Allylation of C(sp 3 )─H Bonds Using a MW/Persulfate Protocol

A base-controlled regioselective synthesis of allyl and vinyl phenyl sulfones

The Minisci‐type reaction between C(sp3)─H bonds and nitrogen‐containing aromatics was carried out using a simple protocol based on the persulfate anion (PS) under microwave (MW) irradiation. The MW/PS protocol is applicable to a wide variety of dehydrogenative coupling reactions of N‐heteroaromatics and C(sp3)─H bonds, leading to the formation of alkylated heteroaromatics. Site‐selectivity is ensured by hydrogen atom transfer (HAT) with the sulfate radical affecting the polar/steric effects in the transition state. The MW/PS protocol was applicable to direct intramolecular cyclization to give five and six‐membered rings fused by pyridine and lutidine, which, in previous methods, it was necessary to use tedious derivatization to imino‐oxyacetic acids as HAT precursors.

Ni-rich LiNi0.8Co0.1Mn0.1O2 oxide functionalized by allyl phenyl sulfone as high-performance cathode material for lithium-ion batteries

Hydrogen atom transfer (HAT) is a fundamental reaction that takes part in a wide variety of chemical and biological processes, with relevant examples that include the action of antioxidants, damage to biomolecules and polymers, and enzymatic and biomimetic reactions. Moreover, great attention is currently devoted to the selective functionalization of unactivated aliphatic C-H bonds, where HAT based procedures have been shown to play an important role. In this Account, we describe the results of our recent studies on the role of structural and medium effects on HAT from aliphatic C-H bonds to the cumyloxyl radical (CumO(•)). Quantitative information on the reactivity and selectivity patterns observed in these reactions has been obtained by time-resolved kinetic studies, providing a deeper understanding of the factors that govern HAT from carbon and leading to the definition of useful guidelines for the activation or deactivation of aliphatic C-H bonds toward HAT. In keeping with the electrophilic character of alkoxyl radicals, polar effects can play an important role in the reactions of CumO(•). Electron-rich C-H bonds are activated whereas those that are α to electron withdrawing groups are deactivated toward HAT, with these effects being able to override the thermodynamic preference for HAT from the weakest C-H bond. Stereoelectronic effects can also influence the reactivity of the C-H bonds of ethers, amines, and amides. HAT is most rapid when these bonds can be eclipsed with a lone pair on an adjacent heteroatom or with the π-system of an amide functionality, thus allowing for optimal orbital overlap. In HAT from cyclohexane derivatives, tertiary axial C-H bond deactivation and tertiary equatorial C-H bond activation have been observed. These effects have been explained on the basis of an increase in torsional strain or a release in 1,3-diaxial strain in the HAT transition states, with kH(eq)/kH(ax) ratios that have been shown to exceed one order of magnitude. Medium effects on HAT from aliphatic C-H bonds to CumO(•) have been also investigated. With basic substrates, from large to very large decreases in kH have been measured with increasing solvent hydrogen bond donor (HBD) ability or after addition of protic acids or alkali and alkaline earth metal ions, with kinetic effects that exceed 2 orders of magnitude in the reactions of tertiary alkylamines and alkanamides. Solvent hydrogen bonding, protonation, and metal ion binding increase the electron deficiency and the strength of the C-H bonds of these substrates deactivating these bonds toward HAT, with the extent of this deactivation being modulated by varying the nature of the substrate, solvent, protic acid, and metal ion. These results indicate that through these interactions careful control over the HAT reactivity of basic substrates toward CumO(•) and other electrophilic radicals can be achieved, suggesting moreover that these effects can be exploited in an orthogonal fashion for selective C-H bond functionalization of substrates bearing different basic functionalities.

Review: 50 refs.

Synergistic CO2 Mediation and Photocatalysis for α-Alkylation of Primary Aliphatic Amines

Silicon-based anodes have received widespread attention because of their high theoretical capacity, which, however, still faces challenges for practical applications due to the large volume changes during repeated charge/discharge processes, despite being developed for many years. Herein, we explore an electrolyte additive, allyl phenyl sulfone (APS), to enhance the interfacial stability and long-term durability of the SiOx/C electrode. It is revealed that additive APS contributes to forming a dense and robust solid electrolyte interphase film with high mechanical strength and favorable lithium-ion diffusion kinetics, which effectively suppresses the parasitic side reactions at the electrode-electrolyte interface. Meanwhile, the strong interaction between APS and trace water/acid in the electrolyte is further beneficial for enhancing the interfacial stability. By incorporating 0.5 wt% APS, the cycling stability of the silicon-based electrode is significantly improved, reserving a capacity of 777 mAh g-1 after 200 cycles at 0.5C and 30 °C (79.3% capacity retention), which well exceeds that of the baseline electrolyte (57.8% capacity retention). More importantly, additive APS effectively promotes the cycling performance of the corresponding SiOx/C||NCM90 (LiNi0.9Co0.05Mn0.05O2) full battery. This work provides valuable understanding in developing new electrolyte additives to enable the commercial application of high-energy density lithium-ion batteries using silicon-based anodes.

Cobaloxime is a versatile 3d‐metal catalyst for dehydrogenative radical coupling reactions. Prior mechanistic studies of cobaloxime catalysis have revealed that cobaloxime(II)‐catalyzed hydrogen atom transfer (HAT) process can control the site‐selectivity and chemoselectivity of radical transformation. However, the relevance of HAT to the enantioselectivity is seldom reported. Herein, our density functional theory studies of the cobaloxime‐chiral amine co‐catalyzed enantioselective coupling of the enamine radical cation with alkene proved that it is the HAT step that determines the enantioselectivity, instead of the previously proposed radical addition. Because the metal–alkene‐coupled (MAC) radical addition is a reversible process while the followed by HAT is the rate‐determining step. Moreover, computational studies suggest that the dynamically changing hydrogen bonding between the radical cation and cobaloxime plays a significant role in harnessing the reactivity and tuning the enantiocontrol. The intra‐ and inter‐molecular hydrogen bonding between the iminium and the cobaloxime fragments contributes to the lower energy barrier of MAC radical addition. Structural analysis and quantitative steric‐electronic effect dissection jointly unveiled that the stronger intermolecular hydrogen bonding between the aminium and the cobaloxime fragments is the dominant factor that stabilizes the (R)‐HAT transition state and guarantees high enantioselectivity.

Cobaloxime is a versatile 3d-metal catalyst for dehydrogenative radical coupling reactions. Prior mechanistic studies of cobaloxime catalysis have revealed that cobaloxime(II)-catalyzed hydrogen atom transfer (HAT) process can control the site-selectivity and chemoselectivity of radical transformation. However, the relevance of HAT to the enantioselectivity is seldom reported. Herein, our density functional theory studies of the cobaloxime-chiral amine co-catalyzed enantioselective coupling of the enamine radical cation with alkene proved that it is the HAT step that determines the enantioselectivity, instead of the previously proposed radical addition. Because the metal-alkene-coupled (MAC) radical addition is a reversible process while the followed by HAT is the rate-determining step. Moreover, computational studies suggest that the dynamically changing hydrogen bonding between the radical cation and cobaloxime plays a significant role in harnessing the reactivity and tuning the enantiocontrol. The intra- and inter-molecular hydrogen bonding between the iminium and the cobaloxime fragments contributes to the lower energy barrier of MAC radical addition. Structural analysis and quantitative steric-electronic effect dissection jointly unveiled that the stronger intermolecular hydrogen bonding between the aminium and the cobaloxime fragments is the dominant factor that stabilizes the (R)-HAT transition state and guarantees high enantioselectivity.

The stereoselective synthesis of all carbon quaternary stereocenters is an important problem in synthetic chemistry due to their common occurrence in bioactive compounds. The zoanthamine class of marine natural products highlights the challenge in constructing such stereocenters. After a summary of the isolation, structure determination, and biological activities of the zoanthamine natural products, published approaches toward their chemical synthesis are reviewed. Synthetic strategies toward the carbocyclic portion of zoanthenol focus on the synthesis of the three challenging quaternary stereocenters located on the central C ring. An unusual acid-mediated SN' cyclization of a nucleophilic arene with an allylic alcohol forms the B ring and diastereoselectively constructs the benzylic C(12) quaternary stereocenter. However, difficulties with late-stage installation of the remaining C(9) quaternary stereocenter compelled the use of C ring synthons containing the vicinal C(9) and C(22) stereocenters installed at an early stage in the synthesis. Desymmetrization of a meso-anhydride containing vicinal quaternary stereocenters accomplishes this goal in an enantioselective fashion. Several C ring synthons bearing the vicinal quaternary stereocenters are elaborated with A ring fragments, and several methods for the formation of the C(11)-C(12) bond in these systems are explored. Ultimately, a radical conjugate addition strategy provides the carbocyclic core of zoanthenol with the correct relative configuration of all three quaternary stereocenters. These efforts toward the synthesis of zoanthenol highlight the difficulty in generating enantioenriched alpha-quaternary cycloalkanones derived from ketones with multiple acidic alpha-hydrogens. The first direct catalytic enantioselective access to such products is achieved by the application of chiral bidentate phosphinooxazoline (PHOX) ligands to Tsuji’s non-enantioselective allylation reactions. Cyclic allyl enol carbonates, silyl enol ethers, and allyl beta-ketoesters all provide uniformly excellent yields and high enantioselectivity in the reaction. The limitations on the substrate scope of the reaction are discussed. Preliminary studies into the mechanism of these allylation reactions with prochiral enolate fragments suggest that they occur by a different mechanism than the outer-sphere nucleophilic attack commonly proposed in the alkylation of prochiral allyl fragments.

A comparison of hydride, hydrogen atom, and proton-coupled electron transfer reactions is presented. Herein, hydride and hydrogen atom transfer refer to reactions in which the electrons and protons transfer between the same donor and acceptor, while proton-coupled electron transfer (PCET) refers to reactions in which the electrons and protons transfer between different centers. Within these definitions, hydride and hydrogen atom transfer reactions are typically electronically adiabatic, hence evolving on a single electronic surface. In contrast, PCET reactions are often electronically nonadiabatic since the electron transfers a longer distance through a proton transfer interface. For all three types of reactions, solute reorganization is important, particularly the hydrogen donor--acceptor mode. Solvent reorganization is critical for hydride transfer and PCET, which involve significant solute charge redistribution, but not for hydrogen atom transfer. Theoretical descriptions and simulation methodology for all three types of reactions are presented, as well as experimentally relevant applications to hydride transfer in enzymes and PCET in solution.

Pterins (also known as pteridines) are common animal colorants that constitute heterocyclic compounds and have the highest nitrogen content of any pigment analyzed from animals. It has been reported that pterins modulate oxidative stress as these molecules are able to scavenge free radicals. Previous reports suggest three possible mechanisms that are responsible for scavenging free radicals; these are electron transfer (ET) reaction, hydrogen atom transfer (HAT) and radical addition. In this paper, the facility to scavenge free radicals (antiradical power) of pterins is analyzed, using density functional theory calculations and considering two possible mechanisms: ET and HAT. For the electron transfer process, considering the electron donor facility of the free radical scavenger molecules, vertical ionization energy of pterins indicates that the antiradical power of those pterins is lower than the antiradical power of any carotenoids (except for tetrahydrobiopterin). In terms of the HAT mechanism, the bond dissociation energy involved in the removal of one hydrogen atom from pterins is higher than for carotenoids (except for sepiapterin and 7,8-dihydrobiopterin). It can be expected that the most reactive molecules are those that have the smallest dissociation energy since the dissociation of the hydrogen atom is the first step of the reaction. This could indicate that some pterins are depicted as poorer antiradicals than carotenoids in terms of the HAT mechanism. Further studies focusing on the third mechanism (radical addition) and the kinetics of the reactions are necessary in order to fully understand the antiradical power of these substances. For this reason, work continues in order to clarify these aspects.

While the bis-alkylation of the dilithio derivative of allyl phenyl sulfone with cis-1,4-dichloro-2-butene produces the cyclopentene product, the similar reaction with the trans-dihalide affords the divinylcyclopropane product which rearranges smoothly, upon refluxing in xylenes, into the 1,4-cycloheptadiene system in 65% overall yield from allyl phenyl sulfone.

Stereocontrolled one-pot synthesis of cycloalkane derivatives possessing a quaternary carbon using allyl phenyl sulfone

Photoredox catalysis can be induced to activate organic substrates or to modulate the oxidation state of transition-metal catalysts via unique single-electron transfer processes, so as to achieve c...