Publications

Shun Wang, Weidi Zeng, Qing An, Lingfei Duan, and Zhiwei Zuo*

Abstract

Photoinduced electron transfer is fundamental to both biological and synthetic processes; however, modulating back electron transfer (BET) remains a formidable challenge in achieving more efficient photocatalytic transformations. In this work, we present a strategy to regulate electron transfer dynamics via ligand-to-metal charge transfer (LMCT) catalysis, wherein the rapid β-scission of alkoxy radicals is harnessed to suppress BET, thereby facilitating the efficient transfer of reducing equivalents to drive transition metal-mediated reductive cross-coupling reactions. By strategically utilizing a diverse array of alcohol reductants, such as methanol and pinacol, we employ a cerium benzoate catalyst to enable reductive processes not through modulation of redox potentials, but by promoting synchronized electron transfer. Detailed mechanistic investigations reveal that the photoinduced electron relay process, governed by LMCT-BET, plays a pivotal role in effectively delivering reducing equivalents to catalytic sites, underscoring its significance in optimizing catalytic efficiency.

Lingfei Duan, Yunzhi Lin, Qing An, Zhiwei Zuo*

Abstract

Ligand-to-metal charge transfer (LMCT) excitation has emerged as a potent strategy for the selective generation of heteroatom-centered radicals, yet its full potential in modulating open-shell radical pathways remains underexplored. Here, we present a photocatalytic methylative cross-coupling reaction that capitalizes on the synergistic interplay between LMCT and Ni catalysis, nabling the use of tert-butanol as an efficient and benign methylating reagent. The electron-deficient ligand 2,6-ditrifluoromethyl benzoate facilitates Ce(IV)-mediated bond scission of tert-butanol, generating a methyl radical that is subsequently captured by the Ni catalytic cycle to form C−CH₃ bonds. Under mild reaction conditions, this strategy affords efficient methylation of sp³ carbons adjacent to carbonyls and sp² centers, demonstrating broad functional group tolerance and applicability in late-stage functionalization of bioactive molecules. Additionally, trideuteromethylative coupling can be facilely achieved using commercial tert-butanol-d10. This approach circumvents the need for traditional tert-butoxy radical precursors, such as peroxides, while strategically modulating the radical pathway to favor β-scissionand suppress unwanted tert-butoxy radical formation in solution. Mechanistic studies reveal that the benzoate ligand plays a crucialrole in enabling LMCT excitation and facilitating methyl radical generation, supporting a concerted Ce−OR and β-C−C bondhomolysis mechanism, further evidenced by the modulation of regioselectivity in alkoxy radical-mediated β-scission.

Huaishuo Liang^‡, Linmei Lai^‡, Kaining Zhang, Wenlong Chen, Mingfeng Li, Yi Yang*, Jian Li* and Zhiwei Zuo*

Abstract

Dehydroxymethylation offers intriguing synthetic opportunities to exploit the ubiquitous C–C bonds in free alcohols as unconventional functional handles;however, its synthetic potential has been constrained by the development of efficient catalysts. In this work, we introduce a robust, bench-stable cerium(IV) benzoate complex, [Ce(TRIPCO2)5Na], which functions as an efficient ligand-to-metal charge transfer (LMCT) catalyst, enabling selective cleavage of α-C(sp3)–C(sp3) bonds in free alcohols. This cerium(IV) catalyst is straightforward to synthesize on a gram scale, providing simple conditions for dehydroxymethylation reactions while eliminating the need for exogenous halide additives. The catalytic efficiency of this complex has been demonstrated in the dehydroxymethylative amination of free alcohols and the seamless one-pot synthesis of N-alkyl pyrazoles. Furthermore, the cerium-LMCT catalyst demonstrates efficacy within a metallaphotoredox paradigm, where the synergistic interplay between cerium-LMCT and nickel catalysis facilitates dehydroxymethylative alkylation, enabling the efficient utilization of alcohol feedstocks for selective C(sp3)–C(sp3) cross-coupling reactions. Mechanistic investigations have elucidated the photoexcitation and redox properties, revealing the selective generation of alkoxy radical intermediates in the presence of benzoate ligand, a critical factor in enabling radical-mediated bond cleavage.

Xuan Jiang^‡, Xu Han^‡, Fu-Dong Lu, Liang-Qiu Lu, Zhiwei Zuo* and Wen-Jing Xiao*

Abstract

Visible light-induced asymmetric organic photochemical synthesis has received growing attention since the first pioneering report into the enantioselective α-alkylation of aldehydes via dual photoredox and amine catalysis. The evolution of this area over the past few decades has provided the synthetic community with a unique tool for obtaining previously challenging, and even unavailable, chiral molecules via an attractive protocol. This review briefly introduces the general stereocontrol strategies for asymmetric photochemical transformations under the classification of organocatalysis, Lewis acid catalysis, and transition metal catalysis. Moreover, opportunities and challenges in this emerging area are noted from this perspective.

Peng Li, Lingfei Duan, Yunzhi Lin, Lingling Chu, Qing An, and Zhiwei Zuo*

Abstract

Direct coupling of free alcohols with electron-rich alkenes—a longstanding challenge due to inherent polarity mismatches—is achieved via a ligand-to-metal charge transfer (LMCT)-enabled catalytic platform featuring cerium(IV) benzoate catalysts. This anti-Markovnikov hydroetherification proceeds through selective activation of free alcohols into alkoxy radicals, facilitated by LMCT homolysis, even in the presence of redox-labile electron-rich alkenes such as enol ethers. Mechanistic studies elucidate the structure of the active Ce(IV) benzoate complex, highlighting its unique selectivity for alkoxy radical generation.

Hui Pan^‡, Qing An^‡, Binh Khanh Mai, Yuegang Chen, Peng Liu* and Zhiwei Zuo*

Abstract

The integration of ligand-to-metal charge transfer (LMCT) catalytic paradigms with radical intermediates has transformed the selective functionalization of inert C–H bonds, facilitating the use of nonprecious metal catalysts in demanding transformations. Notably, aerobic C–H carbonylation of methane to acetic acid remains formidable due to the rapid oxidation of methyl radicals, producing undesired C1 oxygenates. We present an iron terpyridine catalyst utilizing LMCT to achieve exceptional C2/C1 selectivity through synergistic photoexcitation, methyl radical generation, and carbonylation. Mechanistic studies highlight the critical roles of Fe(II) and Fe-carbonyl complexes in bypassing methyl radical oxidation via a radical rebound-like pathway, unlocking unprecedented efficiency in methane aerobic carbonylation.

Yuanli Xu^‡,Wenlong Chen^‡,Ruihua Pu,Jia Ding,Qing An,Yi Yang*,Weimin Liu* and Zhiwei Zuo*

Abstract

The selective incorporation of a deuterium atom into small molecules with high selectivity is highly valuable for medical and chemical research. Unfortunately, this remains challenging due to the complete deuteration caused by commonly used hydrogen isotope exchange strategies. We report the development of a photocatalytic selective monodeuteration protocol utilizing C–C bond as the unconventional functional handle. The synergistic combination of radical-mediated C–C bond scission and deuterium atom transfer processes enables the effective constructions of benzylic CDH moieties with high selectivity for monodeuteration. The combinational use of a bisphosphonium photocatalyst, thiol catalyst, and CH₃OD deuteration agent provides operationally simple conditions for photocatalytic monodeuteration. Moreover, the photoinduced electron transfer process of the bisphosphonium photocatalyst is elucidated through a series of spectroscopy experiments, identifying a peculiar back electron transfer process that can be regulated by subsequent nucleophilic additions.

Qing An, Liang Chang, Hui Pan, Zhiwei Zuo*

Abstract

Chemists have long pursued harnessing light energy and photoexcitation processes for synthetic transformations. Ligand-to-metal charge transfer (LMCT) in high-valent metal complexes often triggers bond homolysis, generating oxidized ligand-centered radicals and reduced metal centers. While photoinduced oxidative activations can be enabled, this process, typically seen as photochemical decomposition, remains underexplored in catalytic applications. To mitigate decomposition during LMCT excitation, we developed a catalytic cycle integrating in situ coordination, LMCT, and ligand homolysis to activate ligated alcohols transiently into alkoxy radicals. This catalytic approach leverages Ce(IV) LMCT excitation and highly reactive alkoxy radical intermediates for selective functionalizations of C(sp3)–H and C(sp3)–C(sp3) bonds under mild conditions. In this Account, we discuss these advancements, highlighting the practical utility of cost-effective cerium salts as catalysts and their potential to develop innovative transformations, addressing long-standing synthetic challenges.

Selective functionalization of chemically inert C(sp3)–H bonds has long posed a significant challenge. We first detail our research using LMCT-enabled alkoxy radical-mediated hydrogen atom transfer (HAT) processes for selective C(sp3)–H functionalizations. Using readily available CeCl3, we established a general protocol for employing free alcohols in the Barton reaction. By integrating LMCT and HAT catalysis, we introduced a selective photocatalytic strategy for functionalizing feedstock alkanes, converting gaseous hydrocarbons into valuable products. Employing simple cerium salts like Ce(OTf)3 and CeCl3, we achieved selective C–H amination of methane and ethane at ambient temperature, achieving turnover numbers of 2900 and 9700, respectively. This catalytic manifold has been further exploited to address the site-selectivity challenge in the C–H functionalization of linear alkanes. The use of methanol as a cocatalyst enabled preferential functionalization of the most electron-rich sites, achieving a high intrinsic selectivity over 12:1 of secondary vs primary sites in pentane and hexane.

Next, we discuss the catalytic utilization of alkoxy-radical-mediated β-scission, a frequently encountered side reaction in HAT transformations, for selective cleavage and functionalization of C–C bonds. The versatility of the LMCT catalytic platform facilitates the generation of alkoxy radicals from various free alcohols. In our initial demonstration of LMCT-enabled C(sp3)–C(sp3) bond activation, we developed a cerium-catalyzed ring-opening and amination of cycloalkanols, providing an effective protocol for cleaving unstrained C–C bonds. This strategy has been successfully applied to various radical cross-coupling processes, leading to innovative transformations such as ring expansions of cycloalkanols, dehydroxymethylative alkylation, amination, alkenylation, and ring expansions of cyclic ketones. These results highlight the synthetic potential of employing LMCT-mediated β-scission and ubiquitous C–C bonds as unconventional functional handles for generating molecular complexity.

Lastly, we delve into our mechanistic investigations. Beyond the catalytic application of Ce(IV) LMCT in various transformations, we have undertaken comprehensive mechanistic studies. These investigations encompass characterization of Ce(IV) alkoxide complexes to elucidate their structures, evaluation of their photoactivity and selectivity in radical generation, and elucidation of kinetic pathways associated with transient LMCT excited states. Our research has revealed ultrafast bond homolysis, back electron transfer, and the selectivity of heteroleptic complexes in homolysis, providing crucial insights for advancing LMCT catalysis.

Zhao-Ran Liu, Xiao-Yu Zhu, Jian-Feng Guo, Cong Ma*, Zhiwei Zuo*, and Tian-Sheng Mei*

Abstract

The merging of transition metal catalysis with electrochemistry has become a powerful tool for organic  synthesis because catalysts can govern the reactivity and selectivity. However, coupling catalysts with  alkyl radical species generated by anodic oxidation remains challenging because of electrode passivation,  dimerization, and overoxidation. In this study, we developed convergent paired electrolysis for the cou pling of nickel catalysts with alkyl radicals derived from photoinduced ligand-to-metal charge-transfer of  cyclic alcohols and iron catalysts, providing a practical method for site-specific and remote arylation of  ketones. The synergistic use of photocatalysis with convergent paired electrolysis can provide alternative  avenues for metal-catalyzed radical coupling reactions.

Liang Chang, Shun Wang, Qing An, Linxuan Liu, Hexiang Wang, Yubo Li, Kaixuan Feng, and Zhiwei Zuo*

Abstract

The selective functionalization of alkanes has long been recognized as a prominent challenge and an arduous task in organic synthesis. Hydrogen atom transfer (HAT) processes enable the direct generation of reactive alkyl radicals from feedstock alkanes and have been successfully employed in industrial applications such as the methane chlorination process, etc. Nevertheless, challenges in the regulation of radical generation and reaction pathways have created substantial obstacles in the development of diversified alkane functionalizations. In recent years, the application of photoredox catalysis has provided exciting opportunities for alkane C–H functionalization under extremely mild conditions to trigger HAT processes and achieve radical-mediated functionalizations in a more selective manner. Considerable efforts have been devoted to building more efficient and cost-effective photocatalytic systems for sustainable transformations. In this perspective, we highlight the recent development of photocatalytic systems and provide our views on current challenges and future opportunities in this field.

Abstract

A synergistic photocatalytic system using a bisphosphonium catalyst and a cobalt catalyst has been developed, enabling the selective oxidation of benzylic alcohols under oxidant-free and environmentally benign conditions. High efficiencies have been obtained for a variety of alcohol substrates, and exclusive selectivity for aldehyde products has been achieved across the board. Furthermore, this photocatalytic system proved to be efficient when performed under continuous-flow conditions, even using a simple and easily assembled continuous-flow setup.

Qing An, Yang-Yang Xing, Ruihua Pu, Menghui Jia, Yuegang Chen, Anhua Hu, Shuo-Qing Zhang, Shuoqing Zhang, Na Yu, Jianbo Du, Yanxia Zhang, Jinquan Chen*, Weimin Liu*, Xin Hong*, and Zhiwei Zuo*

Abstract

The intermediacy of alkoxy radicals in cerium-catalyzed C–H functionalization via H-atom abstraction has been unambiguously confirmed. Catalytically relevant Ce(IV)–alkoxide complexes have been synthesized and characterized by X-ray diffraction. Operando electron paramagnetic resonance and transient absorption spectroscopy experiments on isolated pentachloro Ce(IV) alkoxides identified alkoxy radicals as the sole heteroatom-centered radical species generated via ligand-to-metal charge transfer (LMCT) excitation. Alkoxy-radical-mediated hydrogen atom transfer (HAT) has been verified via kinetic analysis, density functional theory (DFT) calculations, and reactions under strictly chloride-free conditions. These experimental findings unambiguously establish the critical role of alkoxy radicals in Ce-LMCT catalysis and definitively preclude the involvement of chlorine radical. This study has also reinforced the necessity of a high relative ratio of alcohol vs Ce for the selective alkoxy-radical-mediated HAT, as seemingly trivial changes in the relative ratio of alcohol vs Ce can lead to drastically different mechanistic pathways. Importantly, the previously proposed chlorine radical–alcohol complex, postulated to explain alkoxy-radical-enabled selectivities in this system, has been examined under scrutiny and ruled out by regioselectivity studies, transient absorption experiments, and high-level calculations. Moreover, the peculiar selectivity of alkoxy radical generation in the LMCT homolysis of Ce(IV) heteroleptic complexes has been analyzed and back-electron transfer (BET) may have regulated the efficiency and selectivity for the formation of ligand-centered radicals.

Jianbo Du^‡, Xiaokun Yang^‡, Xin Wang, Qing An, Xu He, Hui Pan, and Zhiwei Zuo*

Yilin Chen, Jianbo Du, and Zhiwei Zuo*

Abstract

The Norrish type I reaction represents a powerful approach to cleave C–C bonds of ketones, yet the synthetic application has been limited because of selectivity and practicality problems. Through the catalytic utilization of the ligand-to-metal charge transfer excitation, Chen and colleagues describe a photocatalytic transformation, in which C–C bonds of ketones are exploited as unconventional handles for selective functionalizations. This protocol, with its utilization of blue LED and inexpensive cerium catalyst, has been successfully employed to cleave a broad range of ketones, regardless of cyclic or acyclic, from simple dibenzyl ketone to complex androsterone.