Review
Chemistry, Organic
Zhi-Hao Shang, Jun Pan, Zeyu Wang, Ze-Xin Zhang, Jingjing Wu
Summary: Organoboron compounds are versatile in various fields and their preparation usually requires reactive organometallic reagents or transition metals. However, recent developments in transition-metal-free borylation methodologies using radical chemistry have attracted much attention. Through thermochemical, photochemical, or electrochemical pathways, successful approaches from different radical precursors have been developed. This review provides an overview of recent advances in transition-metal-free radical borylation processes.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Bo Li, Ke Wang, Huifeng Yue, Alwin Drichel, Jingjing Lin, Zhenying Su, Magnus Rueping
Summary: In this study, a mild and visible-light-induced method for the synthesis of aryl borates without the use of base, transition metal-ligand complex, or photoredox catalyst was reported. The reaction showed excellent functional group tolerance and was successfully applied to the late-stage modification of natural products and the synthesis of a drug intermediate.
Article
Chemistry, Multidisciplinary
Mingming Huang, Man Tang, Jiefeng Hu, Stephen A. Westcott, Udo Radius, Todd B. Marder
Summary: A Cu-catalysed borylation reaction can achieve high-yield synthesis of arylboronic esters from aryl alkyl sulfones, while selective cleavage of cyclic sulfones can be achieved through Cu-mediated or Cu-free processes to prepare sulfonyl-containing boronate esters.
CHEMICAL COMMUNICATIONS
(2022)
Review
Chemistry, Multidisciplinary
Lu Luo, Shuai Tang, Jiangyue Wu, Shiwei Jin, Hua Zhang
Summary: Aromatic organoboron compounds, valuable in organic chemistry, have traditionally been synthesized through transition metal-catalyzed aromatic C-H and C-Het borylation. However, with the focus shifting toward sustainable chemistry, transition metal-free C-H and C-Het borylation transformations have emerged as efficient methods. This account highlights recent advances in transition metal-free transformations and discusses areas for further development.
Article
Chemistry, Inorganic & Nuclear
Liang Zhang, Yafei Li, Li Wang, Zhu Cao, Qian Zhang, Yahong Li
Summary: Two new zinc complexes, [(LZn2Et2)-Zn-1](n) (1) and [(LZn2Et2)-Zn-2] (2), were synthesized and found to be catalytically active towards the coupling reaction of aryl iodides with B(2)Pin(2). Compound 1 exhibited higher catalytic activity compared to compound 2.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Tianhang Wang, Zheng-Jun Wang, Minyan Wang, Lei Wu, Xiaowu Fang, Yong Liang, Jiahang Lv, Zhuangzhi Shi
Summary: This study presents a general strategy for constructing beta-borylenamides through C-H borylation, which provides a versatile means of creating stereodefined enamides. The unique advantage of this methodology lies in its stereoconvergent nature, allowing for the utilization of starting materials with both E and Z configurations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Sumon Sarkar, Sidhant Wagulde, Xiangqing Jia, Vladimir Gevorgyan
Summary: This study presents a general, mild, and photoinduced method for selective a-C(sp3)-H borylation of amines. The protocol allows activation of a broad range of acyclic and cyclic amines, enabling highly regio- and diastereoselective syntheses of valuable a-amino-boronates. The utility of this method has been demonstrated in late-stage borylation of structurally complex amines and formal C-H arylation reaction of amines. It is expected to find broad application in organic synthesis and drug discovery.
Article
Chemistry, Multidisciplinary
Puneeth Kumar Someswara Ashwathappa, Takuya Higashi, Vincent Desrosiers, Alvaro A. Omana, Frederic-Georges Fontaine
Summary: We report a metal-free, selective Csp(3)-H borylation of saturated cyclic amines. Piperidine derivatives can be selectively borylated at either the α or β positions depending on the reaction conditions. Mechanistic studies using NMR spectroscopy, calorimetry experiments, and density functional theory computations suggest that piperidine undergoes dehydrogenation through complexation with BBr3 to generate an enamine intermediate, which is then borylated at the α or β position based on the reaction conditions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Antony P. Y. Chan, Martin Jakoobi, Chenxu Wang, Yancong Tian, Nathan Halcovitch, Roman Boulatov, Alexey G. Sergeev
Summary: In this study, rare examples of exclusive benzylic C-H oxidative addition in industrially important methylarenes were reported using simple eta(4)-arene iridium complexes. Mechanistic studies revealed that coordinatively unsaturated eta(2)-arene intermediates are responsible for the selective activation of benzylic C-H bonds and the formation of stable benzyl complexes after trapping with a phosphine ligand.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
K. Keerthika, S. Bazil Muhammed, K. Geetharani
Summary: We describe a protocol for synthesizing trifluoromethylated alkyl boronates from alkenes using the mutual activation of Togni II and bis(catecholato)diboron reagents without the need for a catalyst or additives. This method enables the regioselective synthesis of trifluoromethylated alkyl boronates from unactivated alkenes, including natural products and drug derivatives. The boronic esters in the product can be further used to access a range of trifluoromethyl containing compounds. The reaction mechanism involves the formation of trifluoromethyl and boron centered radicals, with the more Lewis acidic diboron reagent driving the rapid radical formation.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Rachana Meena, Shashank Shekhar, Shabina B. Ansari, Ashwani Tiwari, Jhajan Lal, Damodara N. Reddy
Summary: The discovery of milder and robust strategies for introducing organoboronates in peptides is currently not well developed. This study demonstrates an efficient method for site-selective sp(2)-C7-H borylation of tryptophan using BBr3 directed by a pivaloyl group, under metal-free conditions. The versatility of this approach allows for gram-scale synthesis and modification of C7-borylated N-Phth-Trp(N-Piv)(C7-BPin)-OMe into various C7-substituted derivatives. Furthermore, this strategy enables peptide elongation and late-stage borylation of peptides, natural product Brevianamide F, and drug Oglufanide.
CHEMISTRY-AN ASIAN JOURNAL
(2023)
Article
Chemistry, Applied
Youlu Pan, Jinghao Xu, Hongjie Zhang, Rongrong Hao, Zhengrong Shen, Wenhai Huang
Summary: A metal-free radical relay addition/cyclization reaction has been developed for the functionalization of 5,6-dihydrobenzo[4,5]imidazo[2,1-a]isoquinolines with activated alkenes, ethers, cycloalkanes, toluenes, and alcohols. The protocol offers the advantages of being metal-free, base-free, and having a shorter reaction time.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Yuling Mei, Nan Jiang, Yu Yang, Wan Zhang, Saifeng Qiu, Hong Guo, Jianbo Zhang
Summary: A convenient protocol for the beta-stereoselective synthesis of 2-deoxy- C -arylglycosides has been developed, involving one-step reaction using I (2) /Et (3) SiH. The approach is applicable to a wide range of naphthol moieties and was demonstrated to be effective in the synthesis of 5-aza analogues of aquayamycin.
Article
Chemistry, Organic
Wei Su, Ting-Ting Wang, Xia Tian, Jian-Rong Han, Xiao-Li Zhen, Shi-Ming Fan, Ya-Xin You, Yu-Kun Zhang, Rui-Xiao Qiao, Qiushi Cheng, Shouxin Liu
Summary: Iron-catalyzed direct S(N)2' dehydroxyboration of allylic alcohols has been developed to access (E)-stereoselective allylboronates. The key component involved in this transformation is the six-membered ring transition state formed by allylic alcohols and iron-boron intermediate, which controls the transfer of the boron group and the stereoselectivity.
Article
Chemistry, Multidisciplinary
Zheng-Jun Wang, Xiangyang Chen, Lei Wu, Jonathan J. Wong, Yong Liang, Yue Zhao, Kendall N. Houk, Zhuangzhi Shi
Summary: The research presents a general strategy for site-selective C-H borylation of pyrroles using BBr3 directed by pivaloyl groups, without the need for any metal catalysts. The reaction is influenced by chelation and electronic effects, leading to diverse products with high positional selectivity and downstream transformation capabilities. DFT calculations confirm the preferred positional selectivity of this reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Ruairi O. McCourt, Armido Studer
Summary: A 1,2-difunctionalization reaction of cyclic enol ethers mediated by bis(arylsulfonyl) peroxides is reported. Bis(nosyl) peroxide selectively adds a sulfonyl group at the 3-position of enol ethers, generating an oxocarbenium ion that is trapped by a carboxylic acid nucleophile at the 2-position. The reaction proceeds with good yield and tolerates a variety of cyclic enol ethers as well as different carboxylic acids as the oxocarbenium ion trapping reagents.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Yongjing Wang, Kang Ma, Tiantong Zhang, Philipp Alexander Held, Armido Studer, Harald Fuchs, Zhixin Hu, Zhixiang Sun, You Han, Hong-Ying Gao
Summary: The effect of iodine on modulating the self-assembly structures of organic molecules on metal surfaces was systematically studied. By using low-temperature scanning tunneling microscopy and density functional theory, the transformation of molecular self-assembly structures induced by iodine dosing on the Ag(111) surface was explored. It was found that iodine can modulate the self-assembly structure of organic molecules with weak intermolecular interaction, while those with stronger intermolecular hydrogen bonding are not affected. These findings were confirmed by density functional theory calculations.
JOURNAL OF PHYSICAL CHEMISTRY C
(2023)
Review
Chemistry, Multidisciplinary
Hui Cao, Qiang Cheng, Armido Studer
Summary: The pyridine moiety is widely used in the synthesis of drugs, agrochemicals, catalysts, and functional materials. While direct functionalization of ortho- and para-positions is well-established, meta-selective pyridine C-H functionalization presents more challenges due to the inherent electronic properties of pyridines. In this review, we summarize the current methods for meta-C-H functionalization of pyridines, including the use of directing groups, non-directed metalation, and temporary dearomatization strategies. Recent advances in ligand control and temporary dearomatization are highlighted, while the advantages and limitations of these techniques are discussed, aiming to inspire further developments in this important area.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Florian Lind, Armido Studer
Summary: Acylsilanes, a class of organosilicon compounds, have been gaining increased attention due to their ability to generate carbenes and their usefulness as reagents in organic synthesis. In this study, a novel and efficient route for the synthesis of acylsilanes was reported through alkene hydrosilylation. By using acylhydrosilanes as silylation reagents in rhodium catalyzed alkene hydrosilylations, a wide range of acylsilanes can be accessed in good to excellent yields under mild conditions with high functional group tolerance and atom economy.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Till Drennhaus, Dirk Leifert, Jessika Lammert, Jan Philipp Drennhaus, Klaus Bergander, Constantin G. Daniliuc, Armido Studer
Summary: In this study, enantioenriched chiral indoles were synthesized through a mild and efficient radical cascade reaction using a chiral copper-bisoxazoline complex. The targeted 2-fluoroalkylated 3-(alpha-cyanobenzy-lated) indoles were accessed with excellent enantioselectivity and good yields. Mechanistic studies revealed a negative nonlinear effect which explained the stereochemical outcome. The enantioenriched 3-(alpha-cyanobenzylated) indoles demonstrated scalability and potential utility as hubs for chiral tryptamines, indole-3-acetic acid derivatives, and triarylmethanes, and a formal synthesis of a natural product analogue was disclosed.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Zhe Wang, Nick Wierich, Jingjing Zhang, Constantin G. Daniliuc, Armido Studer
Summary: In this study, a method for direct generation of alkyl radicals from alkylboronic pinacol esters (APEs) through reaction with aminyl radicals is reported. Aminyl radicals are readily generated by visible-light-induced homolytic cleavage of the N-N bond in N-nitrosamines, and C radical generation occurs through nucleohomolytic substitution at boron. As an application, the highly efficient photochemical radical alkyloximation of alkenes with APEs and N-nitrosamines under mild conditions is presented. Various primary, secondary, and tertiary APEs can be used in this scalable transformation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Jonas Elfert, Anup Bhunia, Constantin G. Daniliuc, Armido Studer
Summary: In this study, a radical transformation that enables intramolecular oxygen atom transfer to alkenes using the nitro functionality in nitroarenes as an oxygen donor is disclosed. The reaction proceeds via iron-catalyzed metal hydrogen atom transfer to alkenes and subsequent oxygenation, resulting in alkene hydration. Compared to intermolecular radical oxygenation, the intramolecular variant offers advantages, particularly in terms of diastereoselective radical hydration of conformationally flexible alkenes. The aryl moiety connecting the reactive NO2-functionality to the alkene substrate can be cleaved after oxygen transfer, yielding products derived from a formal diastereoselective intermolecular alkene hydration. Additionally, the resulting aniline entity after oxygen transfer can be used for the construction of nitrogen-containing heterocycles.
Article
Chemistry, Multidisciplinary
Hui Cao, Debkanta Bhattacharya, Qiang Cheng, Armido Studer
Summary: Selective C-H functionalization of pyridines is of great value but not well developed. In this study, a redox-neutral dearomatization-rearomatization strategy was used to achieve meta-C-H functionalization of pyridines through oxazino pyridine intermediates. Notably, by switching to acidic conditions, these intermediates underwent highly selective para-functionalization. A broad range of para-alkylated and arylated pyridines were prepared using both radical and ionic pathways. These mild and catalyst-free methods were also applied in the late-stage para-functionalization of drugs. Furthermore, the regioselective meta,para-difunctionalization of pyridines was achieved by exploiting the pH-dependent reactivity of oxazino pyridines.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Jingjing Zhang, Christian Mueck-Lichtenfeld, Armido Studer
Summary: Chemical activation of water is a hot topic in energy research and enables the conversion of this abundant resource into valuable compounds. In this study, we demonstrate the activation of water using a photocatalytic phosphine-mediated radical process, which involves sequential heterolytic and homolytic cleavage of O-H bonds. The resulting PR3-OH radical intermediate can react with various closed-shell p systems, leading to transfer hydrogenation of the p system and incorporation of hydrogen atoms from water into the product. Experimental and theoretical studies support the importance of the hydrogen atom transfer step in this radical hydrogenation process.
Article
Chemistry, Organic
Shyam Kumar Banjare, Dirk Leifert, Frauke Weidlich, Constantin G. Daniliuc, Fatmah A. Alasmary, Armido Studer
Summary: An oxidative radical cascade addition cyclization approach using eco-friendly iron catalysis and inexpensive tert-butylhydroperoxide (TBHP) as the oxidant has been reported for the synthesis of quinoline-based p-extended polyheterocyclic compounds. This method utilizes readily available ortho-alkynylated aromatic aldehydes as radical precursors and aryl isonitriles as radical acceptors. By applying this approach, quinolines that are p-conjugated with an additional heteroarene moiety can be prepared in a single sequence using indole and thiophene-based carbaldehydes.
Article
Chemistry, Organic
Lena Lezius, Jannik Reimler, Nadine Doeben, Michael Hamm, Constantin G. Daniliuc, Armido Studer
Summary: Cooperative NHC and photoredox catalysis have emerged as an important research field. In this study, a cyclizing aminoacylation of alkenes is achieved through the combination of these two catalytic modes. The key step involves a radical/radical cross-coupling between a persistent ketyl radical and a transient benzylic or aliphatic C-radical, generated through radical cyclization of an oxidatively formed amidyl radical. Various substrates containing an alkene moiety and different acyl fluorides can be used, resulting in moderate to good yields of the products.
Article
Chemistry, Organic
Shyam Kumar Banjare, Dirk Leifert, Frauke Weidlich, Constantin G. Daniliuc, Fatmah A. Alasmary, Armido Studer
Summary: An oxidative radical cascade addition cyclization approach using eco-friendly iron catalysis and inexpensive TBHP as the oxidant has been developed for the synthesis of quinoline-based p-extended polyheterocyclic compounds. This method allows the preparation of quinolines that are p-conjugated with an additional heteroarene moiety in a single sequence.
Article
Chemistry, Multidisciplinary
Anirban Maity, Armido Studer
Summary: 1,2-Aminoxyalkylation of alkenes with alkyl iodides and TEMPONa in the presence of an aryldiazonium salt as an XAT mediator is described. Primary, secondary and tertiary alkyl iodides can serve as C-radical precursors in the 1,2-aminoxyalkylation reaction with electrophilic alkenes. The resulting alkoxyamines can be easily converted to alcohols or ketones through reduction or oxidation, respectively. Mechanistic studies reveal the involvement of aryl radicals generated through SET-reduction of the aryldiazonium salt in the XAT process, allowing the addition of alkyl radicals to alkenes. The trapping of the adduct radicals with TEMPO leads to the formation of 1,2-aminoxyalkylation products. Transition metals are not required for these mild conditions transformations. Direct 1,2-aminoxyperfluoroalkylation of alkenes with perfluoroalkyl halides can be achieved using TEMPONa without the need for an aryldiazonium salt as an XAT mediator.
Article
Chemistry, Multidisciplinary
Lukas Schifferer, Leon Hoppmann, Robin Groeters, Christian Mueck-Lichtenfeld, Constantin G. Daniliuc, Olga Garcia Mancheno
Summary: A solvent-dependent, divergent synthesis of highly functionalized N,S-heterocycles, containing thiazoline and isoquinuclidine or tetrahydroisoquinoline scaffolds, has been reported. This synthesis involves cyclization reactions of isoquinolinium 1,4-zwitterionic thiolates and shows robustness and applicability as demonstrated by efficient upscaling of the reaction and derivatization of the resulting products.
CHEMICAL COMMUNICATIONS
(2023)