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, Organic
Sooyun Choi, Melody C. Guo, Gavin M. Coombs, Scott J. Miller
Summary: An atroposelective synthesis method for N-aryl 1,2,4-triazoles was developed. By utilizing a chiral phosphoric acid catalyst, a cyclodehydration reaction achieved asymmetric induction, resulting in atropisomeric N-aryl 1,2,4-triazoles with up to 91:9 enantiomeric ratio. Further crystallization of the isolated heterocycle enhanced the atropisomeric ratio of several analogs to 99:1 or higher. Additionally, a divergent and substrate-dependent reaction pathway leading to a different heterocyclic product was revealed.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Remi Andres, Qian Wang, Jieping Zhu
Summary: This paper reports the first examples of catalytic enantioselective PSR of tryptamines with alpha-ketoamides, and a new class of easily accessible organocatalysts was developed to achieve excellent yields and enantioselectivities.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Applied
Liu-Yang Pu, Fan Yang, Ji-Qiang Chen, Ying Xiong, Jian-Hua Xie, Qi-Lin Zhou
Summary: The enantioselective total synthesis of the pentacyclic proaporphine alkaloid (-)-misramine was achieved, featuring key reactions including Pictet-Spengler cyclization and Baeyer-Villiger oxidation. The absolute configuration of the pentacyclic framework was determined through X-ray single-crystal analyses.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Applied
Moreshwar B. B. Chaudhari, Prachi Gupta, Patricia Llanes, Miquel A. A. Pericas
Summary: The enantioselective Pictet-Spenlger reaction of tryptamines and diketo compounds catalyzed by a polymer-supported phosphoric acid (TRIP) has been achieved for the first time in continuous flow. A diverse library of quaternary tryptolines has been synthesized in 36-95% yield with 39-99% enantiomeric excess using this approach. The scalability of the reaction has been demonstrated in continuous flow, with a residence time of only 24 minutes. The robust immobilized catalyst has been recycled and reused multiple times in both batch and flow reactions. Synthesis of chiral precursors of Tadalafil, Iboga-type alkaloid (+)-Tabertinggine, and antimalarial spiroindolinones has been successfully achieved in both batch and continuous-flow reactions.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Ahreum Kim, Aram Kim, Sunjung Park, Sangji Kim, Hongil Jo, Kang Min Ok, Sang Kook Lee, Jayoung Song, Yongseok Kwon
Summary: A novel chiral phosphoric acid-catalyzed atroposelective Pictet-Spengler reaction of N-arylindoles has been reported, resulting in highly enantioenriched N-aryl-tetrahydro-beta-carbolines with axial chirality. The introduction of a hydrogen bond donor on the bottom aromatic ring, forming a secondary interaction with the phosphoryl oxygen, is crucial for achieving high enantioselectivity. The transformation is tolerant to a wide variety of substituents and can provide products with up to 98% ee.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Jinlong Zhang, Zeng Gao, Jinlong Qian, Huameng Yang, Maosheng He, Gaoxi Jiang
Summary: A family of axially chiral azepine-containing seven-membered cyclic P,N-ligands, named Indole-azepinap, was prepared using L-alanine as an original chirality source. The direct chromatographic separation of two diastereomeric phosphine oxides on silica gel allowed easy accessibility of these ligands for further structural and electronic modifications. These Indole-azepinaps showed promising results in a Pd-catalyzed asymmetric allylic alkylation with high yields and moderate enantioselectivities.
Article
Chemistry, Organic
Xiaoxiao Song, Yanjun Fan, Zhiming Zhu, Qijian Ni
Summary: We have developed a highly straightforward strategy for the synthesis of a new axially chiral 3-arylindolizine scaffold using chiral phosphoric acid catalyst. The reaction showed good scalability and yielded a series of axially chiral 3-arylindolizines with excellent enantioselectivity. This approach not only has a broad substrate scope and mild reaction conditions, but also demonstrates the potential utility of the formed axially chiral compounds.
Article
Multidisciplinary Sciences
Aaron L. Featherston, Yongseok Kwon, Matthew M. Pompeo, Oliver D. Engl, David K. Leahy, Scott J. Miller
Summary: This study introduces a novel method for controlling the stereochemistry of dinucleotide synthesis using chiral phosphoric acid catalysts, achieving control over the stereogenic phosphorous centers and unprecedented levels of diastereodivergence. The method utilizes two different CPA scaffolds to achieve stereodivergence and does not require stoichiometric activators or chiral auxiliaries, making it a convenient and efficient asymmetric catalysis method for the synthesis of diastereomeric dinucleotides and cyclic dinucleotides of interest in immuno-oncology.
Article
Chemistry, Multidisciplinary
Viraj A. Bhosale, Ivana Cisarova, Martin Kamlar, Jan Vesely
Summary: This study presents a novel chiral phosphoric acid (CPA)-catalyzed reaction, allowing for the asymmetric addition of alpha-fluoro(phenylsulfonyl)methane (FSM) derivatives to in situ generated cyclic N-acyliminium. The process demonstrates high stereoselectivity, leading to the formation of biorelevant isoindolinones containing sulfone and fluorine substituents with excellent stereoselectivities.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Thomas Varlet, Mateja Matisic, Elsa Van Elslande, Luc Neuville, Vincent Gandon, Geraldine Masson
Summary: A diastereodivergent and enantioselective synthesis of chiral spirocyclohexyl-indolenines with four contiguous stereo-genic centers was achieved through a chiral phosphoric acid-catalyzed cycloaddition. By carefully choosing reaction conditions, modular access to two different diastereoisomers with high enantioselectivities was obtained. The functional group manipulation of these compounds provides an efficient access to enantioenriched spirocyclohexyl-indolines and -oxindoles.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Jin Cui, Sadhanendu Samanta, Takumi Watanabe, Masakatsu Shibasaki
Summary: In this report, the efficient synthesis of interesting molecules through direct 1,6-conjugate addition of butenolide to p-quinone methides via Bronsted base catalysis is presented. The reaction exhibits regioselective gamma-attack of butenolide and demonstrates good functional group tolerance.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Yongbiao Guo, Zhenhua Gao, Junchen Li, Xiaojing Bi, Enxue Shi, Junhua Xiao
Summary: This study presents a highly efficient and practical method for the direct synthesis of 2,3-dihydroquinazolinones from diverse aldehydes with excellent yields and enantioselectivity. The method shows improved enantioselectivity for aliphatic aldehydes and wide tolerance to different functional groups. Gram-scale synthesis and simplified work-up procedure demonstrate the practicality of this method.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Letter
Chemistry, Organic
Zhengyu Han, Han Zhuang, Luning Tang, Yu Zang, Wengang Guo, Hai Huang, Jianwei Sun
Summary: A catalytic asymmetric allylic substitution/isomerization process with central chirality transposition has been developed. This process utilizes the ambident reactivity of the 2-indole imine methide generated in situ from racemic tertiary indolylmethanols, allowing regioselective formation of a C-C bond at the 3 position and enantiocontrolled construction of a stereogenic center at the 2-benzylic position.
Article
Chemistry, Organic
Hualing He, Xiaoxue Tang, Yang Cao, Jon C. Antilla
Summary: A catalytic enantioselective reduction of alpha-trifluoromethylated imines has been developed using a BINOL-derived boro-phosphate as catalyst and catecholborane as hydride source. This method provides an efficient route to prepare synthetically useful chiral alpha-trifluoromethylated amines in high yields and excellent enantioselectivities under mild conditions (up to 98% yield and 96% ee).
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Yingfu Lin, William J. Hirschi, Anuj Kunadia, Anirudra Paul, Ion Ghiviriga, Khalil A. Abboud, Rachael W. Karugu, Mathew J. Vetticatt, Jennifer S. Hirschi, Daniel Seidel
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
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, Multidisciplinary
Zhengbo Zhu, Minami Odagi, Nantamon Supantanapong, Weici Xu, Jaan Saame, Helmi-Ulrika Kirm, Khalil A. Abboud, Ivo Leito, Daniel Seidel
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
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
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
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
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.
Article
Chemistry, Organic
Dillon R. L. Rickertsen, Longle Ma, Anirudra Paul, Khalil A. Abboud, Daniel Seidel