organic chemistry tenth edition pdf

solom_fm_i-xxxiv-hr2.qxd 14-10-2009 17:19 Page xxxiv www.EngineeringBooksPDF.com 14 IVA 15 VA 16 VIA 17 VIIA www.EngineeringBooksPDF.com Lanthanum 138.91 89 Barium 137.33 88 Caesium 132.91 87 Francium (223) Actinium (227) # Actinide Series *Lanthanide Series Radium (226) Ra #Ac *La Ba Cs Fr 57 56 55 Zr Y Yttrium 88.906 Sr Strontium 87.62 Rb Rubidium 85.468 40 39 38 37 Ti 59 Pr Praseodymium 140.91 91 Pa Protactinium 231.04 58 Ce Cerium 140.12 90 Th Thorium 232.04 (261) Dubnium (262) Db 105 Tantalum 180.95 Ta 73 Niobium 92.906 Nb 41 Vanadium 50.942 V 23 Rutherfordium Rf 104 Hafnium 178.49 Hf 72 Zirconium 91.224 Titanium 47.867 Sc Scandium 44.956 Ca Calcium 40.078 K Potassium 39.098 22 21 20 19 VB Mn 25 VIIB Tc 43 62 Hassium (277) Hs 108 Osmium 190.23 Os 76 Pm Sm 61 Bohrium (264) Bh 107 Rhenium 186.21 Re 75 (98) Ruthenium 101.07 Ru 44 Iron 55.845 Fe 26 VIIIB Uranium 238.03 U 92 Neptunium (237) Np 93 Plutonium (244) Pu 94 Neodymium Promethium Samarium 144.24 (145) 150.36 Nd 60 Seaborgium (266) Sg 106 Tungsten 183.84 W 74 95.94 Molybdenum Technetium Mo 42 Chromium Manganese 51.996 54.938 Cr 24 VIB 110 Platinum 195.08 Pt 78 Palladium 106.42 Pd 46 Nickel 58.693 Ni 28 10 VIIIB 111 Gold 196.97 Au 79 Silver 107.87 Ag 47 Copper 63.546 Cu 29 11 IB 112 Mercury 200.59 Hg 80 Cadmium 112.41 Cd 48 Zinc 65.409 Zn 30 12 IIB 96 Gadolinium 157.25 Gd 64 (281) Americium (243) Curium (247) Am Cm 95 Europium 151.96 Eu 63 Meitnerium (268) Berkelium (247) Bk 97 Terbium 158.93 Tb 65 (272) Es 99 Holmium 164.93 Ho 67 Thallium 204.38 Tl 81 Indium 114.82 In 49 Gallium 69.723 Ga 31 Aluminum 26.982 Californium Einsteinium (251) (252) Cf 98 Dysprosium 162.50 Dy 66 (285) Mt Uun Uuu Uub 109 Iridium 192.22 Ir 77 Rhodium 102.91 Rh 45 Cobalt 58.933 Co 27 VIIIB Al IVB IIIB Mg Magnesium 24.305 Fermium (257) Fm 100 Erbium 167.26 Er 68 (289) Uuq 114 Lead 207.2 Pb 82 Tin 118.71 Sn 50 Germanium 72.64 Ge 32 Silicon 28.086 Si 14 (258) Mendelevium Md 101 Thulium 168.93 Tm 69 Bismuth 208.98 Bi 83 Antimony 121.76 Sb 51 Arsenic 74.922 As 33 Phosphorus 30.974 P 15 Nitrogen 14.007 N Nobelium (259) No 102 Ytterbium 173.04 Yb 70 Polonium (209) Po 84 Tellurium 127.60 Te 52 Selenium 78.96 Se 34 Sulfur 32.065 S 16 Oxygen 15.999 O Lawrencium (262) Lr 103 Lutetium 174.97 Lu 71 Astatine (210) At 85 Iodine 126.90 I 53 Bromine 79.904 Br 35 Chlorine 35.453 Cl 17 Fluorine 18.998 F Radon (222) Rn 86 Xeno 131.29 Xe 54 Krypton 83.798 Kr 36 Argon 39.948 Ar 18 Neon 20.180 Ne 10 12:00 Na 13 12 11 Carbon 12.011 C He Helium 4.0026 2-10-2009 Sodium 22,990 B Boron 10.811 Berylium 9.0122 Lithium 6.941 Carbon 12.011 Be 13 IIIA LI IUPAC recommendations: Chemical Abstracts Service group notation : C Symbol : Name (IUPAC) : Atomic mass : IIA H Hydrogen 1.0079 Atomic number: ELEMENTS 18 VIIIA OF THE IA P E R I O D I C TA B L E solom_ep_F01-F02v1.qxd Page SOLOMONS solom_ep_F01-F02v1.qxd 2-10-2009 12:00 Page SOLOMONS TABLE 3.1 Relative Strength of Selected Acids and Their Conjugate Bases Acid Strongest acid ϽϪ12 Ϫ10 Ϫ9 Ϫ9 Ϫ7 Ϫ6.5 HSbF6 HI H2SO4 HBr HCl C6H5SO3H ϩ SbF6Ϫ IϪ HSO4Ϫ BrϪ ClϪ C6H5SO3Ϫ Ϫ3.8 Ϫ2.9 (CH3)2O (CH3)2C"O CH3OH2 H3Oϩ HNO3 CF3CO2H HF C6H5CO2H C6H5NH3ϩ CH3CO2H H2CO3 CH3COCH2COCH3 NH4ϩ C6H5OH HCO3Ϫ CH3NH3ϩ H2O CH3CH2OH (CH3)3COH CH3COCH3 HC#CH H2 NH3 CH2"CH2 CH3CH3 Ϫ2.5 Ϫ1.74 Ϫ1.4 0.18 3.2 4.21 4.63 4.75 6.35 9.0 9.2 9.9 10.2 10.6 15.7 16 18 19.2 25 35 38 44 50 CH3OH H2O NO3Ϫ CF3CO2Ϫ FϪ C6H5CO2Ϫ C6H5NH2 CH3CO2Ϫ HCO3Ϫ CH3COHCOCH3 NH3 C6H5OϪ CO32Ϫ CH3NH2 OHϪ CH3CH2OϪ (CH3)3COϪ Ϫ CH2COCH3 HC#CϪ HϪ NH2Ϫ CH2"CHϪ CH3CH2Ϫ www.EngineeringBooksPDF.com Weakest base Increasing base strength Increasing acid strength Conjugate Base (CH3)2OH ϩ (CH3)2C"OH ϩ Weakest acid Approximate pK a Strongest base solom_fm_i-xxxiv-hr2.qxd 14-10-2009 17:19 Page i This online teaching and learning environment integrates the entire digital textbook with the most effective instructor and student resources WRÀWHYHU\OHDUQLQJVW\OH With WileyPLUS: ‡ Students achieve concept mastery in a rich, structured environment that’s available 24/7 ‡ Instructors personalize and manage their course more effectively with assessment, assignments, grade tracking, and more ‡ manage time better ‡study smarter ‡ save money From multiple study paths, to self-assessment, to a wealth of interactive visual and audio resources, WileyPLUS gives you everything you need to personalize the teaching and learning experience » F i n d o u t h ow t o M A K E I T YO U R S » www.wileyplus.com www.EngineeringBooksPDF.com solom_fm_i-xxxiv-hr2.qxd 14-10-2009 17:19 Page ii ALL THE HELP, RESOURCES, AND PERSONAL SUPPORT YOU AND YOUR STUDENTS NEED! 2-Minute Tutorials and all of the resources you & your students need to get started www.wileyplus.com/firstday Student support from an experienced student user Ask your local representative for details! Collaborate with your colleagues, find a mentor, attend virtual and live events, and view resources www.WhereFacultyConnect.com Pre-loaded, ready-to-use assignments and presentations www.wiley.com/college/quickstart Technical Support 24/7 FAQs, online chat, and phone support www.wileyplus.com/support Your WileyPLUS Account Manager Training and implementation support www.wileyplus.com/accountmanager MAKE IT YOURS! www.EngineeringBooksPDF.com solom_fm_i-xxxiv-hr2.qxd 16-10-2009 11:47 Page iii TENTH EDITION Organic Chemistry www.EngineeringBooksPDF.com solom_fm_i-xxxiv-hr2.qxd 14-10-2009 17:19 Page iv www.EngineeringBooksPDF.com solom_fm_i-xxxiv-hr2.qxd 16-10-2009 12:22 Page v TENTH EDITION Organic Chemistry T.W GRAHAM SOLOMONS University of South Florida CRAIG B FRYHLE Pacific Lutheran University JOHN WILEY & SONS, INC www.EngineeringBooksPDF.com solom_fm_i-xxxiv-hr2.qxd 14-10-2009 17:19 Page vi In memory of my beloved son, John Allen Solomons, TWGS To Deanna, in the year of our 25th anniversary CBF ASSOCIATE PUBLISHER Petra Recter PROJECT EDITOR Jennifer Yee MARKETING MANAGER Kristine Ruff SENIOR PRODUCTION EDITOR Elizabeth Swain SENIOR DESIGNER Madelyn Lesure SENIOR MEDIA EDITOR Thomas Kulesa SENIOR ILLUSTRATION EDITOR Sandra Rigby SENIOR PHOTO EDITOR Lisa Gee COVER DESIGNER Carole Anson COVER IMAGE © Don Paulson COVER MOLECULAR ART Norm Christiansen This book was set in 10/12 Times Roman by Preparé and printed and bound by Courier Kendallville The cover was printed by Courier Kendallville This book is printed on acid-free paper Copyright © 2011, 2008, 2004, 2000 John Wiley & Sons, Inc All rights reserved No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Sections 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, website www.copyright.com Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030-5774, (201)748-6011, fax (201)748-6008, website http://www.wiley.com/go/permissions Evaluation copies are provided to qualified academics and professionals for review purposes only, for use in their courses during the next academic year These copies are licensed and may not be sold or transferred to a third party Upon completion of the review period, please return the evaluation copy to Wiley Return instructions and a free of charge return shipping label are available at www.wiley.com/go/returnlabel Outside of the United States, please contact your local representative Library of Congress Cataloging-in-Publication Data Solomons, T W Graham Organic chemistry/T.W Graham Solomons.—10th ed./Craig B Fryhle p cm Includes index ISBN 978-0-470-40141-5 (cloth) Binder-ready version ISBN 978-0-470-55659-7 Chemistry, Organic—Textbooks I Fryhle, Craig B II Title QD253.2.S65 2011 547—dc22 2009032800 Printed in the United States of America 10 www.EngineeringBooksPDF.com solom_STG_G01-G18hr1.qxd 14-10-2009 G-7 16:45 Page 1006 Special Topic G Carbon–Carbon Bond–Forming and Other Reactions TBS O O O O N OTBS Grubbs 1999 second generation catalyst 75% S R R = CH2OMOM TBS O O O O O OH O O N N OTBS S OH S O R R = CH2OMOM [mixture of (Z) and (E, Z) dienes] Epothilone B Another example is ring-opening olefin metathesis polymerization (ROMP), as can be used for synthesis of polybutadiene from 1,5-cyclooctadiene N Cl Review Problem G.9 H Ru Cl n N PCy3 Ph ROMP n What products would form when each of the following compounds is treated with (PCy3)2Cl2Ru " CHPh, one of Grubbs’ catalysts? (a) O (b) OTBDMS O C6H5 H N N O (c) O O (d) O O O N C6H5 OH solom_STG_G01-G18hr1.qxd 14-10-2009 16:45 Page 1007 G.4 Some Background on Transition Metal Elements and Complexes G-8 G.3 The Corey–Posner, Whitesides–House Reaction: Use of Lithium Dialkyl Cuprates (Gilman Reagents) in Coupling Reactions The Corey–Posner, Whitesides–House reaction involves the coupling of a lithium dialkylcuprate (called a Gilman reagent) with an alkyl, alkenyl, or aryl halide The alkyl group of the lithium dialkylcuprate reagent may be primary, secondary, or tertiary However, the halide with which the Gilman reagent couples must be a primary or cyclic secondary alkyl halide if it is not alkenyl or aryl General Reaction R2CuLi ϩ A lithium dialkyl cuprate (a Gilman reagent) RЈ9 X 9999999: R9 R؅ ϩ RCu ϩ LiX Alkenyl, aryl, or 1° or cyclic 2° alkyl halide Specific Example I CH3 (CH3)2CuLi ϩ ϩ CH3Cu Lithium dimethylcuprate ϩ LiI 75% The required lithium dimethylcuprate (Gilman) reagent must be synthesized by a two-step process from the corresponding alkyl halide, as follows Synthesis of an organolithium compound Synthesis of the lithium dialkylcuprate (Gilman) reagent Li R9X 999999: R9 Li 999999: Cul R9 Li R2CuLi ϩ ϩ LiX Lil All of the reagents in a Corey–Posner, Whitesides–House reaction are consumed stoichiometrically The mechanism does not involve a catalyst, as in the other reactions of transition metals that we have studied Show how 1-bromobutane could be converted to the Gilman reagent lithium dibutylcuprate, and how you could use it to synthesize each of the following compounds (a) Review Problem G.10 (b) G.4 Some Background on Transition Metal Elements and Complexes Now that we have seen examples of some important reactions involving transition metals, we consider aspects of the electronic structure of the metals and their complexes Transition metals are defined as those elements that have partly filled d (or f ) shells, either in the elemental state or in their important compounds The transition metals that are of most concern to organic chemists are those shown in the green and yellow portion of the periodic table given in Fig G.1, which include those whose reactions we have just discussed Transition metals react with a variety of molecules or groups, called ligands, to form transition metal complexes In forming a complex, the ligands donate electrons to vacant solom_STG_G01-G18hr1.qxd 14-10-2009 G-9 16:45 Page 1008 Special Topic G Carbon–Carbon Bond–Forming and Other Reactions 1/IA 1 Periods H 1.00797 2/IIA Li Be 6.941 9.01218 11 12 Na Mg 22.98977 24.305 19 20 3/IIIB 4/IVB 5/VB 6/VIB 7/VIIB 21 22 23 24 25 K Ca Sc Ti V 8/VIIIB 9/VIIIB 10/VIIIB 11/IB 26 27 28 29 12/IIB 30 Cr Mn Fe Co Ni Cu Zn 39.098 40.08 44.9559 47.90 50.9414 51.996 54.9380 55.847 58.9332 58.71 63.546 65.38 37 38 39 40 41 42 43 44 45 46 47 48 Rb Sr Y Zr Nb Mo Tc Ru Rh Pd Ag Cd 85.4678 87.62 89.9059 91.22 92.9064 95.94 98.9062 55 56 57 72 73 74 75 101.07 102.9055 76 186.2 190.2 192.22 Valence electrons 107.868 112.40 78 79 80 77 Cs Ba La Hf Ta W Re Os Ir 132.9054 137.34 138.9055 178.49 180.9479 183.85 106.4 Pt Au Hg 195.09 196.9665 200.59 10 11 12 Figure G.1 Important transition elements are shown in the green and yellow portion of the periodic table Given across the bottom is the total number of valence electrons (s and d) of each element orbitals of the metal The bonds between the ligand and the metal range from very weak to very strong The bonds are covalent but often have considerable polar character Transition metal complexes can assume a variety of geometries depending on the metal and on the number of ligands around it Rhodium, for example, can form complexes with four ligands in a configuration called square planar On the other hand, rhodium can form complexes with five or six ligands that are trigonal bipyramidal or octahedral These typical shapes are shown below, with the letter L used to indicate a ligand L L L L L Rh L L Rh Square planar rhodium complex L L L Trigonal bipyramidal rhodium complex L Rh L L L L Octahedral rhodium complex G.5 Electron Counting in Metal Complexes Transition metals are like the elements that we have studied earlier in that they are most stable when they have the electronic configuration of a noble gas In addition to s and p orbitals, transition metals have five d orbitals (which can hold a total of 10 electrons) Therefore, the noble gas configuration for a transition metal is 18 electrons, not as with carbon, nitrogen, oxygen, and so on When the metal of a transition metal complex has 18 valence electrons, it is said to be coordinatively saturated.* *We not usually show the unshared electron pairs of a metal complex in our structures, because to so would make the structure unnecessarily complicated solom_STG_G01-G18hr2.qxd 15-10-2009 12:55 Page 1009 G.5 Electron Counting in Metal Complexes To determine the valence electron count of a transition metal in a complex, we take the total number of valence electrons of the metal in the elemental state (see Fig G.1) and subtract from this number the oxidation state of the metal in the complex This gives us what is called the d electron count, d n The oxidation state of the metal is the charge that would be left on the metal if all the ligands (Table G.1) were removed oxidation state of d n ϭ total number of valence electrons Ϫ the metal in the complex of the elemental metal Then to get the total valence electron count of the metal in the complex, we add to d n the number of electrons donated by all of the ligands Table G.1 gives the number of electrons donated by several of the most common ligands total number of valence electrons ϭ d n ϩ electrons donated by ligands of the metal in the complex Let us now work out the valence electron count of two examples TABLE G.1 Common Ligands in Transition Metal Complexesa Ligand Number of Electrons Donated Count as Negatively charged ligands Hydride, H Alkanide, R Halide, X Allyl anion H:Ϫ R:Ϫ X:Ϫ Ϫ Cyclopentadienyl anion, Cp Ϫ Electrically neutral ligands Carbonyl (carbon monoxide) :C # O: R3P: or Ph3P: Phosphine Alkene C 2 2 C Diene Benzene a Used with permission from the Journal of Chemical Education, Vol 57, No 1, 1980, pp 170-175, copyright © 1980, Division of Chemical Education Example A Consider iron pentacarbonyl, Fe(CO)5, a toxic liquid that forms when finely divided iron reacts with carbon monoxide OC Fe ϩ CO Fe(CO)5 CO Fe or OC CO CO Iron pentacarbonyl From Fig G.1 we find that an iron atom in the elemental state has valence electrons We arrive at the oxidation state of iron in iron pentacarbonyl by noting that the charge on the complex as a whole is zero (it is not an ion), and that the charge on each CO ligand is also zero Therefore, the iron is in the zero oxidation state G-10 solom_STG_G01-G18hr1.qxd G-11 14-10-2009 16:45 Page 1010 Special Topic G Carbon–Carbon Bond–Forming and Other Reactions Using these numbers, we can now calculate d n and, from it, the total number of valence electrons of the iron in the complex dn ϭ Ϫ ϭ total number of ϭ d n ϩ 5(CO) ϭ ϩ 5(2) ϭ 18 valence electrons We find that the iron of Fe(CO)5 has 18 valence electrons and is, therefore, coordinatively saturated Example B Consider the rhodium complex Rh[(C6H5)3P]3H2Cl, a complex that, as we shall see later, is an intermediate in certain alkene hydrogenations L H L Rh L Cl L ‫ ؍‬Ph3P [i.e., (C6H5)3P] H The oxidation state of rhodium in the complex is ϩ3 [The two hydrogen atoms and the chlorine are each counted as Ϫ1 (hydride and chloride, respectively), and the charge on each of the triphenylphosphine ligands is zero Removing all the ligands would leave a Rh3ϩ ion.] From Fig G.1 we find that, in the elemental state, rhodium has valence electrons We can now calculate d n for the rhodium of the complex dn ϭ Ϫ ϭ Each of the six ligands of the complex donates two electrons to the rhodium in the complex, and, therefore, the total number of valence electrons of the rhodium is 18 The rhodium of Rh[(C6H5)3P]3H2Cl is coordinatively saturated total number of valence ϭ dn ϩ 6(2) ϭ ϩ 12 ϭ 18 electrons rhodium G.6 Mechanistic Steps in the Reactions of Some Transition Metal Complexes Much of the chemistry of organic transition metal compounds becomes more understandable if we are able to follow the mechanisms of the reactions that occur These mechanisms, in most cases, amount to nothing more than a sequence of reactions, each of which represents a fundamental reaction type that is characteristic of a transition metal complex Let us examine three of the fundamental reaction types now In each instance we shall use steps that occur when an alkene is hydrogenated using a catalyst called Wilkinson’s catalyst In Section G.7 we shall examine the entire hydrogenation mechanism In Section G.8 we shall see how similar types of steps are involved in the Heck–Mizokori reaction Ligand Dissociation–Association (Ligand Exchange) A transition metal complex can lose a ligand (by dissociation) and combine with another ligand (by association) In the process it undergoes ligand exchange For example, the rhodium complex that we encountered in Example B above can react with an alkene (in this example, with ethene) as follows: L H H2 C L Cl L L ϩ H2 C Rh H C H2 C H2 H ϩ Rh L H L ‫ ؍‬Ph3P [i.e., (C6H5)3P] Cl L solom_STG_G01-G18hr1.qxd 14-10-2009 16:45 Page 1011 G.6 Mechanistic Steps in the Reactions of Some Transition Metal Complexes Two steps are actually involved In the first step, one of the triphenylphosphine ligands dissociates This leads to a complex in which the rhodium has only 16 electrons and is, therefore, coordinatively unsaturated H L L L H L H Rh L H ϩL Rh Cl (18 electrons) Cl (16 electrons) L ‫ ؍‬Ph3P In the second step, the rhodium associates with the alkene to become coordinatively saturated again H2 C H L L H ϩ H2 C Rh L C H2 H Rh CH2 L Cl (16 electrons) H Cl (18 electrons) The complex between the rhodium and the alkene is called a p complex In it, two electrons are donated by the alkene to the rhodium Alkenes are often called p donors to distinguish them from s donors such as Ph3P:, ClϪ, and so on In a p complex such as the one just given, there is also a donation of electrons from a populated d orbital of the metal back to the vacant p* orbital of the alkene This kind of donation is called “back-bonding.” Insertion–Deinsertion An unsaturated ligand such as an alkene can undergo insertion into a bond between the metal of a complex and a hydrogen or a carbon These reactions are reversible, and the reverse reaction is called deinsertion The following is an example of insertion–deinsertion H2 C C H2 L H Rh L H Cl insertion deinsertion (18 electrons) Cl L C H3 Rh L CH H (16 electrons) In this process, a p bond (between the rhodium and the alkene) and a s bond (between the rhodium and the hydrogen) are exchanged for two new s bonds (between rhodium and carbon, and between carbon and hydrogen) The valence electron count of the rhodium decreases from 18 to 16 This insertion–deinsertion occurs in a stereospecific way, as a syn addition of the M H unit to the alkene C C M C H C M H Oxidative Addition–Reductive Elimination Coordinatively unsaturated metal complexes can undergo oxidative addition of a variety of substrates in the following way.* A M ϩ A B oxidative addition M B *Coordinatively saturated complexes also undergo oxidative addition G-12 solom_STG_G01-G18hr1.qxd G-13 14-10-2009 16:45 Page 1012 Special Topic G Carbon–Carbon Bond–Forming and Other Reactions The substrate, A B, can be H H, H X, R X, RCO H, RCO X, and a number of other compounds In this type of oxidative addition, the metal of the complex undergoes an increase in the number of its valence electrons and in its oxidation state Consider, as an example, the oxidative addition of hydrogen to the rhodium complex that follows (L ϭ Ph3P) L H L ϩ Rh H oxidative addition H reductive elimination Cl L L L Rh L Cl (16 electrons) Rh is in ؉1 oxidation state H (18 electrons) Rh is in ؉3 oxidation state Reductive elimination is the reverse of oxidative addition With this background, we are now in a position to examine the mechanisms of two applications of transition metal complexes in organic synthesis G.7 The Mechanism for a Homogeneous Hydrogenation: Wilkinson’s Catalyst The catalytic hydrogenations that we have examined in prior chapters have been heterogeneous processes Two phases were involved: the solid phase of the catalyst (Pt, Pd, Ni, etc.), containing the adsorbed hydrogen, and the liquid phase of the solution, containing the unsaturated compound In homogeneous hydrogenation using a transition metal complex such as Rh[(C6H5)3P]3Cl (Wilkinson’s catalyst), hydrogenation takes place in a single phase, i.e., in solution When Wilkinson’s catalyst is used to carry out the hydrogenation of an alkene, the following steps take place (L ϭ Ph3P) Step L L L ϩ H Rh L Rh H Cl L H L 16 valence electrons Cl Oxidative addition H 18 valence electrons Step H H L L L Rh Rh L Cl H 18 valence electrons H ϩ L L Cl 16 valence electrons Ligand dissociation solom_STG_G01-G18hr1.qxd 14-10-2009 16:45 Page 1013 G.7 The Mechanism for a Homogeneous Hydrogenation: Wilkinson’s Catalyst G-14 Step H2 C H L L H CH2 ∆ H ϩ H2C Rh L CH2 L Cl 16 valence electrons Ligand association Rh Cl H 18 valence electrons Step H2C C H2 L L H Rh L ∆ C H3 Rh L Cl H Cl Insertion CH H 18 valence electrons 16 valence electrons Step Cl CH3 L Rh L ∆ CH2 Cl ϩ H3C Rh Reductive elimination CH L L H 16 valence electrons 14 valence electrons Step H L L Rh Cl ϩ H2 L ∆ Rh Oxidative addition H L Cl 14 valence electrons 16 valence electrons (Cycle repeats from step 3.) Step regenerates the hydrogen-bearing rhodium complex and reaction with another molecule of the alkene begins at step Because the insertion step and the reductive elimination step are stereospecific, the net result of the hydrogenation using Wilkinson’s catalyst is a syn addition of hydrogen to the alkene The following example (with D2 in place of H2) illustrates this aspect H H H ϩ D2 EtO2C CO2Et A cis-alkene (diethyl maleate) Rh(Ph3P)3Cl H CO2Et EtO2C D D A meso compound What product (or products) would be formed if the trans-alkene corresponding to the cisalkene (see the previous reaction) had been hydrogenated with D2 and Wilkinson’s catalyst? Review Problem G.11 solom_STG_G01-G18hr1.qxd 14-10-2009 G-15 16:45 Page 1014 Special Topic G Carbon–Carbon Bond–Forming and Other Reactions THE CHEMISTRY OF Homogeneous Asymmetric Catalytic Hydrogenation: Examples Involving L-DOPA, (S)-Naproxen, and Aspartame University) (The other half of the 2001 prize was awarded to K B Sharpless for asymmetric oxidation reactions See Chapter 8.) Knowles, Noyori, and others developed chiral catalysts for homogeneous hydrogenation that have proved extraordinarily useful for enantioselective syntheses ranging from small laboratory-scale reactions to industrial- (ton-) scale reactions An important example is the method developed by Knowles and co-workers at Monsanto Corporation for synthesis of L-DOPA, a compound used in the treatment of Parkinson’s disease: Development by Geoffrey Wilkinson of a soluble catalyst for hydrogenation [tris(triphenylphosphine)rhodium chloride, Section 7.13 and Special Topic G] led to Wilkinson’s earning a share of the 1973 Nobel Prize in Chemistry His initial discovery, while at Imperial College, University of London, inspired many other researchers to create novel catalysts based on the Wilkinson catalyst Some of these researchers were themselves recognized by the 2001 Nobel Prize in Chemistry, 50% of which was awarded to William S Knowles (Monsanto Corporation, retired) and Ryoji Noyori (Nagoya Asymmetric Synthesis of L-DOPA H3CO AcO COOH NHAc COOH H3CO H2 (100%) [(Rh(R,R)-DIPAMP)COD]ϩBF4Ϫ(cat.) H3Oϩ HO COOH H NHAc AcO H NH2 HO (100% yield, 95% ee [enantiomeric excess]) O ‘ Ac=CH3C ¬ L-DOPA OCH3 P P H3CO COD ‫؍‬ 1,5-Cyclooctadiene (R,R)-DIPAMP (Chiral ligand for rhodium) Another example is synthesis of the over-the-counter analgesic naproxen using a BINAP rhodium catalyst developed by Noyori (Sections 5.11 and 5.18) Asymmetric Synthesis of (S)-Naproxen CH2 H COOH (S)-BINAP-Ru(OCOCH3)2 (0.5 mol%) ϩ H2 CH3 COOH MeOH H3CO H3CO (S)-Naproxen (an anti-inflammatory agent) (92% yield, 97% ee) P(Ph)2 (Ph)2P P(Ph)2 (Ph)2P (S)-BINAP (R)-BINAP (S)-BINAP and (R)-BINAP are chiral atropisomers (see Section 5.18) solom_STG_G01-G18hr1.qxd 14-10-2009 16:45 Page 1015 G-16 G.8 The Mechanism for an Example of Cross-Coupling: The Heck–Mizokori Reaction Catalysts like these are important for asymmetric chemical synthesis of amino acids (Section 24.3D), as well A final example is the synthesis of (S)-phenylalanine methyl ester, a compound used in the synthesis of the artificial sweetener aspartame This preparation employs yet a different chiral ligand for the rhodium catalyst Asymmetric Synthesis of Aspartame COOH (1) (R,R)-PNNP-Rh(I) (cat.), H2 (83% ee) (catalytic asymmetric hydrogenation) (2) MeOH, HA NHAc Ph H3C COOCH3 H NH2 (S)-phenylalanine methyl ester (97% ee after recrystallization) Ph N N (Ph)2P P(Ph)2 CH3 (R,R)-PNNP (Chiral ligand for rhodium) HOOC COOH H2N H (S)-aspartic acid H NH2 NH COOH H O COOCH3 Aspartame The mechanism of homogeneous catalytic hydrogenation involves reactions characteristic of transition metal organometallic compounds A general scheme for hydro- genation using Wilkinson’s catalyst is shown here We have seen structural details of the mechanism in Section G.7 Cl[(C6H5)3P]2Rh Cl[(C6H5)3P]3Rh Ϫ(C6H5)3P Cl[(C6H5)3P]2Rh(H)2 Cl[(C6H5)3P]2Rh H A general mechanism for the Wilkinson catalytic hydrogenation method, adapted with permission of John Wiley & Sons, Inc from Noyori, Asymmetric Catalysis in Organic Synthesis, p 17 Copyright 1994 H2 H Cl[(C6H5)3P]2RhH H G.8 The Mechanism for an Example of Cross-Coupling: The Heck–Mizokori Reaction Having seen steps such as oxidative addition, insertion, and reductive elimination in the context of transition metal–catalyzed hydrogenation using Wilkinson’s catalyst, we can now see how these same types of mechanistic steps are involved in a mechanism proposed for the Heck–Mizokori reaction Aspects of the Heck–Mizokori mechanism are similar to steps proposed for other cross-coupling reactions as well, although there are variations and certain steps that are specific to each, and not all of the steps below are involved or serve the same purpose in other cross-coupling reactions solom_STG_G01-G18hr1.qxd 14-10-2009 G-17 16:45 Page 1016 Special Topic G Carbon–Carbon Bond–Forming and Other Reactions A MECHANISM FOR THE REACTION The Heck–Mizokori Reaction Using an Aryl Halide Substrate GENERAL REACTION Ar ¬X + R Pd catalyst Ar Base (an amine) R MECHANISM Pd(L)4 –2L (L = ligand, e.g., Ph3P) Ar¬X base¬ HX Pd(L)2 Reductive elimination (regenerates catalyst) Oxidative addition (incorporates halide reactant) Coordinatively unsaturated catalyst base H¬Pd(L)2¬ X Ar¬Pd(L)2¬X Ar R Alkene insertion (incorporates alkenyl reactant, forms new C¬C bond) R 1,2-syn elimination (forms the product as a trans alkene) H Ar H Pd(L)2X H R C¬C bond rotation Ar H H Pd(L)2X H R G.9 Vitamin B12: A Transition Metal Biomolecule The discovery (in 1926) that pernicious anemia can be overcome by the ingestion of large amounts of liver led ultimately to the isolation (in 1948) of the curative factor, called vitamin B12 The complete three-dimensional structure of vitamin B12 [Fig G.2(a)] was elucidated in 1956 through the X-ray studies of Dorothy Hodgkin (Nobel Prize, 1964), and in 1972 the synthesis of this complicated molecule was announced by R B Woodward (Harvard University) and A Eschenmoser (Swiss Federal Institute of Technology) The synthesis took 11 years and involved more than 90 separate reactions One hundred coworkers took part in the project Vitamin B12 is the only known biomolecule that possesses a carbon–metal bond In the stable commercial form of the vitamin, a cyano group is bonded to the cobalt, and the cobalt is in the ϩ3 oxidation state The core of the vitamin B12 molecule is a corrin ring [Fig G.2(b)] with various attached side groups The corrin ring consists of four pyrrole solom_STG_G01-G18hr1.qxd 14-10-2009 16:45 Page 1017 G-18 G.9 Vitamin B12: A Transition Metal Biomolecule subunits, the nitrogen of each of which is coordinated to the central cobalt The sixth ligand [(below the corrin ring in Fig G.2(a)] is a nitrogen of a heterocyclic group derived from 5,6-dimethylbenzimidazole The cobalt of vitamin B12 can be reduced to a ϩ2 or a ϩ1 oxidation state When the cobalt is in the ϩ1 oxidation state, vitamin B12 (called B12s) becomes one of the most powerful nucleophiles known, being more nucleophilic than methanol by a factor of 1014 Acting as a nucleophile, vitamin B12s reacts with adenosine triphosphate (Fig 22.2) to yield the biologically active form of the vitamin [Fig G.2(c)] A carbon–cobalt s bond O H2N R O CH3 H2N O CH3 CH3 N ϩ N Co H2N N CH3 O P CH3 O O HO N NH2 O CH3 O H3C N OϪ O O CH3 N H3C HN NH2 CH3 N N NH2 H OH OH H H H H CH3 N N CH2 O Adenine Co O HOCH2 (a) (b) (c) Figure G.2 (a) The structure of vitamin B12 In the commercial form of the vitamin (cyanocobalamin), R " CN (b) The corrin ring system (c) In the biologically active form of the vitamin (5Ј-deoxyadenosylcobalamin), the 5Ј carbon atom of 5Ј-deoxyadenosine is coordinated to the cobalt atom For the structure of adenine, see Section 25.2 See Special Topic H in WileyPLUS 3.0 ␯OϭC–H 3.5 m, broad ␯O–H associated 2000 4.0 CϵN –––m(1–2) –––w–m ␯CϵC w–m ␦Ar–H 2400 (Microns) ␯CϭO s ␦N–H w–overtones ␯CϭC 1800 m 1400 s sk s ␦XC–H2 m–s m ␯C–N ␦O–H m ␦O–H w–m s 1200 ␦–C–H m–s(2) m–s ␦ϭC–H 1600 Typical IR absorption frequencies for common functional groups Absorptions are as follows: ␯ = stretching; ␦ = bending; w = weak; m = medium; s = strong; sk = skeletal From Multiscale Organic Chemistry: A Problem-Solving Approach by John W Lehman © 2002 Reprinted by permission of Pearson Education, Inc., Upper Saddle River, NJ 2.5 s w–m ␯O–H m ␯N–H ␯O–H free 2800 ␯–C–H s ␯ϭC–H m–s ␯ϵC–H m ␯Ar–H ––w–m 3200 10 s 600 16 m–s ␯C–Br m–s m–s s ␦ϵC–H m–s 800 11 12 13 14 ␯C–Cl ␦N–H ␯C–O ␦Ar–H m sk ␦ϭC–H 1000 15:13 Alkane Alkene Alkyne Aromatic 1Њ alcohol 2Њ alcohol 3Њ alcohol Phenol Ether Ester Carboxylic acid Ketone Aldehyde Amide 1Њ amine 2Њ amine 3Њ amine Alkyl chloride Alkyl bromide Nitrile 3600 Frequency (cm–1) 2-10-2009 4000 See Table 2.7 for a Table of IR frequencies solom_ep_B01-B03v1.qxd Page SOLOMONS solom_ep_B01-B03v1.qxd 2-10-2009 15:13 Page SOLOMONS 13C NMR Approximate Chemical Shift Ranges C Cl, Br C N C OR C OH C O C N C N O CH C CH2 C OR 220 O O C R,H C OH 200 180 C C 160 140 C C 120 100 ␦C (ppm) 80 60 40 Type of Carbon Atom Chemical Shift (dd, ppm) 1° Alkyl, RCH3 2° Alkyl, RCH2R 3° Alkyl, RCHR2 0–40 10–50 15–50 Alkyl halide or amine, C Alcohol or ether, O Alkyne, C X qX=Cl, Br, or N r 10–65 50–90 60–90 C Alkene, C 100–170 C Aryl, C 100–170 N 120–130 N 150–180 O Amide, 20 Approximate Carbon-13 Chemical Shifts TABLE 9.2 Nitrile, CH3 C O Carboxylic acid or ester, C O 160–185 O Aldehyde or ketone, C 182–215 solom_ep_B01-B03v1.qxd 2-10-2009 15:13 Page SOLOMONS 1H NMR Approximate Chemical Shift Ranges C OH, NHn C C H O OH C CH O C C C OH Ar CH H O H X,O,N CH C H 12 TABLE 9.1 11 10 dH (ppm) 3Њ,2Њ,1Њ C C CH CH Approximate Proton Chemical Shifts Type of Proton Chemical Shift (dd, ppm) Type of Proton Chemical Shift (dd, ppm) 1° Alkyl, RCH3 2° Alkyl, RCH2R 3° Alkyl, R3CH Allylic, R2C “ C ¬ CH3 0.8–1.2 1.2–1.5 1.4–1.8 1.6–1.9 Alkyl bromide, RCH2Br Alkyl chloride, RCH2Cl Vinylic, R2C " CH2 Vinylic, R2C “ CH 3.4–3.6 3.6–3.8 4.6–5.0 5.2–5.7 ƒ ƒ R Ketone, RCCH3 R 2.1–2.6 ‘ 2.2–2.5 2.5–3.1 3.1–3.3 3.3–3.9 3.3–4.0 O Alcohol hydroxyl, ROH Amino, R NH2 Phenolic, ArOH Carboxylic, RCOH ‘ O a 6.0–8.5 9.5–10.5 ‘ O Benzylic, ArCH3 Acetylenic, RC # CH Alkyl iodide, RCH2I Ether, ROCH2R Alcohol, HOCH2R Aromatic, ArH Aldehyde, RCH The chemical shifts of these protons vary in different solvents and with temperature and concentration 0.5–6.0a 1.0–5.0a 4.5–7.7a 10–13a ... www.EngineeringBooksPDF.com solom_fm_i-xxxiv-hr2.qxd 16-10-2009 11:47 Page iii TENTH EDITION Organic Chemistry www.EngineeringBooksPDF.com solom_fm_i-xxxiv-hr2.qxd 14-10-2009 17:19 Page iv www.EngineeringBooksPDF.com... aspect of our lives that is not in some way dependent on organic chemistry But what is organic chemistry? • Organic chemistry is the chemistry of compounds that contain the element carbon Clearly,... www.EngineeringBooksPDF.com solom_fm_i-xxxiv-hr2.qxd 14-10-2009 17:19 Page xxi Preface “Capturing the Powerful and Exciting Subject of Organic Chemistry? ?? We want our students to learn organic chemistry