Enantioselective Radical Addition/Cross‐Coupling of Organozinc Reagents,Alkyl Iodides,and Alkenyl Boron Reagents

A hybrid transition‐metal/radical process is described that results in the addition of organozinc reagents and alkyl halides across alkenyl boron reagents in an enantioselective catalytic fashion. The reaction can be accomplished both intermolecularly and intramolecularly, providing useful product yields and high enantioselectivities in both manifolds.     

Visible‐Light‐Mediated Decarboxylative Radical Additions to Vinyl Boronic Esters: Rapid Access to γ‐Amino Boronic Esters

The synthesis of alkyl boronic esters by direct decarboxylative radical addition of carboxylic acids to vinyl boronic esters is described. The reaction proceeds under mild photoredox catalysis and involves an unprecedented single‐electron reduction of an α‐boryl radical intermediate to the corresponding anion. The reaction is amenable to a diverse range of substrates, including α‐amino, α‐oxy, and alkyl carboxylic acids, thus providing a novel method to rapidly access boron‐containing molecules of potential biological importance.     

Highly Electron‐Deficient and Air‐Stable Conjugated Thienylboranes

Introduced herein is a series of conjugated thienylboranes, which are inert to air and moisture, and even resist acids and strong bases. X‐ray analyses reveal a coplanar arrangement of the thiophene rings, an arrangement which facilitates p–π conjugation through the boron atoms despite the presence of highly bulky 2,4,6‐tri‐tert‐butylphenyl (Mes*) or 2,4,6‐tris(trifluoromethyl)phenyl (^FMes) groups. Short B???F contacts, which lead to a pseudotrigonal bipyramidal geometry in the ^FMes species, have been further studied by DFT and AIM analysis. In contrast to the Mes* groups, the highly electron‐withdrawing ^FMes groups do not diminish the Lewis acidity of boron toward F^? anions. These compounds can be lithiated or iodinated under electrophilic conditions without decomposition, thus offering a promising route to larger conjugated structures with electron‐acceptor character.     

Acid‐Catalyzed Oxidative Radical Addition of Ketones to Olefins

Based on a mechanistic study, we have discovered a Brønsted acid catalyzed formation of ketone radicals. This is believed to proceed via thermally labile alkenyl peroxides formed in situ from ketones and hydroperoxides. The discovery could be utilized to develop a multicomponent radical addition of unactivated ketones and tert‐butyl hydroperoxide to olefins. The resulting γ‐peroxyketones are synthetically useful intermediates that can be further transformed into 1,4‐diketones, homoaldol products, and alkyl ketones. A one‐pot reaction yielding a pharmaceutically active pyrrole is also described.     

Asymmetric Synthesis of 2,3‐Disubstituted Cyclic Ketones by Enantioselective Conjugate Radical Additions

Enantioselective conjugate radical addition to 2‐acyloxymethyl cycloalkenones proceeds in high yield with outstanding diastereoselectivity and excellent enantioselectivity using chiral salen Lewis acids. The process provides access to 2,3‐disubstituted cycloalkanones, a structural motif present in natural products.     

Enhancing the Acceptor Character of Conjugated Organoborane Macrocycles: A Highly Electron‐Deficient Hexaboracyclophane

We introduce a new boron‐doped cyclophane, the hexabora[1₆]cyclophane B6‐^FMes , in which six tricoordinate borane moieties alternate with short conjugated p‐phenylene linkers. Exocyclic 2,4,6‐tris(trifluoromethyl)phenyl (^FMes) groups serve not only to further withdraw electron density but at the same time sterically shield the boron atoms, resulting in a macrocycle that is both highly electron‐deficient and stable. The optical and electronic properties are compared with those of related linear oligomers and the electronic structure is further evaluated by computational methods. The studies uncover unique properties of B6‐^FMes , including a low‐lying and extensively delocalized LUMO and a wide HOMO–LUMO gap, which arise from the combination of a cyclic π‐system, strong electronic communication between the closely spaced borons, and the attachment of electron‐deficient pendent groups. The binding of small anions to the electron‐deficient macrocycle and molecular model compounds is investigated and emissive exciplexes are detected in aromatic solvents.     

Evidence for Extensive Single‐Electron‐Transfer Chemistry in Boryl Anions: Isolation and Reactivity of a Neutral Borole Radical

Despite the synthesis of a boryl anion by Yamashita et al. in 2006, compounds that show boron‐centered nucleophilicity are still rare and sought‐after synthetic goals. A number of such boryl anions have since been prepared, two of which were reported to react with methyl iodide in apparent nucleophilic substitution reactions. One of these, a borolyl anion based on the borole framework, has now been found to display single‐electron‐transfer (SET) reactivity in its reaction with triorganotetrel halides, which was confirmed by the isolation of the first neutral borole‐based radical. The radical was characterized by elemental analysis, single‐crystal X‐ray crystallography, and EPR spectroscopy, and has implications for the understanding of boron‐based nucleophilic behavior and the emergent role of boron radicals in synthesis. This radical reactivity was also exploited in the synthesis of compounds with rare B? Sn and B? Pb bonds, the latter of which was the first isolated and structurally characterized compound with a “noncluster” B? Pb bond.     

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.     

π‐Conjugated Carbon Radicals at Graphene Oxide to Initiate Ultrastrong Chemiluminescence

Graphene oxide has widely been employed in various fields, but its structure and composition has still not been fully understood. Here we report that freshly prepared graphene oxide exhibits a large number of π‐conjugated carbon radicals at its π‐network plane, which result from the addition reaction of hydroxyl radicals from H₂O₂ onto the conjugated double bonds of graphene oxide. The π‐conjugated carbon radicals can directly initiate the long‐lasting visible chemiluminescence of luminol, which is even stronger than that obtained when horseradish peroxidase and H₂O₂ are used. Previously, graphene oxide was mainly reported to be a quencher of chemiluminescence instead. Remarkably, the reacted radicals can be regenerated, thereby enabling the repetitive initiation of chemiluminescence by re‐treatment of graphene oxide. The results reported here provide a new understanding of the structure, properties, and applications of graphene oxide.     

Arginine‐Facilitated α‐ and π‐Radical Migrations in Glycylarginyltryptophan Radical Cations

We have used model tripeptides GXW (with X being one of the amino acid residues glycine (G), alanine (A), leucine (L), phenylalanine (F), glutamic acid (E), histidine (H), lysine (K), or arginine (R)) to study the effects of the basicity of the amino acid residue on the radical migrations and dissociations of odd‐electron molecular peptide radical cations M^.+ in the gas phase. Low‐energy collision‐induced dissociation (CID) experiments revealed that the interconvertibility of the isomers [G^.XW]⁺ (radical centered on the N‐terminal α‐carbon atom) and [GXW]^.+ (radical centered on the π system of the indolyl ring) generally increased upon increasing the proton affinity of residue X. When X was arginine, the most basic amino acid, the two isomers were fully interconvertible and produced almost identical CID spectra despite the different locations of their initial radical sites. The presence of the very basic arginine residue allowed radical migrations to proceed readily among the [G^.RW]⁺ and [GRW]^.+ isomers prior to their dissociations. Density functional theory calculations revealed that the energy barriers for isomerizations among the α‐carbon‐centered radical [G^.RW]⁺, the π‐centered radical [GRW]^.+, and the β‐carbon‐centered radical [GRW_β^.]⁺ (ca. 32–36 kcal mol⁻¹) were comparable with those for their dissociations (ca. 32–34 kcal mol⁻¹). The arginine residue in these GRW radical cations tightly sequesters the proton, thereby resulting in minimal changes in the chemical environment during the radical migrations, in contrast to the situation for the analogous GGW system, in which the proton is inefficiently stabilized during the course of radical migration.     

Iron‐Induced Regio‐ and Stereoselective Addition of Sulfenyl Chlorides to Alkynes by a Radical Pathway

The radical addition of the Cl? S σ‐bond in sulfenyl chlorides to various C? C triple bonds has been achieved with excellent regio‐ and stereoselectivity in the presence of a catalytic amount of a common iron salt. The reaction is compatible with a variety of functional groups and can be scaled up to the gram‐scale with no loss in yield. As well as terminal alkynes, internal alkynes underwent stereodefined chlorothiolation to provide tetrasubstituted alkynes. Preliminary mechanistic investigations revealed a plausible radical process involving a sulfur‐centered radical intermediate via iron‐mediated homolysis of the Cl? S bond. The resulting chlorothiolation adducts can be readily transformed to the structurally complex alkenyl sulfides by cross‐coupling reactions. The present reaction can also be applied to the complementary synthesis of the potentially useful bis‐sulfoxide ligands for transition‐metal‐catalyzed reactions.