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Comprehensive Summary: A visible light photocatalytic [3+2] cycloaddition of alkynes with readily accessible organic iodides as the C3 synthon is developed herein. By merging halogen atom transfer (XAT) and hydrogen atom transfer (HAT), alkyl/aryl iodides serve as a formal diradical precursor and add across C‐C triple bonds to deliver a number of functionalized cyclopentanes in moderate to high yields with exceptional regio‐ and diastereoselectivity. A reductive radical‐polar crossover mechanism, involving the cascade XAT, radical addition, 1,5‐HAT, polar effect‐promoted 5‐endo annulation, single electron transfer (SET) reduction, and protonation, may account for this unprecedented dehalogenative [3+2] cycloaddition. This work not only expands the repertoire of the traditional RATC methodology, but also provides a robust platform for the expedient assembly of cyclopentanes, a valuable structural motif in the realms of medicinal chemistry and material sciences. [ABSTRACT FROM AUTHOR]

5-endo-trig radical cyclization has long been recognized as one of the most straightforward ways for the construction of densely functionalized five-membered rings. Nevertheless, according to Baldwin's rules, the 5-endo-trig radical cyclization is kinetically disfavored due to stereoelectronic effects and thus usually proceeds via a slow rate, which renders its application a challenging task. In recent years, with the emergence of efficient radical generation methods and effective cyclization strategies, 5-endo-trig radical cyclization has been successfully accelerated to a synthetically useful rate and has been utilized in the access of diverse five-membered carbo- and heterocyclic compounds. This review comprehensively summarizes the methodologies involving the 5-endo-trig radical cyclization process, with particular emphasis on the elucidation of the promoting strategies, which include the polar effect, geometrical constraints, spin delocalization effect, and persistent radical effect. Each of these strategies is discussed in detail, with illustrative examples from recent literature studies to highlight their practical applications and effectiveness. It is anticipated that the in-depth understanding of the 5-endo-trig radical cyclization provided by this review would inspire further innovation of this privileged reaction mode and expand its applications. Moreover, the potent ring-closure-promoting strategies revealed herein would also contribute to achieving other challenges of cyclizations with particular significance for organic synthesis. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Compared to well‐established 1,5‐HAT of N‐centered radicals, the synthetic applications of 1,2‐HAT process were scarce due to the high barrier and constrained three‐membered transition state. Here, we have developed a novel C(sp3)‐H gem‐difluoroallylation via a base assisted formal 1,2‐HAT of amidyl radicals with the reductive quenching cycle of photocatalyst. This transformation enables the efficient formation of α‐aminoalkyl radicals via 1,2‐HAT and showcases good functional group tolerance. Our preliminary mechanistic experiments, along with Density Functional Theory (DFT) calculations demonstrate the feasibility of 1,2‐HAT of amidyl radicals, especially when assisted by a base. Furthermore, our method also succeeds in the Giese addition of electron‐deficient alkenes as well as styrene. [ABSTRACT FROM AUTHOR]

Cyclobutanes are popular structural units in bioactive compounds and versatile intermediates in synthetic chemistry, but their synthesis is challenging owing to high ring strain. In this study, a novel method for highly regio‐ and diastereoselective synthesis of fluoroalkylcyclobutanes bearing vicinal quaternary and tertiary stereocenters is realized by a photocatalytic 4‐exo‐trig cyclization cascade of thioalkynes or trifluoromethylalkenes. Density functional theory calculations reveal that a unique fluorine effect, arising from hyperconjugative π→σ*C‐F interactions, accounts for the regio‐reversed radical addition at the sterically hindered alkene carbon, which facilitates an unprecedented 4‐exo‐trig ring closure. This chemistry enables the direct and controllable construction of medicinally valuable quaternary‐carbon‐containing cyclobutanes from readily available raw materials, nicely complementing the existing methods. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: α‐Fluoroalkyl (Rf) alcohols are privileged motifs in drugs and pharmaceutically active compounds. As such, it is highly desirable to develop efficient methods for assembling these scaffolds. Herein, a visible‐light‐induced cascade radical cyclization of alkenyl fluoroalkyl ketones is developed, producing a variety of decorate α‐Rf cycloalkanols in promising yields with up to >20 : 1 dr selectivity. A radical chain mechanism involving an intramolecular radical addition to the α‐Rf carbonyl group and a subsequent intermolecular hydrogen atom transfer (HAT) has been proposed. Density functional theory (DFT) calculations indicate that a fluorine effect contributes to the radical addition to carbonyls by lowering the π* (C=O) orbital energy of CORf and energy barrier of the HAT between alkoxy radicals and THF, which may be valuable for controllable transformations of fluorinated molecules. [ABSTRACT FROM AUTHOR]

Difluoroalkyl groups and cyclopentenones are both important units in synthetic and medicinal chemistry. The difuoroalkylation coupled with a cyclopentenone formation still remains a challenge. Herein, we report a visible‐light‐induced cascade difluoroalkylative 5‐endo cyclization of ynones with difluoroalkyl bromides to access difluoroalkylated cyclopentenones, which may find wide applications for the concise synthesis of fluorinated cyclic molecules. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The first Cu‐catalyzed 1,2,5‐trifunctionalization of abundant terminal alkynes is realized by merging hydrogen atom transfer and traceless directing strategy with SR as a transient group, delivering highly functionalized aldehydes in moderate to excellent yields with broad substrate scope. The synthetic utility of this method was demonstrated by the gram‐scale reaction and downstream transformations of the resultant products. Given the high efficient installation of three different functional groups in a single reaction, it can serve as a very attractive method for rapidly assembling complex molecules from readily available starting materials. [ABSTRACT FROM AUTHOR]

Cyclopentenes and indenes are important structural scaffolds in synthetic, medical, and material chemistry. Cyclization of alkynes via remote C−H functionalization is an appealing approach to construct these motifs due to its high efficiency and step‐economy. Herein, a traceless directing group strategy was designed to reverse the regioselectivity of radical addition which enabled an unprecedented photocatalytic sulfonylcarbocyclization of terminal alkynes by forming C−C bond on inert C(sp3)−H bond. It offers a facile access to decorated cyclopentenes and indenes under mild conditions. The resultant products could be converted into a set of valuable molecular scaffolds, including a key intermediate of AM‐6226. Mechanistic experiments suggest a radical cascade pathway comprising a Markovnikov‐type sulfonylation, 1,5‐hydrogen atom transfer, 5‐endo‐trig cyclization, and β‐elimination. This study lays further groundwork for the use of anti‐Baldwin 5‐endo‐trig radical cyclization in rapidly assembling five‐membered carbocycles. [ABSTRACT FROM AUTHOR]