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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]

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]

Dehydrogenation of unactivated alkanes to form versatile alkenes is an important but challenging task in synthetic chemistry. Enabled by a radical‐mediated formyl group migration, a novel visible light‐induced remote desaturation of aldehydes is developed, delivering a panel of trifluoromethylated δ,ϵ‐ or γ,δ‐unsaturated aldehydes in moderate to excellent yields with good functional group tolerance at room temperature. Mechanistic studies indicate a reaction pathway comprising the cascade trifluoromethylation of C−C double bonds, intramolecular addition to aldehydes, β‐fragmentation of alkoxy radicals, single electron transfer oxidation, and deprotonation. It provides a good complementary approach to the existing desaturation protocols. [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]

This report describes the site‐selective α‐functionalization of sulfonylamide derivatives through the in‐situ generation of imine intermediates. The N−F sulfonylamides, which could facilitate the elimination to generate imines, are coupled with TBACN to efficiently and mildly afford α‐amino cyanides. Comparing with Strecker reaction, this transformation offers a complementary strategy to efficiently construct α‐amino cyanides from direct α C−H functionalization of sulfonylamindes. The reaction is also characterized by broad substrate scope and flash chromatography column free workup. More importantly, the new two‐electron pathway to generate imines through manipulation of the leaving group allows us to achieve excellent α site‐selectivity. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed three-component reaction between fluoroalkyl bromides, arylboronic acids, and alkenyl aldehydes has been developed and provides facile access to 5-, 6-, or 7-difluoroalkylated ketones under very mild reaction conditions. The resultant products can be smoothly converted into CF2-containing tetrahydronaphthalenes by a novel silver-catalyzed intramolecular decarboxylative cyclization of 5-aryl-2,2-difluoropentanoic acids. [ABSTRACT FROM AUTHOR]

A regio- and stereoselective method for the synthesis of ( E)-α,β-unsaturated carbonyls has been developed v ia a silver-catalyzed tandem epoxide rearrangement/intermolecular carbonyl-heteroalkyne metathesis. Various heteroalkynes including ynol ethers, ynamides, and thioalkynes work well for this transformation, leading to the production of ( E)-α,β-unsaturated esters, amides, and thioesters in moderate to excellent yields with good functional group compatibility. It represents one of the rare examples of regio- and stereoselective intermolecular alkyne-carbonyl metathesis (ACM). [ABSTRACT FROM AUTHOR]

A Cu-catalyzed, highly b-selective borylation of ynamides with bis(pinacolato)diboron as the hydroboration reagent is reported, giving (E)-b-alkenylamide boronates in excellent regio- and stereoselectivity under mild reaction conditions, which provides a complementary regioselectivity to the existing methods. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed trans-hydroalkynylation of N-sulfonyl ynamides has been achieved for the first time, providing α-alkynylation adducts in high yields with excellent regio- and stereoselectivity. The resulting enyne products can serve as the useful precursors for the elaboration of naphthalene derivatives via a platinum-catalyzed cycloisomerization reaction. [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]

For the first time a highly selective α- and β-borylation of thioacetylenes is developed by using bis(pinacolato)diboron (II) or pinacolborane (X). [ABSTRACT FROM AUTHOR]

The obtained products are suitable for subsequent reactions such as Sonogashira couplings or Diels-Alder cyclizations. [ABSTRACT FROM AUTHOR]