N-Heterocyclic Carbenes in Organocatalysis

Abstract

Cover -- Title Page -- Copyright -- Contents -- Preface -- Discovery of Catalysis by Nucleophilic Carbenes -- About the Editor -- Chapter 1 An Overview of NHCs -- 1.1 General Structure of NHCs -- 1.1.1 Classes of NHCs and Related Stable Carbenes -- 1.1.2 Structural Features Common to All NHCs -- 1.1.3 Stabilization of the Carbene Center -- 1.2 NHCs as --Donating Ligands -- 1.2.1 The Nature of Bonding in NHC Adducts -- 1.2.2 Comparing NHC and Phosphine Ligands -- 1.3 Synthesis of NHCs -- 1.3.1 Generation of the Free Carbene -- 1.3.2 Synthetic Routes Toward Azolium Salt NHC Precursors -- 1.4 Quantifying the Electronic Properties of NHCs -- 1.4.1 pKa Measurements of Azolium Salts -- 1.4.2 Tolman Electronic Parameter (TEP) -- 1.4.3 NMR Measurements -- 1.4.4 Nucleophilicity and Lewis Basicity -- 1.4.5 Electrochemical Methods -- 1.4.6 Computational Methods -- 1.5 Quantifying the Steric Properties of NHCs -- 1.5.1 Percentage Buried Volume (%Vbur) -- 1.5.2 Steric Maps -- 1.6 Concluding Remarks -- References -- Chapter 2 Benzoin Reaction -- 2.1 Background and Mechanism -- 2.2 Standard Conditions and Substrate Scope -- 2.3 Enantioselective Homo--benzoin Reactions -- 2.4 Cross--benzoin Reactions -- 2.4.1 Intramolecular Cross--benzoin Reactions -- 2.4.2 Intermolecular Cross--benzoin Reactions -- 2.5 Aza--benzoin Reactions -- 2.5.1 Aza--benzoin Reactions of Aldimines -- 2.5.2 Aza--benzoin Reactions of Ketimines -- References -- Chapter 3 N--Heterocyclic Carbene--catalyzed Stetter Reaction and Related Chemistry -- 3.1 Introduction -- 3.2 Proposed Mechanism of the Stetter Reaction -- 3.3 Intramolecular Stetter Reaction -- 3.4 Intermolecular Stetter Reaction -- 3.5 Cascade Processes Involving Stetter Reaction -- 3.6 NHC--catalyzed Hydroacylation Reactions -- 3.7 Conclusion -- References Chapter 4 N--Heterocyclic Carbene (NHC)--Mediated Generation and Reactions of Homoenolates -- 4.1 Homoenolates~-~An Introduction -- 4.2 N--Heterocyclic Carbenes (NHCs) -- 4.3 NHC--Derived Homoenolates~-~The Beginning -- 4.4 Mechanistic Pathways Available for NHC--Homoenolates -- 4.5 Reaction of NHC--Homoenolates with Ketones and Ketimines -- 4.6 Reaction of NHC--Homoenolates with Michael Acceptors -- 4.7 \textgreek{b}--Protonation of Homoenolates and Subsequent Reactions -- 4.8 Homoenolates in Carbon-Nitrogen Bond Formation -- 4.9 Domino Reactions of Homoenolates -- 4.10 New Precursors for Homoenolates -- 4.11 Conclusion -- References -- Chapter 5 Domino Processes in NHC Catalysis -- 5.1 Introduction -- 5.2 Domino Reactions Involving Homoenolate-Enolate Intermediates -- 5.2.1 Domino Reactions Involving a Michael/Aldol Reaction Sequence -- 5.2.2 Domino Reactions Involving a Michael/Michael Reaction Sequence -- 5.2.3 Domino Reactions Involving a Michael/Mannich Reaction Sequence -- 5.2.4 Domino Reactions Involving a Homo--aldol/Michael Addition Sequence -- 5.3 Domino Reactions Involving Dienolate-Enolate Intermediates -- 5.4 Domino Reactions Involving Unsaturated Acyl Azolium-Enolate Intermediates -- 5.4.1 Domino Reactions Involving a Michael/Aldol Sequence -- 5.4.2 Domino Reactions Involving a Michael/Michael Addition Sequence -- 5.4.3 Domino Reactions Involving a Michael/Mannich Reaction Sequence -- 5.4.4 Domino Reactions Involving a Michael/SN2 Reaction Sequence -- 5.5 Conclusions and Outlook -- References -- Chapter 6 N--Heterocyclic Carbene Catalysis via the \textgreek{a},\textgreek{b}--Unsaturated Acyl Azolium -- 6.1 Introduction -- 6.2 Generation of the \textgreek{a},\textgreek{b}--Unsaturated Acyl Azolium -- 6.3 Esterification of the \textgreek{a},\textgreek{b}--Unsaturated Acyl Azolium -- 6.4 [3+n] Annulations of the \textgreek{a},\textgreek{b}--Unsaturated Acyl Azolium -- 6.4.1 Annulation with Enolates -- 6.4.2 Annulation with Enamines 6.4.3 Annulation with Other Nucleophiles -- 6.5 [2+n] Annulations of the \textgreek{a},\textgreek{b}--Unsaturated Acyl Azolium -- 6.5.1 [2+4] Annulations Terminating in \textgreek{b}--Lactonization -- 6.5.2 [2+4] Annulations Terminating in \textgreek{d}--Lactonization -- 6.5.3 [2+3] Annulations Terminating in \textgreek{b}--Lactonization -- 6.5.4 [2+1] Annulations -- 6.6 Cascades Involving Bond Formation at the \textgreek{g}--Carbon and Acyl Carbon -- 6.6.1 Annulations with Ketones and Imines -- 6.6.2 [4+2] Annulations with Electron--Poor Olefins -- 6.7 Other Reactions of the \textgreek{a},\textgreek{b}--Unsaturated Acyl Azolium -- 6.8 Conclusions and Outlook -- References -- Chapter 7 Recent Activation Modes in NHC Organocatalysis -- 7.1 Introduction -- 7.2 Activation of Carboxylic Acid Derivatives -- 7.2.1 \textgreek{a}--Carbon Activation of Saturated Carboxylic Esters -- 7.2.2 \textgreek{b}--Carbon Activation of \textgreek{a},\textgreek{b}--Unsaturated Carboxylic Compounds -- 7.2.3 Nucleophilic \textgreek{b}--Carbon Activation of Saturated Carboxylic Esters -- 7.2.4 \textgreek{g}--Carbon Activation of \textgreek{a},\textgreek{b}--Unsaturated Carboxylic Esters -- 7.3 Radical Reactions Catalyzed by NHC Organic Catalysts -- 7.3.1 Lessons from Nature -- 7.3.2 Pioneering SET Reactions in NHC Organocatalysis -- 7.3.3 NHC--Catalyzed Reductive \textgreek{b},\textgreek{b}--couplings of Nitroalkenes -- 7.3.4 NHC--Catalyzed Benzylation of Electrophiles -- 7.3.5 NHC--Catalyzed \textgreek{b}--hydroxylation of \textgreek{a},\textgreek{b}--Unsaturated Aldehydes -- 7.3.6 Synthesis of Chiral 3,4--diaryl Cyclopentanones Through SET Process -- 7.3.7 Polyhalides as Oxidants for NHC--Catalyzed Radical Reactions -- 7.3.8 New Mechanisms for Classical Reactions -- 7.4 Summary and Outlook into the Future NHC Organocatalysis -- References -- Chapter 8 N--Heterocyclic Carbene--Catalyzed Reactions via Azolium Enolates and Dienolates -- 8.1 Introduction -- 8.2 Azolium Enolates from \textgreek{a}--Functionalized Aldehydes -- 8.2.1 Synthesis of Carboxylic Compounds -- 8.2.2 Formal [2+4] Cycloaddition -- 8.2.3 Formal [2+2] Cycloaddition 8.2.4 Formal [2+3] Cycloaddition -- 8.3 Azolium Enolate from Ketenes -- 8.3.1 Formal [2+2] Cycloaddition -- 8.3.2 Asymmetric Formal [2+3] Cycloadditions -- 8.3.3 Asymmetric Formal [2+4] Cycloadditions -- 8.3.4 Asymmetric Protonation and Halogenation -- 8.4 Azolium Enolate from Enals -- 8.5 Azolium Enolate from Aldehydes with Oxidant -- 8.6 Azolium Enolates from Activated Esters -- 8.7 Azolium Enolates from Acids -- 8.8 Azolium Dienolate -- 8.9 Conclusions and Outlook -- References -- Chapter 9 N--Heterocyclic Carbenes as Brønsted Base Catalysts -- References -- Chapter 10 NHC--Catalyzed Kinetic Resolution, Desymmetrization, and DKR Strategies -- 10.1 Introduction -- 10.2 NHC--Catalyzed Acylation -- 10.2.1 Acylation of Aliphatic Alcohols -- 10.2.1.1 Acylation of Aliphatic Alcohols -- 10.2.1.2 DKR Involving Acylation of Alcohols -- 10.2.2 Acylation of Phenols -- 10.2.3 Acylation of Amines and Sulfoximines -- 10.3 Benzoin and Stetter Reactions -- 10.3.1 Desymmetrization of Achiral Substrates -- 10.3.2 DKR of Racemic Substrates via Benzoin Condensation -- 10.4 Annulation Reactions -- 10.4.1 Annulation via Azolium Enolate Addition -- 10.4.2 Annulation via Azolium Homoenolate Addition -- 10.4.3 Annulation via \textgreek{g}--Addition -- 10.5 Conclusion -- Acknowledgments -- References -- Chapter 11 N--Heterocyclic Carbenes for Organopolymerization: Metal--Free Polymer Synthesis -- 11.1 Introduction -- 11.2 Main NHCs and Fundamental Mechanisms of NHC--Induced Polymerization -- 11.3 NHC--Mediated Chain--growth Polymerization -- 11.3.1 Ring--opening Polymerization -- 11.3.2 NHC--OROP (in the Presence of an Initiator) -- 11.3.3 Directly NHC--Mediated ROP (in the Absence of an Initiator): Synthesis of Cyclic vs. Linear Polymers -- 11.4 Reaction with Alkyl (meth)acrylates -- 11.4.1 Basic Nucleophilic Reactivity of Stable Carbenes in the Absence of Initiator 11.4.1.1 Ambiphilic Reactivity of Stable Carbenes -- 11.4.1.2 Noncatalytic Reactivity -- 11.4.1.3 Catalytic Reactivity -- 11.4.2 Reactivity of NHCs Toward \textgreek{a},\textgreek{b}--Unsaturated Esters in the Presence of Initiators -- 11.4.3 Reactivity of NHCs in Conjunction with a Lewis Acid: Frustrated Lewis Pair--Type Reactivity -- 11.5 NHC--Mediated Step--growth Polymerization -- 11.6 Conclusion -- References -- Chapter 12 N--Heterocyclic Carbene Catalysis in Natural Product and Complex Target Synthesis -- 12.1 Introduction -- 12.2 NHC--Catalyzed Benzoin Condensations -- 12.2.1 Synthesis of trans--Resorcylide -- 12.2.2 Synthesis of (+)--Sappanone B -- 12.2.3 Synthesis of Cassialoin -- 12.2.4 Synthesis of the Kinamycins and the Monomeric Unit of Lomaiviticin Aglycon -- 12.2.5 Synthesis of ($-$)--Seragakinone A -- 12.2.6 Synthesis of Originally Assigned Structure of Pleospdione -- 12.2.7 Formal Synthesis of Natural Inositols -- 12.2.8 Synthesis of (+)--7,20--Diisocyanoadociane -- 12.3 The Stetter Reaction -- 12.3.1 Annulation Reactions -- 12.3.1.1 Synthesis of Hirsutic Acid C -- 12.3.1.2 Formal Synthesis of Platensimycin -- 12.3.2 Fragment Coupling -- 12.3.2.1 Synthesis of cis--Jasmon and Dihydrojasmon -- 12.3.2.2 Synthesis of the Core of Atorvastatin -- 12.3.2.3 Synthesis of Roseophilin -- 12.3.2.4 Synthesis of trans--Sabinene Hydrate -- 12.3.2.5 Synthesis of (+)--Monomorine I and Related Natural Products -- 12.3.2.6 Synthesis of Haloperidol -- 12.3.2.7 Synthesis of ($-$)--Englerin A -- 12.3.2.8 Synthesis of Piperodione -- 12.4 NHC--homoenolate Equivalents -- 12.4.1 Synthesis of Salinosporamide A -- 12.4.2 Synthesis of Bakkenolides I, J, and S -- 12.4.3 Synthesis of Maremycin B -- 12.4.4 Synthesis of Clausenamide -- 12.4.5 Synthesis of ($-$)--Paroxetine and ($-$)--Femoxetine -- 12.4.6 Synthesis of (S)--Baclofen and (S)--Rolipram -- 12.4.7 Synthesis of 3--Dehydroxy Secu'amine A 12.5 NHC--Catalyzed Aroylation Reactions