DOCSLIB.ORG

Aspects of Asymmetric Nucleophilic Amine Catalysis: Organocatalyst Design and Implementation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Aspects of Asymmetric Nucleophilic Amine Catalysis: Organocatalyst Design and Implementation Aspects of Asymmetric Nucleophilic Amine Catalysis: Organocatalyst Design and Implementation MacMillan Group Meeting Ian Storer February 28, 2005 Asymmetric Nucleophilic Catalysis Outline ! Introduction to N-centred nucleophilic catalysts ! concepts and definitions ! origins and requirements ! Design, development and application of asymmetric nucleophilic catalysts ! Natural alkaloid catalysts - Precejus, Wynberg ! Synthetic alkaloid analogues - Lectka, Hatekeyama, Deng ! Biomimetic histidine containing peptide catalysts - Miller ! Asymmetric DMAP equivalents - Fuji / Fu Useful Reviews: ! Fance, S.; Guerin, D. J.; Miller, S. J.; Leckta, T., Nucleophilic Chiral Amines as Catalysts in Asymmetric Synthesis. Chem Rev. 2003, 103, 2985-3012. ! Miller, S. J. In Search of Peptide-Based Catalysts for Asymmetric Organic Synthesis. Acc. Chem. Res. 2004, 37, 601-610. ! Fu, G. C. Asymmetric Catalysis with "Planar-Chiral" Derivatives of DMAP. Acc. Chem. Res. 2004, 37, 542-547. Definitions ! Lewis base A molecular entity (and the corresponding chemical species) able to provide a pair of electrons and thus capable of coordination to a Lewis acid, thereby producing a Lewis adduct. ! Nucleophilic Catalysis Catalysis by a Lewis base, involving formation of a Lewis adduct as a reaction intermediate. For example, the esterification of anhydrides catalysed by DMAP: IUPAC Compendium of Chemical Terminology Me Me Me Me N N OH R1 R3 1 O O O 2 R O N N R R2 R O R Lewis base O R R3 O R O R Lewis base complex Me Me N N Lewis base ! Implication on Choice of catalyst The catalyst has to be a very effective nucleophile and a good leaving group . Useful Nucleophilic Catalysts ! Commonly applied 'everyday' nucleophilic catalysts Me Me N N Me H N N N N N N N N N PPY DMAP Pyridine Imidazole NMI DABCO Nucleophilic Aromatic Amines nucleophilic teriary amines ! Common applications ! O-acylation - electrophile activation (pyridine, DMAP) ! O-silylation - electrophile activation (imidazole, DMAP) ! Baylis-Hilman reaction - nucleophile activation (DABCO, DMAP) ! Ineffective bases: Nucleophilicity highly sensitive to steric and electronic factors Me Et N N Me Me N Me Me N Me Et Et picoline lutidine collidine TEA good Bronsted bases, poor nucleophilic catalysts Cinchona Alkaloids: Earliest Successful Nucleophilic Asymmetric Catalysts ! First used for a resolution of a racemate in 1853 by Pasteur. H H H H HO N N HO pseudoenantiomers H H R R1 1 N N 1 Cinchonidine (CD) R1 = H Cinchonine (CN) R = H 1 Quinine (QN) R1 = OMe Quinidine (QD) R = OMe ! Several modes of application ! Asymmetric Bronsted bases ! Asymmetric phase transfer reagents (as salts) ! Asymmetric bifunctional catalysts (acid / base) ! Asymmetric nucleophilic catalysts Moncure, R. MacMillan Group Meeting, 2003, web. – contains a more fully discussion of cinchona alkaloids Alkaloids and Derivatives as Nucleophilic Catalysts ! Natural alkaloids site of modification: ether/ ester formation OMe site of inversion of site of modification configuration (epi alkaloids) OH H -pseudoenantiomers N N H site of quaternary salt Quinidine formation, nucleophilic Pracejus (1964) addition or basicity Wynberg (1983) Simpkins (2001) ! Synthetically modified analogues Me OMe OH Et Et O O O O O H N O O N N N N N H benzoylquinine Hatakeyama MeO N N OMe Lectka (2000) (DHQD)2AQN Deng OMe Seminal Findings: Pracejus Methanolysis of Ketenes H ! Pracejus proposed a mechanism involving QN activation of methanol. OH O O N 1–2 mol % quinidine N Ph H MeOH, –110 °C OMe Quinidine Me Ph Me H selective OMe up to 76% ee protonation N H H O HO +MeOH NHR3 Ph H-bond activation OMe Me MeO N Precejus, H.; Mätje, H. J. Prakt. Chem. 4. Reihe. 1964, 24, 195. Precejus, H.; Santleben, R. J. Prakt. Chem. 1972, 314, 157. ! Simpkins proposes alternative nucleophilic mechanism O PhSH O 10 mol % quinidine Bn benzene, –78 °C SPh 79-93% ee Me3Si Bn SiMe H 3 N H HO O SPh selective Bn protonation NR3 MeO N SiMe3 Blake, A. J.; Friend, C. L.; Outram, R. J.; Simpkins, N. S.; Whitehead, A. J. Tetrahedron Lett. 2001, 42, 2877. Catalytic Asymmetric Cycloadditions: Synthesis of !"Lactones OMe H ! An early example of asymmetric nucleophilic catalysis using an alkaloid. OH O O N O 2.5 mol % Amine O N H 1 2 Toluene, –50 °C, 1 h Quinidine R CCl2R 1 R 2 H H CCl2R R1 = H, alkyl, aryl R2 = Cl, alkyl up to 95 % yield 45-98 % ee catalyst O (nucleophile) H O 1 2 R CCl2R H NR3 zwitterionic intermediate ! Unprotected quinidine also catalyses its own acylation at OH ! Wynberg's proposed this stereoselectivity model O Me O CCl3 O O H H CCl3 CH O Me 2 H O Me OR N O H HC Me H H Cl C Me H 3 MeO CCl3 ! In the left TS, the ketene oxygen faces the methylene of the catalyst ring .The chloral approaches the catalyst with the trichloromethyl group facing away from the methyl group of the catalyst to avoid steric strain. ! In the bottom TS, the ring is the dominant form of stereocontrol, and the CCl3 orients itself away from the ring methylene protons. Wynberg, H. J. Am. Chem. Soc. 1982, 104, 166. Wynberg, H. J. Org. Chem. 1985, 50, 1977. Development of Functionalised Alkaloid Analogues: Catalytic Asymmetric Cycloadditions ! !-lactone synthesis: Romo's expansion of Wynberg's method O OMe Me O O O O 2 mol% cat. 2 H CCl2R O H R1 >90% ee O Cl NR3 PhMe, –25 ˚C 2 1 R1 R Cl2C R N i R N N Base: Pr2NEt 3 R1 = H, alkyl, aryl cat. H R2 = Cl, alkyl Acyl-quinidine ! The use of pre-acylated catalyst stops unwanted acylation of the catalyst during the reaction. ! Applies a stoichiometric, non-nucleophilic base to turn over the catalyst. ! In situ ketene generation ! Solubility of the Hunigs salt may be crucial to catalyst turnover. Tennyson, R.; Romo, D. J. Org. Chem. 2000, 65, 7248. Development of Functionalised Alkaloid Analogues: Catalytic Asymmetric Cycloadditions ! !-lactam synthesis: Lectka Ts O Ts 45-65% yield N O N 10 mol% cat. 95-99% ee R1 25-99:1 dr 1 Cl H CO2Et PhMe, –78 ˚C EtO2C R Base: proton sponge OMe cat. or K2CO3 or NaH O Ts N O H Ts O N O R N H CO2Et 3 N cat. N NR3 EtO2C NR3 H R1 R1 Benzoyl-quinidine ! 'Shuttle deprotonation' using excess of a thermodynamic, non-nucleophilic base. ! Concomitant Lewis acid activation of the imine later provided better yields Taggi, A. E.; Hafez, A. M.; Wack, H.; Young, B.; Drury, W. J.; Lectka, T. J.. J. Am. Chem. Soc. 2000, 122, 7831. Taggi, A. E.; Hafez, A. M.; Wack, H.; Young, B.; Ferraris, D.; Lectka, T. J.. J. Am. Chem. Soc. 2002, 124, 6626. ! Proposed transition state Development of Functionalised Alkaloid Analogues: Catalytic Asymmetric Halogenation ! Halogenation: Lectka Cl O Cl Cl O Cl 10 mol% cat. O Cl 1 R1 Cl THF, –78 ˚C R Cl O Cl Cl Cl Base: BEMP or Cl Cl K2CO3 or NaH Cl OMe 65-85% yield O t 99% ee Bu N NEt2 O H P MeN NMe N N H O Benzoyl-quinidine Br Br Br Br O 10 mol% cat. O R1 R1 Cl THF, –78 ˚C O Br Br Base: BEMP or Br Br K2CO3 or NaH 55-80% yield >90% ee Wack, H.; Taggi, A. E.; Hafez, A. M.; Drury, W. J.; Lectka, T. J. J. Am. Chem. Soc. 2001, 123, 1531. Hafez, A. M.; Taggi, A. E.; Wack, H.; Esterbrook, J.; Lectka, T. J. Org. Lett. 2001, 3, 2049. Taggi, A. E.; Wack, H.; Hafez, A. M.; France, S.; Lectka, T. J. Org. Lett. 2002, 4, 627. Development of Functionalised Alkaloid Analogues: Catalytic Asymmetric Baylis-Hillman Reaction ! Natural alkaloid - poor enantioselectivity O OH O OMe O 15 mol% catalyst 2 R R1 R2 up to OH H R1 H 45% ee THF, 30 ˚C, 34 h N cat. N O H O O O O quinidine R1 H R2 R2 R1 R2 R3N NR3 R3N Marko, I. E.; Giles, P. R.; Hindley, N. J. Tetrahedron 1997, 53, 1015. ! Synthetic analogue - better results Me O CF3 OH O CF3 OH O 15 mol% catalyst 31-58% yield 1 O O CF3 R O CF3 91-99% ee R1 H THF, 30 ˚C, 34 h N Me N quinidine analogue O N O CF3 O CF3 ! Mechanism of asymmetric induction not well understood N H ! Hatekayama proposes a 13-membered ring transistion state O Ph H ! Limited substrate scope O Iwabuchi, Y.; Nakatani, M.; Yokoyama, N.; Hatekeyama, S. J. Am. Chem. Soc. 1999, 121, 10219. Et Et N N Ph H H O O H Deng's Application of bis-quinuclidines H MeO N N OMe Ph N N catalyst ! Cyanation O O O 10-35 mol% catalyst O OEt 52-78% yield NC 87-97% ee R1 R2 NC OEt CHCl3, –12 to –24 °C R2 0.5 - 7 days R1 cat. R3N O ! Mechanism of asymmetric induction CN O O NC O not well understood R1 R2 1 R3N OEt R R3N OEt R2 Deng, L. et al. J. Am. Chem. Soc. 2001, 123, 7475. ! Desymmmetrization of meso anhydrides O O R R 5-30 mol% catalyst OH 70-99% yield O MeOH ( ) OMe 90-98% ee ( )n n R Et2O R O O Deng, L. et al. J. Am. Chem. Soc. 2000, 122, 9542. Designing Asymmetric Variants of Known Nucleophilic Amine Catalysts ! Considerations ! Must be nucleophilc, but maintain good leaving group ability ! Must have a valid chiral pocket to transfer asymmetry to product. ! Alkaloids and analogues Me OMe OH Et Et O O O OH H N O O N N N N N H H Quinine Hatakeyama MeO N N OMe Wynberg (DHQD)2AQN Deng ! Synthetic chiral analogues of common nucleophilic heterocycles O Me OH Me Me Me N H N O N H H Fe N Ph Ph N BocHN H O Me Ph Ph N Ph N Fu (1998-current) N Miller Synthetic chiral imidazole equivalents Synthetic chiral DMAP equivalents Biological Role of Nucleophilic Catalysis ! Mechanism of some kinases - role of histidine ATP ADP O O O O O O E N O P O P O P O A O P O O P O P O A 3– O O NDP O O O E N O O NH fast E N NH NTP4– OH OH OH OH NH ! Phosphorylation transfer from ATP is ubiquitous in biological chemistry.
Load more

Recommended publications
  • 4-Dimethylamino Pyridine (Dmap) Catalyst with Fluxional Chirality
    4-DIMETHYLAMINO PYRIDINE (DMAP) CATALYST WITH FLUXIONAL CHIRALITY: SYNTHESIS AND APPLICATIONS A Dissertation Submitted to the Graduate Faculty of the North Dakota State University of Agriculture and Applied Science By Gaoyuan Ma In Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY Major Department: Chemistry and Biochemistry November 2015 Fargo, North Dakota North Dakota State University Graduate School Title 4-Dimethylamino Pyridine (DMAP) Catalyst with Fluxional Chirality: Synthesis and Applications By Gaoyuan Ma The Supervisory Committee certifies that this disquisition complies with North Dakota State University’s regulations and meets the accepted standards for the degree of DOCTOR OF PHILOSOPHY SUPERVISORY COMMITTEE: Prof. Mukund P. Sibi Chair Prof. Gregory R. Cook Prof. Pinjing Zhao Prof. Dean C. Webster Approved: 11/30/2015 Prof. Gregory R. Cook Date Department Chair ABSTRACT Organocatalysis using small organic molecules to catalyze organic transformations, has emerged as a powerful synthetic tool that is complementary to metal-catalyzed transformations and remarkably promote stereoselective synthesis. Our group has designed useful templates, ligands, and additives that use fluxional groups to control and/or enhance stereoselectivity in a variety of asymmetric transformations. A key feature of this strategy is that the size of the fluxional substituent can be varied readily. As an extension of this strategy we became interested in developing efficient and broadly applicable and adjustable 4-dimethylaminopyridine (DMAP) organocatalysts. In our design, we surmised that a fluxional group would be effective in relaying stereochemical information from the fixed chiral center to the catalytic center of DMAP. Presented herein the synthesis of novel fluxionally chiral DMAP catalysts and their application in the acylative kinetic resolution of secondary alcohols and axially chiral biaryls, dynamic kinetic resolution of chiral biaryls with low rotation barriers and allylic substitution reactions.
    [Show full text]
  • Ketenes 25/01/2014 Part 1
    Baran Group Meeting Hai Dao Ketenes 25/01/2014 Part 1. Introduction Ph Ph n H Pr3N C A brief history Cl C Ph + nPr NHCl Ph O 3 1828: Synthesis of urea = the starting point of modern organic chemistry. O 1901: Wedekind's proposal for the formation of ketene equivalent (confirmed by Staudinger 1911) Wedekind's proposal (1901) 1902: Wolff rearrangement, Wolff, L. Liebigs Ann. Chem. 1902, 325, 129. 2 Wolff adopt a ketene structure in 1912. R 2 hν R R2 1905: First synthesis and characterization of a ketene: in an efford to synthesize radical 2, 1 ROH R C Staudinger has synthesized diphenylketene 3, Staudinger, H. et al., Chem. Ber. 1905, 1735. N2 1 RO CH or Δ C R C R1 1907-8: synthesis and dicussion about structure of the parent ketene, Wilsmore, O O J. Am. Chem. Soc. 1907, 1938; Wilsmore and Stewart Chem. Ber. 1908, 1025; Staudinger and Wolff rearrangement (1902) O Klever Chem. Ber. 1908, 1516. Ph Ph Cl Zn Ph O hot Pt wire Zn Br Cl Cl CH CH2 Ph C C vs. C Br C Ph Ph HO O O O O O O O 1 3 (isolated) 2 Wilsmore's synthesis and proposal (1907-8) Staudinger's synthesis and proposal (1908) wanted to make Staudinger's discovery (1905) Latest books: ketene (Tidwell, 1995), ketene II (Tidwell, 2006), Science of Synthesis, Vol. 23 (2006); Latest review: new direactions in ketene chemistry: the land of opportunity (Tidwell et al., Eur. J. Org. Chem. 2012, 1081). Search for ketenes, Google gave 406,000 (vs.
    [Show full text]
  • Organic Electrochemistry: Synthesis and Functionalization of Β-Lactams In
    Heterocyclic Communications 2021; 27: 32–44 Review Article Martina Bortolami, Isabella Chiarotto, Leonardo Mattiello, Rita Petrucci, Daniele Rocco, Fabrizio Vetica and Marta Feroci* Organic electrochemistry: Synthesis and functionalization of β-lactams in the twenty-first century https://doi.org/10.1515/hc-2020-0121 Keywords: cathodic reduction, anodic oxidation, azetidin- received December 01, 2020; accepted March 03, 2021 2-ones, electroorganic synthesis, electrogenerated base Abstract: Organic electrochemistry is a technique that allows for the heterogeneous redox reactions avoiding both the use of stoichiometric amounts of redox reagents and the resulting formation of stoichiometric by-pro- 1 Introduction ducts. In fact, the redox reagent in these reactions is β- ( - - ) - the electron, which is naturally eco-friendly and pro- Lactams azetidin 2 ones; Figure 1 are four membered duces no side compounds. It is therefore quite obvious heterocyclic compounds containing an amide moiety. - that electrochemistry can be classified as a “green” tech- This class of molecules is so famous in medicinal chem nology. The use of this methodology in the synthesis of istry that there is no need to describe their importance in fi - β-lactams is not a novelty, but the growing interest in this the antibiotic eld. In fact, since the discovery of peni β- class of biologically active compounds, due to the dis- cillin in 1928 by Fleming, lactam antibiotics have been covery of new fields of application (after a moment of extensively used as antibacterial agents, their use being decrease in interest due to antibiotic resistance) has less frequent in recent years due to the onset of antibiotic [ ] been a stimulus for the search for more efficient electro- resistance 1,2 .
    [Show full text]
  • Enantioselective Synthesis of Β-Amino Acids: a Review
    l ch cina em Ashfaq et al. di is Med chem 2015, 5:7 e tr M y Medicinal chemistry DOI: 10.4172/2161-0444.1000278 ISSN: 2161-0444 Review Article Open Access Enantioselective Synthesis of β-amino acids: A Review Muhammad Ashfaq1*, RukhsanaTabassum1, Muhammad Mahboob Ahmad2, Nagina Ali Hassan1, Hiroyuki Oku3 and Gildardo Rivera4 1Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur, Pakistan 2Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan 3Department of Chemistry & Chemical Biology, Gunma University Kiryu, Gunma 376-8515, Japan 4Centro de Biotecnología, Genómica, Instituto Politécnico Nacional, 88710, Reynosa, México Abstract The synthesis of enantioselective β-amino acids is being reported in this review on account of their significant properties as proteinogenic, non-proteinogenic role such as neurotransmitter, biosynthesizer and nutritional supplementing materials etc. They are extensively used as chiral starting materials, auxiliaries and catalysts in organic synthesis. According to literature evidences, extensive research has been carried out to develop the methodologies for the synthesis of stereoselective β-amino acids. In this review, we describe recent advances in synthetic routes of enantioselective β-amino acids derivatives with chemical reactions during the last decades and to provide the most suitable route of their synthesis to compete the future challenges. Keywords: β-amino acids; Enantioselective; Synthesis Phosphoramidite ligand was used to obtain adducts in high yields with up to 94% by Fillion et al. through conjugate addition of dialkylzinc Introduction reagents to 2-aryl acrylate (Scheme 3). Deprotection of adduct, followed Enantionselective synthesis of β-amino acids has gained significant by a Curtius rearrangement of the succinic acid derivative resulted in importance because of their interesting pharmacological applications the formation of β-amino acid derivative [14].
    [Show full text]
  • Recent Advances in Enantioselective Photochemical Reactions of Stabilized Diazo Compounds
    molecules Review Recent Advances in Enantioselective Photochemical Reactions of Stabilized Diazo Compounds Ting-Bi Hua, Qing-Qing Yang * and You-Quan Zou y College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, 8 Daxue Road, Yichang 443002, Hubei, China * Correspondence: [email protected] Current address: Department of Organic Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. y Received: 3 August 2019; Accepted: 26 August 2019; Published: 2 September 2019 Abstract: Diazo compounds have proven to be a useful class of carbenes or metal carbenoids sources under thermal, photochemical, or metal-catalyzed conditions, which can subsequently undergo a wide range of synthetically important transformations. Recently, asymmetric photocatalysis has provoked increasing research interests, and great advances have been made in this discipline towards the synthesis of optically enriched compounds. In this context, the past two decades have been the most productive period in the developments of enantioselective photochemical reactions of diazo compounds due to a better understanding of the reactivities of diazo compounds and the emergence of new catalytic modes, as well as easier access to and treatment of stabilized diazo compounds. This review highlights these impressive achievements according to the reaction type, and the general mechanisms and stereochemical inductions are briefly discussed as well. Keywords: diazo compounds; enantioselectivity; photocatalysis; Wolff rearrangement 1. Introduction Diazo compounds are a class of charge neutral organic compounds containing a diazo group bound to a carbon atom, which can resonance into different structures (Figure1a) [ 1]. Since its chemistry has existed for more than a century [2], diazo compounds have been rendered to be versatile building blocks and will continue to play an important role in organic synthesis.
    [Show full text]
  • Enantioselective Organocatalytic Cycloaddition Reactions Between Enolisable Anhydrides and Imines
    Enantioselective organocatalytic cycloaddition reactions between enolisable anhydrides and imines Trinity College Dublin A thesis submitted to the University of Dublin for the degree of Doctor of Philosophy by Aarón Gutiérrez Collar, Under the supervision of Prof. Stephen Connon February 2019 Declaration I declare that this thesis has not been submitted as an exercise for a degree at this or any other university and it is entirely my own work. Due ackowledegments and references are given to the work of others I agree to deposit this thesis in the University’s open access institutional repository or allow the library to do so on my behalf, subject to Irish Copyright Legislation and Trinity College Library conditions of use and acknowledgement. Aarón Gutiérrez Collar S. A. Cronin, A. Gutiérrez Collar, S. Gundala, C. Cornaggia, E. Torrente, F. Manoni, A. Botte, B. Twamley and S. J. Connon, Org. Biomol. Chem., 2016, 14, 6955. A. Gutiérrez Collar, C. Trujillo and S. J. Connon, Chem. Eur. J., Accepted Introduction ..................................................................................................................... 1 1.1 Lactams ............................................................................................................... 1 1.1.1 Biological and medicinal relevance ...................................................................... 1 1.1.2 Principal methods of synthesis and associated challenges .................................... 2 1.1.2.1 Beckmann rearrangement ...................................................................................
    [Show full text]
  • Synthesis of DMAP Tethered Polymer Chains for Reversible Micelle Formation Richard Arthur Fredricks
    Eastern Michigan University DigitalCommons@EMU Master's Theses, and Doctoral Dissertations, and Master's Theses and Doctoral Dissertations Graduate Capstone Projects 2016 Synthesis of DMAP tethered polymer chains for reversible micelle formation Richard Arthur Fredricks Follow this and additional works at: http://commons.emich.edu/theses Part of the Chemistry Commons Recommended Citation Fredricks, Richard Arthur, "Synthesis of DMAP tethered polymer chains for reversible micelle formation" (2016). Master's Theses and Doctoral Dissertations. 770. http://commons.emich.edu/theses/770 This Open Access Thesis is brought to you for free and open access by the Master's Theses, and Doctoral Dissertations, and Graduate Capstone Projects at DigitalCommons@EMU. It has been accepted for inclusion in Master's Theses and Doctoral Dissertations by an authorized administrator of DigitalCommons@EMU. For more information, please contact [email protected]. Synthesis of DMAP Tethered Polymer Chains for Reversible Micelle Formation by Richard Arthur Fredricks Thesis Submitted to the Department of Chemistry Eastern Michigan University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE in Chemistry Thesis Committee: Gregg Wilmes, PhD, Chair Harriet Lindsay, PhD Donald Snyder, PhD December, 2016 Ypsilanti, MI Acknowledgments I would like to thank Dr. Gregg Wilmes. I really appreciate his support with my research and for accommodating my work schedule. I would also like to thank all of the faculty at EMU for everything that I have learned during my time in the chemistry program. I would also like to thank my family and friends for all of the support while I have been earning my degree.
    [Show full text]
  • Annulation with Azaallyl Anions
    Base-Mediated Generation of Ketenimines from Ynamides: [3+2] Annulation with Azaallyl Anions Agathe D’hollander, Eugénie Romero, Kamsana Vijayakumar, Camille Le Houérou, Pascal Retailleau, Robert Dodd, Bogdan Iorga, Kevin Cariou To cite this version: Agathe D’hollander, Eugénie Romero, Kamsana Vijayakumar, Camille Le Houérou, Pascal Retailleau, et al.. Base-Mediated Generation of Ketenimines from Ynamides: [3+2] Annulation with Azaallyl Anions. 2020. hal-02998846 HAL Id: hal-02998846 https://hal.archives-ouvertes.fr/hal-02998846 Preprint submitted on 10 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Base-Mediated Generation of Ketenimines from Ynamides: [3+2] Annulation with Azaallyl Anions. Agathe C. A. D’Hollander,a Eugénie Romero,a Kamsana Vijayakumar,a Camille Le Houérou,a Pascal Retailleau,a Robert H. Dodd,a Bogdan I. Iorga,a Kevin Carioua,b* a Université Paris-Saclay, CNRS, Institut de Chimie des Substances Naturelles, LabEx LERMIT, UPR 2301, 91198, Gif-sur-Yvette, France. b Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, 75005 Paris, France. ABSTRACT: Under basic conditions and heat, ynamides can serve as precursor to ketenimines, whose synthetic potential is often hampered by their difficulty of acces.
    [Show full text]
  • Synthesis and Reactivity of 4-(Trifluoromethyl)Azetidin-2-Ones
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Ghent University Academic Bibliography 1 Synthesis and reactivity of 2 4-(trifluoromethyl)azetidin-2-ones 3 Hang Dao Thi1,2 • Tuyen Van Nguyen2 • Matthias D’hooghe1 4 Received: ....../Accepted: 5 Abstract Because of the beneficial effect of a trifluoromethyl group on the 6 biological properties of bioactive compounds on the one hand and the versatile 7 synthetic potential of β-lactams on the other hand, 4-CF3-β-lactams comprises 8 interesting entities for the preparation of a large variety of CF3-substituted 9 nitrogen-containing target structures with promising biological characteristics. In 10 this review, we present an overview of different building block approach-based 11 routes toward the synthesis of 4-(trifluoromethyl)azetidin-2-ones and the 12 application of the “β-lactam synthon method” for the synthesis of a diverse set of 13 (a)cyclic CF3-substituted molecules by means of ring-opening and ring- 14 transformation reactions. 15 Keywords Heterocycles • Strained molecules • Fluorine chemistry • Cyclizations 16 • Ring opening 17 Matthias D’hooghe [email protected] 1 SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium 2 Institute of Chemistry, Vietnam Academy of Science and Technology, 18- Hoang Quoc Viet, CauGiay, Hanoi, Vietnam 1 1 Introduction 2 The pivotal role of fluorine in medicinal chemistry is reflected by its presence in 3 approximately 25% of the pharmaceuticals on the market and in the development 4 pipeline.
    [Show full text]
  • An Update on the Synthesis and Reactivity of Spiro-Fused Β-Lactams
    The Free Internet Journal Review for Organic Chemistry Archive for Arkivoc 2018, part vi, 314-347 Organic Chemistry An update on the synthesis and reactivity of spiro-fused β-lactams Hang Dao Thi and Matthias D’hooghe* SynBioC Research Group, Department of Green Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium Email: [email protected] Received 11-08-2018 Accepted 12-17-2018 Published on line 03-30-2019 Abstract β-Lactam ring-containing compounds play a pivotal role in drug design and synthetic chemistry. Spirocyclic β- lactams, representing an important β-lactam subclass, have recently attracted considerable interest with respect to new synthetic methodologies and pharmacological applications. The aim of this manuscript is to review the recent progress made in this field, covering publications disseminated between 2011 to 2018 concerning the synthesis and application of spirocyclic β-lactams. In the first part, new approaches to the synthesis of spirocyclic β-lactams, including Staudinger synthesis, cyclization and transformation reactions, will be presented. The reactivity and biological properties of spiro-β-lactams will be described in the second and third part, respectively. Keywords: β-Lactams, spiroazetidin-2-ones, spiro-β-lactams, fused rings DOI: https://doi.org/10.24820/ark.5550190.p010.808 Page 314 ©ARKAT USA, Inc Arkivoc 2018, vi, 314-347 Dao Thi, H. et al. Table of Contents 1. Introduction 2. Synthesis of Spiro-fused β-lactams 2.1. Cyclocondensation reactions 2.1.1. Reactions of acyclic ketenes 2.1.2. Reactions of cyclic ketenes 2.2. Cyclization reactions 2.3.
    [Show full text]
  • R-Imino Esters: Versatile Substrates for the Catalytic, Asymmetric Synthesis of R- and Β-Amino Acids and Β-Lactams
    Acc. Chem. Res. 2003, 36, 10-19 r asymmetric reactions. We envisaged a Lewis acid coor- -Imino Esters: Versatile dinating both the imine N and the ester O atoms simul- Substrates for the Catalytic, taneously in a chelate interaction that could enhance Asymmetric Synthesis of r- and selectivity: â-Amino Acids and â-Lactams ANDREW E. TAGGI, AHMED M. HAFEZ, AND THOMAS LECTKA* Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218. Received May 29, 2002 ABSTRACT The catalytic asymmetric addition of organic nucleophiles to R-imino esters has emerged as one of the most promising and intensely investigated routes to optically enriched R- and â-amino acid derivatives and â-lactams. The importance of R-imino esters stems not only from the vast appeal of the potential product classes,1 but also from their remarkable reactivity as highly elec- trophilic imines. With each passing year, the number of publica- tions concerning the asymmetric alkylation of imino esters grows significantly. The asymmetric alkylation of imines2 and N,O-acetals has been in itself a subject of intense interest.3 In this Account, we wish to illustrate our contribution to this timely field, as well as to Since that time, a profusion of attractive new procedures highlight the seminal contributions of others. has been developed to exploit the electrophilic nature of R-imino esters for catalytic, asymmetric synthesis. For purposes of clarity, we subdivide this account into three 1. Introduction parts: R-imino ester synthesis, R-amino acid synthesis, and the synthesis of â-lactams and â-amino acids (Scheme R-Imino esters have been known in synthetic organic 1).
    [Show full text]
  • Three-Component Approach to Pyridine-Stabilized Ketenimines for the Synthesis of Diverse Heterocycles Nicholas P
    Article Cite This: J. Org. Chem. 2019, 84, 13676−13685 pubs.acs.org/joc Three-Component Approach to Pyridine-Stabilized Ketenimines for the Synthesis of Diverse Heterocycles Nicholas P. Massaro, Aayushi Chatterji, and Indrajeet Sharma* Department of Chemistry and Biochemistry, and Institute of Natural Products Applications and Research Technologies, University of Oklahoma, 101 Stephenson Parkway, Norman, Oklahoma 73019, United States *S Supporting Information ABSTRACT: Ketenimines are versatile synthetic intermedi- ates capable of performing novel transformations in organic synthesis. They are normally generated in situ due to their inherent instability and high level of reactivity. Herein, we report pyridine-stabilized ketenimine zwitterionic salts, which are prepared through click chemistry from readily accessible alkynes and sulfonyl azides. To demonstrate their synonymous reactivity to ketenimines, these salts have been utilized in a cascade sequence to access highly functionalized quinolines including the core structures of an antiprotozoal agent and the potent topoisomerase inhibitor Tas-103. ■ INTRODUCTION with 4-dimethylaminopyridine, but also proceeded in moderate Ketenimines are reactive species exhibiting a diverse array of yield with pyridine as a base (Figures 1 and 3b,c). We then synthetic applications parallel to their isoelectronic cousins, screened non-nucleophilic triethyl amine and 2,6-di-tert-butyl-4- ketenes and allenes.1 Because of the inherent instability and methylpyridine but did not observe the formation of ketenimine reactivity, ketenimines are normally generated in situ for their salt. These results indicate that nucleophilic pyridine bases with applications in organic synthesis.2 Current methods to prepare less steric crowding around the nitrogen of the pyridine ring ketenimines include couplings,3a eliminations,3b rearrange- were necessary for salt formation.
    [Show full text]