Advanced Organic Synthesis (Monson-1971)

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<p>Advanced Organic SynthesisMETHODS AND TECHNIQUES</p> <p>RICHARD S. MONSONDEPARTMENT OF CHEMISTRY CALIFORNIA STATE COLLEGE, HAYWARD HAYWARD, CALIFORNIA</p> <p>ACADEMIC PRESS New York and London</p> <p>COPYRIGHT 1971, BY ACADEMIC PRESS, INC. ALL RIGHTS RESERVED NO PART OF THIS BOOK MAY BE REPRODUCED IN ANY FORN BY PHOTOSTAT, MICROFILM, RETRIEVAL SYSTEM, OR ANY OTHER MEANS, WITHOUT WRITTEN PERMISSION FROM THE PUBLISHERS.</p> <p>ACADEMIC PRESS, INC.</p> <p>Ill Fifth Avenue, New York, New York 10003</p> <p>United Kingdom Edition published by ACADEMIC PRESS, INC. (LONDON) LTD.Berkeley Square House, London WlX 6BA</p> <p>LIBRARY OF CONGRESS CATALOG CARD NUMBER: 75-165531</p> <p>PRINTED IN THE UNITED STATES OF AMERICA</p> <p>ContentsPreface xi</p> <p>I. FUNCTIONAL GROUP MODIFICATIONS 1. Chemical OxidationsI. II. III. IV. V. VI. VII. VIII. IX. X. XI. Chromium Trioxide Oxidation Periodate-Permanganate Cleavage of Olefins Free Radical Oxidation of an Allylic Position Epoxidation of Olefins Baeyer-Villiger Oxidation of Ketones Lead Tetraacetate Oxidation of Cycloalkanols Photolytic Conversion of Cyclohexane to Cyclohexanone Oxime Oxidation of Ethers to Esters Partial Oxidation of an Aliphatic Side Chain Bisdecarboxylation with Lead Tetraacetate Oxidation with Selenium Dioxide References 3 5 7 8 9 11 11 12 13 14 15 16</p> <p>2.I. II. III. IV.</p> <p>Hydride and Related ReductionsReduction by Lithium Aluminum Hydride Mixed Hydride Reduction Reduction with Iridium-Containing Catalysts Reduction of Conjugated Alkenes with Chromium (H) Sulfate References 18 20 22 23 24</p> <p>3. Dissolving Metal ReductionsI. II. III. IV. V. Reduction by Lithium-Amine Reduction by Lithium-Ethylenediamine Reduction of a,/MJnsaturated Ketones by Lithium-Ammonia Reduction of a,/9-Unsaturated Ketones in Hexamethylphosphoric Triamide Reduction of an a,/?-Unsaturated y-Diketone with Zinc References 25 26 27 28 29 30</p> <p>. . . .</p> <p>VI</p> <p>CONTENTS</p> <p>4. HydroborationI. Hydroboration of Olefins as a Route to Alcohols II. Selective Hydroborations Using Bis(3-methyl-2-butyl)borane (BMB) III. Purification of a Mixture of J 9 - 10 - and J1(9)-Octalins References 32 35 37 38</p> <p>5. Catalytic HydrogenationI. II. III. IV. V. Hydrogenation over Platinum Catalyst Low-Pressure Hydrogenation of Phenols over Rhodium Catalysts c/j-4-Hydroxycyclohexanecarboxylic Acid from /?-Hydroxybenzoic Acid 3-Isoquinuclidone from/7-Aminobenzoic Acid Homogeneous Catalytic Hydrogenation References 39 40 41 42 43 44</p> <p>6. The Introduction of HalogenI. II. III. IV. V. Halides from Alcohols by TriphenylphosphineCarbon Tetrahalide Halides from Alcohols and Phenols by Triphenylphosphine Dihalide Allylic and Benzylic Bromination with W-Bromosuccinimide a-Bromination of Ketones and Dehydrobromination Stereospecific Synthesis of /ra/w-4-Halocyclohexanols References 45 46 48 49 51 52</p> <p>7. Miscellaneous Elimination, Substitution, and Addition ReactionsI. II. III. IV. V. VI. VII. VIII. IX. X. XI. XII. Methylenecyclohexane by Pyrolysis of an Amine Oxide The Wolff-Kishner Reduction Dehydration of 2-Decalol Boron Trifluoride Catalyzed Hydrolysis of Nitriles Bridged Sulfides by Addition of Sulfur Dichloride to Dienes Methylation by Diazomethane Oxymercuration: A Convenient Route to Markovnikov Hydration of Olefins . Esterification of Tertiary Alcohols Ketalization Half-EsterificationofaDiol Substitution on Ferrocene Demethylation of Aryl Methyl Ethers by Boron Tribromide References 54 55 56 56 57 58 60 62 63 64 65 66 67</p> <p>. . .</p> <p>CONTENTS</p> <p>VlI</p> <p>II.</p> <p>SKELETAL MODIFICATIONS</p> <p>8. The Diels-Alder ReactionI. II. III. IV. V. 3,6-Diphenyl-4,5-cyclohexenedicarboxylic Anhydride ........... Reactions with Butadiene .................. Catalysis by Aluminum Chloride ................ Generation of Dienes from Diones ................ Reactions with Cyclopentadiene ................. References ....................... 71 72 74 75 77 79</p> <p>9.</p> <p>Enamines as IntermediatesPreparation of the Morpholine Enamine of Cyclohexanone ......... Acylation of Enamines ................... Enamines as Michael Addition Reagents .............. Reactions of Enamines with j3-Propiolactone ............. Reactions of Enamines with Acrolein ............... References ....................... 80 81 82 83 84 86</p> <p>I. II. III. IV. V.</p> <p>10. Enolate Ions as IntermediatesI. II. III. IV. V. VI. VII. Ketones as Enolates: Car bethoxylation of Cyclic Ketones Esters as Enolates: 1,4-Cyclohexanedione and Meerwein's Ester Methylsulfinyl Carbanion as a Route to Methyl Ketones Cyclization with Diethyl Malonate ................ Carboxylations with Magnesium Methyl Carbonate (MMC) Alkylation of j3-Ketoesters .................. The Robinson Annelation Reaction ................ References ....................... ......... ....... .......... ......... 87 90 92 96 97 99 101 103</p> <p>1 1 . The Wittig ReactionI. II. III. IV. V. Benzyl-Containing Ylides .................. Alkyl Ylides Requiring -Butyl Lithium .............. Methylsulfinyl Carbanion in the Generation of Ylides .......... The Wittig Reaction Catalyzed by Ethylene Oxide ........... Cyclopropylidene Derivatives via the Wittig Reaction .......... References ....................... 104 105 106 107 108 110</p> <p>1 2 . Reactions of Trialkylbor anesI. II. III. IV. Trialkylcarbinols from Trialkylboranes and Carbon Monoxide ........ Dialkylketones from Trialkylboranes and Carbon Monoxide-Water ...... The Reaction of Trialkylboranes with Methyl Vinyl Ketone and Acrolein ..... The Reaction of Trialkylboranes with Ethyl Bromoacetate ......... References ....................... Ill 112 114 115 115</p> <p>Viil</p> <p>CONTENTS</p> <p>13. Carbenes as IntermediatesI. Carbene Addition by the Zinc-Copper Couple II. Dibromocarbenes III. Dihalocarbenes from Phenyl(trihalomethyl)mercury Compounds References 116 117 119 120</p> <p>14.</p> <p>Ethynylation 121 123 124 125</p> <p>I. Generation of Sodium Acetylide in Liquid Ammonia II. The Generation of Sodium Acetylide in Tetrahydrofuran III. The Generation of Sodium Acetylide via Dimsylsodium References</p> <p>15. Structural IsomerizationsI. II. III. IV. V. VI. VII. Acid Catalyzed Rearrangement of Saturated Hydrocarbons Photolytic Ring Contraction Isomerization of 1-Ethynylcylohexanol: Three Methods Photolytic Isomerization of 1,5-Cyclooctadiene Oxidative Rearrangement of /3-Diketones Base Catalyzed Rearrangement of 4-Benzoyloxycyclohexanone Allenes from 1,1-Dihalocyclopropanes by Methyllithium References 126 127 129 130 130 131 132 133</p> <p>16. Elimination, Substitution, and Addition Reactions Resulting in Carbon-Carbon Bond FormationI. II. III. IV. V. VI. VII. VIII. IX. X. Xl. XII. Carboxylation of Carbonium Ions Paracyclophane via a 1,6-Hofmann Elimination Diphenylcyclopropenone from Commercial Dibenzyl Ketone Phenylcyclopropane from Cinnamaldehyde Conversion of Alkyl Chlorides to Nitriles in DMSO Photolytic Addition of Formamide to Olefins Intermolecular Dehydrohalogenation Ring Enlargement with Diazomethane Conjugate Addition of Grignard Reagents Dimethyloxosulfonium Methylide in Methylene Insertions Acylation of a Cycloalkane: Remote Functionalization The Modified Hunsdiecker Reaction References 134 136 137 139 140 141 142 143 144 145 147 149 150</p> <p>CONTENTS</p> <p>IX</p> <p>17. Miscellaneous PreparationsI. II. III. IV. Derivatives of Adamantane Percarboxylic Acids Diazomethane Trichloroisocyanuric Acid References 151 153 155 156 157</p> <p>Appendix 1. Examples of Multistep Syntheses Appendix 2. Sources of Organic Reagents Appendix 3. Introduction to the Techniques of SynthesisI. The Reaction II. TheWorkup III. Purification of the Product References Subject Index</p> <p>158 161</p> <p>166 175 178 188 189</p> <p>PrefaceThe developments in organic synthesis in recent years have been as dramatic as any that have occurred in laboratory sciences. One need only mention a few terms to understand that chemical systems that did not exist twenty years ago have become as much a part of the repertoire of the synthetic organic chemist as borosilicate glassware. The list of such terms would include the Wittig reaction, enamines, carbenes, hydride reductions, the Birch reduction, hydroboration, and so on. Surprisingly, an introduction to the manipulations of these reaction techniques for the undergraduate or graduate student has failed to materialize, and it is often necessary for students interested in organic synthesis to approach modern synthetic reactions in a haphazard manner. The purpose of this text is to provide a survey, and systematic introduction to, the modern techniques of organic synthesis for the advanced undergraduate student or the beginning graduate student. An attempt has been made to acquaint the student with a variety of laboratory techniques as well as to introduce him to chemical reagents that require deftness and care in handling. Experiments have been drawn from the standard literature of organic synthesis including suitable modifications of several of the reliable and useful preparations that have appeared in "Organic Synthesis." Other examples have been drawn from the original literature. Where ever possible, the experiments have been adapted to the locker complement commonly found in the advanced synthesis course employing intermediate scale standard taper glassware. Special equipment for the performance of some of the syntheses would include low-pressure hydrogenation apparatus, ultraviolet lamps and reaction vessels, Dry Ice (cold finger) condensers, vacuum sublimation and distillation apparatus, and spectroscopic and chromatographic instruments. In general, an attempt has been made to employ as substrates materials that are available commercially at reasonable cost, although several of the experiments require precursor materials whose preparation is detailed in the text. Some of the reagents are hazardous to handle, but I believe that, under reasonable supervision, advanced students will be able to perform the experiments with safety. Introductory discussion of the scope and mechanism of each reaction has been kept to a minimum. Many excellent texts and reviews exist that provide thorough and accurate discussion of the more theoretical aspects of organic synthesis, and the student is referred to these sources and to the original literature frequently. Since it is the purpose</p> <p>XIl</p> <p>PREFACE</p> <p>of this volume to provide technical procedures, no useful purpose would be served in merely duplicating previously explicated theoretical material. The number of experiments that can be done satisfactorily in a one-semester course varies widely with the physical situation and the individual skills of the student. Therefore, no attempt is made to suggest a schedule. I recommend, however, that a common core of about five experiments be assigned. The remainder of the preparations can then be chosen by individual students as dictated by their interests as well as by the availability of chemicals and special equipment. The common experiments, representing frequently used and important techniques, might be chosen from Chapter 1, Sections I and IV; Chapter 2, Section I; Chapter 3, Section I; Chapter 4, Section I; Chapter 5, Section I; Chapter 6, Sections III and IV; Chapter 7, Sections II and VI; Chapter 8, Section II; Chapter 9, Sections I and II; Chapter 11, Sections I and III; or Chapter 13, Section II. Since many of the other experiments draw on the products of this suggested list, the possibility of multistep syntheses also presents itself, and several such sequences are outlined in Appendix 1. Also included, in Appendix 2, are the commercial suppliers of the chemicals required when these chemicals are not routinely available. Finally, a brief introduction to the techniques of synthesis is given in Appendix 3. Students with no synthetic experience beyond the first-year organic chemistry course are advised to skim through this section in order to acquaint themselves with some of the apparatus and terminology used in the description of synthetic procedures. RICHARD S. MONSON</p> <p>IFUNCTIONAL GROUP MODIFICATIONS</p> <p>1Chemical OxidationsThe controlled oxidation of selected functional groups or specific skeletal positions represents one of the most important aspects of synthetic organic chemistry. The application of a variety of inorganic oxidizing agents to organic substrates has broadened considerably the selectivity with which such oxidations may be carried out. The examples given here are typical of this rapidly expanding area of functional group modification. I. Chromium Trioxide Oxidation A variety of chromium (VI) oxidizing systems have been developed which allow for the oxidation of a wide range of sensitive compounds. One of the most widely used chromium (VI) reagents is the Jones reagent (7), whose use is detailed in the procedure. A related system employs acetic acid as the solvent, and an example of this reagent is also given. A recently discovered (2) oxidizing system promises to become very important for the oxidation of acid-sensitive compounds. The reagent is chromium trioxide-pyridine complex, which may be isolated after preparation and employed in nonaqueous solvents (usually methylene chloride). A remarkable feature of the reagent is that good yields of aldehydes are obtained by direct oxidation of primary alcohols. The preparation of the reagent and its use are given. A. OXIDATION OF A COMMERCIAL MIXTURE OF cis- AND trans-4-t-BuiYLCYCLOHEXANOLH2Cr2O7</p> <p>The chromic acid oxidizing reagent is prepared by dissolving 13.4 g of chromium trioxide in 25 ml of water. To this solution is added 12 ml of concentrated sulfuric acid. An additional minimum quantity of water is added if necessary to dissolve any precipitated salts. A solution of 15.6 g (0.1 mole) of 4-t-butylcyclohexanol in 250 ml of acetone is placed in a 500-ml three-necked flask fitted with a dropping funnel, a thermometer, and</p> <p>4</p> <p>1. CHEMICAL OXIDATIONS</p> <p>a mechanical stirrer. The stirred solution is cooled in a water bath to 20, and the chromic acid oxidizing solution is added from the dropping funnel slowly, so that the temperature of the reaction mixture does not exceed 35. The addition is continued until the orange color of the reagent persists for about 20 minutes. The excess oxidizing agent is destroyed by the addition of a small quantity of isopropyl alcohol (1 ml is usually sufficient). The mixture is decanted into an Erlenmeyer flask, the residual green salts are washed with two 15-ml portions of acetone, and the washings are added to the main acetone solution. Cautiously, sodium bicarbonate (approx. 13 g) is added to the solution with swirling until the pH of the reaction mixture is neutral. The suspension is filtered, and the residue is washed with 10-15 ml of acetone. The filtrate is transferred to a roundbottom flask and concentrated on a rotary evaporator under an aspirator while the flask temperature is maintained at about 50. The flask is cooled and the residue transferred to a separatory funnel. (If solidification occurs, the residue may be dissolved in ether to effect...</p>