Alkylboranes in Conventional and Controlled Radical Polymerization

Utilizations of alkylboranes reagents in radical polymerization are summarized in this minireview. Alkylboranes act as conventional radical initiators or radical chain-transfer agents in free-radical polymerization and controlled radical polymerization. This review discusses various polymerizations operating through different alkylborane reagents with their accompanying mechanisms. The aim of this minireview is to present the state of art of alkylboranes in radical polymerization and to provide the future aspects of this direction. © 2019 Wiley Periodicals, Inc. J. Polym. Sci. 2020 , 58, 14–19     

Effective and Selective Mild Catalytic Hydrodehalogenation of Halocyclopropanes: Preparative Capabilities and Mechanistic Aspects

This review surveys both data obtained by the authors and published data on the partial or full hydrodehalogenation of di- and polyhalocyclopropanes (chlorides and bromides) with Grignard reagents catalyzed by titanium or zirconium compounds. The factors affecting the efficiency and selectivity of the hydrodebromination of bromocyclopropanes are considered: the nature of Grignard reagents (including isotopically labeled reagents), their transformations and effects in catalyzed and uncatalyzed reactions, the participation of solvents, catalytic and stoichiometric amounts of the catalyst, etc. A scheme is proposed in which the key steps of the mechanism of hydrodebromination of bromocyclopropanes includes three blocks of reactions: (a) the generation of a catalytically active Ti(II) species; (b) the hydrodehalogenation of bromocyclopropanes involving electron transfer from a low-valent catalyst species, formation of the cyclopropyl radical, and stabilization of this radical as a result of hydrogen atom transfer from the solvent molecule; and (c) transformations of previously formed radical species, such as dimerization and disproportionation (for example, of radical species generated from Grignard reagents or ether molecules) or the linking of alkyl radicals to radical species produced from solvent molecules.     

One electron C-C bond forming reactions VIA allylstannanes: Scope and limitations

Free radical (or “one-electron”) methodology for carbon-carbon bond forming reactions using allylstannanes is described in detail. Such reactions have the advantages of tolerating quite complex functionality in the substrate and of being nearly stoichiometric in reagents, and not requiring extensive experimentation for application to new substrates.     

Diversity‐Oriented Desulfonylative Functionalization of Alkyl Allyl Sulfones

The diversity‐oriented desulfonylative functionalization of alkyl allyl sulfones with various sulfone‐type reagents by radical chemistry has been developed. The readily installed allylsulfonyl moiety acts as a C‐radical precursor, which is substituted by various functionalities using sulfur‐based radical trapping reagents. The generality of this approach is documented by the successful desulfonylative alkynylation, azidation, trifluoromethylthiolation, sulfenylation, trifluoromethylselenylation, halogenation, and deuteration. The method is compatible with a wide range of functional groups. Considering the deuteration, products are obtained in good yields with a high level of deuterium incorporation.     

Preparation of polycyclic systems by sequential 5-exo-digonal radical cyclization, 1,5-hydrogen transfer from silicon, and 5-endo-trigonal cyclization

Radicals of type 1 undergo 5-exo diagonal cyclization, and the resulting vinyl radical abstracts hydrogen from silicon to afford a silicon-centered radical. This radical closes in a 5-endo trigonal manner to generate radicals of type 4, which are reduced (4 --> 5) by stannane, except when the starting acetylene carries a terminal trimethylstannyl group. In this case, radicals 4 expel trimethylstannyl radical to afford vinyl silanes 6. The stereochemical outcome of the radical cascade 1 --> 5 is controlled by the stereochemistry of the oxygen-bearing carbon in 1 (see starred atom). The sequence can be initiated by carbon-, alpha-substituted carbon-, oxyacyl-, and carbamoyl radicals and generates a silicon-containing ring fused onto a carbocycle or heterocycle. Numerous examples are described, as well as a number of transformations of the final cyclization products, especially their response to n-Bu(4)NF and to BF(3).OEt(2), reagents that cleave the newly formed carbon-silicon bond.     

Ni-Catalyzed Cross Coupling of Aryl Grignard Reagents with Aryl Halides in a Nonpolar Solvent and an Efficient Synthesis of Biaryls Under Neat Conditions

This study details Ni-catalyzed cross coupling of aryl Grignard reagents with aryl halides in toluene, a nonpolar solvent with a high boiling point. The reaction was applied for the synthesis of various biaryls in good yields without the introduction of a large steric ligand. The Kumada-Tamao-Corriu(KTC) reaction in toluene was then successfully modified to proceed under neat conditions for the efficient syntheses of symmetrical biaryls, particularly in large-scale preparations. Unactivated aryl chlorides show higher reactivity than aryl bromides, particularly under neat conditions. Mechanistic investigations suggest a radical procedure for the catalytic cycle, and the origin of the radical intermediates being aryl halides.     

A tin hydride designed to facilitate removal of tin species from products of stannane-mediated radical reactions

The stannane 1, which is simple to prepare, behaves like the conventional reagents Bu3SnH and Ph3SnH in standard free radical reactions, but with the special characteristic that the tin-containing byproducts are easily and very largely removed by mild hydrolysis (LiOH-water-THF or TsOH-water-THF), which converts them into base-soluble (aqueous NaHCO3) materials. The performance of stannane 1 was evaluated for a range of radical reactions involving halides, selenides, Barton-McCombie deoxygenation, and enyne cyclization. In several cases the effectiveness of the workup procedure in removing tin species was monitored by 1H NMR.     

Design of polyaromatic hydrocarbon-supported tin reagents: a new family of tin reagents easily removable from reaction mixtures

We report in this paper the preparation and use of stannanes 11, 12a, and 12b, compounds whose 3-pyrenylpropyl side chain affinity for activated carbon simplifies tin removal and product isolation. Our pyrene-supported reagents can be used for radical reductions and cyclizations (11), radical and cationic allylations (12a), and Stille couplings (12b) in much the same way as tributyltin derivatives.     

C−As Bond Formation Reactions for the Preparation of Organoarsenic(III) Compounds

Potential widespread applications of organoarsenic chemistry have been limited by the inherent lack of safe and effective As?C bond formation reactions. Several alternative reagents and methods have been developed in the last few decades to address the hazards and drawbacks associated with traditional arsenic synthetic strategies. Herein, this minireview summarizes the advances made in nucleophilic, electrophilic, radical and metal‐mediated As(III)?C bond formations while specifically highlighting the behavior of arsenic synthons with various well‐established reagents (eg. Grignard reagents, organolithium compounds, organometallic reagents, radical initiators and Lewis/Brønsted bases). Avenues for asymmetric synthesis are also discussed, as are recent advances in organoarsenic chemistry suggesting that arsines exhibit novel reactivities independent from that of other relatively more well explored Group V cogeners.     

Cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic and benzylic Grignard reagents and their application to tandem radical cyclization/cross-coupling reactions

Details of cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic Grignard reagents are disclosed. A combination of cobalt(II) chloride and 1,2-bis(diphenylphosphino)ethane (DPPE) or 1,3-bis(diphenylphosphino)propane (DPPP) is suitable as a precatalyst and allows secondary and tertiary alkyl halides--as well as primary ones--to be employed as coupling partners for allyl Grignard reagents. The reaction offers a facile synthesis of quaternary carbon centers, which has practically never been possible with palladium, nickel, and copper catalysts. Benzyl, methallyl, and crotyl Grignard reagents can all couple with alkyl halides. The benzylation definitely requires DPPE or DPPP as a ligand. The reaction mechanism should include the generation of an alkyl radical from the parent alkyl halide. The mechanism can be interpreted in terms of a tandem radical cyclization/cross-coupling reaction. In addition, serendipitous tandem radical cyclization/cyclopropanation/carbonyl allylation of 5-alkoxy-6-halo-4-oxa-1-hexene derivatives is also described. The intermediacy of a carbon-centered radical results in the loss of the original stereochemistry of the parent alkyl halides, creating the potential for asymmetric cross-coupling of racemic alkyl halides.     

Synthesis and applications of thiosulfonates and selenosulfonates as free-radical reagents

Chalcogenative sulfones (thiosulfonates and selenosulfonates), as reactants for organic transformations, are widely used and interesting because of their potential to react with nucleophiles, electrophiles, and free radicals. As stable radical reagents, the synthesis and applications of chalcogenative sulfones have opened up a novel pathway to synthesize many kinds of compounds containing sulfur or selenium motifs. However, despite the numerous recent works on the synthesis and applications of thiosulfonates and selenosulfonates as radical reagents, no review has yet provided a summary of the literature. In this paper, we aim to review the synthesis and applications strategies of chalcogenative sulfones as radical reagents reported over the past several decades. Different types of catalysis are discussed in this review: (i) metal catalysis; (ii) visible-light catalysis; (iii) synergistic catalysis; and (iiii) other types. Concurrently, in visible-light catalysis and metallaphotoredox catalysis sections, we highlight that developing relatively environmentally friendly synthetic methods in this area is always a great challenge, but also a persistent pursuit. Finally, the scopes, limitations, mechanisms, and existing problems of some reactions are described briefly.     

Formation of grignard reagents from aryl halides: effective radical probes hint at a nonparticipation of dianions in the mechanism

We have prepared highly efficient radical probes 2a-b involving the hex-5-enyl rearrangement. The reaction of 2a-b with active magnesium leads to the cyclized products 4a-b, providing a direct evidence of radical intermediates during the formation of aryl Grignard reagents. The variations of yields for cyclized products 4a-b as a function of structural modifications in 2a-b suggest that the intervention of dianions is not necessary to explain the observed results.     

Air-Stable Organoradical Boron Reagents

Both organic radicals and organoboron reagents have been broadly investigated, but the combination of them via direct C−H borylation as organic radical building blocks has never been achieved. Herein, a series of organoradical boron reagents, such as TTM-Bpin and TTM-BOH , were synthesized through the key step of C−H borylation of substrate TTM-H ((2,6-dichlorophenyl) bis(2,4,6-trichlorophenyl)methyl) radical for the first time. They are air stable enough to be stored in the solid state for several months under dark conditions, and fully investigated through single crystal analysis, EPR and DFT calculations. Furthermore, they can smoothly work in the standard Suzuki–Miyaura coupling (SMC) reaction with retention of the carbon radical center. Meanwhile, these radical species bearing different boron units display fluorescent character and are potentially applied for the collective synthesis of luminescent organic radicals, as well as other functionalized open-shell materials.     

Transition-metal-free trifluoromethylaminoxylation of alkenes

No transition metal! Fluorinated hypervalent-iodine reagents react with TEMPONa in the presence of an alkene under mild conditions to give the corresponding perfluoroalkylaminoxylation products. These radical addition/trapping reactions occur with high stereoselectivity using commercially available reagents, and the product alkoxyamines are readily transformed into the corresponding alcohols.     

Strategies for generating peptide radical cations via ion/ion reactions

Several approaches for the generation of peptide radical cations using ion/ion reactions coupled with either collision induced dissociation (CID) or ultraviolet photo dissociation (UVPD) are described here. Ion/ion reactions are used to generate electrostatic or covalent complexes comprised of a peptide and a radical reagent. The radical site of the reagent can be generated multiple ways. Reagents containing a carbon–iodine (C―I) bond are subjected to UVPD with 266‐nm photons, which selectively cleaves the C―I bond homolytically. Alternatively, reagents containing azo functionalities are collisionally activated to yield radical sites on either side of the azo group. Both of these methods generate an initial radical site on the reagent, which then abstracts a hydrogen from the peptide while the peptide and reagent are held together by either electrostatic interactions or a covalent linkage. These methods are demonstrated via ion/ion reactions between the model peptide RARARAA (doubly protonated) and various distonic anionic radical reagents. The radical site abstracts a hydrogen atom from the peptide, while the charge site abstracts a proton. The net result is the conversion of a doubly protonated peptide to a peptide radical cation. The peptide radical cations have been fragmented via CID and the resulting product ion mass spectra are compared to the control CID spectrum of the singly protonated, even‐electron species. This work is then extended to bradykinin, a more broadly studied peptide, for comparison with other radical peptide generation methods. The work presented here provides novel methods for generating peptide radical cations in the gas phase through ion/ion reaction complexes that do not require modification of the peptide in solution or generation of non‐covalent complexes in the electrospray process. Copyright © 2015 John Wiley & Sons, Ltd.     

Mechanism of Iodine(III)-Promoted Oxidative Dearomatizing Hydroxylation of Phenols: Evidence for a Radical-Chain Pathway

The oxidative dearomatization of phenols with the addition of nucleophiles to the aromatic ring induced by hypervalent iodine(III) reagents and catalysts has emerged as a highly useful synthetic approach. However, experimental mechanistic studies of this important process have been extremely scarce. In this report, we describe systematic investigations of the dearomatizing hydroxylation of phenols using an array of experimental techniques. Kinetics, EPR spectroscopy, and reactions with radical probes demonstrate that the transformation proceeds by a radical-chain mechanism, with a phenoxyl radical being the key chain-carrying intermediate. Moreover, UV and NMR spectroscopy, high-resolution mass spectrometry, and cyclic voltammetry show that before reacting with the phenoxyl radical, the water molecule becomes activated by the interaction with the iodine(III) center, causing the Umpolung of this formally nucleophilic substrate. The radical-chain mechanism allows the rationalization of all existing observations regarding the iodine(III)-promoted oxidative dearomatization of phenols.     

Acyl Radicals from Aromatic Carboxylic Acids by Means of Visible‐Light Photoredox Catalysis

Simple and abundant carboxylic acids have been used as acyl radical precursor by means of visible‐light photoredox catalysis. By the transient generation of a reactive anhydride intermediate, this redox‐neutral approach offers a mild and rapid entry to high‐value heterocyclic compounds without the need of UV irradiation, high temperature, high CO pressure, tin reagents, or peroxides.     

Self-protection: the advantage of radical oligomeric mixtures in organic synthesis

Atom-transfer radical oligomers of allyl iodoacetates were converted to 4-pentenoic acids upon treatment with zinc. Reactions of the radical oligomers of various omega-alkenyl iodoacetates with Grignard reagents afforded the corresponding substituted tetrahydrofuran derivatives. These results indicated that radical oligomeric mixtures not only serve as versatile intermediates in organic synthesis, but also exhibit unique advantages in that the oligomeric mixtures are self-protected and the deoligomerization functions as the simultaneous deprotection.     

Internal Perfluoroolefins in the Synthesis of Organofluorine Compounds

The review discusses reactions of internal perfluoroolefins with nucleophilic reagents. Modes ofgeneration of carbon-centered anions, radical species containing perfluoroalkyl groups are considered.     

Cover Feature: Fluoroalkyl Sulfoximines for Versatile Photocatalytic Radical Fluoroalkylations (Chem. Rec. 9/2023)

Fluoroalkyl sulfoximines, which serve as electron-accepting fluoroalkyl radical sources, are easy-to-handle, solid, and bench-stable chemicals. Fluoroalkyl radicals can be generated from sulfoximine reagents using strong one-electron injectors, such as a highly reducing photoredox catalyst in the excited state. Our group has developed photocatalytic radical di- and mono-fluoromethylation and α-monofluoroalkylation of olefins with the corresponding fluoroalkyl sulfoximines. In this personal account, appropriate combinations of fluoroalkyl sulfoximines and photoredox catalysts, leading to successful radical fluoroalkylation, have been discussed.