Sila‐ and Germacarboxylic Acids: Precursors for the Corresponding Silyl and Germyl Radicals

Silicon‐containing compounds are widely used as synthetic building blocks, functional materials, and bioactive reagents. In particular, silyl radicals are important intermediates for the synthesis and transformation of organosilicon compounds. Herein, we describe the first protocol for the generation of silyl radicals by photoinduced decarboxylation of silacarboxylic acids, which can be easily prepared in high yield on a gram scale and are very stable to air and moisture. Irradiation of silacarboxylic acids with blue LEDs (455 nm) in the presence of a commercially available photocatalyst releases silyl radicals, which can further react with various alkenes to give the corresponding silylated products in good‐to‐high yields with broad functional‐group compatibility. This reaction proceeds in the presence of water, enabling efficient deuterosilylation of alkenes with D₂O as the deuterium source. Germyl radicals were similarly obtained.     

BCl3‐Mediated Ene Reaction of Sulfur Dioxide and Unfunctionalized Alkenes

The first ene reactions of SO₂ and unfunctionalized alkenes are reported. Calculations suggest that the endergonic ene reactions of SO₂ with alkenes can be used to generate β,γ‐unsaturated sulfinyl and sulfonyl compounds. Indeed, in the presence of one equivalent of BCl₃, the unstable sulfinic acid form stable sulfinic acid?BCl₃ complexes that can be reacted in situ with NCS to generate corresponding sulfonyl chlorides, or with a base to generate corresponding sulfinates. The latter can be reacted with electrophiles to generate sulfones, or with silyl chloride to form β,γ‐unsaturated silyl sulfinates. The sulfinic acid?BCl₃ complexes can be reacted with ethers that act as oxygen nucleophiles to produce corresponding sulfinic esters. Thus one‐pot, three‐component synthesis of β,γ‐unsaturated sulfonamides, sulfinyl esters and sulfones have been developed starting from alkenes and sulfur dioxide (reagent and solvent).     

Regio- and stereoselective functionalization of alkenes with emphasis on mechanistic insight and sustainability concerns

Alkene is an attractive substrate for chemists due to its easy availability and reactivity towards large number of reactants affording diverse range of organic compounds. It reacts under ionic and free radical mechanisms including single electron transfer (SET). In this review, strategies used for C–C and C-heteroatom functionalization of alkene has been discussed with emphasis on the regio, stereoselectivity, mechanistic detail and sustainability aspects. These strategies mainly follow the free radical mechanism, and the highly reactive carbon radicals show uncontrollable regio- and stereoselectivities. Thus these strategies still need to be focused; especially in the asymmetric versions. The regio- and stereoselectivities of functionalization of alkenes have been highlighted and debated. In addition, the hazardous reagents such as Cl₂, Br₂ I₂, CO, peroxides, and benzene have also been discussed with the emphasis on their impact on the environment. Their plausible green alternatives have also been suggested, such as MX as halogen replacement; CO surrogates (formaldehyde etc.); sustainable aromatic solvents as benzene replacement. The non-green strategies relying on pre-formed silyl hydride and their green alternative strategies such as transfer hydrogenations have also been indicated. The applications of the functionalization of alkenes for the total synthesis of bioactive compounds have also been discussed in detail. In addition, future perspectives are also highlighted for further developments in the functionalization of alkenes.     

Titanocene-catalyzed carbosilylation of alkenes and dienes using alkyl halides and chlorosilanes

A new method for regioselective carbosilylation of alkenes and dienes has been developed by the use of a titanocene catalyst. This reaction proceeds efficiently at 0 degrees C in THF in the presence of Grignard reagents by the combined use of alkyl halides (R'-X, X = Br or Cl) and chlorotrialkylsilanes (R3'Si-Cl) as the alkylating and silylating reagents, respectively. Terminal alkenes having aryl or silyl substituents (YRC=CH2, Y = Ar or Me3Si, R = H or Me) afford addition products YRC-(SiR'3)-CH2R' in good yields, whereas 1-octene and internal alkenes were sluggish. When 2,3-disubstituted 1,3-butadienes were used instead of alkenes, alkyl and silyl units are introduced at the 1- and 4-positions giving rise to allylsilanes in high yields under similar conditions. The present reaction involves (i) addition of alkyl radicals toward alkenes or dienes, and (ii) electrophilic trapping of benzyl- or allylmagnesium halides with chlorosilanes. The titanocene catalyst plays important roles in generation of these active species, i.e., alkyl radicals and benzyl- or allylmagnesium halides.     

New Radical Borylation Pathways for Organoboron Synthesis Enabled by Photoredox Catalysis

Radical borylation using N‐heterocyclic carbene (NHC)‐BH₃ complexes as boryl radical precursors has emerged as an important synthetic tool for organoboron assembly. However, the majority of reported methods are limited to reaction modes involving carbo‐ and/or hydroboration of specific alkenes and alkynes. Moreover, the generation of NHC‐boryl radicals relies principally on hydrogen atom abstraction with the aid of radical initiators. A distinct radical generation method is reported, as well as the reaction pathways of NHC‐boryl radicals enabled by photoredox catalysis. NHC‐boryl radicals are generated via a single‐electron oxidation and subsequently undergo cross‐coupling with the in‐situ‐generated radical anions to yield gem‐difluoroallylboronates. A photoredox‐catalyzed radical arylboration reaction of alkenes was achieved using cyanoarenes as arylating components from which elaborated organoborons were accessed. Mechanistic studies verified the oxidative formation of NHC‐boryl radicals through a single‐electron‐transfer pathway.     

Free Radical Chemistry of Phosphasilenes

Understanding the characteristics of radicals formed from silicon‐containing heavy analogues of alkenes is of great importance for their application in radical polymerization. Steric and electronic substituent effects in compounds such as phosphasilenes not only stabilize the Si=P double bond, but also influence the structure and species of the formed radicals. Herein we report our first investigations of radicals derived from phosphasilenes with Mes, Tip, Dur, and NMe₂ substituents on the P atom, using muon spin spectroscopy and DFT calculations. Adding muonium (a light isotope of hydrogen) to phosphasilenes reveals that: a) the electron‐donor NMe₂ and the bulkiest Tip‐substituted phosphasilenes form several muoniated radicals with different rotamer conformations; b) bulky Dur‐substituted phosphasilene forms two radicals (Si‐ and P‐centred); and c) Mes‐substituted phosphasilene mainly forms one species of radical, at the P centre. These significant differences result from intramolecular substituent effects.     

Reactions of gas phase amino acids with the prevailing radicals in biomass thermal treatments

Amino acids, N-containing compounds, hold a significant importance in various field. Within the biomass energy sector, amino acids constitute a large fraction of the biomass's nitrogen content. As such, it is essential to comprehend their combustion chemistry; most specifically their biomolecular interactions with governing radicals in the pyrolytic and combustion media that prevail during thermal utilization of biomass. Herein, we have employed quantum chemical calculations and reaction rate theory to investigate reactions of a selected set of amino acids with H, CH₃, NH₂, OH, HO₂, and HS radicals. Thermo-kinetic calculations have been performed to determine the rates of hydrogen abstraction by these six radicals across all possible reaction channels for three specific amino acids: alanine, cysteine, and methionine. The investigation of other amino acids like glycine, threonine, and other models have been carried out for α-C positions as the most probable abstractable sites. The study also examines the individual effects of different substituents (COOH, NH₂, HS, and CH₂) and uncovers significant insights. Notably, the presence of the COOH group introduces polar effects that counterintuitively deactivate the thermodynamically favored α-abstraction pathway. Presented thermo-kinetic values are anticipated to complement existing biomass kinetic models and to improve current understanding of chemical events that participate in the complex nitrogen transformation reactions in biomass.     

Synthesis,Reactions and Applications of Phosphorus Containing Carbon Centered Radicals

A general method for synthesis of C_n-C (n=1, 2...) phosphonate bonds involving a reaction of 1-diethoxy-phosphorylalkan-1-, -2-and -3-yl radicals 1,3,6 with alkenes 4, a new example of functional group interconversion in 1-heterosubstituted phosphonates and synthesis of useful phosphoroorganic compounds and methylenomycin B are described.     

Generation of Aryl Radicals through Reduction of Hypervalent Iodine(III) Compounds with TEMPONa: Radical Alkene Oxyarylation

A novel method for selective generation of aryl radicals from diaryliodonium salts and iodanylidene malonates with sodium 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPONa) as a single‐electron transfer (SET) reducing reagent is described. In the presence of various alkenes, aryl radicals formed after SET‐reduction of hypervalent iodine compounds undergo alkene addition and the adduct radicals that are thus generated are efficiently trapped by the concomitantly generated TEMPO radical to eventually afford oxyarylated products in moderate to very good yields. The efficiency of aryl radical generation of various iodine(III) reagents is studied and the generation of an iodanylidene malonate aryl radical is also investigated by computational methods.     

Catalytic Reactions with Hydrosilane and Carbon Monoxide [New synthetic methods (30)]

The reagent hydrosilane/carbon monoxide opens up new possibilities for organic synthesis. Four cases will be discussed: 1. The reaction of olefins with hydrosilane (trialkylsilane) and carbon monoxide in the presence of Co, Ru, and Rh complexes leads to enol silyl ethers having one more carbon atom that the olefins. 2. Cyclic ethers underto carbonylative ring opening to ω-siloxyaldehydes when reacted with hydrosilane and carbon monoxide in the presence of Co₂(CO)₈ as catalysts 3. Aldehydes are catalytically converted into the next higher α-siloxyaldehydes or 1,2-bis(siloxy)alkenes depending on the reaction conditions used. 4. The reaction of alkyl acetates proceeds in various ways depending on the nature of the alkyl group; enol silyl ethers or alkenes are optained.–Mechanisms of these Co₂(CO)₈ catalyzed reactions using hydrosilane and carbon monoxide are discussed in which HCo(CO)_n or R₃SiCo(CO)_nL function as catalytically active agents. With these species there are four types of catalytic cycles.–The synthetic possibilities of these catalytic reactions have still not been fully explored.     

Activation of Homolytic SiZn and SiHg Bond Cleavage,Mediated by a Pt0 Complex,via Novel PtZn and PtHg Compounds

The thermally stable [(tBuMe₂Si)₂M] (M=Zn, Hg) generate R₃Si^. radicals in the presence of [(dmpe)Pt(PEt₃)₂] at 60–80 °C. The reaction proceeds via hexacoordinate Pt complexes, (M=Zn ( 2 a and 2 b ), M=Hg ( 3 a and 3 b )) which were isolated and characterized. Mild warming or photolysis of 2 or 3 lead to homolytic dissociation of the Pt? MSiR₃ bond generating silyl radicals and novel unstable pentacoordinate platinum paramagnetic complexes (M=Zn ( 5 ), Hg ( 6 )) whose structures were determined by EPR spectroscopy and DFT calculations.     

Formation of CC Bonds by Addition of Free Radicals to Alkenes

There are many reactions in which CC bonds are formed by addition of free radicals to alkenes. Information about the mechanism is important for the synthesis of specific target molecules. The rate of addition of alkyl radicals to alkenes is controlled by steric and polar effects. The stabilities of the educts and products are of only limited importance, since the transition states for these exothermic reactions occur very early on the reaction coordinate. Variations in reactivity and selectivity can be described using frontier orbital theory: for nucleophilic radicals the dominant interactions are those between SOMO's and LUMO's, and for electrophilic radicals those between SOMO's and HOMO's. The large differences in the steric effects of α - and β- substituents of alkenes can be explained by postulating an unsymmetrical transition state— the radical approaches one of the C atoms preferentially. Regioand stereoselectivities can be predicted and are determined, in general, by steric effects.     

Amides as precursors of imidoyl radicals in cyclisation reactions

Amides have been successfully used as precursors of imidoyl radicals for radical cyclisation. The amides have been converted to imidoyl selanides via reaction with phosgene to yield imidoyl chlorides followed by reaction with potassium phenylselanide. Imidoyl selanides were reacted with tributyltin hydride (Bu₃SnH) as the radical mediator with triethylborane or AIBN as initiators to yield imidoyl radicals for cyclisation reactions. Imidoyl radicals have been cyclised onto alkenes to yield 2,3-substituted-indoles and -quinolines and also onto pyrroles and indoles to give bi- and tricyclic heteroarenes.     

Visible Light-Promoted Ring-Opening Alkenylation of Cyclic Hemiacetals through β-Scission of Alkoxy Radicals

The chemistry of alkoxy radicals was extensively explored during the period of 1960s to 1990s, but it has remained dormant for the past few decades. Recently, alkoxy radicals attract the attentions again, because new methods for generating alkoxy radical species have emerged. These newly developed methods are mainly based on the photolysis by visible light under mild conditions, thus allowing for new transformations of the carbon-centered radical species that are generated from the β-scission or hydrogen abstraction of the alkoxy radicals. Herein, we demonstrate that the alkoxy radicals derived from cyclic hemiacetals can be generated through visible-light-induced electron transfer with sodium iodide and triphenylphosphine as the catalyst. The alkoxy radicals subsequently undergo β-scission to generate carbon-centered radicals, which are trapped by cinnamic acids, aryl alkenes, vinylboronic acid and silyl enol ether to deliver the corresponding C—C bond forming products. This catalytic method for ring-opening alkenylation reaction of cyclic hemiacetal derivatives under visible-light irradiation conditions demonstrates the compatibility of the visible light-promoted alkoxy radical generation method with various carbon radical trapping processes. This work opens up new possibilities for the application of alkoxy radicals in organic synthesis.      

Transition-Metal-Free Three-Component Radical 1,2-Amidoalkynylation of Unactivated Alkenes

A transition-metal-free radical 1,2-amidoalkynylation of unactivated alkenes is presented. α-Amido-oxy acids were used as amidyl radical precursors, which were oxidized by an organic photoredox catalyst (4CzlPN). The electrophilic N-radicals chemoselectively reacted with various aliphatic alkenes and the adduct radicals were then trapped by ethynylbenziodoxolone (EBX) reagents to eventually provide the amidoalkynylation products. These transformations, which were conducted under practical and mild conditions, showed high functional group tolerance and broad substrate scope. Mechanistic studies supported the radical nature of these cascades.     

Unprecedented aromatic homolytic substitutions and cyclization of amide-iminyl radicals: experimental and theoretical study

Amide-iminyl radicals are versatile and efficient intermediates in cascade radical cyclizations of N-acylcyanamides. They are easily trapped by alkenes or (hetero-)aromatic rings and cyclize into a series of new heterocyclic compounds which bear a pyrroloquinazoline moiety. As an illustration of the synthetic importance of these compounds, the total synthesis of the natural antitumor compound luotonin A was achieved through a tin-free radical cascade cyclization process. Not only do amide-iminyl radicals lead to new tetracyclic heterocycles but these nitrogen-centered radical species also react in aromatic homolytic substitutions. Indeed, the amide-iminyl radical moiety unprecedentedly displaces methyl, methoxy, and fluorine radicals from an aromatic carbon atom. This seminal reaction in the field of radical chemistry has been developed experimentally and its mechanism has additionally been investigated by a theoretical study.     

Initiation of Radical Chain Reactions of Thiol Compounds and Alkenes without any Added Initiator: Thiol‐Catalyzed cis/trans Isomerization of Methyl Oleate

A kinetic study of the dodecanethiol‐catalyzed cis/trans isomerization of methyl oleate (cis‐ 2 ) without added initiator was performed by focusing on the initiation of the radical chain reaction. The reaction orders of the rate of isomerization were 2 and 0.5 for 1 and cis‐ 2 , respectively, and an overall kinetic isotope effect k_H/k_D of 2.8 was found. The initiation was shown to be a complex reaction. The electron‐donor/‐acceptor (EDA) complex of dodecanethiol ( 1 ) and cis‐ 2 formed in a pre‐equilibrium reacts with thiol 1 to give a stearyl and a sulfuranyl radical through molecule‐assisted homolysis (MAH) of the sulfur–hydrogen bond. Fragmentation of the latter gives the thiyl radical, which catalyzes the cis/trans isomerization. A computational study of the EDA complex, MAH reaction, and the sulfuranyl radical calculated that the activation energy of the isomerization was in good agreement with the experimental result of E_A=82 kJ M ^?1. Overall, the results may explain that the thermal generation of thiyl radicals without any initiator is responsible for many well‐known thermally initiated addition reactions of thiol compounds to alkenes and their respective polymerizations and for the low shelf‐life stability of cis‐unsaturated thiol compounds and of mixtures of alkenes and thiol compounds.     

L3C3P3: Tricarbontriphosphide Tricyclic Radicals and Cations Stabilized by Cyclic (alkyl)(amino)carbenes

Alkynes usually oligomerize to give rings with a conjugated π‐electron system. In contrast, phosphaalkynes, R?C≡P, frequently give compounds with polycyclic structures, which are thermodynamically more stable than the corresponding π‐conjugated isomers. The syntheses of the first C₃P₃ tricyclic compounds are reported with either radical or cationic ground states stabilized by cyclic (alkyl)(amino)carbenes (CAACs). These compounds may be considered as examples of tricarbontriphosphide coordinated by carbenes and are likely formed via trimerization of the corresponding mono‐radicals CAAC‐CP^.. The mechanism for the formation of these tricarbontriphosphide radicals has been rationalized by a combination of experiments and DFT calculations.     

Photoredox-Catalyzed Addition of Carbamoyl Radicals to Olefins: A 1,4-Dihydropyridine Approach

Functionalization with C1-building blocks are key synthetic methods in organic synthesis. The low reactivity of the most abundant C₁-molecule, carbon dioxide, makes alternative carboxylation reactions with CO₂-surrogates especially important. We report a photoredox-catalyzed protocol for alkene carbamoylations. Readily accessible 4-carboxamido-Hantzsch esters serve as convenient starting materials that generate carbamoyl radicals upon visible light-mediated single-electron transfer. Addition to various alkenes proceeded with high levels of regio- and chemoselectivity.     

Cyclization of 1-(carbamoyl)dichloromethyl radicals upon activated alkenes. A new entry to 2-azabicyclo[3.3.1]nonanes

The synthesis of 2-azabicyclo[3.3.1]nonanes using a radical cyclization process as the piperidine ring-forming step is described. The reaction involves 1-(carbamoyl)-dichloromethyl radicals which react intramolecularly with simple or activated alkenes, such as enol acetates or silyl enol ethers.