Transition-Metal-Free Three-Component Radical 1,2-Amidoalkynylation of Unactivated Alkenes

A transition-metal-free radical 1,2-amidoalkynylation of unactivated alkenes is presented. α-Amido-oxy acids were used as amidyl radical precursors, which were oxidized by an organic photoredox catalyst (4CzlPN). The electrophilic N-radicals chemoselectively reacted with various aliphatic alkenes and the adduct radicals were then trapped by ethynylbenziodoxolone (EBX) reagents to eventually provide the amidoalkynylation products. These transformations, which were conducted under practical and mild conditions, showed high functional group tolerance and broad substrate scope. Mechanistic studies supported the radical nature of these cascades.     

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.     

Manganese-Catalyzed Hydroarylation of Unactivated Alkenes

Transition-metal-catalyzed hydroarylation of unactivated alkenes with strategic use of remote coordinating functional groups has received significant attention recently to address the issues of both low reactivity and poor selectivity. The bidentate 8-aminoquinoline amide group is the most successfully adopted in unactivated alkenes for Pd and Ni catalysis. We describe the first manganese-catalyzed hydroarylation of unactivated alkenes bearing diverse simple functionalities with arylboronic acids. A series of δ- and γ-arylated amides, ketones, pyridines, and amines was accessed with excellent regioselectivity and in high yields. Hydroalkenylation of unactivated alkenes was also shown to be applicable under this manganese-catalysis regime. The method features earth-abundant manganese catalysis, easily available substrates, broad functional-group tolerance, and excellent regioselective control.     

Regioselective,Asymmetric Formal Hydroamination of Unactivated Internal Alkenes

We report the regioselective and enantioselective formal hydroamination of unsymmetrical internal alkenes catalyzed by a copper catalyst ligated by DTBM‐SEGPHOS. The regioselectivity of the reaction is controlled by the electronic effects of ether, ester, and sulfonamide groups in the homoallylic position. The observed selectivity underscores the influence of inductive effects of remote substituents on the selectivity of catalytic processes occurring at hydrocarbyl groups, and the method provides direct access to various 1,3‐aminoalcohol derivatives with high enantioselectivity.     

A General Acid‐Mediated Hydroaminomethylation of Unactivated Alkenes and Alkynes

In comparison to the extensively studied metal‐catalyzed hydroamination reaction, hydroaminomethylation has received significantly less attention despite its considerable potential to streamline amine synthesis. State‐of‐the‐art protocols for hydroaminomethylation of alkenes rely largely on transition‐metal catalysis, enabling this transformation only under highly designed and controlled conditions. Here we report a broadly applicable, acid‐mediated approach to the hydroaminomethylation of unactivated alkenes and alkynes. This methodology employs cheap, readily available, and bench‐stable reactants and affords the desired amines with excellent functional group tolerance and impeccable regioselectivity. The broad scope of this transformation, as well as mechanistic investigations and in situ domino functionalization reactions are reported.     

可见光促进下氟烷基砜对芳基烯烃的自由基氟烷基化反应

自由基氟烷基化是向有机分子中引入氟烷基的一类非常重要的方法,也是目前有机化学研究的热点之一.近几年来,由于广泛的官能团兼容性和温和的反应条件等优点,可见光促进的氧化还原催化反应得到了长足的发展,已经成为化学键的构建和活化的有力工具.因此,光氧化还原催化的自由基氟烷基化反应,作为向有机化合物中引入氟烷基的有效途径,受到了广泛关注.本文报道了我们发展的氟烷基砜作为一类方便易得的新型氟烷基自由基前体,在可见光氧化还原催化下实现对烯烃的自由基氟烷基化反应.该反应可以高效地向芳基烯烃中引入三氟甲基、二氟甲基、1,1-二氟乙基、苯基二氟甲基等各种含氟烷基基团,并实现对芳基烯烃的双官能团化转化.     

Catalytic Enantioselective Functionalization of Unactivated Terminal Alkenes

Terminal alkenes are readily available functional groups which appear in α‐olefins produced by the chemical industry, and they appear in the products of many contemporary synthetic reactions. While the organic transformations that apply to alkenes are amongst the most studied reactions in all of chemical synthesis, the number of reactions that apply to nonactivated terminal alkenes in a catalytic enantioselective fashion is small in number. This Minireview highlights the cases where stereocontrol in catalytic reactions of 1‐alkenes is high enough to be useful for asymmetric synthesis.     

Manganese‐Catalyzed Hydroarylation of Unactivated Alkenes

Transition‐metal‐catalyzed hydroarylation of unactivated alkenes with strategic use of remote coordinating functional groups has received significant attention recently to address the issues of both low reactivity and poor selectivity. The bidentate 8‐aminoquinoline amide group is the most successfully adopted in unactivated alkenes for Pd and Ni catalysis. We describe the first manganese‐catalyzed hydroarylation of unactivated alkenes bearing diverse simple functionalities with arylboronic acids. A series of δ‐ and γ‐arylated amides, ketones, pyridines, and amines was accessed with excellent regioselectivity and in high yields. Hydroalkenylation of unactivated alkenes was also shown to be applicable under this manganese‐catalysis regime. The method features earth‐abundant manganese catalysis, easily available substrates, broad functional‐group tolerance, and excellent regioselective control.     

Photoredox‐Controlled β‐Regioselective Radical Hydroboration of Activated Alkenes with NHC‐Boranes

In this Communication, we report an unprecedented β‐regioselective radical inverse hydroboration (compared with ionic hydroboration) of α,β‐unsaturated amides with NHC‐BH₃ enabled by photoredox catalysis. Density functional theory (DFT) calculations show that the unique photoredox cycle is a key factor to control the β‐regioselective radical hydroboration, by lowering the energy barrier in comparison with other pathways. This protocol provides a general and convenient route to construct a wide range of structurally diverse β‐borylated amides in synthetically useful yields under mild conditions.     

Enantioselective Copper‐Catalyzed Carboetherification of Unactivated Alkenes

Chiral saturated oxygen heterocycles are important components of bioactive compounds. Cyclization of alcohols onto pendant alkenes is a direct route to their synthesis, but few catalytic enantioselective methods enabling cyclization onto unactivated alkenes exist. Herein reported is a highly efficient copper‐catalyzed cyclization of γ‐unsaturated pentenols which terminates in C? C bond formation, a net alkene carboetherification. Both intra‐ and intermolecular C? C bond formations are demonstrated, thus yielding functionalized chiral tetrahydrofurans as well as fused‐ring and bridged‐ring oxabicyclic products. Transition‐state calculations support a cis‐oxycupration stereochemistry‐determining step.     

Difunctionalization of Alkenes and Alkynes via Intermolecular Radical and Nucleophilic Additions

Popular and readily available alkenes and alkynes are good substrates for the preparation of functionalized molecules through radical and/or ionic addition reactions. Difunctionalization is a topic of current interest due to its high efficiency, substrate versatility, and operational simplicity. Presented in this article are radical addition followed by oxidation and nucleophilic addition reactions for difunctionalization of alkenes or alkynes. The difunctionalization could be accomplished through 1,2-addition (vicinal) and 1,n-addition (distal or remote) if H-atom or group-transfer is involved in the reaction process. A wide range of moieties, such as alkyl (R), perfluoroalkyl (R_f), aryl (Ar), hydroxy (OH), alkoxy (OR), acetatic (O₂CR), halogenic (X), amino (NR₂), azido (N₃), cyano (CN), as well as sulfur- and phosphorous-containing groups can be incorporated through the difunctionalization reactions. Radicals generated from peroxides or single electron transfer (SET) agents, under photoredox or electrochemical reactions are employed for the reactions.     

Highly Regioselective Copper-Catalyzed Transfer Hydrodeuteration of Unactivated Terminal Alkenes

Catalytic transfer hydrodeuteration of unactivated alkenes is challenging because of the requirement that chemically similar hydrogen and deuterium undergo selective insertion across a π-bond. We now report a highly regioselective catalytic transfer hydrodeuteration of unactivated terminal alkenes across a variety of heteroatom- or heterocycle-containing substrates. The base-metal-catalyzed reaction is also demonstrated on two complex natural products. Reaction studies indicate modular conditions that can also be extended to perform either an alkene transfer hydrogenation or transfer deuteration.     

Photocatalytic Aerobic Phosphatation of Alkenes

A catalytic regime for the direct phosphatation of simple, non‐polarized alkenes has been devised that is based on using ordinary, non‐activated phosphoric acid diesters as the phosphate source and O₂ as the terminal oxidant. The title method enables the direct and highly economic construction of a diverse range of allylic phosphate esters. From a conceptual viewpoint, the aerobic phosphatation is entirely complementary to traditional methods for phosphate ester formation, which predominantly rely on the use of prefunctionalized or preactivated reactants, such as alcohols and phosphoryl halides. The title transformation is enabled by the interplay of a photoredox and a selenium π‐acid catalyst and involves a sequence of single‐electron‐transfer processes.     

Copper Hydride Catalyzed Hydroamination of Alkenes and Alkynes

Over the past few years, CuH‐catalyzed hydroamination has been discovered and developed as a robust and conceptually novel approach for the synthesis of enantioenriched secondary and tertiary amines. The success in this area of research was made possible through the large body of precedent in copper(I) hydride catalysis and the well‐explored use of hydroxylamine esters as electrophilic amine sources in related copper‐catalyzed processes. This Minireview details the background, advances, and mechanistic investigations in CuH‐catalyzed hydroamination.     

Palladium(II)-Catalyzed Enantioselective Azidation of Unactivated Alkenes

The first Pd-catalyzed enantioselective azidation of unactivated alkenes has been established by using readily accessible 1-azido-1,2-benziodoxol-3(1H)-one (ABX) as an azidating reagent, which affords a wide variety of structurally diverse 3-N₃-substituted piperidines in good yields with excellent enantioselectivity. The reaction features good functional-group compatibility and mild reaction conditions. Notably, both an electrophilic azidating reagent and the sterically bulky chiral pyridinyl-oxazoline (Pyox) ligand are crucial to the successful reaction.     

Efficient Cu‐catalyzed Atom Transfer Radical Addition Reactions of Fluoroalkylsulfonyl Chlorides with Electron‐deficient Alkenes Induced by Visible Light

Fluoroalkylsulfonyl chlorides, R_fSO₂Cl, in which R_f=CF₃, C₄F₉, CF₂H, CH₂F, and CH₂CF₃, are used as a source of fluorinated radicals to add fluoroalkyl groups to electron‐deficient, unsaturated carbonyl compounds. Photochemical conditions, using Cu mediation, are used to produce the respective α‐chloro‐β‐fluoroalkylcarbonyl products in excellent yields through an atom transfer radical addition (ATRA) process. Facile nucleophilic replacement of the α‐chloro substituent is shown to lead to further diverse functionalization of the products.     

二氧化碳参与的自由基型烯烃双官能团化反应

二氧化碳(CO₂)是一种理想的C1合成子. 利用其参与化学转化合成羧酸和含羰基杂环等具有高附加值的产品, 具有重要意义. 另一方面, 烯烃的双官能团化反应是有机合成化学中的一类重要反应, 可以将简单易得的烯烃快速高效地转化为结构多样性的重要化合物. 然而, 由于CO₂反应活性较低, 而且烯烃官能团化反应的选择性难以控制, CO₂参与的烯烃双官能团化反应具有较高的挑战性. 近年来, 自由基化学的蓬勃发展为该类反应的开发提供了新的策略, 实现了一些重要转化反应. 基于此, 从CO₂参与烯烃的氧-烷基化反应、碳羧基化反应、硅羧基化反应、硫羧基化反应以及双羧基化反应等反应入手, 全面总结和深入分析了最近几年CO₂参与的自由基型烯烃双官能团化反应进展; 在介绍上述进展的同时, 重点阐述了其可能经历的四类自由基化学历程. 最后对该领域的未来发展方向进行了展望, 希望为该领域的进一步发展提供一些思路.