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48 pages, 7355 KB

Open AccessReview

The Merger of Transition Metal and Photocatalysis: Recent Advances and Prospects in Asymmetric Intermolecular 1,2-Difunctionalization of Alkenes

by Chenkai Zhai, Quan Liu, Shengyong Zhang and Wei He

Catalysts 2026, 16(3), 284; https://doi.org/10.3390/catal16030284 - 23 Mar 2026

Viewed by 208

Abstract

Unsaturated carbon–carbon bonds are fundamental building blocks in organic compounds. The difunctionalization of olefins allows for the rapid construction of drugs and complex molecular architectures. This transformation, which simultaneously installs two distinct functional groups across a carbon–carbon double bond, has therefore emerged as [...] Read more.

Unsaturated carbon–carbon bonds are fundamental building blocks in organic compounds. The difunctionalization of olefins allows for the rapid construction of drugs and complex molecular architectures. This transformation, which simultaneously installs two distinct functional groups across a carbon–carbon double bond, has therefore emerged as prominent research frontier in organic chemistry. In recent years, the synergy between photoredox and transition metal catalysis has emerged as a powerful and sustainable platform for constructing C-X bonds. This review covers advances since 2018 in the asymmetric difunctionalization of olefins enabled by synergistic visible light photoredox and transition metal catalysis, encompassing the construction of both carbon–carbon and carbon–heteroatom bonds. It systematically summarizes the reaction conditions, substrate scope, mechanisms, and merits and limitations of these catalytic systems, aiming to provide a useful reference for researchers in this field. Full article

(This article belongs to the Section Catalysis for Pharmaceuticals)

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36 pages, 8069 KB

Open AccessReview

Hydrazine Derivatives as C-Centered Radical Precursors for C-C Bond Formation Reactions

by Elena R. Lopat’eva, Igor B. Krylov and Alexander O. Terent’ev

Molecules 2026, 31(1), 67; https://doi.org/10.3390/molecules31010067 - 24 Dec 2025

Viewed by 851

Abstract

Organic monosubstituted hydrazine derivatives (Ar-NHNH₂, RC(O)-NHNH₂, Alkyl-NHNH₂) are synthetically available, atom-efficient and stable sources of C-centered radicals upon oxidation with extrusion of the energetically favorable N₂ molecule. This review summarizes the synthetic application of monosubstituted hydrazine [...] Read more.

Organic monosubstituted hydrazine derivatives (Ar-NHNH₂, RC(O)-NHNH₂, Alkyl-NHNH₂) are synthetically available, atom-efficient and stable sources of C-centered radicals upon oxidation with extrusion of the energetically favorable N₂ molecule. This review summarizes the synthetic application of monosubstituted hydrazine derivatives (arylhydrazines, carbazates, acylhydrazides, hydrazine carboxamides and alkylhydrazines) in free-radical C-C bond-forming reactions. The main application directions in this field are (a) alkene difunctionalization, (b) cascade cyclization initiated by the addition of hydrazine-derived C-centered radicals to acrylamides and isonitriles, and (c) CH-functionalization of (hetero)arenes via C-centered radical addition followed by oxidative dehydrogenation (re-aromatization). Full article

(This article belongs to the Section Organic Chemistry)

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31 pages, 8823 KB

Open AccessReview

Recent Advances in Carbon-Centered Radical-Initiated Olefin Transformation Chemistry

by Huazhan Ren, Ming Hu and Jinheng Li

Catalysts 2025, 15(5), 461; https://doi.org/10.3390/catal15050461 - 8 May 2025

Cited by 1 | Viewed by 3366

Abstract

In recent years, carbon-centered radical-initiated olefin transformation reactions, including alkene Heck-type alkylation, alkene hydroalkylation, and alkene difunctionalization reactions, have attracted increasing attention and been extensively developed. This review summarizes the recent advances in carbon-centered radical-initiated olefin transformation chemistry, such as radical-mediated alkene Heck-type [...] Read more.

In recent years, carbon-centered radical-initiated olefin transformation reactions, including alkene Heck-type alkylation, alkene hydroalkylation, and alkene difunctionalization reactions, have attracted increasing attention and been extensively developed. This review summarizes the recent advances in carbon-centered radical-initiated olefin transformation chemistry, such as radical-mediated alkene Heck-type alkylation, alkene hydroalkylation, and radical-mediated alkene difunctionalization reactions. This area of research is divided into several sections based on the types of olefin transformation reactions and the divergent formation processes of the carbon-centered radicals. Drawing extensively on our group’s investigations, we show that efficient olefin transformation strategies have gained significant traction in synthetic chemistry due to their ability to rapidly install functional groups and enhance molecular complexity. Full article

(This article belongs to the Special Issue Recent Catalysts for Organic Synthesis)

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8 pages, 1753 KB

Open AccessCommunication

Copper(I)-Photocatalyzed Addition of Trichloromethanesulfenyl Chloride to Olefinic Compounds

by Nejc Petek, Tilen Zorko, Martin Škrinjar, Uroš Grošelj, Jurij Svete, Drago Kočar and Bogdan Štefane

Molecules 2025, 30(3), 661; https://doi.org/10.3390/molecules30030661 - 2 Feb 2025

Viewed by 1536

Abstract

Atom transfer radical addition (ATRA) reactions are essential transformations in organic synthetic chemistry that enable the atom-economic difunctionalization of abundant olefin feedstocks. In this way, a rich chemical space can be opened up by well-planned combinations of simple starting materials. To build an [...] Read more.

Atom transfer radical addition (ATRA) reactions are essential transformations in organic synthetic chemistry that enable the atom-economic difunctionalization of abundant olefin feedstocks. In this way, a rich chemical space can be opened up by well-planned combinations of simple starting materials. To build an efficient photocatalytic transformation, the reactivity of trichloromethanesulfenyl chloride toward alkenes and alkynes was investigated under photocatalytic Cu(I) reaction conditions. In this study, we found that trichloromethanesulfenyl chloride can be added to a series of olefins (such as styrenes and electron-rich and -poor olefins) in the presence of 1 mol% [Cu(dmp)₂]BF₄ photocatalyst and blue LED irradiation, producing α-chloro trichloromethylthioethers in good yields. Experimental and theoretical (DFT) mechanistic studies are consistent with the proposed radical chain mechanism of transformation. This study may serve as a valuable reference for the development of new coupling reactions that are economical and highly efficient processes. Full article

(This article belongs to the Section Organic Chemistry)

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38 pages, 11490 KB

Open AccessFeature PaperReview

Radical-Mediated Trifunctionalization Reactions

by Qiang Zhang, Xiaoming Ma, Sanjun Zhi and Wei Zhang

Molecules 2024, 29(15), 3620; https://doi.org/10.3390/molecules29153620 - 31 Jul 2024

Cited by 7 | Viewed by 4089

Abstract

Synthetic radicals have intrinsic power for cascading and multifunctional reactions to construct diverse molecular scaffolds. In the previous review series, we covered 1,2-difunctionalizations, remote 1,3-, 1,4-, 1,5-, 1,6-, and 1,7-difunctionalizations, addition followed by cyclization reactions, and cycloaddition-initiated difunctionalizations. Presented in this paper are [...] Read more.

Synthetic radicals have intrinsic power for cascading and multifunctional reactions to construct diverse molecular scaffolds. In the previous review series, we covered 1,2-difunctionalizations, remote 1,3-, 1,4-, 1,5-, 1,6-, and 1,7-difunctionalizations, addition followed by cyclization reactions, and cycloaddition-initiated difunctionalizations. Presented in this paper are radical addition-initiated trifunctionalization reactions of alkenes, alkynes, and their derivatives. After the initial radical addition, there are different pathways, such as group or hydrogen atom transfer, cyclization, and radical coupling, to complete the second and third functionalizations. Full article

(This article belongs to the Special Issue Featured Reviews in Organic Chemistry 2024)

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57 pages, 18372 KB

Open AccessReview

Radical Cyclization-Initiated Difunctionalization Reactions of Alkenes and Alkynes

by Sanjun Zhi, Xiaoming Ma and Wei Zhang

Molecules 2024, 29(11), 2559; https://doi.org/10.3390/molecules29112559 - 29 May 2024

Cited by 8 | Viewed by 5608

Abstract

Radical reactions are powerful in the synthesis of diverse molecular scaffolds bearing functional groups. In previous review articles, we have presented 1,2-difunctionalizations, remote 1,3-, 1,4-, 1,5-, 1,6- and 1,7-difunctionalizations, and addition followed by cyclization reactions. Presented in this paper is radical cyclization followed [...] Read more.

Radical reactions are powerful in the synthesis of diverse molecular scaffolds bearing functional groups. In previous review articles, we have presented 1,2-difunctionalizations, remote 1,3-, 1,4-, 1,5-, 1,6- and 1,7-difunctionalizations, and addition followed by cyclization reactions. Presented in this paper is radical cyclization followed by the second functionalization reaction. The second functionalization could be realized by atom transfer reactions, radical or transition metal-assisted coupling reactions, and reactions with neutral molecules, cationic and anionic species. Full article

(This article belongs to the Special Issue Cyclization Reactions in Organic Synthesis: Recent Developments)

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19 pages, 1615 KB

Open AccessArticle

Visible Light-Mediated Monofluoromethylation/Acylation of Olefins by Dual Organo-Catalysis

by Jiuli Xia, Yunliang Guo, Zhiguang Lv, Jiaqiong Sun, Guangfan Zheng and Qian Zhang

Molecules 2024, 29(4), 790; https://doi.org/10.3390/molecules29040790 - 8 Feb 2024

Cited by 7 | Viewed by 2803

Abstract

Monofluoromethyl (CH₂F) motifs exhibit unique bioactivities and are considered privileged units in drug discovery. The radical monofluoromethylative difunctionalization of alkenes stands out as an appealing approach to access CH₂F-containing compounds. However, this strategy remains largely underdeveloped, particularly under metal-free [...] Read more.

Monofluoromethyl (CH₂F) motifs exhibit unique bioactivities and are considered privileged units in drug discovery. The radical monofluoromethylative difunctionalization of alkenes stands out as an appealing approach to access CH₂F-containing compounds. However, this strategy remains largely underdeveloped, particularly under metal-free conditions. In this study, we report on visible light-mediated three-component monofluoromethylation/acylation of styrene derivatives employing NHC and organic photocatalyst dual catalysis. A diverse array of α-aryl-β-monofluoromethyl ketones was successfully synthesized with excellent functional group tolerance and selectivity. The mild and metal-free CH₂F radical generation strategy from NaSO₂CFH₂ holds potential for further applications in fluoroalkyl radical chemistry. Full article

(This article belongs to the Special Issue Green Catalysis in Organic Synthesis)

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9 pages, 1237 KB

Open AccessCommunication

Photoinduced Synthesis of Sulfonyl-Containing Phosphorothioates via a Three-Component Reaction

by Xianda Wu, Minghong Chen, Shuiyun Zheng, Jie Wu, Gang Liu and Fu-Sheng He

Molecules 2023, 28(23), 7869; https://doi.org/10.3390/molecules28237869 - 30 Nov 2023

Viewed by 2584

Abstract

Both sulfonyl and phosphorothioate are important privileged structural motifs which are widely presented in pharmaceuticals and agrochemicals. Herein, we describe an efficient approach to synthesizing sulfonyl-containing phosphorothioates by merging photoredox and copper catalysis at room temperature. This protocol is compatible with a wide [...] Read more.

Both sulfonyl and phosphorothioate are important privileged structural motifs which are widely presented in pharmaceuticals and agrochemicals. Herein, we describe an efficient approach to synthesizing sulfonyl-containing phosphorothioates by merging photoredox and copper catalysis at room temperature. This protocol is compatible with a wide range of substrates and can be applied to the late-stage modification of complex molecules. Control experiments are conducted to demonstrate the generation of the sulfonyl radical in the transformation. Full article

(This article belongs to the Section Organic Chemistry)

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50 pages, 11448 KB

Open AccessReview

Recent Advances in Photoredox-Catalyzed Difunctionalization of Alkenes

by Yong Liu, Huan Liu, Xiao Liu and Zhangpei Chen

Catalysts 2023, 13(7), 1056; https://doi.org/10.3390/catal13071056 - 30 Jun 2023

Cited by 53 | Viewed by 12567

Abstract

Alkenes and their related analogs are ideal starting materials for organic synthesis, and the selective difunctionalization of alkenes, which allows the simultaneous introduction of two neighboring bonds, has gained considerable attention in recent years. In particular, the photoredox-catalyzed difunctionalization of alkenes has also [...] Read more.

Alkenes and their related analogs are ideal starting materials for organic synthesis, and the selective difunctionalization of alkenes, which allows the simultaneous introduction of two neighboring bonds, has gained considerable attention in recent years. In particular, the photoredox-catalyzed difunctionalization of alkenes has also been accomplished, which has been regarded as an increasingly powerful tool for the synthesis of miscellaneous interesting molecular scaffolds in an environmentally benign and economical manner. Several exquisite strategies have been developed to facilitate this transformation, such as photosensitizer-catalyzed redox reactions, electron donor-acceptor (EDA) complexes-mediated photoreactions, and atom transfer radical addition (ATRA) reactions. This literature review briefly describes the most recent key progress on the photoredox-catalyzed 1,2-difunctionalization of various structurally diverse alkenes, including 1,2-dicarbofunctionalization, 1,2-carboheterofunctionalization, and 1,2-diheterofunctionalization, with a special emphasis on the mechanistic details. Full article

(This article belongs to the Special Issue Application of Photocatalysts in Organic Synthesis)

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18 pages, 3287 KB

Open AccessFeature PaperReview

Copper-Catalyzed Diastereo- and Enantioselective Borylative Cyclization

by Srimanta Manna

Catalysts 2022, 12(7), 734; https://doi.org/10.3390/catal12070734 - 2 Jul 2022

Cited by 9 | Viewed by 4049

Abstract

Copper-catalyzed enantioselective borylative cyclization with various electrophiles via difunctionalization of unsaturated hydrocarbons is a powerful tool for the generation of interesting boron-containing carbocycles and heterocycles processes involving a chiral organocopper intermediate. Alkenes, allenes, and alkynes are versatile and easily accessible substrates that can [...] Read more.

Copper-catalyzed enantioselective borylative cyclization with various electrophiles via difunctionalization of unsaturated hydrocarbons is a powerful tool for the generation of interesting boron-containing carbocycles and heterocycles processes involving a chiral organocopper intermediate. Alkenes, allenes, and alkynes are versatile and easily accessible substrates that can be subjected to a wide range of reactions to produce densely functionalized, enantioenriched products. In this chapter, I discuss copper-catalyzed alkenes, allenes, and alkynes borofunctionalization and enantioselective cyclization via chiral organocopper intermediate. Copper-catalyzed enantioselective borylative cyclization and regiodivergent functionalization of alkenes, allenes, and alkynes, as well as the current mechanistic understanding of such processes, are given special attention in this review. Full article

(This article belongs to the Special Issue Recent Advances in Asymmetric Catalysis)

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13 pages, 2274 KB

Open AccessArticle

Photoinitiated Multicomponent Anti-Markovnikov Alkoxylation over Graphene Oxide

by Liang Nie, Xiangjun Peng, Haiping He, Jian Hu, Zhiyang Yao, Linyi Zhou, Ming Yang, Fan Li, Qing Huang and Liangxian Liu

Molecules 2022, 27(2), 475; https://doi.org/10.3390/molecules27020475 - 12 Jan 2022

Cited by 3 | Viewed by 2432

Abstract

The development of graphene oxide–based heterogeneous materials with an economical and environmentally–friendly manner has the potential to facilitate many important organic transformations but proves to have few relevant reported reactions. Herein, we explore the synergistic role of catalytic systems driven by graphene oxide [...] Read more.

The development of graphene oxide–based heterogeneous materials with an economical and environmentally–friendly manner has the potential to facilitate many important organic transformations but proves to have few relevant reported reactions. Herein, we explore the synergistic role of catalytic systems driven by graphene oxide and visible light that form nucleophilic alkoxyl radical intermediates, which enable an anti-Markovnikov addition exclusively to the terminal alkenes, and then the produced benzyl radicals are subsequently added with N–methylquinoxalones. This photoinduced cascade radical difunctionalization of olefins offers a concise and applicable protocol for constructing alkoxyl–substituted N–methylquinoxalones. Full article

(This article belongs to the Special Issue New Approach in Multicomponent Reactions)

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54 pages, 24757 KB

Open AccessReview

Recent Advances on the Halo- and Cyano-Trifluoromethylation of Alkenes and Alkynes

by Bo Fu, Jorge Escorihuela, Jianlin Han, Santos Fustero, Pablo Barrio, Mikiko Sodeoka, Shintaro Kawamura, Alexander Sorochinsky and Vadim A. Soloshonok

Molecules 2021, 26(23), 7221; https://doi.org/10.3390/molecules26237221 - 28 Nov 2021

Cited by 28 | Viewed by 7452

Abstract

Incorporation of fluorine into organic molecules is a well-established strategy in the design of advanced materials, agrochemicals, and pharmaceuticals. Among numerous modern synthetic approaches, functionalization of unsaturated bonds with simultaneous addition of trifluoromethyl group along with other substituents is currently one of the [...] Read more.

Incorporation of fluorine into organic molecules is a well-established strategy in the design of advanced materials, agrochemicals, and pharmaceuticals. Among numerous modern synthetic approaches, functionalization of unsaturated bonds with simultaneous addition of trifluoromethyl group along with other substituents is currently one of the most attractive methods undergoing wide-ranging development. In this review article, we discuss the most significant contributions made in this area during the last decade (2012−2021). The reactions reviewed in this work include chloro-, bromo-, iodo-, fluoro- and cyano-trifluoromethylation of alkenes and alkynes. Full article

(This article belongs to the Special Issue Featured Reviews in Organic Chemistry)

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31 pages, 9594 KB

Open AccessFeature PaperReview

Difunctionalization of Alkenes and Alkynes via Intermolecular Radical and Nucleophilic Additions

by Hongjun Yao, Wenfei Hu and Wei Zhang

Molecules 2021, 26(1), 105; https://doi.org/10.3390/molecules26010105 - 28 Dec 2020

Cited by 116 | Viewed by 11735

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Organic Synthesis)

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23 pages, 11957 KB

Open AccessReview

Alkene Difunctionalization Using Hypervalent Iodine Reagents: Progress and Developments in the Past Ten Years

by Ji Hoon Lee, Sungwook Choi and Ki Bum Hong

Molecules 2019, 24(14), 2634; https://doi.org/10.3390/molecules24142634 - 19 Jul 2019

Cited by 76 | Viewed by 10799

Abstract

Hypervalent iodine reagents are of considerable relevance in organic chemistry as they can provide a complementary reaction strategy to the use of traditional transition metal chemistry. Over the past two decades, there have been an increasing number of applications including stoichiometric oxidation and [...] Read more.

Hypervalent iodine reagents are of considerable relevance in organic chemistry as they can provide a complementary reaction strategy to the use of traditional transition metal chemistry. Over the past two decades, there have been an increasing number of applications including stoichiometric oxidation and catalytic asymmetric variations. This review outlines the main advances in the past 10 years in regard to alkene heterofunctionalization chemistry using achiral and chiral hypervalent iodine reagents and catalysts. Full article

(This article belongs to the Special Issue Advances in the Chemistry of Hypervalent Iodine Compounds)

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