结合可见光促进氧化还原和镍催化的碳碳键合成进展

结合可见光促进氧化还原和镍催化的碳碳键合成研究,是对过渡金属催化的交叉偶联反应的重要补充,具有广阔的发展空间和应用前景,是近年来有机光化学合成的前沿热点领域之一。本文依据反应设计的模式划分,小结目前该领域的研究进展。     

C=C Bond Oxidative Cleavage of BODIPY Photocages by Visible Light

Photocages for protection and the controlled release of bioactive compounds have been widely investigated. However, the vast majority of these photocages employ the cleavage of single bonds and high-energy ultraviolet light. The construction of a photoactivation system that uses visible light to cleave unsaturated bonds still remains a challenge. Herein, we report a regioselective oxidative cleavage of C=C bonds from a boron-dipyrrolemethene (BODIPY)-based photocage by illumination at 630 nm, resulting in a free aldehyde and a thiol fluorescent probe. This strategy was demonstrated in live HeLa cells, and the generated α-formyl-BODIPY allowed real-time monitoring of aldehyde release in the cells. In particular, it is shown that a mannose-functionalized photocage can target HepG2 cells.     

碳-氟键断裂用于构建氟代异噁唑化合物

含氟异噁唑骨架是许多药物及农药分子中的重要结构单元,其中单氟代异噁唑类化合物的合成方法还比较有限.从易得的α-三氟甲基-β-羰基酯出发,发展了基于碱促进的碳氟键断裂策略的氟代异噁唑化合物合成方法,该反应条件温和,操作简便,官能团兼容性良好,可以中等到较好的收率得到一系列3-氟代异噁唑化合物,且所得产物可进一步转化为生物活性分子的类似物.     

可见光促进的光氧化还原催化的三氟甲基化反应

全氟烷基化反应,特别是三氟甲基化反应一直是有机化学领域的研究热点。近几年来,可见光促进的光氧化还原催化的有机化学反应,因其本身所固有的条件温和、绿色和环保等优点而倍受合成化学家的青睐。该方法学也被成功地应用于一系列三氟甲基化反应。本文主要按照三氟甲基源分类,总结了近年来可见光促进的光氧化还原催化的三氟甲基化反应的研究进展,并对其发展趋势进行了展望。     

可见光促进的苄位Csp3-H键活化官能团化反应

近年来,可见光促进的光致氧化还原催化活化有机小分子在合成化学中蓬勃发展.该策略一般以过渡金属有机络合物或有机染料作为光敏剂,在可见光照射下,其通过与底物发生单电子转移（SET）发生相互作用,利用反应过程中形成的自由基或自由基离子中间体,实现C-X（X=C,N,O……）键节能高效、高选择性、绿色性构建.本文根据不同的关键反应中间体,就可见光促进的苄位C_sp3-H键活化官能团化近年来取得进展进行简要归总.     

Late‐Stage Functionalization of Biologically Active Heterocycles Through Photoredox Catalysis

The direct C? H functionalization of heterocycles has become an increasingly valuable tool in modern drug discovery. However, the introduction of small alkyl groups, such as methyl, by this method has not been realized in the context of complex molecule synthesis since existing methods rely on the use of strong oxidants and elevated temperatures to generate the requisite radical species. Herein, we report the use of stable organic peroxides activated by visible‐light photoredox catalysis to achieve the direct methyl‐, ethyl‐, and cyclopropylation of a variety of biologically active heterocycles. The simple protocol, mild reaction conditions, and unique tolerability of this method make it an important tool for drug discovery.     

Visible Light Photoredox Catalysis Using Ruthenium Complexes in Chemical Biology

The development of bioorthogonal reactions have had a transformative impact in chemical biology and the quest to expand this toolbox continues. Herein we review recent applications of ruthenium-catalyzed photoredox reactions used in chemical biology.     

A Desulfurative Strategy for the Generation of Alkyl Radicals Enabled by Visible‐Light Photoredox Catalysis

Herein, we present a new desulfurative method for generating primary, secondary, and tertiary alkyl radicals through visible‐light photoredox catalysis. A process that involves the generation of N‐centered radicals from sulfinamide intermediates, followed by subsequent fragmentation, is critical to forming the corresponding alkyl radical species. This strategy has been successfully applied to conjugate addition reactions that features mild reaction conditions, broad substrate scope (>60 examples), and good functional‐group tolerance.     

Metal‐Free Carbonylations by Photoredox Catalysis

The synthesis of benzoates from aryl electrophiles and carbon monoxide is a prime example of a transition‐metal‐catalyzed carbonylation reaction which is widely applied in research and industrial processes. Such reactions proceed in the presence of Pd or Ni catalysts, suitable ligands, and stoichiometric bases. We have developed an alternative procedure that is free of any metal, ligand, and base. The method involves a redox reaction driven by visible light and catalyzed by eosin Y which affords alkyl benzoates from arene diazonium salts, carbon monoxide, and alcohols under mild conditions. Tertiary esters can also be prepared in high yields. DFT calculations and radical trapping experiments support a catalytic photoredox pathway without the requirement for sacrificial redox partners.     

可见光促进的氧化还原催化反应在天然产物全合成中的应用

可见光促进的光氧化还原催化在近年来取得了重要进展, 许多可见光光氧化还原的反应被用于复杂分子的构建. 本文概述了这一领域的最新成果, 重点介绍该策略作为关键步骤在天然产物及类天然产物化合物的全合成中的应用.     

Controlled Trifluoromethylation Reactions of Alkynes through Visible‐Light Photoredox Catalysis

The control of a reaction that can form multiple products is a highly attractive and challenging concept in synthetic chemistry. A set of valuable CF₃‐containing molecules, namely trifluoromethylated alkenyl iodides, alkenes, and alkynes, were selectively generated from alkynes and CF₃I by environmentally benign and efficient visible‐light photoredox catalysis. Subtle differences in the combination of catalyst, base, and solvent enabled the control of reactivity and selectivity for the reaction between an alkyne and CF₃I.     

Catalytic Carbocation Generation Enabled by the Mesolytic Cleavage of Alkoxyamine Radical Cations

A new catalytic method is described to access carbocation intermediates via the mesolytic cleavage of alkoxyamine radical cations. In this process, electron transfer between an excited state oxidant and a TEMPO‐derived alkoxyamine substrate gives rise to a radical cation with a remarkably weak C?O bond. Spontaneous scission results in the formation of the stable nitroxyl radical TEMPO^. as well as a reactive carbocation intermediate that can be intercepted by a wide range of nucleophiles. Notably, this process occurs under neutral conditions and at comparatively mild potentials, enabling catalytic cation generation in the presence of both acid sensitive and easily oxidized nucleophilic partners.     

Recent Advances in Visible-Light-Mediated Amide Synthesis

Visible-light photoredox catalysis has attracted tremendous interest within the synthetic community. As such, the activation mode potentially provides a more sustainable and efficient platform for the activation of organic molecules, enabling the invention of many controlled radical-involved reactions under mild conditions. In this context, amide synthesis via the strategy of photoredox catalysis has received growing interest due to the ubiquitous presence of this structural motif in numerous natural products, pharmaceuticals and functionalized materials. Employing this strategy, a wide variety of amides can be prepared effectively from halides, arenes and even alkanes under irradiation of visible light. These methods provide a robust alternative to well-established strategies for amide synthesis that involve condensation between a carboxylic acid and amine mediated by a stoichiometric activating agent. In this review, the representative progresses made on the synthesis of amides through visible light-mediated radical reactions are summarized.     

Radical Fluoroalkylation of Isocyanides with Fluorinated Sulfones by Visible‐Light Photoredox Catalysis

The radical fluoroalkylation of isocyanides with fluorinated sulfones is enabled by visible‐light photoredox catalysis. A wide range of readily available mono‐, di‐, and trifluoromethyl heteroaryl sulfones can thus be used as efficient radical fluoroalkylation reagents under mild conditions. This method not only describes a new synthetic application of fluorinated sulfones, but also provides a new route to fluoroalkyl radicals.     

A Rhodium Catalyst Superior to Iridium Congeners for Enantioselective Radical Amination Activated by Visible Light

A bis‐cyclometalated rhodium(III) complex catalyzes a visible‐light‐activated enantioselective α‐amination of 2‐acyl imidazoles with up to 99 % yield and 98 % ee. The rhodium catalyst is ascribed a dual function as a chiral Lewis acid and, simultaneously, as a light‐activated smart initiator of a radical‐chain process through intermediate aminyl radicals. Notably, related iridium‐based photoredox catalysts reported before were unsuccessful in this enantioselective radical C?N bond formation. The surprising preference for rhodium over iridium is attributed to much faster ligand‐exchange kinetics of the rhodium complexes involved in the catalytic cycle, which is crucial to keep pace with the highly reactive and thus short‐lived nitrogen‐centered radical intermediate.     

Recent Advances in Photo-mediated Radiofluorination

Carbon-fluorine bond formations have received a lot of attention because organofluorine compounds are widely used in pharmaceutical, agricultural, and materials science applications. In particular, the incorporation of fluorine-18, which is a commonly used radioisotope for radiopharmaceuticals for positron emission tomography (PET), a molecular imaging tool for the visualization of biochemical events, human metabolism processes, and the measurement and diagnosis of diseases in humans, plays a crucial role in clinical and preclinical studies. Several synthetic methodologies for carbon-fluorine-18 bond formation have been developed. However, conventional fluorination methods have some remaining drawbacks such as the high temperature and basic environment. Photo-induced catalysis is an emerging technique that allow chemists to achieve the synthesis of target molecular architectures under mild conditions. Moreover, several radiofluorination strategies have been developed via photocatalysis. In this review, we focused on describing recent advances in the field of light-mediated radiofluorination.     

Recent Advances in Visible-Light Photoredox Catalysis for the Thiol-Ene/Yne Reactions

Visible-light photoredox catalysis has been established as a popular and powerful tool for organic transformations owing to its inherent characterization of environmental friendliness and sustainability in the past decades. The thiol-ene/yne reactions, the direct hydrothiolation of alkenes/alkynes with thiols, represents one of the most efficient and atom-economic approaches for the carbon-sulfur bonds construction. In traditional methodologies, harsh conditions such as stoichiometric reagents or a specialized UV photo-apparatus were necessary suffering from various disadvantages. In particular, visible-light photoredox catalysis has also been demonstrated to be a greener and milder protocol for the thiol-ene/yne reactions in recent years. Additionally, unprecedented advancements have been achieved in this area during the past decade. In this review, we will summarize the recent advances in visible-light photoredox catalyzed thiol-ene/yne reactions from 2015 to 2021. Synthetic strategies, substrate scope, and proposed reaction pathways are mainly discussed.     

Expedient Trifluoromethylacylation of Styrenes Enabled by Photoredox Catalysis

Herein,we disclosed a photoredox enabled protocol for trifluoromethylacylation of styrenes through a radical-carboanion cascade and subsequent oxidation.With a broad range of aldehydes and inexpensive Langlois reagent as acyl and CF3 precursor,respectively,the alkene motif could be readily converted into β-trifluoromethyl ketones in moderate to good yields and with excellent regioselectivity.Besides CF3,di-,mono-and non-fluorinated C-radicals were revealed amenable in this reaction,providing good opportunity for the construction of structurally diverse ketones of interest in pharmaceutical research.Additionally,the utility of this protocol was further demonstrated by successful extension to trifluoromethylarylation and-alkylation by employing arylcyanide or acrylates in place of carbonyls.     

Anti-Markovnikov Hydroazidation of Alkenes by Visible-Light Photoredox Catalysis

The anti-Markovnikov hydroazidation of alkenes has been accomplished under visible-light irradiation by using [Ir(dF(CF₃)ppy)₂(dtbbpy)]PF₆ as the photocatalyst and trimethylsilyl azide as the azidating agent. The reactions were greatly facilitated by water, the beneficial effect of which can be attributed to its participation in the reaction as the hydrogen donor, as indicated by deuterium isotope experiments. The reactions proceed under solvent free conditions in the presence of water. 4-Dimethylaminopyridine also exhibited a beneficial effect on the reactions. The present method enabled hydroazidation of several types of unactivated alkenes with good yields and high regioselectivity.     

Regioselective Arene C−H Alkylation Enabled by Organic Photoredox Catalysis

Expanding the toolbox of C?H functionalization reactions applicable to the late‐stage modification of complex molecules is of interest in medicinal chemistry, wherein the preparation of structural variants of known pharmacophores is a key strategy for drug development. One manifold for the functionalization of aromatic molecules utilizes diazo compounds and a transition‐metal catalyst to generate a metallocarbene species, which is capable of direct insertion into an aromatic C?H bond. However, these high‐energy intermediates can often require directing groups or a large excess of substrate to achieve efficient and selective reactivity. Herein, we report that arene cation radicals generated by organic photoredox catalysis engage in formal C?H functionalization reactions with diazoacetate derivatives, furnishing sp²–sp³ coupled products with moderate‐to‐good regioselectivity. In contrast to previous methods utilizing metallocarbene intermediates, this transformation does not proceed via a carbene intermediate, nor does it require the presence of a transition‐metal catalyst.