Denitrogenative Transformation of Nitrogen Heterocycles E-Book
151,99 €
Mehr erfahren.
- Herausgeber: Wiley-VCH
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
Comprehensive resource exploring a unique chemical transformation that generates new compounds with diverse properties for modern organic synthesis research
Denitrogenative Transformation of Nitrogen Heterocycles explores all 10 polynitrogen heterocycles that are known to undergo denitrogenative transformations to date. Following highlights on the remarkable modifications encountered in the synthesis of nitrogen heterocycles, the chapters use a reaction-based approach to explain denitrogenative transformations in detail.
This book covers the exponential growth in scientific literature in the last few decades for denitrogenative reactions of polynitrogen heterocycles which play a key role in natural products, medicinal chemistry, pharmaceuticals, biochemistry, and material sciences. This book also discusses denitrogenative cascade reactions, which accomplish powerful transformations from simple polynitrogen heterocycles to more complex molecules in modern synthetic chemistry.
Written by a highly qualified academic with significant experience in the field, Denitrogenative Transformation of Nitrogen Heterocycles covers sample topics including:
- Transannulation of N-sulfonyl-1,2,3-triazoles with polar multiple bonds such as carbonyls and nitriles and non-polar multiple bonds such as alkenes, alkynes, and allenes
- Insertion of azavinyl carbenes to C–X/X–X bond, denitrogenative rearrangements of N-sulfonyl-1,2,3-triazoles, and denitrogenative transformations of NH- and N-fluoroalkyl-1,2,3-triazoles
- Metal-catalyzed and metal-free denitrogenative transformations of pyridotriazoles and denitrogenative transannulation of benzotriazoles and thiadiazoles
- Denitrogenative transformations of tetrazoles and radical denitrogenative transformations of polynitrogen heterocycles
The first book of its kind on the subject, Denitrogenative Transformation of Nitrogen Heterocycles is an essential reference for researchers and scientists working in organic chemistry, organometallic chemistry, and transition metal catalysis, as well as academics and industry professionals in related fields.
Sie lesen das E-Book in den Legimi-Apps auf:
Seitenzahl: 655
Veröffentlichungsjahr: 2024
Ähnliche
Table of Contents
Cover
Table of Contents
Title Page
Copyright
Dedication
Preface
1 Synthesis of Diverse Nitrogen Heterocycles Explored in Denitrogenative Transformations
1.1 Introduction
1.2 Synthesis of 1,2,3-Triazoles
1.3 Synthesis of 1,2,3-Thiadiazoles
1.4 Synthesis of Tetrazoles
1.5 Synthesis of 3-Aminoindazoles
1.6 Synthesis of Benzotriazinones
1.7 Summary and Outlook
References
2 Transannulation of
N
-Sulfonyl-1,2,3-triazoles with Polar Multiple Bonds
2.1 Introduction
2.2 Reaction of
N
-Sulfonyl-1,2,3-triazoles with Carbonyls
2.3 Reaction of
N
-Sulfonyl-1,2,3-triazoles with Nitriles
2.4 Reaction of
N
-Sulfonyl-1,2,3-triazoles with Polar Multiple Bonds Beyond Carbonyls and Nitriles
2.5 Conclusion
References
3 Transannulation of
N
-Sulfonyl-1,2,3-triazoles with Nonpolar Multiple Bonds such as Alkenes, Alkynes, and Allenes
3.1 Introduction
3.2 Transannulation of
N
-Sulfonyl-1,2,3-triazoles with Alkenes
3.3 Transannulation of
N
-Sulfonyl-1,2,3-triazoles with 1,3-Dienes
3.4 Transannulation of
N
-Sulfonyl-1,2,3-triazoles with Alkynes
3.5 Transannulation of
N
-Sulfonyl-1,2,3-triazoles with Allenes
3.6 Summary and Outlook
References
4 Transannulations of
N
-Sulfonyl-1,2,3-triazoles with Carbo/Heterocycles
4.1 Introduction
4.2 Transannulations with Ring Retention
4.3 Transannulations with Ring Opening
4.4 Summary and Outlook
References
5 Insertion of Azavinyl Carbenes to C—H/
X
—H Bond
5.1 Abbreviations
5.2 Introduction
5.3 Insertion Reactions of
N
1-Sulfonyl-1,2,3-triazoles
5.4 Insertion Reactions of 5-Iodo-1,2,3-triazoles
5.5 Summary and Outlook
Acknowledgment
References
6 Insertion of Azavinyl Carbenes to C—
X
/
X
—
X
Bond
6.1 Introduction
6.2 1,3-Difunctionalization
6.3 [2,3]-Sigmatropic Rearrangement Reactions
6.4 Insertion into
X
—
X
bonds
6.5 Conclusion
References
7 Denitrogenative Rearrangements of
N
-Sulfonyl-1,2,3-triazoles
7.1 Introduction to Carbenes
7.2 Metal Carbenoids
7.3 Metal Carbenoids Derived from Diazo Compounds
7.4 α-Imino Metal Carbenoids and Their Reactivity
7.5 Denitrogenative Rearrangements of
N
-Sulfonyl-1,2,3-triazoles Through Azadiene Formation
7.6 Denitrogenative Rearrangements of
N
-Sulfonyl-1,2,3-triazoles Through Zwitterionic Intermediate
7.7 Denitrogenative Rearrangements of
N
-Sulfonyl-1,2,3-triazoles Through Ylide Formation
7.8 Denitrogenative Rearrangements of
N
-Sulfonyl-1,2,3-triazoles Through Ketenimine Formation
7.9 Conclusion
Acknowledgments
References
8 Denitrogenative Transformations of
NH
- and
N
-Fluoroalkyl-1,2,3-triazoles
8.1 Introduction
8.2 Denitrogenation of
NH
-1,2,3-Triazoles
8.3 Denitrogenation of
N
-Fluoroalkyl-1,2,3-triazoles
8.4 Summary and Outlook
Acknowledgments
References
9 Asymmetric Perspective on Denitrogenative Transformation of 1,2,3-Triazoles
9.1 Introduction
9.2 Rhodium-Catalyzed Cyclopropanation Reactions
9.3 Rhodium-Catalyzed C—H Insertion Reactions
9.4 Rhodium-Catalyzed Transannulation Reactions
9.5 Miscellaneous Reactions
9.6 Application in Natural Product and Total Synthesis
9.7 Summary and Outlook
Acknowledgments
References
10 Denitrogenative Transformations of 3-Diazoindolin-2-imines
10.1 Introduction
10.2 Synthesis of 3-Diazoindolin-2-imines
10.3 Insertion Reactions of 3-Diazoindolin-2-imines
10.4 Annulation Reactions of 3-Diazoindolin-2-imines
10.5 Miscellaneous Reactions
10.6 Summary and Outlook
References
11 Metal-Catalyzed Denitrogenative Transformations of Pyridotriazoles
11.1 Introduction
11.2 Rhodium-Catalyzed Transannulation of Pyridotriazoles
11.3 Palladium-Catalyzed Ring-Opening of [1,2,3]Triazolo[1,5-
a
]pyridines
11.4 Copper-Catalyzed Denitrogenative Transannulation of Pyridotriazoles
11.5 Cobalt-Catalyzed Transannulation of Pyridotriazoles with Isothiocyanates and Xanthate Esters
11.6 Ruthenium-Catalyzed Transannulation of Pyridotriazoles with Naphthoquinones
11.7 Summary and Conclusion
Acknowledgments
References
12 Metal-Free Denitrogenative Transformation of Pyridotriazoles
12.1 Introduction
12.2 Acid-Catalyzed Denitrogenative Transformation of Pyridotriazoles
12.3 Denitrogenative Transformations of Pyridotriazoles for Forming C—C and C—
X
Bond
12.4 Thermolysis and Photolysis of Pyridotriazoles
12.5 Light-Induced Transformations of Pyridotriazoles
12.6 Summary and Outlook
Acknowledgments
References
13 Recent Development in Denitrogenative Transannulation of Benzotriazoles
13.1 Introduction
13.2 Common Route for the Synthesis of Benzotriazole Precursors
13.3 Transannulation of Benzotriazole-Appended Scaffolds
13.4 Conclusions and Future Perspective
Acknowledgments
References
14 Denitrogenative Transannulation of Thiadiazoles
14.1 Introduction
14.2 Rh-Catalyzed Reaction of 1,2,3-Thiadiazoles with Alkynes
14.3 Rh-Catalyzed Reaction of 1,2,3-Thiadiazoles with Alkenes
14.4 Rh-Catalyzed Reaction of 1,2,3-Thiadiazoles with Carbonyl Compounds
14.5 Rh-Catalyzed Reaction of 1,2,3-Thiadiazoles with Nitriles
14.6 Rh-Catalyzed Reaction of 1,2,3-Thiadiazoles with Imines
14.7 Rh-Catalyzed Reaction of 1,2,3-Thiadiazoles with Phosphaalkynes
14.8 Rh-Catalyzed Reaction of 1,2,3-Thiadiazoles with Aziridines
14.9 Conclusions
References
15 Denitrogenative Transformations of Benzotriazinones and Related Compounds
15.1 Introduction
15.2 Metal-Catalyzed Denitrogenative Transformations
15.3 Nickel and Palladium-Catalyzed Denitrogenative Transannulation Reactions
15.4 Nickel-Catalyzed Denitrogenative Cross-Coupling Reactions
15.5 Pd-Catalyzed Cross-Coupling Reactions
15.6 Visible-Light-Mediated Denitrogenative Reactions
15.7 Metal-free Denitrogenative Transformations
15.8 Thermolysis
15.9 Lewis-Acid-Mediated Denitrogenation Reactions
15.10 Electrochemical Denitrogenative Transformations
15.11 Related Compounds
15.12 Conclusions and Outlook
References
16 Denitrogenative Transformations of 3-Aminoindazoles
16.1 Introduction
16.2 Coupling with Conjugated Unsaturated Systems
16.3 Coupling with Thiols and Diselenides
16.4 Denitrogenative Transannulation of 3-Aminoindazoles
16.5 N—N Bond Cleavage of 3-Aminoindazoles
16.6 Conclusion and Outlook
References
17 Denitrogenative Transformations of Tetrazoles and Pyridotetrazoles
17.1 Introduction
17.2 Rh-Catalyzed Denitrogenative Annulation of Monocyclic Tetrazoles
17.3 Ir-Catalyzed Denitrogenative C(sp
2
)—H Amination of Pyridotetrazoles
17.4 Intermolecular Denitrogenative Annulation of Pyridotetrazoles via Mn-Nitrene Intermediate
17.5 Denitrogenative Transformation of Pyridotetrazoles via Metalloradical Mechanism
17.6 Summary and Outlook
References
18 Radical Denitrogenative Transformations of Polynitrogen Heterocycles
18.1 Introduction
18.2 Radical Denitrogenation of Benzotriazinones and Benzothiatriazines
18.3 Radical Denitrogenation of Triazoles and Benzotriazoles
18.4 Radical Denitrogenation of Pyridotriazoles
18.5 Radical Denitrogenation of Substituted 3-Aminoindazoles
18.6 Summary and Outlook
References
19 Application of Denitrogenative Transformations in Synthesis of Natural Products
19.1 Introduction
19.2 Enantioselective Synthesis of (
R
)-Cycloprodigiosin
19.3 Synthesis of Uhle’s Ketone
19.4 Total Synthesis of (+)-Lysergol
19.5 Total Synthesis of (–)-Chanoclavine I
19.6 Total Syntheses of Tuberostemospiroline and Stemona-Lactam R
19.7 Total Synthesis of (+)-Petromyroxol
19.8 Synthesis of (±)-GSK1360707
19.9 Access to the Framework of Aspidosperma and Kopsia Indole Alkaloids
19.10 Total Synthesis of (±)-Aurantioclavine
19.11 Total Synthesis of Nakafuran-8
19.12 Photo-Induced Denitrogenative Transformation to Assemble an Indole Alkaloid Framework
19.13 Total Synthesis of Newbouldine and Withasomnine
19.14 Conclusion
References
Index
End User License Agreement
List of Illustrations
Chapter 1
Figure 1.1 Representative drug molecules containing N-heterocycles.
Figure 1.2 Representative drug molecules and natural products synthesized th...
Scheme 1.1 Synthesis of
NH
-triazoles
via
N-protected triazoles.
Scheme 1.2 Synthesis of
NH
-triazoles by using Banert cascade.
Scheme 1.3 Synthesis of diverse
NH
-triazoles.
Scheme 1.4 Synthesis of
NH
-triazoles through three-component reactions.
Scheme 1.5 Synthesis of 4-aryl-
NH
-1,2,3-triazoles.
Scheme 1.6 Synthesis of various
NH
-triazoles.
Scheme 1.7 Synthesis of
N
-sulfonyl-1,2,3-triazoles from
NH
-triazoles.
Scheme 1.8 Synthesis of
N
-sulfonyl-1,2,3-triazoles through CuAAC.
Scheme 1.9 Cu-catalyzed synthesis of
N
-sulfonyl-1,2,3-triazoles.
Scheme 1.10 Synthesis of multisubstituted
N
-sulfonyl-1,2,3-triazoles.
Scheme 1.11 Synthesis of diverse
N
-sulfonyl-1,2,3-triazoles.
Scheme 1.12 Synthesis of
N
-trifluoromethyl-1,2,3-triazoles.
Scheme 1.13 Synthesis of
N
-perfluoroalkyl-1,2,3-triazoles.
Scheme 1.14 Synthesis of 5-iodo-1,2,3-triazoles.
Scheme 1.15 Cu-catalyzed synthesis of 5-iodo-1,2,3-triazoles.
Scheme 1.16 Synthesis of pyridotriazoles.
Scheme 1.17 Synthesis of triazoloindoles.
Scheme 1.18 Synthesis of benzotriazole derivatives.
Scheme 1.19 Synthesis of 1,2,3-thiadiazoles.
Scheme 1.20 Synthesis of 1
H
-tetrazoles.
Scheme 1.21 Metal nanoparticles-catalyzed synthesis of 1
H
-tetrazoles.
Scheme 1.22 Synthesis of pyridotetrazoles.
Scheme 1.23 Synthesis of pyridotetrazoles from 2-halopyridines.
Scheme 1.24 Synthesis of diverse pyridotetrazoles.
Scheme 1.25 Synthesis of tetrazolo[1,5-
a
]quinolines.
Scheme 1.26 Synthesis of various tetrazolo[1,5-
a
]quinolines.
Scheme 1.27 Synthesis of 3-aminoindazoles from 2-halobenzonitriles.
Scheme 1.28 Synthesis of various substituted 3-aminoindazoles.
Scheme 1.29 Synthesis of benzotriazinones.
Scheme 1.30 Synthesis of various N-substituted benzotriazinones.
Scheme 1.31 Synthesis of benzothiazinones.
Chapter 2
Scheme 2.1 Discovery of
N
-sulfonyl-1,2,3-triazole as carbene precursor.
Scheme 2.2 General reaction mode of
N
-sulfonyl-1,2,3-triazoles with carbonyl...
Scheme 2.3 Asymmetric synthesis of oxazolines.
Scheme 2.4 Synthesis of oxazoles from
N
-sulfonyl-1,2,3-triazoles and aldehyd...
Scheme 2.5 Synthesis of dihydropyrroles.
Scheme 2.6 Synthesis of dihydropyrrole derivatives.
Scheme 2.7 Synthesis of 6-substituted piperidin-3-ones.
Scheme 2.8 Synthesis of 6-alkoxy piperidin-3-one.
Scheme 2.9 Diastereoselective synthesis of oxabicyclo[2.2.1]heptene core.
Scheme 2.10 Synthesis of heterobridged benzodioxepine derivatives.
Scheme 2.11 Synthesis of 2,5-epoxy-1,4-benzoxazepines.
Scheme 2.12 Synthesis of 3-aminoquinolines.
Scheme 2.13 Synthesis of azepino-fused diindoles.
Scheme 2.14 Reaction of
N
-sulfonyl-1,2,3-triazoles with 1,3-diketones.
Scheme 2.15 Substrate-controlled synthesis of (fused)pyrroles.
Scheme 2.16 Rh-catalyzed stereoselective synthesis of diaminoenones.
Scheme 2.17 Diastereoselective synthesis of spiroindanones.
Scheme 2.18 Synthesis of indole alkaloid scaffolds.
Scheme 2.19 Rh(II)-catalyzed transannulation of
N
-sulfonyl-1,2,3-triazoles w...
Scheme 2.20 Synthesis of 2-bromo-1-sulfonyl imidazole and their utilization....
Scheme 2.21 Annulation of triazoles and
N
-cyanosulfoximines.
Scheme 2.22 Lewis acid-catalyzed synthesis of imidazoles.
Scheme 2.23 Metal-free synthesis of [6,5,5,6]-tetracyclic spiroindolines.
Scheme 2.24 Reactions of
N
-sulfonyl-1,2,3-triazoles with isocyanates and iso...
Scheme 2.25 Synthesis of
N
-acylamidines.
Scheme 2.26 Synthesis of thiazoles from
N
-sulfonyl-1,2,3-triazoles and thion...
Scheme 2.27 Synthesis of pyrroles and pyrazines.
Chapter 3
Scheme 3.1 Generation of metal-catalyzed α-imino metal...
Scheme 3.2 Asymmetric cyclopropanation reactions of triazoles with alkenes....
Scheme 3.3 Synthesis of dihydropyrroles from
NH
triazoles. (a) Cyclopropanat...
Scheme 3.4 Asymmetric cyclopropanation of triazole with styrenes.
Scheme 3.5 Asymmetric cyclopropanation of aryloxy triazoles with styrenes.
Scheme 3.6 Asymmetric cyclopropanation of triazoles with pinacol allyl boron...
Scheme 3.7 Enantioselective synthesis of C3-symmetric triangular macrocycles...
Scheme 3.8 Catalyst-free diastereoselective cyclopropanation of 4-phthalimid...
Scheme 3.9 Rhodium(II)-catalyzed dihydropyrrole synthesis from methoxystyren...
Scheme 3.10 Mechanism of Rh(II)-catalyzed dihydropyrrole synthesis from elec...
Scheme 3.11 Rh(II)-catalyzed transannulation of triazoles with
N
-vinyl indol...
Scheme 3.12 Rh(II)-catalyzed transannulation of triazoles with cyclic vinyl ...
Scheme 3.13 Mechanism for Rh(II)-catalyzed synthesis of THF-DPs and THP-DPs....
Scheme 3.14 Rh(II)-catalyzed transannulation of triazoles with acyclic vinyl...
Scheme 3.15 Mechanism of Rh(II)-catalyzed transannulation for pyrrole synthe...
Scheme 3.16 Rh(II)-catalyzed piperidine-fused
trans
-cycloalkenes synthesis f...
Scheme 3.17 Mechanism of Rh(II)-catalyzed synthesis of piperidine-fused
tran
...
Scheme 3.18 Rh(II)-catalyzed tandem cycloisomerization of methylenecycloprop...
Scheme 3.19 Rh(II)-catalyzed transannulation of triazoles tethered with MCP....
Scheme 3.20 Mechanism of Rh(II)-catalyzed reaction of triazole tethered with...
Scheme 3.21 Rh(II)-catalyzed intramolecular cyclization of 4-alkenyl-
N
-sulfo...
Scheme 3.22 Mechanism of Rh(II)-catalyzed intramolecular cyclization of 4-al...
Scheme 3.23 Rh(II)-catalyzed transannulation of 4-alkenyl-triazoles with (a)...
Scheme 3.24 Rh(II)-catalyzed transannulation of 4-aryl-
N
-sulfonyl-triazoles ...
Scheme 3.25 Mechanism for Rh(II)-catalyzed transannulation of triazoles with...
Scheme 3.26 Rh(II)-catalyzed reactions of triazoles with cyclic silyl dienol...
Scheme 3.27 Rh(II)-catalyzed intramolecular transannulation of triazoles tet...
Scheme 3.28 Mechanism of Rh(II)-catalyzed intramolecular
aza
-Cope reaction o...
Scheme 3.29 Nickel-catalyzed transannulation of
N
-sulfonyl-1,2,3-triazoles w...
Scheme 3.30 Mechanism of Ni-catalyzed transannulation of
N
-sulfonyl-1,2,3-tr...
Scheme 3.31 Rh(II)/Ag(I)-catalyzed transannulation of triazoles with alkynes...
Scheme 3.32 Mechanism of Rh(II)/Ag(I)-catalyzed transannulation of triazoles...
Scheme 3.33 Rh(III)-catalyzed dual C(sp
2
)—H bond activation of 4-aryl-
N
-sulf...
Scheme 3.34 Mechanism of Rh(III)-catalyzed dual C(sp
2
)—H bond activation of ...
Scheme 3.35 Rh(II)-catalyzed intramolecular transannulation of triazoles tet...
Scheme 3.36 Silver-catalyzed intramolecular cyclization of 4-(2-ethynylaryl)...
Scheme 3.37 Mechanism of silver-catalyzed intramolecular cyclization of 4-(2...
Scheme 3.38 Nickel-catalyzed transannulation of triazoles with (a) acyclic a...
Scheme 3.39 Treatment of isopyrroles with electrophilic agents.
Scheme 3.40 Mechanism of Ni-catalyzed transannulation of triazoles with alle...
Scheme 3.41 Rh(II)-catalyzed transannulation of triazoles with allenes.
Scheme 3.42 Rh(II)-catalyzed reactions of triazoles with allenols.
Scheme 3.43 Mechanism of Rh(II)-catalyzed reactions of allenols with triazol...
Scheme 3.44 Denitrogenation of
N
-sulfonyl-1,2,3-triazoles results in the Rh-...
Scheme 3.45 Intramolecular transannulation of triazoles tethered with allene...
Chapter 4
Scheme 4.1 Generation and transannulation reactions of Rh-AVCs.
Scheme 4.2 Dearomatizing intramolecular annulation of arenes with Rh-AVCs.
Scheme 4.3 Intramolecular annulation of arene-triazole-triazole hybrids.
Scheme 4.4 Intramolecular annulation of diaryl ether-triazole hybrids.
Scheme 4.5 Intermolecular annulation of arenes with 1-sulfonyl-1,2,3-triazol...
Scheme 4.6 Intermolecular annulation of arenes with 4-phthalimido-1-sulfonyl...
Scheme 4.7 Regiodivergence in annulation of indoles with 1-sulfonyl-1,2,3-tr...
Scheme 4.8 Tetracyclic spiroindolines prepared by annulation of indoles with...
Scheme 4.9 Intramolecular Rh-AVCs insertion into the C—H bond of indoles.
Scheme 4.10 Rh-AVCs in the “cyclopropanation/Cope rearrangement” reaction se...
Scheme 4.11 Annulation of furans with cyclohexenyl-substituted Rh-AVCs.
Scheme 4.12 Transannulation of 8-azaheptafulvenes with Rh-AVCs.
Scheme 4.13 Possible routes for the furan ring opening under action of Rh-AV...
Scheme 4.14 Synthesis of pyrroles by transannulation of furans with 1-sulfon...
Scheme 4.15 Mechanism for the transannulation of furans to pyrroles.
Scheme 4.16 Synthesis of 1,2-dihydropyridines from furans and 1-sulfonyl-1,2...
Scheme 4.17 Synthesis of fused pyridines by Rh-AVC-mediated transannulation ...
Scheme 4.18 Mechanism for the transannulation of isoxazoles to pyrroles.
Scheme 4.19 Synthesis of pyrazines and pyrroles by transannulation of isoxaz...
Scheme 4.20 Synthesis of pyrimidines by transannulation of isoxazoles with R...
Scheme 4.21 Regiodivergence in annulation of isoxazoles with 1-sulfonyl-1,2,...
Scheme 4.22 Synthesis of quinazolines from benzo[
c
]isoxazoles and 1-sulfonyl...
Scheme 4.23 Mechanism for the formation of quinazolines from benzo[
c
]isoxazo...
Scheme 4.24 Synthesis of imidazoles by transannulation of benzo[
d
]isoxazoles...
Scheme 4.25 Synthesis of imidazoles from 1,2,4-oxadiazole derivatives and 1-...
Scheme 4.26 Synthesis of 2,6,8-triazabicyclo[3.2.1]octa-3,6-dienes and (2-am...
Scheme 4.27 Mechanism of the catalytic reaction of pyrazoles with 1-sulfonyl...
Scheme 4.28 Synthesis of pyrroles by transannulation of 1,2,3-triazoles with...
Scheme 4.29 Rh(II)-catalyzed reaction of 1-tosyl-1,2,3-triazoles with arylox...
Scheme 4.30 Rh(II)-catalyzed reaction of 1-sulfonyl-1,2,3-triazoles with gly...
Scheme 4.31 Rh(II)-catalyzed reaction of 1-sulfonyl-1,2,3-triazoles with oxe...
Scheme 4.32 Rh(II)-catalyzed reaction of 1-sulfonyl-1,2,3-triazoles with cyc...
Scheme 4.33 Rh(II)-catalyzed reactions of 1-sulfonyl-1,2,3-triazoles with 2
H
Scheme 4.34 Mechanism of the catalytic reaction of 1-sulfonyl-1,2,3-triazole...
Scheme 4.35 Rh(II)-catalyzed reaction of 1-sulfonyl-1,2,3-triazoles with spi...
Scheme 4.36 Synthesis of indoles from 2
H
-azirines and 1-sulfonyl-1,2,3-triaz...
Scheme 4.37 Rh(II)-catalyzed reaction of 1-sulfonyl-1,2,3-triazoles with bic...
Scheme 4.38 Rh(II)-catalyzed reaction of 1-sulfonyl-1,2,3-triazoles with imi...
Scheme 4.39 Rh(II)-catalyzed reaction of 1...
Scheme 4.40 Rh(II)-catalyzed reaction of 1-sulfonyl-1,2,3-triazoles with 1,3...
Scheme 4.41 Rh(II)-catalyzed reaction of 1-sulfonyl-1,2,3-triazoles with tii...
Scheme 4.42 Rh(II)-catalyzed reaction of 1-sulfonyl-1,2,3-triazoles with thi...
Chapter 5
Scheme 5.1 Types of C/
X
—H insertion reactions of AVCs.
Scheme 5.2 Insertion of Rh-AVCs to nonactivated aliphatic C—H bonds.
Scheme 5.3 Intramolecular transannular CH-insertion of Rh-AVCs.
Scheme 5.4 Insertion of Rh-AVCs to allylic C—H bonds.
Scheme 5.5 Insertion of Rh-AVCs to benzylic C—H bonds.
Scheme 5.6 Approach to β-arylpyrrolidines starting...
Scheme 5.7 Insertion of Rh-AVCs to distal allylic/benzylic C—H bonds.
Scheme 5.8 Insertion of Rh-AVCs to β-C—H bonds in silanes.
Scheme 5.9 Intramolecular insertion of Rh-AVCs to α-C—H bonds of ethers.
Scheme 5.10 Intramolecular insertion of Rh-AVCs to C—H bonds of
N
-benzylanil...
Scheme 5.11 Synthesis of saturated five-membered (hetero)cycles
via
intramol...
Scheme 5.12 Insertion of Rh-AVCs to aromatic C—H bonds of anilines.
Scheme 5.13 Insertion of Rh-AVCs to C—H bonds of azulenes.
Scheme 5.14 Insertion of Rh-AVCs to aromatic C—H bonds of aryl ethers.
Scheme 5.15 Insertion of electrophilic Rh-AVCs to C—H bonds of arenes.
Scheme 5.16 Chemoselective intramolecular insertion of Rh-AVCs to aromatic o...
Scheme 5.17 Synthesis of indanones and tetralones
via
intramolecular CH-inse...
Scheme 5.18 Approach to indoles
via
intramolecular insertion of Rh-AVCs to a...
Scheme 5.19 Chemoselectivity of indole preparation
via
intramolecular insert...
Scheme 5.20 Synthesis of dihydroindoles
via
intramolecular insertion of Rh-A...
Scheme 5.21 Approach to 2-aminobenzofurans
via
cascade triggered by intramol...
Scheme 5.22 Approach to acridones
via
intramolecular CH-insertion of Rh-AVCs...
Scheme 5.23 Approach to fluorenes
via
intramolecular CH-insertion of Rh-AVCs...
Scheme 5.24 Approach to benzofulvenes
via
intramolecular CH-insertion of Rh-...
Scheme 5.25 Catalyst-free thermal CH-insertion of AVCs to indoles and pyrrol...
Scheme 5.26 Insertion of Rh-AVCs to indole C—H bonds.
Scheme 5.27 Approach to tryptamine analogs by the reaction of Rh-AVCs with i...
Scheme 5.28 Directing group-assisted Rh(III) catalysis for the regioselectiv...
Scheme 5.29 Atroposelective Rh(III)-catalyzed CH-insertion of AVCs to indole...
Scheme 5.30 Insertion of Rh-AVCs to C—H bonds of electron-rich azaheterocycl...
Scheme 5.31 Heteroannulation
via
Rh-AVC CH-insertion followed by intramolecu...
Scheme 5.32 Asymmetric approach to 1,2-dihydro...
Scheme 5.33 Approach to 3-aminocarbazoles...
Scheme 5.34 One-pot conversion of Rh-AVC CH-insertion products to azepino[5,...
Scheme 5.35 Diazepane annulation
via
intramolecular Rh-AVC CH-insertion.
Scheme 5.36 Intramolecular Rh-AVC insertion to C3—H bond of indole.
Scheme 5.37 Intramolecular Rh-AVC insertion to C2—H bond of indole.
Scheme 5.38 Rh-catalyzed denitrogenative hydration of STs.
Scheme 5.39 Approach to indanones
via
Rh-AVC hydration followed by intramole...
Scheme 5.40 Rh-catalyzed assembly of tryptamines from STs, paraformaldehyde,...
Scheme 5.41 Formal 1,3-insertion of Rh-AVCs to various O—H bonds.
Scheme 5.42 Rh-AVC OH-insertion to silanols followed by Mukaiyama aldol reac...
Scheme 5.43 Oxidative annulation of AVCs to...
Scheme 5.44 OH-insertion of Rh-AVCs to allyl alcohols followed by Claisen re...
Scheme 5.45 Divergent substrate-dependent reactions of Rh-AVCs with allenols...
Scheme 5.46 OH-insertion of Rh-AVCs to γ-hydroxyacrylates and MBH adducts.
Scheme 5.47 Oxidative cyclization of the coupling products obtained from Rh-...
Scheme 5.48 OH-insertion of Rh-AVCs to benzoquinone derived allyl alcohols....
Scheme 5.49 Approach to pyrrolidines from STs and 2-(hydroxymethyl)allyl car...
Scheme 5.50 OH-insertion of Rh-AVCs to propargyl alcohols.
Scheme 5.51 OH-insertion of Rh-AVCs to 2-furfuryl alcohols.
Scheme 5.52 OH-insertion of Rh-AVCs to benzyl alcohols.
Scheme 5.53 Intramolecular OH-insertion of Rh-AVCs.
Scheme 5.54 Domino reactions involving intramolecular OH-insertion of Rh-AVC...
Scheme 5.55 OH-insertion of Rh-AVCs to glycidols.
Scheme 5.56 OH-insertion of Rh-AVCs to halohydrins.
Scheme 5.57 Rearrangement of β-oxyenamines to α-aminoketones.
Scheme 5.58 Rh-AVC insertion to tropolones.
Scheme 5.59 Rh-AVC insertion to enol form of 1,3-diketones.
Scheme 5.60 Rh-AVC insertion to
N
-acylhydrazones.
Scheme 5.61 Rh-AVC insertion to lactim form of various azaheterocycles.
Scheme 5.62 Approach to fused imidazolidinones
via
domino reaction of Rh-AVC...
Scheme 5.63 Rh-catalyzed reaction of STs with isatins.
Scheme 5.64 Rh-catalyzed reaction of STs with 3-arylideneoxindoles.
Scheme 5.65 Formal 1,3-insertion of Rh-AVCs to various N—H bonds.
Scheme 5.66 NH-insertion of Rh-AVCs to carbazoles.
Scheme 5.67 NH-insertion of Rh-AVCs to anilines.
Scheme 5.68 Assembly of 3-aminopyrroles based on NH-insertion of Rh-AVCs.
Scheme 5.69 NH-insertion of Rh-AVCs to β-enamino esters.
Scheme 5.70 NH-insertion of Rh-AVCs to β-enaminones.
Scheme 5.71 Approach to 2,3-dehydropiperazines involving Rh-AVC NH-insertion...
Scheme 5.72 NH-insertion of Rh-AVCs to 2-vinylanilines.
Scheme 5.73 NH-insertion of Rh-AVCs to 2-(hydroxymethyl)anilines.
Scheme 5.74 NH-insertion of Rh-AVCs to 2-acylanilines.
Scheme 5.75 Conversion of STs to boron
aza
-enolates and subsequent
aza
-aldol...
Scheme 5.76 Ni-catalyzed denitrogenative hydroboration of STs with HBpin.
Scheme 5.77 Insertion of Rh-AVCs to Si—H bond.
Scheme 5.78 Ni-catalyzed denitrogenative reaction of STs with
H
-phosphine ox...
Scheme 5.79 Annulation-triggered ring-opening of 5-iodo-1,2,3-triazoles.
Scheme 5.80 Cu-catalyzed capture of 2-(1-diazoalkyl)benzoxazoles with amines...
Scheme 5.81 Cu-catalyzed SH-insertion of 2-(1-diazoalkyl)benzoxazoles.
Scheme 5.82 Noncatalytic sulfonylative trapping of 2-(1-diazoalkyl)benzoxazo...
Scheme 5.83 NH- and SH-insertions triggered by cyclization of 2-(5-iodotriaz...
Chapter 6
Scheme 6.1 Formation and reactivity of
α
-imino carbenes.
Scheme 6.2 Reaction of triazoles with cyclic oxygen N-heterocycles.
Scheme 6.3 (a) Synthesis of dihydromorpholine ring systems. (b) Episulfi...
Scheme 6.4 Synthesis of tetrahydrofuranes and larger ring systems from oxeta...
Scheme 6.5 (a) Reaction of cyclic acetals with triazoles. (b) Reaction o...
Scheme 6.6 (a) Reaction of triazoles with acyl sulfides. (b) Reaction of thi...
Scheme 6.7 (a) Reactions of 6.7b with triazoles. (b) Reactions of 6.7g w...
Scheme 6.8 (a) Reactions of 6.8b with triazoles. (b) Reaction of acyl seleni...
Scheme 6.9 (a) Synthesis of polycyclic heterocycle 6.9c and benzodiazepine-i...
Scheme 6.10 Reaction of 2-oxopyridines with triazoles.
Scheme 6.11 [2,3]-sigmatropic rearrangement reaction of 6.11e followed by hy...
Scheme 6.12 (a) Reaction of allyl ether substituent attached to the 4-positi...
Scheme 6.13 (a) Allylic sulfides in the reaction with triazoles. (b) One...
Scheme 6.14 Sommelet-–Hauser-type rearrangement...
Scheme 6.15 Synthesis of thioacetals
via
S—S bond insertion reaction.
Chapter 7
Figure 7.1 Structure and types of carbenes.
Figure 7.2 Bonding and types of metal carbenoids.
Figure 7.3 Metal carbenoids derived from diazo compounds and their classific...
Figure 7.4 Dimroth rearrangement of 5-amino-1,2,3-triazoles.
Figure 7.5 Synthesis and reactivity profile of
N
-sulfonyl 1,2,3-triazoles.
Scheme 7.1 Ring expansion and rearrangement reactions in Rh-AVCs. (a) Ring e...
Scheme 7.2 1,2-Sulfur migration in Rh-AVCs.
Scheme 7.3 Synthesis of 1,2-dihydropyridine derivatives.
Scheme 7.4 1,2-acyl migration in Rh-AVCs.
Scheme 7.5 Synthesis of 4-aminooxazolidinones.
Scheme 7.6 Synthesis of various functionalized N-heterocycles. (a) Reaction ...
Scheme 7.7 Synthesis of butenolide tethered homotryptamine derivatives.
Scheme 7.8 1,2-Aryl migration in Rh-AVCs.
Scheme 7.9 1,3-Hydroxy and acyloxy migration in Rh-AVCs. (a) 1,3-Acyloxy mig...
Scheme 7.10 Synthesis of azepane derivatives. (a) 1,3-Hydroxy migration. (b)...
Scheme 7.11 Synthesis of 2-tetrasubstituted saturated heterocycles.
Scheme 7.12 Synthesis of 4-bromo-1,2-dihydroisoquinolines.
Scheme 7.13 Synthesis of dihydroisoquinoline and 2-aminoindanone derivatives...
Scheme 7.14 Synthesis of indole-substituted indanones.
Scheme 7.15 Synthesis of functionalized enamides.
Scheme 7.16 Synthesis of
N
-substituted 2-pyridones.
Scheme 7.17 Rh(II)-catalyzed Grob-type fragmentation of oxonium ylides.
Scheme 7.18 Metal-free synthesis of 2-aminonaphthalenes.
Scheme 7.19 Metal-free synthesis of α-cyano sulfones.
Chapter 8
Scheme 8.1 Schematic representation of the utilization of
N-
EWG-substituted ...
Scheme 8.2 Synthesis of 2,3-dihydropyrroles from
NH
-triazoles and triflic an...
Scheme 8.3 Mechanism of
NH
-triazole cleavage after acylation.
Scheme 8.4 Ring opening of
NH
-1,2,3-triazoles with acyl halides.
Scheme 8.5 Preparation of β-enamido triflat...
Scheme 8.6 One-pot two-step synthesis of β-fluoroacylenamido triflates.
Scheme 8.7 Preparation of fluoroalkylated oxazoles and 2-acylaminoketones fr...
Scheme 8.8 Synthesis of 2-unsubstituted oxazole from
NH
-1,2,3-triazole and t...
Scheme 8.9 Formation of oxazoles from 2-trimethylsilyl-1,2,3-triazoles and a...
Scheme 8.10 One-pot synthesis of 2-fluoroalkyl-imidazoles and 3-fluoroalkyl-...
Scheme 8.11 Synthesis of bis(enamides) 8.11b and oxazoles 8.11c by denitroge...
Scheme 8.12 Synthesis of benzoxazoles from
NH
-benzotriazoles.
Scheme 8.13 Synthesis of
o
-iodoacetanilide by AlI
3
-mediated cleavage of N1-a...
Scheme 8.14 Denitrogenation of
NH
-1,2,3-triazoles with thiophosgene.
Scheme 8.15 Preparation of multifunctional
N
-alkenyl compounds by denitrogen...
Scheme 8.16 Synthesis of cyclic enaminones by cleavage of 4-(1-hydroxycyclob...
Scheme 8.17 Preparation and reactivity of
N
-fluoroalkyl ketenimines 8.17a.
Scheme 8.18 Rhodium(II)-catalyzed reactions of
N
-fluoroalkyl-1,2,3-triazoles...
Scheme 8.19 Rhodium(II)-catalyzed reactions of 4-cyclohexenyl-substituted
N
-...
Scheme 8.20 Rh(II)-catalyzed ring opening and defluorinative annulation of
N
Scheme 8.21 Triflic and fluorosulfonic acid-mediated transformation of
N
-flu...
Scheme 8.22 Boron trifluoride-mediated conversion of
N
-fluoroalkyl-1,2,3-tri...
Scheme 8.23 Aluminum trihalide-mediated conversion of
N
-fluoroalkyl-1,2,3-tr...
Scheme 8.24 Evidence of the vinyl cation intermediate in the formation of im...
Scheme 8.25 Aluminum trihalide-mediated transformation of
N
-fluoroalkyl-5-al...
Chapter 9
Scheme 9.1 Asymmetric functionalization of metallocarbenes. (a) Metallocarbe...
Scheme 9.2 Rh(II)-catalyzed asymmetric cyclopropanation.
Scheme 9.3 Reactivity of
N
-triflyl azavinyl carbenes.
Scheme 9.4 Azavinyl carbenes derived from 1,2,4-triazolyl-substituted-1,2,3-...
Scheme 9.5 Enantioselective synthesis of piperidine-fused
trans
-cycloalkanes...
Scheme 9.6 Enantioselective synthesis of cyclopropylmethanamines.
Scheme 9.7 Synthesis of enantiopure [3] CPPC.
Scheme 9.8 Asymmetric synthesis of chiral carbon isotope hydrocarbons.
Scheme 9.9 Synthesis of crypto-optically active compounds.
Scheme 9.10 Asymmetric C—H insertion of unactivated sp
3
C—H bonds.
Scheme 9.11 Asymmetric C—H insertion of allylic and benzylic of sp
3
C—H bond...
Scheme 9.12 Stepwise stereoselective synthesis of β-arylpyrrolidines.
Scheme 9.13 Asymmetric C—H insertion of silicon-substituted alkanes.
Scheme 9.14 Distal site-selective δ C—H insertion of allylic alcohols.
Scheme 9.15 Asymmetric synthesis of oxazolines.
Scheme 9.16 Asymmetric synthesis of pyrroloindolines via formal [3 + 2]-cycl...
Scheme 9.17 One-pot enantioselective synthesis of 2,3-dihydropyrroles.
Scheme 9.18 Plausible mechanism for enantioselective synthesis of 2,3-dihydr...
Scheme 9.19 Enantioselective synthesis of....
Scheme 9.20 Bimetallic relay catalysis mechanism.
Scheme 9.21 Enantioselective synthesis of α-aminoketones.
Scheme 9.22 Enantioselective synthesis of dihydro-β-carbolines.
Scheme 9.23 Synthesis of chiral sulfinylamidines.
Scheme 9.24 Enantioselective synthesis of cycloprodigiosin.
Scheme 9.25 Asymmetric synthesis of (+)-Lysergol.
Scheme 9.26 Synthesis of nakafuran-8.
Chapter 10
Figure 10.1 Indole embedded α-imino metal carbenoid.
Scheme 10.1 Synthesis of 3-diazoindolin-2-imine.
Scheme 10.2 Rhodium catalyzed N—H bond insertion reactions of 3-diazoindolin...
Scheme 10.3 Rhodium catalyzed synthesis of 2-(3-arylallylidene)-3-oxindoles....
Scheme 10.4 Copper-catalyzed insertion of
H
-phosphine oxides into 3-diazoind...
Scheme 10.5 BF
3
·OEt
2
catalyzed S—H...
Scheme 10.6 Copper catalyzed synthesis of 3,3-diaryl-2-imino-indoles.
Scheme 10.7 Directing group-assisted C—H bond insertion reactions.
Scheme 10.8 TfOH-catalyzed reactions of 3-diazoindolin-2-imines with electro...
Scheme 10.9 Carbene insertion into internal alkenyl...
Scheme 10.10 Rh-catalyzed C—S bond insertion of 3-diazoindolin-2-imines with...
Scheme 10.11 Copper-catalyzed synthesis of 3,3-disubstituted indoline deriva...
Scheme 10.12 Rh-catalyzed reactions of 3-diazoindolin-2-imines with aniline ...
Scheme 10.13 Palladium-catalyzed synthesis of 3-haloindol-2-amines.
Scheme 10.14 Rhodium-catalyzed transformations of 3-diazoindolin-2-imines....
Scheme 10.15 Reactions of diazoimines with 2,5-disubstituted furan and dihyd...
Scheme 10.16 Synthesis of isoquinoline-fused indoles.
Scheme 10.17 [4 + 2]-Annulation of benzamides and 3-diazoindolin-2-imines....
Scheme 10.18 Rhodium-catalyzed reactions of sulfoximines with 3-diazoindolin...
Scheme 10.19 Acid-catalyzed synthesis of thiazolo[4,5-
b
]indol-2-amines.
Scheme 10.20 Synthesis of 5
H
-pyrazino[2,3-
b
]indoles.
Scheme 10.21 Rhodium-catalyzed reaction of 3-diazoindolin-2-imines with 2
H
-a...
Scheme 10.22 Synthesis of 1,3’-biindoles.
Scheme 10.23 Copper-catalyzed synthesis of 3-indolyl-4
H
-chromen-4-ones.
Scheme 10.24 Rhodium catalyzed reactions of 3-diazoindolin-2-imines with 1,3...
Scheme 10.25 Rh(II)-catalyzed denitrogenative transannulation of benzo[d]iso...
Scheme 10.26 Rhodium-catalyzed synthesis of azepino, azocino, and azonino di...
Scheme 10.27 Copper-catalyzed synthesis of spiro[cyclopropane-1,3′-indolin]-...
Scheme 10.28 Copper-catalyzed synthesis of spiro[imidazolidine-4,3′-indolin]...
Scheme 10.29 Copper-catalyzed [4 + 1]-annulation of enaminothiones with diaz...
Scheme 10.30 [4 + 1]-Annulation of diazoimines with 2-(arylamino)ethanols....
Scheme 10.31 Rh-catalyzed [4 + 1]-annulation of 3-diazoindolin-2-imine with
Scheme 10.32 Ru(II)-catalyzed synthesis of fused α-carbolines.
Scheme 10.33 Rhodium-catalyzed reactions of diazoimines with aryl- and acryl...
Scheme 10.34 Pd(II)-catalyzed arylation of diazoimines with arylboronic acid...
Scheme 10.35 BF
3
·Et
2
O-catalyzed arylation...
Scheme 10.36 Reaction of diazoimines with allyltrimethylsilanes.
Scheme 10.37 Synthesis of 3-((trifluoromethyl)thio)-2-aminoindoles.
Scheme 10.38 Gold catalyzed synthesis of 2-iminoindolin-3-ones and their con...
Scheme 10.39 Synthesis of 2,3-diiminoindoles from diazoimines and benzo[c]is...
Scheme 10.40 Stereoselective synthesis of (
E
)-3-arylideneindolin-2-imines....
Scheme 10.41 Rhodium catalyzed transformation of diazoimines with nitrosoare...
Chapter 11
Figure 11.1 Formation of rhodium carbenoid intermediate.
Figure 11.2 Metal-catalyzed transannulation of pyridotriazoles.
Figure 11.3 Rh-catalyzed annulation and insertion reaction of diazo compound...
Scheme 11.1 First metallocarbene intermediate by denitrogenation of pyridotr...
Scheme 11.2 Rh-catalyzed transannulation of pyridotriazoles with alkynes.
Scheme 11.3 Rh-catalyzed transannulation of pyridotriazoles with nitriles.
Scheme 11.4 Proposed plausible reaction mechanism for Rh(II)-catalyzed trans...
Scheme 11.5 Rh-catalyzed rearrangement of 3-iminocyclopropenes into N-fused ...
Scheme 11.6 Mechanistic rationale for regiodivergent rearrangement reaction ...
Scheme 11.7 Rhodium-catalyzed NH insertion of pyridyl carbenes.
Scheme 11.8 Rh(III)-catalyzed transannulation of pyridotriazole with 2-pheny...
Scheme 11.9 Plausible reaction mechanism transannulation of pyridotriazole w...
Scheme 11.10 Synthesis of 1,2-benzothiazines by from
S
-aryl Sulfoximines and...
Scheme 11.11 Plausible reaction mechanism transannulation of pyridotriazole ...
Scheme 11.12 Rhodium-catalyzed [2 + 1]-cyclopropanation, palladium-catalyzed...
Scheme 11.13 Rh(III)-catalyzed annulation between
N
-phenylbenzimidamides and...
Scheme 11.14 Plausible reaction mechanism of pyridotriazole with
N
-phenylben...
Scheme 11.15 Rhodium (II)-catalyzed formal [4 + 1]-cycloaddition of pyridotr...
Scheme 11.16 Plausible reaction mechanism of pyridotriazole with propargyl a...
Scheme 11.17 Palladium-catalyzed arylation of [1,2,3]triazolo[1,5-
a
]pyridine...
Scheme 11.18 Pd-catalyzed regioselective synthesis of 2,6-disubstituted pyri...
Scheme 11.19 Plausible reaction mechanism for Pd(II) catalyzed arylation of ...
Scheme 11.20 Pd-catalyzed synthesis of 2-oxo-1-phenyl-1-(pyridin-2-yl)propyl...
Scheme 11.21 Proposed mechanism for the Pd-catalyzed reaction of pyridotriaz...
Scheme 11.22 Cu-Catalyzed transannulation with alkynes.
Scheme 11.23 Cu-Catalyzed intramolecular transannulation.
Scheme 11.24 Cu(I)-catalyzed transannulation with benzyl amines.
Scheme 11.25 Proposed mechanism for Cu(I)-catalyzed transannulation of pyrid...
Scheme 11.26 Cu(I)-catalyzed decarboxylative transannulation of pyridotriazo...
Scheme 11.27 Co-catalyzed transannulation of pyridotriazoles with isothiocya...
Scheme 11.28 Plausible reaction mechanism for Co-catalyzed tranasannulation ...
Scheme 11.29 Ru-catalyzed transannulation of pyridotriazole.
Scheme 11.30 Plausible reaction mechanism for Tr-catalyzed tranasannulation ...
Chapter 12
Figure 12.1 Ring-chain isomerism of pyridotriazoles and its catalytic transf...
Scheme 12.1 BF
3
.
OEt
2
-catalyzed transannulation of pyridotriazoles with nitri...
Scheme 12.2 In(OTf)
3
-catalyzed denitrogenative transannulation of pyridotria...
Scheme 12.3 Transannulation of pyridotriazoles with isothiocyanates.
Scheme 12.4 Pyridoindoloindolizines synthesis through Lewis-acid mediated tr...
Scheme 12.5 Pyridylalkylamine derivatives from pryridotriazoles. (a) Reactio...
Scheme 12.6 Acid-mediated synthesis of methylene-substituted isoquinolines....
Scheme 12.7 Metal-free cross coupling of arylboronic acids with pyridotriazo...
Scheme 12.8 Synthesis of
gem
-di-halo products from pyridotriazoles.
Scheme 12.9 Cyclopropanedicarbonitrile synthesis via thermolysis of pyridotr...
Scheme 12.10 Photolysis of substituted pyridotriazoles.
Scheme 12.11 Cyclopropanation and ylide formation from pyridotriazoles.
Scheme 12.12 Flash vacuum thermolysis of 3-acyl substituted pyridotriazoles....
Scheme 12.13 Light-induced arylation,
X
—H insertion, and cyclopropanation of...
Chapter 13
Figure 13.1 Fundamental properties of benzotriazole synthons.
Figure 13.2 Benzotriazole used as a precursor in organic transformation in d...
Scheme 13.1 Ring cleavage chemistry of 1,2,3-triazoles and benzotriazole. (a...
Scheme 13.2 The denitrogenative reactions of benzotriazoles I leading to a d...
Scheme 13.3 Common synthetic pathway for construction of benzotriazole precu...
Scheme 13.4 Pd-catalyzed cycloaddition of benzotriazoles with internal alkyn...
Scheme 13.5 Ir-catalyzed cycloaddition of benzotriazoles with terminal alkyn...
Scheme 13.6 Pd-catalyzed [2 + 2 + 1]-cycloaddition of benzotriazoles with in...
Scheme 13.7 Pd-catalyzed [2 + 2 + 2] cycloaddition of benzotriazoles with in...
Scheme 13.8 Pd-catalyzed [3 + 2]-cycloaddition of benzotriazoles with allene...
Scheme 13.9 Pd-catalyzed [3 + 2]-cycloaddition of benzotriazoles with
N
-alle...
Scheme 13.10 Pd-catalyzed carbonylative cyclization of benzotriazoles with c...
Scheme 13.11 Cu-catalyzed three-component denitrogenative cyclization reacti...
Scheme 13.12 The synthesis of quinoxalines through radical addition to
N
-vin...
Scheme 13.13 Intramolecular cyclization of benzotriazole derivatives using s...
Scheme 13.14 Intramolecular cyclization of benzotriazole derivatives using (...
Scheme 13.15 Intramolecular cyclizations of benzotriazole derivatives using ...
Scheme 13.16 AlCl
3
-mediated cyclization of
N
-acylbenzotriazoles for the synt...
Scheme 13.17 Flash vacuum pyrolysis of 1-benzoylbenzotriazole phenylhydrazon...
Scheme 13.18 Synthesis of 3-acetyl-1,2,4-benzotriazine through flash vacuum ...
Scheme 13.19 BtRC-mediated synthesis of 3-Aryl-1,2,4-benzotriazines 13.19c f...
Scheme 13.20 AllylSmBr/HMPA: A potential SET reagent for the synthesis of 3-...
Scheme 13.21 3-Aryl-1,2,4-benzotriazine derivatives obtained without HMPA wi...
Scheme 13.22 NBS-promoted synthesis of bromo-dihydrobenzofurans derivative....
Chapter 14
Scheme 14.1 Transannulation reactions of 1,2,3-thiadiazoles with unsaturated...
Scheme 14.2 Rh-catalyzed reaction of 1,2,3-thiadiazoles with alkynes.
Scheme 14.3 Rh-catalyzed intramolecular transannulation reactions of alkynyl...
Scheme 14.4 Rh-catalyzed transannulation reactions of 4-vinyl-1,2,3-thiadiaz...
Scheme 14.5 Rh-Catalyzed 1,1-hydroacylation of thioacyl carbenes with alkyny...
Scheme 14.6 Scope of thiadiazoles.
Scheme 14.7 Synthesis of oligomeric compounds.
Scheme 14.8 Synthesis of thiophenes from thiadiazoles and alkenes
via
Rh-cat...
Scheme 14.9 Scope of 1,2,3-thiadiazoles.
Scheme 14.10 Asymmetric (3 + 2) transannulations of norborenes.
Scheme 14.11 Scope of α,β-enals and 1,2,3-thiadiazoles.
Scheme 14.12 Scope of 5
H
-1,2,3-thiadiazoles and 1,3-dicarbonyls.
Scheme 14.13 Scope of nitriles.
Scheme 14.14 Scope of thiadiazoles.
Scheme 14.15 Synthesis of pentaoligomeric arylenes.
Scheme 14.16 Substrate scope of thiadiazoles bearing a cyanoalkoxycarbonyl g...
Scheme 14.17 Reactions of thioacyl carbenes with cyanoepoxides.
Scheme 14.18 Reaction with alk-2-enenitriles and alk-2-ynenitrile.
Scheme 14.19 Scope of (2 + 2 + 2) annulations.
Scheme 14.20 Reaction of 1,2,3-thiadiazoles with phosphaalkynes.
Scheme 14.21 Scope of 1,2,3-thiadiazoles and 2-arylaziridines.
Chapter 15
Scheme 15.1 Generation of reactive intermediates upon denitrogenation of 1,2...
Scheme 15.2 Ni-catalyzed denitrogenative synthesis of 1(2
H
)-isoquinolones.
Scheme 15.3 Nickel-catalyzed denitrogenative synthesis of dihydroisoquinolin...
Scheme 15.4 Ni-catalyzed reaction of 1,2,3-benzotriazin-4(3
H
)-ones with 1,3-...
Scheme 15.5 Ni-catalyzed reaction pathway of 1,2,3-benzotriazin-4(3
H
)-ones w...
Scheme 15.6 Ni-catalyzed reaction of 1,2,3-benzotriazin-4(3
H
)-ones with acti...
Scheme 15.7 Ni-catalyzed denitrogenative transannulation of 1,2,3-benzotriaz...
Scheme 15.8 Ni-catalyzed annulation reaction of 1,2,3-benzotriazin-4(3
H
)-one...
Scheme 15.9 Pd-catalyzed reaction of 1,2,3-benzotriazin-4(3
H
)-ones and isocy...
Scheme 15.10 Pd-catalyzed annulation reaction of 1,2,3-benzotriazin-4(3
H
)-on...
Scheme 15.11 Pd-catalyzed coupling reaction of 1,2,3-benzotriazin-4(3
H
)-ones...
Scheme 15.12 Mechanism proposed for denitrogenative annulation of 1,2,3-benz...
Scheme 15.13 Pd-catalyzed denitrogenative transannulation of 1,2,3-benzotria...
Scheme 15.14 Reaction of 1,2,3-benzotriazin-4(3
H
)-ones and organoboronic aci...
Scheme 15.15 Proposed mechanism for the Ni(0)-catalyzed denitrogenative cros...
Scheme 15.16 Ni(0)-catalyzed denitrogenative
ortho
-substitutions of 1,2,3-be...
Scheme 15.17 Ni-catalyzed cross-electrophile coupling reactions for the synt...
Scheme 15.18 Ni-catalyzed and manganese-assisted reaction mechanism of 1,2,3...
Scheme 15.19 Ni-catalyzed cross-electrophile coupling reactions for the synt...
Scheme 15.20 Ni-Catalyzed, zinc-assisted reaction mechanism of 1,2,3-benzotr...
Scheme 15.21 Ni-catalyzed cross-electrophile coupling reactions for the synt...
Scheme 15.22 Ni(0)-catalyzed denitrogenative coupling of 1,2,3-benzotriazin-...
Scheme 15.23 Pd-catalyzed cross-coupling reaction for the synthesis of
o
-fun...
Scheme 15.24 Pd-catalyzed cross-coupling reaction for the synthesis of
o
-alk...
Scheme 15.25 Generation of radical ion intermediate from 1,2,3-benzotriazin-...
Scheme 15.26 Visible-light mediated reaction of 1,2,3-benzotriazin-4(3
H
)-one...
Scheme 15.27 Mechanistic pathway for the synthesis of isoquinolones.
Scheme 15.28 Visible-light induced phosphorylation of 1,2,3-benzotriazin-4(3
Scheme 15.29 Visible-light induced borylation of 1,2,3-benzotriazin-4(3
H
)-on...
Scheme 15.30 Visible-light-promoted denitrogenative
ortho
-selenylation react...
Scheme 15.31 Synthesis of
N
-isoxazolyl-2-iodobenzamides from 1,2,3-benzotria...
Scheme 15.32 Synthesis of 4
H
-tetrazolo[1,5-
a
] [1,4]benzodiazepine-6-ones fro...
Scheme 15.33 Trifluoroacetic acid-mediated reaction of 1,2,3-benzotriazin-4(...
Scheme 15.34 Reaction of 1,2,3-benzotriazin-4(3
H
)-ones with organosulfonic a...
Scheme 15.35 Reaction of 1,2,3-benzotriazin-4(3
H
)-ones with sodium sulfide....
Scheme 15.36 Thermolysis of 1,2,3-benzotriazin-4(3
H
)-ones.
Scheme 15.37 Denitrogenative cleavage reaction of 1,2,3-benzotriazin-4(3
H
)-o...
Scheme 15.38 Denitrogenative cleavage reaction of 1,2,3-benzotriazin-4(3
H
)-o...
Scheme 15.39 Electrochemical transannulation of 1,2,3-benzotriazin-4(3
H
)-one...
Scheme 15.40 Pd-catalyzed denitrogenative synthesis of 3-iminothiaisoindolin...
Scheme 15.41 Ni-catalyzed denitrogenative synthesis of 3,4-dihydro-1,2-benzo...
Scheme 15.42 Visible-light mediated Ru-catalyzed reaction of 1,2,3,4-benzoth...
Scheme 15.43 Mechanistic pathway for the synthesis of biaryl sultams.
Scheme 15.44 Metal-free reaction of 1,2,3,4-benzothiatriazine-1,1(2
H
)-dioxid...
Scheme 15.45 Nickel-catalyzed denitrogenative reaction of 1,2,3,4-benzothiat...
Chapter 16
Scheme 16.1 Synthetic value and challenge of denitrogenative transformations...
Scheme 16.2 Denitrogenative ring-opening of 3-aminoindazoles for the synthes...
Scheme 16.3 Denitrogenative ring-opening of 3-aminoindazoles for the synthes...
Scheme 16.4 C3-cyanoarylation of quinoxalin-2(1
H
)-ones via denitrogenative r...
Scheme 16.5 Olefinic C—H cyanoarylation of ketene dithioacetals via denitrog...
Scheme 16.6 C—H cyanoarylation of Enamines via denitrogenative ring-opening ...
Scheme 16.7 Denitrogenation of 3-aminoindazoles for the synthesis cyanoaryla...
Scheme 16.8 Denitrogenation of 3-aminoindazoles for the synthesis of isoquin...
Scheme 16.9 Denitrogenative radical coupling reaction for the synthesis of 1...
Scheme 16.10 Cascade denitrogenative transannulation/hydrolyzation of 3-amin...
Scheme 16.11 Denitrogenative transannulation of 3-aminoindazoles for the syn...
Scheme 16.12 Oxidative N—N bond cleavage of 3-aminoindazoles for the synthes...
Chapter 17
Figure 17.1 Pioneering studies of pyridotetrazole.
Figure 17.2 Denitrogenative annulation of monocyclic tetrazoles through meta...
Figure 17.3 Denitrogenative C(sp
2
)—H amination of pyridotetrazoles via Ir–ni...
Figure 17.4 Mechanistic studies for supporting electrocyclization pathway. (...
Figure 17.5 Mn-catalyzed denitrogenative annulation of pyridotetrazoles.
Figure 17.6 Fe-catalyzed intermolecular denitrogenative annulation of pyrido...
Figure 17.7 Fe
II
-catalyzed intramolecular denitrogenative C(sp
3
)—H amination...
Figure 17.8 Mechanism of intramolecular denitrogenative C(sp
3
)—H amination....
Figure 17.9 Fe
II
-catalyzed intramolecular rearrangement over C(sp
3
)—H aminat...
Figure 17.10 Intramolecular radical C(sp
2
)—H amination.
Figure 17.11 Intermolecular radical C(sp
3
)—H amination.
Figure 17.12 Intermolecular radical C—N cross-coupling reaction.
Chapter 18
Scheme 18.1 Denitrogenative transformations of poly-nitrogen heterocycles. (...
Scheme 18.2 Synthesis of isoquinolones using visible-light-promoted denitrog...
Scheme 18.3 Control experiments and proposed mechanism. (a) Radical trapping...
Scheme 18.4 Synthesis of biaryl sultams and plausible mechanism. (a) Synthes...
Scheme 18.5 Synthesis of biaryl sultams and control experiments. (a) Synthes...
Scheme 18.6 Visible-light-induced denitrogenative phosphorylation of benzotr...
Scheme 18.7 Visible-light-promoted denitrogenative
ortho
-selenylation, appli...
Scheme 18.8 Plausible mechanism.
Scheme 18.9 Synthesis of α-oxygenated amidines from triazoles...
Scheme 18.10 Plausible mechanism.
Scheme 18.11 Synthesis of α-oxygenated amidines from tria...
Scheme 18.12 Postulated mechanism for the formation of benzothiazoles.
Scheme 18.13 Intermolecular radical addition to vinyltriazoles.
Scheme 18.14 Possible mechanism.
Scheme 18.15 Visible-light-mediated
ortho
-functionalizations. (a) Borylation...
Scheme 18.16 Plausible mechanism for the alkylation of benzotriazole.
Scheme 18.17 Synthesis of 2-substituted indoles. (a) Synthesis of
N
-benzoyl ...
Scheme 18.18 Proposed mechanism.
Scheme 18.19 Visible-light-induced C(sp
2
)—P bond formation by denitrogenativ...
Scheme 18.20 Synthesis of phenanthridines and control experiments. (a) Synth...
Scheme 18.21 Proposed mechanism.
Scheme 18.22 Transannulations of pyridotriazole with amine derivatives and c...
Scheme 18.23 Plausible mechanism.
Scheme 18.24 Cobalt(II)-catalyzed transannulations and cyclopropanations. (a...
Scheme 18.25 Control experiments and proposed mechanism. (a) Control experim...
Scheme 18.26 Co-catalyzed transannulation of pyridotriazoles with isothiocya...
Scheme 18.27 Copper-catalyzed synthesis of aromatic nitrile-containing (hete...
Scheme 18.28 Plausible mechanism.
Scheme 18.29 Copper-catalyzed synthesis of aromatic nitrile-containing (hete...
Scheme 18.30 Cu-catalyzed aromatic metamorphosis of 3-aminoindazoles. (a) Su...
Scheme 18.31 Proposed mechanism.
Scheme 18.32 Cu-catalyzed denitrogenative transannulation of 3-aminoindazole...
Scheme 18.33 Proposed mechanism for 1-amino isoquinolines.
Scheme 18.34 Cu-catalyzed synthesis of disubstituted indanones. (a) 2,2-Desu...
Scheme 18.35 Proposed mechanism.
Chapter 19
Scheme 19.1 (a) Proposed pyrrole annulation strategy. (b) Enantioselective s...
Scheme 19.2 (a) Natural products with 3,4-fused indole skeletons. (b) Synthe...
Scheme 19.3 Total synthesis of (+)-lysergol.
Scheme 19.4 Total synthesis of (−)-chanoclavine I.
Scheme 19.5 Total synthesis of stemona-lactam R.
Scheme 19.6 Total syntheses of (+)-petromyroxol.
Scheme 19.7 (a) Stereodivergent synthesis of saturated 2,3-disubstituted tet...
Scheme 19.8 Synthesis of the antidepressant agent (±)-GSK1360707.
Scheme 19.9 (a) Selected examples of indole alkaloids. (b) Synthetic route t...
Scheme 19.10 Total synthesis of (±)-aurantioclavine.
Scheme 19.11 Total synthesis of nakafuran-8.
Scheme 19.12 Photo-induced denitrogenative annulation of 1-alkenylbenzotriaz...
Scheme 19.13 Total synthesis of (a) newbouldine and (b) withasomnine.
Guide
Cover
Table of Contents
Title Page
Copyright
Dedicatoin
Preface
Begin Reading
Index
End User License Agreement
Pages
iii
iv
v
xvii
xviii
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
413
414
415
416
417
418
419
420
421
422
423
424
425
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
Denitrogenative Transformation of Nitrogen Heterocycles
Synthesis, Reactions and Applications
Edited by Pazhamalai Anbarasan
Editor
Prof. Pazhamalai AnbarasanDepartment of ChemistryIndian Institute of Technology MadrasChennai 600036Tamil NaduIndia
Cover Images:© aiperfectportraits/pixabay,Courtesy of Prof. Pazhamalai Anbarasan
All books published by WILEY-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.
Library of Congress Card No.: applied for
British Library Cataloguing-in-Publication DataA catalogue record for this book is available from the British Library.
Bibliographic information published by the Deutsche NationalbibliothekThe Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d-nb.de>.
© 2025 WILEY-VCH GmbH, Boschstraße 12, 69469 Weinheim, Germany
All rights reserved (including those of translation into other languages, text and data mining and training of artificial technologies or similar technologies). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.
Print ISBN: 978-3-527-35316-3ePDF ISBN: 978-3-527-84483-8ePub ISBN: 978-3-527-84484-5oBook ISBN: 978-3-527-84485-2
Dedicated to all the contributors in this field
Preface
Development of elegant synthetic methodologies for the construction of diverse structural motifs in pharmaceuticals, materials, and total synthesis of biologically important natural products is highly desirable in modern organic synthesis. Nitrogen heterocycles are unique structural moieties living in the core of various drug molecules and possessing the ability to act as ligands as well as directing groups in transition metal catalysis. More importantly, polynitrogen heterocycles such as N-sulfonyl-1,2,3-triazoles have been found to be shelf-stable and safe-to-handle diazo surrogate in various denitrogenative transformations to access structurally complex molecules of biological importance. Hence, development of methodologies exploiting these N-heterocycles including 5-iodotriazoles, F-containing triazoles, tetrazoles, aminoindazoles, benzotriazinones, and so on as synthetic tools has caught significant attention of researchers in past years. Therefore, a book that comprehends all type of nitrogen heterocycles in denitrogenative transformation got our attention.
The ready accessibility of a diverse range of these N-heterocycles is the key attribute for high reliance of chemists on related methodologies. Hence, the book begins with Chapter 1 highlighting the remarkable modifications encountered in the advancement of synthesis of these N-heterocycles with better yields and selectivity. Interestingly, these modifications yielded metal-free, cost-economical, and greener conditions which can even sustain in water.
The core of the book consists of 13 chapters (Chapters 2–14), which discuss the extensively studied chemistry of N-sulfonyl-1,2,3-triazoles and its analogs such as pyridotriazoles, triazoloindoles, benzotriazoles, and thiadiazoles. These diazo surrogates can afford access to unique α-diazoimine without the requirement of any additional coupling partner for generation of metal carbenoids. The beginning of a long story was crafted with simple trapping of the chain isomer of pyridotriazole and N-sulfonyl-1,2,3-triazole with Rh(II) catalyst to generate corresponding rhodium azavinyl carbenoid producing nitrogen as green by-product. Generally, this strategy revolves around the donor–acceptor metal carbenoids, which are compatible in plenty of denitrogenative transformations such as transannulations, ylide formations and rearrangements, and insertion with diverse coupling partners including alkyne, nitrile, carbonyl, carbo/heterocycles, etc. The beauty of this carbenoid system lies in the presence of an imino group next to it which facilitates the construction of various complex N-heterocycles in atom and step-economical, and waste-free manner. Of note, denitrogenative transformations of benzotriazoles involve generation of diazonium salt instead of diazoimine.
Just like the cherry on the cake, Chapters 15–17 are the beautiful addition in this book showcasing the diversity present in these N-heterocycles while keeping the key reactivity intact. These chapters introduce the denitrogenative transformations of few unique heterocycles such as benzotriazinones, 3-aminoindazoles, tetrazoles, and pyridotetrazoles, which can facilitate access into distinguished N-containing building blocks. Next, Chapter 18 flashes a light on the aspect of radical denitrogenative transformations exclusively. Eventually, the book ends at where it began as Chapter 19 emphasizes the importance of N-heterocycles in synthesis of some natural products exploiting denitrogenative transformation as key step.
Last but not the least, N-heterocycles as diazo surrogates have omitted the requirement of slow addition of carbene source in reaction mixture in contrary to traditional diazo compounds and created ample scope to tune the reactivity of the metal carbenoids by introducing electronically different substituents around. Still the chemistry of these heterocycles offers a plenty of opportunities for further development of these synthetic tools and their applications as the book depicts three major limitations manifested in the system: (i) synthesis of triazoloindoles, pyridotriazoles, thiadiazoles, and benzotriazinones are still quite underdeveloped; (ii) a diverse range of transition metal catalysts have been screened over years, but mostly, rhodium(II) carboxylates are found to be productive in denitrogenative transformation of N-heterocycles; (iii) application of these diazo surrogates in asymmetric transformations based on denitrogenative transformations is still in its infancy. Hence, further development of synthetic methodologies to attain better accessibility and applicability is desirable due to the growing demand of these heterocycles as synthetic tool. Furthermore, development of methodologies involving the photo and electrochemical denitrogenative transformations could pave the way toward a completely new synthetic arena of these nitrogen heterocycles in near future.
Pazhamalai Anbarasan
Indian Institute of Technology MadrasChennai, Tamil Nadu, India
1Synthesis of Diverse Nitrogen Heterocycles Explored in Denitrogenative Transformations
Monalisa Akter and Pazhamalai Anbarasan
Department of Chemistry, Indian Institute of Technology Madras, Chennai, Tamil Nadu, India
1.1 Introduction
Nitrogen heterocycles are extensively present in numerous drug molecules which manifest potent therapeutic activities such as antibacterial, anticancer, antiallergic, potassium-channel activator, antiplatelet, glucosidase, and HIV-1 reverse transcriptase inhibitory activities (Figure 1.1) [1].
Beside living in the core of biologically active molecules, N-heterocycles can act as ligands as well as directing groups in various transition metal catalysis. Importantly, polynitrogen heterocycles can participate in various fruitful transformations that pave the way to access structurally complex molecules of biological importance (Figure 1.2). In this context, N-sulfonyl-1,2,3-triazole and its analogs have been exclusively exploited as safe-to-handle diazo surrogates in various denitrogenative transformations. These methods yield a diverse range of structural motifs to facilitate structural modification and total synthesis of natural products and drug molecules [2–4]. Over a period of time, denitrogenative transformations of some related heterocycles such as 5-iodotriazoles [5], F-containing triazoles [6–8], tetrazoles [9, 10], pyridotetrazoles [11], and aminoindazoles [12] have also been explored and established as efficient synthetic tools.
Consequently, easily accessible, atom-economical, and widely compatible synthetic methodologies to access these diverse N-heterocycles are highly desirable. This chapter briefly showcases the development of such primitive to advanced synthetic methodologies to serve the aforementioned purposes.
1.2 Synthesis of 1,2,3-Triazoles
1.2.1 Synthesis of NH-Triazoles
NH-triazole is one of the polynitrogen heterocycles that undergoes denitrogenative transformation and their recent development emphasized its importance as a building block and their elegant synthesis. Initially, NH-triazoles were prepared via the deprotection of various N-protected triazoles. In this context, various organic azides with removable protecting groups such as benzyl [13], tropylium [14], trimethylsilyl [15, 16], tosyl [17, 18], (trimethylsilyl)ethoxymethyl (SEM) [19], and p-methoxybenzyl [20] azides have been explored along with sodium azide [21, 22]. Later, Sharpless and co-workers [23] introduced three more organic azides, azidomethyl pivalate, azidomethyl morpholine-4-carboxylate, and azidomethyl N,N-diethylcarbamate, which deliver a base-labile N-protected triazole (Scheme 1.1).
Figure 1.1 Representative drug molecules containing N-heterocycles.
Figure 1.2 Representative drug molecules and natural products synthesized through denitrogenative transformations.
Scheme 1.1 Synthesis of NH-triazoles via N-protected triazoles.
Source: Adapted from Sharpless [23].
In 1989, Banert [24] demonstrated an efficient strategy to synthesize NH-triazoles from propargyl azides under mild conditions (Scheme 1.2). Mechanistically, propargyl azide 1.2b is obtained by treatment of propargyl halide 1.2a with sodium azide, which undergoes a [3, 3]-sigmatropic rearrangement to generate the reactive allenyl azides 1.2c that readily cyclizes to triazafulvene intermediate 1.2d. Finally, the intermediate 1.2d is trapped by various nucleophiles to afford corresponding triazole 1.2e.
Scheme 1.2 Synthesis of NH-triazoles by using Banert cascade.
Source: Adapted from Banert [24].
Despite its high reliability and wide substrate scope, its synthetic utility was hardly explored. In 2005, Sharpless and co-workers [25] exclusively studied this pathway to access diverse NH-triazoles and expanded the scope of nucleophiles involved in the process (Scheme 1.3). Recently, Topczewski and co-workers [26] exploited silver(I) fluoride as nucleophile, which facilitated access to α-fluorinated NH-1,2,3-triazoles 1.3e in excellent yields.
Scheme 1.3 Synthesis of diverse NH-triazoles.
In 2016, Dehaen and co-workers [27] disclosed the synthesis of various mono-, di-, and tri-substituted triazoles 1.4c from the reaction of enolizable ketones 1.4a, NH4OAc, and nitrophenyl azide 1.4b under mild acidic condition (Scheme 1.4). Simultaneously, a β-cyclodextrin-mediated multicomponent synthesis of NH-triazoles 1.4e from propynals 1.4d, trimethylsilyl azide, and malononitrile in water was reported by Medvedeva and co-workers [28]. Besides, the use of amine in place of malononitrile under microwave irradiation furnished the imine-substituted triazole with a shorter reaction time [29]. Subsequently, Guan and co-workers [30–33] accomplished the synthesis of various 4-aryl-NH-1,2,3-triazoles 1.4g through three-component reaction of aldehydes 1.4f, nitromethane, and NaN3. Later, Negrón-Silva and co-workers [34] developed a heterogeneous catalytic system consisting of Al-MCM-41 and sulfated zirconia to accomplish the same synthesis.
Scheme 1.4 Synthesis of NH-triazoles through three-component reactions.
In 2019, Shu and Wu reported a molecular iodine-mediated cascade [4 + 1] cyclization of N-tosylhydrazones 1.5a and sodium azide in presence of MsOH to access 4-aryl-NH-1,2,3-triazoles 1.5b (Scheme 1.5) [35]. Subsequently, the group of Gao and Shu achieved the synthesis of 4-aryl-NH-1,2,3-triazoles 1.5dvia an iodine-mediated condensation-cyclization of α-azido ketones 1.5c with p-toluenesulfonyl hydrazide [36]. Recently, Wu and co-workers demonstrated the synthesis of NH-triazole under azide-free conditions via an iodine-mediated [2 + 2 + 1] cyclization of methyl ketones 1.5e, p-toluenesulfonyl hydrazide, and 1-aminopyridinium iodide 1.5f[37]. Solvent-free synthesis of 4-aryl-NH-1,2,3-triazoles 1.5i has been demonstrated by Matsugi and co-workers [38] from benzyl ketones 1.5h exploiting diphenyl phosphorazidate in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).
Scheme 1.5 Synthesis of 4-aryl-NH-1,2,3-triazoles.
Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles 1.6b was reported by Wen and Wan, which involves water-mediated cycloaddition reactions of enaminones 1.6a and tosyl azide (Scheme 1.6) [39, 40]. Instead of enaminones, Gribanov et al. [41] employed alkylnitriles 1.6c and azide 1.6d in the presence of KOtBu for the synthesis of 5-amino-1,2,3-triazoles 1.6e, which on subsequent Dimroth rearrangement affords 1.6f at elevated temperature under solvent-free conditions in one pot.
Scheme 1.6 Synthesis of various NH-triazoles.
1.2.2 Synthesis of N-Sulfonyl-1,2,3-triazoles
For years, a large number of N-sulfonyl-1,2,3-triazoles have been extensively exploited as diazo surrogate in numerous denitrogenative transformations. In general, sulfonylation of NH-1,2,3-triazoles 1.7a with sulfonyl chlorides could furnish the corresponding N-sulfonyl-1,2,3-triazoles 1.7b (Scheme 1.7). But the major drawback of this strategy is the formation of a mixture of regioisomeric products 7.2 and 1.7c, which significantly reduces its efficiency and applicability [42].
Scheme 1.7 Synthesis of N-sulfonyl-1,2,3-triazoles from NH-triazoles.
Source: Adapted from Beryozkina and Fan [42].
On the other hand, 1,2,3-triazoles 1.8d were readily achieved through the copper-catalyzed azide-alkyne cycloaddition (CuAAC) as reported by Sharpless and co-workers in 2002 (Scheme 1.8) [43–45]. This reaction appeared to be the most effective click reaction over the traditional Huisgen cycloaddition due to its remarkably high regioselectivity and yields. Various 1,4-disubstituted triazoles 1.8d could be synthesized from terminal alkynes 1.8a and azides 1.8b (Scheme 1.8). However, the use of sulfonyl azides led to the formation of various secondary products 1.8g instead of the desired triazoles 1.8dvia the generation of ketenimine intermediate 1.8f [46, 47]. The formation of ketenimine was due to the poor stability of the copper-triazole species 1.8c.
Scheme 1.8 Synthesis of N-sulfonyl-1,2,3-triazoles through CuAAC.
Source: Adapted from Sharpless [43].
To increase the stability of sulfonyl substituted 1.8c and for the synthesis of sulfonyltriazoles, in 2007, for the first time, Chang, Fokin and co-workers utilized stoichiometric amount of base, 2,6-dimethylpyridine in the CuI-catalyzed selective synthesis of 4-substituted N-sulfonyl-1,2,3-triazoles from the corresponding terminal alkynes and sulfonyl azides (Scheme 1.9) [48, 49]. Subsequently, Fu and co-workers [50] reported an inexpensive catalytic system by exploiting the thioanisole as ligand in combination with CuBr in water medium at room temperature. It was emphasized that the addition of sulfur-containing ligands could inhibit cleavage of N1—N2 bond and stabilize the 5-cuprated triazole species. Two years later, Pérez and co-workers [51] demonstrated the synthesis of N-sulfonyl-1,2,3-triazoles using well-defined copper complex, [Tpm*,BrCu(NCCH3)]BF4. On the other hand, Raushel and Fokin [52] employed Cu(I)-thiophene-2-carboxylate (CuTC) complex, in the absence of external ligand, under mild conditions for more efficient and general synthesis of N-sulfonyltriazoles (Scheme 1.9).
Scheme 1.9 Cu-catalyzed synthesis of N-sulfonyl-1,2,3-triazoles.
In 2011, Hu and co-workers [53] reported 2-aminophenol as a suitable ligand in copper-catalyzed highly selective synthesis of N-sulfonyltriazoles. Herein, it was proposed that 2-aminophenol plays a dual role as a reductant and ligand. Importantly, the first triazole possessing two electron-withdrawing groups was synthesized successfully by using this strategy. In 2018, Cazin and co-workers [54] employed Cu(I)-NHC complexes for the selective synthesis of 4-substituted 1,2,3-triazoles through click reaction.
But the limitation of all these above-mentioned methods remains in the selective synthesis of 1,4-disubstituted triazoles. Croatt and co-workers [55] documented the synthesis of 5-substituted N-sulfonyl-1,2,3-triazoles 1.10c from corresponding terminal alkynes 1.10a and sulfonyl azides 1.10b using a strong base, such as n-BuLi (Scheme 1.10). Interestingly, the synthesis of various 1,4,5-trisubstituted triazoles was also achieved by trapping the 4-lithio-1,5-disubstituted triazole in the reaction mixture with suitable electrophiles. In 2008, Ramachary and co-workers reported the first proline-catalyzed synthesis of 4,5-disubstituted triazoles 1.10f from Hagemann’s ester 1.10d and tosyl azides 1.10e[56]. Later, Anbarasan and co-workers [57] accomplished a general proline-mediated synthesis of a diverse range of 4,5-disubstituted 1,2,3-triazoles 1.10i with excellent regioselectivity from substituted 1,3-dicarbonyl compounds 1.10g and sulfonyl azides 1.10h through enamine-azide cycloaddition.
Scheme 1.10 Synthesis of multisubstituted N-sulfonyl-1,2,3-triazoles.
In 2016, Zhang and co-worker [58] achieved the synthesis of 4-substituted 1,2,3-triazoles 1.11c from (Z)-arylvinyl bromides 1.11a and sulfonyl azides through the generation of arylacetylene (Scheme 1.11). This strategy involves KOH-promoted HBr elimination from the vinylbromide 1.11a followed by a copper-catalyzed [3 + 2] cycloaddition of the resulted alkyne 1.11b with azide. Subsequently, Ma and co-workers [59] reported a regioselective synthesis of 5-sulfamido-N-sulfonyl-1,2,3-triazoles 1.11f in high yields through a Cu-catalyzed cycloaddition of terminal alkynes 1.11d and sulfonyl azides 1.11e using 1.2 equivalents of LiOtBu. Most recently, Kim and co-workers [60] reported the first continuous flow synthesis of N-sulfonyl-1,2,3-triazoles.
