Transition Metal-Catalyzed Heterocycle Synthesis via C-H Activation E-Book
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- Herausgeber: Wiley-VCH
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
Reflecting the tremendous growth of this hot topic in recent years, this book covers C-H activation with a focus on heterocycle synthesis.
As such, the text provides general mechanistic aspects and gives a comprehensive overview of catalytic reactions in the presence of palladium, rhodium, ruthenium, copper, iron, cobalt, and iridium. The chapters are organized according to the transition metal used and sub-divided by type of heterocycle formed to enable quick access to the synthetic route needed. Chapters on carbonylative synthesis of heterocycles and the application of C-H activation methodology to the synthesis of natural products are also included.
Written by an outstanding team of authors, this is a valuable reference for researchers in academia and industry working in the field of organic synthesis, catalysis, natural product synthesis, pharmaceutical chemistry, and crop protection.
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Seitenzahl: 738
Veröffentlichungsjahr: 2015
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Table of Contents
Cover
Related Titles
Title Page
Copyright
Dedication
List of Contributors
Foreword 1
Foreword 2
Preface
Chapter 1: Computational Studies of Heteroatom-Assisted C−H Activation at Ru, Rh, Ir, and Pd as a Basis for Heterocycle Synthesis and Derivatization
1.1 Introduction
1.2 Palladium
1.3 Ruthenium, Rhodium, and Iridium
1.4 Conclusions
Acknowledgments
References
Chapter 2: Pd-Catalyzed Synthesis of Nitrogen-Containing Heterocycles
2.1 Introduction
2.2 General Consideration on Palladium Chemistry
2.3 Heterocycle Synthesis via C(sp
3
)−H Activation
2.4 Heterocycles via C(sp
2
)−H Activation
2.5 Conclusions
References
Chapter 3: Pd-Catalyzed Synthesis of Oxygen-Containing Heterocycles
3.1 Introduction
3.2 Palladium-Catalyzed C−H Activation/C−C Formation to Construct Oxacycles
3.3 Palladium-Catalyzed C−H Activation/C−O Formation to Construct Oxacycles
3.4 Conclusions
References
Chapter 4: Pd-Catalyzed Synthesis of Other Heteroatom-Containing Heterocycles
4.1 Introduction
4.2 Sulfur-Containing Heterocycles
4.3 Phosphorus-Containing Heterocycles
4.4 Silicon-Containing Heterocycles
4.5 Summary and Conclusions
References
Chapter 5: Rh-Catalyzed Synthesis of Nitrogen-Containing Heterocycles
5.1 Introduction
5.2 Synthesis of Five-Membered Nitrogen Heterocycles
5.3 Synthesis of Six-Membered Nitrogen Heterocycles
5.4 Synthesis of Quaternary Ammonium Salts
5.5 Synthesis of Seven-Membered Nitrogen Heterocycles
5.6 Summary and Conclusions
References
Chapter 6: Rh-Catalyzed Synthesis of Oxygen-Containing Heterocycles
6.1 Introduction
6.2 Synthesis of Five-Membered Oxygen-Containing Heterocycles
6.3 Synthesis of Six-Membered Oxygen-Containing Heterocycles
6.4 Synthesis of Seven-, Eight-, and Nine-Membered Oxygen-Containing Heterocycles
6.5 Summary and Conclusions
References
Chapter 7: Ruthenium-Catalyzed Synthesis of Heterocycles via C−H Bond Activation
7.1 Introduction
7.2 Ruthenium-Catalyzed Heterocycle Synthesis via Intramolecular C−C Bond Formation Based on C−H Bond Activation
7.3 Ruthenium-Catalyzed Heterocycle Synthesis via Intramolecular C−N Bond Formation Based on C−H Bond Activation
7.4 Ruthenium-Catalyzed Heterocycle Synthesis via Intermolecular C−C/C−O Bond Formation Based on C−H Bond Activation
7.5 Ruthenium-Catalyzed Heterocycle Synthesis via Intermolecular C−C/C−N Bond Formation Based on C−H Bond Activation
7.6 Summary and Conclusions
References
Chapter 8: Cu-Catalyzed Heterocycle Synthesis
8.1 Introduction
8.2 Four-Membered-Ring Formation
8.3 Five-Membered-Ring Formation
8.4 Six-Membered-Ring Formation
8.5 Summary
References
Chapter 9: Fe- and Ag-Catalyzed Synthesis of Heterocycles
9.1 Introduction
9.2 Iron-Catalyzed Synthesis of Heterocycles
9.3 Silver-Catalyzed Synthesis of Heterocycles
9.4 Conclusion and Outlook
References
Chapter 10: Heterocycles Synthesis via Co-Catalyzed C−H Bond Functionalization
10.1 Introduction
10.2 Heterocycle Synthesis via Low-Valent Cobalt-Catalyzed C−H Activation
10.3 Heterocycle Synthesis via High-Valent Cobalt-Catalyzed C−H Activation
10.4 Heterocycle Synthesis via C−H Functionalization under Co(II)-Based Metalloradical Catalysis
10.5 Summary and Conclusions
References
Chapter 11: Ir-Catalyzed Heterocycles Synthesis
11.1 Introduction
11.2 Ir-Catalyzed Heterocyclization by
ortho
-Aryl C−H Activation
11.3 Ir-Catalyzed Heterocyclization by Benzylic C−H Activation
11.4 Ir-Catalyzed Heterocyclization by sp
3
C−H Activation
11.5 Heterocyclization by Ir Catalyst as Lewis Acid
11.6 Ir-Catalyzed Heterocyclization by C−H Bond Activation through Transfer Hydrogenation
11.7 Miscellaneous Reactions
11.8 Summary and Conclusions
References
Chapter 12: Au- and Pt-Catalyzed C−H Activation/Functionalizations for the Synthesis of Heterocycles
12.1 Introduction
12.2 Synthesis of
O
-Heterocycles
12.3 Synthesis of
N
-Heterocycles
12.4 Synthesis of
S
-Heterocycles
12.5 Synthesis of
O
-Heterocycles and
N
-Heterocycles
12.6 Synthesis of Fused Polycyclic Polyheterocycles
12.7 Conclusions
References
Chapter 13: Heterocycle Synthesis Based on Visible-Light-Induced Photocatalytic C−H Functionalization
13.1 Introduction
13.2
de novo
Synthesis of Heterocycles
13.3 Direct C−H Functionalization of Heteroarenes
13.4 Summary and Outlook
References
Chapter 14: Heterogeneous C−H Activation for the Heterocycle Synthesis
14.1 Introduction
14.2 Heterogeneous Pd-Catalyzed Heterocycle Synthesis via C−H Activation
14.3 Heterogeneous Photocatalysis for the Heterocycle Synthesis via C−H Activation
14.4 Summary
References
Chapter 15: Transition Metal-Catalyzed Carbonylative Synthesis of Heterocycles via C−H Activation
15.1 Introduction
15.2 Cobalt-Catalyzed Heterocyclic Synthesis via Carbonylative C−H Activation
15.3 Rhodium-Catalyzed Heterocyclic Synthesis via Carbonylative C−H Activation
15.4 Ruthenium-Catalyzed Heterocyclic Synthesis via Carbonylative C−H Activation
15.5 Palladium-Catalyzed Heterocyclic Synthesis via Carbonylative C−H Activation
15.6 Summary and Outlook
References
Chapter 16: Synthesis of Natural Products and Pharmaceuticals via Catalytic C−H Functionalization
16.1 Introduction
16.2 Natural Products Containing Heteroaromatics
16.3 Summary
References
Index
End User License Agreement
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Guide
Cover
Table of Contents
Foreword 1
Preface
Begin Reading
List of Illustrations
Chapter 1: Computational Studies of Heteroatom-Assisted C−H Activation at Ru, Rh, Ir, and Pd as a Basis for Heterocycle Synthesis and Derivatization
Figure 1.1 Computed reaction profile for C−H activation in Pd(OAc)
2
(Me
2
NCH
2
Ph). Energies are in kcal/mol and include a correction for zero-point energies; selected distances in Å [8].
Figure 1.2 C−H activation transition states derived from
4
, involving internal (
TS4A
) and external (
TS4B
) deprotonation. Computed free energies in kcal mol
−1
and key distances in Å [10].
Figure 1.3 (a) Pd-catalyzed formation of dihydrobenzofurans and (b) alternative transition states for C(sp
3
)−H activation with computed free energies relative to Pd(Ar)(OAc)(PMe
3
),
7
, in kcal mol
−1
[12].
Figure 1.4 (a) Pd-catalyzed formation of cyclobutarenes and (b) transition state for C(sp
3
)−H activation via deprotonation of a C−H bond that is geminal to an agostic interaction; key distances in Å [14].
Figure 1.5 Pd-catalyzed formation of indolinones (experiment, R = Cy, R′ =
t
Bu) with selected key intermediates based on B3LYP calculations (R = Me, R′ = Me, relative free energies in kcal mol
−1
) [18].
Figure 1.6 Cyclometalation transition state structures for (a)
N
-methylbenzylimine at Pd(OAc)
2
in acetic acid [19]; (b)
N
-methoxybenzamide at Pd(OAc)
2
in methanol [20]; and (c) an anionic alanine amide species at Pd(2-Me−C
5
H
4
N)(HCO
3
) (PhthN = phthalimido; Ar
F
= 4-C
6
F
4
−CF
3
) [21].
Figure 1.7
Meta
selectivity via remote CN directing groups: (a) Pd-catalyzed alkenylation of
16–17
in the presence of an MPAA coligand via computed C−H activation transition state
TS16
featuring deprotonation by the
N
-acyl group (Ar = 2-C
6
H
4
−CN) [22] and (b) Pd/Ag-catalyzed alkenylation of
18–19
via computed heterobimetallic C−H activation transition state
TS18
[23].
Figure 1.8 (a) Pd-catalyzed amination of N-arylbenzamides (experiment, R =
t
Bu, Ar = 4-C
6
F
4
CF
3
, X = Cl, OAc,OBz) and (b) computed CsF-stabilized heterobimetallic transition state (R = Ar = H) [25].
Figure 1.9 Computed C−H activation transition state for C(sp
3
)−H bond activation of oxazolines (R
1
= R
2
=
t
Bu,
25a
; R
1
= Et, R
2
=
i
Pr,
25b
), highlighting the preferred
anti
arrangement for
25a
[30].
Figure 1.10 Enantioselective indoline formation from
R
-
26
via Pd−NHC intermediate
27.
Free energies (at 413 K) for the enantio-determining C−H activation transition states leading to products
cis
-/
trans
-
28
and
29
are indicated in kcal mol
−1
[31a].
Figure 1.11 Computed reaction profile for C−H activation of benzene at Pd(κ
2
-CO
2
H)
2
; MP4(SDQ) energies are in kcal mol
−1
and selected distances in Å [32].
Figure 1.12 Computed transition state for C−H bond activation of C
6
F
5
H at Pd(Ph)(HCO
3
)(P
t
Bu
2
Me), with selected distances in Å [33].
Figure 1.13 Computed free energy activation barriers (kcal mol
−1
) for C−H activation of selected heterocycles at Pd(Ph)(OAc)(PMe
3
) [35].
Figure 1.14 The activation strain model illustrated for C−H activation of benzene at Pd(Ph)(κ
2
-OAc)(PMe
3
) with component energies indicated in kcal mol
−1
[37a].
Figure 1.15 Different reactivity trends in the direct arylation of thiazole and 2-methylthiophene [42].
Figure 1.16 C4 versus C5 selectivity in the direct arylation of 2-phenyl-3-methoxythiophene [45].
Figure 1.17 Pd-catalyzed
meta
-selective alkenylation of pyridine in the presence of an MPAA coligand (experiment R =
n
Bu; computed R = Et) [46].
Figure 1.18 Computed free energy activation barriers (kcal mol
−1
) for C−H activation at Pd(Ph)(κ
2
-OAc)(PMe
3
) for
N
-methylimidazole and oxazole (with and without bound CuCl), thiozole, and thiazole
N
-oxide [37c].
Figure 1.19 Computed key stationary points with energies in kcal mol
−1
for the reactions of thiophene and
N
-methylimidazole at a Pd(OAc)
2
catalyst [52].
Figure 1.20 Proposed mechanism for the direct arylation of pyridine
N
-oxides in the Pd(OAc)
2
/P
t
Bu
3
system.
Figure 1.21 Direct, C8-selective arylation of QNO by Pd(OAc)
2
in acetic acid and the proposed computed transition state [57].
Figure 1.22 C−H activation transition state for cyclometalation of 2-phenylpyridine at {
cis
-Ru(Cl)
2
(IMe)} in the presence of bicarbonate base [60].
Figure 1.23 (a) Cyclometalation of
N
-alkylimines (
H-L
1–5
) and 2-phenylpyridine (
H-L
6
) at [MCl
2
Cp*]
2
(M = Rh, Ir); relative experimental and computed reactivities for substrates
H-L
1–6
at [MCl
2
Cp*]
2
, (b) M = Rh, and (c) M = Ir. Computed data (kcal mol
−1
) give the overall free energy changes, Δ
G
calc
, for M = Rh and calculated activation barriers, Δ
G
‡
calc
, for M = Ir [61].
Figure 1.24 Computed free energy reaction profiles (kcal mol
−1
) for C−H activation of
H-L
3
at [MCl
2
Cp*]
2
for M = Ir (in CH
2
Cl
2
) and M = Rh (in MeOH). Computed C−H activation transition states are shown with key distances in Å (Rh, plain text; Ir, italics) and nonparticipating H atoms omitted for clarity.
Figure 1.25 Comparison of OMe-assisted and σ-bond metathesis transition states at [Ir]R species ([Ir] = Ir(acac)
2
; R = OMe,
TS50
[68]; R = PhCH
2
CH
2
,
TS51
[69]). Key selected distances are given in Å.
Figure 1.26 Key distances (Å) and relative free energies (kcal mol
−1
) in transition states for C(sp
3
)−H activation (
TS54
) and C(sp
2
)−H activation (
TS55
) of an α-imidazolium ester,
53
, at Ir(OAc)
2
Cp*.
Figure 1.27 Computed catalytic cycle for the coupling of
N
-acetoxybenzamide with acetylene at Rh(OAc)
2
Cp [75]. Computed free energies of intermediates and transition states are given in kcal mol
−1
, with the latter indicated in square brackets, and are quoted relative to the reactants at 0.0 kcal mol
−1
.
Figure 1.28 (a) Reactions of PhC(O)NH(OR) (OR = OMe, OPiv) with ethene at Rh(OAc)
2
Cp* [76]. Key stationary points (kcal mol
−1
; free energies quoted relative to the reactants at 0.0 kcal mol
−1
) for (b) alkenylation for OR = OMe and OPiv (in italics); data for the onward reaction of
III
OR
for OMe only; and (c) C(sp
3
)−N coupling for OR = OPiv. Double arrows indicate several steps are involved with the energy of the highest transition state between the two minima indicated in square brackets.
Figure 1.29 Regioselective dihydroisoquinolone formation with Rh-cyclopentadienyl catalysts [77].
Figure 1.30 Rh-catalyzed lactam formation from
N
-acetoxybenzamide and 3-methylhexa-1,2,5-triene [78].
Figure 1.31 Rh-catalyzed benzocyclopentanone formation from benzophenone ammonium salts and α-diazoesters (R = CO
2
i
Pr) [80].
Figure 1.32 Key stationary points on free energy profiles (kcal mol
−1
) for the Rh(OAc)
2
Cp*-catalyzed reaction of 2-acetyl-1-arylhydrazines with diphenylacetylene to give indoles [81]. Double arrows indicate several steps are involved, with the energy of the highest transition state between the two minima indicated in square brackets.
Figure 1.33 (a) Rh- and Ru-catalyzed oxidative coupling of 5-methyl-3-phenylpyrazole and 4-octyne to form a pyrazoloisoquinoline. (b) Key stationary points on the free energy profiles (kcal mol
−1
) for (i) {RhCp*} (BP86(DCE), red), (ii) {RhCp*} (BP86-D3(DCE), blue), and (iii) {Ru(
p
-cymene)} (BP86-D3(MeOH), black), quoted relative to reactants set to 0.0 kcal mol
−1
in each case [84].
a
8.6 kcal mol
−1
corresponds to the lowest point on the profile and is the N−H-activated form of
I.
b
The formation of
II
from
I
involves several steps and
TS(I–II)
is the highest point in this process.
Figure 1.34 Rate-limiting transition states with key distances (Å) for the C−H activation of 5-methyl-3-phenylpyrazole at {Rh(OAc)Cp*} (
TS(I–II)
Rh
) and {Ru(OAc)(
p
-cymene)} (
TS(I–II)
Ru
). Associated experimental and computed
k
H
/k
D
KIE data are also shown [84].
Figure 1.35 (a) Ru-catalyzed oxidative coupling of benzylamines with 2-butyne to form isoquinolones; (b) transition state for C−H activation via external deprotonation with key distances (Å); and (c) key stationary points on the free energy profile (kcal mol
−1
; energies quoted relative to the reactants at 0.0 kcal mol
−1
). Double arrows indicate several steps are involved, with the energy of the highest transition state between the two minima indicated in square brackets [85].
Figure 1.36 (a) Ir-catalyzed isocoumarin formation [86] and (b) Rh-catalyzed phosphaisocoumarin formation [87].
Figure 1.37 (a) Rh-catalyzed alkenylation of
m
-tolyldimethylcarbamate with ethyl acrylate and (b) key stationary points on the free energy profile (kcal mol
−1
; energies quoted relative to the reactants at 0.0 kcal mol
−1
) [90].
Figure 1.38 Rh-catalyzed alkenylation reactions: (a) 3-phenylpyrazole with H
2
C=CHR (R = Ph, CO
2
Me) [92] and (b)
N
-methoxybenzamide with dimethyl-2-vinylcyclopropane-1,1-dicarboxylate [93].
Figure 1.39 Gp 9-catalyzed amination of
N-tert
-butylbenzamide with organic azides, along with the structure of the AMLA-4 C−H activation transition state,
TS60
, with key distances in Å.
Chapter 2: Pd-Catalyzed Synthesis of Nitrogen-Containing Heterocycles
Figure 2.1 Nitrogen-containing heterocycles.
Scheme 2.1 C(sp
3
)−H activation strategies: (a) the allylic C−H activation and (b) the unactivated C−H activation. DG = directing group.
Scheme 2.2 Larock's allylic C−H activation.
Scheme 2.3 Broggini's allylic C−H activation.
Scheme 2.4 White's allylic C−H activation.
Scheme 2.5 A macrolactonization reaction via allylic C−H activation.
Scheme 2.6 Poli's allylic C−H activation.
Scheme 2.7 Synthesis of indolines by C(sp
3
)−H activation.
Scheme 2.8 The relative reactivity of activated versus unactivated C−H bonds.
Scheme 2.9 Intramolecular competition experiment.
Scheme 2.10 Proposed mechanism for indoline formation.
Scheme 2.11 Azetidine formation.
Scheme 2.12 Synthesis of pyrrolidine via C−H activation.
Scheme 2.13 Heterocycle synthesis via C−H activation.
Scheme 2.14 Controlled experiment.
Scheme 2.15 Heterocycle synthesis via four-membered-ring cyclopalladation complex.
Scheme 2.16 Scope of aziridination reaction.
Scheme 2.17 Scope of the C−H carbonylation reaction.
Scheme 2.18 Pd-catalyzed C(sp
3
)−H carbonylation.
Scheme 2.19 Carbazole synthesis via C(sp
2
)−H activation.
Scheme 2.20 Indazole synthesis via C(sp
2
)−H activation.
Scheme 2.21 Proposed mechanistic hypothesis for C(sp
2
)−H activation.
Scheme 2.22 Carbazole synthesis via C(sp
2
)−H activation.
Scheme 2.23 Formation of
N
-glycosyl carbazoles.
Scheme 2.24 Indoline synthesis via C(sp
2
)−H activation.
Scheme 2.25 Synthesis of condensed pyrroloindoles via intramolecular C(sp
2
)−H activation.
Scheme 2.26 Proposed mechanistic pathways.
Chapter 3: Pd-Catalyzed Synthesis of Oxygen-Containing Heterocycles
Figure 3.1 Selected examples of functional molecules containing oxacycles.
Scheme 3.1 General pathways for the synthesis of oxacycles. (a) C−H activation/C−O formation and (b) C−H activation/C−C formation.
Scheme 3.2 Pd-catalyzed intramolecular arylation of phenol derivatives.
Scheme 3.3 Pd-catalyzed intramolecular C−H arylation reaction to construct sultones.
Scheme 3.4 Pd-catalyzed synthesis of dibenzofurans via intramolecular C−H arylation.
Scheme 3.5 Pd-catalyzed intramolecular C−H arylation of indoles.
Scheme 3.6 Synthesis of coumarins and 3,4-dihydrocoumarins.
Scheme 3.7 Pd(II)-catalyzed reaction of phenols with acrylates.
Scheme 3.8 The one-pot process of sequential dehydrogenation-oxidative Heck cyclization.
Scheme 3.9 Palladium-catalyzed directed C−H alkenylation of phenols.
Scheme 3.10 Pd(II)-catalyzed C−H alkenylation/C−O cyclization of flavones.
Scheme 3.11 Palladium-catalyzed cycloaddition of alkynyl aryl ethers with internal alkynes.
Scheme 3.12 Palladium-catalyzed domino reaction.
Scheme 3.13 Palladium-catalyzed synthesis of benzofurans.
Scheme 3.14 Palladium-catalyzed one-pot synthesis of benzofurans.
Scheme 3.15 Palladium-catalyzed oxidative annulation of phenols and alkynes.
Scheme 3.16 Pd-catalyzed oxidative coupling of benzoic acids and vinyl arenes.
Scheme 3.17 Pd(II)-catalyzed hydroxyl-directed C−H olefination.
Scheme 3.18 Formation of oxygen-containing tricyclic heterocycles.
Scheme 3.19 Construction of polycyclic oxacycles based on Catellani reaction.
Scheme 3.20 Palladium-catalyzed synthesis of benzolactones.
Scheme 3.21 Pd-catalyzed C−H carbonylation of benzoic and phenylacetic acid derivatives.
Scheme 3.22 Pd-catalyzed C−H carbonylation synthesis of isatoic anhydrides.
Scheme 3.23 Pd-catalyzed C−H carbonylation synthesis of oxaphosphorinanone oxides.
Scheme 3.24 Pd-catalyzed synthesis of oxaphosphorinanone oxides via C−H carbonylation.
Scheme 3.25 Pd-catalyzed C−H carbonylation of phenol to prepare lactones.
Scheme 3.26 Pd-catalyzed C−H carbonylation of phenol to prepare lactones.
Scheme 3.27 Pd-catalyzed C−H carbonylation to prepare polycyclic heterocyclic compounds.
Scheme 3.28 Pd-catalyzed C−H carbonylation of diaryl ethers to prepare xanthones.
Scheme 3.29 Pd-catalyzed C−H carboxylation of 2-hydroxystyrenes to prepare coumarins.
Scheme 3.30 Pd-catalyzed C−H activation/C−O cyclization of aliphatic alcohol.
Scheme 3.31 Enantioselective synthesis of highly functionalized 2,3-dihydrobenzofurans.
Scheme 3.32 Pd-catalyzed silanol-directed C−H oxygenation.
Scheme 3.33 Pd-catalyzed C−H activation/C−O cyclization of 2-arylphenols.
Scheme 3.34 Pd(II)-catalyzed enantioselective C−H activation/C−O bond formation.
Scheme 3.35 Pd(II)-catalyzed C−H activation/C−O cyclization to benzofuranones.
Scheme 3.36 Pd(II)-catalyzed C−H activation/C−O cyclization of biphenyl carboxylic acid.
Scheme 3.37 Pd-catalyzed C(sp
2
and sp
3
)−H activation/C−O bond formation.
Scheme 3.38 Synthesis of oxazole and thiazole derivatives.
Scheme 3.39 Palladium-catalyzed cyclization of alkenoic acids to synthesize lactones.
Scheme 3.40 Synthesis of oxazolidinones via allylic C−H oxidation.
Scheme 3.41 Synthesis of chromans, isochromans, and pyrans via allylic C−H oxidation.
Scheme 3.42 Oxidative cyclization of 4-alkenoic acid derivatives.
Chapter 4: Pd-Catalyzed Synthesis of Other Heteroatom-Containing Heterocycles
Scheme 4.1 Pd-catalyzed direct synthesis of benzo[
b
]thiophenes from thioenols.
Scheme 4.2 The proposed mechanism.
Scheme 4.3 Palladium-catalyzed synthesis of dibenzothiophenes from aryl sulfoxides.
Scheme 4.4 Palladium-catalyzed arylation of 2-bromo-diaryl sulfoxides.
Scheme 4.5 Synthesis of dibenzothiophenes by Pd-catalyzed dual C−H activation.
Scheme 4.6 Synthesis of sulfur-bridged polycycles via Pd-catalyzed dehydrogenative cyclization.
Scheme 4.7 Pd-catalyzed regioselective C−S bond cleavage of thiophenes.
Scheme 4.8 The proposed mechanism.
Scheme 4.9 Palladium-catalyzed synthesis of 2-substituted benzothiazoles.
Scheme 4.10 Palladium-catalyzed synthesis of 2-aminobenzothiazoles.
Scheme 4.11 Pd- and Cu-catalyzed regioselective synthesis of 2-aminobenzothiazoles.
Scheme 4.12 Synthesis of sugar-based benzothiazoles through C−S coupling.
Scheme 4.13 Palladium-catalyzed synthesis of 2-trifluoromethylbenzothiazoles.
Scheme 4.14 Synthesis of sultones via Pd-catalyzed intramolecular direct arylation.
Scheme 4.15 Pd-catalyzed intramolecular coupling reaction of benzenesulfonic acid 2-bromophenyl esters.
Scheme 4.16 Pd-catalyzed intramolecular coupling reaction of 2-bromobenzenesulfonic acid phenyl esters.
Scheme 4.17 Pd-catalyzed synthesis of tricyclic sultones.
Scheme 4.18 Pd-catalyzed intramolecular coupling reaction to synthesize polycyclic sultams.
Scheme 4.19 The proposed mechanism.
Scheme 4.20 Synthesis of skeletally diverse benzofused sultams based on a central α-halo benzene sulfonamide.
Scheme 4.21 The several methods for the synthesis of phospholes.
Scheme 4.22 Pd-catalyzed synthesis of dibenzophosphole oxides.
Scheme 4.23 Proposed mechanism for the formation of dibenzophosphole oxides.
Scheme 4.24 Pd-catalyzed synthesis of a phosphine oxide with a chiral phosphorus center via C−H phosphination.
Scheme 4.25 Pd-catalyzed intramolecular direct arylation reactions of ortho-halodiaryl-phosphine oxides.
Scheme 4.26 Pd-catalyzed direct synthesis of phosphole derivatives from triarylphosphines.
Scheme 4.27 A possible mechanism.
Scheme 4.28 Pd-catalyzed C−H activation/C−O bond formation.
Scheme 4.29 Palladium-catalyzed carbonylation of C−H bonds of phosphonic and phosphinic acids.
Scheme 4.30 Proposed mechanism of carbonylation.
Scheme 4.31 Pd-catalyzed C−H intramolecular amination oriented by a phosphinamide group.
Scheme 4.32 Synthesis of functionalized 9-silafluorenes via palladium-catalyzed intramolecular direct arylation.
Scheme 4.33 Palladium-catalyzed intramolecular coupling of 2-[(2-pyrrolyl)silyl]aryl triflates through 1, 2-silicon migration.
Scheme 4.34 A plausible mechanism.
Scheme 4.35 Pd-catalyzed asymmetric synthesis of Si-stereogenic dibenzosiloles.
Scheme 4.36 Proposed reaction pathways to dibenzosilole and its isomer.
Scheme 4.37 Arylation of TBDPS-protected
o
-bromophenols.
Scheme 4.38 The transformation of oxasilacycles and azasilacycle to arylated phenols and aniline.
Chapter 5: Rh-Catalyzed Synthesis of Nitrogen-Containing Heterocycles
Scheme 5.1 A possible mechanism for the synthesis of
N
-heterocycles by C−H bond activation.
Scheme 5.2 Proposed catalytic mechanism for indole formation.
Chapter 6: Rh-Catalyzed Synthesis of Oxygen-Containing Heterocycles
Scheme 6.1 Selected examples of natural products, pharmaceuticals, and biologically active compounds with oxygen-containing heterocycles.
Scheme 6.2 (a) Synthesis of 3-substituted phthalides from aldehydes and aromatic acids and (b) synthesis of 3-alkylidenephthalides from benzoic acids.
Scheme 6.3 Synthesis of phthalides from benzimidates and aldehydes.
Scheme 6.4 Synthesis of phthalides by oxidative coupling of aldehydes.
Scheme 6.5 Synthesis of benzofurans from
N
-phenoxyacetamides and alkynes.
Scheme 6.6 Synthesis of furans via Rh(III)-catalyzed alkenyl C−H functionalization.
Scheme 6.7 Dehydrogenative Heck reaction of salicylaldehydes with electron-deficient olefins.
Scheme 6.8 Mechanism studies.
Scheme 6.9 Synthesis of benzoxaphosphole 1-oxides from arylphosphonic acid monoethyl esters and alkenes.
Scheme 6.10 Synthesis of dihydrobenzofuro[2,3-d]oxazoles from aryloxyacetamide and alkynes.
Scheme 6.11 Synthesis of dihydrobenzofuran via Rh(III)-catalyzed C−H functionalization of aromatic imines with tethered 1,1-disubstituted alkenes by Rovis. (a) Mechanistic hypothesis; (b) Rh(III)-catalyzed intramolecular hydroarylation; and (c) Rh(III)-catalyzed intramolecular amidoarylation.
Scheme 6.12 Rh(III)-catalyzed intramolecular amidoarylations by Glorius.
Scheme 6.13 Synthesis of chiral dihydrobenzofurans via Rh(III)-catalyzed enantioselective hydroarylation.
Scheme 6.14 Synthesis of dibenzofuran via decarbonylative C−H arylation of 2-aryloxybenzoic acids.
Scheme 6.15 Synthesis of naphtho[1,8-
bc
]pyran derivatives from 1-naphthols and alkynes.
Scheme 6.16 Synthesis of isochromenes by oxidative annulation of benzyl alcohols with alkynes by Miura and Tanaka.
Scheme 6.17 Synthesis of naphtho[1,8-
bc
]pyrans via Rh(III)-catalyzed oxidative coupling of substituted benzoylacetonitriles with alkynes.
Scheme 6.18 Synthesis of benzopyrans from 2-aryl-3-hydroxy-2-cyclohexenone.
Scheme 6.19 Synthesis of tetracyclic naphthoxazoles from naphthoquinone.
Scheme 6.20 Synthesis of 2
H
-chromene via rhodium(III)-catalyzed annulation of cyclopropenes with
N
-phenoxyacetamides.
Scheme 6.21 Proposed mechanism.
Scheme 6.22 Synthesis of 2,2-disubstituted 2
H
-chromenes from 2-alkenylphenols and allenes.
Scheme 6.23 (a) Synthesis 2,3-disubstituted chromones by oxidative coupling between salicylaldehydes and internal alkynes by Miura and Satoh and (b) synthesis of chromone and chromane from salicylaldehyde and styrene by Glorius.
Scheme 6.24 (a) Synthesis of 3,4-diphenylisocoumarin via oxidative coupling of benzoic acids with alkynes; (b) synthesis of 3,4-diphenylisocoumarin under air; (c) synthesis of functionalized α-pyrone by oxidative coupling of substituted acrylic acids with alkynes; and (d) synthesis of 3-substituted isocoumarins from benzoic acids and geminal-substituted vinyl acetates.
Scheme 6.25 (a) Synthesis of phosphaisocoumarins from phenylphosphinic acids and (b) synthesis of phosphaisocoumarins from arylphosphonic acid monoesters.
Scheme 6.26 Synthesis of isocoumarins from
N
,
N
-diethyl-
O
-benzoylhydroxylamine and alkynes.
Scheme 6.27 Synthesis of (4-benzylidene)isochroman-1-ones from benzamides and propargyl alcohols.
Scheme 6.28 Synthesis of diverse bisheterocycles.
Scheme 6.29 Synthesis of dihydropyrans from acetylenic sulfones.
Scheme 6.30 Synthesis of dihydrobenzopyrans via intramolecular hydroarylation or amidoarylation. (a) Intermolecular hydroarylation; (b) intermolecular amidoarylation; and (c) intermolecular Heck-type reaction.
Scheme 6.31 Synthesis benzoxepines via Rh(III)-catalyzed annulation of
o
-vinylphenols with alkynes.
Scheme 6.32 Synthesis of 1,2-oxazepines from
N
-phenoxyacetamides and α,β-unsaturated aldehydes.
Scheme 6.33 Synthesis of 3,4-fused indole skeletons via intramolecular cyclization of tethered alkynes.
Chapter 7: Ruthenium-Catalyzed Synthesis of Heterocycles via C−H Bond Activation
Scheme 7.1 Proposed mechanism for ruthenium-catalyzed indole synthesis from 2,6-xylylisocyanides.
Scheme 7.2 Proposed mechanism for ruthenium-catalyzed pyrrolidone synthesis from allylic formamides.
Scheme 7.3 Proposed mechanism for ruthenium-catalyzed intramolecular olefin hydrocarbamoylation through direct activation of the formyl C−H bond.
Scheme 7.4 Proposed mechanism for ruthenium-catalyzed intramolecular olefin hydrocarbamoylation through initial activation of the N−H bond.
Scheme 7.5 Proposed mechanism for ruthenium-catalyzed benzofuran synthesis from
N
-phenoxypivalamide.
Scheme 7.6 Proposed mechanism for ruthenium-catalyzed cyclocarbonylation of yne-aldehydes.
Scheme 7.7 Proposed mechanism for ruthenium-catalyzed cyclization of amines with alkynes.
Scheme 7.8 Proposed mechanism for ruthenium-catalyzed cyclization of benzamides with alkynes.
Scheme 7.9 Proposed mechanism for ruthenium-catalyzed oxidative annulations of isoquinolones with alkynes.
Scheme 7.10 Proposed mechanism for ruthenium-catalyzed 3-(1
H
-indol-1-yl)propanamide synthesis from phenylpyrazolidin-3-ones.
Scheme 7.11 Proposed mechanism for ruthenium-catalyzed oxidative alkenylation and cyclization of
N
-methoxybenzamides.
Scheme 7.12 Proposed mechanism for ruthenium-catalyzed oxidative alkenylation and cyclization of aromatic nitriles.
Scheme 7.13 Proposed mechanism for ruthenium-catalyzed three-component coupling reaction of α,β-unsaturated imines with CO and alkenes.
Scheme 7.14 Proposed mechanism for ruthenium-catalyzed carbonylation and cyclization of aliphatic amides.
Chapter 8: Cu-Catalyzed Heterocycle Synthesis
Scheme 8.1 Cu(OAc)
2
catalyzed lactams formation using 5-methoxyquinolyl as directing group.
Scheme 8.2 CuCl catalyzed lactams formation using 5-methoxyquinolyl as directing group.
Scheme 8.3 CuI catalyzed synthesis of 2-monosubstituted and 2,5-disubstituted pyrroles.
Scheme 8.4 Cu(OAc)
2
catalyzed synthesis of 3-Azabicyclo[3.1.0] hex-2-enes and 4-carbonylpyrroles.
Scheme 8.5 CuI catalyzed synthesis of polysubstituted pyrroles.
Scheme 8.6 Copper catalyzed synthesis of 2,3,4-trisubstituted pyrroles.
Scheme 8.7 The regiocontrolled formation of pyrroles via a formal [3+2] cycloaddition of isocyanides and electron-deficient alkynes.
Scheme 8.8 Cu(NTf
2
)
2
-catalyzed synthesis of pyrroles from ethoxycarbonyl vinyl azides and ethyl acetoacetate.
Scheme 8.9 CuOTf-catalyzed synthesis of polysubstituted pyrroles from diazoketones, nitroalkenes, and amines.
Scheme 8.10 Cu(OAc)
2
-promoted oxidative coupling of enamides with electron-deficient alkynes for the synthesis of multisubstituted NH pyrroles.
Scheme 8.11 CuPF
6
-catalyzed pyrrolidines formation via radical aminohydroxylation of double bonds of unsaturated
N
-benzoyloxyamines.
Scheme 8.12 A Cu-Xantphos system for the synthesis of pyrrolidine and piperidine derivatives.
Scheme 8.13 Intramolecular diastereoselective aminooxygenation of unactivated alkenes to pyrrolidines.
Scheme 8.14 Copper catalyzed synthesis of 2-chloromethylpyrrolidines.
Scheme 8.15 1,3-dipolar cycloaddition of azomethine ylides to electron-deficient alkenes for the construction of pyrrolidines.
Scheme 8.16 [Cu(OTf)]
2
· C
6
H
6
catalyzed the substituted pyrrolidine synthesis through three-component reaction.
Scheme 8.17 [Cu(hfacac)
2
] catalyzed 3-pyrrolines synthesis via intermolecular [4+1] cycloaddition.
Scheme 8.18 CuI-catalyzed synthesis of a multisubstituted indole skeleton from
N
-aryl enaminones.
Scheme 8.19 CuBr catalyzed synthesis of 2-(aminomethyl) indoles and polycyclic indole derivatives from N-protected ethynylanilines, amines, and aldehydes.
Scheme 8.20 Polysubstituted indole derivatives synthesis via three-component reaction of 2-ethynylaniline, sulfonyl azide, and nitroolefin.
Scheme 8.21 CuBr catalyzed the synthesis of 3-aroylindoles from
o
-alkynylated
N
,
N
-dimethylamines.
Scheme 8.22 Copper-catalyzed enantioselective intramolecular aminooxygenation of olefins.
Scheme 8.23 Cu(OTf)
2
/2,2′-bipyridyl system for the synthesis of indolines.
Scheme 8.24 Intermolecular enantioselective alkyl Heck-type coupling cascade for the formation of functionalized chiral indolines, pyrrolidines.
Scheme 8.25 The enantioselective alkene aminohalogenation reaction.
Scheme 8.26 Cu(OTf)
2
-catalyzed enantioselective alkene hydroamination/cyclization to enantioenriched 2-methylindolines.
Scheme 8.27 Synthesis of fused indolines from 2-ethynylarylmethylenecyclopropane with sulfonyl azide.
Scheme 8.28 CuI-catalyzed trifluoromethylation of N-protected allylaniline and homoallylaniline derivatives with Togni's reagent.
Scheme 8.29 Cu(OAc)
2
-mediated indolines synthesis via intramolecular aromatic C−H amination.
Scheme 8.30 The intramolecular synthesis of 3,3-disubstituted oxindoles through C(sp
3
)−H and Ar−H coupling of anilides.
Scheme 8.31 Cu(MeCN)
4
PF
6
-catalyzed one-pot synthesis of trifluoromethylated oxindoles.
Scheme 8.32 Cu(NO
3
)
2
· 2.5H
2
O-catalyzed synthesis of trifluoromethylated oxindoles.
Scheme 8.33 Cu
2
O catalyze oxidative alkylarylation of acrylamides with simple alkanes to alkyl-substituted oxindoles.
Scheme 8.34 Synthesis of 3,3-disubstituted oxindoles from arylation– and vinylation– carbocyclization of electron-deficient alkenes with diaryliodonium salts.
Scheme 8.35 Synthesis of 3-(2-oxo-2-arylethyl)indolin-2-ones from
N
-alkyl-
N
-phenylacrylamides and aryl aldehydes.
Scheme 8.36 CuCl
2
-catalyzed intramolecular C−H oxidation/acylation protocol for the synthesis of indoline-2,3-diones.
Scheme 8.37 Cu(OAc)
2
-catalyzed synthesis of indoline-2,3-dione derivatives from secondary anilines and ethyl glyoxalate.
Scheme 8.38 [CuI(bpy)]
2
/O
2
-catalyzed intramolecular oxidative C−H amination reaction of 2-aminoacetophenones.
Scheme 8.39 Cu(OAc)
2
· H
2
O catalyzed synthesis of isatins from tertiary amines.
Scheme 8.40 CuBr-catalyzed regioselective [3+2] cyclization of pyridines with alkenyldiazoacetates.
Scheme 8.41 Intramolecular synthesis of carbazoles from Nsubstituted 2-amidobiphenyls.
Scheme 8.42 Copper-catalyzed synthesis of carbazoles from 2-aminobiphenyls via intramolecular C−H amination using MnO
2
as terminal oxidant.
Scheme 8.43 Cu
2
O-catalyzed synthesis of 1,4-disubstituted imidazoles from alkylisocyanides and arylisocyanidesa.
Scheme 8.44 CuI/BF
3
· Et
2
O catalyzed trisubstituted imidazoles formation from ketones and benzylamines.
Scheme 8.45 CuI-catalyzed intramolecular aerobic [3+2] annulation reaction of
N
-alkenyl amidines to bi- and tricyclic amidines.
Scheme 8.46 Cu(OAC)
2
-catalyzed synthesis of 4-acetoxymethyl-4,5-dihydroimidazoles and dihydroimidazoles.
Scheme 8.47 Cu(OAC)
2
-catalyzed synthesis of dihydroimidazoles.
Scheme 8.48 CuI-catalyzed synthesis of polysubstituted imidazole derivatives via intermolecular [3+2] cycloaddition reaction of nitroolefins and amidines.
Scheme 8.49 Synthesis of 1,2,4-trisubstituted imidazoles from amidines and terminal alkynes.
Scheme 8.50 Cu(OAc)
2
-catalyzed synthesis of substituted benzimidazoles and substituted
N
-methyl-2-arylbenzimidazoles.
Scheme 8.51 Synthesis of benzimidazoles from benzamidines and boronic acids.
Scheme 8.52 Three-component reaction for the synthesis of functionalized benzimidazoles.
Scheme 8.53 Synthesis of 1,2-disubstituted benzimidazoles from arylcarbodiimides.
Scheme 8.54 Synthesis of 2-substituted benzimidazoles, benzoxazoles, and benzothiazoles from primary amines.
Scheme 8.55 Cu(OAc)
2
-catalyzed synthesis of imidazobenzimidazole derivatives.
Scheme 8.56 CuCl
2
-catalyzed synthesis of imidazo[1,5-
a
]pyridines, imidazo[1,5-
a
]imidazoles, and imidazo[5,1-
a
]isoquinolines.
Scheme 8.57 synthesis of pyrido[1,2-
a
]benzimidazoles from
N
-aryl-2-aminopyridines.
Scheme 8.58 Three-component coupling reaction of aryl, heteroaryl, and alkyl aldehydes with 2-aminopyridines and terminal alkynes.
Scheme 8.59 Copper-catalyzed intramolecular dehydrogenative aminooxygenation.
Scheme 8.60 Synthesis of imidazo[1,2-a]pyridines from aminopyridines and nitroolefins.
Scheme 8.61 Synthesis of heteroaromatic imidazo[1,2-
a
]pyridines.
Scheme 8.62 CuBr-catalyzed synthesis of multifunctional imidazo[1,5-a]pyridines.
Scheme 8.63 Synthesis of imidazo[1,2-
a
]pyridine derivatives.
Scheme 8.64 Synthesis of imidazo[1,2-a]pyridine derivatives from pyridine with ketone oxime esters.
Scheme 8.65 Synthesis of tetrasubstituted pyrazoles from enamines and nitriles.
Scheme 8.66 Intramolecular synthesis of pyrazoles and indazoles via oxidative C(sp
2
)−H amination.
Scheme 8.67 Intramolecular dehydrogenative cyclization reaction of
N
,
N
-disubstituted hydrazones to pyrazoles.
Scheme 8.68 Synthesis of pyrazolo[1,5-
a
]pyridine derivatives.
Scheme 8.69 Cu(OAc)
2
-catalyzed oxidative tandem cyclization for the synthesis of polysubstituted oxazoles.
Scheme 8.70 Synthesis of polyarylated oxazoles from benzylamine and benzil derivatives.
Scheme 8.71 2,5-Disubstituted oxazole preparation from enamides.
Scheme 8.72 Synthesis of dihydrooxazoles from
N
-alkylamidines through direct C−H oxygenation.
Scheme 8.73 Synthesis of 2-arylbenzoxazoles through intramolecular oxidative C−O coupling reaction.
Scheme 8.74 Intramolecular synthesis of 2-arylbenzoxazole from
N
-benzyl bisaryloxime ethers.
Scheme 8.75 Synthesis of 1,5-disubstituted tetrazoles by two C(sp
3
)−H and one C−C bond cleavages.
Scheme 8.76 Doubly intramolecular alkene carboetherification of unactivated alkenols to form tetrahydrofurans.
Scheme 8.77 Enantioselective carboetherification reaction for the synthesis of tetrahydrobenzofuran.
Scheme 8.78 Synthesis of multisubstituted dibenzofurans from
o
-arylphenols.
Scheme 8.79 Regioselective synthesis of polysubstituted benzofurans from phenols and alkynes.
Scheme 8.80 Synthesis of 2,4,6-trisubstituted pyridine derivative from aromatic methylamines and ketones.
Scheme 8.81 Copper-catalyzed synthesis of 3,5-diarylpyridines and 2-(1
H
)-pyridones.
Scheme 8.82 Synthesis of multisubstituted pyridine N-oxide derivatives.
Scheme 8.83 Synthesis of quinolines from 2-aminobenzyl alcohol with ketones.
Scheme 8.84 Cu(OTf)
2
-catalyzed synthesis of quinoline-2-carboxylates.
Scheme 8.85 Synthesis of highly substituted quinolines from
N
-(2-alkynylaryl)enamine carboxylates.
Scheme 8.86 Synthesis of 4-carbonylquinolines through aerobic oxidative intramolecular cyclization of enynes.
Scheme 8.87 Synthesis of 4-sulfonamidoquinolines from sulfonyl azides with alkynyl imines.
Scheme 8.88 Synthesis of polysubstituted quinolines through oxidative dehydrogenative annulation of anilines and aldehydes.
Scheme 8.89 Synthesis of highly conjugated cyclopenta[c]quinolines.
Scheme 8.90 Oxidative cyclization of N-methylanilines with electron-deficient olefins to substituted tetrahydroquionoline.
Scheme 8.91 Synthesis of oxindoles, thio-oxindoles, 3,4-dihydro-1
H
-quinolin-2-ones, and 1,2,3,4-tetrahydroquinolines.
Scheme 8.92 Synthesis of isoquinolin-1-ylphosphonate from N′-(2-alkynylbenzylidene) hydrazides with diethyl phosphite.
Scheme 8.93 Synthesis of 3-(aminomethyl)isoquinolines from 2-ethynylbenzaldehydes, paraformaldehyde, secondary amine, and
t
-BuNH
2
.
Scheme 8.94 Quinolinone synthesis through oxidative (sp3)−H functionalization–carbocyclization–ketonization cascade.
Scheme 8.95 Synthesis of 2-quinolones ring from 3,3-diarylacrylamides.
Scheme 8.96 Synthesis of highly functionalized dihydroquinolinones from cinnamamides with benzyl hydrocarbons.
Scheme 8.97 Synthesis of
N
-aryl acridones from 2-(aryllamino)benzophenones.
Scheme 8.98 Synthesis of 10-methylacridin-9(10
H
)-ones from 2-(methylamino)benzophenones.
Scheme 8.99 Synthesis of acridone derivatives from 2-aminobenzophenones.
Scheme 8.100 Synthesis of acridones via intramolecular cyclization.
Scheme 8.101 Synthesis of phenanthridine derivatives from biaryl-2-carbonitriles and Grignard reagents.
Scheme 8.102 Synthesis of 6-alkyl-substituted phenanthridine derivatives.
Scheme 8.103 Synthesis of quinazolines from amidines and DMSO.
Scheme 8.104 Synthesis of indolo[1,2-
c
]quinazoline derivatives.
Scheme 8.105 Synthesis of 5-substituted imidazo/benzimidazo[2,1-
b
]quinazolinones.
Scheme 8.106 Synthesis of 2-hetarylquinazolin-4(3
H
)-ones.
Scheme 8.107 Synthesis of cinnolines from
N
-methyl-
N
-phenylhydrazones.
Scheme 8.108 Synthesis of dihydropyrimidin-4-ones .
Scheme 8.109 Synthesis of 1,4-dihydropyrazine derivatives.
Scheme 8.110 Synthesis of benzo- or naphtho-2,3-dihydro-1,3-oxazines.
Scheme 8.111 Synthesis of benzoxazine derivatives.
Scheme 8.112 Synthesis of dihydro-oxazinone derivatives.
Scheme 8.113 Enantioselective synthesis of
N
-sulfonyl-protected
trans
-3-amino-4-arylchromans.
Scheme 8.114 Synthesis of benzopyrans from phenols and 1,3-dienes.
Scheme 8.115 Synthesis of benzolactones from 2-arylbenzoic acids.
Scheme 8.116 Synthesis of trifluoromethylated coumarins.
Scheme 8.117 Synthesis of coumarins from substituted ketene S,S-acetals.
Scheme 8.118 Synthesis of substituted iminocoumarin derivatives.
Scheme 8.119 Synthesis of 3-triazolyl-2-iminochromenes.
Scheme 8.120 Synthesis of iminocoumarin aryl methyl ethers.
Scheme 8.121 Synthesis of xanthone derivatives via
ortho
-acylation of phenols with aryl aldehydes.
Scheme 8.122 Synthesis of N,S-heterocycle sultam derivatives.
Scheme 8.123 Synthesis of sultams via intermolecular aminoarylation of aliphatic alkenes.
Scheme 8.124 Synthesis of Benzo[
b
][1,4]thiazine-4-carbonitriles.
Chapter 9: Fe- and Ag-Catalyzed Synthesis of Heterocycles
Scheme 9.1 Synthesis of Benzimidazoles from Aryl Azides.
Scheme 9.2 Synthesis of indoles via Amination of Alkyl C(sp
3
)−H Bonds with Azides.
Scheme 9.3 Synthesis of Indoles via Intramolecular C−H Amination.
Scheme 9.4 Synthesis of 1
H
-Indazoles and 1
H
-Pyrazoles via Intramolecular C(sp
2
)−H Amination.
Scheme 9.5 Synthesis of Oxazolidino[4,5:1,2][60]fullerenes.
Scheme 9.6 Synthesis of Imidazopyridines by Oxidative Diamination of Nitroalkenes with 2-Aminopyridines
Scheme 9.7 Synthesis of 1,2-Thiazinane 1,1-Dioxides via Intramolecular Allylic C(sp
3
)−H Amination.
Scheme 9.8 Synthesis of Quinolines by Tandem Reaction of Anilines with 2-Aryloxiranes.
Scheme 9.9 Synthesis of Benzoxazoles by Tandem C(sp
3
)−H Oxidative Amination.
Scheme 9.10 Synthesis of Dihydroquinazolines and Quinolines.
Scheme 9.11 Synthesis of Pyrido [1,2-
e
]purines via Direct Intramolecular C(sp
2
)−H Amination.
Scheme 9.12 Synthesis of Pyrido[1,2-
a
]indoles via Intramolecular C(sp
2
)−H Amination of 2-Benzhydrylpyridines.
Scheme 9.13 Direct C(sp
2
)−H Oxidative Coupling to Build Indoles.
Scheme 9.14 Synthesis of 3-(2-Oxoethyl)indolin-2-ones by 1,2-Difunctionalization of Alkenes.
Scheme 9.15 Synthesis of Chloro-Containing Oxindoles via 1,2-Carbochloromethylation of Alkenes.
Scheme 9.16 1,2-Alkylarylation with Activated Alkenes Using Peroxides as Alkyl Resource.
Scheme 9.17 1,2-Carbonylarylation of
N
-Arylacrylamides with Alcohols.
Scheme 9.18 1,2-Alkoxycarbonylarylation of
N
-aryl acrylamides for the Construction of Alkoxycarbonylated Oxindoles.
Scheme 9.19 1,2-Aryldifluoromethylation of Activated Alkenes with PhSO
2
CF
2
I.
Scheme 9.20 Synthesized of 6-Carboxylated Phenanthridines.
Scheme 9.21 Synthesis of Quinolines by C−H functionalization/oxidative coupling tandem reaction.
Scheme 9.22 [4+2] Annulation of
ortho
-Nitroanilines with Phenethylamines.
Scheme 9.23 Construction of Polysubstituted Benzofurans through Annulation of Simple Phenols and β-Keto Esters.
Scheme 9.24 Cross-Dehydrogenative-Coupling between Phenols and α-Substituted β-Ketoesters.
Scheme 9.25 Synthesis of 2,3-Dihydrobenzofurans by Oxidative Cross-Coupling of Phenols with Alkenes.
Scheme 9.26 Oxidative Cross-Coupling/Cyclization of Simple Phenols with Alkenes.
Scheme 9.27 Microwave-Promoted Synthesis of 9-Substituted Xanthenes.
Scheme 9.28 Intramolecular Cyclization for the Construction of Xanthones.
Scheme 9.29 Synthesis of Dihydrofuran-2(3
H
)-ones through C(sp
3
)−H Hydyoxylations.
Scheme 9.30 Intramolecular Cyclization of Alkyl C(sp
3
)−H Bonds with the Free N−H Bonds.
Scheme 9.31 C(sp
3
)-H Amination between Two Different Types of C−H Bonds.
Scheme 9.32 Arylphosphorylation of
N
-Arylacrylamides with Ph
2
P(O)H for the Synthesis of Phosphorylated Oxindoles.
Scheme 9.33 1,2-Carboazidation of Arylacrylamides with TMSN
3
.
Scheme 9.34 1,2-Alkylarylation of Activated Alkenes with α-C(sp
3
)−H Bonds of 1,3-Dicarbonyl compounds.
Scheme 9.35 1,2-Acylarylation of Activated Alkenes.
Scheme 9.36 Synthesis of Benzo[c]chromen-6-ones by C−H functionalization/C−O Cyclization.
Scheme 9.37 1,2-Arylphosphorylation of Activated Alkynes to access 3-Phosphonated coumarins.
Scheme 9.38 Synthesis of Benzo[
b
]phosphole Oxides through Silver-Mediated C−H Activation.
Scheme 9.39 Possible Mechanism of Silver-Mediated Synthesis of Benzo[
b
]phosphole Oxides.
Chapter 10: Heterocycles Synthesis via Co-Catalyzed C−H Bond Functionalization
Scheme 10.1 Co
2
(CO)
8
-catalyzed ortho-carbonylation of benzaldimine (a) and azobenzene (b) leading to
N
-heterocycles.
Scheme 10.2 Reaction of azobenzene derivative and diphenylacetylene.
Scheme 10.3 Co
2
(CO)
8
-catalyzed synthesis of quinoline derivatives from
N
,
N
-diallylaniline (a) and from
N
-benzylideneaniline and
N
,
N
-diallylaniline (b).
Scheme 10.4 Annulation of α,β-unsaturated imine and internal alkyne. r.r. refers to regioisomer ratio (major regioisomers are shown).
Scheme 10.5 Intramolecular C2-alkylation of indole leading to dihydropyrroloindole or tetrahydropyridoindole derivative.
Scheme 10.6 Early examples of cobalt-catalyzed intramolecular hydroacylation using cobalt(0)-phosphine (a) and Cp*-cobalt(I) (b) catalysts.
Scheme 10.7 Enantioselective intramolecular hydroacylation of ketones (a) and olefins (b) using cobalt–chiral diphosphine catalysts.
Scheme 10.8 Addition of arylzinc reagent to alkyne involving 1,4-cobalt migration.
Scheme 10.9 Synthesis of benzo[
b
]thiophenes and benzo[
b
]selenophenes through cobalt-catalyzed migratory arylzincation and copper-mediated/copper-catalyzed chalcogenative cyclization.
Scheme 10.10 Synthesis of benzo[
b
]phospholes through one-pot multicomponent coupling.
Scheme 10.11 The first examples of Cp*Co
III
-catalyzed C−H functionalization.
Scheme 10.12 Pyrroloindolone synthesis through Cp*Co
III
-catalyzed annulation of
N
-carbamoyl-indole and internal alkyne.
Scheme 10.13 Indazole synthesis through Cp*Co
III
-catalyzed C−H functionalization/dehydrative cyclization of azobenzene and aldehyde.
Scheme 10.14 Furan synthesis through Cp*Co
III
-catalyzed C−H functionalization/deaminative cyclization of α,β-unsaturated oxime and aldehyde.
Scheme 10.15 Cp*Co
III
-catalyzed condensation of 2-arylpyridine and diazoester.
Scheme 10.16 Cobalt-catalyzed oxidative annulation of 8-aminoquinoline-bearing benzamide and alkyne (
Q
= 8-quinolinyl).
Scheme 10.17 Cobalt-catalyzed oxidative annulation of 8-aminoquinoline-bearing benzamide and olefin (
Q
= 8-quinolinyl).
Scheme 10.18 Cobalt-catalyzed oxidative carbonylation of 8-aminoquinoline-bearing benzamide (
Q
= 8-quinolinyl).
Scheme 10.19 Intramolecular benzylic C−H amination with arylsulfonyl azide catalyzed by [Co(TPP)].
Scheme 10.20 Intramolecular benzylic and homobenzylic C−H amination with phosphoryl azide catalyzed by cobalt(II)–porphyrin complex.
Scheme 10.21 Intramolecular C−H amination with sulfamoyl azide catalyzed by cobalt(II)–porphyrin complex.
Scheme 10.22 Enantioselective intramolecular C−H alkylation with acceptor/acceptor-substituted diazo compound catalyzed by chiral cobalt(II)–porphyrin complex.
Chapter 11: Ir-Catalyzed Heterocycles Synthesis
Scheme 11.1
Scheme 11.2
Figure 11.1 Structure of (
S
,
S
)-Me-tfb*
Scheme 11.3
Scheme 11.4
Scheme 11.5
Scheme 11.6
Scheme 11.7
Figure 11.2 Structure of Ligand
Scheme 11.8
Scheme 11.9
Scheme 11.10
Scheme 11.11
Scheme 11.12
Scheme 11.13
Scheme 11.14
Scheme 11.15
Scheme 11.16
Scheme 11.17
Scheme 11.18
Scheme 11.19
Scheme 11.20
Scheme 11.21
Chapter 12: Au- and Pt-Catalyzed C−H Activation/Functionalizations for the Synthesis of Heterocycles
Scheme 12.1 Au-catalyzed synthesis of β-alkynyl-γ-butenolides.
Scheme 12.2 Au-catalyzed synthesis of benzofurans.
Scheme 12.3 Au-catalyzed synthesis of dihydrobenzofurans.
Scheme 12.4 A two-step synthetic approach to construct aryl benzofuranone skeleton via Au-catalyzed aryl C−H functionalization followed by lactonization.
Scheme 12.5 Au-catalyzed synthesis of allene-substituted tetrahydrofuran.
Scheme 12.6 Au-catalyzed synthesis of aryl lactones.
Scheme 12.7 Au-catalyzed synthesis of 3-alkynyl polysubstituted furans.
Scheme 12.8 Au-catalyzed synthesis of 1-alkynyl-1
H
-isochromenes.
Scheme 12.9 Au-catalyzed synthesis of isoflavanones.
Scheme 12.10 Au-catalyzed synthesis of coumarin derivatives.
Scheme 12.11 Au-catalyzed synthesis of 3-chromanol.
Scheme 12.12 Two possible mechanisms for Au-catalyzed synthesis of 3-chromanol from epoxides 23.
Scheme 12.13 Au-catalyzed synthesis of complex α-pyrones.
Scheme 12.14 Au-catalyzed synthesis of chroman-3-ones.
Scheme 12.15 Au-catalyzed synthesis of 1
H
-isochromene derivatives.
Scheme 12.16 Proposed mechanism for the unprecedented dimerization formation via Au-catalyzed benzylic C−H activation.
Scheme 12.17 Au-catalyzed synthesis of aminoindolizines.
Scheme 12.18 Au-catalyzed synthesis of dihydropyrazoles.
Scheme 12.19 Au-catalyzed synthesis of bicyclic and tricyclic pyrroles.
Scheme 12.20 Au-catalyzed synthesis of indolines.
Scheme 12.21 Au-catalyzed synthesis of functional indoles and indolin-3-ones.
Scheme 12.22 Au-catalyzed synthesis of 2-alkylindoles.
Scheme 12.23 Au-catalyzed synthesis of
N
-protected indoles.
Scheme 12.24 Au-catalyzed synthesis of 3-acyloxindole derivatives.
Scheme 12.25 Application of Au-catalyzed hydroarylation in the synthesis of flinderoles B and C.
Scheme 12.26 Au-catalyzed synthesis of lactam.
Scheme 12.27 Au-catalyzed synthesis of 2,3-dihydro-1
H
-pyrrolizines.
Scheme 12.28 Au-catalyzed synthesis of fused pyrroles.
Scheme 12.29 Au-catalyzed synthesis of quinoline derivatives.
Scheme 12.30 Au-catalyzed synthesis of azaisoflavanones.
Scheme 12.31 Au-catalyzed synthesis of (spiro)cyclopentapyridinones.
Scheme 12.32 Au-catalyzed synthesis of dihydroquinoline.
Scheme 12.33 Au-catalyzed hydroarylation in the synthesis of (−)-rhazinilam.
Scheme 12.34 Au-catalyzed synthesis of 1,2-dihydroquinolines.
Scheme 12.35 Pt-catalyzed synthesis of quinoline derivatives.
Scheme 12.36 Pt-catalyzed synthesis of quinaldine derivatives.
Scheme 12.37 Au-catalyzed synthesis of piperidinones.
Scheme 12.38 Total synthesis of (+)-lentiginosine via a key Au catalysis.
Scheme 12.39 Proposed mechanism for Au-catalyzed synthesis of piperidinones.
Scheme 12.40 Gold/Brønsted acid cocatalyzed synthesis of cyclic aminals.
Scheme 12.41 Au-catalyzed synthesis of tetrahydrobenz[
b
]azepin-4-ones.
Scheme 12.42 Au-catalyzed synthesis of azepan-4-ones.
Scheme 12.43 Au-catalyzed synthesis of benzothiepinones.
Scheme 12.44 Au-catalyzed synthesis of tricyclic furan and pyrrole.
Scheme 12.45 Au-catalyzed synthesis of tetrahydrooxepin and tetrahydroazepin.
Scheme 12.46 Au-catalyzed synthesis of tricyclic thiophene/furan or thiophene/pyrrole.
Scheme 12.47 Au-catalyzed synthesis of tetrahydrofuran or pyrrolidine derivatives.
Scheme 12.48 Au-catalyzed synthesis of 3-methylenetetrahydrofuran or 3-methylenepyrrolidine derivatives.
Scheme 12.49 Pt- and Au-catalyzed synthesis of 1,2-dihydroquinolines and chromenes.
Scheme 12.50 Pt- and Au-catalyzed synthesis of chromenes, dihydroquinolines, and coumarins.
Scheme 12.51 Total synthesis of deguelin via a key Pt(II) catalysis.
Scheme 12.52 Au-catalyzed synthesis of 1,3-dihydroindeno[2,1-
c
]pyran and 2,3-dihydro-1
H
-indeno[2,1-
c
]pyridine derivatives.
Scheme 12.53 Au-catalyzed synthesis of dihydrobenzopyrans and tetrahydroquinolines.
Scheme 12.54 Au-catalyzed synthesis of azepino[4,5-
b
]indole and indoloazocines.
Scheme 12.55 Au-catalyzed synthesis of 4,5,6,7-tetrahydrofuro[2,3-
c
]pyridine derivatives.
Scheme 12.56 Synthesis of seven-membered ring-fused furans and thiophene.
Scheme 12.57 Au-catalyzed synthesis of hexahydroquinolizinones.
Scheme 12.58 Au(I)/chiral Brønsted acid cocatalyzed strategy for the synthesis of enantiomerically enriched aza-heterocyclic scaffolds.
Scheme 12.59 Au(I)/chiral Brønsted acid cocatalyzed synthesis of pyrrole-embedded aza-heterocycles.
Scheme 12.60 Au- or Pt-catalyzed synthesis of pyrrolopyridinones and pyrroloazepinones.
Scheme 12.61 Au- or Pt-catalyzed synthesis of thiophenoazepinones, azepinoindoles, and azepinobenzothiophenes.
Scheme 12.62 Pt-catalyzed synthesis of pyrrolo[3,2-c]azepin-4-one derivatives.
Scheme 12.63 Pt-catalyzed synthesis of indoloazepinones.
Scheme 12.64 Au-catalyzed synthesis of spiro or fused dihydrofurans and dihydropyrans.
Scheme 12.65 Au-catalyzed synthesis of fused tetrahydrofurans and tetrahydropyrans.
Scheme 12.66 Au-catalyzed synthesis of ring-fused tetrahydroazepines.
Scheme 12.67 Au-catalyzed asymmetric synthesis of ring-fused tetrahydroazepines.
Scheme 12.68 Pt-catalyzed synthesis of fused polycyclic heterocycles.
Chapter 13: Heterocycle Synthesis Based on Visible-Light-Induced Photocatalytic C−H Functionalization
Scheme 13.1 Mechanism profile of visible-light-induced photocatalysis.
Scheme 13.2 Main pathways for visible-light-induced photocatalytic α-amino C−H functionalization.
Scheme 13.3 Possible mechanism for the [3+2] cycloaddition reactions.
Scheme 13.4 Visible-light-mediated intramolecular oxidative cyclization of diamines.
Scheme 13.5 Visible-light
-
mediated tandem aerobic C−H/C−N cleavage.
Scheme 13.6 [3+2] cycloaddition reactions of
N
-substituted hydroxylamines with alkenes.
Scheme 13.7 Visible-light-induced intramolecular trapping of α-amino radicals.
Scheme 13.8 Visible-light-induced synthesis of 3-formyl indole derivatives.
Scheme 13.9 Visible-light-induced intramolecular oxidative cyclization.
Scheme 13.10 Visible-light-induced radical cyclization of tertiary amines and maleimides.
Scheme 13.11 Radical cyclization of tertiary amines and 2-benzylidenemalononitriles.
Scheme 13.12 Benzylic C−H activation by photoredox catalysis.
Scheme 13.13 Visible-light-induced intramolecular alkylation of indoles and pyrroles.
Scheme 13.14 Visible-light-induced intramolecular radical cyclization.
Scheme 13.15 Visible-light-induced cyclization of trifluoroacetimidoyl chlorides with alkynes.
Scheme 13.16 Visible-light-mediated synthesis of 2-substituted benzothiazoles.
Scheme 13.17 Visible-light-induced
N
-aryl indole synthesis.
Scheme 13.18 Visible-light-induced carbazoles synthesis.
Scheme 13.19 Visible-light-induced δ-viniferin synthesis.
Scheme 13.20 Visible-light-induced oxidative [3+2] cycloadditions of phenols and styrenes.
Scheme 13.21 Photocatalytic radical cyclization of
N
-arylacrylamides.
Scheme 13.22 Visible-light-mediated somophilic isocyanide insertion reactions.
Scheme 13.23 Visible-light-mediated oxidative Heck reactions.
Scheme 13.24 Visible-light-mediated direct C−H alkylation of electron-rich heterocycles.
Scheme 13.25 Total synthesis of gliocladin
C
enabled by visible-light photoredox catalysis.
Scheme 13.26 Visible-light-induced C−H alkylation of indoles without photocatalyst.
Scheme 13.27 Visible-light-induced direct C−H methylation of biologically active heterocycles.
Scheme 13.28 Visible-light-mediated α-arylation of α-amino carbonyl compounds.
Scheme 13.29 Preparation of LY2784544 enabled by visible-light photoredox catalysis.
Scheme 13.30 Visible-light-mediated C−H oxyalkylation of electron-deficient heteroarenes.
Scheme 13.31 Mechanism of C−H trifluoromethylation of heteroarenes.
Scheme 13.32 Heterogeneous catalytic approaches for the C−H trifluoromethylation of heteroarenes.
Scheme 13.33 Direct C−H difluoromethylation of electron-rich heteroarenes.
Scheme 13.34 Visible-light-mediated direct C−H difluoromethylation of heteroarenes. (a) Cho's work and (b) Qing's work.
Scheme 13.35 Visible-light-mediated direct C−H arylation of electron-rich heterocycles.
Scheme 13.36 Visible-light-mediated direct C−H arylation of
N
-heteroarenes.
Scheme 13.37 Visible-light-mediated direct C−H arylation of isoquinoline.
Scheme 13.38 Visible-light-mediated direct C−H amination of heteroarenes.
Scheme 13.39 Visible-light-mediated direct C−H amination of pyridines.
Scheme 13.40 Visible-light-mediated direct C−H imidation of heteroarenes without catalyst.
Scheme 13.41 Visible-light-mediated direct C−H amidation of electron-rich heteroarenes.
Scheme 13.42 Visible-light-mediated 3-sulfenylation of
N
-methylindoles.
Scheme 13.43 Visible-light-mediated direct C−H thiocyanation of indoles.
Chapter 14: Heterogeneous C−H Activation for the Heterocycle Synthesis
Scheme 14.1 Screening of heterogeneous catalysts.
Scheme 14.2 Three-phase tests.
Scheme 14.3 Intramolecular enantioselective arylation of carbonyl compounds.
Figure 14.1 The Pd/Fe
3
O
4
/L system.
Scheme 14.4 Comparison Pd/Fe
3
O
4
/L with homogeneous Pd−L complexes.
Scheme 14.5 Proposed mechanism for the C−N bond formation via C−H functionalization.
Scheme 14.6 Scope of C−N bond formation via C−H functionalization catalyzed by Pd/C.
Scheme 14.7 Direct synthesis of isoquinolones from benzamides and alkynes.
Scheme 14.8 Pd/CeO
2
-catalyzed oxidative synthesis of indoles.
Scheme 14.9 Direct synthesis of isoquinolones from benzamides and alkynes.
Scheme 14.10 Preparation of benzimidazole derivatives.
Scheme 14.11 Proposed mechanism for the oxidative synthesis of two-substituted benzimidazoles.
Scheme 14.12 Proposed reaction mechanism for the photoredox of tertiary anilines and maleimides with surface-modified TiO
2
.
Scheme 14.13 Schematic overview of the possible reaction pathways.
Chapter 15: Transition Metal-Catalyzed Carbonylative Synthesis of Heterocycles via C−H Activation
Scheme 15.1 Deuterium-labeling experiments.
Scheme 15.2 Other amides compared to the
N
,
N
-bidentate system.
Scheme 15.3 Carbonylation of vinylic halides.
Scheme 15.4
N
-Ethyl-
N
-methyl aniline for the C−N cleavage.
Scheme 15.5 Explanation of intermediates.
Scheme 15.6 Catalytic process versus stepwise pathway.
Scheme 15.7 Zhang's procedure for the synthesis of phenanthridinones.
Scheme 15.8 Acid- or base-free procedure.
Scheme 15.9
18
O-Labeling experiments.
Chapter 16: Synthesis of Natural Products and Pharmaceuticals via Catalytic C−H Functionalization
Figure 16.1 Two distinct modes of C−H functionalization in the synthesis of indole alkaloids: indole substitution and indole synthesis. (a) C−H functionalization of indoles and (b) formation of indoles by C−H functionalization.
Scheme 16.1 Synthesis of dragmacidin D and eudistomin U enabled by C−H arylation of indoles at the C3 position.
Scheme 16.2 Syntheses of clavicipitic acid and chanoclavine-I enabled by C−H alkenylation of indoles at the C3 position.
Scheme 16.3 Synthesis of complex natural products by using Pd-mediated intramolecular C−H alkylation of indoles at the C2 position.
Scheme 16.4 Synthesis of a PKC inhibitor made possible by C−H alkylation of an indole at the C2 position.
Scheme 16.5 Synthesis of clavicipitic acid using C−H alkenylation of an indole at the C4 position as the key step.
Scheme 16.6 Synthesis of hippadine enabled by C−H borylation of an indole at the C7 position.
Scheme 16.7 Synthesis of dictyodendrin B showcasing three different types of heteroarene C−H functionalization.
Scheme 16.8 Synthesis of paullone using oxidative Larock indole synthesis.
Scheme 16.9 Formal synthesis of horsfiline using intermolecular C−H coupling.
Scheme 16.10 Synthesis of dimebolin using a nitrenoid C−H insertion reaction.
Scheme 16.11 An early contribution for the synthesis of a pyrrole-containing natural product by using an intramolecular C−H arylation strategy.
Scheme 16.12 Synthesis of rhazinal: a comparison of intramolecular and intermolecular C−H functionalization strategies.
Scheme 16.13 Synthesis of rhazinilam and its congeners, kopsiyunnanine C3, and aspidospermidine.
Scheme 16.14 Synthesis of lamellarins I and C accomplished by a series of C−H functionalization events.
Scheme 16.15 Synthesis of dictyodendrins A and F that relies on three C−H functionalizations.
Scheme 16.16 Synthesis of carbazole-containing natural products by C−H arylation.
Scheme 16.17 Synthesis of carbazole alkaloids enabled by an ideal type of bond formation: C−H/C−H coupling.
Scheme 16.18 Synthesis of clausine C and glycozoline.
Scheme 16.19 Synthesis of frondosin B via benzofuran C−H alkenylation.
Scheme 16.20 Synthesis of diptoindonesin G using benzofuran C−H arylation as a key step.
Scheme 16.21 Synthesis of (+)-lithospermic acid by the groups of Ellman and Bergman.
Scheme 16.22 Synthesis of lithospermic acid by Yu's group, involving two key C−H functionalization steps.
Figure 16.2 The synthesis of natural products containing dihydrobenzofuran units by intramolecular C−H insertion.
Scheme 16.23 Synthesis of morphine facilitated by a metal carbenoid C−H insertion reaction.
Scheme 16.24 Synthesis of JNK3 inhibitors using intramolecular C−H alkylation of imidazoles as a key step.
Scheme 16.25 Two syntheses of tyrosine kinase inhibitor that showcase the efficiency of C−H functionalization in polyarylated imidazole synthesis.
Scheme 16.26 Synthesis of oxazole-contained natural products and pharmaceuticals using C−H arylation.
Scheme 16.27 Synthesis of oxazole-contained biologically active compounds by Ni-catalyzed C−H arylation.
Scheme 16.28 Synthesis of muscoride A using decarboxylative C−H arylation of oxazoles as a key step.
Scheme 16.29 Synthesis of annuloline and siphonazole B using C−H alkenylation of oxazoles at the C2 position.
Scheme 16.30 Synthesis of luotonin B and rutaecarpine using intramolecular C−H arylation.
Scheme 16.31 Synthesis of vasicoline using intramolecular C−H arylation.
Scheme 16.32 Synthesis of norchelerythrine using intramolecular C−H arylation.
Scheme 16.33 Synthesis of nitidine and NK109 using Catellani-type tandem C−H arylation/
N
-arylation.
Scheme 16.34 Formal synthesis of LTB4 antagonist and MCH-1R receptor modulator using a sp
3
C−H arylation/intramolecular C−H amination cascade.
Scheme 16.35 Formal synthesis of tipifarnib: formation of quinolinones using C−H alkenylation and cyclization.
Scheme 16.36 Synthesis of oxychelerythrine using a C−H alkenylation/annulation reaction.
Scheme 16.37 Synthesis of a sodium channel inhibitor and an antimalarial agent using a pyridine
N
-oxide C−H arylation reaction.
Scheme 16.38 Synthesis of complanadine A and complanadine B by C−H borylation or arylation.
Scheme 16.39 Synthesis of anabashine using a C−H arylation of iminopyridium ylides.
Scheme 16.40 Synthesis of preclamol employing a C3-selective C−H arylation of pyridines.
Scheme 16.41 Synthesis of celecoxib using a Pd-catalyzed C−H arylation.
Scheme 16.42 Synthesis of GABA agonists using a C−H arylation of imidazopyrimidines.
Scheme 16.43 C−H arylation of indazoles: synthesis of YD-3, YC-1, and nigellidine hydrobromide.
Figure 16.3 Synthesis of pyrrolidine-containing natural products and pharmaceuticals using Rh-catalyzed C−H insertion.
Scheme 16.44 Synthesis of pseudoheliotridane using ruthenium-catalyzed C−H insertion.
Scheme 16.45 Synthesis of aeruginosins using two sp
3
C−H functionalization reactions.
List of Tables
Chapter 14: Heterogeneous C−H Activation for the Heterocycle Synthesis
Table 14.1 Scope of Pd(OH)
2
-C-catalyzed intramolecular direct arylation reactions.
a
Table 14.2 C−N bond formation via C−H functionalization catalyzed by Pd nanomaterials.
a
Table 14.3 Visible-light-mediated cyclization of tertiary anilines and maleimides with TiO
2
/NiO as photocatalyst.
a
Chapter 15: Transition Metal-Catalyzed Carbonylative Synthesis of Heterocycles via C−H Activation
Table 15.1 Scope of the cyclocarbonylation of acetylene
[a]
Table 15.2 Scope of the carbonylation of aldimines
[a]
Table 15.3 Scope of the carbonylation of amides
[a]
Table 15.4 Represented examples of the carbonylation of amides toward phthalimides
[a]
Table 15.5 Selected examples for the preparation of indenones from aromatic imines
[a]
Table 15.6 Selected products for the carbonylation of α,β-unsaturated imines
[a]
Table 15.7 Bidentate system for the carbonylation of amides
[a]
Table 15.8 Represented products for the C(sp
3
)−H carbonylation
[a]
Table 15.9 Selected examples for the carbonylative isoquinoline-1,3(2
H
,4
H
)-dione preparation
[a]
Table 15.10 Represented examples for the carbonylation of
ortho
-phenyl phenol
[a]
Table 15.11 Selected products of
α
-methylene-
β
-lactam formation through the carbonylation of
N
-allylamines
[a]
Table 15.12 Scope for the fluoren-9-one synthesis via the carbonylation of
ortho
-halobiarys
[a]
Table 15.13 Selected examples of the carbonylation of aromatic acid
[a]
Table 15.14 Represented substrates for the carbonylation of C(sp
3
)−H bonds
[a]
Table 15.15 Phthalimide synthesis via Pd(II)-catalyzed carbonylative C−H functionalization of
N
-alkoxybenzamides
[a]
Table 15.16 The palladium-/copper-catalyzed oxidative C−H alkenylation/
N
-dealkylative carbonylation of tertiary anilines
[a]
Table 15.17 The palladium-catalyzed double carbonylation of aniline C−H bonds to prepare isatin
[a]
Table 15.18 Selected benzolactam synthesis from carbonylation of secondary amines
[a]
Table 15.19 Carbonylation of quaternary α-amino acid esters toward benzolactam synthesis
[a]
Table 15.20 Selected examples for the carbonylation of secondary amine
[a]
Table 15.21 Carbonylation for the highly substituted endocyclic enol lactone synthesis
[a]
Table 15.22 Carbonylation of tertiary alcohol
[a]
Table 15.23 Represented products for the carbonylation of aryl urea derivatives
[a]
Table 15.24 Selected examples for the carbonylative synthesis of quinazolin-4(3
H
)-ones
[a]
Table 15.25 Carbonylation of
N
-alkylanilines toward to isatoic anhydrides
[a]
Table 15.26 Double C−H carbonylative activation of diaryl ether for the synthesis of xanthones
[a]
Table 15.27 Carbonylative synthesis of 1,3-oxazin-6-ones from palladium-catalyzed alkenyl C−H bond activation in the enamides
[a]
Table 15.28 Carbonylation of
ortho
-amino biaryl
[a]
Table 15.29 Carbonylation of
ortho
-hydroxy biaryl
[a]
Table 15.30 2-Quinolinone synthesis from carbonylative [3+2+1] annulation of
N
-pyridyl anilines with internal alkynes and Mo(CO)
6
[a]
Table 15.31 Carbonylative γ-C−H functionalization of aliphatic acid
[a]
Table 15.32 Selected examples for the pyridocarbonylation of
N
-pyridyl anilines to form 11
H
-pyrido[2,1-
b
]-quinazolin-11-one
[a]
Table 15.33 Pd(II)-catalyzed carbonylative phosphaannulation of phosphonic and phosphinic acid to prepare oxaphosphorinanone oxides
[a]
Table 15.34 Selected products for silanol-directed carbonylation toward salicylic acid synthesis
[a]
