Organic chemistry t w graham solomons, craig b fryhle 10ed

ô ã iU W , > KZ A ' >t : /; > i l > *V < * & s f l* * W G R A H A M S O LO M O N S CRAIG B FRYHLE O R G A N IC CHEM ISTRY lOe P e r io d ic T able of the E l e m e n t s 18 V IIIA IA H Atom ic nu m b e r-^ Hydrogen 1.0079 11A c Symbol —> Name (IUPAC) Atom ic m ass —> IUPAC re co m m e n d a tio n s^ Chemical Abstracts Service group notation —> Carbon 12.011 He 13 14 15 16 17 IMA IVA VA V IA V IIA Helium 4.0026 10 LI Be B c N F Ne Lithium 6.941 Berylium 9.0122 Boron 10.811 Carbon 12.011 Nitrogen 14.007 Oxygen 15.999 Fluorine 18.998 Neon 20.180 11 12 13 14 15 16 17 18 Na Mg Sodium 22,990 Magnesium 24.305 10 NIB IVB VB VIB VI IB V IIIB V IIIB 19 20 21 22 23 24 25 26 27 V Cr Mn AI Si P S Cl Ar MB Aluminum 26.982 Silicon 28.086 Phosphorus 30.974 Sulfur 32.065 Chlorine 35.453 Argon 39.948 30 31 32 33 34 35 36 11 12 V IIIB IB 28 29 K Ca Sc Ti Fe Co Ni Cu Zn Ga Ge As Se Br Kr Potassium 39.098 Calcium 40.078 Scandium 44.956 Titanium 47.867 Vanadium 50.942 Chromium 51.996 Manganese 54.938 Iron 55.845 Cobalt 58.933 Nickel 58.693 Copper 63.546 Zinc 65.409 Gallium 69.723 Germanium 72.64 Arsenic 74.922 Selenium 78.96 Bromine 79.904 Krypton 83.798 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 Mo Tc Rb Sr Y Zr Nb Rubidium 85.468 Strontium 87.62 Yttrium 88.906 Zirconium 91.224 Niobium 92.906 55 56 57 72 73 Molybdenum Technetium 95.94 (98) 74 75 Ru Rh Pd Ag Cd In Sn Sb Te I Xe Ruthenium 101.07 Rhodium 102.91 Palladium 106.42 Silver 107.87 Cadmium 112.41 Indium 114.82 Tin 118.71 Antimony 121.76 Tellurium 127.60 Iodine 126.90 Xeno 131.29 76 77 78 79 80 81 82 83 84 85 86 Cs Ba *La Hf Ta w Re Os Ir Pt Au Hg TI Pb Bi Po At Rn Caesium 132.91 Barium 137.33 Lanthanum 138.91 Hafnium 178.49 Tantalum 180.95 Tungsten 183.84 Rhenium 186.21 Osmium 190.23 Iridium 192.22 Platinum 195.08 Gold 196.97 Mercury 200.59 Thallium 204.38 Lead 207.2 Bismuth 208.98 Polonium (209) Astatine (210) Radon (222) 87 88 89 104 105 106 107 108 109 110 111 112 Fr Ra #Ac Rf Db sg Bh Hs Mt Francium (223) Radium (226) Actinium (227) Rutherfordium (261) Dubnium (262) Seaborgium (266) Bohrium (264) Hassium (277) Meitnerium (268) 58 59 60 61 62 63 69 70 71 Pr Nd Pm ‘ Lanthanide Series Ce Cerium 140.12 90 # Actinide Series Praseodymium Neodymium Promethium 114 Uun Uuu Uub Uuq (281) (272) (285) (289) 64 65 66 67 68 Sm Eu Gd Tb Dy Ho Er Tm Yb Lu Europium 151.96 Gadolinium 157.25 Terbium 158.93 Dysprosium 162.50 Holmium 164.93 Erbium 167.26 Thulium 168.93 Ytterbium 173.04 Lutetium 174.97 95 96 97 98 99 100 101 102 103 140.91 144.24 (145) Samarium 150.36 91 92 93 94 Th Pa U Np Pu Am Cm Bk Cf Es Fm Md No Lr Thorium 232.04 Protactinium 231.04 Uranium 238.03 Neptunium (237) Plutonium (244) Americium (243) Curium (247) Berkelium (247) Californium (251) Einsteinium (252) Fermium (257) Mendelevium Nobelium (259) Lawrencium (262) (258) Relative S trength o f Selected Acids and Their C onjugate Bases Acid S tro n g est acid t T O C o 00 ■a W eakest acid H SbF HI H2SO HBr HCl C H5SO+sH A p p ro x im ate pK a < -1 -1 C o n ju g ate Base -9 -9 -7 - S bF 6Ih s o 4BrClC H5S O (CH 3)2O+H + (CH 3)2C = O H - - (CH 3)2O (CH 3)2C = O c h 3o+h2 H3O+ hno3 c f 3c o 2h HF c h 5c o 2h C H5NH3 + c h 3c o 2h h 2c o c h 3c o c h 2c o c h n h 4+ C H5OH h c o 3c h n h 3+ h 2o c h 3c h 2o h (CH 3)3COH c h 3c o c h H C #C H H2 nh3 c h 2= c h c h 3c h - - - 0.18 3.2 4.21 4.63 4.75 6.35 9.0 9.2 9.9 c h 3o h 10.2 10.6 15.7 16 18 19.2 25 35 38 44 50 W eakest base h 2o NO CF 3CO FC H5CO C H5NH c h 3c o 2h c o 3c h 3c o h c o c h :3 NH3 C H5O CO 32c h 3n h OHc h 3c h 2o (CH 3)3C O - c h 2c o c h H C#CHn h 2c h 2= c h c h 3c h 2- S tro n g est base From multiple study paths, to self-assessment, to a wealth of interactive visual and audio resources, WHeyPLUS gives you everything you need to personalize the teaching and learning experience »Find out how to M A K E IT Y O U R S » www.wileyplus.com p ALL THE HELP, RESOURCES, AND PERSONAL SUPPORT YOU AND YOUR STUDENTS NEED! ■Jst DAY0F AND BEYOND! -M in u te Tutorials a n d all WILEY TLUS Student Partner Program FACULTY NETWORK S tu d e n t s u p p o r t fr o m an C o l l a b o r a t e w ith yo u r c o lle a g u e s , o f the resources you & your e x p e r ie n c e d stu de nt user fin d a m e n to r, a tte n d v i r t u a l a n d live students need to g e t s ta rt e d A sk y o u r local re p re s e n ta tiv e events, a n d v i e w resources w w w w ile y p lu s c o m /first d a y fo r d e ta ils ! w w w W hereFacultyConnect.com WILEY PLUS QuickStart V P r e - l o a d e d , re a d y - to -u s e Technical S u p p o r t / Your W i l e y PLUS assignments a n d p re sen ta tion s FAQs, online chat, Account M a n a g e r a n d phone s u p p o r t T in in g a n d im p le m e n ta tio n s u p p o r t w w w w ile y co m /co lle g e /q u ick sta rt w w w w i l e y p l u s c o m / s u p p o r t w w w w ile y p lu s c o m /a cc o u n tm a n a g e r WILEY P L U S MAKE IT YOURS! www.wileyplus.com Organic Chemistry T E NT H EDITION Organic Chemistry T.W GRAHAM SOLOMONS University o f South Florida CRAIG B FRYHLE Pacific Lutheran University JOHN WILEY & SONS, INC In m em ory o f m y b e lo ve d son, John A llen Solomons, TWGS To Deanna, in the year o f 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 instruc­ tions 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 G-7 S p e c ia l T o p ic G TBS O O C a r b o n -C a r b o n B o n d -F o r m in g a n d O t h e r R e a c tio n s O Grubbs 1999 second generation catalyst 75% * TBS O X) O O OH O [mixture of (Z) and (E, Z) dienes] Another example is ring-opening olefin metathesis polymerization (ROMP), as can be used for synthesis of polybutadiene from 1,5-cyclooctadiene n ReviewProblemG.9 What products would form when each of the following compounds is treated with (PCy3)2C!2Ru= CHPh, one of Grubbs’ catalysts? (a ) „a O^ C 6H5 (b) OTBDMS A N xh O (C) O''''"""'"' ,,"""\O (d) O N O OH G S o m e B a c k g ro u n d o n T n s itio n M e t a l E le m e n ts a n d C o m p le x e s G-8 G.3 The Corey-Posner, W hitesides-House Reaction: Use o f 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 R' — X A lith iu m d ia lk y l c u p te (a G ilm an rea ge n t) A lk e n y l, aryl, o r 1° o r c y c lic 2° a lk y l h a lid e R— R' - RCu LiX Specific Example (CH3)2CuLi h CH3Cu L ith iu m d im e th y lc u p te Lil 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 R— X R— Li Li Cul R— Li R2CuLi 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 transi­ tion 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 ReviewProblemG.10 G.4 Som e Background on Transition M e ta l Elem ents 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 (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 to form In forming a complex, the ligands donate electrons to vacant d transitionmetalcomplexes ligands, G-9 S p e c ia l T o p ic G C a r b o n -C a r b o n B o n d -F o r m in g a n d O t h e r R e a c tio n s 1/IA H o 1.00797 2/IIA Li Be 6.941 9.01218 11 12 Na Mg 22.98977 24.305 3/IIIB 4/IVB 5/VB 19 20 21 22 23 /VIB 7/VIIB 24 25 /VIIIB 26 9/VIIIB 10/VIIIB 28 27 11/IB 12/IIB 29 30 Cr Mn Fe Co Ni Cu Zn Ti V 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 K Ca Sc 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 101.07 102.9055 106.4 107.868 112.40 55 56 57 72 73 74 75 76 77 78 79 80 Hf Cs Ba La 132.9054 137.34 Ta W Re Os 138.9055 178.49 180.9479 183.85 186.2 190.2 Valence electrons Ir 192.22 Pt Au Hg 195.09 196.9665 200.59 11 Figure G.1 Im p o rta n t tra n sitio n elem ents are shown in th e green and ye llo w p o rtio n o f th e p e rio d ic ta b le Given across th e b o tto m is th e to ta l num ber o f valence electrons (s and d) o f each elem ent 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 On the other hand, rhodium can form complexes with five or six ligands that are trigonal bipyramidal or octahedral These typi­ cal shapes are shown below, with the letter L used to indicate a ligand squareplanar LK \T L 4«¡&L L K,:Rh— I L L L I L Square planar rhodium complex Trigonal bipyramidal rhodium complex L L /i L — Rh— L Octahedral rhodium complex G.5 Electron Counting in M e ta l Com plexes 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 orbitals, transition metals have five orbitals (which can hold a total of electrons) Therefore, the noble gas configuration for a transition metal is 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 * d p 18electrons, coordinativelysaturated *We not usually show the unshared electron pairs of a metal complex in our structures, because to so would make the structure unnecessarily complicated G E le c tro n C o u n tin g in M e t a l C o m p le x e s 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 sub­ tract from this number the oxidation state of the metal in the complex This gives us what is called the electron count, 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 d dn dn=total number of valence electrons _ of the elemental metal oxidation state of the metal in the complex inthecomplex, dn Then to get the total valence electron count of the metal we add to 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 = of the metal in the complex dn+electrons donated by ligands Let us now work out the valence electron count of two examples C om m on L ig a n d s in T r a n s it io n M e t a l C o m p le x e s Ligand Number of Electrons Donated Count as Negatively charged ligands Hydride, H Alkanide, R Halide, X Allyl anion Cyclopentadienyl anion, Cp Electrically neutral ligands Carbonyl (carbon monoxide) :C # O: Phosphine R3 P: or Ph3 P: \ / Alkene C=C / \ Diene Benzene aUsed w ith perm ission from the Journal of Chemical c o p y rig h t © 1980, Division o f Chemical Education Education, Vol 57, No 1, 1980, pp 170-175, E x a m p le A Consider iron pentacarbonyl, Fe(CO)5, a toxic liquid that forms when finely divided iron reacts with carbon monoxide CO OCV Fe + CO -» F e (C O )5 or I ^ F e — CO O C ^ 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 G-11 S p e c ia l T o p ic G C a r b o n -C a r b o n B o n d -F o r m in g a n d O t h e r R e a c tio n s 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= - = = d n+5(CQ) = total number of valence electrons 8 + (2 ) = 18 We find that the iron of Fe(CO) has 18 valence electrons and is, therefore, coordinatively saturated E x a m p le B Consider the rhodium complex Rh[(C6 H5 )3 P]3 H2 Cl, a complex that, as we shall see later, is an intermediate in certain alkene hydrogenations H 1Rh ^ %, I L = PhgP [i.e., (C6H5)3P] L ^ l NH L Cl H The oxidation state of rhodium in the complex is +3 [The two hydrogen atoms and the chlorine are each counted as - (hydride and chloride, respectively), and the charge on each of the triphenylphosphine ligands is zero Removing all the ligands would leave a Rh3+ 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=9 - = Each of the six ligands of the complex donates two electrons to the rhodium in the com­ plex, and, therefore, the total number of valence electrons of the rhodium is 18 The rhodium of Rh[(C6 H5 )3 P]3 H2Cl is coordinatively saturated total number of valence = ^ + electrons rhodium (2 ) = + 12 = 18 G.6 M echanistic Steps in the Reactions o f Som e Transition M e ta l Complexes Much of the chemistry of organic transition metal compounds becomes more understand­ able 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 repre­ sents a fundamental reaction type that is characteristic o f 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 we shall see how similar types of steps are involved in the Heck-Mizokori reaction 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 ig a n d D is s o c ia tio n - A s s o c ia tio n ( L ig a n d E x c h a n g e ) H 2C = i= C H2 H L ,''v L Rh L ^ l ^ H H h 2c = c h :Rh' Cl Cl L = PhgP [i.e., (C H ) P] G M e c h a n is tic S te p s in t h e R e a c tio n s o f S o m e T n s itio n M e t a l C o m p le x e s Two steps are actually involved In the first step, one of the triphenylphosphine lig­ ands dissociates This leads to a complex in which the rhodium has only 16 elec­ trons and is, therefore, coordinatively unsaturated H L H I '"^R h" L L Rh- L L H L H Cl Cl (18 e le ctro n s) (16 e le ctro n s) L _ Ph3P In the second step, the rhodium associates with the alkene to become coordinatively saturated again h 2c H L ^ = c h L R h— H H Rh H 2C = C H *Cl H Cl (16 e le ctro n s) (18 e le ctro n s) complex The complex between the rhodium and the alkene is called a p 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 Ph3 P:, CP, and so on In a p complex such as the one just given, there is also a donation of electrons from a populated orbital of the metal back to the vacant p * orbital of the alkene This kind of donation is called “back-bonding.” d An unsaturated ligand such as an alkene can undergo in ser­ tioninto a bond between the metal of a complex and a hydrogen or a carbon These reactions are reversible, and the reverse reaction is called d einsertion I n s e r tio n - D e in s e r tio n The following is an example of insertion-deinsertion H 2C = i= C H I^ L Cl H L Rh I I insertion :R h — , - Cl deinsertion CH3 L / c h , L H H (18 e le ctro n s) (16 e le ctro n s) 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 of the M— H unit to the alkene synaddition I> C = |= C ^ ^ ^ C— i / M— H M C \ H Coordinatively unsaturated metal com­ plexes can undergo oxidative addition of a variety of substrates in the following way.* O x id a tiv e A d d itio n - R e d u c tiv e E lim in a tio n A ;m : A— B oxidative addition ;m : B *Coordinatively saturated complexes also undergo oxidative addition G-12 G-13 S p e c ia l T o p ic G C a r b o n -C a r b o n B o n d -F o r m in g a n d O t h e r R e a c tio n s 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 Consider, as an example, the oxidative addition of hydrogen to the rhodium complex that follows (L = Ph3P) andinitsoxidationstate H L Rh oxidative addition H— H Rh reductive elimination Cl L Cl H (18 electrons) Rh is in +3 oxidation state (16 electrons) Rh is in +1 oxidation state Reductiveeliminationis the reverse of oxidative addition With this background, we are now in a position to examine the mechanisms of two applications of transi­ tion metal complexes in organic synthesis G.7 The Mechanism fo r a Hom ogeneous H ydrogenation: Wilkinson's Catalyst The catalytic hydrogenations that we have examined in prior chapters have been hetero­ geneous 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 com­ plex such as Rh[(C6H5)3 P]3Cl (Wilkinson’s catalyst), hydrogenation takes place , i.e., in solution When Wilkinson’s catalyst is used to carry out the hydrogenation of an alkene, the fol­ lowing steps take place (L = Ph3P) inasin­ glephase Step1 H L La ' Rhr^ H— H -> Cl l 16 valence electrons Oxidative addition Rh Cl H H 18 valence electrons Step H L ///„,, I Ä*\\L ^Rh" L ^ l ^ Cl H 18 valence electrons H L Rh— H L Cl 16 valence electrons L Ligand dissociation G T h e M e c h a n is m f o r a H o m o g e n e o u s H y d r o g e n a tio n : W ilk in s o n 's C a ta ly s t G-14 Step H2 C =i=C H H L Rh— H + H,C= =c h , H L ig an d a s s o c ia tio n Rh L ^ l X Cl H Cl 16 v a le n c e e le c tro n s 18 v a le n c e e le ctro n s Step4 h 2c = = c h L L H :Rh H Cl / H3 Rh— Ch ^ In s e rtio n L ^ C l H 18 v a le n ce e le c tro n s 16 v a le n c e e le ctro n s Step5 Cl CH3 , , :Rh — CH2 Rh— Cl H3C CH , H 16 v a le n c e e le c tro n s R e d u ctive e lim in a tio n 14 v a le n c e e le ctro n s Step6 H , , Rh Cl H2 , O x id a tiv e a d d itio n Rh— H , Cl 14 v a le n c e e le c tro n s 16 v a le n c e e le ctro n s (C ycle re p e a ts fro m ste p 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 of hydrogen to the alkene The following example (with D2 in place of H2) illustrates this aspect synaddition H H D2 EtO2 C^ ^C ü2Et A c/s-alken e (d ie th y l m aleate) Rh(Ph3P)3a H H EtO2 C ^ _^ *C O 2Et D D A m eso c o m p o u n d cis- What product (or products) would be formed if the trans-alkene corresponding to the alkene (see the previous reaction) had been hydrogenated with D2 and Wilkinson’s catalyst? ReviewProblemG.11 G-15 S p e c ia l T o p ic G C a r b o n -C a r b o n B o n d -F o r m in g a n d O t h e r R e a c tio n s THE CHEMISTRY OF H o m o g e n e o u s A s y m m e t r i c C a t a l y t i c H y d r o g e n a t i o n : E x a m p l e s I n v o lv in g l- D O P A , ( S ) - N a p r o x e n , a n d A s p a r t a m e 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 earn­ ing 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 University) (The other half of the 2001 prize was awarded to K B Sharpless for asymmetric oxidation reactions See Chapter ) 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 devel­ oped by Knowles and co-workers at Monsanto Corporation for synthesis of l-DOPA, a compound used in the treatment of Parkinson's disease: A s ym m etric Synthesis o f l-D O PA H CO _COOH NHAc H CO COOH H2 (100%) [(Rh(R,R)-DIPAMP)COD]+BF4 ~(cat.) AcO HO COOH H3 O+ H NHAc AcO H NH, HO (100 %yield, 95% ee [enantiomeric excess]) O L-DOPA II (R,R)-DIPAMP (Chiral ligand for rhodium) COD = 1,5-Cyclooctadiene 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) A s ym m etric Synthesis o f (S)-Naproxen CH2 m nu COOH H + (S)-BINAP-Ru(OCOCH3 ) (0.5 mol%) Ho — MeOH H3CO CH3 COOH ' H3CO (S)-Naproxen (an anti-inflammatory agent) (92%yield, 97% ee) P(Ph ) (Ph)2P P(Ph ) (Ph)2P (R)-BINAP (S)-BINAP (S)-BINAP and (R)-BINAP are chiral atropisomers (see Section 5.18) G-16 G T h e M e c h a n is m f o r an E x a m p le o f C ro s s -C o u p lin g : T h e H e c k -M iz o k o r i R e a c tio n Catalysts like these are important for asymmetric chem­ ical 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 A s ym m etric Synthesis o f A sp artam e COOH NHAc (1 ) (KH)-PNNP-Rh(I) (cat.), H2 (83% ee) (catalytic asymmetric hydrogenation) (2) MeOH, HA Ph H NH (S)-phenylalanine methyl ester (97% ee after recrystallization) Ph > - N ' C >C (Ph)2P: CO O CH3 N— =P(Ph)2 CH, (R,R)-PNNP (Chiral ligand for rhodium) H / / z HOOC COOH H2 N H (S )-a s p a rtic acid NH COOH COOCH 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 A general mechanism fo r th e W ilkinson catalytic h yd rogenation m e th o d , adapted w ith perm ission o f John W ile y & Sons, Inc from N oyori, Asymmetric Catalysis in Organic Synthesis, p 17 C o p y rig h t 1994 (Cft)3P > Cl[(C6H5)3P]2Rh Cl[(C6H5)3P]2RhH H G.8 The Mechanism fo r an Exam ple o f Cross-Coupling: The H e ck -M izo ko ri 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 cer­ tain 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 G-17 S p e c ia l T o p ic G C a r b o n -C a r b o n B o n d -F o r m in g a n d O t h e r R e a c tio n s A MECHANISM FOR THE REACTION T h e H e c k - M i z o k o r i R e a c t i o n U s in g a n A ry l H a l i d e S u b s t r a t e G E N E R A L R E A C T IO N Ar— X + ^ R B Pd,cala'ysl > Base (an amine) ^ M E C H A N IS M Pd(L)4 - 21- (L = ligand, e.g., Ph3 P) Ar— X base — HX Pd(L)2 Coordinatively unsaturated catalyst Reductive elimination (regenerates catalyst) base Oxidative addition (incorporates halide reactant) H— Pd(L)2— X Ar— Pd(L)2— X f Ar R Alkene insertion (incorporates alkenyl reactant, forms new C—C bond) ,2 -syn elimination (forms the product as a trans alkene) Ar Ar H H R —C bond rotation H h G.9 Vitam in B ^ : A Transition M e ta l 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 vit­ amin B 12 The complete three-dimensional structure of vitamin B 12 [Fig G.2(a)] was elu­ cidated 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 co­ workers took part in the project Vitamin B 12 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 +3 oxidation state The core of the vitamin B 12 molecule is a [Fig G.2( )] with various attached side groups The corrin ring consists of four pyrrole b corrinring G-18 G V ita m in B 12: A T n s itio n M e t a l B io m o le c u le subunits, the nitrogen of each of which is coordinated to the central cobalt The sixth lig­ and [(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 B 12 can be reduced to a + or a +1 oxidation state When the cobalt is in the +1 oxidation state, vitamin B 12 (called B 12s) becomes one of the most pow­ erful nucleophiles known, being more nucleophilic than methanol by a factor of 14 Acting as a nucleophile, vitamin B 12s 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 OH OH (c) (a) Figure G.2 (a) The structu re o f vitam in B1 In th e com m ercial fo rm o f th e vitam in (cyanocobalamin), R = CN (b) The corrin ring system (c) In th e b io lo g ica lly active fo rm o f th e vitam in (5'-deoxyadenosylcobalam in), th e ' carbon atom o f '-d e oxyadenosine is coord in a te d to th e cobalt atom For th e structure o f adenine, see Section 25.2 fw iL E ’T 'to See Special Topic H in WileyPLUS S e e Table 2.7 for a Table o f IR frequencies Frequency (cm 40 0 3600 3200 2800 2400 2000 1800 v- Alkane Alkene Alkyne Aromatic 1° alcohol 2° alcohol 3° alcohol Phenol Ether Ester Carboxyllc acid Ketone Aldehyde Amide 1° amine 2° amine 3° amine Alkyl chloride Alkyl bromide N itrile 1600 1400 800 1000 5= ■H 5= -H =C ertor •-H vO- free 600 sk vC= =C 1200 H i>0- H H sociated broad '-H C= vO= -H XI- 2.5 N-H N vN-H r 3.0 3.5 v= déisr 'I I1 'I I I 4.0 I vC-B W -W-id I ll'l'i I I I I (Microns) T y p ic a l IR a b s o r p t io n fr e q u e n c ie s fo r c o m m o n fu n c tio n a l g r o u p s 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 I I I 10 I I 11 12 13 14 16 2 0 1S 0 5c (p p m ) A p p r o x im a t e C a r b o n - C h e m ic a l S h ifts r TABLE ^ Type of Carbon Atom Chemical Shift (S, ppm) 1° Alkyl, RCH3 2° Alkyl, RCH2R 3° Alkyl, RCHR2 G-4G 1G-5G 15-5G i Alkyl halide or amine, — C—X I X= Cl, Br, or N — 1G-65 Alcohol or ether, C O 5G-9G Alkyne, ỗ = 6G-9G \ Alkene, Aryl, Nitrile, _ C— 1GG-17G GG-17G C G-1 SG C= N O Amide, C 15G-18G N O Carboxylic acid or ester, C O 16G-1S5 O Aldehyde or ketone, C 182-215 A p p r o x im a te Type of Proton Chemical Shift (5, ppm) 1° Alkyl, RCH3 2° Alkyl, RCH2R 3° Alkyl, R3 CH Allylic, r 2c = C— CH3 I R Ketone, RCCH3 II O P r o to n C h e m ic a l S h ifts - 1.2-1.5 1.4—1 1.6-1.9 - Benzylic, ArCH3 Acetylenic, RC # CH Alkyl iodide, RCH2 I Ether, ROCH2R Alcohol, HOCH2R 2.2-2.5 2.5-S.1 S.1-S.S 5.5-S.9 3.3-4.0 Type of Proton Chemical Shift (S, ppm) Alkyl bromide, RC^Br Alkyl chloride, RCH2 CI Vinylic, R2 C " CH2 Vinylic, R2 C = C H I R S.4-S.6 5.6 -S 4.6-5.0 5.2-5.7 Aromatic, ArH Aldehyde, RCH II O 6.0-8.5 9.5-10.5 Alcohol hydroxyl, ROH Amino, R9 NH2 Phenolic, ArOH Carboxylic, RCOH II O 0.5-6.0 1.0-5.0a 4.5-7.7a - Sa aThe chemical shifts o f these protons vary in d iffe re n t solvents and w ith te m p e tu re and concentration a ... Molecular Structure 1 We Are Stardust A to m ic Structure The Structural Theory o f Organic Chemistry Chemical Bonds: The O cte t Rule H ow to W rite Lewis Structures Exceptions to the O cte t Rule... electrons to form a single bond betw een the hydrogen atom and the carbon atom (see below), and w e use three pairs to form a triple b o n d betw een the carbon atom and the nitrogen atom This... pair to jo in the carbon and nitrogen C— N We use three pairs to form single bonds betw een the carbon and three hydrogen atom s We use tw o pairs to form single bonds betw een the nitrogen atom