Article
Chemistry, Organic
Fuchao Yu, Daniel A. Valles, Weijie Chen, Scott D. Daniel, Ion Ghiviriga, Daniel Seidel
Summary: Secondary alicyclic amines are converted to alpha-aminonitriles by adding TMSCN to their corresponding imines, which are generated in situ via the oxidation of amine-derived lithium amides with simple ketone oxidants. Amines with an existing a-substituent undergo regioselective alpha'-cyanation, even if the C-H bonds at that site are less activated. Amine alpha-arylation can be combined with alpha'-cyanation to produce difunctionalized products in a single step.
Article
Chemistry, Multidisciplinary
Priyankar Jha, Saddam Husen, Ravindra Kumar
Summary: An efficient redox-neutral method has been developed for alpha-Csp(3)-H functionalization of secondary cyclic amines via concurrent N-arylation/formal cross dehydrogenation coupling. The operationally simple protocol is highly atom economical and environmentally benign, with an E-factor of approximately 0.5. The reaction mechanism has been explained based on control experiments and examination of reactive intermediates by mass spectrometry.
Article
Chemistry, Inorganic & Nuclear
Jagannath Rana, Palaniyappan Nagarasu, Murugan Subaramanian, Akash Mondal, Vedichi Madhu, Ekambaram Balaraman
Summary: The general and efficient C(alpha)-alkylation of oxindoles with unactivated secondary alcohols as alkylating agents catalyzed by a newly developed NNN-Mn(II) complex demonstrates the importance of the NH moiety in the complex and M-L cooperation during the catalytic transformation.
Article
Chemistry, Organic
Xiaochen Ji, Zhonglin Yang, Xinzhuang Wu, Guo-Jun Deng, Huawen Huang
Summary: This study describes a photoredox neutral decarboxylative hydroxyalkylation reaction of heteroarenes with alpha-keto acids under mild conditions. Stable and readily available alpha-keto acids were used as hydroxyalkylating reagents, with CO2 released as the byproduct. A variety of aromatic and aliphatic alpha-keto acids were successfully converted into hydroxyalkylated heteroarenes, providing a new approach for the synthesis of valuable products.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Heng Li, Jinwen Tong, Yan Zhu, Cong Jiang, Ping Liu, Peipei Sun
Summary: In this study, an efficient electrochemical Minisci reaction was developed to synthesize 3-hydroxyalkylquinoxalin-2(1H)-ones. The reaction involved hydrogen-atom transfer driven alpha-C(sp(3))-H functionalization of alcohols, and did not require transition metals or chemical oxidants. The reaction showed good compatibility with primary or secondary alcohols and a wide range of quinoxalinones, leading to high yields of the desired products.
Article
Chemistry, Organic
Jae Hyun Kim, Anirudra Paul, Ion Ghiviriga, Daniel Seidel
Summary: Enolizable cyclic imines obtained in situ from lithium amides by oxidation with simple ketone oxidants can be readily alkylated with a range of enolates to provide mono- and polycyclic beta-aminoketones in a single operation, including the natural product (+/-)-myrtine. Nitrile anions also serve as competent nucleophiles in these transformations promoted by BF3 etherate. Moreover, beta-aminoesters derived from ester enolates can be converted to the corresponding beta-lactams.
Article
Chemistry, Organic
Man Wang, Ming Li, Long Zhang, Ran Song, Daoshan Yang, Jian Lv
Summary: Photoredox catalysis involving Ir-III in combination with DABCO as a dual hydrogen-bonding donor and organic base can enable the direct gamma-C(sp(3))-H activation of saturated alpha-keto esters, leading to the synthesis of various 4-indolyl substituted 2-hydroxy-3-enoic acid esters. This method offers high yields and high enantioselectivity.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Subhradeep Dutta, Jae Hyun Kim, Kamal Bhatt, Dillon R. L. Rickertsen, Khalil A. Abboud, Ion Ghiviriga, Daniel Seidel
Summary: A new strategy utilizing imine-BF3 complexes to access alpha-functionalized alicyclic amines is presented. These complexes can be easily prepared and react with a variety of organometallic nucleophiles to form alpha-functionalized azacycles. The in situ preparation of imine-BF3 complexes allows for the direct synthesis of alpha-functionalized morpholines and piperazines from their parent amines.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(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
Xukai Zhou, Daniel Pyle, Zining Zhang, Guangbin Dong
Summary: Here we present the development of a deacylative thiolation reaction for diverse methyl ketones. This reaction is redox-neutral and heavy-metal-free, providing a novel approach for site-specific introduction of thioether groups at unactivated aliphatic positions. It exhibits excellent functional group tolerance and wide substrate scope, enabling late-stage derivatization. The reaction relies on efficient condensation between the activation reagent and ketone substrates, leading to aromatization-driven C-C fragmentation and rapid radical coupling with thiosulfonates. Experimental and computational mechanistic studies suggest a radical chain pathway.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
David F. Leon Rayo, Ali Mansour, Wenbin Wu, Benjamin N. Bhawal, Fabien Gagosz
Summary: This study presents a unique approach for the electrophilic Au-catalyzed alpha-C-H bond functionalization of tertiary amines. The success of this transformation relies on the synergistic effects of electronic, steric, and conformational factors induced by a malonate unit in the substrate. The application of this new reactivity to the synthesis of tetrahydro-gamma-carboline products is of great significance for the development of bioactive alkaloid natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Guozhe Guo, Yong Yuan, Xiazhen Bao, Xuehui Cao, Tongzhi Sang, Jiayuan Wang, Congde Huo
Summary: The study presents a novel visible-light induced redox-neutral decarboxylative cross coupling reaction, which successfully synthesized a variety of symmetrical and unsymmetrical 3,3'-bisindolylmethane derivatives from indole-3-acetic acid NHPI esters and indoles. Additionally, the reaction can be easily adapted for the preparation of a wide range of diarylmethane derivatives.
Review
Chemistry, Organic
Weijie Chen, Daniel Seidel
Summary: This review provides a comprehensive overview of condensation-based methods for C-H bond functionalization of amines using azomethine ylides as key intermediates, which allow rapid transformation of simple starting materials into complex amines.
SYNTHESIS-STUTTGART
(2021)
Article
Chemistry, Inorganic & Nuclear
Gayathri B. Gange, Amanda L. Humphries, Mark D. Smith, Dmitry V. Peryshkov
Summary: In this study, we report the reactivity of carboranyl diphosphine with terminal alkynes, resulting in the formation of boron-containing phosphacycles. The reaction combines the activation of electron-deficient alkynes by phosphine groups and the redox behavior of carborane clusters, leading to the formation of a fused product of alkenylphosphonium cycle and reduced carborane cluster.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Zeyu Shao, Junqi Zhou, Ziyu Wang, Biao Liu, Liang-Hua Zou, Cheng Wang, Jian Wen
Summary: A metal-free allylic C(sp(3))-H alkylation method based on [2,3]-sigmatropic rearrangement strategies has been developed, allowing the allylic C(sp(3))-H alkylation of a wide range of alpha-alkylstyryl sulfonium salts. This protocol enables facile access to allylated carbon quaternary centers in moderate to good yields. The one-pot procedure, product derivatization, and late-stage functionalization demonstrate the practicality of this protocol in organic synthesis.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Anirudra Paul, Jae Hyun Kim, Scott D. Daniel, Daniel Seidel
Summary: Despite efforts by practitioners, direct alpha-C-H bond functionalization of unprotected alicyclic amines is rare. A new method utilizing N-lithiated alicyclic amines has been developed, providing a convenient approach to achieve functionalization reactions under mild conditions. This method offers a new pathway for the synthesis of beta-amino ketones with regioselective alpha'-alkylation, and potential for one-pot synthesis of polycyclic dihydroquinolones.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Jae Hyun Kim, Anirudra Paul, Ion Ghiviriga, Daniel Seidel
Summary: Enolizable cyclic imines obtained in situ from lithium amides by oxidation with simple ketone oxidants can be readily alkylated with a range of enolates to provide mono- and polycyclic beta-aminoketones in a single operation, including the natural product (+/-)-myrtine. Nitrile anions also serve as competent nucleophiles in these transformations promoted by BF3 etherate. Moreover, beta-aminoesters derived from ester enolates can be converted to the corresponding beta-lactams.
Article
Chemistry, Medicinal
Stephanie L. Slania, Deepankar Das, Ala Lisok, Yong Du, Zirui Jiang, Ronnie C. Mease, Steven P. Rowe, Sridhar Nimmagadda, Xing Yang, Martin G. Pomper
Summary: Two new small molecules, QCP01 and [In-111]QCP02, based on (4-quinolinoyl)-glycyl-2-cyanopyrrolidine were synthesized and characterized for imaging of fibroblast activation protein (FAP). Both molecules demonstrated nanomolar inhibition of FAP and selective binding to FAP-expressing tumors in vivo. [In-111]QCP02 showed high uptake in FAP-positive tumors, indicating its potential as an imaging agent for FAP-targeted therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Weijie Chen, Daniel Seidel
Summary: Polycyclic lactams are prepared in a single operation from otoluamides and cyclic amines, utilizing transient cyclic imines generated in situ from lithium amides and simple ketone oxidants. The annulation process involves imines like 1-pyrroline and 1-piperideine engaging lithiated o-toluamides, with undesired side reactions suppressed through careful selection of reaction conditions.
Article
Chemistry, Organic
Daniel A. Valles, Subhradeep Dutta, Anirudra Paul, Khalil A. Abboud, Ion Ghiviriga, Daniel Seidel
Summary: This one-pot procedure allows for the sequential, regioselective, and diastereoselective introduction of the same or two different substituents to the alpha- and alpha'-positions of unprotected azacycles using corresponding organolithium compounds. Various azacycles like pyrrolidines, piperidines, azepanes, and piperazines are included in the scope of this transformation.
Review
Chemistry, Organic
Weijie Chen, Daniel Seidel
Summary: This review provides a comprehensive overview of condensation-based methods for C-H bond functionalization of amines using azomethine ylides as key intermediates, which allow rapid transformation of simple starting materials into complex amines.
SYNTHESIS-STUTTGART
(2021)
Article
Multidisciplinary Sciences
O. C. Rogers, D. M. Rosen, L. Antony, H. M. Harper, D. Das, X. Yang, I Minn, R. C. Mease, M. G. Pomper, S. R. Denmeade
Summary: Prostate cancer cells have low proliferative rate and high levels of prostate-specific proteases. Utilizing PSMA inhibitors conjugated with toxins can selectively kill prostate cancer cells, demonstrating selective toxicity in vitro.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Organic
Subhradeep Dutta, Bowen Li, Dillon R. L. Rickertsen, Daniel A. Valles, Daniel Seidel
Summary: This review provides a concise overview of the methods that enable the functionalization of sp(3) C-H bonds in amines and their derivatives.
Article
Chemistry, Organic
Anirudra Paul, Camille Vasseur, Scott D. Daniel, Daniel Seidel
Summary: Relatively unstable cyclic imines, generated from alicyclic amines via oxidation of their lithium amides with simple ketone oxidants, react with aryllithium compounds containing a leaving group on an ortho-methylene functionality to form polycyclic isoindolines in a single step. The transformation can be applied to pyrrolidine, piperidine, azepane, azocane, and piperazine.
Article
Radiology, Nuclear Medicine & Medical Imaging
Catherine A. Foss, Alvaro A. Ordonez, Ravi Naik, Deepankar Das, Andrew Hall, Yunkou Wu, Robert F. Dannals, Sanjay K. Jain, Martin G. Pomper, Andrew G. Horti
Summary: The study presents the radiosynthesis of JNJ-28312141 and its specific binding to CSF1R+ macrophages, delineating granulomatous lesions in a murine model of pulmonary TB using PET.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)
Article
Chemistry, Multidisciplinary
Alafate Adili, Angie B. Korpusik, Daniel Seidel, Brent S. Sumerlin
Summary: Visible light-mediated direct decarboxylation is a versatile technique for the synthesis of functional materials with tailored compositions and properties. This process allows for the generation of carbon-centered radicals in polymer chains without the need for preactivation of acid groups. It can be used to obtain challenging copolymers and trigger degradation of polymer backbones.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Sharath Chandra Mallojjala, Victor O. Nyagilo, Stephanie A. Corio, Alafate Adili, Anuradha Dagar, Kimberly A. Loyer, Daniel Seidel, Jennifer S. Hirschi
Summary: The mechanistic study of three intermolecular anti-Markovnikov alkene hydrofunctionalization reactions has provided detailed insights into the reaction pathways and rate-limiting steps. These findings can guide the development of asymmetric versions of these reactions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Fuchao Yu, Daniel A. Valles, Weijie Chen, Scott D. Daniel, Ion Ghiviriga, Daniel Seidel
Summary: Secondary alicyclic amines are converted to alpha-aminonitriles by adding TMSCN to their corresponding imines, which are generated in situ via the oxidation of amine-derived lithium amides with simple ketone oxidants. Amines with an existing a-substituent undergo regioselective alpha'-cyanation, even if the C-H bonds at that site are less activated. Amine alpha-arylation can be combined with alpha'-cyanation to produce difunctionalized products in a single step.
Article
Chemistry, Organic
Alafate Adili, Aniket V. V. Sole, Bishwaprava Das, Megan E. Matter, Daniel Seidel
Summary: In the presence of a thiourea-carboxylic acid catalyst, N-9-fluorenyltryptamines undergo highly enantioselective Pictet-Spengler reactions with a range of aldehydes. The reaction exhibits good compatibility with aromatic aldehydes, accepting diverse substituents at various positions on the ring. Electron-deficient tryptamines can also be used as substrates. Furthermore, the fluorenyl protecting group can be easily removed without affecting the enantioselectivity of the product.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Physical
Alafate Adili, John-Paul Webster, Chenfei Zhao, Sharath Chandra Mallojjala, Moises A. Romero-Reyes, Ion Ghiviriga, Khalil A. Abboud, Mathew J. Vetticatt, Daniel Seidel
Summary: The enantioselective oxa-Pictet-Spengler reactions of tryptophol with aldehydes were successfully conducted under weakly acidic conditions using a combination of indoline HCl salt and bisthiourea compound as catalysts. Mechanistic investigations determined the roles of both catalysts and confirmed the involvement of oxocarbenium ion intermediates, ruling out alternative scenarios. A stereochemical model derived from density functional theory calculations provided the basis for the development of a highly enantioselective stereodivergent variant with racemic tryptophol derivatives.