Recent Advances in Total Synthesis Via Metathesis Reactions
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Organic Synthesis: Handout 1
Prof Tim Donohoe: Strategies and Taccs in Organic Synthesis: Handout 1 Organic Synthesis III 8 x 1hr Lectures: Michaelmas Term Weeks 5-8 2016 Mon at 10am; Wed at 9am Dyson Perrins lecture theatre Copies of this handout will be available at hEp://donohoe.chem.ox.ac.uk/page16/index.html 1/33 Prof Tim Donohoe: Strategies and Taccs in Organic Synthesis: Handout 1 Organic Synthesis III Synopsis 1) Introduc5on to synthesis: (i) Why do we want to synthesise molecules- what sort of molecules do we need to make? (ii) What aspects of selecvity do we need to accomplish a good synthesis (chemo-, regio- and stereoselecvity)? (iii) Protecng group chemistry is central to any syntheAc effort (examples and principles) (iv) What is the perfect synthesis (performed in industry versus academia)? 2) The chiral pool: where does absolute stereochemistry come from? 3) Retrosynthesis- learning to think backwards (revision from first and second year). Importance of making C-C bonds and controlling oxidaAon state. Umpolung 4) Some problems to think about 5) Examples of retrosynthesis/synthesis in ac5on. 6) Ten handy hints for retrosynthesis 7) Soluons to the problems Recommended books: General: Organic Chemistry (Warren et al) Organic Synthesis: The DisconnecRon Approach (S. Warren) Classics in Total Synthesis Volumes I and II (K. C. Nicolaou) The Logic of Chemical Synthesis (E. J. Corey) 2/33 View Article Online / Journal Homepage / Table of Contents for this issue 619461 Strychniqae and BYucine. Pavt XLII. 903 Prof Tim Donohoe: Strategies and Taccs in Organic Synthesis: Handout 1 (i) Why do we want to synthesise complex molecules? Isolated from the Pacific Yew in 1962 Prescribed for prostate, breast and ovarian cancer Unique mode of acRon 1x 100 year old tree = 300 mg Taxol Isolated in 1818- poisonous Stuctural elucidaon took R. -
Olefin Metathesis in Aqueous Media Offers a New, Broad M
Green Chemistry CRITICAL REVIEW View Article Online View Journal | View Issue Olefin metathesis in aqueous media Cite this: Green Chem., 2013, 15, 2317 Jasmine Tomasek and Jürgen Schatz* The worldwide undisputable and unattainable chemist is nature, using water as a solvent of choice in biosynthesis. Water as a solvent not only indicates “green chemistry” but is also inevitable in biochemical reactions as well as syntheses of several pharmaceutical products. In the last few decades, several organic reactions were successfully carried out under aqueous conditions, a powerful and attractive tool in Received 3rd June 2013, organic synthesis metathesis reaction. This review summarises advances made in metathesis reaction in Accepted 12th July 2013 aqueous media. Two main strategies can be distinguished: the design of water soluble catalysts to obtain DOI: 10.1039/c3gc41042k homogeneous conditions and using commercially available catalysts to utilize the advantages of hetero- www.rsc.org/greenchem geneous conditions. reactions, meaning coupling reactions of cyclic and acyclic Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Introduction alkenes or alkynes as well as polymerisation reactions In organic chemistry, C–C coupling reactions open a wide (Scheme 1).1 Accordingly, the metathesis has been of great range of applications for effective synthesis, which otherwise interest since its discovery in the mid-1950s3 and reveals a would be difficult or even hardly feasible. The olefin meta- powerful tool for both industrial applications, -
Enantioselective Total Synthesis of (-)-Deoxoapodine
Enantioselective total synthesis of (-)-deoxoapodine The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Kang, Taek, et al., "Enantioselective total synthesis of (-)- deoxoapodine." Angewandte Chemie International Edition 56, 44 (Sept. 2017): p. 13857-60 doi 10.1002/anie.201708088 ©2017 Author(s) As Published 10.1002/anie.201708088 Publisher Wiley Version Author's final manuscript Citable link https://hdl.handle.net/1721.1/125957 Terms of Use Creative Commons Attribution-Noncommercial-Share Alike Detailed Terms http://creativecommons.org/licenses/by-nc-sa/4.0/ HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Angew Manuscript Author Chem Int Ed Engl Manuscript Author . Author manuscript; available in PMC 2018 October 23. Published in final edited form as: Angew Chem Int Ed Engl. 2017 October 23; 56(44): 13857–13860. doi:10.1002/anie.201708088. Enantioselective Total Synthesis of (−)-Deoxoapodine Dr. Taek Kang§,a, Dr. Kolby L. White§,a, Tyler J. Mannb, Prof. Dr. Amir H. Hoveydab, and Prof. Dr. Mohammad Movassaghia aDepartment of Chemistry, Massachusetts Institute of Technology Cambridge, MA 02139 (USA) bDepartment of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467 (USA) Abstract The first enantioselective total synthesis of (−)-deoxoapodine is described. Our synthesis of this hexacyclic aspidosperma alkaloid includes an efficient molybdenum-catalyzed enantioselective ring-closing metathesis reaction for desymmetrization of an advanced intermediate that introduces the C5-quaternary stereocenter. After C21-oxygenation, the pentacyclic core was accessed via an electrophilic C19-amide activation and transannular spirocyclization. A biogenetically inspired dehydrative C6-etherification reaction proved highly effective to secure the F-ring and the fourth contiguous stereocenter of (−)-deoxoapodine with complete stereochemical control. -
Richard R. Schrock Department of Chemistry 6-331, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
MULTIPLE METAL-CARBON BONDS FOR CATALYTIC METATHESIS REACTIONS Nobel Lecture, December 8, 2005 by Richard R. Schrock Department of Chemistry 6-331, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA. It’s my great priviledge to be here today, in a position I never thought pos- sible. I hope the story that I will tell you will give you some idea what I have contributed to the area for which the Nobel Prize in Chemistry was awarded this year. The story begins thirty two years ago in 1973, the year the Nobel Prize was shared by G. Wilkinson and E. O. Fischer. Wilkinson’s Nobel Lecture1 con- cerned the nature of a single bond between a transition metal and a carbon atom in an alkyl group, and emphasized the fact that the metal-carbon bond is not inherently weak. E. O. Fischer in his Nobel Lecture2 summarized the extensive chemistry of transition metal “carbene” complexes3,4 that contain a metal-carbon double bond discovered by him and his group in 1964 (Fig 1).5 He also reported new “carbyne” complexes that contain a metal-carbon triple bond.6 It was clear that metal-carbon single bonds were of great importance in the emerging area of homogeneous catalysis. However, no catalytic reac- tions involving species that contain metal-carbon double or triple bonds were known. When I went to the Central Research Department of E. I. DuPont de Nemours and Company in 1972, transition metal organometallic chemistry and homogeneous catalysis were of great interest as a consequence of their huge potential in organic chemistry and therefore in industry. -
The Total Synthesis of Securinine and Other Methodology Studies
University of Windsor Scholarship at UWindsor Electronic Theses and Dissertations Theses, Dissertations, and Major Papers 2010 The total synthesis of securinine and other methodology studies Bhartesh Dhudshia University of Windsor Follow this and additional works at: https://scholar.uwindsor.ca/etd Recommended Citation Dhudshia, Bhartesh, "The total synthesis of securinine and other methodology studies" (2010). Electronic Theses and Dissertations. 8275. https://scholar.uwindsor.ca/etd/8275 This online database contains the full-text of PhD dissertations and Masters’ theses of University of Windsor students from 1954 forward. These documents are made available for personal study and research purposes only, in accordance with the Canadian Copyright Act and the Creative Commons license—CC BY-NC-ND (Attribution, Non-Commercial, No Derivative Works). Under this license, works must always be attributed to the copyright holder (original author), cannot be used for any commercial purposes, and may not be altered. Any other use would require the permission of the copyright holder. Students may inquire about withdrawing their dissertation and/or thesis from this database. For additional inquiries, please contact the repository administrator via email ([email protected]) or by telephone at 519-253-3000ext. 3208. The Total Synthesis of Securinine and Other Methodology Studies by Bhartesh Dhudshia A Dissertation Submitted to the Faculty of Graduate Studies through the Department of Chemistry and Biochemistry in Partial Fulfillment of the Requirements -
Hoveyda–Grubbs Catalysts with an N→Ru Coordinate Bond in a Six-Membered Ring
Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors Kirill B. Polyanskii1, Kseniia A. Alekseeva1, Pavel V. Raspertov1, Pavel A. Kumandin1, Eugeniya V. Nikitina1, Atash V. Gurbanov2,3 and Fedor I. Zubkov*1 Full Research Paper Open Access Address: Beilstein J. Org. Chem. 2019, 15, 769–779. 1Organic Chemistry Department, Faculty of Science, Peoples’ doi:10.3762/bjoc.15.73 Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation, 2Centro Received: 23 October 2018 de Química Estrutural, Instituto Superior Técnico, Universidade de Accepted: 25 February 2019 Lisboa, Av. Rovisco Pais, 1049–001 Lisbon, Portugal and 3Organic Published: 22 March 2019 Chemistry Department, Baku State University, Z. Xalilov Str. 23, Az 1148 Baku, Azerbaijan This article is part of the thematic issue "Progress in metathesis chemistry III". Email: Fedor I. Zubkov* - [email protected] Guest Editors: K. Grela and A. Kajetanowicz * Corresponding author © 2019 Polyanskii et al.; licensee Beilstein-Institut. License and terms: see end of document. Keywords: CM; cross metathesis; Hoveyda–Grubbs catalyst; olefin metathesis; RCM; ring-closing metathesis; ring-opening cross metathesis; ROCM; ruthenium metathesis catalyst; styrene; 2-vinylbenzylamine Abstract A novel and efficient approach to the synthesis of 2-vinylbenzylamines is reported. This involves obtaining 2-vinylbenzylamine ligands from tetrahydroisoquinoline by alkylation and reduction followed by the Hofmann cleavage. The resultant 2-vinylbenzyl- amines allowed us to obtain new Hoveyda–Grubbs catalysts, which were thoroughly characterised by NMR, ESIMS, and X-ray crystallography. -
New Insights Into the Mechanism of Alkene Metathesis
ACADEMIA ROMÂNĂ Rev. Roum. Chim., Revue Roumaine de Chimie 2011, 56(4), 299-316 http://web.icf.ro/rrch/ Dedicated to Professor Alexandru T. Balaban on the occasion of his 80th anniversary REVIEW NEW INSIGHTS INTO THE MECHANISM OF ALKENE METATHESIS Carmen I. MITAN,* Valerian DRAGUTAN and Ileana DRAGUTAN Institute of Organic Chemistry, Roumanian Academy, Spl. Independentei, 202 B, sect. 6, Bucharest, Roumania Received September 8, 2010 The diversity of alkene metathesis reactions, presently applied to their full potential in synthesis of complex scaffolds and assemblies or as key steps in the total synthesis of natural products, demands a deep understanding of the intricate metathesis mechanism since not all of the catalysts are efficient for all of the substrates, nor do they trigger the identical mechanistic pathways, though they share the same main intermediates (the generally accepted metallacarbene and metallacyclobutane). Beyond that, metathesis processes are occasionally complicated by the occurrence of side reactions resulting in a number of by-products. Unveiling the influence of reaction conditions, and in particular of the catalytic system and the active species generated thereof during metathesis of a chosen substrate is paramount for obtaining high yields in the targeted product, at low costs. This paper focuses on relevant kinetic and mechanistic aspects reported to date for alkene metathesis induced by Ru-alkylidene complexes, concentrating on the interplay ligand dissociation – initiation step – overall catalytic activity, as determined by the catalyst structure. INTRODUCTION∗ Metathesis encompasses a range of well- established synthetic methodologies such as ring- Alkene metathesis is basically a catalytic closing metathesis (RCM), ring-opening metathesis transalkylidenation reaction formally occurring by (ROM), cross-metathesis (CM), enyne metathesis scission of two olefinic carbon-carbon double bonds (EM), acyclic diene metathesis (ADMET) and ring- with formation of two new C=C bonds (Scheme 1).1 opening metathesis polymerization (ROMP). -
Total Synthesis of ( )-Hennoxazole a Vol
ORGANIC LETTERS − 2007 Total Synthesis of ( )-Hennoxazole A Vol. 9, No. 6 1153-1155 Thomas E. Smith,* Wen-Hsin Kuo, Victoria D. Bock, Jennifer L. Roizen, Emily P. Balskus, and Ashleigh B. Theberge Department of Chemistry, Williams College, Williamstown, Massachusetts 01267 [email protected] Received January 31, 2007 ABSTRACT An enantioselective, convergent, total synthesis of the antiviral marine natural product (−)-hennoxazole A has been completed in 17 steps, longest linear sequence, from serine methyl ester and in 9 steps from an achiral bisoxazole intermediate. Elaboration of a thiazolidinethione allowed for rapid assembly of the pyran-based ring system. Key late-stage coupling was effected by deprotonation of the bisoxazole methyl group, followed by alkylation with an allylic bromide side chain segment. Marine natural products have become increasingly important Williams,5 and Shioiri6 laboratories.7 In this communication, as lead compounds for the development of new drugs as a we report the shortest asymmetric total synthesis of hen- consequence of their intriguing structural diversity and noxazole A to date. biological activity.1 Hennoxazole A (1), first isolated by The development of relatively mild conditions for the Scheuer from the marine sponge Polyfibrospongia, displays preparation of oxazoles has made the late-stage assembly of antiviral activity against herpes simplex type 1, as well as these ring systems a common, albeit not always efficient, peripheral analgesic behavior.2 The two contiguous 2,4- strategy in the synthesis -
Dissertation Reactivity and Selectivity in The
DISSERTATION REACTIVITY AND SELECTIVITY IN THE POLYMERIZATION OF MULTIFUNCTIONAL ACRYLIC MONOMERS BY CHIRAL ZIRCONOCENIUM CATALYSTS Submitted by Fernando Vidal Peña Department of Chemistry In partial fulfillment of the requirements For the Degree of Doctor of Philosophy Colorado State University Fort Collins, Colorado Summer 2017 Doctoral Committee: Advisor: Eugene Y.-X. Chen Richard G. Finke Steven Strauss Ellen Fisher David Wang Copyright by Fernando Vidal Peña 2017 All Rights Reserved ABSTRACT REACTIVITY AND SELECTIVITY IN THE POLYMERIZATION OF MULTIFUNCTIONAL ACRYLIC MONOMERS BY CHIRAL ZIRCONOCENIUM CATALYSTS Described in this dissertation are the results of investigating the reactivity and selectivity in the polymerization of multifunctional acrylic monomers by chiral cationic zirconocenium catalysts. The unprecedented precision polymer synthesis method developed in this workthe polymerization of polar divinyl monomers that is not only living but also simultaneously chemoselective and stereoselectivehas enabled the synthesis of well-defined highly stereoregular functionalized polymers bearing reactive C=C bonds on every chiral repeat unit. Thus, under ambient conditions, chiral ansa-ziroconocenium catalysts of the appropriate symmetry (C2- vs CS-ligated) have afforded highly isotactic and highly syndiotactic double-bond- carrying polymers, respectively, with controlled molecular weights and narrow dispersities. The enantiomorphic-site controlled, conjugate-addition coordination polymerization mechanism is responsible for the observed -
Grubbs Alkene Metathesis Precursors
Computational and Theoretical Chemistry 996 (2012) 57–67 Contents lists available at SciVerse ScienceDirect Computational and Theoretical Chemistry journal homepage: www.elsevier.com/locate/comptc On the electronic structure of second generation Hoveyda–Grubbs alkene metathesis precursors ⇑ Francisco Nuñez-Zarur a, Jordi Poater b, Luis Rodríguez-Santiago a, Xavier Solans-Monfort a, Miquel Solà b, , ⇑ Mariona Sodupe a, a Departament de Química, Universitat Autònoma de Barcelona, 08193 Bellaterra, Cerdanyola del Vallès, Spain b Institut de Química Computacional and Departament de Química, Universitat de Girona, Campus de Montilivi, 17071 Girona, Catalonia, Spain article info abstract Article history: Hoveyda–Grubbs complexes are commonly used catalysts in alkene metathesis. They are precursors of Received 8 June 2012 the catalytic species and need to be activated before entering into the real catalytic cycle. This activation Accepted 10 July 2012 can determine in a large extent the performance of the catalyst and thus, it is important to understand Available online 24 July 2012 the factors that influence their activation and stability. In the present work, the electronic structure of 15 different Hoveyda–Grubbs precatalysts is analyzed by means of DFT quantum chemical calculations. Keywords: Electronic delocalization measures and aromaticity indices have been used to study the influence of the Alkene metathesis Hoveyda ligand substituents on the RuÁÁÁO interaction and the metal carbene bond, and to analyze Hoveyda–Grubbs catalyst whether or not the 5-membered metal containing ring exhibits metalloaromaticity. Results show that DFT Metalloaromaticity these complexes do not exhibit any metalloaromaticity, although delocalization measures indicate that there is a certain p electron delocalization on the Hoveyda ligand. -
Ring Closing Enyne Metathesis: a Powerful Tool for the Synthesis of Heterocycles
TUTORIAL REVIEW www.rsc.org/csr | Chemical Society Reviews Ring closing enyne metathesis: A powerful tool for the synthesis of heterocycles He´le`ne Villar,ab Marcus Fringsa and Carsten Bolm*a Received 2nd August 2006 First published as an Advance Article on the web 4th October 2006 DOI: 10.1039/b508899m The ring closing metathesis (RCM) is a powerful method in organic synthesis for the preparation of cyclic compounds by formation of new carbon–carbon bonds. In the past years a particular subclass of the RCM, the ring closing enyne metathesis (RCEYM), has attracted attention due to its synthetic potential in the generation of ring structures with 1,3-diene moieties, which can subsequently be further functionalised. In this tutorial review mechanistic considerations will be described and the synthetic power of this useful and attractive carbon–carbon bond forming reaction will be illustrated by recent examples of RCEYM applications in the preparation of heterocyclic compounds. 1. Introduction and both academia and industry largely benefited from their findings. The Nobel Prize in Chemistry 2005 was equally shared by Yves Metathesis, with its multiple facets, has become one of the Chauvin (Institut Franc¸ais du Pe´trole, Rueil-Malmaison, most important chemical transformations.2–7 Depending on France), Robert H. Grubbs (California Institute of the type of unsaturated bond involved in the metathesis Technology, Pasadena, USA) and Richard R. Schrock process, three major categories of olefin metathesis can be (Massachusetts Institute of Technology, Cambridge, USA) distinguished: diene, enyne and diyne metathesis. The struc- for their outstanding contributions in the area of olefin tural change, which occurs during the process, can be further 1 metathesis reactions. -
A Ruthenium-Based Catalytic System with Switchable Selectivity Between Cyclotrimerization and Enyne Metathesis/Diels–Alder Reactions of Terminal Alkynes☆
Catalysis Communications 41 (2013) 12–16 Contents lists available at SciVerse ScienceDirect Catalysis Communications journal homepage: www.elsevier.com/locate/catcom Short Communication A ruthenium-based catalytic system with switchable selectivity between cyclotrimerization and enyne metathesis/Diels–Alder reactions of terminal alkynes☆ Solmaz Karabulut ⁎, Begüm Sariaslan, Bengi Özgün Öztürk Hacettepe University, Department of Chemistry, 06800, Beytepe-Ankara, Turkey article info abstract Article history: In this study, we report a practical catalytic system, [RuCl2(p-cymene)]2/IPr (IPr: 1,3-bis(2,6 diisopropylphenyl) Received 19 March 2013 imidazol-2-ylidene), that can switch between cyclotrimerization and cross enyne metathesis. The Received in revised form 14 June 2013 cyclotrimerization reaction of phenylacetylene catalyzed by [RuCl2(p-cymene)]2 can be switched to enyne me- Accepted 14 June 2013 tathesis by the introduction of a sterically hindered N-heterocyclic carbene. The 1,3-diene formed during this re- Available online 27 June 2013 action reacts with dienophiles to form the Diels–Alder adduct. A practical one-pot synthesis method, utilizing enyne metathesis/Diels–Alder reactions, was used to construct cyclic compounds in an efficient manner. Keywords: Enyne metathesis © 2013 The Authors. Published by Elsevier B.V. All rights reserved. Diels–Alder reactions One-pot synthesis Switchable catalysis 1. Introduction al. reported a novel method that utilizes ring closing metathesis of 1,7-octadiene as an in situ source of ethylene in tandem enyne Olefin metathesis is a useful synthetic tool for the creation of metathesis/Diels–Alder reactions [17]. A switchable catalytic system carbon–carbon bonds [1]. Numerous applications of metathesis based on exchange of the active sites of the Grubbs second generation have been developed to construct a wide variety of organic materials catalyst was reported to promote two distinct annulation reactions to containing double bonds [2].