Eosin Y as a direct hydrogen-atom transfer photocatalyst for the C3-H acylation of quinoxalin-2(1H)-ones

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

Electrophotocatalytic Si–H Activation Governed by Polarity-Matching Effects

It has been well-demonstrated that the combination of photosensitive (PS), hydrogen atom transfer (HAT) and single electron transfer (SET) processes can achieve efficient radical-mediated organic synthesis, but such reaction systems are usually homogeneous, requiring additional HAT agents and can only activate one substrate. Here, we constructed two crystalline porous materials, Zr/Hf-NDI, which possess excellent light absorbing capacity and a confined radical microenvironment, making them able to integrate PS, HAT, and SET processes to simultaneously activate two substrates. Thus, as heterogeneous photocatalysts, they exhibited excellent catalytic performance for the carbon radical-mediated cross-coupling reaction between alcohols and o-phenylenediamine (OPD) to synthesize benzimidazoles (yield > 99%). More importantly, they displayed very good substrate compatibility, especially for OPD substrates with electron-withdrawing groups, even surpassing those of noble metal catalysts. In situ characterizations combined with theoretical calculations showed that the high activity of these catalysts arose from: (i) the metal-oxo clusters and radical NDI˙- ligands can form hydrogen bonding traction activation for the alcohol substrate, and thus facilitate it to generate key intermediate α-carbon radical through a HAT process; (ii) the OPD substrate, acting as an electron donor, forms strong D-A interaction with the NDI ligand and activates the NDI and itself into radicals NDI˙- and OPD˙+, respectively, via an SET process, further promoting the reaction. To the best of our knowledge, this is the best performing crystalline porous catalyst for photocatalytic carbon radical-induced benzimidazole synthesis.

The selective functionalization of inactive CH bonds is a subject of continuous exploration by synthetic organic chemists. Recent approaches relying on hydrogen atom transfer (HAT) processes have led to a tremendous revival in this field, due to the ability to activate inert CH bonds becoming more easily under mild conditions. HAT is applicable to a wider range of applications, possessing a higher tolerance of functional groups. Many synthetic methods based on HAT have been widely reported in the last few years. Recently, developments in mild methods for generating various central radicals have enabled them to be utilized in HAT processes, which in turn led to the development of remote C(sp 3 )H functionalization reactions for alcohols, amines, amides, and related compounds. This article mainly covers recent advances in 1, n ‐HAT ( n = 4–8) methods involving photocatalytic, electrocatalytic, and metal‐catalytic approaches to CH functionalization reactions.

ConspectusIn the past decade, visible-light-mediated photocatalysis has emerged as an applicable strategy for the generation of diverse radical species via single electron transfer (SET) and energy transfer (EnT) processes. Within this context, visible-light-mediated hydrogen atom transfer (HAT) has attracted major interest due to its mild and environmentally benign conditions applied in the selective activation of C-H bonds. Strategies employing C- and heteroatom-centered radical species to selectively activate C-H bonds have become versatile tools due to their mildness and good functional group compatibility for synthesizing value-added products. In this regard, a review on C-centered radical-promoted HAT processes was reported by Gevorgyan's group ( Chem. Sci. 2020, 11, 12974, DOI: 10.1039/d0sc04881j), and a review on visible-light-promoted remote C-H functionalization via 1,5-HAT was recently reported by Zhu's group ( Chem. Soc. Rev. 2021, 50, 7359, DOI: 10.1039/d0cs00774a). Compared to N- and O-centered radical-promoted HAT processes, C(sp3)-centered radical-promoted HAT is more challenging and less explored due to the small differences in C-H bond dissociation energies. Additionally, in the realm of C-centered radical-promoted HAT, the generation of C-centered radicals has mostly involved SET processes, while the EnT-mediated C-centered radical-promoted HAT process has been less discussed because of the considerable scarcity of related reports.As a result of the rapid advancement of EnT catalysis in synthetic chemistry, C-C-centered biradical species can be readily generated from C═C double bonds via the EnT process using a photocatalyst under visible-light irradiation. An array of transformations (such as cycloaddition and isomerization) involving these C-C-centered biradical species have been reported. Our group recognized these C-C-centered biradicals as practical initiators of the HAT process in C-H functionalization reactions and devoted considerable effort to this field. Initially, we used a triplet excited allene moiety to realize remote sp3 C-H bond activation successfully. Later, a visible-light-induced triplet biradical HAT reaction of diarylethylenes was disclosed by our group. To further enhance its synthetic applicability, we applied simple styrene derivatives to realize such a novel EnT-mediated HAT process. Detailed control experiments combined with comprehensive density functional theory calculations elucidated the reaction mechanisms of these biradical-mediated HAT reactions along with the subsequent transformations of the obtained products.In addition to the advancements achieved in our group, Bach, Petersen, and others also reported such EnT-mediated HAT processes utilizing aryl acrylamide or aryl acrylate derivatives. Given the rapid progress over the past 5 years and the lack of focused discussion in this area, it is necessary to highlight these reports as a complement to the area of visible-light-mediated HAT via carbon-to-carbon processes. We anticipate that this Account will offer worthwhile insights and serve as guidance for future related research.

Developing methods to directly transform C(sp3) -H bonds is crucial in synthetic chemistry due to their prevalence in various organic compounds. While conventional protocols have largely relied on transition metal catalysis, recent advancements in organocatalysis, particularly with radical NHC catalysis have sparked interest in the direct functionalization of "inert" C(sp3) -H bonds for cross C-C coupling with carbonyl moieties. This strategy involves selective cleavage of C(sp3) -H bonds to generate key carbon radicals, often achieved via hydrogen atom transfer (HAT) processes. By leveraging the bond dissociation energy (BDE) and polarity effects, HAT enables the rapid functionalization of diverse C(sp3)-H substrates, such as ethers, amines, and alkanes. This mini-review summarizes the progress in carbene organocatalytic functionalization of inert C(sp3)-H bonds enabled by HAT processes, categorizing them into two sections: 1) C-H functionalization involving acyl azolium intermediates; and 2) functionalization of C-H bonds via reductive Breslow intermediates.

New role for photoexcited organic dye, Na2 eosin Y via the direct hydrogen atom transfer (HAT) process in photochemical visible-light-induced synthesis of spiroacenaphthylenes and 1H-pyrazolo[1,2-b]phthalazine-5,10-diones under air atmosphere

The development of efficient methods for synthesizing β-silyl amines has long been a significant goal in organic synthesis. Previous methods mainly relied on the use of prefunctionalized substrates or special reagents. Herein, we present a visible-light-promoted synthesis approach for β-silyl amines, utilizing a combination of photoinduced energy and hydrogen atom transfer processes. Using flow chemistry technology, a variety of valuable skeletons, including β-silyl amines and α-amino esters, can be produced from readily available feedstocks such as hydrosilanes and simple alkanes. Moreover, the strategy's full-process fluidized production capability highlights its potential for industrial-scale manufacturing. Mechanistic studies revealed that oxime esters can act as radical precursors as well as hydrogen atom transfer reagents.

The decatungstate anion (W10O324-) appears to exhibit especially interesting properties as a photocatalyst. Because of its unique photocatalytic properties, it is now recognised as a promising tool in organic chemistry. This study examines recent advances in decatungstate chemistry, primarily concerned with synthetic and, to some degree, mechanistic challenges. In this short review we have selected to give a number of illustrative examples that demonstrate the various applications of decatungstate in the hydrogen atom transfer (HAT) process.

In this study, we developed a novel electrochemical protocol that enables the functionalization of inherently inert C(sp3)−H bonds. In this protocol, one‐electron oxidation of acetic acid was used to successfully generate methyl radical, which cleaves the benzylic C(sp3)−H bonds of the substrates via a hydrogen atom transfer (HAT) process, and further reaction with the formed species yields the targeted C(sp3)−H functionalized products. To the best of our knowledge, this is the first example of the use of acetic acid in a HAT process. Notably the reaction has environment‐friendly and fine atom economy nature: the reaction is driven by the electrochemical conditions in the absence of expensive or hazardous reagents, producing only gaseous small molecules, hydrogen, carbon dioxide, and methane, as side products.

Radical-involved enantioselective oxidative C-H bond functionalization by a hydrogen-atom transfer (HAT) process has emerged as a promising method for accessing functionally diverse enantioenriched products, while asymmetric C(sp3 )-H bond amination remains a formidable challenge. To address this problem, described herein is a dual CuI /chiral phosphoric acid (CPA) catalytic system for radical-involved enantioselective intramolecular C(sp3 )-H amination of not only allylic positions but also benzylic positions with broad substrate scope. The use of 4-methoxy-NHPI (NHPI=N-hydroxyphthalimide) as a stable and chemoselective HAT mediator precursor is crucial for the fulfillment of this transformation. Preliminary mechanistic studies indicate that a crucial allylic or benzylic radical intermediate resulting from a HAT process is involved.

Radical additions to heteroaromatic bases are frequently employed for the rapid synthesis of complex products using C–H functionalization strategies. The conditions that are commonly employed are typically harsh, routinely requiring stoichiometric oxidants and other additives. In search for milder reaction environments allowing late‐stage functionalization, we present the alkylation of N‐heteroarenes using primary alcohols and ethers as radical precursors, where the corresponding alkyl radical is formed via hydrogen atom transfer process with a photoredox catalyzed chlorine atom generation as HAT agent. Furthermore, we explore the reduction of the heteroarenes in moderate to high yields when using secondary alcohols.

Y-H bond functionalization has always been the focus of research interest in the area of organic synthesis. Direct hydrogen atom transfer (HAT) from the Y-H bond is one of the most efficient and practical methods to activate the Y-H bond. Recently, nitrogen centered radical cations were broadly utilized as H-abstraction catalysts to activate Y-H bonds via the HAT process. As a type of HAT catalyst, the H-affinity of nitrogen centered radical cations is a significant thermodynamic parameter to quantitatively evaluate the thermodynamic H-abstraction potentials of nitrogen centered radical cations. In this work, the pK a values of 120 protonated N-containing compounds in acetonitrile (AN) are predicted, and the H-affinities of 120 nitrogen centered radical cations in AN are derived from the reduction potentials of nitrogen centered radical cations and pK a of protonated N-containing compounds using Hess' law. This work focuses on the H-abstraction abilities of 120 nitrogen centered radical cations in AN to enrich the molecule library of novel HAT catalysts or H-abstractors and provides valuable thermodynamic guidelines for the application of nitrogen centered radical cations in Y-H bond functionalization.

Described here are hydrogen atom transfer (HAT) reactions from high-spin cobalt(II) tris(2,2′-bi-2-imidazoline) (CoIIIIH22bim) to the hydrogen atom acceptors, 2,2,6,6-tetramethyl-1-piperidinyl-oxyl (TEMPO), 2,4,6-tri-tert-butylphenoxyl radical (tBu3ArO˙), and benzoquinone (BQ). The cobalt product is the oxidized and deprotonated, low-spin cobalt(III) complex (CoIIIIIIHbim), and the organic products are TEMPOH, tBu3ArOH, or hydroquinone, respectively. These reactions are formally spin forbidden because the spin state of the reactants is different from that of the products. For instance, quartet CoIIIIH22bim plus doublet RO˙ can have a triplet or quintet ground state, while the CoIIIIIIHbim + ROH product state is a singlet. Kinetics measured in the forward and reverse directions and thermochemical measurements provide a detailed picture of the reactions. The reactions are quite slow: the reaction of 10 mM CoIIIIH22bim with excess TEMPO requires roughly a day at ambient temperatures to reach equilibrium. This is 3400 times slower than the related reaction of the iron analogue FeIIIIH22bim, which is 2 kcal mol−1 more uphill. Mechanistic analyses show that the TEMPO reaction occurs by hydrogen atom transfer (HAT), and this is likely for the tBu3ArO˙ and BQ reactions as well. This is an unusually well defined spin-forbidden HAT system, which serves as a model for more complex multi-spin state HAT processes such as those suggested to occur in cytochrome P450 and metal-oxo model systems. In principle, HAT could occur before, after, or concerted with spin change. Computational studies indicate a reaction mechanism involving pre-equilibrium spin state interconversion of quartet 44CoIIIIH22bim to its doublet excited state 22CoIIIIH22bim, followed by spin-allowed HAT to the organic acceptor. This mechanism is consistent with the available kinetic, thermochemical and spectroscopic measurements. It indicates that the slow rates are due to the large change in geometry between CoIIIIH22bim and CoIIIIIIHbim, rather than any inherent difficulty in changing spin state. The implications of these results for other spin-forbidden or ‘two-state’ HAT processes are discussed.

A general catalytic methodology for the synthesis of pyrazolines from α -diazo compounds and conjugated alkenes is reported. The direct hydrogen atom transfer (HAT) process of α -diazo compounds promoted by the tert -butylperoxy radical generates electrophilic diazomethyl radicals, thereby reversing the reactivity of the carbon atom attached with the diazo group. The regiocontrolled addition of diazomethyl radicals to carbon-carbon double bonds followed by intramolecular ring closure on the terminal diazo nitrogen and tautomerization affords a diverse set of pyrazolines in good yields with excellent regioselectivity. This strategy overcomes the limitations of electron-deficient alkenes in traditional dipolar [3+2]-cycloaddition of α -diazo compounds with alkenes. Furthermore, the straightforward formation of the diazomethyl radicals provides umpolung reactivity, thus opening new opportunities for the versatile transformations of diazo compounds.