Article
Chemistry, Multidisciplinary
Christian A. Gomez, Dibyendu Mondal, Qian Du, Natalie Chan, Jared C. Lewis
Summary: Directed evolution was used to engineer variants of SadX, resulting in site-selective azidation and succinylation of amino acids and amines. This study provides a promising starting point for evolving SadX variants that can functionalize structurally distinct substrates and enable enzymatic C-H functionalization with non-native functional groups.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Chemistry, Multidisciplinary
Huang Junrong, Yang Min, Dai Chuan, Zhou Yajun, Fang Huilong, Zhu Lizhi, Yin Feng, Li Zigang
Summary: In recent years, the development of selective synthesis methods has enabled direct C-H bond functionalization approaches, providing opportunities to break non-traditional chemical bonds and attain more diversity in inactive sites for natural products. Among these approaches, direct oxidation of inert C-H bonds is a common method for natural product diversification, and optimizing this method can be a powerful and efficient strategy in both synthetic and medicinal chemistry.
FRONTIERS IN CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Johannes Buechler, Sumire Honda Malca, David Patsch, Moritz Voss, Nicholas J. Turner, Uwe T. Bornscheuer, Oliver Allemann, Camille Le Chapelain, Alexandre Lumbroso, Olivier Loiseleur, Rebecca Buller
Summary: The authors used machine learning to engineer WelO5* halogenase variants, enabling the regioselective chlorination of unactivated carbon-hydrogen bonds. Late-stage functionalization of natural products offers a promising route for creating novel entities.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Qian-Yu Li, Shiyan Cheng, Ziqi Ye, Tao Huang, Fuxing Yang, Yu-Mei Lin, Lei Gong
Summary: This study developed a simplified photochemical system using iron(III) halides as multifunctional reagents and air as a green oxidant to achieve the direct and selective coupling of benzenes with aliphatic hydrocarbons. The method showed high yields and commendable chemo-, site-selectivity, and demonstrated the potential of iron halides in sustainable synthesis.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Cui-Lian Zeng, Hao Wang, Di Gao, Zhen Zhang, Dong Ji, Wei He, Cheng-Kou Liu, Zhao Yang, Zheng Fang, Kai Guo
Summary: This study presents a green and gentle Minisci-type reaction method, in which the cross-dehydrogenative coupling of heteroarenes with aliphatic C(sp(3))-H bonds is achieved under visible-light irradiation. This method does not require oxidants or transition metal catalysts, and only the catalytic equivalent of CF3SO2Na and room temperature are needed to ensure an efficient reaction.
Review
Chemistry, Physical
Renata Siedlecka
Summary: The oxyfunctionalization of non-activated C-H bonds has gained significant attention in recent years. Various catalytic systems capable of efficiently and selectively carrying out this transformation, inspired by enzymatic systems, have been described. This review article summarizes the development of metal complex-catalyzed selective functionalization of saturated C-H bonds since 2010, with brief references to previous studies for clarity. The practical applications of these findings in synthesis are also highlighted.
Article
Chemistry, Multidisciplinary
Yujie Han, Junjie Shi, Songrong Li, Tingting Dan, Wenwen Yang, Mingyu Yang
Summary: This article presents a transition metal-free strategy for late-stage peptide modification, which involves site-selective functionalization under visible light to cyclize the linear aliphatic side chain at the peptide N-terminus into a proline skeleton, with excellent regio- and stereo-selectivity.
Article
Chemistry, Organic
Xiaoxiang Zhang, Chenrui Liu, Yingying Zhang, Fang Shen, Wanxing Wei, Zhuan Zhang, Taoyuan Liang
Summary: Catalysis by organo-chalconium catalysts, which can bind and activate substrates through attractive, non-covalent interactions, is an important approach in organic and organometallic chemistry. The study presents a new strategy for direct C2,3-H difunctionalization of indoles with unactivated amines using an organo-chalconium catalyst generated from the reaction of iodine and chalconium reagents. This strategy allows for the assembly of complex molecular architectures and late-stage functionalization of natural products and pharmaceutical compounds, optimizing their bioactivity and pharmacokinetic properties.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Multidisciplinary Sciences
Kelvin Pak Shing Cheung, Jian Fang, Kallol Mukherjee, Andranik Mihranyan, Vladimir Gevorgyan
Summary: Aliphatic allylic amines are complex and biorelevant molecules that are present in a wide range of compounds. The direct allylic C-H amination of alkenes is the simplest method to obtain these motifs. However, using widely available internal alkenes with aliphatic amines remains a synthetic challenge. We report a general solution to these problems using a blue light-induced open-shell approach and a mild oxidant.
Article
Chemistry, Physical
Juner Zhang, Ailiena O. Maggiolo, Edwin Alfonzo, Runze Mao, Nicholas J. Porter, Nayla M. Abney, Frances H. Arnold
Summary: This study demonstrates that engineered enzymes can achieve new-to-nature C-H alkylation with distinct selectivities. The research also reveals that minimal changes to the enzyme's structure can tune its chemoselectivity.
Article
Chemistry, Multidisciplinary
Mingda Li, Yangbin Jin, Yupeng Chen, Wanqing Wu, Huanfeng Jiang
Summary: This paper reports a new catalytic system for the efficient oxidative amination of unactivated olefins with primary aliphatic amines, leading to the formation of secondary allylic amines. The reaction proceeds through allylic C(sp3)-H activation and nucleophilic amination. The utility of this method is demonstrated in the late-stage modification and streamlined synthesis of drug molecules.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Letter
Chemistry, Multidisciplinary
Lixin Zhang, Xueting Liu, Xinye Wang, Guoliang Zhu, Heng Song, Ronghai Cheng, Nathchar Naowarojna, Catherine E. E. Costello, Pinghua Liu
Summary: In their recent publication, Cen, Wang, Zhou et al. reported the crystal structure of a ternary complex of the non-heme iron endoperoxidase FtmOx1 and concluded that it supports the CarC-like mechanistic model for catalysis. However, they failed to accurately describe the CarC-like and COX-like models and address their differences, and their data is consistent with the COX-like model after careful analysis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Lian Wu, Zhanfeng Wang, Yixin Cen, Binju Wang, Jiahai Zhou
Summary: The high-resolution X-ray crystal structure of the ternary complex FtmOx1 center dot 2OG center dot fumitremorgin B and its catalytic mechanism were reported. In response to criticism from Zhang, Costello, Liu et al., the authors address their questions and provide structural clarifications and new computational results that support the CarC-like mechanistic model.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Chemistry, Multidisciplinary
Qi Zhang, Bing-Feng Shi
Summary: The review summarizes recent advancements in achieving selective functionalization of remote C(sp(3))-H bonds in transition metal-catalyzed C-H functionalization reactions, showcasing strategies such as specific substrate selection, switching of the regiodetermining step, utilization of ring strain in metallacycles, multiple non-covalent interactions, and favorable reductive elimination.
Article
Chemistry, Physical
Alexandra M. Zima, Oleg Y. Lyakin, Anna A. Bryliakova, Dmitrii E. Babushkin, Konstantin P. Bryliakov, Evgenii P. Talsi
Summary: The effect of HClO4 on the reactivity and selectivity of catalyst systems based on nonheme iron complexes has been studied. The addition of HClO4 improves the catalytic efficiency and oxidation selectivity, and also increases the reaction rate of key oxygen-transferring intermediates. The effect is attributed to the reversible protonation of the Fe=O moiety.
Article
Chemistry, Multidisciplinary
Yuyang Dong, Kwangmin Shin, Binh Khanh Mai, Peng Liu, Stephen L. Buchwald
Summary: This paper reports an asymmetric olefin hydromethylation protocol enabled by CuH catalysis, in which methyl tosylate is used as a methyl source and iodide ion converts it into the active reactant methyl iodide. The method demonstrates broad applicability and tolerance.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Edward Miller, Binh Khanh Mai, Jacquelyne A. Read, William C. Bell, Jeffrey S. Derrick, Peng Liu, F. Dean Toste
Summary: Developing strategies to study reactivity and selectivity in flexible catalyst systems has become an important topic of research. In this study, a combined experimental and computational approach was used to investigate the mechanistic role of an achiral DABCOnium cofactor in a regio- and enantiodivergent bromocyclization reaction. It was found that electron-deficient aryl substituents resulted in rigidified transition states, driving the selectivity of the reaction, while electron-rich aryl groups led to more flexible transition states, where interactions between the catalyst and substrate were more important.
Article
Chemistry, Physical
Amit Kumar Simlandy, Warabhorn Rodphon, Turki M. Alturaifi, Binh Khanh Mai, Hui-Qi Ni, John A. Gurak Jr, Peng Liu, Keary M. Engle
Summary: A redox-neutral catalytic coupling of nitroalkanes and unactivated alkenes is reported in this study, which proceeds by a directed carbopalladation mechanism. The combination of PdI2 as the precatalyst and HFIP solvent enables the reaction uniquely. Structurally complex nitroalkane products, including nitro-containing carbo- and heterocycles, can be prepared under convenient conditions without the use of toxic or corrosive reagents. The reaction mechanism is examined through deuterium labeling experiments and isolation of a catalytically relevant intermediate. Different catalytic activation modes are utilized to demonstrate orthogonal methods for site-selective functionalization of a polyfunctional nitroalkyl ketone. Density functional theory (DFT) calculations reveal that the carbopalladation transition state is stabilized by a Na·I interaction and H·I hydrogen bond with HFIP.
Article
Chemistry, Multidisciplinary
Ruihan Wang, Yidong Wang, Ruiqi Ding, Parker B. Staub, Christopher Z. Zhao, Peng Liu, Yi-Ming Wang
Summary: A newly-developed cationic cyclopentadienyliron dicarbonyl complex enables the conversion of propylene to its allylic C-C bond coupling products under catalytic conditions. This approach is also applicable to the allylic functionalization of simple alpha-olefins with distinctive branched selectivity. Experimental and computational studies reveal the allylic deprotonation of the metal-coordinated alkene as the turnover-limiting step and provide insights into the multifaceted roles of the newly designed ligand in promoting allylic C-H functionalization with enhanced reactivity and stereoselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Changmin Xie, Jacob Kim, Binh Khanh Mai, Shixuan Cao, Rong Ye, Xin-Yi Wang, Peng Liu, Ohyun Kwon
Summary: This research describes a catalytic asymmetric reaction for the synthesis of chiral compounds using specific oxidants and reductants. The reaction is conducted under mild conditions and exhibits a wide substrate scope, high yield, and excellent enantioselectivity. The study also demonstrates the effectiveness of the designed catalyst and successfully synthesizes seven biologically active compounds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Tobias Koengeter, Can Qin, Binh Khanh Mai, Qinghe Liu, Yucheng Mu, Peng Liu, Amir H. Hoveyda
Summary: This paper presents a stereoretentive strategy for catalytic cross-metathesis reaction between tri-, Z- or E-di, or monosubstituted olefins and Z- or E-2-bromo-2-butene, leading to the formation of various trisubstituted alkenyl bromides. The method is applicable for the generation of products containing polar moieties or sterically hindered alkenes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Amit Kumar Simlandy, Turki M. Alturaifi, Johny M. Nguyen, Lucas J. Oxtoby, Quynh Nguyen Wong, Jason S. Chen, Peng Liu, Keary M. Engle
Summary: We report a transient directing group (TDG) strategy for site-selective palladium-catalyzed reductive Heck-type hydroalkenylation and hydroalkynylation of alkenylaldehydes using alkenyl and alkynyl bromides. This strategy allows for the construction of a stereocenter at the delta-position with respect to the aldehyde. Computational studies reveal the beneficial roles of rigid TDGs, such as L-tert-leucine, in promoting TDG binding and inducing high levels of enantioselectivity in alkene insertion.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Hui-Qi Ni, Malkanthi K. Karunananda, Tian Zeng, Shenghua Yang, Zhen Liu, K. N. Houk, Peng Liu, Keary M. Engle
Summary: Multistep organic synthesis allows the conversion of simple chemical feedstocks into more complex products with specific functions. This study introduces a novel approach to organic reactions that can generate multiple valuable products with different carbon skeletons in a single operation. Through a palladium-catalyzed reaction, a single alkene starting material can be converted into two structurally distinct products, demonstrating the potential for simultaneous access to diverse compounds. The findings of this study provide insights into the mechanistic details of this unique catalytic system and establish a new method for small-molecule library synthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Jingfeng Huo, Yue Fu, Melody J. Tang, Peng Liu, Guangbin Dong
Summary: In this research, the first nickel-catalyzed Catellani-type annulation of aryl triflates and chlorides was achieved to form various benzocyclobutene-fused norbornanes in high efficiency. Mechanistic studies revealed an unexpected outer-sphere concerted metalation/deprotonation pathway and the essential roles of the base and the triflate anion. Compared to palladium catalysis, the reaction showed a broad functional group tolerance and enhanced regioselectivity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Jicheng Wu, Peijing Jia, Rositha Kuniyil, Peng Liu, Weiping Tang
Summary: In this study, we report an efficient method for the stereoselective synthesis of challenging α-linked glycoconjugates using a Rh-II/chiral phosphoric acid (CPA)-cocatalyzed dynamic kinetic anomeric O-alkylation. By exploring various parameters of the cocatalytic system, we achieved excellent anomeric selectivity, excellent diastereoselectivity, broad substrate scope, and high efficiency for this glycosylation reaction. DFT calculations suggested that the anomeric selectivity was determined by steric interactions between the C2-carbon of the carbohydrate and the phenyl group of the metal carbenoid, while diastereoselectivity at the newly generated stereogenic center was influenced by π-π interactions with the C2-OBn substituent on the carbohydrate substrate.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Dennis A. Kutateladze, Binh Khanh Mai, Yuyang Dong, Yu Zhang, Peng Liu, Stephen L. Buchwald
Summary: A copper hydride-catalyzed approach has been developed for the synthesis of Z-configured trisubstituted alkenes with high stereo- and regioselectivity. This method provides a valuable strategy for accessing challenging classes of alkenes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Lei Cheng, Dian Li, Binh Khanh Mai, Zhiyu Bo, Lida Cheng, Peng Liu, Yang Yang
Summary: The merger of photoredox catalysis and PLP biocatalysis enables the development of a new synthetic method for preparing valuable noncanonical amino acids, allowing controlled formation of chiral products.
Article
Chemistry, Physical
Wenzhen Fu, Natalia M. M. Neris, Yue Fu, Yunlong Zhao, Benjamin Krohn-Hansen, Peng Liu, Yang Yang
Summary: This study describes a metalloredox biocatalysis strategy to repurpose natural cytochromes P450 for catalysing asymmetric radical cyclization to arenes through an unnatural electron transfer mechanism. Directed evolution yielded a series of engineered P450 aromatic radical cyclases with complementary selectivities. The excellent tunability of this metalloenzyme family provides an exciting platform for utilizing free radical intermediates in asymmetric catalysis.
Article
Chemistry, Physical
Amit Kumar Simlandy, Warabhorn Rodphon, Turki M. Alturaifi, Binh Khanh Mai, Hui-Qi Ni, John A. Gurak, Peng Liu, Keary M. Engle
Summary: We report a redox-neutral catalytic coupling of nitroalkanes and unactivated alkenes that proceeds by a directed carbopalladation mechanism. The reaction is enabled by the combination of PdI2 as the precatalyst and HFIP solvent. Complex nitroalkane products, including nitro-containing carbo- and heterocycles, can be prepared under convenient conditions without the need for toxic or corrosive reagents.
Article
Chemistry, Multidisciplinary
Gaoyuan Zhao, Upasana Mukherjee, Lin Zhou, Yue Wu, Wang Yao, Jaclyn N. Mauro, Peng Liu, Ming-Yu Ngai
Summary: This study reports the first direct strategy to synthesize C2-ketonyl-2-deoxysugars, important carbohydrate mimetics, from 1-bromosugars and silyl enol ethers via an excited-state palladium-catalyzed 1,2-spin-center shift process. The reaction is step-economic, has a broad substrate scope, high functional group tolerance, and can be used in the late-stage functionalization of natural product- and drug-glycoconjugates.
