛋白质中(Scheme 1),其高效构建始终是合成化学与化学生物学中的核心问题之一[1].尽管酰胺键构筑的方法已得以发展,但在温和、水相条件下,由低活化态底物(如醛或醇)直接实现选择性酰胺化仍具挑战性.现有策略多依赖高活化酰基试剂或复杂酶体系(Scheme 2),限制了其在绿色与生物相容条件下的应用前景[2].
A catalytic system comprising a readily available chiral binaphthyl-based P-N-O tridentate ligand and iridium has been developed for the highly efficient asymmetric hydrogenation of simple aromatic ketones. Using prochiral aromatic ketones as substrates, this system gives the corresponding chiral alcohols in up to >99% yield and 97% enantioselectivity under mild conditions. Systematic optimization of reaction conditions revealed that (R)-2-(((2'-(diphenylphosphaneyl)-[1,1'-binaphthalen]-2-yl)amino)methyl)phenol (L1) as the ligand, Ba(OH)2 as the base additive, and 95% (phi) ethanol as the solvent were critical for achieving excellent performance. The catalytic system exhibits good substrate generality, being applicable to various aromatic ketones and heteroaromatic ketones with different substituents. Furthermore, this method was successfully applied to the synthesis of (S)-3-(dimethylamino)-1-(thiophen-2-yl)propan-1-ol, a key chiral intermediate of the antidepressant (S)-duloxetine, affording the target product with 98% yield and 90% ee, which fully demonstrates its great application potential in practical synthesis.
Pyridinium 1,4-zwitterionic thiolates and their quinolinium/isoquinolinium analogs have recently emerged as novel multifunctional synthons with broad synthetic utility.These compounds have attracted wide synthetic interest for being air-stable,odorless,easy-to-handle and readily available.In this review,the advances in pyridinium 1,4-zwitterionic thiolates and their quinolinium/isoquinolinium analogs for organic transformations are summarized:as key synthons for heterocycle construction via formal[3+m]and[5+m]annulations,and as sulfur-transfer reagent to convert isocyanides to isothiocya-nates.These methods provide efficient access to diverse nitrogen-and/or sulfur-containing scaffolds,enabling efficient synthe-sis of structurally diverse molecules.
N-Alkylamines,amides,and sulfonamides,a class of important nitrogen-containing structural units,are ubiquitous in pharmaceutical molecules,agrochemicals,and functional materials.To this end,the efficient and precise synthesis of such substructures is of great significance for molecular design and late-stage modification.Among various synthetic approaches,C—N bond formation represents one of the key strategies.However,traditional C—N bond formation strategies heavily rely on pre-functionalized substrates under strong oxidative/reductive conditions,or elevated reaction temperature,which often suffer from over-alkylation,competitive side reactions,poor regio-and chemoselectivity,limited compatibility with molecular complexity.Over past years,visible-light-driven hydroamination,hydroamidation,and hydrosulfonamidation of alkenes have achieved efficient synthesis of N-alkylamines,amides,and sulfonamides by direct cross-coupling of simple alkenes with various nitrogen sources under mild conditions through different reaction mechanisms such as single-electron transfer,proton-coupled electron transfer,and hydrogen atom transfer.These reactions utilize alkenes as alkylation reagents,demonstrating excellent step-economy and functional group compatibility.This review summarizes the progress and key reaction pathways in the field of visible-light-catalyzed hydroamination,hydroamidation,and hydrosulfonamidation of alkenes,with an emphasis on selectivity control and scope of different catalytic systems,and provides an outlook on future developments in this area,aiming to offer theoretical and practical guidance for further development and application to target synthesis in related areas.
硫基手性分子,特别是含硫(Ⅳ)手性中心的分子[1],在制药、手性助剂、不对称催化(如有机催化剂和配体)、农用化学品及功能材料领域具有重要应用价值.相较于已取得成熟进展的碳手性中心合成研究,硫手性中心分子的高效、立体选择性合成仍是当前有机合成领域的一大挑战.
手性3,4-二氢异喹啉酮是异喹啉生物碱的重要骨架,普遍存在于天然产物和药物分子中(图1)[1],也是合成1,2,3,4-四氢异喹啉生物碱的关键中间体[2].因此,发展高效构建手性3,4-二氢异喹啉酮骨架的方法具有十分重要的意义.
Chiral organoselenium compounds are widely found in bioactive molecules,natural products,pharmaceutical agents,and functional materials.They also serve as important intermediates and catalysts in organic synthesis.Given the sig-nificance of such compounds,the synthesis of chiral organoselenium compounds has long been a hot research topic in organic chemistry.In recent years,the development of environmentally benign and cost-effective methods for synthesizing chiral or-ganoselenium compounds has attracted considerable attention.The research progress in the synthesis of chiral organoselenium compounds under different catalytic systems over the past decade is reviewed.This review is organized into three catalytic systems:metal-free catalysis,metal catalysis,and photocatalysis,and the research progress of each system is discussed in de-tail.Additionally,the challenges and future directions in the synthesis of chiral organoselenium compounds are also discussed.
Catharanthine,an iboga-type indole alkaloid isolated from Catharanthus roseus,features a pentacyclic framework with three stereocenters.As a key structural fragment of the anticancer drugs vinblastine and its analogue vincristine,its complex and unique chemical architecture has made it a hotspot in synthetic studies.In recent years,its complete biosynthetic pathway has been elucidated and functionally reconstructed in heterologous systems,such as yeast and Nicotiana benthamiana.Since 1969,18 research groups have reported chemical syntheses of catharanthine,encompassing racemic,asymmetric,and biomimetic syntheses,as well as various transition-metal-catalyzed approaches.This review chronologically summarizes the advances in both the biosynthesis and chemical synthesis of catharanthine and offers perspectives on future research directions.
Over the past two decades,the low-valent organoactinide complexes containing redox-active non-innocent ligands have become one of the most promising research frontiers in organometallic chemistry due to their fundamental importance and their extensive applications in organic synthesis,chemical engineering and catalytic processes.Among these,low-valent organouranium complexes have received widespread attention because of their unique structural properties and their potential applications in group transfer and catalysis.Currently,low-valent organouranium complexes containing redox-active non-innocent ligands,in particularly those derived from 2,2'-bipyridine,1,4-diazabutadienes,pyridine diimines and arenes have been regarded as one of the most remarkable research hotspots in organometallic chemistry.This review summarizes the ad-vances in the preparation of such complexes and their reactivity in small molecule activation.
Sulfonyl derivative-mediated radical-type aryl migration reactions represent a pivotal strategy for achieving func-tional group migration,molecular skeleton rearrangement,and the efficient construction of substituted aromatic compounds,and they hold significant application value in the field of precision synthesis of complex molecules.Classified by the structural types of sulfonyl derivatives,this review systematically summarizes the latest research progress in aryl(hetero)aryl migration reactions mediated by sulfonamides,aryl sulfone derivatives,sulfonic acid esters,and other sulfonyl compounds in recent years.It focuses particularly on discussing the design concepts and mechanistic investigations of various reactions,and also provides an outlook on the future development directions of this field.
Carbohydrates,among the most abundant biomolecules in nature,play crucial roles in the synthesis of bioactive molecules,drug development,and materials science.The selective oxidation of sugar hydroxyl groups represents a key strate-gy for synthesizing carbohydrate derivatives and achieving functional group interconversion.However,the inherent polyhy-droxy structure and the similar reactivity of their hydroxyl groups present significant challenges for selective modification.Traditional methods rely on tedious protection/deprotection steps,leading to lengthy and inefficient synthetic routes.In recent years,the direct selective catalytic oxidation of unprotected sugars has emerged as a prominent research focus.This strategy significantly streamlines synthetic pathways,enhances atom economy,and reduces environmental impact.This review summa-rizes the progress in selective catalytic oxidation of unprotected or minimally protected sugars,providing a critical discussion of various catalytic systems employed in this field,including metal catalysis,photocatalysis,and electrocatalysis.
Silver-catalyzed decarboxylative C(sp(2))-H alkylation of cyclic aldimines with monoalkyl oxalates via C-O bond cleavage has been realized under mild reaction conditions. The corresponding products were generated in moderate to good yields (30%similar to 80%) with wide substrate scope. In addition, the late-stage modification of tyrosine-and estrone-derived cyclic aldimines was investigated, and this catalytic system was further extended to five-and seven-membered cyclic aldimines. The reactions proceeded smoothly, affording the corresponding products in moderate yields. The mechanistic studies show that the reaction undergoes a radical pathway.
Transition metal-catalyzed asymmetric cyclization reactions of 1,3-dienes represent a powerful strategy for the construction of chiral cyclic compounds,with broad applications in the synthesis of natural products,pharmaceuticals,and functional materials.The recent advances in this field are systematically reviewed,focusing on two major cyclization modes:1,2-and 1,4-cyclication.Detailed discussions are provided,including Heck reactions,C-H bond activation,Wacker-type oxidations,and π-Lewis base catalysis.These methods enable efficient and highly enantioselective construction of various ring systems ranging from five to eight membered cycles,demonstrating good functional group compatibility and substrate diversity.Despite considerable advances,several challenges still persist,including ambiguous reaction mechanisms,narrow substrate scope,and poor stereocontrol.Future developments should focus on in-depth mechanistic elucidation,the design of economical metal catalysts,and the expansion of substrate generality to enhance the utility of these transformations.
α-Alkylidene-γ-lactone skeletons,which possess multiple biological properties,are core structural motifs found in numerous natural products and active pharmaceuticals.Over the past several years,significant progress has been made in the development of efficient and selective catalytic methods for the synthesis of α-alkylidene-γ-lactones under relatively mild conditions with new synthetic technologies.However,a comprehensive summary of this field has yet to be established in the literature of the past decade.The typical α-alkylidene-γ-lactone-containing natural and unnatural bioactive molecules,as well as highlights the recent advancements in the preparation of α-alkylidene-γ-lactone derivatives are introduced.It is hoped that this overview will inspire the development of novel strategies for accessing diverse α-alkylidene-γ-lactones and facilitate their applications in drug discovery.
Carboxylic acids are a class of chemicals with abundant sources,structural diversity,stability,and cost-effectiveness,representing the second largest class of commercially available organic building blocks after amines.The past decade has witnessed the rapid development of photoinduced radical decarboxylative transformation of alkyl carboxylic acids.However,the progress in the decarboxylative transformation of aryl carboxylic acids is slow,mianly due to the relatively reluctant decarboxylation of O-centered aryl carboxylate radicals and the subsequent very reactive aryl radicals,suffering severe competitive pathways.In the latest five years,ligand-to-metal charge transfer(LMCT)-driven photoinduced metal-catalyzed/mediated decarboxylative transformation of aryl carboxylic acids(carboxylates)has gained some achievements,such as copper-catalyzed/mediated halogenation,hydroxylation,sulfoximination,borylation,halosulfonylation,thianthrenation,allylation,thiolation and hydrogenation,iron-catalyzed thiolation and bromination.Further development is highly expected to realize new types of reactions through smart design and control of reaction conditions.For instance,the merger of LMCT and transition metal catalysis might provide an opportunity to achieve the decarboxylative cross-coupling of aryl carboxylic acids.
The development of novel chiral phosphine ligands is a key area of research in organic synthesis.An efficient syn-thetic method for the preparation of helically chiral monophosphorus ligands was reported.Using this approach,four structur-ally distinct,helically chiral,bowl-shaped monophosphorus ligands were successfully synthesized.Their catalytic activities were systematically evaluated in palladium-catalyzed C-C and C-N bond-forming reactions.Enantiopure ligands were ob-tained via HPLC resolution.Although these reactions did not achieve high enantiocontrol,the ligands demonstrated a unique helical chiral cavity and excellent catalytic activity.These findings suggest that this class of compounds warrants further ex-ploration in other asymmetric catalytic reactions.
Multi-substituted benzo[b]thiophene skeleton is an important synthetic intermediate. A series of multi-substituted benzo[b]thiophene-4-ol derivatives were successfully constructed from 3-substituted 1-(thiophen-3-yl)prop-2-en-1-one and nitroso compound via organobase-promoted cycloaddition reactions. Optimization experiments showed that the best experimental conditions were as follows: using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (2.5 mmol) as base, 3-substituted 1-(thiophen-3-yl)prop-2-en-1-one (1.0 mmol) and nitroso compound (1.2 mmol) reacted in N,N-dimethylformamide (DMF) at room temperature for 8 h, affording multi-substituted benzo[b]thiophen-4-ol derivatives in 88% yield. The compositions and structures have been characterized by 1H NMR, 13C NMR and HRMS (ESI). The mechanism for the reaction was proposed. The menthod has the characteristics of mild conditions and practical efficiency.
