Modern Aryne Chemistry E-Book
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- Herausgeber: Wiley-VCH GmbH
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
A groundbreaking book to offer a a comprehensive account of important reactions involving arynes
Modern Aryne Chemistry is the first book on the market to offer a conceptual framework to the reactions related to arynes. It also provides a systematic introduction to the cycloaddition reactions, insertion reactions and transition-metal-catalyzed transformations of arynes. The author, a noted expert on the topic, highlights a novel strategy for carbon-carbon and carbon-heteroatom bond construction using arynes.
The book reveiws the recent use of aryne chemistry for the development of new multicomponent reactions. New advances in this area has shown rapid emergence of a new class of reactions classified under rearrangement reactions. The author also includes information on aryne methods that have been employed for the synthesis of several natural products. The simplicity and sophistication of the synthetic strategy using arynes can serve as a springboard for organic chemists to explore new possibilities and imagine applications of the concept of arynes. This important book:
- Presents a one-of-kind comprehensive guide to arynes reactions
- Offers a proven approach to the synthesis of natural product and polymers
- Reviews the most recent developments in the carbon-carbon and carbon-heteroatom bond-forming reactions involving arynes
Written for organic, pharmaceutical, medicinal, natural products, and catalytic Chemists, Modern Aryne Chemistry offers a comprehensive review of the fundamentals of reactions related to arynes and the most recent developments in the field.
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Veröffentlichungsjahr: 2021
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Table of Contents
Cover
Title Page
Copyright
Foreword
Preface
1 Introduction to the Chemistry of Arynes
1.1 Introduction
1.2 History of Arynes
1.3 Characterization of the Aryne Intermediates
1.4 Ortho-Arynes with Substitution
1.5 Ortho-Arynes of Heterocycles
1.6 Other Arynes
1.7 Methods of Aryne Generation
1.8 Possible Reactivity Modes of Arynes
1.9 Domino Aryne Generation
1.10 Arynes for the Synthesis of Large Polycyclic Aromatic Compounds
1.11 Arynes in Natural Product Synthesis
1.12 Concluding Remarks
References
2 Aryne Cycloadditions for the Synthesis of Functional Polyarenes
2.1 Introduction
2.2 Aryne Cycloaddition Reactions: General Considerations
2.3 Aryne-Mediated Synthesis of Functional Polyarenes
References
3 Dipolar Cycloaddition Reactions of Arynes and Related Chemistry
3.1 Introduction
3.2 1,3-Dipolar Cycloaddition Reactions of Arynes
3.3 Other [n+2] Dipolar Cycloaddition Reactions of Arynes
3.4 Formal Cycloaddition Reactions of Arynes
3.5 Summary
References
Note
4 Recent Insertion Reactions of Aryne Intermediates
4.1 Introduction
4.2 Amination and Related Transformations
4.3 Transformations Involving Bond Formation with Nucleophilic Carbons
4.4 Etherification and Related Transformations
4.5 Sulfanylation and Related Transformations
4.6 Transformations Involving Bond Formation with Other Heteroatom Nucleophiles
4.7 Conclusions
References
5 Multicomponent Reactions Involving Arynes and Related Chemistry
5.1 Introduction
5.2 Classification of Multicomponent Reactions
5.3 Carbon Nucleophile–Based Multicomponent Reactions
5.4 Nitrogen Nucleophile–Based Multicomponent Reactions
5.5 Oxygen Nucleophile–Based Multicomponent Reactions
5.6 Phosphorus Nucleophile–Based Multicomponent Reactions
5.7 Sulfur Nucleophile–Based Multicomponent Reactions
5.8 Halogen Nucleophile–Based Multicomponent Reactions
5.9 Miscellaneous
5.10 Conclusive Remarks
References
6 Transition-Metal-Catalyzed Reactions Involving Arynes and Related Chemistry
6.1 Introduction
6.2 Metal-Catalyzed Cyclotrimerization and Cocyclization of Arynes
6.3 Metal-Catalyzed Annulation with Arynes via C—H and N—H Bond Activation
6.4 Transition-Metal-Catalyzed Three-Component Coupling Reactions
6.5 Metal-Catalyzed Addition of Metal–Metal (or) Metal–Carbon and C—X bonds into Arynes
6.6 Metal-Catalyzed CO Insertion Reactions of Arynes
6.7 Metal-Catalyzed [3+2] Cycloaddition of Arynes
References
7 Molecular Rearrangements Triggered by Arynes
7.1 Introduction
7.2 Rearrangements Involved in the Monofunctionalization of Arynes
7.3 Rearrangements Involved in the 1,2-Difunctionalization of Arynes
7.4 Rearrangements Involved in the 1,2,3-Trifunctionalization of Arynes
7.5 Rearrangements Involved in the Multicomponent Reactions with Two or More Aryne Molecules
7.6 Conclusions
References
8 New Strategies in Recent Aryne Chemistry
8.1 Introduction
8.2 New Aryne Generation Methods
8.3 Aryne Regioselectivity
8.4 Recent Advances in Aryne Multifunctionalization
8.5 Conclusions
References
9 Hetarynes, Cycloalkynes, and Related Intermediates
9.1 Introduction to Hetarynes
9.2 Challenges in Hetarynes
9.3 Different Types of Hetarynes
9.4 Methods of Preparation
9.5 Reactions of Hetarynes
9.6 Applications in Synthesis
9.7 Introduction to Cycloalkynes
9.8 History of Cycloalkynes
9.9 Different Types of Cycloalkynes
9.10 Methods of Cycloalkyne Generation
9.11 Reactions of Cycloalkynes
9.12 Application in Synthesis
9.13 Strained Cyclic Allenes
9.14 Conclusions
References
10 Hexadehydro Diels–Alder (HDDA) Route to Arynes and Related Chemistry
10.1 Introduction
10.2 History
10.3 Early Demonstration of New Modes of Aryne-Trapping Reactivity: Ag- and B-Promoted Carbene Chemistry
10.4 De novo Construction of Arenes: A New Paradigm for Synthesis of Highly Substituted Benzenoid Natural Products
10.5 Diradical Mechanism of the HDDA Cycloisomerization of Triyne to Benzyne
10.6 Additional Contributions from the Lee Group (University of Illinois, Chicago (UIC))
10.7 Additional Notable Modes of Aryne Reactivity
10.8 New Reaction Modes and New Mechanistic Understanding
10.9 New Routes to Polycylic, Highly Fused Aromatic Products
10.10 One-Offs
10.11 Outgrowths from HDDA Chemistry
10.12 GuidelinesandPracticalIssues: Strategic Considerations
10.13 GuidelinesandPracticalIssues: Experimental Considerations
References
11 Applications of Benzynes in Natural Product Synthesis
11.1 Introduction
11.2 General Reactivities of Benzynes
11.3 Strategies Based on Nucleophilic Additions to Benzynes
11.4 Addition–Fragmentation Reactions
11.5 Strategies Based on [4+2] Cycloadditions
11.6 Strategies Based on [2+2] Cycloadditions
11.7 Strategies Based on Benzyne–Ene Reactions
11.8 Recent Advances
References
Note
Index
End User License Agreement
List of Tables
Chapter 11
Table 11.1 Benzyne precursors used in natural product synthesis.
List of Illustrations
Chapter 1
Scheme 1.1 Initial observations by Stoermer and Kahlert.
Scheme 1.2 Proposed structures of benzyne.
Scheme 1.3 Regioselectivity in aryne reactions.
Scheme 1.4 Robert's
14
C-labeling experiment.
Scheme 1.5 Photochemistry of arynes.
Figure 1.1 Reason for the enhanced electrophilicity of arynes.
Scheme 1.6 Structures of metal-bound benzyne.
Scheme 1.7 Natural atomic charges (above) and atomic populations of LUMO coe...
Scheme 1.8 Studies on naphthynes.
Scheme 1.9 Generation and dissociation of 3,4-pyridyne and 2,3-pyridyne.
Scheme 1.10 Possibility of uncommon benzynes.
Scheme 1.11 Possible formation of
m
-benzyne and
p
-benzyne intermediates.
Scheme 1.12 The Bergman cyclization.
Scheme 1.13 Aryne generation from halobenzene.
Scheme 1.14 Metal–halogen exchange/elimination route to arynes.
Scheme 1.15 Arynes from anthranilic acid derivatives.
Scheme 1.16 Arynes from benzothiadiazole dioxide and amino benzotriazole....
Scheme 1.17 Arynes from phenyl(2-(trimethylsilyl)phenyl)iodonium triflates....
Scheme 1.18 Arynes using HDDA strategy.
Scheme 1.19 Arynes from
ortho
-borylaryl triflates.
Scheme 1.20 Arynes via Pd(II)-catalyzed C–H activation.
Scheme 1.21 Arynes via Grob fragmentation.
Scheme 1.22 Kobayashi's method of aryne generation.
Scheme 1.23 Possible modes of reactivity of arynes.
Scheme 1.24 Wittig and Huisgen's aryne cycloaddition experiment.
Scheme 1.25 Diels–Alder reactions of tropones with arynes.
Scheme 1.26 Reaction of styrenes with arynes.
Scheme 1.27 Tandem [4+2]/[2+2] cycloaddition involving arynes and indene....
Scheme 1.28 [2+2] Cycloaddition involving arynes and enamides.
Scheme 1.29 1,3-Dipolar cycloaddition of arynes.
Scheme 1.30 [3+2] Cycloaddition reaction of diazo compounds with arynes.
Scheme 1.31
N
-Arylation of amines.
Scheme 1.32 Insertion of arynes to amides and β-keto esters.
Scheme 1.33 Metal-catalyzed coupling reaction of arynes.
Scheme 1.34 MCCs involving arynes, isocyanides, and aldehydes or activated i...
Scheme 1.35 Aryne aza-Claisen rearrangement.
Scheme 1.36 Domino aryne strategy and the indoline synthesis.
Scheme 1.37 Polycyclic aromatic hydrocarbons (PAHs) synthesis using arynes....
Scheme 1.38 Selected examples of natural product synthesized using the aryne...
Chapter 2
Figure 2.1 Structure of benzyne (1) and AFM image of
o
-aryne 2.
Scheme 2.1 Wittig's first aryne cycloaddition.
Scheme 2.2 Classical methods for aryne generation.
Scheme 2.3 Kobayashi's method for aryne generation.
Scheme 2.4 [4+2] Cycloaddition of benzyne (1) and cyclopentadienone 15.
Scheme 2.5 Reaction of benzyne (1) and 1,2-dichloroethylene.
Scheme 2.6 Suzuki's stereospecific [2+2] cycloaddition.
Figure 2.2 Compound 25 obtained by three consecutive [2+2] cycloadditions....
Scheme 2.7 Dimerization of benzyne to yield biphenylene (26).
Scheme 2.8 First palladium-catalyzed [2+2+2] cycloaddition of arynes.
Scheme 2.9 First palladium-catalyzed [2+2+2] cocyclotrimerization of arynes ...
Scheme 2.10 Thummel's synthesis of tetracene (35).
Scheme 2.11 Müllen's synthesis of pentacene (42).
Scheme 2.12 Neckers's synthesis of hexacene (47).
Scheme 2.13 Gourdon's synthesis of heptacene (51) and benzo-fused acenes 52,...
Scheme 2.14 Gribble's synthesis of tetracenes 35 and 57.
Scheme 2.15 Rickborn's synthesis of tetracene (35).
Scheme 2.16 Hamura's synthesis of substituted pentacene 69.
Scheme 2.17 Hart's bisaryne synthesis of dodecamethyltetracene (76).
Scheme 2.18 Gribble's bisaryne synthesis of tetracenes 35 and 81.
Scheme 2.19 Rickborn's synthesis of pentacene (42).
Scheme 2.20 Hart's and Schlüter's synthesis of epoxyacenes.
Scheme 2.21 Wudl's synthesis of heptacene 98.
Scheme 2.22 Hamura's synthesis of substituted pentacene 105.
Scheme 2.23 Peña's synthesis and STM image of decacene (115).
Scheme 2.24 Bettinger's synthesis of undecacene (118).
Scheme 2.25 Pascal's synthesis of twisted substituted pentacene123.
Scheme 2.26 Zhang's synthesis of dodecatwistacene127.
Scheme 2.27 Wudl's synthesis of benzo-fused substituted heptacene130.
Scheme 2.28 Pérez–Peña's synthesis of benzo-fused substituted acenes.
Scheme 2.29 Nuckolls's synthesis of substituted pentacenes144.
Scheme 2.30 Kitamura's synthesis of substituted tetracenes146.
Scheme 2.31 Cycloadditions of benzyne to the bay region of perylene (147)....
Scheme 2.32 Cycloadditions of arynes to the bay region of perylene (147)....
Scheme 2.33 Cycloadditions of arynes to the bay region of bisanthene155.
Scheme 2.34 Cycloadditions of arynes to the bay region of perylenebisimides....
Scheme 2.35 Synthesis of perylene derivatives by tandem aryne cycloadditions...
Scheme 2.36 Kelly's synthesis of molecular ratchet172.
Scheme 2.37 Synthesis of triptycene sensors for explosives.
Scheme 2.38 Synthesis of starphenes 179.
Scheme 2.39 Synthesis of mesogenic tetrabenzopentaphenes 180.
Scheme 2.40 Synthesis of trinaphthylenes 183 by Maly and coworker.
Scheme 2.41 Synthesis of twisted [16]cloverphene 189.
Scheme 2.42 (a) Synthesis and (b) AFM image of threefold symmetric nanograph...
Scheme 2.43 Synthesis and AFM image of dendriphene 194.
Scheme 2.44 Synthesis of biphenylene-based starphenes197.
Scheme 2.45 Hamura's synthesis of starphenes 206.
Scheme 2.46 Generation and coupling of aryne 208 on Ag(111).
Scheme 2.47 Synthesis of hexabenzotriphenylene (212) and their conformers....
Scheme 2.48 Synthesis of double helicene215.
Scheme 2.49 Enantioselective synthesis of pentahelicene219.
Scheme 2.50 Synthesis of hexapole pentahelicene 222.
Scheme 2.51 Synthesis of triscoranylene227.
Scheme 2.52 Synthesis of heterocyclic helicenes.
Scheme 2.53 Pérez's synthesis of angular and congested PAHs 235 and 237.
Scheme 2.54 Functionalization of C
60
by aryne cycloadditions.
Scheme 2.55 Synthesis of a fullerobenzyne precursor.
Figure 2.3 Molecular models of paddle-wheel nanostructures.
Scheme 2.56 Functionalization of carbon nanotubes by aryne cycloadditions....
Scheme 2.57 Functionalization of carbon nanohorns by aryne cycloadditions....
Scheme 2.58 Functionalization of graphene by aryne cycloadditions.
Scheme 2.59 Synthesis of C
60
-graphene hybrids259.
Chapter 3
Scheme 3.1 General scheme of 1,
n
-dipolar cycloaddition of arynes.
Figure 3.1 Classification of typical linear 1,3-dipoles.
Figure 3.2 Cyclic 1,3-dipoles: Sydnones and Münchnones.
Figure 3.3 3-Oxidopyridinium dipole.
Scheme 3.2 [3+2] Cycloaddition of arynes with diazomethane derivatives.
Scheme 3.3 [3+2] Cycloaddition of arynes with acylated diazomethane derivati...
Scheme 3.4 [3+2] Cycloaddition of arynes with subsequent acyl/silyl migratio...
Scheme 3.5 [3+2] Cycloaddition of arynes with α-substituted α-diazophosphona...
Scheme 3.6 Silver-catalyzed [3+2] cycloaddition of arynes with diazo compoun...
Scheme 3.7 [3+2] Cycloaddition of arynes with
N
-tosylhydrazones.
Scheme 3.8 [3+2] Cycloaddition of arynes with azides in general.
Figure 3.4 Some selected aryne precursors applied to [3+2] aryne cycloadditi...
Scheme 3.9 [3+2] Cycloaddition of in situ–generated arynes with in situ–gene...
Scheme 3.10 Regioselectivity of unsymmetrical benzyne in [3+2] cycloaddition...
Figure 3.5 Regioselectivity rationales: (a) Aryne distortion and (b) natural...
Scheme 3.11 [3+2] Cycloaddition of pyridynes with azides.
Scheme 3.12 [3+2] Cycloaddition of indolynes and benzofuranyne with azides....
Scheme 3.13 [3+2] Cycloaddition of arynes with in situ–generated nitrile oxi...
Scheme 3.14 [3+2] Cycloaddition of arynes with nitrile oxides: another varia...
Scheme 3.15 [3+2] Cycloaddition of arynes with in situ–generated nitrile imi...
Scheme 3.16 [3+2] Dipolar cycloaddition of aryne with an α, β-unsaturated ni...
Scheme 3.17 [3+2] Dipolar cycloaddition of arynes with isolated nitrones....
Scheme 3.18 [3+2] Dipolar cycloaddition of arynes with sugar-derived nitrone...
Scheme 3.19 [3+2] Dipolar cycloaddition with
N-
vinyl-α,β-unsaturated nitrone...
Scheme 3.20 Cycloaddition of arynes with oxaziridines.
Scheme 3.21 [3+2] Cycloaddition of arynes with nitrones in situ generated fr...
Scheme 3.22 [3+2] Cycloaddition of arynes with ketoxime-derived nitrones and...
Scheme 3.23 [3+2] Dipolar cycloaddition of arynes with azomethine imines.
Scheme 3.24 Failed [3+2] cycloaddition of arynes with azomethine ylide.
Scheme 3.25 [3+2] Dipolar cycloaddition of arynes with azomethine ylides....
Scheme 3.26 [3+2] Dipolar cycloaddition of arynes with pyridinium
N
-oxides....
Scheme 3.27 [3+2] Dipolar cycloaddition of arynes with quinolinium
N
-oxides....
Scheme 3.28 [3+2] Dipolar cycloaddition of arynes with acridinium
N
-oxides....
Scheme 3.29 [3+2] Dipolar cycloaddition of arynes with isoquinolinium
N
-oxid...
Scheme 3.30 [3+2] Dipolar cycloaddition of aryne with a dihydroisoquinoliniu...
Scheme 3.31 [3+2] Dipolar cycloaddition of arynes with
N
-tosylpyridinium and...
Scheme 3.32 Divergent outcome from [3+2] dipolar cycloaddition of arynes wit...
Scheme 3.33 [3+2] Dipolar cycloaddition of aryne with a special
N
-tosylpyrid...
Scheme 3.34 Divergent outcome from [3+2] cycloaddition of
N
-tosylisoquinolin...
Scheme 3.35 [3+2] Dipolar cycloaddition of arynes with in situ–generated pyr...
Scheme 3.36 [3 + 2] Dipolar cycloaddition of arynes with indolizines.
Scheme 3.37 [3+2] Dipolar cycloaddition of arynes with Sydnones.
Scheme 3.38 [3+2] Dipolar cycloaddition of arynes with thiazolidine-derived ...
Scheme 3.39 [3+2] Dipolar cycloaddition of fused arynes with Sydnones.
Scheme 3.40 [3+2] Dipolar cycloaddition of arynes with Münchnones.
Scheme 3.41 [4+2] Cycloaddition of arynes with aurated pyrylium species.
Scheme 3.42 [5+2]/[2+2] Cycloaddition of arynes with vinylogous pyridinium i...
Scheme 3.43 [3+2] Dipolar cycloaddition of arynes with 3-oxidopyridinium spe...
Scheme 3.44 [7+2] Dipolar cycloaddition of arynes with 3-imidopyridinium spe...
Scheme 3.45 Dipolar cycloaddition of 3-methoxybenzyne with 3-oxidopyridinium...
Scheme 3.46 Borylation of aryne precursors: more arynes and more dipolar cyc...
Scheme 3.47 Sequential cycloaddition of 1,3-benzdiyne from disilylaryl ditri...
Scheme 3.48 Sequential cycloaddition of 1,4-benzdiyne from benzobis(oxadisil...
Scheme 3.49 Formal [3+2] cycloaddition of arynes with
N
-Boc-2-methyleneglyci...
Scheme 3.50 Formal [4+2] cycloaddition of arynes with
N
-acylenamines.
Scheme 3.51 Formal [3+2] cycloaddition of arynes with 2-azidoacrylates.
Scheme 3.52 Formal [3+2] cycloaddition of arynes with α-halo-
N
-alkoxyamides....
Scheme 3.53 Evidence supporting involvement of a 2-electron hetero-TMM.
Scheme 3.54 Formal [3+2] cycloaddition of arynes with
N,N
-dimethylhydrazonyl...
Scheme 3.55 Formal [3+2] cycloaddition of arynes with
N,N
-dialkylhydrazones....
Scheme 3.56 Formal [3+2] cycloaddition of arynes with
N,N
-dimethylhydrazones...
Scheme 3.57 Formal [3+2] cycloaddition of arynes with
N
-monosubstituted hydr...
Scheme 3.58 [3+2] Cycloaddition of arynes with vinyl sulfides.
Scheme 3.59 [3+2] Cycloaddition of arynes with vinyl sulfides: further aryla...
Scheme 3.60 Formal [3+2] cycloaddition of arynes with ketene dithioacetals....
Scheme 3.61 Formal [3+2] cycloaddition of arynes with 1,2,5-thiadiazoles.
Chapter 4
Figure 4.1 Typical reactions of benzyne.
Figure 4.2 Addition reactions of amines to arynes.
Figure 4.3 Regioselective amination reactions of arynes.
Figure 4.4 Aryne amination reactions by various nitrogen nucleophiles.
Figure 4.5 Various
N
-arylation reactions involving arynes.
Scheme 4.1 Transformation via aminomagnesiation of benzyne
Figure 4.6 Carboamination reactions of benzyne with amides.
Figure 4.7 Other carboamination and aminocyanation reactions of benzyne.
Figure 4.8 Other carboamination reactions of benzyne.
Figure 4.9 Thioamination reactions of arynes.
Figure 4.10 Phosphinyl-/phosphinoamination and chloroamination reactions of ...
Figure 4.11 Silylamination reactions of arynes.
Figure 4.12 Transformations via carbolithiation of arynes.
Figure 4.13 Synthesis of benzocyclobutenes via arynes.
Figure 4.14 Acylalkylation reactions of arynes.
Figure 4.15 Various acylalkylation reactions of benzyne.
Figure 4.16 Acylalkylation reactions of benzyne with cyclic ketones.
Figure 4.17 Reactions of benzyl phenyl ketone, imidoester, and amidine with ...
Figure 4.18 Synthesis of cyclic compounds by acylalkylation reactions of ben...
Scheme 4.2 Reaction of benzyne with an alkynyl ether
Figure 4.19 Synthesis of multisubstituted cyclic compounds by acylalkylation...
Figure 4.20 Reactions of benzyne with various compounds having an active met...
Figure 4.21 Reactions of benzyne with other compounds having an active methy...
Figure 4.22 Reactions of benzyne with aminoacrylates.
Figure 4.23 Benzyne transformations involving C—C and C—H bond formations.
Figure 4.24 α-Phenylation of β-carbonyl amide or ester derivatives with benz...
Figure 4.25 Addition reactions of phenols or carboxylic acids to benzyne.
Figure 4.26 Oxysulfanylations of arynes.
Figure 4.27 Transformations of arynes involving C—O and C—N bond formations....
Figure 4.28 Reactions of arynes with various thiols and sulfinates.
Figure 4.29 Reactions of sulfides with benzyne.
Figure 4.30 Carbosulfanylation of benzyne.
Figure 4.31 Various transformations of arynes involving C–S and C–X formatio...
Figure 4.32 Disulfanylations of benzyne with disulfides.
Figure 4.33 Sulfanylstannylation and silylsulfanylations of arynes.
Figure 4.34 Bismuthosulfanylation and phosphinosulfanylation of benzyne.
Figure 4.35 Reactions of arynes with various thiocarbonyl compounds.
Figure 4.36 Reactions of benzyne with organophosphorus compounds.
Figure 4.37 Stannylphosphination, silylphosphination, and diphosphination of...
Figure 4.38 Borylzincation and diiodination of benzyne.
Figure 4.39 Chloroacylation and chloroarylation of benzyne.
Chapter 5
Scheme 5.1 Classification of multicomponent reactions involving arynes.
Scheme 5.2 Three-component reaction of arynes, isocyanides, and CO
2
.
Scheme 5.3 Three-component reaction of arynes, isocyanides, and CO
2
.
Scheme 5.4 Three-component reaction of arynes, isocyanides, and H
2
O.
Scheme 5.5 Deuterium incorporation reaction using D
2
O.
Scheme 5.6 Three-component reaction of arynes, α-isocyanoacetamides, and H
2
O...
Scheme 5.7 Three-component reaction of arynes, active methylene compounds, a...
Scheme 5.8 Reaction pathways for three-component reaction of arynes, active ...
Scheme 5.9 Three-component reaction of arynes, active methylene compounds, a...
Scheme 5.10 A reaction pathway for three-component reaction of arynes, activ...
Scheme 5.11 Four-component reaction of arynes, aziridines, H
2
O, and a fluori...
Scheme 5.12 Three-component reaction of arynes, aziridines, and carboxylic a...
Scheme 5.13 Three-component reaction of arynes, aziridines, and trifluoroace...
Scheme 5.14 Three-component reaction of arynes, aziridines, and aldehydes....
Scheme 5.15 Three-component reaction of arynes, DABCO, and thiols.
Scheme 5.16 Three-component reaction of arynes, anilines, and carbonyl compo...
Scheme 5.17 Three-component reaction of arynes, anilines, and CO
2.
Scheme 5.18 Three-component reaction of arynes,
N
-heterocycles, and aldehyde...
Scheme 5.19 Three-component reaction using arynes and sulfuryl fluoride.
Scheme 5.20 Three-component reaction of arynes, imines, and pronucleophiles....
Scheme 5.21 Three-component reaction of arynes, imines, and chloroform.
Scheme 5.22 Three-component reaction of arynes, oxazolines, and chloroform....
Scheme 5.23 Three-component reaction of arynes, imines, and carbon tetrachlo...
Scheme 5.24 Three-component reaction of arynes, imines, and electron-deficie...
Scheme 5.25 Reaction of arynes with carbodiimides.
Scheme 5.26 Three-component reaction of arynes, carbodiimides, and alkynes....
Scheme 5.27 Three-component reaction of arynes, carbodiimides, and H
2
O/alcoh...
Scheme 5.28 Three-component Reaction of arynes, quinolines, and aldehydes....
Scheme 5.29 Three-component reaction of arynes,
N
-heteroaromatics, and pronu...
Scheme 5.30 Three-component reaction of arynes,
N
-heteroaromatics, and carbo...
Scheme 5.31 Three-component reaction of arynes,
N
-heteroaromatics, and dialk...
Scheme 5.32 Three-component reaction of arynes, diazene, and
α
-bromoket...
Scheme 5.33 Three-component reaction of arynes, sodium nitrite, and aldehyde...
Scheme 5.34 Three-component reaction of arynes, DMF, and acetylene dicarboxy...
Scheme 5.35 Three-component reaction of arynes, DMF, and
N
,
S
-keteneacetals....
Scheme 5.36 Three-component reaction of arynes, DMF, and sulfonyl allenes....
Scheme 5.37 Three-component [4+1] cycloaddition using arynes and DMF.
Scheme 5.38 Three-component reaction of arynes, DMF, and diaryliodonium salt...
Scheme 5.39 Three-component reaction of arynes, DMF, and allyl bromides.
Scheme 5.40 Three-component reaction of arynes, DMF, and aroyl cyanides.
Scheme 5.41 Three-component reaction of arynes, DMSO, and alkyl bromides....
Scheme 5.42 Three-component reaction of arynes, DMSO, and acetylene dicarbox...
Scheme 5.43 Three-component reaction of arynes, aryl allyl sulfoxides, and c...
Scheme 5.44 Three-component reaction of arynes, cyclic ethers, and alcohols....
Scheme 5.45 Four-component reaction of arynes, cyclic ethers, amines, and CO
Scheme 5.46 Three-component reaction using arynes and perfluoroalkoxides....
Scheme 5.47 Three-component reaction of arynes, phosphorodiamidite, and CO
2.
Scheme 5.48 Three-component reaction of arynes, phosphines, and ketones.
Scheme 5.49 Three-component reaction of arynes, phosphines, and aldehydes....
Scheme 5.50 Three-component reaction of arynes, cyclic thioethers, and pronu...
Scheme 5.51 Four-component reaction of arynes, cyclic thioethers, a proton s...
Scheme 5.52 Four-component reaction of arynes, cyclic thioethers, H
2
O, and a...
Scheme 5.53 Four-component Reaction of arynes, cyclic thioethers, H
2
O, and p...
Scheme 5.54 Four-component reaction of arynes, cyclic thioethers, H
2
O, and t...
Scheme 5.55 Three-component reaction of arynes, a fluoride, and I
+
equiv...
Scheme 5.56 Four-component reaction of arynes, a chloride, alkyl chlorides, ...
Scheme 5.57 Three-component reaction of arynes, potassium salts, and aldehyd...
Scheme 5.58 Three-component reaction of arynes, borylzincate, and allyl brom...
Scheme 5.59 Three-component reaction using triflyloxy-substituted benzocyclo...
Chapter 6
Scheme 6.1 Aryne generation and general metal-catalyzed reactions.
Scheme 6.2 Cyclotrimerization and cocyclization employing arynes.
Scheme 6.3 Palladium-catalyzed [2+2+2] cocyclotrimerization of arynes.
Scheme 6.4 Palladium-catalyzed [2+2+2] cycloaddition of arynes with alkynes....
Scheme 6.5 Synthesis of cloverphenes and tetrabenzoheptaphene by using Pd-ca...
Scheme 6.6 Palladium-catalyzed reaction of arynes with allylic chlorides or ...
Scheme 6.7 Pd-catalyzed cocyclotrimerization of benzynes with a bicyclic alk...
Scheme 6.8 Pd-catalyzed [2+2+2] cycloaddition of benzodiynes with arynes....
Scheme 6.9 Pd-catalyzed [2+2+2] cocyclization of substituted diynes with ary...
Scheme 6.10 Pd-catalyzed cocyclotrimerization of benzynes with allenes.
Scheme 6.11 Palladium-catalyzed coupling of alkenes with arynes.
Scheme 6.12 Pd-catalyzed [2+2+2] cycloaddition of arynes from methyl 2-bromo...
Scheme 6.13 Pd-catalyzed [2+2+2] cycloaddition of arynes from benzoic acids ...
Scheme 6.14 Pd-catalyzed trimerization of (2-bromophenyl)boronic esters via ...
Scheme 6.15 Cocyclization of arynes with conjugated dienes by Pd/NHC ligand....
Scheme 6.16 Palladium-catalyzed cyclotrimerization of substituted indole-bas...
Scheme 6.17 Ni-catalyzed cocyclotrimerization of arynes with diynes.
Scheme 6.18 Ni-Catalyzed cocyclotrimerization of arynes with allenes.
Scheme 6.19 Ni-catalyzed [2+2+2] cycloaddition of arynes with alkynes/eneyne...
Scheme 6.20 Ni-catalyzed [2+2+2] cycloaddition of 3,4-pyridyne with 1,3-diyn...
Scheme 6.21 Ni-catalyzed [2+2+2] cycloaddition of arynes with unactivated al...
Scheme 6.22 Ni-catalyzed [2+2+2] cycloaddition of enynes and arynes.
Scheme 6.23 Ni(0)-catalyzed cycloaddition of arynes, activated alkenes, and ...
Scheme 6.24 Gold-catalyzed self-trimerization of arynes.
Scheme 6.25 Au(I)-catalyzed benzannulation of
o
-alkynyl(oxo)benzenes with ar...
Scheme 6.26 Palladium-catalyzed carbocyclization of 2-halobiaryls with aryne...
Scheme 6.27 Palladium-catalyzed carbocyclization of aromatic halides with ar...
Scheme 6.28 Pd-catalyzed annulations of
o
-halobenzaldehydes with arynes.
Scheme 6.29 Palladium-catalyzed three-component coupling of aromatic halides...
Scheme 6.30 Pd-catalyzed annulation of 1-(2-bromophenyl)-1
H
-indoles with ben...
Scheme 6.31 Pd-catalyzed three-component coupling of aromatic iodides with b...
Scheme 6.32 Pd-catalyzed carbocylization strategy of arynes.
Scheme 6.33 Palladium-catalyzed annulation of 2-(2-iodophenoxy)-1-substitute...
Scheme 6.34 Pd-catalyzed cascade biscarbocyclization reactions.
Scheme 6.35 Pd-catalyzed [3+2] cycloaddition of (diarylmethylene)cyclopropa[
Scheme 6.36 Palladium-catalyzed reaction of arynes with propargylic carbonat...
Scheme 6.37 Palladium-catalyzed annulation of substituted
o
-halostyrenes wit...
Scheme 6.38 Pd-catalyzed carboannulation of arynes with allyl-substituted io...
Scheme 6.39 Palladium-catalyzed annulation of
N
-(2-halophenyl)formamides wit...
Scheme 6.40 Palladium-catalyzed cascade reaction of
ortho
-halostryrenes with...
Scheme 6.41 Palladium-catalyzed cascade reaction of
N
-(2-phenylallyl)sulfona...
Scheme 6.42 Palladium-catalyzed domino Heck spirocyclization of arynes.
Scheme 6.43 Synthesis of 9,10-dihydrophenanthrenes by Pd-catalyzed carbopall...
Scheme 6.44 Pd(0)-catalyzed chemoselective [3+2] spiroannulation of 2-halobi...
Scheme 6.45 Palladium-catalyzed annulation of arynes with
ortho-
halobenzamid...
Scheme 6.46 Synthesis of
N
-acylcarbazoles by palladium-catalyzed cyclization...
Scheme 6.47 Synthesis of phenanthridines by palladium-catalyzed domino annul...
Scheme 6.48 Pd-catalyzed annulation of aryl ketone
O
-acetyloximes with aryne...
Scheme 6.49 Phenanthridinones by Pd-catalyzed C–H annulation of
N
-methoxyben...
Scheme 6.50 Synthesis of phenanthridinones via palladium-catalyzed oxidative...
Scheme 6.51 Pd(II)-catalyzed synthesis of quinolinones by acrylamides and ar...
Scheme 6.52 Synthesis of coumestans and natural product flemichapparin C.
Scheme 6.53 Pd(OAc)
2
/photoredox-catalyzed synthesis of phenanthridinones.
Scheme 6.54 Pd(II)-catalyzed oxidative annulation of
N
-methyl benzylamines w...
Scheme 6.55 Pd(II)-catalyzed direct synthesis of dibenzosultams by C-H activ...
Scheme 6.56 Palladium-catalyzed 8-amino quinoline directed decarbonylative a...
Scheme 6.57 Ni-catalyzed denitrogenative/annulation of 1,2,3-benzotriazin-4-...
Scheme 6.58 Copper-mediated C–H/N–H annulation reaction of benzamides with a...
Scheme 6.59 Cu-mediated C-H/N-H annulation of indolobenzamides and arynes....
Scheme 6.60 Pd-catalyzed bis-allylation of arynes.
Scheme 6.61 Pd-catalyzed three-component coupling of arynes with allylic hal...
Scheme 6.62 Three-component Stille and Suzuki coupling reactions of arynes....
Scheme 6.63 Pd-catalyzed Sonogashira-type coupling of arynes.
Scheme 6.64 Cooperative palladium- and copper-catalyzed three-component coup...
Scheme 6.65 Pd-catalyzed three-component Heck-type coupling of arynes.
Scheme 6.66 Pd-catalyzed three-component coupling of arynes, terminal alkyne...
Scheme 6.67 Pd-catalyzed three-component coupling of arynes, isocyanides, an...
Scheme 6.68 Ni(0)-catalyzed three-component coupling of arynes with α,β-unsa...
Scheme 6.69 Copper-catalyzed three-component carboamination of arynes.
Scheme 6.70 CuI-Catalyzed three-component reaction of arynes.
Scheme 6.71 Copper-catalyzed multicomponent coupling reaction of arynes.
Scheme 6.72 Multicomponent reactions of terminal alkynes, arynes, and allyli...
Scheme 6.73 Cu-catalyzed multicomponent coupling of arynes with terminal alk...
Scheme 6.74 [(IPr)CuCl]-catalyzed synthesis of isocoumarins from multicompon...
Scheme 6.75 Trifluoromethylation–allylation of aryne with [CuCF
3
].
Scheme 6.76 Copper-catalyzed iodoalkynylation reaction of arynes, terminal a...
Scheme 6.77 Synthesis of
H
-pyrazolo[5,1-
a
]isoquinolines via three-component ...
Scheme 6.78 Palladium-catalyzed carbon–Sn bond addition to arynes.
Scheme 6.79 Palladium-catalyzed bis-silylation/bis-stannylation of arynes....
Scheme 6.80 Direct ArS–CN addition to aryne C—C multiple bonds by Pd catalys...
Scheme 6.81 Synthesis of 2,3-disubstituted benzofurans by palladium catalyst...
Scheme 6.82 Platinum-catalyzed addition of B
2
pin
2
to arynes.
Scheme 6.83 Platinum-catalyzed diborylation reaction of indolynes with bis(p...
Scheme 6.84 Cu-catalyzed vicinal-diborylation of arynes.
Scheme 6.85 Copper-catalyzed synthesis of
ortho
-stannylbiaryls from arynes a...
Scheme 6.86 Copper-catalyzed terminal alkynes sp C—H bond addition to arynes...
Scheme 6.87 Gold and copper cocatalyzed coupling reactions of terminal alkyn...
Scheme 6.88 Copper-catalyzed two-component coupling reactions.
Scheme 6.89 Copper-catalyzed bromo alkynylation of arynes.
Scheme 6.90 Copper-mediated 1,2-bis(trifluoromethylation) of arynes.
Scheme 6.91 Synthesis of
ortho
-trifluoromethyl iodoarenes from the multicomp...
Scheme 6.92 Silver-catalyzed formal insertion of arynes into R
f
—I bonds.
Scheme 6.93 Copper-catalyzed bromoalkynylation and hydroalkynylation from HD...
Scheme 6.94 Silver-mediated fluorination, trifluoromethylation, and trifluor...
Scheme 6.95 Synthesis of triarylphosphine oxides from diarylphosphine oxides...
Scheme 6.96 Metal-catalyzed carbonylative coupling of arynes with CO or ally...
Scheme 6.97 Aryne reactions with six-membered palladacycle.
Scheme 6.98 Palladium-catalyzed reaction of aryne, CO, and 2-iodoaniline for...
Scheme 6.99 Pd-catalyzed cyclocarbonylation of arynes for the synthesis of 1...
Scheme 6.100 Silver-catalyzed [3+2] cycloaddition reaction of iminoesters wi...
Scheme 6.101 AgOTf-catalyzed reaction of 2-alkynylbenzaldoximes with arynes....
Chapter 7
Scheme 7.1 Reaction of benzyne with triethylamine.
Scheme 7.2 Reaction of benzyne with (aminomethyl)silanes.
Scheme 7.3 Reaction of benzyne with an
N
-benzyl glycinate.
Scheme 7.4 Aryne-triggered [1,2]-Stevens rearrangement of 1,2,3,4-tetrahydro...
Scheme 7.5 Aryne-triggered Sommelet–Hauser rearrangement of tertiary benzyli...
Scheme 7.6 Benzyne-induced [1,4]-rearrangement.
Scheme 7.7 Aryne-triggered [2,3]-Stevens rearrangement of tertiary allylic a...
Scheme 7.8 Aryne-triggered [2,3]-Stevens rearrangement of cyclic allylic ami...
Scheme 7.9 Aryne-triggered [2,3]-Stevens rearrangement of tertiary propargyl...
Scheme 7.10 Benzyne-promoted Curtius-type rearrangement of acyl hydrazides....
Scheme 7.11 Three-component reaction of pyridines, arynes, and isatins.
Scheme 7.12 Aryne-triggered [1,2]-Stevens rearrangement of benzylic thioethe...
Scheme 7.13 Benzyne-triggered [2,3]-Stevens rearrangement of allylic thioeth...
Scheme 7.14 Aryne-trigger [2,3]-Stevens rearrangement of various allylic thi...
Scheme 7.15 Aryne-trigger [2,3]-Stevens rearrangement of propargylic thioeth...
Scheme 7.16 Formal insertion of benzyne into a cyclic ketone.
Scheme 7.17 Formal insertion of an aryne into an α-lithiated malonate or an ...
Scheme 7.18 Formal insertion of arynes into β-ketoesters.
Scheme 7.19 Formal insertion of arynes into malonates and 1,3-diketones.
Scheme 7.20 Formal insertion of arynes into 1,3-diketones. (a) Formal insert...
Scheme 7.21 Formal insertion of arynes into α-substituted ketones. (a) Forma...
Scheme 7.22 Formal insertion of arynes into
N
-tosylacetimidates or
N
-tosylac...
Scheme 7.23 Formal insertion of arynes into secondary amides.
Scheme 7.24 Formal insertion of arynes into imides, ureas, and cyanamides. (...
Scheme 7.25 Formal insertion of arynes into tertiary amides.
Scheme 7.26 Formal insertion of arynes into acyl–oxygen and acyl–halogen σ-b...
Scheme 7.27 Formal insertion of arynes into C–P and C–S bonds. (a) Formal in...
Scheme 7.28 Formal insertion of arynes into ethoxyacetylene.
Scheme 7.29 Formal insertion of arynes into imidazolidines.
Scheme 7.30 Formal insertion of arynes into phosphoryl amides.
Scheme 7.31 Formal insertion of arynes into organophosphorus acids and sulfi...
Scheme 7.32 Formal insertion of arynes into N–O bonds.
Scheme 7.33 Formal insertion of arynes into various heteroatom–heteroatom bo...
Scheme 7.34 Reaction of arynes with β-(2-isocyanophenyloxy)acrylates (or ana...
Scheme 7.35 Three-component reaction of arynes, isocyanides, and carbon diox...
Scheme 7.36 Reaction of benzyne with 2-arylidene-1,3-indandiones.
Scheme 7.37 Aryne-triggered aza-Claisen rearrangement of tertiary allylic am...
Scheme 7.38 Aryne-triggered propargyl Claisen rearrangement.
Scheme 7.39 Reaction of arynes with
N
-hydroxyindoles.
Scheme 7.40 Reaction of arynes with nitrosoarenes.
Scheme 7.41 Reaction of arynes with thioamides.
Scheme 7.42 Reaction of benzyne with diazo compounds.
Scheme 7.43 Reaction of arynes with pyridine
N
-oxides.
Scheme 7.44 Reaction of arynes with acyl hydrazides.
Scheme 7.45 Reaction of arynes with 1-aroyl-3,4-dihydroisoquinolines.
Scheme 7.46 Reaction of arynes with aryl sulfonamides.
Scheme 7.47 Three-component reaction of arynes, tertiary aromatic amines, an...
Scheme 7.48 Three-component reaction of arynes, tertiary aromatic amines, an...
Scheme 7.49 Reaction of arynes with vinyl sulfoxides.
Scheme 7.50 Reaction of arynes with diaryl sulfoxides or sulfilimines. (a) R...
Scheme 7.51 Synthesis of triflones.
Scheme 7.52 Three-component reaction of arynes, allyl sulfoxides, and alkyl ...
Scheme 7.53 Three-component reaction of nitriles with two aryne molecules....
Scheme 7.54 Three-component reaction of 4-hydroxycoumarins with two aryne mo...
Scheme 7.55 Three-component reaction of thioureas with two aryne molecules....
Scheme 7.56 Three-component reaction of oximes with two aryne molecules.
Scheme 7.57 Four-component reaction of imidazoles with three benzyne molecul...
Chapter 8
Scheme 8.1 Two general aryne generation strategies.
Scheme 8.2 Olofson's early study on PhCl-LiTMP system.
Scheme 8.3 Study on PhCl-LiTMP system. (a) C—H bond arylation of heterocycle...
Scheme 8.4 LDAM as bulky base for aryne generation.
Scheme 8.5 Uchiyama's conditions.
Scheme 8.6 Aryne generation via elimination of HOTf. (a) Elimination of HOTf...
Scheme 8.7 Aryne generation via elimination of aryliodonio group. (a) Staurt...
Scheme 8.8 Suzuki's
o
-iodoaryl triflate as aryne precursor. (a)
o
-iodoaryl t...
Scheme 8.9 Knochel's aryne precursors.
Scheme 8.10 Other ortho-difunctionalized aryne precursors. (a) Silyl-based d...
Scheme 8.11 Pd-catalyzed aryne generation by Hu.
Scheme 8.12 Pd-mediated aryne generation from methyl 2-bromobenzoates.
Scheme 8.13 Pd-mediated aryne generation from benzoic acids.
Scheme 8.14 Pd-mediated aryne generation from
o
-bromoaryl boronic esters....
Scheme 8.15 Alkynyllithium-catalyzed aryne generation.
Scheme 8.16 Regioselective controls in intermolecular aryne reactions.
Scheme 8.17 Steric effect by 3-alkyl groups on arynes. (a) Kazmaier's study ...
Scheme 8.18 TMS as sterically congested group by Schlosser.
Scheme 8.19 Silyl as sterically congested group by Akai.
Scheme 8.20 Garg-Houk's study on silyl group as bulky group.
Scheme 8.21 Boronic ester as sterically congested group by Akai.
Scheme 8.22 Geometry-optimized substituted benzynes and hetarynes. (a) Subst...
Scheme 8.23 Silyl groups as ED inductive groups by Suzuki.
Scheme 8.24 Ikawa-Akai's work on 3-silyl- and 3-borylbenzynes. (a) nucleophi...
Scheme 8.25 Regiocomplementary [3+2] cycloaddition reactions by Tokiwa-Akai....
Scheme 8.26 Reversing regioselectivity on 4,5-indolyne.
Scheme 8.27 Manipulating regioselectivity on 3,4-pyridyne. (a) internal ange...
Scheme 8.28 Suzuki's study on small ring-fused arynes.
Scheme 8.29 Benzdiynes and benztriynes.
Scheme 8.30 1,2-benzdiyne process and equivalents. (a) General scheme of 1,2...
Scheme 8.31 Reaction of TPBT with protected thiobenzamides. (a) reaction bet...
Scheme 8.32 Diamination reactions with TPBT reagent. (a) vicinal diamination...
Scheme 8.33 Domino aryne nucleophilic-ene cascade.
Scheme 8.34 Naphthyne from 1,2-benzdiyne-HDDA cascade.
Scheme 8.35 Aryne trifunctionalization through Grob fragmentation. (a) Li's ...
Scheme 8.36 1,2-Benzdiyne processes through σ-bond insertion of N—Si and S—S...
Scheme 8.37 3-Silylbenzyne as 1,2-benzdiyne equivalent.
Scheme 8.38 Suzuki's 1,3-benzdiyne strategy.
Scheme 8.39 Ikawa-Akai's 1,3-benzdiyne strategy.
Scheme 8.40 Kitamura's hybrid 1,3-benzdiyne equivalent.
Scheme 8.41 1,4-Benzdiyne from bis(sulfonyloxy)diiodobenzene10.
Scheme 8.42 Total synthesis of actinorhodin via 1,4-benzdiyne equivalent 12....
Scheme 8.43 1,4-bis(trimethylsilyl)phenyl 2,5-bis(triflate)15 as 1,4-benzdiy...
Scheme 8.44 Nanographenes from 1,4-benzdiyne strategy.
Scheme 8.45 Ikawa-Akai's 1,4-benzdiyne strategy.
Scheme 8.46 Kitamura's hybrid 1,4-benzdiyne equivalent.
Scheme 8.47 Total synthesis of Vineomcinone B
2
methyl ester by Martin.
Scheme 8.48 Suzuki's synthesis of tetraketone29.
Scheme 8.49 Suzuki's synthesis of TCBBs33 and 34.
Scheme 8.50 Suzuki's synthesis of hexaredialene38.
Scheme 8.51 Aryne trifunctionalization from simple benzynes.
Chapter 9
Scheme 9.1 Elimination–addition (EA) mechanism.
Scheme 9.2 Addition–elimination (AE
n
) mechanism.
Scheme 9.3 Abnormal addition–elimination (AE
a
) mechanism.
Scheme 9.4 5-Membered hetarynes.
Scheme 9.5 6-Membered hetarynes.
Scheme 9.6 2,3-Benzofuranyne from 3-bromobenzofuran.
Scheme 9.7 Unsuccessful attempt to generate 2,3-indolyne.
Scheme 9.8 2,3-Benzothiophyne trapping in a Diels–Alder adduct.
Scheme 9.9 Attempt to trap 3,4-pyrrolyne.
Scheme 9.10 2,3-Thiophyne trapping with thiophene as diene.
Scheme 9.11 3,4-Thiophyne trapping in a Diels–Alder adduct.
Scheme 9.12 2,3-Pyridyne generation from metal halide.
Scheme 9.13 2,3-Pyridyne generation from 3-bromo-2-chloropyridine.
Scheme 9.14 2,3-Pyridyne generation via oxidation of
N
-aminotriazolo-pyridin...
Scheme 9.15 Mild method for 2,3-pyridyne generation.
Scheme 9.16 Thermolysis of diazonium carboxylates for 3,4-pyridyne generatio...
Scheme 9.17 3,4-Pyridyne generation from
N
-aminotriazolo-pyridine.
Scheme 9.18 3,4-Pyridyne generation from 3-bromo-4-(phenylsulfinyl)pyridine....
Scheme 9.19 3,4-Pyridyne generation from
ortho
-trialkylsilyl pyridyl triflat...
Scheme 9.20 4,5-Indolyne generation from 5-bromoindole.
Scheme 9.21 4,5-Indolyne intermediate for the total synthesis of Makaluvamin...
Scheme 9.22 Successful trapping of all three indolyne with furan.
Scheme 9.23 Indolyne generation from silyltriflate precursor.
Scheme 9.24 6,7-Indolyne generation from dichloro precursor.
Scheme 9.25 6,7-Indolyne generation through proton–lithium exchange.
Scheme 9.26 6,7-Indolyne generating and trapping with ene reaction.
Scheme 9.27 3,4-Quinolyne generation from halo derivative.
Scheme 9.28 7,8-Quinolyne generation and trapping.
Scheme 9.29 Possible 3,4-isoquinolyne intermediate generation.
Scheme 9.30 3,4-Dehydro-1,5-naphthyridine generation.
Scheme 9.31 Cycloaddition of 4,5-pyrimidyne.
Scheme 9.32 Pyridyne-
N
-oxides generation.
Scheme 9.33 Indolinyne generation via HDDA.
Scheme 9.34 Substitution effect on the selectivity of cycloaddition.
Scheme 9.35 Selectivity control in cycloaddition reaction.
Scheme 9.36 Selectivity of Indolyne for cycloaddition with benzyl azide.
Scheme 9.37 Selective nucleophilic addition on 2,3-pyridyne.
Scheme 9.38 Regioselectivity issue in nucleophilic addition reaction for 3,4...
Scheme 9.39 Selectivity in presence of different nucleophiles.
Scheme 9.40 Selective nucleophilic addition using substitution effect.
Scheme 9.41 Urea insertion onto hetarynes.
Scheme 9.42 Bis(pinacolato)diboron insertion to indolynes.
Scheme 9.43 Regioselectivity for 3,4-pyridyne insertion.
Scheme 9.44 Perlolidine synthesis by Singh and coworkers.
Scheme 9.45 Ellipticine synthesis by Moody and coworkers.
Scheme 9.46 Hetaryne-mediated eupolauramine synthesis by Couture.
Scheme 9.47 (
S
)-Macrostomine synthesis by Comins.
Scheme 9.48 Lysergic acid synthesis by Julia and coworkers.
Scheme 9.49 Trikentrin and herbindole synthesis by Buszek group.
Scheme 9.50 Dodecahydrotriphenylene from 1,2-dibromocyclohexene.
Scheme 9.51 Coupling of phenyllithium with l-chlorocyclohexene.
Scheme 9.52
14
C-Labelled l-chlorocyclohexene with phenyllithium.
Scheme 9.53 Probability of allenic intermediate.
Scheme 9.54 Trapping of cycloalkynes.
Scheme 9.55 Different types of cycloalkynes.
Scheme 9.56 Generation of cyclohexyne from 1-chlorocyclohexene.
Scheme 9.57 Generation of cyclohexyne from iodonium salt.
Scheme 9.58 Generation of cycloalkyne from enol triflates.
Scheme 9.59 Generation of cycloalkynes from 1,2-dihalocycloalkenes.
Scheme 9.60 Generation of cycloalkyne from aminotriazole anion.
Scheme 9.61 Generation of norbornyne.
Scheme 9.62 Generation of cycloalkyne from 1,2-bis-hydrazones.
Scheme 9.63 Generation of cycloalkyne from vinylidene carbene.
Scheme 9.64 Fluoride-induced cyclohexyne generation.
Scheme 9.65 Fluoride-induced generation of 3,4-oxacyclohexyne.
Scheme 9.66 Pyrolysis of isoxazolone.
Scheme 9.67 Fluoride-induced generation of 2,3-piperidyne.
Scheme 9.68 Fluoride-induced generation of 3,4-piperidyne.
Scheme 9.69 Fluoride-induced generation of cyclohexenynone.
Scheme 9.70 Generation of tetrahydro naphthalenes via Diels–Alder reaction....
Scheme 9.71 Generation of PAH via Diels–Alder reaction with cyclohexyne.
Scheme 9.72 [2+2] Cycloaddition.
Scheme 9.73 1,3-Dipolar cycloaddition.
Scheme 9.74 1,3-Dipolar cycloaddition of benzyl azide and cyclohexyne.
Scheme 9.75 Alkenylation using thiophenols.
Scheme 9.76 Cyclohexyne insertion into β-keto ester.
Scheme 9.77 Cyclohexyne insertion into cyclic ketones.
Scheme 9.78 Synthesis of guanacastepenes O and N.
Scheme 9.79 1,2-Cycloalkadienes.
Scheme 9.80 Generation of 1,2-cyclohexadiene from 1-bromocyclohexene.
Scheme 9.81 Generation of 1,2-cyclohexadiene via rearrangement of cyclopropy...
Scheme 9.82 Generation of 1,2-cyclohexadiene via pyrolysis of ketene.
Scheme 9.83 Fluoride-induced generation of 1,2-cyclohexadiene.
Scheme 9.84 Preparation of the silyl triflate precursor of 1,2-cyclohexadien...
Scheme 9.85 Preparation of azacyclic allene precursor.
Scheme 9.86 Preparation of oxacyclic allene precursor.
Scheme 9.87 Generation of 1,2,3-cyclohexatriene.
Scheme 9.88 Diels–Alder reaction of 1,2-cycloalkadiene.
Scheme 9.89 Diels–Alder reaction of enantioenriched cyclic allene.
Scheme 9.90 [2+2] cycloaddition with styrene.
Scheme 9.91 1,3-Dipolar cycloaddition with nitrones.
Chapter 10
Figure 10.1 Diels–Alder reactions of progressively less saturated pairs of 4...
Figure 10.2 First example, from 1898 [2a], of what today can be termed a tet...
Figure 10.3 Earliest examples of triyne cycloisomerizations to benzynes. (a)...
Figure 10.4 (a) The unanticipated transformation leading to the recognition ...
Figure 10.5 (a) Examples of three-atom tethers (ABC) that enable the HDDA cy...
Figure 10.6 (a) Ag(I) promotion of carbene reactivity (C–H insertion) within...
Figure 10.7 Strategic advantage of de novo arene ring construction demonstra...
Figure 10.8 Impact of substituents on rates of HDDA reactions (of 45) vs. cl...
Figure 10.9 Highlights of contributions from the Lee group (University of Il...
Figure 10.10 Examples of Diels–Alder trapping of often inert, aromatic “dien...
Figure 10.11 Examples of (notably chemoselective) reactions of HDDA benzynes...
Figure 10.12 Additional examples of (notably chemoselective) reactions of HD...
Figure 10.13 Examples of three-component reactions of HDDA benzynes. (a) Ali...
Figure 10.14 Various dihydrogen-transfer reagents reduce the benzyne by conc...
Figure 10.15 Additional examples of new classes of aryne-trapping reactions....
Figure 10.16 Examples of readily accessed, fused-ring, polycyclic aromatic m...
Figure 10.17 More examples of readily accessed fused-ring, polycyclic aromat...
Figure 10.18 Miscellaneous examples, demonstrating novel modes of trapping. ...
Figure 10.19 Miscellaneous examples, demonstrating novel modes of trapping. ...
Figure 10.20 Intervention of other, faster processes starting from potential...
Figure 10.21 The aza-HDDA reaction gives 3,4-pyridynes (cf. 166) or 2,3-pyri...
Figure 10.22 Strategic difference between (a) classical aryne net substituti...
Figure 10.23 Selective self-dimerization reactions of a class of triyne subs...
Figure 10.24 Traceless tethers, demonstrated here by reductive cleavage of a...
Chapter 11
Figure 11.1 Four typical reactivities of benzynes: (1) nucleophilic addition...
Scheme 11.1 Syntheses of dibenzopyrrocoline alkaloids [4].
Scheme 11.2 Asymmetric synthesis of cryptaustoline.
Scheme 11.3 (a) Syntheses of makaluvamine A.and (b) isobatzelline C.
Scheme 11.4 Syntheses of dictyodendrin A.
Scheme 11.5 (a) Syntheses of acronycine.and (b) quinazolinone alkaloids....
Scheme 11.6 Synthesis of indolactam V.
Scheme 11.7 Synthesis of hinckdentine A.
Scheme 11.8 Synthesis of liphagal.
Scheme 11.9 Synthesis of toxyloxanthone B.
Scheme 11.10 Synthesis of vitamin E core.
Scheme 11.11 Synthesis of chelidonine.
Scheme 11.12 Synthesis of
ent
-clavilactone B.
Scheme 11.13 Intramolecular addition in the synthesis of xylopinine.
Scheme 11.14 Synthesis of papaverine.
Scheme 11.15 Annulation of a benzyne in the synthesis of dictyodendrins.
Scheme 11.16 Synthesis of (a) welwitindolinone alkaloid.and (b) tubingen...
Scheme 11.17 Addition–fragmentation reactions of benzyne with (a) acetone or...
Scheme 11.18 Synthesis of dynemicin A.
Scheme 11.19 Synthesis of fredericamycin A.
Scheme 11.20 Syntheses of (a) curvularin.(b) turkiyenine.and (c) cos...
Scheme 11.21 Synthesis of
ent
-gilvocarcin M.
Scheme 11.22 Synthesis of arizonins B1.
Scheme 11.23 Synthesis of rifsaliniketal.
Scheme 11.24 Synthesis of spiroxin C.
Scheme 11.25 Synthesis of rishirilide B.
Scheme 11.26 Syntheses of (a) granaticin A.and (b) arnottin I.
Scheme 11.27 Synthesis of isokidamycin.
Scheme 11.28 Synthesis of nomitidine.
Scheme 11.29 Syntheses of ningalins D and G.
Scheme 11.30 Synthesis of trikentrins.
Scheme 11.31 Synthesis of pseudopterosin aglycon.
Scheme 11.32 Intramolecular Benzyne–Diene [4+2] cycloaddition.
Scheme 11.33 Syntheses of aporphine alkaloids.
Scheme 11.34 Syntheses of aristolactam alkaloids.
Scheme 11.35 The [2+2] cycloaddition strategy.
Scheme 11.36 Synthesis of taxodione.
Scheme 11.37 Synthesis of nanaomycin D.
Scheme 11.38 Synthesis of aquayamycin.
Scheme 11.39 Synthesis of goupiolone A.
Scheme 11.40 Synthesis of cycloinumakiol.
Scheme 11.41 Synthesis of
ortho
-methylbenzaldehydes.
Scheme 11.42 Synthesis of chelidonine.
Scheme 11.43 Synthesis of tubingensin B.
Scheme 11.44 Synthesis of (+)-CC-1065.
Scheme 11.45 Synthesis of crinine.
Scheme 11.46 [4+2] Cycloaddition in the synthesis of
ent
-Sch 47555.
Scheme 11.47 Synthesis of vineomycinone B
2
methyl ester.
Scheme 11.48 Synthesis of tetracenomycins C and X.
Scheme 11.49 Synthesis of actinorhodin.
Scheme 11.50 Synthesis of pyrroloindole187.
Scheme 11.51 Benzyne cascade reaction and the synthesis of ibutamoren mesyla...
Scheme 11.52 Syntheses of taiwanins.
Scheme 11.53 Syntheses of retrojusticidin B and justicidin B.
Scheme 11.54 Pd-catalyzed benzyne reactions toward
N
-methylcrinasiadine [105...
Scheme 11.55 [4+2] Cycloaddition in the synthesis of isocryptolepine.
Scheme 11.56 Synthesis of tylophorine.
Scheme 11.57 Palladium-catalyzed reaction toward flemichapparin C.
Scheme 11.58 Synthesis of koenidine.
Scheme 11.59 Syntheses of selaginpulvilins.
Guide
Cover
Table of Contents
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Modern Aryne Chemistry
Edited by
Akkattu T. Biju
Editor
Prof. Akkattu T. Biju
Department of Organic Chemistry
Indian Institute of Science
Bangalore – 560012
India
Cover
Cover Image: (background)
PublicDomainPictures/Pixabay (inset) Courtesy of Akkattu T. Biju
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Foreword
Arynes as fleeting intermediates in organic reactions were first recognized by Stoermer and Kahlert in 1902, but the solid experimental evidence of their (benzyne) involvement came through the seminal 14C tracer studies by J. D. et al. (1953) on the amination of haloarenes, and very recently Pavlićek et al. (2015) have directly observed surface-generated benzyne by atomic force microscopy (AFM). Concurrently, many preparatively useful methods for generating arynes have been devised and their diverse reactivity landscape has been extensively explored and profiled. A breakthrough in the exploitation of arynes in wide range of productive applications in organic synthesis, including total synthesis of natural products, came about through Kobayashi’s discovery (1983) that stable 2-(trimethylsilyl)aryl triflates (now commercially available) undergo facile fluoride-mediated 1,2-elimination to generate arynes safely and efficiently. This convenient access to arynes gave a major fillip to mapping the diverse and potentially rich synthetic utility of these highly reactive intermediates in the syntheses of arenes harboring structural complexity and fostering molecular diversity. The next steps in the advance of aryne arena came from the hexadehydro-Diels–Alder reaction developed by Hoye, domino generation of arynes by Li, and the development of heteroarynes by Garg among many other tactical innovations that have immensely enriched the field and amplified the expanse of aryne chemistry. Intramolecular variants, domino and tandem reactions with embellished arynes still offer innovative chemical spaces that await unraveling. While chemical explorations of aryne reactivity cover a vast and varied arena, they can be broadly categorized under lead headings like pericyclic reactions, insertion reactions, multicomponent reactions, transition-metal-catalyzed transformations, and a variety of unforeseen and interesting molecular rearrangements.
The landscape of aryne chemistry has grown by leaps and bounds since the publication of R. W. Hoffmann’s seminal monograph Dehydrobenzene and Cycloalkynes over half a century ago in 1967. A recent SciFinder search on “benzyne” and “aryne” led to −7500 and −4500 hits, respectively – clearly indicative of a fertile field and the traction it has drawn in the recent decades. These developments in aryne chemistry have been periodically captured in several timely and authoritative accounts and reviews covering diverse facets of this growing field. Nevertheless, there is a much-felt need among students and researchers in the field for an authoritative book that provides a broad, up-to-date coverage of multifaceted advances in aryne chemistry with a nuanced lens on developments that are of topical interest and likely to dominate future directions and activities and also provide a fuller flavor of the field.
Against this background and to fill a widely felt void, Akkattu T. Biju, an accomplished contributor in the arena, has put together an authoritative and timely collection of contributions from leading practitioners in the field of aryne chemistry under the title Modern Aryne Chemistry. This book is primarily aimed at highlighting some of the recent advances in carbon–carbon and carbon–heteroatom bond-forming reactions of arynes, as highly reactive and versatile electrophilic species, with numerous, contextual synthetic applications.
The first chapter of the book introduces the chemistry of arynes. This overarching contribution by Akkattu T. Biju (IISc Bangalore) describes the history of arynes, various methods for their generation, characterization techniques, and possible modes of reactivity. A detailed account of the application of arynes in cycloaddition reactions has been presented in the second chapter by E. Guitián from Universidade de Santiago de Compostela, Spain. The synthetic potential of arynes for accessing various polycyclic aromatic hydrocarbons (PAHs) and nanographenes has been highlighted in this chapter. The focal theme of the third chapter of the book compiled by F. Shi (WuXi AppTec Co., Ltd. Wuhan), and P. Li (Henan University) is on dipolar cycloaddition reactions of arynes and provides the interception of arynes with various dipoles for the synthesis of benzo-fused heterocycles. An overview “Recent advances in the insertion reactions of arynes” forms the fourth chapter by S. Yoshida and T. Hosoya from Tokyo Medical and Dental University, Japan. This chapter provides an interesting feature of aryne intermediates to insert into various element-to-element bonds to form 1,2-disubstituted arenes. A variety of nucleophiles can add to arynes and the generated aryl anion can be intercepted with electrophiles to orchestrate multicomponent reactions. Which are highlighted in this chapter. A complete coverage of transition-metal-free aryne multicomponent reactions for the synthesis of complex 1,2-disubstituted arenes has been presented by H. Yoshida from Hiroshima University in the fifth chapter.
The sixth chapter of the book by C.-H. Cheng (National Tsing Hua University, Taiwan), M. Jeganmohan (IIT Madras), and K. Parthasarathy (University of Madras) provides a detailed account of the transition-metal-catalyzed reactions involving arynes. Transition-metal-catalyzed cycloisomerization reactions, C—H and N—H bond activations involving arynes leading to annulation reactions, three-component coupling reactions, etc. are described in this chapter. Arynes serve as versatile precursors for a number of molecular rearrangements, resulting in the synthesis of diverse and structurally attractive organic compounds that are otherwise difficult to access. The recent developments in molecular rearrangements triggered through aryne intermediates are summarized in the seventh chapter by S.-K. Tian from University of Science and Technology of China, Hefei. The eighth chapter of the book is dedicated to the new strategies and latest developments in this field and deals with new methods of aryne generation, addresses the regioselectivity and multifunctionalization issues in aryne chemistry, and is authored by Y. Li from Chongqing University. A brief history of hetarynes, cycloalkynes and related potential intermediates, different methods of their generation, various types of reactions and applications in total synthesis are briefly discussed in the ninth chapter by Akkattu T. Biju (IISc Bangalore). The penultimate chapter contributed by T. R Hoye (University of Minnesota) offers the hexadehydro Diels–Alder (HDDA) route to arynes and related chemistry. Although this reaction was first revealed in 1997, it received an expansive growth after a report in 2012 demonstrating its potential as a general strategy for generating reactive benzyne intermediates from simple triyne precursors. The potential applications of arynes in the synthesis of natural products and biologically active molecules have been highlighted by K. Suzuki (Tokyo Institute of Technology) and H. Takikawaa (Kyoto University) in the last chapter of this monograph.
It is expected that in addition to the pedagogic value of the book for the students and the general reader, the simplicity and sophistication of the synthetic strategies using aryne chemistry will also inspire and entice a wide range of organic chemists to explore new reactivity patterns and imaginative applications in total synthesis, material science, and chemical biology. It is reasonable to believe that aryne chemistry will continue to flourish and lead to many interesting/serendipitous observations in the future to enrich organic chemistry. Thus, from a wider perspective, this timely book is expected to serve many purposes to augment and advance organic chemistry and its interfaces.
Hyderabad-500046, India
4 December 2020
Goverdhan Mehta,
Dr. Kallam Anji Reddy Chair
School of Chemistry
University of Hyderabad
Preface
Carbon–carbon and carbon–heteroatom bond-forming reactions constitute the backbone of synthetic organic chemistry. When it comes to the utilization of the ring strain in these bond-forming reactions, arynes have always been at the forefront (having low-lying lowest unoccupied molecular orbital [LUMO] with a strain energy of 63 kcal mol−1). Arynes are highly reactive intermediates, which are generated in situ due to their high reactivity. The chemistry of this century-old intermediate, which marked its birth in history with the vague evidence of its existence provided by Stoermer and Kahlert in 1902, has gained outstanding acceleration toward the end of the twentieth century. This unstable intermediate has been characterized using various spectroscopic methods by different research groups. In the course of time, various research groups have developed several methods for the mild generation of arynes. However, the procedure became much simpler since 1983 when Kobayashi uncovered a facile and mild method for generation of arynes from 2-(trimethylsilyl) aryl triflates using simple fluoride sources. Moreover, the reagent-free and metal-free generation and reactivity of arynes generated utilizing the concept of intramolecular hexadehydro Diels–Alder reaction (HDDA) of triynes at elevated temperature has also been studied in detail.
Arynes, being a polarizable intermediate, have a diverse reactivity profile due to their affinity toward charged and uncharged electron donors. Arynes serve as excellent dienophile and dipolarophile in pericyclic reactions such as Diels–Alder reactions, [2+2] cycloadditions and dipolar cycloaddition reactions. Arynes hold the potential to arylate a number of molecules like alcohols, amines, and thiols and to insert into various element–element σ-bonds and π-bonds. Transition-metal-free multicomponent couplings (MCCs) and molecular rearrangements are the emerging class of reactivity of arynes. Moreover, arynes undergo a variety of transition-metal catalyzed reactions. A consecutive double nucleophilic addition realizing the concept of multifunctionalization of aryne using a novel domino aryne precursor was uncovered recently by Li and coworkers. Cycloaddition reactions involving arynes give access to the synthesis of large polycyclic aromatic hydrocarbons (PAHs) that are analogous to nanosized graphene substructures. The applications of arynes are not only limited to developing novel bond-forming reactions but also in natural product synthesis. The synthesis and reactivities of several five- and six-membered hetarynes, and strained cycloalkynes have also been a subject of interest for chemists. A book on arynes is a need of the hour as the area has crossed several milestones ever since the first book on arynes Dehydrobenzene and Cycloalkynes by R. W. Hoffmann was published in 1967. The lack of an update to this book incorporating all the developments in the past five decades made us realize this collection of information on arynes. The focus of the present book is on the history, diverse reactivity, and application of arynes in organic synthesis. Moreover, details on hetarynes, domino generation of arynes, and HDDA method of aryne generation have also been included in the book. As the chemistry of arynes has achieved considerable growth and continues expanding further, with the strong support of Wiley-VCH, we decided to bring out a new book under the title Modern Aryne Chemistry to highlight the developments occurred in this interesting area. Eleven chapters highlighting the history, different modes of reactivity, and the application of arynes are presented in this book.
The foundation of this book is based on the excellent contributions of all the colleagues working in aryne chemistry, and I am thankful to them. Moreover, I would like to thank all the authors, who have contributed enormously to this project, for their valuable time, efforts as well as the expertise to make this book a source of encouragement for beginners as well as advanced chemists practicing synthetic organic chemistry. It is anticipated that the diverse reactivity and application of arynes will inspire a broad range of organic chemists to explore new opportunities and creative applications of this concept and thereby unraveling some of the remaining challenges in this field. I am also thankful to Dr Lifen Yang (Program Manager, Books & References) and Ms Katherine Wong (Senior Managing Editor) at Wiley-VCH for their unconditional support and valuable advices in organizing/developing this book.
India
30 November 2020
Akkattu T. Biju
Associate Professor
Department of Organic Chemistry
Indian Institute of Science,
Bangalore 560012
