Search

Due to the innate highly reactive properties and short life‐time, organic free radicals can often serve as promoters or intermediates to engage in various radical transformations, which are often otherwise difficult to access by ionic pathway‐based mechanisms. With the evolvement of radical chemistry, chiral radical catalyzed‐transformations have recently emerged as an attractive and robust platform for synthesis of chiral molecules of interest. Herein, we highlight several creative and strategic advances in chiral radical catalyst design, cyclization reaction achievements, and future challenges. Key Scientists: In the 1980s, some pioneering studies by Feldman and Oshima revealed that the thiyl radical could catalyze cyclization of vinylcyclopropane with alkenes, providing access to racemic cyclopentanes. In 1996, Brian P. Roberts reported an interesting enantioselective hydrosilylation of prochiral alkenes by using thioglucose‐derived chiral thiyl radical catalysts. Since then, chiral radical catalysis has become an emerging and promising catalytic strategy in organic synthesis. However, this field has not been extensively explored further until the Maruoka group in 2014 achieved the asymmetric C—C bond formation by employing a newly designed indanol core‐based chiral thiyl radical catalyst. In this protocol, an enantioselective radical cyclization of vinylcyclopropanes with electron‐rich alkenes was developed. In 2020, Chen and Xiao disclosed a nitrogen radical‐catalyzed version of this reaction. Later, this strategy was further expanded to metalloradical catalyzed asymmetric radical cascade cyclization reactions by Zhang in 2021. Later on, Wang, Fu and Zhang et al. described a novel class of boryl radical‐catalyzed asymmetric radical cycloisomerization reactions, further showcasing enormous synthetic potential of chiral radical catalysis. This Emerging Topic has focused on asymmetric radical cyclization reactions involving diverse chiral radical catalysts. [ABSTRACT FROM AUTHOR]

Radical‐involved multicomponent difunctionalization of 1,3‐dienes has recently emerged as a promising strategy for rapid synthesis of valuable allylic compounds in one‐pot operation. However, the expansion of radical scope and enantiocontrol remain two major challenges. Herein, we describe an unprecedented photoinduced copper‐catalyzed highly enantioselective three‐component radical 1,2‐azidooxygenation of 1,3‐dienes with readily available azidobenziodazolone reagent and carboxylic acids. This mild protocol exhibits a broad substrate scope, high functional group tolerance, and exceptional control over chemo‐, regio‐ and enantioselectivity, providing practical access to diverse valuable azidated chiral allylic esters. Mechanistic studies imply that the chiral copper complex is implicated as a bifunctional catalyst in both the photoredox catalyzed azidyl radical generation and enantioselective radical C−O cross‐coupling. [ABSTRACT FROM AUTHOR]

The C(sp3)–N bond is ubiquitous in natural products, pharmaceuticals, biologically active molecules and functional materials. Consequently, the development of practical and efficient methods for C(sp3)–N bond formation has attracted more and more attention. Compared to the conventional ionic pathway-based thermal methods, photochemical processes that proceed through radical mechanisms by merging photoredox and transition-metal catalyses have emerged as powerful and alternative tools for C(sp3)–N bond formation. In this review, recent advances in the burgeoning field of C(sp3)–N bond formation via metallaphotoredox catalysis have been highlighted. The contents of this review are categorized according to the transition metals used (copper, nickel, cobalt, palladium, and iron) together with photocatalysis. Emphasis is placed on methodology achievements and mechanistic insight, aiming to inspire chemists to invent more efficient radical-involved C(sp3)–N bond-forming reactions. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Catalytic four‐component radical carbonylation of unactivated alkenes has recently been recognized as a robust protocol for rapid construction of various structurally diverse carbonyl compounds. Given the significance of fluorine‐containing groups, this reaction class has been extensively applied to assembly of a variety of perfluoroalkyl carboxylic acid derivatives by transition metal catalysis. Herein, we report a visible‐light‐driven radical relay 1,2‐perfluoroalkylation aminocarbonylation of unactivated alkenes using CO gas as carbonyl source and 4CzIPN as organic photocatalyst. A wide range of alkenes and amines were well tolerated, providing the valuable β‐perfluoroalkylated amides with generally good yields and high chemoselectivity. [ABSTRACT FROM AUTHOR]

Transition‐metal‐catalyzed radical relay cross‐coupling reactions of 1,3‐dienes have recently emerged as one of the most powerful methods for construction of structurally diverse allylic compound in a single chemical step. However, there still has been limited success in expanding substrate scope of radical precursors and coupling partners, as well as exploring catalytic asymmetric variants. Herein, we report a copper‐catalyzed enantioselective three‐component 1,2‐alkylesterification of 1,3‐dienes using cycloalkyl hydroperoxides as the carbonyl‐containing alkyl radical sources and carboxylic acids as O‐nucleophiles under mild and redox‐neutral conditions. This protocol features broad substrate scope and good functional group tolerance with respect to each component, providing practical access to a variety of distally keto‐functionalized allylic esters with high enantioselectivity. Mechanistic studies suggest the involvement of a sequential radical relay and C−O cross‐coupling in this three‐component radical reaction. [ABSTRACT FROM AUTHOR]

Radical single carbonylation reactions with CO constitute a direct and robust strategy toward various carbonyl compounds from readily available chemicals, and have been extensively studied over the past decades. However, realizing highly selective catalytic systems for controlled radical double carbonylation reactions has remained a substantial challenge, particularly for the more advanced multicomponent variants, despite their great potential value. Herein, we report a visible‐light‐driven radical relay five‐component radical double aminocarbonylation reaction of unactivated alkenes using CO under metal‐free conditions. This protocol provides direct access to valuable γ‐trifluoromethyl α‐ketoamides with good yields and high chemoselectivity. Crucial was the identification of distinct dual roles of amine coupling partners, sequentially acting as electron donors for the formation of photoactive electron donor‐acceptor (EDA) complexes with radical precursors and then as a CO acceptor via nitrogen radical cations to form carbamoyl radicals. Cross‐coupling of carbamoyl radicals with the acyl radicals that are formed in an alkene‐based relay process affords double aminocarbonylation products. [ABSTRACT FROM AUTHOR]

The intermolecular three-component alkene vicinal dicarbofunctionalization (DCF) reaction allows installation of two different carbon fragments. Despite extensive investigation into its ionic chemistry, the enantioseletive radical-mediated versions of DCF reactions remain largely unexplored. Herein, we report an intermolecular, enantioselective three-component radical vicinal dicarbofunctionalization reaction of olefins enabled by merger of radical addition and cross-coupling using photoredox and copper dual catalysis. Key to the success of this protocol relies on chemoselective addition of acyl and cyanoalkyl radicals, generated in situ from the redox-active oxime esters by a photocatalytic N-centered iminyl radical-triggered C-C bond cleavage event, onto the alkenes to form new carbon radicals. Single electron metalation of such newly formed carbon radicals to TMSCN-derived L1Cu(II)(CN)2 complex leads to asymmetric cross-coupling. This three-component process proceeds under mild conditions, and tolerates a diverse range of functionalities and synthetic handles, leading to valuable optically active β–cyano ketones and alkyldinitriles, respectively, in a highly enantioselective manner (>60 examples, up to 97% ee). Vicinal dicarbofunctionalization (DCF) reactions of alkenes have been extensively explored in ionic chemistry but the enantioselective radical mediated version of DCF remains largely unexplored. Here, the authors demonstrate a radical vicinal DCF reaction of olefins by merging of radical addition and cross-coupling using photoredox and copper dual catalysis. [ABSTRACT FROM AUTHOR]

Abstract: The control of selectivity in the reactions of the highly reactive open‐shell carbon radicals is an attractive but often challenging task. Building on the strategy of photoinduced iminyl radical‐mediated C−C bond cleavage, we have developed photocatalytic neophyl rearrangement and reduction of distal carbon radicals under visible light irradiation of O‐acyl oximes. This mild protocol tolerates a wide range of readily available O‐acyl oximes, enabling facile synthesis of diversely substituted α,β‐unsaturated nitriles and β‐functionalized saturated nitriles in a highly selective manner. [ABSTRACT FROM AUTHOR]

Abstract: A room‐temperature, visible‐light‐driven N‐centered iminyl radical‐mediated and redox‐neutral C−C single bond cleavage/radical addition cascade reaction of oxime esters and unsaturated systems has been accomplished. The strategy tolerates a wide range of O‐acyl oximes and unsaturated systems, such as alkenes, silyl enol ethers, alkynes, and isonitrile, enabling highly selective formation of various chemical bonds. This method thus provides an efficient approach to various diversely substituted cyano‐containing alkenes, ketones, carbocycles, and heterocycles. [ABSTRACT FROM AUTHOR]

An efficient visible light photocatalytic and external oxidant-free N-radical 5-exo cyclization/addition/aromatization cascade of β,γ-unsaturated hydrazones is described, which provides a practical route to various biologically interesting dihydropyrazole-fused benzosultams in satisfactory yields. [ABSTRACT FROM AUTHOR]

A cooperative TEMPO and photoredox catalytic strategy was applied for the first time to the direct conversion of N−H and O−H bonds into N- and O-centred radicals, enabling a general and selective oxidative radical oxyamination and dioxygenation of various β,γ-unsaturated hydrazones and oximes. In the reaction, O2 was employed not only as a terminal oxidant but also as the oxygen source. This protocol provided efficient access to the synthesis of various synthetically and biologically important pyrazoline, pyridazine and isoxazoline derivatives under metal-free and mild reaction conditions. Mechanistic studies revealed that the cooperative organophotocatalytic system functions through two single-electron-transfer (SET) processes. [ABSTRACT FROM AUTHOR]

A visible-light photocatalytic generation of N-centered hydrazonyl radicals has been accomplished for the first time. This approach allows efficient intramolecular addition of hydrazonyl radical to terminal alkenes, thus providing hydroamination and oxyamination products in good yields. Importantly, the protocol involves deprotonation of an NH bond and photocatalytic oxidation to an N-centered radical, thus obviating the need to prepare photolabile amine precursors or the stoichiometric use of oxidizing reagents. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Catalytic four‐component radical carbonylation of unactivated alkenes has recently been recognized as a robust protocol for rapid construction of various structurally diverse carbonyl compounds. Given the significance of fluorine‐containing groups, this reaction class has been extensively applied to assembly of a variety of perfluoroalkyl carboxylic acid derivatives by transition metal catalysis. Herein, we report a visible‐light‐driven radical relay 1,2‐perfluoroalkylation aminocarbonylation of unactivated alkenes using CO gas as carbonyl source and 4CzIPN as organic photocatalyst. A wide range of alkenes and amines were well tolerated, providing the valuable β‐perfluoroalkylated amides with generally good yields and high chemoselectivity. [ABSTRACT FROM AUTHOR]

Review: 50 refs. [ABSTRACT FROM AUTHOR]