Advanced Organic Chemistry

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1 Reinhard Bruckner Advanced Organic Chemistry Reaction Mechanisms An Imprint of Elsevier San Diego San Francisco New York Boston London Sydney Tokyo

2 -- Foreword Preface to the English Edition Preface to the German Edition Acknowledgments xv xvii xix xxiii 1 Radical SUbstitution Reactions at the Saturated C Atom Bonding and Preferred Geometries in C Radicals, Carbenium Ions and Carbanions Preferred Geometries Bonding Stability of Radicals Reactive Radicals Unreactive Radicals Relative Rates of Analogous Radical Reactions The Bell-Evans-Polanyi Principle The Hammond Postulate Radical Substitution Reactions: Chain Reactions Radical Initiators Radical Chemistry of Alkylmercury(II) Hydrides Radical Halogenation of Hydrocarbons Simple and Multiple Chlorinations Regioselectivity of Radical Chlorinations Regioselectivity of Radical Brominations Compared to Chlorinations Rate Law for Radical Halogenations; Reactivity/Selectivity Principle Chemoselectivity of Radical Brominations Autoxidations Defunctionalizations via Radical Substitution Reactions Simple Defunctionalizations Defunctionalization via 5-Hexenyl Radicals: Competing Cyclopentane Formation Nucleophilic Substitution Reactions at the Saturated C Atom Nucleophiles and Electrophiles; Leaving Groups Good and Poor Nuc1eophiles

3 vi 2.3 Leaving Groups and the Quality of Leaving Groups SN2 Reactions: Kinetic and Stereochemical Analysis- Substituent Effects on Reactivity Energy Profile and Rate Law for SN2 Reactions: Reaction Order Stereochemistry of SN2 Substitutions A Refined Transition State Model for the SN2 Reaction; Crossover Experiment and Endocyclic Restriction Test Substituent Effects on SN2 Reactivity SN 1 Reactions: Kinetic and Stereochemical Analysis; Substituent Effects on Reactivity Energy Profile and Rate Law of SNl Reactions; Steady State Approximation Stereochemistry of SNl Reactions; Ion Pairs Solvent Effects on SNl Reactivity Substituent Effects on SNl Reactivity When Do SN Reactions at Saturated C Atoms Take Place According to the SNl Mechanism and When Do They Take Place According to the SN2 Mechanism? Unimolecular SN Reactions That Do Not Take Place via Simple Carbenium Ion Intermediates: Neighboring Group Participation Conditions for and Features of SN Reactions with Neighboring Group Participation Increased Rate through Neighboring Group Participation Stereoselectivity through Neighboring Group Participation Preparatively Useful SN2 Reactions: Alkylations Additions to the Olefinic C=C Double Bond The Concept of cis and trans Addition Vocabulary of Stereochemistry and Stereoselective Synthesis I Isomerism, Diastereomers/Enantiomers, Chirality Chemoselectivity, Diastereoselectivity/Enantioselectivity, Stereospecificity/Stereoconvergence Additions That Take Place Diastereoselectivity as cis Additions A Cycloaddition Forming Three-Membered Rings Additions to C=C Double Bonds That Are Related to Cycloadditions and Form Three-Membered Rings, Too eis-hydration of Olefins via the Hydroboration/Oxidation/Hydrolysis Reaction Sequence Heterogeneously Catalyzed Hydrogenation Enantioselective cis Additions to C=C Double Bonds Vocabulary of Stereochemistry and Stereoselective Synthesis II: Topicity, Asymmetric Synthesis 106

4 vii Asymmetric Hydroboration of Achiral Olefins Thought Experiment I on the Hydroboration of Chiral Olefins with Chiral Boranes: Mutual Kinetic Resolution Thought Experiments II and III on the Hydroboration of Chiral Olefins with Chiral Boranes: Reagent Control of Diastereoselectivity, Matched/Mismatched Pairs, Double Stereodifferentiation Thought Experiment IV on the Hydroboration of Chiral Olefins with Chiral Dialkylboranes: Kinetic Resolution Catalytic Asymmetric Synthesis: Sharpless Oxidations of Allyl Alcohols 113 Additions That Take Place Diastereoselectively as trans Additions (Additions via Onium Intermediates) Addition of Bromine The Formation of Halohydrins; Halolactonization and Haloetherification Solvomercuration of Olefins: Hydration of C=C Double Bonds through Subsequent Reduction Additions That Take Place or Can Take Place without Stereocontrol Depending on the Mechanism Additions via Carbenium Ion Intermediates Additions via "Carbanion" Intermediates {3-EIiminations Concepts of Elimination Reactions The Concept of a,{3- and 1,n-Elimination The Terms syn- and anti-elimination When Are Stereogenic syn- and anti-selective Eliminations Stereoselective? Formation of Regioisomeric Olefins by {3-Elimination: Saytzeff and Hofmann Product(s) The Synthetic Value of Het 1 /Het 2 in Comparison to H/Het Eliminations {3-Eliminations of H/Het via Cyclic Transition States {3-Eliminations of H/Het via Acyclic Transition States: The Mechanistic Alternatives E2 Eliminations of H/Het and the E2/S N 2 Competition Substrate Effects on the E2/S N 2 Competition Base Effects on the E2/S N 2 Competition A Stereoelectronic Effect on the E2/S N 2 Competition The Regioselectivity of E2 Eliminations One-Pot Conversion of an Alcohol to an Olefin

5 viii El Elimination of H/Het from Rtert-X and the E1/S N l Competition Energy Profiles and Rate Laws for El Eliminations The Regioselectivity of El Eliminations El Eliminations in Protecting Group Chemistry E1cb Eliminations Unimolecular E1cb Eliminations: Energy Profile and Rate Law Nonunimolecular E1cb Eliminations: Energy Profile and Rate Law Elcb Eliminations in Protecting Group Chemistry 158 {3-Eliminations of Het l /Het Fragmentation of {3-Heterosubstituted Organometallic Compounds Julia-Lythgoe Synthesis of trans-olefins Peterson Olefination Oxaphosphetane Fragmentation, Last Step of Wittig and Horner-Wadsworth-Emmons Reactions Corey-Winter Reaction Substitution Reactions on Aromatic Compounds Electrophilic Aromatic Substitutions via Wheland Complexes ("Ar-SE Reactions") Mechanism: Substitution of H+ vs ipso-substitution Thermodynamic Aspects of Ar-SE Reactions Kinetic Aspects of Ar-SE Reactions: Reactivity and Regioselectivity in Reactions of Electrophiles with Substituted Benzenes Ar-SE Reactions via Wheland Complexes: Individual Reactions Ar-Hal Bond Formation by Ar-SE Reaction Ar-S03H Bond Formation by Ar-SE Reaction Ar-N0 2 Bond Formation by Ar-SE Reaction Ar-N=N Bond Formation by Ar-SE Reaction Ar-Alkyl Bond Formations by Ar-SE Reaction Ar-C(OH) Bond Formation by Ar-SE Reactions and Associated Secondary Reactions Ar-C(=O) Bond Formation by Ar-SE Reaction Ar-C(=O)H Bond Formation through Ar-SE Reaction Electrophilic Substitution Reactions on Metallated Aromatic Compounds Electrophilic Substitution Reactions of ortho-lithiated Benzene and Naphthalene Derivatives

6 ix Electrophilic Substitution Reactions in Aryl Grignard and Aryllithium Compounds That Are Accessible from Aryl Halides Electrophilic Substitutions on Arylboronic Acids and Arylboronic Esters Nucleophilic Substitution Reactions in Aryldiazonium Salts Nucleophilic Substitution Reactions via Meisenheimer Complexes Mechanism Examples of Reactions of Preparative Interest A Special Mechanistic Case: Reactions of Aryl Sulfonates with NaOH/KOH in a Melt Nucleophilic Aromatic Substitution via Arynes, cine Substitution '2lt Nucleophilic Substitution Reactions on the Carboxyl Carbon 221 (Except through Enolates) 6.1 C=O-Containing Substrates and Their Reactions with Nucleophiles Mechanisms, Rate Laws, and Rate of Nucleophilic Substitution Reactions at the Carboxyl Carbon Mechanism and Rate Laws of SN Reactions on the Carboxyl Carbon SN Reactions on the Carboxyl Carbon: The Influence of Resonance Stabilization of the Attacked C=O Double Bond on the Reactivity of the Acylating Agent SN Reactions on the Carboxyl Carbon: The Influence of the Stabilization of the Tetrahedral Intermediate on the Reactivity Activation of Carboxylic Acids and of Carboxylic Acid Derivatives Activation of Carboxylic Acids and Carboxylic Acid Derivatives in Equilibrium Reactions Conversion of Carboxylic Acids into Isolable Acylating Agents Complete in Situ Activation of Carboxylic Acids Selected SN Reactions of Heteroatom Nucleophiles on the Carboxyl Carbon Hydrolysis of Esters Lactone Formation from Hydroxycarboxylic Acids Forming Peptide Bonds SN Reactions of Heteroatom Nucleophiles with Carbonic Acid Derivatives SN Reactions of Hydride Donors, Organometallics, and Heteroatom-Stabilized "Carbanions" on the Carboxyl Carbon When Do Pure Acylations Succeed, and When Are Alcohols Produced? 260

7 x Acylation of Hydride Donors: Reduction of Carboxylic Acid Derivatives to Aldehydes Acylation of Organometallic Compounds and Heteroatom-Stabilized "Carbanions": Synthesis of Ketones Additions of Heteroatom NucIeophiIes to Heterocumulenes. Additions of Heteroatom NucIeophiles to Carbonyl Compounds and Follow-up Reactions Additions of Heteroatom Nucleophiles to Heterocumulenes Mechanism of the Addition of Heteroatom Nucleophiles to Heterocumulenes Examples of the Addition of Heteroatom Nucleophiles to Heterocumulenes Additions of Heteroatom Nucleophiles to Carbonyl Compounds On the Equilibrium Position of Addition Reactions of Heteroatom Nucleophiles to Carbonyl Compounds Hemiacetal Formation Oligomerization/Polymerization of Carbonyl Compounds Addition of Heteroatom Nucleophiles to Carbonyl Compounds in Combination with Subsequent SNl Reactions: Acetalizations Mechanism Formation of O,O-Acetals Formation of S:S-Acetals Formation of N,N-Acetals Addition of Nitrogen Nucleophiles to Carbonyl Compounds in Combination with Subsequent El Eliminations: Condensation Reactions of Nitrogen Nucleophiles with Carbonyl Compounds Addition of Hydride Donors and Organometallic Compounds to Carbonyl Compounds Suitable Hydride Donors and Organometallic Compounds and a Survey of the Structure of Organometallic Compounds Chemoselectivity of the Addition of Hydride Donors to Carbonyl Compounds Diastereoselectivity of the Addition of Hydride Donors to Carbonyl Compounds Diastereoselectivity of the Addition of Hydride Donors to Cyclic Ketones

8 r Diastereoselectivity of the Addition of Hydride Donors to a-chiral Acyclic Carbonyl Compounds Diastereoselectivity of theaddition of Hydride Donors to,b-chiral Acyclic Carbonyl Compounds Enantioselective Addition of Hydride Donors to Carbonyl Compounds Addition of Organometallic Compounds to Carbonyl Compounds Simple Addition Reactions of Organometallic Compounds Enantioselective Addition of Organozinc Compounds to Carbonyl Compounds: Chiral Amplification Diastereoselective Addition of Organometallic Compounds to Carbonyl Compounds l,4-additions of Organometallic Compounds to a,,b-unsaturated Ketones xi 9 Reaction of Ylides with Saturated or a,,b.unsaturated Carbonyl Compounds YlideslYlenes Reactions of S Ylides with Saturated Carbonyl Compounds or with Michael Acceptors: Three-Membered Ring Formation Mechanism for the Formation of Cyclopropanes and Epoxides Stereoselectivity and Regioselectivity of Three-Membered Ring Formation from S Ylides Condensation of P Ylides with Carbonyl Compounds: Wittig Reaction Nomenclature and Preparation of P Ylides Mechanism of the Wittig Reaction Horner-Wadsworth-Emmons Reaction Horner-Wadsworth-Emmons Reactions with Achiral Substrates Horner-Wadsworth-Emmons Reactions between Chiral Substrates: A Potpourri of Stereochemical Special ties Chemistry of the Alkaline Earth Metal Enolates Basic Considerations Notation and Structure of Enolates Preparation of Enolates by Deprotonation Other Methods for the Generation of Enolates

9 xii Survey of Reactions between Electrophiles and Enolates and the Issue of Ambidoselectivity Alkylation of Quantitatively Prepared Enolates and Aza-Enolates; Chain-Elongating Syntheses of Carbonyl Compounds and Carboxylic Acid Derivatives Chain-Elongating Syntheses of Carbonyl Compounds Chain-Elongating Syntheses of Carboxylic Acid Derivatives Hydroxyalkylation of Enolates with Carbonyl Compounds ("Aldol Addition"): Synthesis of,b-hydroxyketones and,b-hydroxyesters Driving Force of Aldol Additions and Survey of Reaction Products Stereocontrol Condensation of Enolates with Carbonyl Compounds: Synthesis of Michael Acceptors Aldol Condensations Knoevenagel Reaction A Knoevenagel Reaction "with a Twist" Acylation of Enolates Acylation of Ester Enolates Acylation of Ketone Enolates Michael Additions of Enolates Simple Michael Additions Tandem Reactions Consisting of Michael Addition and Consecutive Reactions Rearrangements Nomenclature of Sigmatropic Shifts Molecular Origins for the Occurrence of [1,2]-Rearrangements [1,2]-Rearrangements in Species with a Valence Electron Sextet [l,l]-rearrangements of Carbenium Ions [1.2]-Rearrangements in Carbenes or Carbenoids [1,2 J-Rearrangements without the Occurrence of a Sextet Intermediate Hydroperoxide Rearrangements Baeyer-Villiger Rearrangements Oxidation of Organoborane Compounds Beckmann Rearrangement Curtius Rearrangement Claisen Rearrangement Classical Claisen Rearrangement Claisen-Ireland Rearrangements

10 ,. 12 Thermal Cycloadditions 477 xiii 12.1 Driving Force and Feasibility of One-Step [2 + 4]- and [2 + 2]-Cycloadditions Transition State Structures of Selected One-Step [2 + 4]- and [2 + 2]-Cycloadditions Stereostructure of the Transition States of One-Step [2 + 4]- Cycloadditions Frontier Orbital Interactions in the Transition States of One-Step [2 + 4]-Cycloadditions Frontier Orbital Interactions in the Transition States of the Unknown One-Step Cycloadditions of Alkenes or Alkynes to Alkenes Frontier Orbital Interactions in the Transition State of One-Step [2 + 2]-Cycloadditions Involving Ketenes Diels-Alder Reactions Stereoselectivity of Diels-Alder Reaetions Substituent Effects on Reaction Rates of Diels-Alder Reactions Orientation Selectivity of Diels-Alder Reactions Simple Diastereoselectivity of Diels-Alder Reactions [2 + 2]-CycIoadditions with Dichloroketene ,3-Dipolar Cycloadditions ,3-Dipoles Frontier Orbital Interactions in the Transition States of One-Step 1,3-Dipolar Cycloadditions; Sustmann Classification ,3-Dipolar Cycloadditions of Diazoalkanes ,3-Dipolar Cycloadditions of Nitrile Oxides ,3-Dipolar Cycloadditions and 1,3-Dipolar Cycloreversions as Steps in the Ozonolysis of Alkenes A Tricky Reaction of Inorganic Azide Transition Metal-Mediated Alkenylations, Arylations, and Alkynylations Alkenylation and Arylation of Copper-Bound Organyl Groups Alkenylation and Arylation of Grignard Compounds Palladium-Catalyzed Alkenylation and Arylation of Organometallic Compounds A Prelude: Preparation of Haloalkenes and Alkenylboronic Acid Derivatives, Important Building Blocks for Palladium-Mediated C,C Couplings 526

11 xiv Alkenylation and Arylation of Boron-Bound Groups Alkenylation and Arylation of Zinc-Bound Functionalized Groups Alkenylation and Arylation of Copper Acetylides Alkynylation of Copper Acetylides Heck Reactions Oxidations and Reductions Oxidation States of Organic Chemical Compounds, Oxidation Numbers in Organic Chemical Compounds, and Organic Chemical Redox Reactions Cross- to Redox Reactions Already Discussed in Chapters 1-13 Oxidations Oxidations in the Series Alcohol -> Aldehyde -> Carboxylic Acid Oxidative Cleavages Oxidations at Heteroatoms Reductions Reductions R sp3 -X -> R sp3 -H or R sp3 -X -> R sp3-m One-Electron Reductions of Carbonyl Compounds and Esters; Reductive Coupling Reductions of Carboxylic Acid Derivatives to Alcohols or Amines Reductions of Carboxylic Acid Derivatives to Aldehydes Reductions of Carbonyl Compounds to Alcohols Reductions of Carbonyl Compounds to Hydrocarbons Hydrogenation of Alkenes Reductions of Aromatic Compounds and Alkynes Index 613