Article
Chemistry, Organic
Shuai Han, Yu Guo, Wei Zhang, Jinjin Chen, Zhen Wang, Yao-Fu Zeng
Summary: A general and efficient strategy for alpha-heterofunctionalization of aryloxy-activated amides has been developed. This strategy allows the reaction with various nucleophiles, including amines, alcohols, phenols, carboxylic acids, and thiols, under mild conditions with excellent regioselectivity. The synthetic value of this method has been demonstrated through the late-stage modification of biological molecules. Furthermore, a preliminary mechanism for this umpolung reaction has been proposed.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Jiahua Chen, Jun Wei Lim, Derek Yiren Ong, Shunsuke Chiba
Summary: The synthesis of alpha-tertiary amines was achieved by iteratively adding carbon nucleophiles to N,N-dialkyl carboxamides, forming anionic tetrahedral carbinolamine intermediates. These intermediates were then treated with bromotrimethylsilane followed by organomagnesium or organolithium reagents to produce alpha-tertiary amines. The use of (trimethylsilyl)methylmagnesium bromide as the second nucleophile allowed for aza-Peterson olefination, resulting in the formation of 1,1-diarylethylenes after acidic work-up.
Review
Chemistry, Applied
Ilya N. Egorov, Sougata Santra, Grigory Zyryanov, Adinath Majee, Alakananda Hajra, Oleg N. Chupakhin
Summary: This review focuses on the asymmetric addition reactions of non-carbon nucleophiles to imines. Chiral catalysts are used to achieve control over the stereochemistry of the addition reactions.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Jiabin Shen, Zhihao Wang, Yuru Zhang, Jun Xu, Chao Shen, Pengfei Zhang
Summary: In this study, we report the discovery of a convenient and efficient method to construct various C-X bonds using a copper catalytic system. This strategy offers mild reaction conditions and easy formation of different C-X bonds (C-O, C-Cl, C-Br, C-I, C-F and C-S). This methodology provides a universal and practical approach for synthesizing potentially bioactive nafimidone derivatives, thereby expanding the compound library for medicinal screening purposes.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Jaehee Lee, Xuan Ju, Miseon Lee, Qi Jiang, Hwanjong Jang, Wan Shin Kim, Linglin Wu, Suja Williams, Xiao-Jun Wang, Xingzhong Zeng, Jenna Payne, Zhengxu S. Han
Summary: The copper-catalyzed regioselective and stereospecific coupling between aziridines and in situ generated pyridine Grignard reagents is reported in this study. This method enables the synthesis of beta-pyridylethylamines with diverse structures and functionalities, which are potential scaffolds for the synthesis of biologically active compounds commonly found in pharmaceuticals. Additionally, the synthesis of challenging chiral dihydroazaindoles was achieved through mild one-pot reaction conditions involving aziridine opening and nucleophilic cyclization.
Article
Chemistry, Multidisciplinary
Sebastian Heindl, Margaux Riomet, Jan Matyasovsky, Miran Lemmerer, Nicolas Malzer, Nuno Maulide
Summary: A chemoselective and robust protocol for the gamma-oxidation of beta,gamma-unsaturated amides has been developed, showcasing the synthetic utility of the products obtained through radical cyclisation reactions and oxidation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Yan He, Qimeng Liu, Tian Gong, Yunfei Liu, Xinying Zhang, Xuesen Fan
Summary: A convenient synthesis protocol for alpha-substituted-beta-oxo azaheterocycles has been developed using oxoammonium salt-promoted cascade reaction. Nucleophiles such as acetyl or cyano group-containing active methylene compounds or morpholines were reacted with saturated cyclic amines, leading to the formation of different intermediates. The chemoselectivity of these reactions was investigated through experimental studies and DFT calculations.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Hanbin Lu, Canhua Zhou, Zhe Wang, Terumasa Kato, Yan Liu, Keiji Maruoka
Summary: A three-component coupling reaction of α, β, γ, δ-unsaturated carbonyl compounds with alkylsilyl peroxides catalyzed by Fe(OTf)(2) under mild reaction conditions is achieved in the presence of certain heteronucleophiles (ROH and indole). Various α, β, γ, δ-diene carbonyl substrates with different substituents can be successfully employed by combining them with different alkylsilyl peroxides. This new approach is also applicable to the double functionalization of diene substrates.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Tiffany Q. Chen, P. Scott Pedersen, Nathan W. Dow, Remi Fayad, Cory E. Hauke, Michael C. Rosko, Evgeny O. Danilov, David C. Blakemore, Anne-Marie Dechert-Schmitt, Thomas Knauber, Felix N. Castellano, David W. C. MacMillan
Summary: In this study, a general catalytic method for direct decarboxylative halogenation of (hetero)aryl carboxylic acids was reported, accommodating an exceptionally broad scope of substrates. The research leveraged an aryl radical intermediate towards two divergent functionalization pathways.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Jigyansa Sahoo, Jeetendra Panda, Santanab Giri, Gokarneswar Sahoo
Summary: An investigation into the sensitivity of reaction conditions to a highly utilized protocol has been reported. The mono-Boc functionalization of prolinol can be controlled for the exclusive synthesis of N-Boc, O-Boc, or oxazolidinone derivatives. A successful chemoselective functionalization of the nucleophilic sites of prolinol by exploiting the relative acidity difference of NH and OH along with the reversed nucleophilicity of the corresponding conjugate bases N- and O- is reported. This protocol has also been used for the synthesis of several O-functionalized prolinol derived organocatalysts, few of which have been newly reported.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Fangyuan Chen, Junyuan Tang, Yinhui Wei, Jingyuan Tian, Hui Gao, Wei Yi, Zhi Zhou
Summary: This study successfully utilized alpha-allenols as innovative three-carbon annulation components in the Rh(iii)-catalyzed redox-neutral C-H coupling of N-phenoxyacetamides, leading to the assembly of 4-alkylidene chroman-2-ol frameworks through an unusual [3+3] annulation. Mechanistic studies revealed that synergistic coordination modes between the dual directing groups and the rhodium metal center are responsible for the observed exclusive selectivity in this transformation.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Arpan Das, Pallavi Sarkar, Subir Maji, Swapan K. Pati, Swadhin K. Mandal
Summary: A class of stable mesoionic N-heterocyclic imines (mNHIs) with highly polarized exocyclic imine moiety were synthesized. These mNHIs exhibit the highest basicity and donor ability among reported NHIs. The superior nucleophilicity of newly designed mNHIs was exploited to couple inert primary amides under reductive conditions and hetero-couple amide and amine using CO2. These catalytic transformations were used for the diversification of biologically active drug molecules under metal-free conditions. The mechanism was explored through control experiments and characterization of key intermediates using spectroscopic and crystallographic techniques.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Ramdas Sreedharan, Thirumanavelan Gandhi
Summary: alpha-Branched amines bearing beta-carbonyl in isoindolinones were synthesized via the aroylation of C(sp (3))-H carbon adjacent to the nitrogen atom. Unactivated tertiary amides and unactivated alkyl esters were used as electrophile sources. The reaction showed high functional group compatibility and could be applied to a range of substrates, including organometallic ferrocenyl esters and indole methyl esters with an acidic NH moiety.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Haipeng Hu, Cuilin Wang, Xin Wu, Yangu Liu, Guizhou Yue, Gehong Su, Juhua Feng
Summary: The catalytic alpha-C-H fluorination of aryl acetic acids was achieved with good functional group tolerance in the presence of a boron catalyst. A series of alpha-fluoro aryl acetic acids were obtained in a single step with high yields (up to 96%). The catalytic reaction was employed for the synthesis of bioactive molecules and the modification of profen drugs.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Xiaoqiang Lei, Yuanhe Li, Yang Lai, Shengkun Hu, Chen Qi, Gelin Wang, Yefeng Tang
Summary: An unprecedented strain-driven dyotropic rearrangement has been achieved, allowing for the efficient access to alpha-methylene-gamma-butyrolactones with remarkable structural diversity. The reaction demonstrates excellent efficiency, high stereospecificity, predictable chemoselectivity, and broad substrate scope, making it a powerful tool for synthesizing MBL-containing molecules of natural or synthetic origin. Both experimental and computational evidence suggest a dualistic pattern for the reaction, with an asynchronous concerted mechanism likely for hydrogen migration and a stepwise process involving a phenonium ion intermediate favored for aryl migration. The synthetic potential of the reaction is exemplified by its application in constructing natural products and relevant scaffolds efficiently.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Multidisciplinary
Philipp Spiess, Saad Shaaban, Daniel Kaiser, Nuno Maulide
Summary: Umpolung is a term describing the reversal of innate polarity, which has become an important tool in synthetic organic chemistry. In this Account, the authors provide an overview of established methods and summarize their findings in the rapidly developing field of umpolung of carbonyl derivatives. They focus on the alpha-umpolung of amides enabled by electrophilic activation and the enolonium chemistry of ketones enabled by hypervalent iodine reagents. The authors discuss the challenges and achievements of these reactions, as well as mechanistic aspects. Rating: 8/10.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Minghao Feng, Anthony J. J. Fernandes, Ana Sirvent, Eleonora Spinozzi, Saad Shaaban, Nuno Maulide
Summary: We present a simple method for the direct amination of unfunctionalized, native carbonyls (amides and ketones) by transferring a free amino group (NH2) from a commercially available nitrogen source. Mild conditions enable the production of primary a-amino carbonyls, allowing for diverse in situ functionalization reactions, such as peptide coupling and Pictet-Spengler cyclization, that take advantage of the presence of the unprotected primary amine.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
J. Patrick Zobel, Anna M. Wernbacher, Leticia Gonzalez
Summary: The mechanism of reverse intersystem crossing (rISC) in metal-based TADF emitters is still not clear, as the small singlet/triplet energy gaps necessary for thermal rISC in donor-acceptor systems with charge-transfer excited states have spin-orbit couplings that are too small for effective rISC. In this study, the first nonadiabatic dynamics simulation of rISC process in a carbene-copper(I)-carbazolyl TADF emitter is reported. Efficient rISC on a picosecond time scale is demonstrated, involving an intermediate higher-lying triplet state of metal-to-ligand charge transfer character ((MLCT)-M-3) that enables large spin-orbit couplings with the lowest singlet charge transfer state. The mechanism is completed in the S-1 state where the complex can return to a co-planar coordination geometry with high fluorescence efficiency.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Pauline Adler, Marion Gras, Michael Smietana
Summary: Amides are important functional groups in organic chemistry, and their direct coupling from carboxylic acids and amines is challenging and often results in non-atom-economic reactions with non-recoverable by-products. This study reports a new catalytic approach for the direct preparation of amides using organocatalysis and a substoichiometric amount of activating agent. The method is efficient, mild, and compatible with a wide range of substrates, including those with chiral stereocenters and SPPS.
Article
Chemistry, Multidisciplinary
Philipp Spiess, Ana Sirvent, Irmgard Tiefenbrunner, Jules Sargueil, Anthony J. Fernandes, Ana Arroyo-Bondia, Ricardo Meyrelles, David Just, Alexander Prado-Roller, Saad Shaaban, Daniel Kaiser, Nuno Maulide
Summary: p-Toluenesulfonyl (Tosyl) and nitrobenzenesulfonyl (Nosyl) are widely used sulfonyl protecting groups for amines in organic synthesis. However, p-toluenesulfonamides are difficult to remove in multistep synthesis, while nitrobenzenesulfonamides are not stable under various reaction conditions. In this study, we introduce a new sulfonamide protecting group called Nms, which overcomes these limitations and shows superiority in terms of stability and cleavability.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Physical
Madlen Maria Reiner, Brigitta Bachmair, Maximilian Xaver Tiefenbacher, Sebastian Mai, Leticia Gonzalez, Philipp Marquetand, Christoph Dellago
Summary: We propose a rare event sampling scheme, the Nonadiabatic Forward Flux Sampling (NAFFS), which combines the trajectory surface hopping (TSH) method with the forward flux sampling (FFS) method. NAFFS is applied to two relevant excited-state models and provides insights into transition rate constants in regimes that cannot be explored through traditional TSH simulations. The comparison with brute-force TSH simulations shows that NAFFS is significantly more efficient, making it a valuable tool for studying rare nonadiabatic events in excited-state dynamics.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Chemistry, Organic
Nuno Maulide, Irmgard Tiefenbrunner, Bogdan R. Brutiu, Tobias Stopka
Summary: We have developed an isothiouronium salt reagent for the straightforward synthesis of cyanomethyl thioesters with excellent functional group tolerance and without the need for thiols. Furthermore, we demonstrate that the obtained products can be used for amide synthesis in either a two-step or one-pot approach.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Phillip S. Grant, Ricardo Meyrelles, Oliver Gajsek, Gerhard Niederacher, Boris Maryasin, Nuno Maulide
Summary: Cationic cyclopropanation is a rare but important biosynthetic pathway involving the formation of a new sigma-C-C bond through the elimination of carbocations. Despite the historical influence of bioinspired synthetic chemistry, cationic cyclopropanation has not been widely used due to the preference of carbocations for competing elimination pathways. In this study, we conducted a synthetic and computational investigation of cationic cyclopropanation using 6,8-cycloeudesmanes as a platform, and successfully applied it to the synthesis of complex cyclopropanes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Minghao Feng, Anthony J. Fernandes, Ricardo Meyrelles, Nuno Maulide
Summary: We report a new method for preparing chiral α-amino amides by directly aminating amides using chiral sulfinamides. This method involves a [2,3]-sigmatropic rearrangement of a crucial sulfonium intermediate. Quantum chemical calculations provide predictive insights into the important E/Z selectivity of the amino-vinyloxy-sulfonium species.
Article
Chemistry, Multidisciplinary
David Hernandez-Castillo, Roland E. P. Nau, Marie-Ann Schmid, Stefanie Tschierlei, Sven Rau, Leticia Gonzalez
Summary: Understanding the factors that determine the luminescence lifetime of transition metal compounds is crucial for applications in photocatalysis and photodynamic therapy. This study challenges the commonly accepted idea that emission lifetimes can be controlled by optimizing the energy barrier or gap between different excited states. Instead, an extended kinetic model that considers all the pathways related to multiple isomers is found to accurately predict temperature-dependent emission lifetimes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Miran Lemmerer, Nuno Maulide
Summary: The combination of Lewis bases with alpha, beta-unsaturated carbonyls enables the in-situ generation of enolates, eliminating the need for strong Bronsted bases. This approach has been widely employed in arylation reactions in various contexts. This conceptual article provides an overview of the developed strategies, highlighting their features.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Physical
Jin Wen, Sebastian Mai, Leticia Gonzalez
Summary: In this study, the excited-state dynamics of an overcrowded alkene in solution were investigated using a QM/MM approach. The results from spectroscopy and radial distribution function analysis revealed similar solvent orientation with the molecular motor between the electronic excited state and the ground state.
JOURNAL OF PHYSICAL CHEMISTRY A
(2023)
Article
Chemistry, Physical
Nadja K. Singer, Katharina Schloegl, J. Patrick Zobel, Marko D. Mihovilovic, Leticia Gonzalez
Summary: Understanding the thermal isomerization mechanism of azobenzene derivatives is crucial for designing photoswitches with adjustable half-lives. Through quantum chemical calculations, nonadiabatic transition state theory, and photosensitized experiments, we unravel the thermal Z/E isomerization of a heteroaromatic azoswitch, phenylazo-1,3,5-trimethylpyrazole, and predict two pathways at room temperature, involving different reaction mechanisms and spin-orbit couplings.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Mark Stitch, Davide Avagliano, Daniel Graczyk, Ian P. Clark, Leticia Gonzalez, Michael Towrie, Susan J. Quinn
Summary: This study explores the sensitivity of an infrared probe to G-quadruplex structures and demonstrates its potential as a sensitive reporter of biological environments.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
David Just, Carlos R. Goncalves, Uros Vezonik, Daniel Kaiser, Nuno Maulide
Summary: A simple method for the direct formation of aminolactones from unactivated alkenes has been reported in this study, filling the gap in this field. The method utilizes cheap and readily available reactants, and exhibits excellent functional group tolerance and chemoselectivity. The synthetic versatility of the products has been demonstrated through a range of transformations.
