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.     

Oxidative Catalysis Using the Stoichiometric Oxidant as a Reagent: An Efficient Strategy for Single‐Electron‐Transfer‐Induced Tandem Anion–Radical Reactions

Oxidative single‐electron transfer‐catalyzed tandem reactions consisting of a conjugate addition and a radical cyclization are reported, which incorporate the mandatory terminal oxidant as a functionality into the product.     

Atom‐Transfer Radical Addition Reactions Catalyzed by RuCp* Complexes: A Mechanistic Study

Kinetic and spectroscopic analyses were performed to gain information about the mechanism of atom‐transfer radical reactions catalyzed by the complexes [RuCl₂Cp*(PPh₃)] and [RuClCp*(PPh₃)₂] (Cp*=pentamethylcyclopentadienyl), in the presence and in the absence of the reducing agent magnesium. The reactions of styrene with ethyl trichloroacetate, ethyl dichloroacetate, or dichloroacetonitrile were used as test reactions. The results show that for substrates with high intrinsic reactivity, such as ethyl trichloroacetate, the oxidation state of the catalyst in the resting state is +3, and that the reaction is zero‐order with respect to the halogenated compound. Furthermore, the kinetic data suggest that the metal catalyst is not directly involved in the rate‐limiting step of the reaction.     

Stereoselective Triplet‐Sensitised Radical Reactions of Furanone Derivatives

The stereo‐ and regioselectivity of triplet‐sensitised radical reactions of furanone derivatives have been investigated. Furanones 7 a , b were excited to the ³ππ* state by triplet energy transfer from acetone. Intramolecular hydrogen abstraction then occurred such that hydrogen was transferred from the tetrahydropyran to the β position of the furanone moiety. Radical combination of the tetrahydropyranyl and the oxoallyl radicals led to the final products 8 a , b . In the intramolecular reaction, overall, a pyranyl group adds to the α position of the furanone. The effect of conformation was first investigated with compounds 9 a , b carrying an additional substituent on the tether between the furanone and pyranyl moiety. Further information on the effect of conformation and the relative configuration at the pyranyl anomeric centre and the furanone moiety was obtained from the transformations of the glucose derivatives 12 , 14 , 17 and 18 . Radical abstraction occurred at the anomeric centre and at the 5′‐position of the glucosyl moiety. Computational studies of the hydrogen‐abstraction step were carried out with model structures. The activation barriers of this step for different stereoisomers and the abstraction at the anomeric centre and at the 6‘‐position of the tetrahydropyranyl moiety were calculated. The results of this investigation are in accordance with experimental observations. Furthermore, they reveal that the reactivity and regioselectivity are mainly determined in the hydrogen‐abstraction step. Intramolecular hydrogen abstraction (almost simultaneous electron and proton transfer) in ³ππ* excited furanones only takes place under restricted structural conditions in a limited number of conformations that are defined by the relative configuration of the substrates. It is observed that in the biradical intermediate, back‐hydrogen transfer occurs leading to the starting compound. In the case of glucose derivatives, this reaction led to epimerisation at the anomeric centre.     

Well-Defined,Molecular Bismuth Compounds: Catalysts in Photochemically Induced Radical Dehydrocoupling Reactions

A series of diorgano(bismuth)chalcogenides, [Bi(di-aryl)EPh], has been synthesised and fully characterised (E=S, Se, Te). These molecular bismuth complexes have been exploited in homogeneous photochemically-induced radical catalysis, using the coupling of silanes with TEMPO as a model reaction (TEMPO=(tetramethyl-piperidin-1-yl)-oxyl). Their catalytic properties are complementary or superior to those of known catalysts for these coupling reactions. Catalytically competent intermediates of the reaction have been identified. Applied analytical techniques include NMR, UV/Vis, and EPR spectroscopy, mass spectrometry, single-crystal X-ray diffraction analysis, and (TD)-DFT calculations.     

Radical Alkyne peri‐Annulation Reactions for the Synthesis of Functionalized Phenalenes,Benzanthrenes, and Olympicene

Radical cyclization reactions at a peri position were used for the synthesis of polyaromatic compounds. Depending on the choice of reaction conditions and substrate, this flexible approach led to Bu₃Sn‐substituted phenalene, benzanthrene, and olympicene derivatives. Subsequent reactions with electrophiles provided synthetic access to previously inaccessible functionalized polyaromatic compounds.     

Photoinduced Radical Borylation of Alkyl Bromides Catalyzed by 4‐Phenylpyridine

Utilizing pyridine catalysis, we developed a visible‐light‐induced transition‐metal‐free radical borylation reaction of unactivated alkyl bromides that features a broad substrate scope and mild reaction conditions. Mechanistic studies revealed a novel nucleophilic substitution/photoinduced radical formation pathway, which could be utilized to trigger a variety of radical processes.     

Design of Leaving Groups in Radical CC Fragmentations: Through‐Bond 2c–3e Interactions in Self‐Terminating Radical Cascades

Radical cascades terminated by β‐scission of exocyclic C?C bonds allow for the formation of aromatic products. Whereas β‐scission is common for weaker bonds, achieving this reactivity for carbon–carbon bonds requires careful design of radical leaving groups. It has now been found that the energetic penalty for breaking a strong σ‐bond can be compensated by the gain of aromaticity in the product and by the stabilizing two‐center, three‐electron “half‐bond” present in the radical fragment. Furthermore, through‐bond communication of a radical and a lone pair accelerates the fragmentation by selectively stabilizing the transition state. The stereoelectronic design of radical leaving groups leads to a new, convenient route to Sn‐functionalized aromatics.     

Reactions of Ruthenium Vinylidene and Acetylide Complexes Containing Trichloromethyl Groups: Preparation of a Cyclobutenonyl Complex by Solid‐State Photolysis

Solid‐state route to a cyclobutenone : Ruthenium perchlorocyclobutenonyl complex 2 is obtained by solid‐state photoisomerization of ruthenium trichloroacetyl acetylide complex 1 . The four‐membered ring is sufficiently robust that transfer of the intact ligand could be readily achieved in a reaction of 2 with an enyne. Cyclobutenedionyl complex 3 was obtained by hydrolysis of 2 in H₂O/THF.

     

Visible‐Light Photoredox Catalysis: Direct Synthesis of Sulfonated Oxindoles from N‐Arylacrylamides and Arylsulfinic Acids by Means of a Cascade C−S/C−C Formation Process

A novel photocatalytic synthesis of sulfonated oxindoles from N‐arylacrylamides and arylsulfinic acids was developed by means of a cascade C?S/C?C bond‐formation process. This method provides mild, efficient, and atom‐economical access to various sulfonated oxindoles in water.     

Organic Photocatalytic Cyclization of Polyenes: A Visible‐Light‐Mediated Radical Cascade Approach

A visible‐light‐mediated, organic photocatalytic stereoselective radical cascade cyclization of polyprenoids is described. The desired cascade cyclization products are achieved in good yields and high stereoselectivities with eosin Y as photocatalyst in hexafluoro‐2‐propanol. The catalyst system is also suitable for 1,3‐dicarbonyl compounds, which require only catalytic amounts of LiBr to promote the formation of the corresponding enols.     

Copper‐Catalyzed Difunctionalization of Activated Alkynes by Radical Oxidation–Tandem Cyclization/Dearomatization to Synthesize 3‐Trifluoromethyl Spiro[4.5]trienones

A copper‐catalyzed difunctionalizing trifluoromethylation of activated alkynes with the cheap reagent sodium trifluoromethanesulfinate (NaSO₂CF₃ or Langlois’ reagent) has been developed incorporating a tandem cyclization/dearomatization process. This strategy affords a straightforward route to synthesis of 3‐(trifluoromethyl)‐spiro[4.5]trienones, and presents an example of difunctionalization of alkynes for simultaneous formation of two carbon–carbon single bonds and one carbon–oxygen double bond.     

Controlling Chain Coupling and Single‐Chain Ligation by Two Colours of Visible Light

While photochemical synthesis offers access to spatiotemporal reaction control, its potential to selectively address specific reactions by the colour of light is usually limited by ubiquitous spectral absorption overlaps of the reactive groups. Herein, a new concept is introduced that actively suppresses one ligation reaction by triggering the cycloreversion of the [2+2] cycloaddition of styrylpyrene. Combination of the photoreversible styrylpyrene chemistry with the [4+4] cycloaddition of 9‐triazolylanthracene makes it possible to initially induce chain coupling using UV light and to subsequently ligate the formed single‐chain nanoparticle (SCNP) with a second polymer chain using blue light. Seizing upon the first sequence‐independent λ‐orthogonal reactivity established here, the same macromolecular architecture was obtained in reverse irradiation sequence, by blue and subsequent violet light irradiation—completely foregoing high‐energy UV light.     

Copper‐Catalyzed Double Additions and Radical Cyclization Cascades in the Re‐Engineering of the Antibacterial Pleuromutilin

A general synthetic sequence involving simply prepared starting materials provides rapid access to diverse, novel tricyclic architectures inspired by pleuromutilin. Sm^II‐mediated radical cyclization cascades of dialdehydes, prepared using a new, one‐pot, copper‐catalyzed double organomagnesium addition to β‐chlorocyclohexenone, proceed with complete sequence selectivity and typically with high diastereocontrol to give analogues of the target core. Our expedient approach (ca. 7 steps) allows non‐traditional, de novo synthetic access to analogues of the important antibacterial that can′t be prepared from the natural product by semisynthesis.     

Visible Light Mediated Aryl Migration by Homolytic C−N Cleavage of Aryl Amines

The photocatalytic preparation of aminoalkylated heteroarenes from haloalkylamides via a 1,4‐aryl migration from nitrogen to carbon, conceptually analogous to a radical Smiles rearrangement, is reported. This method enables the substitution of amino groups in heteroaromatic compounds with aminoalkyl motifs under mild, iridium(III)‐mediated photoredox conditions. It provides rapid access to thienoazepinone, a pharmacophore present in multiple drug candidates for potential treatment of different conditions, including inflammation and psychotic disorders.     

Tandem Radical Cyclization for the Construction of Difluoro‐Containing Oxindoles and Quinoline‐2,4‐diones

Cu‐catalyzed direct difluoromethylation of activated alkenes through a difluoromethyl radical addition/cyclization to afford difluorinated oxindoles and quinoline‐2,4‐diones has been developed. This method provides convenient access to a variety of oxindoles and quinoline‐2,4‐diones under mild conditions via a proposed tandem radical cyclization process, while tolerating various functional groups well. Moreover, a facile method to construct diverse difluorinated quinoline‐2,4‐diones by visible‐light photoredox catalysis under mild conditions was presented.