Carbon Radicals Research Articles

Installation of O‐Heterocycles to N‐Heteroarenes via an Et3B/O2‐Mediated Radical Reaction of α‐Alkoxy and α‐Alkoxyacyl Tellurides

AbstractWe report a radical‐based method that links highly oxygenated O‐heterocycles and N‐heteroarenes. Treatment of α‐alkoxy or α‐alkoxyacyl tellurides with Et3B under air at room temperature generated α‐alkoxy carbon radicals, which were then added to protonated N‐heteroarenes. Regeneration of aromaticity proceeded in situ without an additional oxidant, leading to O‐heterocycle‐functionalized N‐heteroarenes. The present method enables the formation of hindered C(sp3)−C(sp2) bonds between five O‐heterocycles and five N‐heteroarenes under mild conditions.

The coupling of alkylboronic acids and esters with Baylis–Hillman derivatives by Lewis base/photoredox dual catalysis

Utilizing Lewis base/photoredox dual catalysis, carbon radicals generated from either alkylboronic acids or esters were coupled with Baylis–Hillman derivatives under visible light irradiation. This protocol provides a mild and operationally simple method for the synthesis of a variety of α,β-unsaturated carbonyl compounds in a broad scope of the substrates. The mechanism of Lewis base activation and reductive quenching cycle was probably involved.

Interaction of Radicals with σ-Holes.

The noncovalent interactions of the CH3•, Cl•, CF3•, and C(CH3)3• radicals with CF3X molecules (X = Cl, Br, I) have been investigated using CCSD(T)/aug-cc-pVTZ energy calculations on MP2/aug-cc-pVTZ-optimized geometries. The electrophilic chlorine atom prefers to complex with the equatorial belt of the heavier halogen X, whereas the nucleophilic radicals CH3• and C(CH3)3• coordinate preferentially with the σ-hole of X to give C3 v complexes. Complexation energies are generally small, ranging up to 5 kcal mol-1 for CF3I with either the chlorine atom or the tBu radical. Within the continuum from pure one-electron (SOMO-LUMO) to pure three-electron (SOMO-HOMO) bonds, the results can be interpreted in terms of predominantly one-electron bonds for nucleophilic radicals but closer to three-electron bonds for the chlorine atom. The trifluoromethyl radical binds very weakly via interhalogen interactions; the carbon radical center plays no role in the bonding.

Copper-Catalyzed Amide Radical-Directed Cyanation of Unactivated Csp3–H Bonds

A method for site-selective intermolecular δ/ε-Csp3-H cyanation of aliphatic sulfonamides is developed using TsCN as the cyanating reagent, catalyzed by a Cu(I)/phenanthroline complex. The mild, expeditious, and modular protocol allows efficient remote Csp3-H cyanation with good functional group tolerance and high regioselectivity. Mechanistic studies indicate that the reaction might proceed through a Cu(I)-mediated N-F bond cleavage to generate an amidyl radical, 1,5-HAT, and cyano group transfer of the resulting carbon radical with TsCN.

Reprint of: Recent advances in the functionalization of allenes via radical process

This review is focused on the recent advances in the functionalization of allenes via radical process. Different radical partners including carbon radicals and heteroatom radicals are discussed in the reactions of allenes. Generally, the radical formed in situ would attack the allene at the central carbon leading to allyl radical intermediate. However, the formation of alkenyl radical intermediate from allene could be observed as well in some cases with high regioselectivity and stereoselectivity.

Effect of the Composition of the Lubricating Medium on the Structure of Surface Layers Formed by the Friction of a Servovite Film

The tribological characteristics of a brass–steel friction pair in aqueous solutions of saturated carboxylic acids are studied. With an increase in the length of the carbon radical in the acid molecule used as the organic component of the lubricant composition upon the friction of brass on steel, the coefficient of friction decreases and wear reduces. A servovite film is found to form on tribocoupled surfaces during frictional interaction. In the series of monobasic carboxylic acids R–COOH (R = CnH2n + 1, n = 0–5) used as a lubricating medium, from formic acid to caproic acid, the roughness of the film surface decreases and its continuity increases. The servovite film is formed by copper nanoclusters of predominantly ellipsoidal shape up to 40 nm in height, tightly packed and directed along the slip of the counterbody.

Heterometallic CoIIIZnII Schiff Base Catalyst for Mild Hydroxylation of C(sp3)–H Bonds of Unactivated Alkanes: Evidence for Dual Mechanism Controlled by the Promoter

The novel Schiff base complex [CoIIIZnIIL3Cl2]·CH3OH (1) was synthesized by interaction of zinc powder, cobalt(II) chloride and methanol solution of the pre-formed HL in air (HL is the product of condensation of o-vanillin and methylamine) and characterized by IR, UV-Vis and NMR spectroscopy, ESI-MS and single crystal X-ray diffraction analysis. In the heterometallic core of 1 the two metal centers are bridged by deprotonated phenoxy groups of the L− ligands with the cobalt-zinc separation of 3.123 Å. Catalytic investigations demonstrated a pronounced activity of 1 towards mild alkane oxidation with m-chloroperbenzoic acid (m-CPBA) as an oxidant and cis-1,2-dimethylcyclohexane (cis-1,2-DMCH) as the model substrate. The influence of the nature of different promoting agents of various acidities (from HOTf to pyridine) on the catalytic process was studied in detail and a pronounced activity of 1 in the presence of nitric acid promoter was found, also showing a high retention of stereoconfiguration of the substrate (>99% for cis-1,2-DMCH). The best achieved yield of tertiary cis-alcohol based on the oxidant was 61%, with a turnover number (TON) of 198 for nitric acid as promoter. The 18O-incorporations into the alcohols when the reactions were performed under 18O2 atmosphere using acetic and nitric acid promoters, suggest that the cis-1,2-DMCH hydroxylation proceeds by two distinct pathways, a non-stereoselective and a stereoselective one (with and without involvement of a long-lived free carbon radical, respectively). The former dominates in the case of acetic acid promoter and the latter is realized in the case of HNO3 promoter.

Theoretical Study of Ni-Catalyzed C-N Radical-Radical Cross-Coupling.

A computational study was carried out to investigate the mechanism and the origin of chemoselectivity in nickel-catalyzed C-N radical-radical cross-coupling reaction. The global electrophilicity index ω° and global nucleophilicity index N° were used to quantitatively describe the electrophilic or nucleophilic character of the carbon radical, nitrogen radical, and Ni(II) complex. The calculated ω° and N° values indicate that introduction of nickel makes C-N cross-coupling to be a facile process. Detailed theoretical results show that the cross-coupling occurs through the combination of Ni(I) complex with a nitrogen-centered radical, a minimum energy crossing point to form the singlet Ni(II) complex, and radical addition of the nucleophilic carbon-centered radical lead to C-N bond formation. On the basis of the theoretical results, a generalized scheme is provided to clarify the origin of the chemoselectivity in nickel-catalyzed C-N radical-radical cross-coupling.

Copper-catalyzed remote C(sp3)\u2013H azidation and oxidative trifluoromethylation of benzohydrazides

The Hofmann-Löffler-Freytag (HLF) reaction is a prototypical example of radical-based remote functionalization of unactivated C(sp3)–H bond. While 1,5-hydrogen atom transfer (1,5-HAT) of the amidyl radical is thermodynamically favorable and is well-established, the method for the subsequent functionalization of the translocated carbon radical is still limited. We report herein two catalytic remote C(sp3)–H functionalization protocols. Cu(MeCN)4PF6-catalyzed reaction of 2-alkyl benzohydrazides 3 with TMSN3 in the presence of MeCO2OtBu affords the γ-azido amides 4, while CuCl-catalyzed reaction of 3 with Togni’s reagent provides 2-(β-trifluoromethylvinyl)benzamides 5 via an oxidative δ-trifluoromethylation of the alkyl group. Mechanistic studies suggest that the γ-azidation of benzohydrazides 3 goes through 1,5-HAT followed by a Cu-mediated azido transfer cascade, while the oxidative δ-trifluoromethylation of 3 proceeds via, after 1,5-HAT process, a radical-polar crossover mechanism.

Investigating the Mechanism of Palladium-Catalyzed Radical Oxidative C(sp3 )-H Carbonylation: A DFT Study.

Palladium (Pd)-catalyzed radical oxidative C-H carbonylation of alkanes is a useful method for functionalizing hydrocarbons, but there is still a lack of understanding of the mechanism, which restricts the application of this reaction. In this work, density functional theory (DFT) calculations were carried out to study the mechanism for a Pd-catalyzed radical esterification reaction. Two plausible reaction pathways have been proposed and validated by DFT calculations. The computational results reveal that the generated alkyl radical prefers to add to the carbon monoxide (CO) molecule to form a carbonyl radical before bonding with the Pd species. Radical addition onto Pd followed by CO migratory insertion was unfavorable owing to the high energy barrier of the migratory insertion step. The regioselectivity of the C(sp3 )-H carbonylation was also investigated by DFT. The results show that the regioselectivity is controlled by both the bond dissociation energy of the reacting C-H bond and the stability of the corresponding generated carbon radical. Competitive side reactions also affected the yield and regioselectivity owing to the rapid consumption of the stable radical intermediate.

Copper-Catalyzed Oxidative sp3-Carbon Radical Cross-Coupling with Trialkylphosphites Leading to α-Phosphonyl 1,3-Dicarbonyl Compounds.

A copper-catalyzed radical Csp3-H/P(OR)3 cross-coupling reaction for the formation of Csp3-P bonds is described. A range of 1,3-dicarbonyl compounds and trialkylphosphites were coupled in this fashion to give the corresponding products in moderate to good yields. This protocol provides direct access to α-phosphonyl 1,3-dicarbonyl compounds.

Enantioselective Construction of Quaternary All-Carbon Centers via Copper-Catalyzed Arylation of Tertiary Carbon-Centered Radicals.

An enantioselective copper-catalyzed arylation of tertiary carbon-centered radicals, leading to quaternary all-carbon stereocenters, has been developed herein. The tertiary carbon-centered radicals, including both benzylic and nonbenzylic radicals, were produced by the addition of trifluoromethyl radical to α-substituted acrylamides, and subsequently captured by chiral aryl copper(II) species to give C-Ar bonds with excellent enantioselectivity. Importantly, an acylamidyl (CONHAr) group adjacent to the tertiary carbon radical is essential for the asymmetric radical coupling. The reaction itself features broad substrate scope, excellent functional group compatibility and mild conditions.

Tracking the Process of a Solvothermal Domino Reaction Leading to a Stable Triheteroarylmethyl Radical: A Combined Crystallographic and Mass‐Spectrometric Study

AbstractA new free carbon radical was obtained in a microwave‐assisted solvothermal reaction of the primary amine (1‐methyl‐1H‐benzo[d]imidazol‐2‐yl)methanamine with FeCl3⋅6 H2O in methanol at 140 °C. Through a combination of crystallography and electrospray ionization mass spectrometry, the reaction process was studied. The longest domino reaction includes 14 steps and forms up to 12 new covalent bonds (9 C−N and 3 C−C bonds) and 3 five‐membered heterocycles. For the first time, the homolytic cleavage of a C−O bond was used to synthesize a triarylmethyl radical.

Tracking the Process of a Solvothermal Domino Reaction Leading to a Stable Triheteroarylmethyl Radical: A Combined Crystallographic and Mass-Spectrometric Study.

A new free carbon radical was obtained in a microwave-assisted solvothermal reaction of the primary amine (1-methyl-1H-benzo[d]imidazol-2-yl)methanamine with FeCl3 ⋅6 H2 O in methanol at 140 °C. Through a combination of crystallography and electrospray ionization mass spectrometry, the reaction process was studied. The longest domino reaction includes 14 steps and forms up to 12 new covalent bonds (9 C-N and 3 C-C bonds) and 3 five-membered heterocycles. For the first time, the homolytic cleavage of a C-O bond was used to synthesize a triarylmethyl radical.

Hydrogen Spillover Mechanisms over a Graphite Surface

Four different mechanisms of hydrogen spillower over carbon surface are considered in the framework of a single quantum-chemical approach. Two of them, described in the literature, are the physical migration of a bonded hydrogen atom along the surface and the edge of the graphene. One of the mechanisms proposed by the author does not include the migration of atomic hydrogen, but is realized via a transfer of carbon radical over a carbon sheet and generation of H atom in another place. Calculated activation energies of all four mechanisms are compared.

Carbonylation of tertiary carbon radicals: synthesis of lactams.

Herein, we disclose an interesting iron-catalyzed approach for the carbonylation of a tertiary carbon radical. The tertiary carbon radical generated from a 1,5-hydrogen atom transfer can be captured by CO gas smoothly. Various six-membered lactams were constructed chemo-selectively in high yields.

Mitochondria targeted and NADH triggered photodynamic activity of chloromethyl modified Ru(ii) complexes under hypoxic conditions.

Three chloromethyl-modified Ru(ii) complexes were designed and synthesized as mitochondria targeting photosensitizers, which can generate carbon radicals in the presence of NADH under visible light irradiation, cause DNA cleavage and covalent binding in Ar-saturated solutions, and lead to apoptosis of human ovarian carcinoma SKOV-3 cells under hypoxic conditions (3% O2), demonstrating a new mode of type I mechanism to overcome the limitation of hypoxia in photodynamic therapy (PDT).

C–C bridged Ni(II) complexes bearing β‐keto‐9‐fluorenyliminato ligands prepared by different in situ bonding mechanisms and their use in catalytic (co)polymerization of norbornene and styrene

Two C–C bridged Ni(II) complexes bearing β‐keto‐9‐fluorenyliminato ligands with electron‐withdrawing groups (─CF3), Ni{PhC(O)CHC[N(9‐fluorenyl)]CF2}2 (Ni1) and Ni{CF3C(O)CHC[N(9‐fluorenyl)]Ph}2 (Ni2), were synthesized by metal coordination reaction and different in situ bonding mechanisms. The C–C bridged bonds of Ni1 were formed by in situ intramolecular trifluoromethyl and 9‐fluorenyl carbon–carbon cross‐coupling reaction and those of Ni2 were formed by in situ intramolecular 9‐fluorenyl carbon–carbon radical coupling reaction mechanism. The obtained complexes were characterized using 1H NMR spectroscopy and elemental analyses. The crystal and molecular structures of Ni1 and Ni2 with C–C bridged configuration were determined using X‐ray diffraction. Ni1 and Ni2 were used as catalysts for norbornene (NB) polymerization after activation with B(C6F5)3 and the catalytic activities reached 106 gpolymer molNi−1 h−1. The copolymerization of NB and styrene catalyzed by the Ni1/B(C6F5)3 system showed high activity (105 gpolymer molNi−1 h−1) and the catalytic activities decreased with increasing feed content of styrene. All vinyl‐type copolymers exhibited high molecular weight (104 g mol−1), narrow molecular weight distribution (Mw/Mn = 1.71–2.80), high styrene insertion ratios (11.13–50.81%) and high thermal stability (Td > 380°C) and could be made into thin films with high transparency in the visible region (400–800 nm).

1,2-H Atom Rearrangements in Benzyloxyl Radicals.

The rate constants for solvent-assisted 1,2-H atom rearrangements in para-substituted benzyloxyl radicals were studied with density functional theory. The rate of the radical rearrangement, calculated through transition state theory with Eckhart tunneling corrections, was shown to be drastically impacted by the presence of both implicit and explicit solvent molecules, with a quantitative agreement with laser flash photolysis studies for a variety of electron-donating and -withdrawing substituents. The rate of rearrangement was found to be correlated to the distance between the rearranging hydrogen atom and the α-carbon in the transition state, which could be modified through the para substituent and the type of assisting solvent molecule (e.g., water, ethanol, methanol, acetic acid, or a mixture of the latter). Natural bond orbital analysis showed that the rearrangement does not proceed through a hydrogen radical but through a quasi-proton exchange and charge transfer between the benzyl carbon and the adjacent oxygen atom. Energetic and spin population results indicated that electron-withdrawing groups induce faster rearrangement kinetics. Understanding 1,2-H atom shifts in benzyloxyl radicals are essential for tuning the rate of superoxide production in aqueous systems, as the resonance-stabilized carbon radical produced from the rearrangement can bind oxygen and decompose to produce superoxide radical anion, an important reactive intermediate in environmental and biological systems.

Photochemical generation of radicals from alkyl electrophiles using a nucleophilic organic catalyst.

Chemists extensively use free radical reactivity for applications in organic synthesis, materials science, and life science. Traditionally, generating radicals requires strategies that exploit the bond dissociation energy or the redox properties of the precursors. Here, we disclose a photochemical catalytic approach that harnesses different physical properties of the substrate to form carbon radicals. We use a nucleophilic dithiocarbamate anion catalyst, adorned with a well-tailored chromophoric unit, to activate alkyl electrophiles via an SN2 pathway. The resulting photon-absorbing intermediate affords radicals upon homolytic cleavage induced by visible light. This catalytic SN2-based strategy, which exploits a fundamental mechanistic process of ionic chemistry, grants access to open-shell intermediates from a variety of substrates that would be incompatible with or inert to classical radical-generating strategies. We also describe how the method's mild reaction conditions and high functional group tolerance could be advantageous for developing C-C bond-forming reactions, for streamlining the preparation of a marketed drug, for the late-stage elaboration of biorelevant compounds and for enantioselective radical catalysis.