Solvents as Reagents in Organic Synthesis E-Book
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- Herausgeber: Wiley-VCH Verlag GmbH & Co. KGaA
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
Written by highly renowned and experienced authors, this is the only reference on the application of solvents as reagents.
Clearly structured, the text describes various methods for the activation and reaction of these small molecules, highlighting the synthetic opportunities as well as process-oriented advantages. To this end, all relevant types of solvents are covered separately and emphasized with numerous synthetic examples, while taking care to explain applications so as to avoid undesired side reactions.
The result is a unique resource for every synthetic chemist and reaction engineer in industry and academia working on the methodical optimization of synthetic transformations.
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Seitenzahl: 680
Veröffentlichungsjahr: 2017
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Table of Contents
Cover
Title Page
Copyright
List of Contributors
Chapter 1: The Applications of Water as Reagents in Organic Synthesis
1.1 Introduction
1.2 Incorporation of Hydrogen Atom from the Water
1.3 Incorporation of Oxygen Atom from the Water
1.4 Incorporation of Hydroxyl Group from Water
1.5 Traceless Promotion of the Reactions by Water
1.6 Conclusions
References
Chapter 2: The Applications of Toluene and Xylenes
2.1 Application of Toluene and Xylenes as Reagents
2.2 Oxidation of Methyl Group into Common Functionalities
2.3 Application of Methyl Group as Acyl Building Block
2.4 Application as Alkyl Building Block
2.5 Application as Esters Building Block
2.6 Application as Alcohols Building Block
References
Chapter 3: The Applications of 1,4-Dioxane, THF, and Ethers as Versatile Building Blocks in Organic Synthesis
3.1 Introduction
3.2 Cleavage of C(sp
3
)−H of Ethers
3.3 Cleavage of C−O of Ethers
3.4 Cleavage of C−C Bonds of Ethers
3.5 Conclusion
References
Chapter 4: The Application of Dichloromethane and Chloroform as Reagents in Organic Synthesis
4.1 The Application of Dichloromethane and Chloroform as Reagents in Organic Synthesis
References
Chapter 5: The Applications of Acetone and Ethyl Acetate
5.1 Acetone
5.2 Ethyl Acetate
References
Chapter 6: N,N-Dimethylformamide and N,N-Dimethylacetamide as Carbon, Hydrogen, Nitrogen, and/or Oxygen Sources
6.1 Introduction
6.2 Amination
6.3 Amidation and Thioamidation
6.4 Amidination
6.5 Formylation and Related Domino Reactions
6.6 Carbonylation
6.7 Cyanation
6.8 Insertion Reactions
6.9 Miscellaneous Reactions
Acknowledgments
References
Chapter 7: The Applications of DMSO
7.1 A Brief Introduction of DMSO
7.2 Name Reactions
7.3 As Reaction Reagents
7.4 As Multifunctional Catalyst/Reagent in Self-Sorting Reaction System
7.5 Summary and Perspectives
Acknowledgments
References
Chapter 8: Acetonitrile as Reagents in Organic Synthesis: Reactions and Applications
8.1 Introduction
8.2 Transition-Metal-Catalyzed Cross-Coupling of Acetonitrile and Nitriles
8.3 Free-Radical-Initiated C−H Functionalization of Acetonitrile and Nitriles
8.4 Summary and Outlook
Acknowledgments
References
Chapter 9: The Applications of Nitromethane as Reagent and Solvent in Organic Synthesis
9.1 Introduction
9.2 Reactions with Aldehydes
9.3 Reactions with Imines
9.4 Reactions with Ketones
9.5 Michael Reaction
9.6 Other Reactions
References
Chapter 10: Alcohol as a Reagent in Homogeneous Catalysis
10.1 Introduction
10.2 Alcohol as
O
-nucleophile
10.3 Alcohol Oxidation or α-C−H Functionalization (Alcohol as
C
-nucleophile)
10.4 Alcohol as Electrophile
10.5 Conclusion
References
Chapter 11: Synchronous Application of Hydrocarbons as Solvents and Reagents in Transition-Metal Catalysis
11.1 Introduction
11.2 Aromatic Hydrocarbons
11.3 Aliphatic Hydrocarbons
11.4 Conclusions
Acknowledgments
References
Index
End User License Agreement
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Guide
Cover
Table of Contents
Begin Reading
List of Illustrations
Chapter 1: The Applications of Water as Reagents in Organic Synthesis
Scheme 1.1 Enantioselective synthesis of (+)-sertraline and (+)-indatraline.
Scheme 1.2 Catalyst-free sulfonylation of activated alkenes in water.
Scheme 1.3 Silver(I)-catalyzed hydroazidation of ethynyl carbinols.
Scheme 1.4 Silver-catalyzed hydroazidation of alkynes and the application to access to 1,5-fused 1,2,3-triazoles.
Scheme 1.5 Formation of 2
H
-1,2,3-triazol-4-ols from α-azido esters.
Scheme 1.6 Triphenylphosphinecarboxamide: An effective reagent for the reduction of azides.
Scheme 1.7 Visible-light-induced hydrodifluoromethylation of alkenes.
Scheme 1.8 Two cascade reactions to synthesize substituted furocoumarins.
Scheme 1.9 Hydroxyphosphinylation reaction of 3-cyclopropylideneprop-2-en-1-ones.
Scheme 1.10 TfOH-catalyzed domino cycloisomerization/hydrolytic defluorination of 2,3-allenyl perfluoroalkyl ketones.
Scheme 1.11 Synthesis of benzyl derivatives via oxidation of stilbenes in an I
2
–H
2
O system.
Scheme 1.12 Copper-catalyzed oxidative cyclization of 1,5-enynes to access to 3-formyl-1-indenones.
Scheme 1.13 Rh(II)-catalyzed denitrogenative hydration reaction of
N
-sulfonyl-1,2,3-triazoles.
Scheme 1.14 The Wacker oxidation reaction for the synthesis of methyl ketones.
Scheme 1.15 Efficient and highly aldehyde selective Wacker oxidation.
Scheme 1.16 Pd(II)-catalyzed direct oxygenation of allylic C−H bond with H
2
O.
Scheme 1.17 Anti-Markovnikov oxidation of β-alkyl styrenes with H
2
O as the terminal oxidant.
Scheme 1.18 Synthesis of arylcarboxyamides from aryl diazonium salts and isocyanides.
Scheme 1.19 Synthesis of benzamides by a multicomponent reaction involving arynes, isocyanides, and H
2
O.
Scheme 1.20 Pd(II)-catalyzed nitrile-directed C−H activation for the synthesis of fluorenones.
Scheme 1.21 Ruthenium-catalyzed cyclization of aromatic nitriles with alkenes.
Scheme 1.22 Synthesis of 3,3-disubstituted 2,3-dihydroazanaphthoquinones.
Scheme 1.23 Cu(II)-catalyzed monohydration of methylenemalononitriles.
Scheme 1.24 Enantioselective approach to polycyclic polyprenylated acylphloroglucinols via CAIMCP.
Scheme 1.25 Visible-light-initiated direct oxysulfonylation of alkenes.
Scheme 1.26 I
2
/aqueous TBHP-catalyzed coupling of amides with methylarenes.
Scheme 1.27 Synthesis of monofluorinated arylhydrazones.
Scheme 1.28 Oxidation of aliphatic C−H bonds in amino-containing molecules.
Scheme 1.29 Cu(I)-catalyzed Aza-Diels–Alder/nucleophilic addition/ring-opening reaction.
Scheme 1.30 Cu/Fe-cocatalyzed Meyer–Schuster-like rearrangement of propargylic amines.
Scheme 1.31 [(NHC)Au
I
]-catalyzed acid-free alkyne hydration.
Scheme 1.32 Regiospecific hydration of
N
-(diphenylphosphinoyl)propargyl amines.
Scheme 1.33 Pt(II)-catalyzed hydrative carbocyclizations of oxo-alkyne-nitrile functionalities.
Scheme 1.34 Ruthenium-catalyzed intramolecular carbocyclization of alkynes.
Scheme 1.35 Pd/Cu-catalyzed intermolecular cyclization of enediyne compounds and alkynes.
Scheme 1.36 Pd(II)-catalyzed bimolecular carbocyclizations of enediynes to 2,6-diacylnaphthalenes.
Scheme 1.37 Copper-catalyzed intramolecular oxidative 6-
exo-trig
cyclization of 1,6-enynes.
Scheme 1.38 Intramolecular
ipso
-halocyclization of 4-(
p
-unsubstituted-aryl)-1-alkynes leading to spiro[4,5]trienones.
Scheme 1.39 Nitrative cyclization of
N
-aryl imines with
t
-BuONO to 3-nitroindoles.
Scheme 1.40 Cascade nitration/cyclization of 1,7-enynes with
t
-BuONO and H
2
O.
Scheme 1.41 Synthesis of disubstituted isoxazoles from homopropargylic alcohol.
Scheme 1.42 Nitrative spirocyclization mediated by TEMPO.
Scheme 1.43 Nitrative cyclization of 1-ethynyl-2-(vinyloxy)benzenes with
t
-BuONO.
Scheme 1.44 Metal-free [4+2] annulation of arylalkynes with
tert
-butyl nitrite.
Scheme 1.45 Palladium-catalyzed oxidative 6-
exo-trig
cyclization of 1,6-enynes.
Scheme 1.46 Tunable cascade reactions of alkynols with alkynes.
Scheme 1.47 Rh(II)-catalyzed three-component reactions leading to β-aryl isoserine derivatives.
Scheme 1.48 Highly α-selective hydrolysis of α,β-epoxyalcohols.
Scheme 1.49 Difluorohydroxylation of indoles using Selectfluor as a fluorinating reagent.
Scheme 1.50 Halohydroxylation reaction of allenes.
Scheme 1.51 Lewis-acid-catalyzed synthesis of (
E
)-α,β-unsaturated acids.
Scheme 1.52 Rh(II)-catalyzed tandem reactions for the syntheses of dihydroisobenzofurans and indanones.
Scheme 1.53 Gold(I)-catalyzed ring-expanding spiroannulation of cyclopropenones with enynes.
Scheme 1.54 Anti-Markovnikov hydration of alkenes via triple relay catalysis.
Scheme 1.55 Pd-catalyzed transformation of terminal alkenes into primary allylic alcohols.
Scheme 1.56 Synthesis of
N
-aryl β-amino alcohols from aziridines, arynes, and water.
Scheme 1.57 PhI(OCOCF
3
)
2
-mediated cyclization of
o
-(1-alkynyl)benzamides.
Scheme 1.58 Carbohydroxylation of styrenes with aryldiazonium salts.
Scheme 1.59 Palladium-catalyzed C(sp
3
)–H hydroxylation with H
2
O as the oxygen source.
Scheme 1.61 Rh(III)-catalyzed [3+2]/[5+2] annulation of 4-aryl 1,2,3-triazoles with internal alkynes.
Scheme 1.60 Synthesis of functionalized 2-hydroxyflavanone derivatives.
Scheme 1.62 Copper-catalyzed arylation/C−C bond activation to access to α-aryl ketones.
Scheme 1.63 Cu-catalyzed oxidative amidation–diketonization of terminal alkynes.
Scheme 1.64 I
2
/TBHP-mediated synthesis of sulfonamides and β-arylsulfonyl enamines.
Scheme 1.65 Synthesis of substituted imidazopyridines and thiazoles from styrenes in water.
Scheme 1.66 Asymmetric hetero-Diels–Alder reaction of diazenes catalyzed by chiral silver phosphate.
Scheme 1.67 Rh (III)-catalyzed [3+2] annulation of 5-aryl-2,3-dihydro-1
H
-pyrroles with internal alkynes.
Scheme 1.68 Pd(II)-catalyzed
ortho
-trifluoromethylation of benzylamines.
Scheme 1.69 Base-promoted formal arylation of benzo[
d
]oxazoles with acyl chloride.
Scheme 1.70 Cu(II)-catalyzed CDC reaction between allylic C−H bonds and α-C−H bonds of ketones or aldehydes.
Chapter 2: The Applications of Toluene and Xylenes
Figure 2.1 Structure of Toluene and Xylene Isomers.
Figure 2.2 Conversion of Toluene Derivatives to Different Products.
Scheme 2.1
Scheme 2.2
Scheme 2.3
Scheme 2.4
Scheme 2.5
Scheme 2.6
Scheme 2.7
Scheme 2.8
Scheme 2.9
Scheme 2.10
Scheme 2.11
Scheme 2.12
Scheme 2.13
Scheme 2.14
Scheme 2.15
Scheme 2.16
Scheme 2.17
Scheme 2.18
Scheme 2.19
Scheme 2.20
Scheme 2.21
Scheme 2.22
Scheme 2.23
Scheme 2.24
Scheme 2.25
Scheme 2.26
Scheme 2.27
Scheme 2.28
Scheme 2.29
Scheme 2.30
Scheme 2.31
Scheme 2.32
Scheme 2.33
Scheme 2.34
Scheme 2.35
Scheme 2.36
Scheme 2.37
Scheme 2.38
Scheme 2.39
Scheme 2.40
Scheme 2.41
Scheme 2.42
Scheme 2.43
Scheme 2.44
Scheme 2.45
Scheme 2.46
Scheme 2.47
Scheme 2.48
Chapter 3: The Applications of 1,4-Dioxane, THF, and Ethers as Versatile Building Blocks in Organic Synthesis
Scheme 3.1 Autoxidation of diethyl ether at room temperature.
Scheme 3.2 Cross-dehydrogenative coupling reactions of ethers to form C−C, C−N, and C−O bonds.
Scheme 3.3 CDC reaction of ethers with 1, 3-dicarbonyl compounds to form C−C bonds.
Scheme 3.4 CDC reaction of ethers with ketones to form C−C bonds.
Scheme 3.5 CDC reaction of ethers with α-amino carbonyl compounds to form C−C bonds.
Scheme 3.6 CDC reaction of ethers with
N
,
N
-dialkylanilines to form tricyclic compounds.
Scheme 3.7 CDC reaction of ethers with olefins to construct allylic ethers.
Scheme 3.8 CDC reaction of ethers with benzene derivatives.
Scheme 3.9 CDC reaction of ethers with benzothiazole, benzoxazole or benzimidazole.
Scheme 3.10 More CDC reactions of ethers with azoles.
Scheme 3.11 Regioselective CDC reaction of ethers with indoles.
Scheme 3.12 Regioselective CDC reactions of ethers with coumarins and flavones.
Scheme 3.13 Regioselective CDC reaction of ethers with quinoline
N
-oxides.
Scheme 3.14 Tandem reaction of 2-alkynylbenzaldoximes with cyclic ethers.
Scheme 3.15 Tandem reaction of 2-alkynylbenzaldoximes with cyclic ethers.
Scheme 3.16 α-C−H amination of ethers with imidazole, 1
H
-pyrazole, 1
H
-1,2,4-triazole, and benzimidazole.
Scheme 3.17 Other azoles used in α-C−H amination of ethers.
Scheme 3.18 α-C−H amination of ethers with
N
-alkoxyamides.
Scheme 3.19 Two different methods to form THP ether and THF ether.
Scheme 3.20 CrCl
2
-mediated C−O bond formation of ether with alcohol.
Scheme 3.21 The CDC reaction of ethers with phenol derivatives or β-ketoesters.
Scheme 3.22 The CDC reaction of ethers with oximes.
Scheme 3.23 The CDC reaction of ethers with carboxylic acids to form C−O bonds.
Scheme 3.24 α-Acyloxylation reaction of ethers with diverse substrates.
Scheme 3.25 C−S bond formation of ethers with various S sources.
Scheme 3.26 Early examples of the addition of ethers to CC bonds.
Scheme 3.27 Recent examples of the addition of ethers to CC bonds with transition metal catalysts.
Scheme 3.28 More examples of the addition of ethers to CC bonds with transition metal catalysts.
Scheme 3.29 Addition of ethereal radical to CC bonds followed by insertion to CC bonds.
Scheme 3.30 The addition of ethers to CC bonds with transition metal catalysts.
Scheme 3.31 Proposed mechanism involving ethereal C−H oxidation addition on Rh(I).
Scheme 3.32 Decarboxylative alkenylation and alkylation reactions with ethers.
Scheme 3.33 Tunable decarboxylative alkylation reactions of cinnamic acids with ethers.
Scheme 3.34 Plausible mechanisms for radical alkenylation and alkynylation of ethers.
Scheme 3.35 Representative examples of radical alkenylation and alkynylation of ethers.
Scheme 3.36 Et
3
B-promoted α-C−H hydroxyalkylation of ethers under air.
Scheme 3.37 Lewis acids-/air-mediated α-C−H hydroxyalkylation or aminoalkylation of ethers.
Scheme 3.38 A plausible mechanism for the metal-catalyzed intermolecular carbenoid insertion with alkanes or α-C−H bond of ethers.
Scheme 3.39 Rh-catalyzed asymmetric C−H insertion into THF.
Scheme 3.40 C(sp
3
)−H arylation of THF with arylmagnesium bromide.
Scheme 3.41 Oxidative C(sp
3
)−H arylation of ethers with arylboronic acids.
Scheme 3.42 C−O cleavage under acidic conditions.
Scheme 3.43 C−O cleavage under Lewis acidic conditions.
Scheme 3.44 C−O cleavage under organometallic reagents.
Scheme 3.45 C−O cleavage involving peroxides.
Scheme 3.46 C−O cleavage involving ZnMe
2
and O
2
.
Scheme 3.47 Synthesis of heterocycles involving C−O cleavage.
Scheme 3.48 Direct aryl hydroxylation using 1,4-dioxane as the source of the hydroxyl group.
Scheme 3.49 C−C cleavage of ethers.
Chapter 4: The Application of Dichloromethane and Chloroform as Reagents in Organic Synthesis
Scheme 4.1
Scheme 4.2
Scheme 4.3
Scheme 4.4
Scheme 4.5
Scheme 4.6
Scheme 4.7
Scheme 4.8
Scheme 4.9
Scheme 4.10
Scheme 4.11
Scheme 4.12
Scheme 4.13
Scheme 4.14
Scheme 4.15
Scheme 4.16
Scheme 4.17
Scheme 4.18
Scheme 4.19
Scheme 4.20
Scheme 4.21
Scheme 4.22
Scheme 4.23
Scheme 4.24
Scheme 4.25
Scheme 4.26
Scheme 4.27
Scheme 4.28
Scheme 4.29
Scheme 4.30
Scheme 4.31
Scheme 4.32
Scheme 4.33
Scheme 4.34
Scheme 4.35
Scheme 4.36
Scheme 4.37
Scheme 4.38
Scheme 4.39
Scheme 4.40
Scheme 4.41
Scheme 4.42
Scheme 4.43
Scheme 4.44
Scheme 4.45
Scheme 4.46
Scheme 4.47
Scheme 4.48
Scheme 4.49
Scheme 4.50
Scheme 4.51
Scheme 4.52
Scheme 4.53
Scheme 4.54
Scheme 4.55
Scheme 4.56
Scheme 4.57
Scheme 4.58
Scheme 4.59
Scheme 4.60
Scheme 4.61
Scheme 4.62
Scheme 4.63
Scheme 4.64
Scheme 4.65
Scheme 4.66
Scheme 4.67
Scheme 4.68
Scheme 4.69
Scheme 4.70
Scheme 4.71
Scheme 4.72
Scheme 4.73
Scheme 4.74
Scheme 4.75
Scheme 4.76
Scheme 4.77
Scheme 4.78
Scheme 4.79
Scheme 4.80
Scheme 4.81
Chapter 5: The Applications of Acetone and Ethyl Acetate
Scheme 5.1 General form of aldol reaction involving ketone as nucleophile.
Scheme 5.2 Proline-catalyzed asymmetric aldol reaction of acetone and aldehydes.
Scheme 5.3 Enamine-activation-based mechanism of the proline-catalyzed aldol reaction.
Scheme 5.4 DMTC-catalyzed asymmetric aldol reaction of acetone and aldehydes.
Figure 5.1 Some chiral amines used in asymmetrical aldol reaction.
Scheme 5.5 Asymmetrical aldol reactions of isatins and acetone.
Scheme 5.6 Benzyl-alcohol-based Claisen–Schmidt reaction.
Scheme 5.7 l-proline-catalyzed synthesis of enones and cyclohexanones.
Scheme 5.8 l-Proline-catalyzed asymmetric Mannich reaction.
Scheme 5.9 Three-component Mannich reaction catalyzed by chiral sulfoxide.
Scheme 5.10 Asymmetric Mannich reactions of trifluoromethyl ketimines and acetone.
Scheme 5.11 Asymmetrical Mannich reactions of 3-substituted-2
H
-1,4-benzoxazines and acetone.
Scheme 5.12 Asymmetrical Mannich reactions of benzo[e][1,2,3]oxathiazine 2,2-dioxides and acetone.
Scheme 5.13 Enantioselective synthesis of β-amino ketones of five-membered structure.
Scheme 5.14 Asymmetric Mannich reaction of seven-membered ketimines.
Scheme 5.15 Asymmetric Mannich reactions of different cyclic ketimines and acetone.
Scheme 5.16 The synthesis of alcohols and substituted malonitrile using acetone.
Scheme 5.17 Different synthesis of benzodiazepines.
Scheme 5.18 Multicomponent synthesis of benzodiazepinyl phosphonates.
Scheme 5.19 Acetone-based multicomponent synthesis of azine heterocyles.
Scheme 5.20 Acetone-based multicomponent synthesis of pyridin-2(
1H
)-one.
Scheme 5.21 Divergent syntheses involving the single nucleophilic addition of the methyl of acetone.
Scheme 5.22 Reactions involving the transformation of both methyl groups in acetone.
Scheme 5.23 Acetone-based three-component reactions for the synthesis of anilines.
Scheme 5.24 Acetone-participated multicomponent reactions for pyridine synthesis.
Scheme 5.25 Acetone-based three-component synthesis of quinolines.
Scheme 5.26 Cross-coupling reactions of acetone with aryl halides/tosylates.
Scheme 5.27 Carbonylative coupling reaction of aryl iodide, CO, and acetone.
Scheme 5.28 Selective acetylation of primary alcohols with ethyl acetate.
Scheme 5.29 Selective acetylation of the primary alcohols in carbohydrates.
Scheme 5.30 Selective acetylation of thioglycosides.
Scheme 5.31 NHC-catalyzed acetylation of secondary alcohols.
Scheme 5.32 Lanthanum(III) -catalyzed acetylation of secondary/tertiary alcohols.
Scheme 5.33 Enzyme-catalyzed acetylation of bile acids.
Scheme 5.34 Asymmetric synthesis of acetates via ketone-based acetylation.
Scheme 5.35 Transesterification between ethers and ethyl acetate.
Scheme 5.36 MWI-assisted amidation of ethyl acetate.
Scheme 5.37 Enzymatic resolution of primary amines via ethyl-acetate-based acetylation.
Scheme 5.38 Acetylation of sulfonamides.
Scheme 5.39 Synthesis of tertiary alcohols using
C
-nucleophiles and ethyl acetate.
Scheme 5.40
n
-BuLi-promoted α-acetylation of phosphine oxide.
Scheme 5.41 Nucleophilic addition of the α-carbon in ethyl acetate to acrolein.
Scheme 5.42 Ethyl-acetate-participated synthesis of pyridin-2-ones.
Chapter 6: N,N-Dimethylformamide and N,N-Dimethylacetamide as Carbon, Hydrogen, Nitrogen, and/or Oxygen Sources
Scheme 6.1
Scheme 6.2
Scheme 6.3
Scheme 6.4
Scheme 6.5
Scheme 6.6
Scheme 6.7
Scheme 6.8
Scheme 6.9
Scheme 6.10
Scheme 6.11
Scheme 6.12
Scheme 6.13
Scheme 6.14
Scheme 6.15
Scheme 6.16
Scheme 6.17
Scheme 6.18
Scheme 6.19
Scheme 6.20
Scheme 6.21
Scheme 6.22
Scheme 6.23
Scheme 6.24
Scheme 6.25
Scheme 6.26
Scheme 6.27
Scheme 6.28
Scheme 6.29
Scheme 6.30
Scheme 6.31
Scheme 6.32
Scheme 6.33
Scheme 6.34
Scheme 6.35
Scheme 6.36
Scheme 6.37
Scheme 6.38
Scheme 6.39
Scheme 6.40
Scheme 6.41
Scheme 6.42
Figure 6.43
Scheme 6.44
Scheme 6.45
Scheme 6.46
Scheme 6.47
Scheme 6.48
Scheme 6.49
Scheme 6.50
Scheme 6.51
Scheme 6.52
Scheme 6.53
Scheme 6.54
Scheme 6.55
Scheme 6.57
Scheme 6.58
Scheme 6.56
Scheme 6.59
Scheme 6.60
Scheme 6.61
Scheme 6.62
Scheme 6.63
Scheme 6.64
Scheme 6.65
Scheme 6.66
Scheme 6.67
Scheme 6.68
Scheme 6.69
Scheme 6.70
Scheme 6.71
Scheme 6.72
Scheme 6.73
Scheme 6.74
Scheme 6.75
Scheme 6.76
Scheme 6.77
Scheme 6.78
Scheme 6.79
Scheme 6.80
Scheme 6.81
Scheme 6.82
Scheme 6.83
Chapter 7: The Applications of DMSO
Scheme 7.1
Scheme 7.2
Scheme 7.3
Scheme 7.4
Scheme 7.5
Scheme 7.6
Scheme 7.7
Scheme 7.8
Scheme 7.9
Scheme 7.10
Scheme 7.11
Scheme 7.12
Scheme 7.13
Scheme 7.14
Scheme 7.15
Scheme 7.16
Scheme 7.17
Scheme 7.18
Scheme 7.19
Scheme 7.20
Scheme 7.21
Scheme 7.22
Scheme 7.23
Scheme 7.24
Scheme 7.25
Scheme 7.26
Scheme 7.27
Scheme 7.28
Scheme 7.29
Scheme 7.30
Scheme 7.31
Scheme 7.32
Scheme 7.33
Scheme 7.34
Scheme 7.35
Scheme 7.36
Scheme 7.37
Scheme 7.38
Scheme 7.39
Scheme 7.40
Scheme 7.41
Scheme 7.42
Scheme 7.43
Scheme 7.44
Scheme 7.45
Scheme 7.46
Scheme 7.47
Scheme 7.48
Scheme 7.49
Scheme 7.50
Scheme 7.51
Scheme 7.52
Scheme 7.53
Scheme 7.54
Scheme 7.55
Scheme 7.56
Scheme 7.57
Scheme 7.58
Scheme 7.59
Scheme 7.60
Scheme 7.61
Scheme 7.62
Chapter 8: Acetonitrile as Reagents in Organic Synthesis: Reactions and Applications
Scheme 8.1 S
N
Ar of aryl fluorides with secondary nitriles and KHMDS.
Scheme 8.2 Proposed mechanism for the addition of secondary nitriles to fluoroarenes.
Scheme 8.3 Ruthenium complex-catalyzed direct addition of acetonitrile to aldehydes.
Scheme 8.4 Ruthenium complex-catalyzed direct addition of acetonitrile to imines.
Scheme 8.5 Palladium-catalyzed decarboxylative coupling of cyanoacetate salts with aryl halides and triflates for the synthesis of a-aryl nitriles.
Scheme 8.6 Synthesis of anastrozole.
Scheme 8.7 Palladium-catalyzed R-arylation of nitriles.
Scheme 8.8 Catalytic α-arylation of nitriles with aryl bromides by Pd(OAc)
2
/
16
.
Scheme 8.9 Catalytic α-arylation of nitriles with chlorobenzene by Pd(OAc)
2
/
16
.
Scheme 8.10 Palladium-catalyzed coupling of α-trimethylsilylpropionitrile.
Scheme 8.11 Palladium-catalyzed coupling of α-trimethylsilylcyclohexanecarbonitrile.
Scheme 8.12 Palladium-catalyzed coupling of zinc cyanoalkyl reagents of secondary nitriles.
Scheme 8.13 Synthetic application for the preparation of verapamil.
Scheme 8.14 Palladium-catalyzed carbonylation of aryl iodides and trimethylsilylacetonitrile.
Scheme 8.15 Palladium-catalyzed carbonylative α-arylation to β-ketonitriles.
Scheme 8.16 Palladium-catalyzed site-selective cyanomethylation of unactivated C(sp
3
)−H bonds.
Scheme 8.17 Catalyst-contorlled α-monoallylation of aryl acetonitriles.
Scheme 8.18 Palladium-catalyzed allylation of nitriles with allyl alcohol activated by CO
2
.
Scheme 8.19 Proposed CO
2
-catalyzed C−O bond activation.
Scheme 8.20 Ni-catalyzed synthesis of α-arylnitriles.
Scheme 8.21 Copper-catalyzed aerobic oxidative coupling of aromatic alcohols and acetonitrile to β-ketonitriles.
Scheme 8.22 Probable reaction mechanism.
Scheme 8.23 Rh-catalyzed preparation of reduced Knoevenagel adducts with CO as a deoxygenative agent.
Scheme 8.24 Bond dissociation energy of the C−H bond.
Scheme 8.25 1,2-Ayl migration reaction of unactivated alkenes with acetonitrile under metal-free conditions.
Scheme 8.26 Activated nitriles with 1,2-diaryl allylic alcohols.
Scheme 8.27 A possible mechanism of nitriles with 1,2-diaryl allylic alcohols.
Scheme 8.28 Copper Copper-catalyzed 1,2-aryl migration reaction of unactivated alkenes with acetonitriles.
Scheme 8.29 Metal Metal-promoted 1,2-alkylarylation of activated alkenes with acetonitriles.
Scheme 8.30 Nitro Nitro-substituted oxindoles obtained via radical cascade reaction.
Scheme 8.31 Visible-light-promoted 1,2-alkylarylation of activated alkenes with acetonitriles.
Scheme 8.32 Copper-promoted 1,2-alkylarylation of unactivated alkenes with acetonitriles.
Scheme 8.33 Copper Copper-promoted 1,2-oxylalkylation of unactivated alkenes with acetonitrile.
Scheme 8.34 1,2-oyalkylation of activated alkenes with acetonitrile.
Scheme 8.35 Copper-catalyzed 1,2-oyalkylation of unactivated alkenes with acetonitrile.
Scheme 8.36 Copper-catalyzed 1,2-oxylalkylation of olefinic amides with acetonitrile.
Scheme 8.37 Three-component carboetherification of unactivated alkenes with acetonitrile and alcohols.
Scheme 8.38 Three-component reactions of alkenes with alkylnitriles and water.
Scheme 8.39 1,2-Hydroalkylation of unactivated alkenes with acetonitrile.
Scheme 8.40 Radical CDC reaction of 1,3-dicarbonyl compounds with acetonitrile.
Chapter 9: The Applications of Nitromethane as Reagent and Solvent in Organic Synthesis
Scheme 9.1 Two-step continuous-flow transformations for the synthesis of nitro-containing compounds.
Scheme 9.2 Three-step continuous-flow transformations.
Chapter 10: Alcohol as a Reagent in Homogeneous Catalysis
Scheme 10.1
Scheme 10.2
Scheme 10.3
Scheme 10.4
Scheme 10.5
Scheme 10.6
Scheme 10.7
Scheme 10.8
Scheme 10.9
Scheme 10.10
Scheme 10.11
Scheme 10.12
Scheme 10.13
Scheme 10.14
Scheme 10.15
Scheme 10.16
Scheme 10.17
Scheme 10.18
Scheme 10.19
Scheme 10.20
Scheme 10.21
Scheme 10.22
Scheme 10.23
Scheme 10.24
Scheme 10.25
Scheme 10.26
Scheme 10.27
Scheme 10.28
Scheme 10.29
Scheme 10.30
Scheme 10.31
Scheme 10.32
Scheme 10.33
Scheme 10.34
Scheme 10.35
Scheme 10.36
Scheme 10.37
Scheme 10.38
Scheme 10.39
Scheme 10.40
Scheme 10.41
Scheme 10.42
Scheme 10.43
Scheme 10.44
Scheme 10.45
Scheme 10.46
Scheme 10.47
Scheme 10.48
Scheme 10.49
Scheme 10.50
Scheme 10.51
Scheme 10.52
Scheme 10.53
Scheme 10.54
Scheme 10.55
Scheme 10.56
Scheme 10.57
Scheme 10.58
Scheme 10.59
Scheme 10.60
Scheme 10.61
Scheme 10.62
Scheme 10.63
Scheme 10.64
Scheme 10.65
Scheme 10.66
Scheme 10.67
Scheme 10.68
Scheme 10.69
Scheme 10.70
Scheme 10.71
Scheme 10.72
Scheme 10.73
Scheme 10.74
Chapter 11: Synchronous Application of Hydrocarbons as Solvents and Reagents in Transition-Metal Catalysis
Scheme 11.1
Scheme 11.2
Scheme 11.3
Scheme 11.4
Scheme 11.5
Scheme 11.6
Scheme 11.7
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
Scheme 11.22
Scheme 11.23
Scheme 11.24
Scheme 11.25
Scheme 11.26
Scheme 11.27
Scheme 11.28
Scheme 11.29
Scheme 11.30
Scheme 11.31
Scheme 11.32
Scheme 11.33
Scheme 11.34
Scheme 11.35
Scheme 11.36
Scheme 11.37
Scheme 11.38
Scheme 11.39
Scheme 11.40
Scheme 11.41
Scheme 11.42
Scheme 11.43
Scheme 11.44
Scheme 11.45
Scheme 11.46
Scheme 11.47
Scheme 11.48
Scheme 11.49
Scheme 11.50
Scheme 11.51
Scheme 11.52
Scheme 11.53
Scheme 11.54
Scheme 11.55
Scheme 11.56
Scheme 11.57
Scheme 11.58
Scheme 11.59
Scheme 11.60
Scheme 11.61
Scheme 11.62
Scheme 11.63
Scheme 11.64
Scheme 11.65
Scheme 11.66
Scheme 11.67
Scheme 11.68
Scheme 11.69
Scheme 11.70
Scheme 11.71
Scheme 11.72
Scheme 11.73
Scheme 11.74
Scheme 11.75
Scheme 11.76
Scheme 11.77
Scheme 11.78
Scheme 11.79
Scheme 11.80
Scheme 11.81
Scheme 11.82
Scheme 11.83
Scheme 11.84
Scheme 11.85
Scheme 11.86
Scheme 11.87
Scheme 11.88
Scheme 11.89
Scheme 11.90
Scheme 11.91
Scheme 11.92
Scheme 11.93
Scheme 11.94
Scheme 11.95
Scheme 11.96
Scheme 11.97
Scheme 11.98
Scheme 11.99
Scheme 11.100
Scheme 11.101
Scheme 11.102
Scheme 11.103
Scheme 11.104
Scheme 11.105
Scheme 11.106
Scheme 11.107
Scheme 11.108
Scheme 11.109
Scheme 11.110
Scheme 11.111
Scheme 11.112
Scheme 11.113
Scheme 11.114
Scheme 11.115
Scheme 11.116
Scheme 11.117
Scheme 11.118
Scheme 11.119
Scheme 11.120
Scheme 11.121
Scheme 11.122
List of Tables
Chapter 2: The Applications of Toluene and Xylenes
Table 2.1 Physical properties
Chapter 3: The Applications of 1,4-Dioxane, THF, and Ethers as Versatile Building Blocks in Organic Synthesis
Table 3.1 Physical properties and C−H BDEs of some representative ethers and alkanes with comparable molecular weight
Chapter 4: The Application of Dichloromethane and Chloroform as Reagents in Organic Synthesis
Table 4.1 Examples for dichlorocarbene addition to alkene halides
Table 4.2 Examples for dichlorocarbene addition to alkenes bearing various functional groups
Chapter 5: The Applications of Acetone and Ethyl Acetate
Table 5.1 Asymmetric aldol reactions of acetone and aldehydes catalyzed by different chiral amines (selected examples)
Table 5.2 Selected examples of acetone-based
E
-selective Claisen–Schmidt reaction
Table 5.3 Selected examples of acetylation reactions employing ethyl acetate as acetylating reagent
Table 5.4 Selected examples of catalytic amidation of ethyl acetate
Table 5.5 Selected examples of the catalytic hydrogenation of ethyl acetate
Chapter 7: The Applications of DMSO
Table 7.1 DMSO properties
Table 7.2 Heterocyclic Molecules Prepared Through Self-Sorting Reactions.
Solvents as Reagents in Organic Synthesis
Reactions and Applications
Edited by Xiao-FengWu
Editor
Dr. Xiao-Feng Wu
Albert-Einstein-Str. 29a
18059 Rostock
Germany
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List of Contributors
Jian Cao
Hangzhou Normal University
Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education
Science Park of HZNU Hangzhou 311121
PR China
Narendra R. Chaubey
Banaras Hindu University
Department of Chemistry (Centre of Advanced Study) Institute of Science
Varanasi 221005
India
Zhengkai Chen
Zhejiang Sci-Tech University
Department of Chemistry
Hangzhou 310018
PR China
Xue-Qiang Chu
Soochow University
Key Laboratory of Organic Synthesis of Jiangsu Province
College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology
Suzhou 215123
PR China
Yi Fang
Soochow University
Key Laboratory of Organic Synthesis of Jiangsu Province
College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology
Suzhou 215123
PR China
Qing-He Gao
Xinxiang Medical University
School of Pharmacy
District of Hongqi
Henan Xinxiang 453003
PR China
Feng Han
State Key Laboratory for Oxo Synthesis and Selective Oxidation
Suzhou Research Institute of LICP
Lanzhou Institute of Chemical Physics (LICP)
Chinese Academy of Sciences
Lanzhou 730000
PR China
Shun-Jun Ji
Soochow University
Key Laboratory of Organic Synthesis of Jiangsu Province
College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology
Suzhou 215123
PR China
Jean Le Bras
CNRS – Université de Reims Champagne-Ardenne
Institut de Chimie Moléculaire de Reims
UMR 7312, B.P. 1039
51687 Reims Cedex 2
France
Ping Liu
Nanjing Normal University
College of Chemistry and Materials Science
Jiangsu Provincial Key Laboratory of Material Cycle Processes and Pollution Control
Jiangsu Collaborative Innovation Center of Biomedical Functional Materials
Nanjing 210023
PR China
Chao Liu
State Key Laboratory for Oxo Synthesis and Selective Oxidation
Suzhou Research Institute of LICP
Lanzhou Institute of Chemical Physics (LICP)
Chinese Academy of Sciences
Lanzhou 730000
PR China
Jacques Muzart
CNRS – Université de Reims Champagne-Ardenne
Institut de Chimie Moléculaire de Reims
UMR 7312, B.P. 1039
51687 Reims Cedex 2
France
Krishna Nand Singh
Banaras Hindu University
Department of Chemistry (Centre of Advanced Study) Institute of Science
Varanasi 221005
India
Jin-Bao Peng
Zhejiang Sci-Tech University
Department of Chemistry
Hangzhou 310018
PR China
Xinxin Qi
Zhejiang Sci-Tech University
Department of Chemistry
Xiasha Campus
Hangzhou 310018
PR China
Hongjun Ren
Zhejiang Sci-Tech University
Department of Chemistry
Hangzhou 310018
PR China
Johannes Schranck
Solvias AG
Römerpark 2
4303 Kaiseraugst
Switzerland
Neetu Singh
Banaras Hindu University
Department of Chemistry Centre of Advanced Study Institute of Science
Varanasi 221005
India
Peipei Sun
Nanjing Normal University
College of Chemistry and Materials Science
Jiangsu Provincial Key Laboratory of Material Cycle Processes and Pollution Control
Jiangsu Collaborative Innovation Center of Biomedical Functional Materials
Nanjing 210023
PR China
Wei Sun
State Key Laboratory for Oxo Synthesis and Selective Oxidation
Suzhou Research Institute of LICP
Lanzhou Institute of Chemical Physics (LICP)
Chinese Academy of Sciences
Lanzhou 730000
PR China
Anis Tlili
Université Lyon 1
Institute of Chemistry and Biochemistry (ICBMS-UMR CNRS 5246), CNRS
Villeurbanne France
Jie-Ping Wan
Jiangxi Normal University
College of Chemistry and Chemical Engineering
Nanchang 330022
PR China
Shun-Yi Wang
Soochow University
Key Laboratory of Organic Synthesis of Jiangsu Province College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology
Suzhou 215123
PR China
An-Xin Wu
Key Laboratory of Pesticide & Chemical Biology Ministry of Education College of Chemistry
Central China Normal University
Hubei Wuhan 430079
PR China
Xiao-Feng Wu
Zhejiang Sci-Tech University
Department of Chemistry Xiasha Campus
Hangzhou 310018
PR China
and
Universität Rostock
Leibniz-Institut für Katalyse e.V. an der
Albert-Einstein-Straße 29a
18059 Rostock
Germany
Chungu Xia
State Key Laboratory for Oxo Synthesis and Selective Oxidation
Suzhou Research Institute of LICP
Lanzhou Institute of Chemical Physics (LICP)
Chinese Academy of Sciences
Lanzhou 730000
PR China
Jia-Chen Xiang
Key Laboratory of Pesticide & Chemical Biology Ministry of Education College of Chemistry
Central China Normal University
Hubei Wuhan 430079
PR China
Li-Wen Xu
Hangzhou Normal University
Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education
Science Park of HZNU Hangzhou 311121
PR China
Guanghui Zhang
Purdue University
School of Chemical Engineering
West Lafayette IN 47907
USA
Chapter 1The Applications of Water as Reagents in Organic Synthesis
Zhengkai Chen and Hongjun Ren
Zhejiang Sci-Tech University, Department of Chemistry, Hangzhou, 310018, PR China
1.1 Introduction
Water due to its low cost, easy availability, nontoxic and nonflammable properties has been considered one of the most ideal and promising solvents in organic synthesis from the green and sustainable point of view. Furthermore, with regard to enormous enzyme-catalyzed biosynthesis in nature, water serves as a favorable medium for the versatile synthesis of a variety of complicated molecules and compounds. Over the past decades, considerable efforts had been devoted into the organic reactions by using water as solvent from economy and environment perspectives [1]. Even more, the proposed concept of “in-water” and “on-water” further stimulated the booming development of the utilization of water as solvent for organic synthesis [1e, 2]. Therefore, in recent years, more and more general organic reactions were successfully exploited to perform in water instead of organic solvents to achieve sustainable and environmental benefits.
From a different perspective, the water itself could also be applied as a useful reagent to participate in the reaction through incorporating a hydrogen or oxygen atom or hydroxyl group into the target product. Generally, water is indispensable for various hydrolysis reactions. As a hydrogen source, water is used to quench numerous susceptible reaction systems by providing active hydrogen. Meanwhile, as a versatile nucleophile, the hydroxyl group could be readily introduced into the specific reaction sites by the employment of water as hydroxyl precursor. The hydroxyl group could also be readily oxidized to carbonyl group during the reaction. It is worth mentioning that, in some cases, the presence of water could obviously improve the efficiency of the reaction, albeit the exact reason is elusive for some special reactions.
This chapter is divided into the following four parts for further discussion: (i) incorporation of hydrogen atom from water; (ii) incorporation of oxygen atom from water; (iii) incorporation of hydroxyl group from water; and (iv) traceless promotion of the reactions by water.
1.2 Incorporation of Hydrogen Atom from the Water
Aggarwal and coworkers demonstrated a versatile strategy through lithiation/borylation/protodeboronation of a homoallyl carbamate for the highly enantioselective synthesis of (+)-sertraline and (+)-indatraline, which served as potent inhibitors (Scheme 1.1) [3]. It was observed that the presence of the alkene could hamper the lithiation/borylation process, so the modifications of the reaction conditions were necessary by the use of 12-crown-4, TMSCl, H2O or a solvent switch to achieve 1,2-metalate rearrangement in order to ensure high yields and enantioselectivity. As for the protodeboronation step of tertiary boronic ester, the amount of water played a crucial role in the reaction. In 2010, the same group had disclosed a simple approach for the protodeboronation of tertiary boronic esters employing CsF-H2O or TBAF·3H2O with complete stereoselectivity to access to diverse enantioenriched tertiary alkanes [4].
Scheme 1.1 Enantioselective synthesis of (+)-sertraline and (+)-indatraline.
A catalyst-free sulfonylation of activated alkenes with sulfonyl hydrazides in water for highly efficient construction of monosubstituted ethyl sulfones was demonstrated by Wang and coworkers (Scheme 1.2) [5]. Remarkably, the reaction proceeded through without any catalyst, additive, ligand, or organic solvent, with the release of N2 as single by-product. The results of control experiments indicated that an anion pathway was involved in the reaction and the α-hydrogen atom of β-sulfone esters originated from water.
Scheme 1.2 Catalyst-free sulfonylation of activated alkenes in water.
The sulfinyl anion I was first formed assisted by water with the release of one molecule of N2, which could transform into sulfur-centered anion II through resonance process in the presence of water. The sulfur-centered anion readily added to the activated alkene to give the oxygen-centered anion III, followed by another resonance interaction leading to the carbon-centered anion IV. Finally, the proton transfer of intermediate IV from hydronium ions to deliver the desired β-sulfone ester product.
A silver(I)-catalyzed chemo- and regioselective hydroazidation of ethynyl carbinols for the construction of 2-azidoallyl alcohols was developed by Bi and coworkers (Scheme 1.3) [6]. In this transformation, trimethylsilyl azide (TMS-N3) was chosen as the optimal azide source and the pendent hydroxyl group directed the chemo- and regioselectivity of hydroazidation by stabilizing the vinyl azide products. Catalyzed by 10 mol% Ag2CO3, a wide range of secondary and tertiary ethynyl carbinols bearing different substituents could be transformed into the corresponding products in good to excellent yields.
Scheme 1.3 Silver(I)-catalyzed hydroazidation of ethynyl carbinols.
The observation data of control experiments implied that the residual water in the DMSO played the critical role in the reaction. The initial step of the plausible pathway involved the generation of silver acetylide intermediate I. Meanwhile, the hydrazoic acid (HN3) was in situ formed by silver-catalyzed hydrolysis of TMS-N3, which added to the intermediate I to lead to vinyl silver intermediate II. Under the promotion of a trace amount of H2O in the DMSO solvent, the protonation of intermediate II released the final product. As a class of functionalized synthetic intermediates, 2-azidoallyl alcohols could be readily transformed into NH aziridines under the mild reaction conditions.
1.2.1 1,2,3-Triazoles
Inspired by the previous work of silver(I)-catalyzed hydroazidation of ethynyl carbinols, Bi and coworkers extended their study to the general hydroazidation of unactivated alkynes (Scheme 1.4a) [7]. The key point of the progress lay in the necessity of a trace amount of water in DMSO with regard to hydroazidation of ethynyl carbinols. Therefore, it was speculated that a stoichiometric amount of H2O could enhance the reactivity of the reaction and the relevant experiments confirmed the hypothesis. The condition screening of the amount of H2O demonstrated 2.0 equiv. of H2O was appropriate for high efficiency. Furthermore, it was essential to control the reaction time to circumvent the further conversion of vinyl azides to nitriles. The protocol featured readily accessible starting materials, mild reaction conditions, broad substrate scope, and good scalability.
Scheme 1.4 Silver-catalyzed hydroazidation of alkynes and the application to access to 1,5-fused 1,2,3-triazoles.
The significance of the aforementioned synthetic method was embodied in the application for the assembly of several valuable heterocyclic frameworks. In 2015, the strategy of hydroazidation of unactivated alkynes was combined with alkyne-azide 1,3-dipolar cycloaddition reaction to access to a variety of piperidine-fused 1,2,3-triazoles by Bi and coworkers (Scheme 1.4b) [8]. Under silver-catalyzed conditions, the treatment of diyne with TMS-N3 in the presence of H2O gave rise to pharmaceutically relevant 1,5-fused 1,2,3-triazoles in excellent yields. The reaction was assumed to undergo the tandem hydroazidation/alkyne-azide 1,3-dipolar cycloaddition sequence, which presented a concise method for the synthesis of structurally complicated fused heterocyclic compounds in one pot.
Taylor and coworkers developed a variant of Staudinger reaction on α-azido esters with trialkyl phosphines for the formation of 2H-1,2,3-triazol-4-ols (Scheme 1.5) [9]. In this reaction, phosphazides were generated from the reaction of trialkyl phosphines with α-azido esters in THF/H2O, which underwent intramolecular cyclization to afford the desired products. Upon using PPh3, the major product was the reduced amine from the classic Staudinger pathway [10]. As shown in Scheme 1.5, phosphazide I could cyclize to deliver intermediate II, which occurred hydrolysis to give intermediate III. The final product was formed by the protonation of intermediate III and the following isomerization. Notably, phosphazide I could lose nitrogen and release iminophosphorane V, followed by the hydrolysis of intermediate V to produce α-amino ester.
Scheme 1.5 Formation of 2H-1,2,3-triazol-4-ols from α-azido esters.
In 2014, an efficient modification toward Staudinger reaction for the facile reduction of azides had been realized by Ito, Abe, and coworkers (Scheme 1.6) [11]. As for traditional Staudinger reaction, the formed iminophosphorane intermediate could undergo additional hydrolysis process for long reaction times to convert into the primary amines. In the current transformation, the triphenylphosphinecarboxamide (TPPc) derivatives were designed depending on the fact that the specific substituent was introduced at the ortho position of the phenyl ring of triphenylphosphine (TPP), which could promote the hydrolysis process through neighboring group participation effect. Under the improved conditions, the reaction could be completed in 10 min to 2 h to produce the primary amines in high yields without the need for additional hydrolysis process.
Scheme 1.6 Triphenylphosphinecarboxamide: An effective reagent for the reduction of azides.
A visible-light-induced hydrodifluoromethylation of alkenes by the use of bromodifluoromethylphosphonium bromide as the precursor of difluorocarbene for the direct synthesis of the difluoromethylated alkanes was achieved by Qing and coworkers (Scheme 1.7) [12]. For the first time, the CF2H radical was generated from fluorinated phosphonium salts, which could be readily synthesized from the reaction of PPh3 and CF2Br2 in quantitative yield. The results of mechanistic investigations implied that the formation process of CF2H radical (Scheme 1.7). The reaction of bromodifluoromethylphosphonium bromide with H2O generated difluorocarbene, from which the HCF2I or HCF2Br was formed and reacted with PPh3 to give difluoromethylphosphonium salts. Another pathway involved the capture of difluorocarbene by PPh3 and subsequent treatment of H2O or HBr to deliver difluoromethylphosphonium salts, which could undergo a single-electron transfer (SET) process mediated by fac-[IrIII(ppy)3]* to lead to the CF2H radical.
Scheme 1.7 Visible-light-induced hydrodifluoromethylation of alkenes.
1.3 Incorporation of Oxygen Atom from the Water
Two facile one-pot copper-catalyzed reactions for the generation of furo[3,2-c]coumarins and chlorofuro[3,2-c]coumarins using 2-(1-alkynyl)-2-alken-1-one derivatives as starting materials was disclosed by Hu and Cheng (Scheme 1.8) [13]. One reaction involved CuCl-catalyzed cascade addition/cyclization/oxidation sequence of 2-(1-alkynyl)-2-alken-1-one in the presence of water. Another protocol utilized CuBr as catalyst and excess CuCl2 as chlorinated reagent. The proposed mechanism indicated that in the two processes, Lewis acid Cu(I) salt activated the carbonyl group to facilitate the Michael addition of H2O to the CC bond, which was the key step of the reaction.
Scheme 1.8 Two cascade reactions to synthesize substituted furocoumarins.
An unexpected example about the hydroxyphosphinylation reaction of 3-cyclopropylideneprop-2-en-1-ones for the introduction of hydroxyl group and phosphorus group via C−P bond cleavage was developed by Wu and coworkers (Scheme 1.9) [14]. The transformation utilized a highly activated analogue of allene and tertiary phosphine as starting material to construct highly functionalized 1-dialkylphinyl-3-oxo-(1Z)-alkenyl cyclopropanols in a regio- and stereoselective manner under the metal-free conditions. Mechanistic study indicated that the high strain in the CC bond of allene substrate played a significant role in the hydroxyphosphinylation reaction. Intriguingly, based on the proposed mechanism, the oxygen atom of hydroxyl group in the product originated from O2 and the oxygen atom of PO bond came from additional H2O.
Scheme 1.9 Hydroxyphosphinylation reaction of 3-cyclopropylideneprop-2-en-1-ones.
A metal-free TfOH-catalyzed domino cycloisomerization/hydrolytic defluorination reaction of n-perfluoroalkyl allenones for the assembly of furanyl perfluoroalkyl ketones was developed by Ma and coworkers (Scheme 1.10) [15]. The additional water was necessary for the reaction since the oxygen atom of the carbonyl group in the product came from H2O based on 18O-labelling experiments. The reaction proceeded through nucleophilic attack from the carbonyl oxygen, 1,2-phenyl shift, aromatization, nucleophilic attack of water, and elimination of HF sequence. The whole domino reaction process was solely catalyzed by H+ from TfOH to deliver a wide range of furan-2-yl perfluoroalkyl ketones in good yields.
Scheme 1.10 TfOH-catalyzed domino cycloisomerization/hydrolytic defluorination of 2,3-allenyl perfluoroalkyl ketones.
In 2013, Sun and coworkers described an I2–H2O mediated highly chemoselective synthesis of benzyl derivatives through oxidation of stilbenes without the use of any acid and metal (Scheme 1.11) [16]. A wide variety of substituted stilbenes were viable substrates for the protocol and the corresponding benzyl products could be constructed in high yields. Isotopic labeling experiments verified that the oxygen atom of the benzils derived from water and molecular oxygen participated in the reaction. The reaction pathway presumably involved the generation of an iodonium ion, the attack of water to the iodonium ion and sequential oxidation with iodine in water under air.
Scheme 1.11 Synthesis of benzyl derivatives via oxidation of stilbenes in an I2–H2O system.
A Cu(0)/Selectfluor mediated oxidative cyclization of 1,5-enynes in the presence of water with C−C bond cleavage for the synthesis of 3-formyl-1-indenone derivatives was described by Liu and coworkers (Scheme 1.12) [17]. The reaction involved water-participated oxygen-insertion β-carbon elimination and the cleavage of C−C bond sequence. The 18O-labeling experiment unambiguously suggested that both of the carbonyl oxygen atoms in the product came from water. On the basis of preliminary mechanistic studies, the o-alkynyl epoxide served as an intermediate for the reaction and oxycupration of the triple bond and the following ring opening of the epoxide moiety constituted the key steps of the reaction. The C−C bond was cleaved assisted by Selectfluor to deliver benzoyl fluoride.
Scheme 1.12 Copper-catalyzed oxidative cyclization of 1,5-enynes to access to 3-formyl-1-indenones.
A Rh(II)-catalyzed denitrogenative hydration reaction of N-sulfonyl-1,2,3-triazoles with water for the synthesis of a series of biologically active α-amino ketones was demonstrated by Murakami and coworkers (Scheme 1.13) [18]. N-Sulfonyl-1,2,3-triazoles could be readily available from copper-catalyzed 1,3-dipolar cycloaddition reaction (CuAAC) of N-sulfonyl azides and terminal alkynes. In the transformation, the key intermediate α-imino rhodium-(II) carbenoid II was in situ generated assisted by rhodium catalyst, which underwent insertion into the O−H bond of water to produce α-imino alcohol III. Finally, the imine–enamine tautomerization and the following keto–enol tautomerization sequence led to the desired α-amino ketone products. The protocol achieved regioselective 1,2-aminohydroxylation of terminal alkynes, which served as a complement to the example reported by Chang and Fokin employing a copper(I) catalyst to realize 1,1-aminohydroxylation of terminal alkynes [19].
Scheme 1.13 Rh(II)-catalyzed denitrogenative hydration reaction of N-sulfonyl-1,2,3-triazoles.
The Wacker oxidation reaction was a typical and powerful tool for the oxidation of olefins to synthesize ketones in the presence of palladium(II) catalyst, water, and co-oxidant [20]. Usually, the reaction occurred in Markovnikov selectivity from the majority of terminal olefins. In 1959, researchers at Wacker Chemie utilized catalytic PdCl2 and a stoichiometric amount of CuCl2 with bubbling O2 to realize the hydration of olefins (Scheme 1.14). Afterward, the Wacker process was extensively investigated by synthetic chemists to overcome several key limitations. In recent years, the aldehyde-selective Wacker oxidation had been well developed in the field of anti-Markovnikov functionalization of unbiased alkenes, which could produce a range of synthetically versatile aldehydes.
Scheme 1.14 The Wacker oxidation reaction for the synthesis of methyl ketones.
A Pd(II)-catalyzed aldehyde-selective Wacker oxidation of aryl-substituted olefins in the presence of 1,4-benzoquinone was described by Grubbs and coworkers (Scheme 1.15) [21], which was greatly different from the classical Wacker oxidation of providing methyl ketones. As demonstrated by the previous works, t-BuOH was used in Wacker oxidation to improve the aldehyde selectivity and BQ was widely applied as a hydrogen acceptor and two-electron oxidant in Pd(II)-catalyzed reactions. Noteworthy was that high yield of aldehyde products was obtained with respect to more electron-deficient aromatic substrates. The reaction mechanism was similar to the previous work of the same author, in which the Pd-catalyzed oxidation and acid-catalyzed hydrolysis process were involved in the reaction.
Scheme 1.15 Efficient and highly aldehyde selective Wacker oxidation.
The direct oxygenation of an allylic C−H bond catalyzed by palladium using H2O as oxygen source for the production of (E)-alkenyl aldehydes was developed by Jiang and coworkers (Scheme 1.16) [22]. During the process, allylic C−H bond cleavage occurred and an allyl-palladium species was formed as the key intermediate. The choice of DDQ as oxidant could greatly promote the reaction efficiency. The substrate scope was broad and diverse (E)-alkenyl aldehyde products were afforded in high yields with good stereoselectivity. The kinetic isotopic experiments implied that the activation of the allyl C(sp3)−H bond was involved in the rate-determining step.
Scheme 1.16 Pd(II)-catalyzed direct oxygenation of allylic C−H bond with H2O.
A plausible reaction mechanism is shown in Scheme 1.16. π-Allylpalladium species I was generated from the reaction of alkene and Pd(II) through the allylic C−H bond activation. Subsequently, the nucleophilic attack of H2O into intermediate I afforded the oxidative allylic oxygenation products III and III′, which existed as an equilibrating mixture. Finally, the desired aldehyde product was formed by DDQ promoted oxidation of III and III′.
The direct anti-Markovnikov dehydrogenative oxygenation of β-alkyl styrenes under external-oxidant-free conditions by the use of the synergistic effect of photocatalysis and proton-reduction catalysis was presented by Lei and coworkers (Scheme 1.17) [23]. In this transformation, water was applied as single terminal oxidant for the construction of a series of carbonyl compounds. The reaction proceeded through an alkene radical cation intermediate, which was in situ formed by the photoinduced system, followed by the nucleophilic attack of water to give distonic radical cation. Subsequently, the deprotonation of the distonic radical cation produced the anti-Markovnikov intermediate, which underwent single-electron oxidation, elimination, and keto–enol tautomerism sequence to lead to the final carbonyl products. The synergistic effect of this dual catalytic system was vital for the single anti-Markovnikov selectivity. The results of control experiments indicated that the oxygen atom of carbonyl group was derived from water.
Scheme 1.17 Anti-Markovnikov oxidation of β-alkyl styrenes with H2O as the terminal oxidant.
A transition-metal-free carboxyamidation reaction by the use of aryl diazonium tetrafluoroborates and isocyanides as coupling partners for the synthesis of arylcarboxyamides under mild conditions was achieved by Zhu and Xia (Scheme 1.18) [24]. It is worth mentioning that arylcarboxyamides could not be directly assembled by the aminocarbonylation of aryl diazonium salts with amines in the presence of CO. The reaction was realized in the absence of transition-metal catalysts in aqueous media at low temperature and exhibited broad substrate scope with moderate to high efficiency.
Scheme 1.18 Synthesis of arylcarboxyamides from aryl diazonium salts and isocyanides.
A radical mechanism involving hydroxide- or polar-solvent-induced dediazoniation is proposed in Scheme 1.18. Aryl radical I was first formed via homolytic dediazoniation process, which included SET from hydroxide or acetone to aryl diazonium salt. The reaction of aryl radical I with isocyanide delivered a key imidoyl radical intermediate II, followed by oxidation by aryl diazonium cation to lead to a nitrilium intermediate III. Finally, the hydration and tautomerization of intermediate III in the presence of H2O could afford the desired arylcarboxyamide product.
One year later, the transition-metal-free multicomponent reaction involving arynes and isocyanides with H2O for the preparation of benzamide derivatives was reported by Biju and coworkers (Scheme 1.19) [25]. The 1,3-zwitterionic intermediate generated from isocyanide and aryne could be intercepted by different electrophiles for the synthesis of diverse benzannulated heterocycles. The treatment of isocyanide and 2-(trimethylsilyl)aryl triflate mediated by KF in the presence of 18-crown-6 in THF, followed by the addition of water led to benzamide products in good yields. The reaction proceeded through the protonation of in situ generation of 1,3-zwitterionic aryl anion intermediate and the subsequent hydrolysis of the resultant iminium species with H2O. By contrast, the formation of amides through the reaction of isocyanides and water with an aryne from aryldiazonium 2-carboxylate had been previously described by Rigby and Laurent [26], which exhibited narrow substrate scope and moderate isolated yields.
Scheme 1.19 Synthesis of benzamides by a multicomponent reaction involving arynes, isocyanides, and H2O.
A palladium-catalyzed nitrile-directed remote C−H activation with the insertion of nitrile for the construction of a range of polysubstituted fluorenones was developed by Hsieh and coworkers (Scheme 1.20) [27]. The reaction parameters were evaluated to promote the cyclization of the nitrile substrate instead of hydrolysis to amide. AgTFA was found to reduce the rate of hydrolysis and the combination of TFA and DMA was chosen as the optimal cosolvent to suppress the formation of amide. The reaction was supposed to undergo nitrile-directed remote C−H bond activation catalyzed by Pd(TFA)2 to form imine-palladium intermediate, followed by the hydrolysis in the presence of H2O and TFA to furnish the desired product. The dual C−H bond activation protocol could be realized by the use of aryl nitrile and aryl iodine with the slightly modified reaction conditions.
Scheme 1.20 Pd(II)-catalyzed nitrile-directed C−H activation for the synthesis of fluorenones.
A ruthenium-catalyzed oxidative annulation of aromatic nitriles with activated alkenes to provide various Z-stereoselective 3-methyleneisoindolin-1-ones was disclosed by Jeganmohan and Reddy (Scheme 1.21) [28]. In this reaction, Cu(OAc)2 was applied as a Lewis acid to activate the nitrile group of benzonitrile, followed by hydration in the presence of H2O to deliver benzamide. In fact, the amide group was the actual directing group of the reaction. Subsequently, the transformation proceeded through ortho-metalation with ruthenium catalyst, coordinative insertion of alkene into the Ru−C bond, and β-hydride elimination sequence to furnish the alkenylated product. Finally, ruthenium species assisted aza-Michael addition to produce the 3-methyleneisoindolin-1-one product. Of note, the Z-stereoselectivity of product was controlled by the intramolecular hydrogen-bonding.
Scheme 1.21 Ruthenium-catalyzed cyclization of aromatic nitriles with alkenes.
A Pd(OAc)2/H2O-mediated simultaneous alkyne oxidation and nitrile hydration of ortho-alkynylarenenitriles for the construction of various 3,3-disubstituted 2,3-dihydroazanaphthoquinones were accomplished by Srinivasan and Sakthivel (Scheme 1.22) [29]. Although the reaction required stoichiometric amount of expensive Pd(OAc)2 to ensure high efficiency, the alternative condition of choosing 4 equiv. of iodine at 150 °C also enabled the completion of reaction with some compromise in the 70% yield. It is noteworthy that the alkyne moiety was oxidized by DMSO with the assistance of Pd(OAc)2 and the nitrile group underwent hydrolysis to form amide with water. In addition, the alkyne oxidation preceded nitrile hydration process.
Scheme 1.22 Synthesis of 3,3-disubstituted 2,3-dihydroazanaphthoquinones.
The hydration of nitriles to amides gained tremendous attention in the past decades due to the great importance of functionalized amides, which could be applied as versatile building blocks and pharmacologically interesting molecules. Traditionally, the hydration of nitriles was realized by the use of strong acid or base catalysis [30], suffering from numerous drawbacks, such as harsh reaction conditions and excessive hydrolysis. Therefore, the considerable efforts had been made to develop efficient catalytic hydration of nitriles [31]. Nevertheless, the hydration of dinitriles had only a few reports since the challenge was that the possibility of mono- and dehydration was equal.
