Article
Chemistry, Physical
Haifeng Zheng, Kan Wang, Isa Faghihi, Wendell P. Griffith, Hadi Arman, Michael P. Doyle
Summary: Metal-free electrophile addition to vinyl diazo compounds leads to highly selective formal [3 + 2] cyclization, 1,2-difunctionalization of alkenes, and C-H functionalization. Diverse electrophilic reagents can be used to generate highly reactive intermediates, enabling the synthesis of various substituted alpha-diazo esters with high yields and selectivities. Further transformations such as migration, oxidation, ring-expansion, and conjugate addition demonstrate the potential utility of this method.
Review
Chemistry, Applied
Parmjeet Kaur, Vikas Tyagi
Summary: This review highlights the recent progress in iron-catalyzed chemical and enzymatic carbene-transfer reactions using diazo compounds as carbene precursor, emphasizing the use of iron as a catalyst in organic synthesis.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Review
Chemistry, Multidisciplinary
Susana Estopina-Duran, James E. Taylor
Summary: This review outlines recent advances in Bronsted acid-catalysed dehydrative substitution reactions for C-C, C-O, C-N and C-S bond formation. It highlights the wide range of processes accessible using simple alcohols as the formal electrophile, while discussing current limitations and possible future research directions.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Wengang Guo, Ying Zhou, Hongling Xie, Xin Yue, Feng Jiang, Hai Huang, Zhengyu Han, Jianwei Sun
Summary: In this study, the first metal-free asymmetric H-X bond insertion of its kind was achieved by utilizing visible light as a promoter and a chiral phosphoric acid as a catalyst. Under mild conditions, alpha-diazoesters and aryl amines smoothly underwent N-H bond insertion to form enantioenriched alpha-aminoesters with high efficiency and good enantioselectivity. The key to success was the use of DMSO as an additive, which facilitated the rapid capture of the highly reactive free carbene intermediate to form a domesticated sulfoxonium ylide.
Review
Chemistry, Organic
Xie Yang, Xuan Jun
Summary: This review summarizes the recent developments in the photocatalytic generation of radicals from diazo compounds, including the formation of diazomethyl radicals, carbon radicals, carbyne radicals, and allene radicals. Additionally, the future development direction and challenges in this field are prospected.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Chemistry, Applied
Jan Radolko, Peter Ehlers, Peter Langer
Summary: The review focuses on recent advancements in the field of transition-metal-catalyzed reactions of N-tosylhydrazones, highlighting the use of different transition metals as catalysts, synthetic applications, mechanistic studies, and applications in domino and multicomponent reactions.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Physical
Ayan Dasgupta, Emma Richards, Rebecca L. Melen
Summary: Carbenes generated from diazo compounds serve as key intermediates for organic synthesis. Recent studies have shown that triarylboranes can be used as catalysts for the in situ generation of these reactive carbenes. These reactions have potential applications in the synthesis of pharmaceuticals and agrochemicals.
Article
Chemistry, Physical
Nicole S. Willeit, Wilhelm Klein, Peter Coburger, Elke Fritz-Langhals, Thomas F. Faessler
Summary: Single-site catalysis is an important strategy for optimizing heterogeneous catalytic reactions. A synthetic protocol for synthesizing four cluster compounds with transition metals embedded in a polyhedral cluster has been presented. The catalytic potential of the compounds has been investigated for various olefin isomerisation reactions. The results show that these single-site homogeneous catalysts can significantly increase the efficiency of catalysts and allow for sustainable use of expensive and less abundant transition metals.
Article
Chemistry, Inorganic & Nuclear
Sofya S. Kuvshinova, Yulia Nelyubina, Vladimir A. Larionov, Daria V. Vorobyeva, Sergey N. Osipov, Dmitry A. Loginov
Summary: Novel Rh and Ir complexes were synthesized and their structures were determined by X-ray diffraction. The compounds prepared, as well as related derivatives, efficiently catalyze the alkylation of N-(pyrimidin-2-yl)indole with methyl 3,3,3-trifluoro-2-diazopropionate.
JOURNAL OF ORGANOMETALLIC CHEMISTRY
(2021)
Review
Chemistry, Applied
Daksh Singh Davas, Srashti Bhardwaj, Raju Sen, Dinesh Kumar Gopalakrishnan, Janakiram Vaitla
Summary: This review surveys the coupling of two carbene precursors for the synthesis of alkenes. The key factor for selective carbene coupling is the difference in carbene generation rate between the two precursors. This strategy requires careful selection of precursors and fine-tuning of reaction conditions to achieve the desired chemo- and stereoselectivity. The review covers inter- and intramolecular coupling of diazo compounds as well as cross-coupling between diazo and non-diazo compounds.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Minghui Qi, Muhammad Suleman, Jiale Fan, Ping Lu, Yanguang Wang
Summary: Here, a copper(I)-catalyzed ring expansion reaction of isoxazoles with 4-diazoisoquinolin-3ones is reported, providing a series of densely substituted novel spiro[isoquinoline-4,2'-[1,3]oxazin]-3-ones in good to excellent yields. The prominent features of this methodology include broad substrate scope, readily available starting materials, cheap catalyst, mild reaction conditions, and scalability.
Article
Chemistry, Multidisciplinary
Shu-Sen Li, Shuo Sun, Jianbo Wang
Summary: The catalytic asymmetric trifluoromethylation of cyclic ketones via a Sc-III/chiral bisoxazoline-catalyzed homologation reaction using 2,2,2-trifluorodiazoethane (CF3CHN2) as the CF3 source is an efficient method to generate chiral alpha-trifluoromethyl cyclic ketones with excellent diastereoselectivity and enantioselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Biochemistry & Molecular Biology
Olga Bakulina, Anna Inyutina, Dmitry Dar'in, Mikhail Krasavin
Summary: This review summarizes recent developments in multicomponent reactions of diazo compounds, analyzing the role of diazo reagents and the type of interaction between components. In contrast to previous reviews mostly focused on metal catalyzed transformations, this work covers a substantial amount of organocatalytic or catalyst-free methodologies.
Article
Chemistry, Organic
Shuai Zhao, Xiang-Xiang Chen, Nan Gao, Mingcheng Qian, Xin Chen
Summary: The cyclopropanation reaction of 3-diazooxindoles with arenes was successfully achieved for the first time using visible-light irradiation, leading to the synthesis of a series of spiro[norcaradiene-7,3'-indolin]-2'-ones with high yields and excellent diastereoselectivities. The synthetic utility of this catalyst-free photochemical methodology was further demonstrated through controllable rearrangement and epoxidation reactions.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Feifei He, Rene M. Koenigs
Summary: In this study, the tris(pentafluorophenyl)borane-catalyzed reaction of carbazole heterocycles with aryldiazoacetates was reported. It was demonstrated that selective N-H or C-H functionalization could be achieved with good yields under different substrate conditions. The method showed promising application potential in 41 examples.
Article
Cardiac & Cardiovascular Systems
Dmytro O. Kryshtal, Daniel J. Blackwell, Christian L. Egly, Abigail N. Smith, Suzanne M. Batiste, Jeffrey N. Johnston, Derek R. Laver, Bjorn C. Knollmann
Summary: The main mechanism of antiarrhythmic action of flecainide is likely through inhibition of RyR2-mediated arrhythmogenic Ca release, rather than solely through sodium channel block. Experimental results in cardiomyocytes and mouse models have both confirmed this.
CIRCULATION RESEARCH
(2021)
Correction
Chemistry, Multidisciplinary
Suzanne M. Batiste, Jeffrey N. Johnston
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Abigail N. Smith, Jeffrey N. Johnston
Summary: The reinvestigation into the macrocyclooligomerization (MCO) of a tetradepsipeptide revealed a paradox where the MCO of depsipeptide monomers could result in impossible ring sizes, leading to unexpected findings of 18- and 30-membered cyclic oligomeric depsipeptides (CODs). An alternative method for preparing authentic 18- and 36-membered macrocycles was reported, providing definitive analytical characterization for each ring size. The study also included recharacterization and reassignment of two macrocycles originally reported in the MCO series, along with updated data on yields and isothermal titration calorimetry after the implementation of new critical protocols.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jade A. Bing, Nathan D. Schley, Jeffrey N. Johnston
Summary: This research presents a comparative analysis of non-fluorinated and alpha-fluoro nitroalkanes in their additions to azomethines, revealing an unusual crossover and reversal in diastereoselection.
Article
Cardiac & Cardiovascular Systems
Chantal J. M. van Opbergen, Navratan Bagwan, Svetlana R. Maurya, Joon-Chul Kim, Abigail N. Smith, Daniel J. Blackwell, Jeffrey N. Johnston, Bjorn C. Knollmann, Marina Cerrone, Alicia Lundby, Mario Delmar
Summary: This study reveals the relationship between exercise, catecholaminergic stimulation, Ca-i(2+) homeostasis, and arrhythmogenesis in PKP2-deficient hearts. Training disrupts Ca-i(2+) homeostasis in PKP2cKO hearts, leading to proarrhythmogenic changes facilitated by intracellular beta-adrenergic receptors and hyperphosphorylation of phospholamban. The findings suggest potential treatments for arrhythmogenic right ventricular cardiomyopathy and highlight the importance of PKP2 and phospholamban in arrhythmogenesis.
Article
Chemistry, Organic
Madelaine P. Thorpe, Abigail N. Smith, Michael S. Crocker, Jeffrey N. Johnston
Summary: The accessibility of bromonitromethane as a reagent for chemical synthesis has decreased recently, but this study presents a re-investigation and optimization of various preparations and the development of safe operating principles. This results in a reproducible procedure that offers a straightforward and sustainable way to obtain this critical reagent.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Michael S. Crocker, Zihang Deng, Jeffrey N. Johnston
Summary: Amide synthesis is widely used in drug development and peptide synthesis, but waste elimination in this process has had limited success. Umpolung amide synthesis has been developed as a method for enantioselective synthesis, but it cannot forge N-aryl amides. This study presents a direct synthesis method for N-aryl amides using a simple Bronsted base as a promoter, using alpha-fluoronitroalkanes and N-aryl hydroxyl amines.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Medicinal
Abigail N. Smith, Madelaine P. Thorpe, Daniel J. Blackwell, Suzanne M. Batiste, Corey R. Hopkins, Nathan D. Schley, Bjorn C. Knollmann, Jeffrey N. Johnston
Summary: The synthesis of N-Me and N-H analogues of ent-verticilide was described to enable a structure-activity relationship study based on cardiac ryanodine receptor (RyR2) calcium ion channel inhibition. The study found that a high degree of N-methyl amide content is critical for activity in the ent-verticilide series but not entirely so for the ent-verticilide B1 series.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Ivor Smajlagic, Jeffrey N. Johnston, Travis Dudding
Summary: The fluorine atom has a strong and mysterious influence on chemical reactions, as evidenced by its recent discovery of causing diastereodivergence in an enantioselective aza-Henry reaction. This study comprehensively examined the cases of alpha-fluoro nitronate additions to aldimines, revealing the non-covalent interactions dictating anti-selectivity (alpha-aryl) versus syn-selectivity (alpha-alkyl) and the secondary orbital interaction between fluorine and the activated azomethine.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Jade A. Bing, Jeffrey N. Johnston
Summary: The synthesis of 7-membered carbocyclic fi-fluoro-amines is achieved by combining the enantioselective aza-Henry reaction of aliphatic N-Boc imines and ring-closing metathesis. Reductive denitration is used to obtain both diastereomers of the fi-fluoro amine carbocycle, each with high enantiomeric excess.
Article
Pharmacology & Pharmacy
Daniel J. Blackwell, Abigail N. Smith, Tri Do, Aaron Gochman, Jeffrey Schmeckpeper, Corey R. Hopkins, Wendell S. Akers, Jeffrey N. Johnston, Bjorn C. Knollmann
Summary: This study developed a bioassay to measure the concentrations of nat-verticilide and ent-verticilide in murine plasma and correlated plasma concentrations with antiarrhythmic efficacy. The results showed that ent-verticilide has favorable pharmacokinetic properties and reduces ventricular arrhythmias in the nanomolar range, warranting further drug development.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)
Article
Cardiac & Cardiovascular Systems
Kyungsoo Kim, Daniel J. Blackwell, Samantha L. Yuen, Madelaine P. Thorpe, Jeffrey N. Johnston, Razvan L. Cornea, Bjorn C. Knollmarnn
Summary: Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of stroke and morbidity. Variants on chromosome 4q25, near the PITX2 gene, have been identified as the strongest genetic risk factors for AF in humans. This study found that deficiency in Pitx2 leads to hyperactivation of the cardiac ryanodine receptor (RyR2), which is associated with increased susceptibility to AF. Treatment with the RyR2 inhibitor ent-verticilide reduces the incidence and duration of AF, suggesting that targeting hyperactive RyR2 may be a promising approach to treat atrial arrhythmias caused by Pitx2 deficiency.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Jenna L. Payne, Zihang Deng, Andrew L. Flach, Jeffrey N. Johnston
Summary: In recent years, enantioselective halolactonization reactions have grown rapidly, but most are only effective in forming smaller rings (6,5,4-membered). The formation of highly selective seven-membered epsilon-lactones is rare and has never been achieved without conformational bias. This study describes the first highly enantioselective 7-exo-trig iodolactonizations of conformationally unbiased epsilon-unsaturated carboxylic acids, using a combination of a bifunctional BAM catalyst, I-2, and I(iii) reagent (PhI(OAc)(2):PIDA).
Meeting Abstract
Biophysics
Jacob A. Schwarz, Daniel Blackwell, Abigail N. Smith, Robyn T. Rebbeck, Jeffrey N. Johnston, Bjorn C. Knollmann, Razvan L. Cornea
BIOPHYSICAL JOURNAL
(2022)
Correction
Multidisciplinary Sciences
Suzanne M. Batiste, Jeffrey N. Johnston
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)