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. 2017 Jul 12;117(13):9163-9227.
doi: 10.1021/acs.chemrev.6b00661. Epub 2016 Dec 12.

Transition-Metal-Catalyzed C-H Bond Addition to Carbonyls, Imines, and Related Polarized π Bonds

Joshua R Hummel  1 , Jeffrey A Boerth  1 , Jonathan A Ellman  1
Affiliations

Transition-Metal-Catalyzed C-H Bond Addition to Carbonyls, Imines, and Related Polarized π Bonds

Joshua R Hummel et al. Chem Rev. .

Abstract

The transition-metal-catalyzed addition of C-H bonds to carbonyls, imines, and related polarized π bonds has emerged as a particularly efficient and powerful approach for the construction of an incredibly diverse array of heteroatom-substituted products. Readily available and stable inputs are typically employed, and reactions often proceed with very high functional group compatibility and without the production of waste byproducts. Additionally, many transition-metal-catalyzed C-H bond additions to polarized π bonds occur within cascade reaction sequences to provide rapid access to a diverse array of different heterocyclic as well as carbocyclic products. This review highlights the diversity of transformations that have been achieved, catalysts that have been used, and types of products that have been prepared through the transition-metal-catalyzed addition of C-H bonds to carbonyls, imines, and related polarized π bonds.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1
Reversibility of C–H Bond Additions to Aldehydes
Scheme 2
Scheme 2
Capture of Reversibly Formed Alcohols via Reaction with the Directing Group for C–H Functionalization
Scheme 3
Scheme 3
Rh(III)-Catalyzed Arene C–H Bond Addition to Electron-Deficient Aldehydes
Scheme 4
Scheme 4
Rh(III)-Catalyzed Arene C–H Bond Addition to Activated Aromatic Aldehydes
Scheme 5
Scheme 5
Rh(III)-Catalyzed Alkenyl C–H Addition to Activated Aromatic Aldehydes
Scheme 6
Scheme 6
Rh(III)-Catalyzed C2 Functionalization of Indoles with Ethyl Glyoxylate
Scheme 7
Scheme 7
Ru(II)-Catalyzed C7 Functionalization of Indolines with Ethyl Glyoxylate
Scheme 8
Scheme 8
Ir-Catalyzed Coupling Reaction of N-Methylimidazole and Aldehydes in the Presence of Hydrosilane
Scheme 9
Scheme 9
Proposed Reaction Mechanism for Ir-Catalyzed Coupling Reaction
Scheme 10
Scheme 10
Ir-Catalyzed Meta C–H Functionalization of Pyridines with Aldehydes and Triethylsilane
Scheme 11
Scheme 11
Mn-Catalyzed Arene C–H Addition to Aldehydes followed by Silylation
Scheme 12
Scheme 12
Re-Catalyzed Alkene C–H Bond Addition to Aldehydes followed by Silylation
Scheme 13
Scheme 13
Pd-Catalyzed Oxidative C–H Acylation with Aryl Aldehydes
Scheme 14
Scheme 14
Pd-Catalyzed Oxidative C–H Acylation of 2-Phenoxypyridines with Aldehydes
Scheme 15
Scheme 15
Pd-Catalyzed Oxidative C–H Acylation using an O-Methyl Oxime Directing Group
Scheme 16
Scheme 16
Pd-Catalyzed Ortho C–H Acylation of Anilides with Aldehydes
Scheme 17
Scheme 17
Pd-Catalyzed Ortho C–H Acylation of 2-Arylbenzoxazoles
Scheme 18
Scheme 18
Pd-Catalyzed Oxidative C–H Acylation of Azobenzenes with Aldehydes
Scheme 19
Scheme 19
Pd-Catalyzed Ortho C–H Acylation of an Aminocarbonylated Azobenzene
Scheme 20
Scheme 20
Pd-Catalyzed Oxidative C–H Acylation of N-Benzyltriflamides with Aldehydes
Scheme 21
Scheme 21
Pd-Catalyzed Synthesis of Hydroxyisoindolinones via an Oxidative C–H Acylation/Annulation Cascade
Scheme 22
Scheme 22
Synthesis of Imino Carboxylic Acids using Pd/Lewis Acid Cooperative Catalysis
Scheme 23
Scheme 23
Pd-Catalyzed 1,2-Benzisoxazole Synthesis by C–H Activation/[4+1] Annulation
Scheme 24
Scheme 24
Pd-Catalyzed Nitrogen Directed Ortho C–H Acylation of 3,5-Diarylisoxazoles
Scheme 25
Scheme 25
Pd-Catalyzed Pyridine-Directed C3 Acylation of Benzofurans and Benzothiophenes with Aryl Aldehydes
Scheme 26
Scheme 26
Pd-Catalyzed C2 Acylation of Indoles with Aryl and Alkyl Aldehydes
Scheme 27
Scheme 27
Pd-Catalyzed C2 Acylation and C2/C7 Diacylation of Indoles
Scheme 28
Scheme 28
Pd-Catalyzed C7 Acylation of a C2/C3 Disubstituted Indole
Scheme 29
Scheme 29
Pd-Catalyzed C7 Acylation of Indolines with Aldehydes
Scheme 30
Scheme 30
Rh(III)-Catalyzed Oxidative C–H Acylation of Benzamides with Aryl Aldehydes
Scheme 31
Scheme 31
Rh(III)-Catalyzed Synthesis of Hydroxyisoindolinones
Scheme 32
Scheme 32
Rh(III)-Catalyzed Oxidative C2 Acylation of Indoles with Aryl and Alkyl Aldehydes
Scheme 33
Scheme 33
Rh(III)-Catalyzed Oxidative Ortho Acylation of Aryl Ketone O-Methyl Oximes with Aryl and Alkyl Aldehydes
Scheme 34
Scheme 34
Ru-Catalyzed Oxidative C–H Acylation of Phenols with Aldehydes
Scheme 35
Scheme 35
Re-Catalyzed Synthesis of Isobenzofurans
Scheme 36
Scheme 36
Re-Catalyzed Synthesis of Indenones via Dehydrative Trimerization of Aryl Aldehydes
Scheme 37
Scheme 37
Re(I)-Catalyzed Synthesis of N-Aryl-2H-Indazoles
Scheme 38
Scheme 38
Rh(III)-Catalyzed Synthesis of Phthalides by Cascade Addition and Cyclization of Benzimidates with Aldehydes
Scheme 39
Scheme 39
Rh(III)-Catalyzed Synthesis of Phthalides from Aromatic Acids and Aldehydes
Scheme 40
Scheme 40
Phthalide Synthesis using Dual Rh(III) and Amine Catalysis for Oxidative Aldehyde Coupling by Directed C–H Functionalization
Scheme 41
Scheme 41
Rh(III)-Catalyzed Synthesis of Furans by an Alkene C–H Bond Addition/Cyclization Cascade
Scheme 42
Scheme 42
Rh(III)-Catalyzed Indazole Synthesis by C–H Bond Functionalization and Cyclative Capture
Scheme 43
Scheme 43
Rh(III)-Catalyzed 3-Aryl-(2H)-Indazole Synthesis from Azobenzenes and α- Keto Aldehydes
Scheme 44
Scheme 44
Co(III)-Catalyzed Synthesis of N-Aryl-2H-Indazoles
Scheme 45
Scheme 45
Reversibility of Co(III)-Catalyzed C–H Functionalization Using Deuterated Azobenzenes
Scheme 46
Scheme 46
Reversibility of Co(III)-Catalyzed Aldehyde Insertion Using a Synthetic Intermediate
Scheme 47
Scheme 47
Co(III)-Catalyzed Synthesis of Furans
Scheme 48
Scheme 48
Rh(I)-Catalyzed Intramolecular Aldehyde Coupling
Scheme 49
Scheme 49
Mn-Catalyzed C–H Bond Addition to Unactivated Aldehydes to Access Alcohols
Scheme 50
Scheme 50
Pd-Catalyzed Nucleophilic Additions of Heteroarenes to Isatins
Scheme 51
Scheme 51
Pd-Catalyzed Addition of Acetonitrile to Isatins
Scheme 52
Scheme 52
Rh(III)-Catalyzed Additions of Aryl C–H Bonds to Activated Ketones
Scheme 53
Scheme 53
Rh(III)-Catalyzed Additions of Indole and Indoline C–H Bonds to Activated Ketones
Scheme 54
Scheme 54
Rh(III)-Catalyzed Additions of Aryl C–H Bonds to Cyclopropenones
Scheme 55
Scheme 55
Synthesis of Benzofurans via a Cationic Palladium Complex
Scheme 56
Scheme 56
Possible Pathways for Benzofuran Formation
Scheme 57
Scheme 57
Ir(I)-Catalyzed Synthesis of Benzofurans and Indoles
Scheme 58
Scheme 58
Ir-Catalyzed Ketone Addition a Key Step in cis-Clavicipitic Acid Synthesis
Scheme 59
Scheme 59
Ir(I)-Catalyzed Asymmetric Hydroarylation of α-Ketoamides
Scheme 60
Scheme 60
Asymmetric Intramolecular Hydroacylation of Ketones via Rh(I) Catalysis
Scheme 61
Scheme 61
Proposed Mechanism of Rh(I)-Catalyzed Aldehyde C–H Bond Addition to Ketones
Scheme 62
Scheme 62
Synthesis of Phthalides via Rh(I)-Catalyzed C–H Activation of Aldehydes
Scheme 63
Scheme 63
Rh(I)-Catalyzed Synthesis of Chiral Benzoxazepinones
Scheme 64
Scheme 64
Rh(I)-Catalyzed Synthesis of Chiral Benzoxazecinones
Scheme 65
Scheme 65
Intermolecular Coupling of Aldehydes and α-ketoamides via Rh(I) Catalysis
Scheme 66
Scheme 66
Co-Catalyzed Enantioselective Intramolecular Hydroacylation of Ketones
Scheme 67
Scheme 67
Pd-Catalyzed Benzylic C–H Bond Addition of 2-Methyl Azaarenes to N-Sulfonyl Aldimines
Scheme 68
Scheme 68
Rh(III)-Catalyzed Arene C–H Bond Additions to Boc and Sulfonyl Imines
Scheme 69
Scheme 69
Mechanism of Rh(III)-Catalyzed Arylation of Imines via C–H Functionalization
Scheme 70
Scheme 70
Rh(III)-Catalyzed C–H Bond Additions to N-Sulfonyl Imines
Scheme 71
Scheme 71
Rh(III)-Catalyzed Synthesis of Branched Amines by Amide Directed C–H Bond Additions to Imines
Scheme 72
Scheme 72
Rh(III)-Catalyzed Alkene C–H Bond Additions to Aryl Aldimines
Scheme 73
Scheme 73
Rh(III)-Catalyzed Pyrrole Synthesis
Scheme 74
Scheme 74
Rh(III)-Catalyzed Indole C–H Bond Addition to N-Sulfonylaldimines
Scheme 75
Scheme 75
Rh(III)-Catalyzed (Hetero)Arene C–H Bond Additions to Cyclic Imines
Scheme 76
Scheme 76
Rh(III)-Catalyzed Asymmetric C–H Bond Additions to N-Perfluorobutanesulfinyl Imines
Scheme 77
Scheme 77
Rh(III)-Catalyzed Synthesis of 3-Aminoisoindolin-1-ones
Scheme 78
Scheme 78
Rh(III)-Catalyzed Synthesis of 3-(Diarylmethylene)isoindolin-1-ones
Scheme 79
Scheme 79
Co-Catalyzed C–H Bond Additions to N-Aromatic Aldimines
Scheme 80
Scheme 80
Co(III)-Catalyzed Directed C–H Bond Additions to N-Sulfonyl Imines
Scheme 81
Scheme 81
Co(III)-Catalyzed Indole C–H Bond Additions to N-Sulfonyl Imines
Scheme 82
Scheme 82
Seminal Report of Rh-Catalyzed Direct C–H Bond Addition to Isocyanates
Scheme 83
Scheme 83
Rh(III)-Catalyzed Aryl and Alkenyl C–H Bond Additions to Isocyanates
Scheme 84
Scheme 84
Rh(III)-Catalyzed Synthesis of Pyrimidinones via Isocyanate Addition
Scheme 85
Scheme 85
C–H Functionalization of Ferrocenes with Isocyanates
Scheme 86
Scheme 86
Rh(III)-Catalyzed C–H Bond Additions of O-Methoxy Oximes with Isocyanates
Scheme 87
Scheme 87
Alkenyl C–H Bond Additions of O-Methoxy Oximes with Isocyanates
Scheme 88
Scheme 88
Rh(III)-Catalyzed Synthesis of Phthalimides
Scheme 89
Scheme 89
Rh(III)-Catalyzed C–H Functionalization/Decarboxylation of Benzoic Acids
Scheme 90
Scheme 90
Rh(III)-Catalyzed C–H Bond Additions of Azobenezenes to Isocyanates
Scheme 91
Scheme 91
Rh(III)-Catalyzed C–H Bond Additions of Indoles and Pyrroles to Isocyanates
Scheme 92
Scheme 92
Reversibility of Pyrimidine Directed Indole C–H Bond Addition to Isocyanates
Scheme 93
Scheme 93
Rh(III)-Catalyzed Aminocarbonylation of Indoles and Pyrroles
Scheme 94
Scheme 94
Aminocarbonylation at the C7 Position of an Indole
Scheme 95
Scheme 95
Ir-Catalyzed Amidation of N-methylimidazole
Scheme 96
Scheme 96
Re-Catalyzed Synthesis of Phthalimidines via C–H Bond Activation
Scheme 97
Scheme 97
Re-Catalyzed Amidation of Heteroaromatic Aldimines
Scheme 98
Scheme 98
Re-Catalyzed C–H Bond Additions of Imidates with Isocyanates
Scheme 99
Scheme 99
Re-Catalyzed C–H Aminocarbonylation of Azobenzenes
Scheme 100
Scheme 100
Ru(II)-Catalyzed Aryl C–H Bond Additions to Isocyanates
Scheme 101
Scheme 101
Ru(II)-Catalyzed Phthalimide Synthesis via C–H Activation
Scheme 102
Scheme 102
Ru(II)-Catalyzed Amidation of Heteroaromatic Amides
Scheme 103
Scheme 103
Ru(II)-Catalyzed Synthesis of Phthalimides from Benzoic Acids and Isocyanates
Scheme 104
Scheme 104
Co(III)-Catalyzed C–H Bond Additions to Isocyanates
Scheme 105
Scheme 105
Co(III)-Catalyzed Additions of Arene C–H Bonds to Isocyanates
Scheme 106
Scheme 106
Co(III)-Catalyzed Additions of Alkene C–H Bonds to Isocyanates
Scheme 107
Scheme 107
Mn-Catalyzed C–H Aminocarbonylation with Isocyanates
Scheme 108
Scheme 108
An Early Example of a Metal-Catalyzed C–H Bond Addition to an Isocyanide
Scheme 109
Scheme 109
Pd-Catalyzed Quinazoline Synthesis via C–H Bond Additions to Isocyanides
Scheme 110
Scheme 110
Pd(II)-Catalyzed C3 Amidation of Indoles via C–H Activation
Scheme 111
Scheme 111
Rh(III)-Catalyzed Annulation of N-Tosylbenzamide with Isocyanide
Scheme 112
Scheme 112
Cu-Catalyzed Additions of N-benzoyl 8-Aminoquinolines to Isocyanides
Scheme 113
Scheme 113
Ni-Catalyzed Additions of N-benzoyl 8-Aminoquinolines to Isocyanides
Scheme 114
Scheme 114
Pd-Catalyzed Coupling of Arenes and Nitriles
Scheme 115
Scheme 115
Pd-Catalyzed Coupling of Various Arenes and Benzonitriles
Scheme 116
Scheme 116
Pd-Catalyzed Acylation of Free N–H Indoles with Nitriles
Scheme 117
Scheme 117
Pd-Catalyzed Acylation of Substituted and Free N–H Indoles with Nitriles
Scheme 118
Scheme 118
Pd-Catalyzed Addition of Thiophenes to Nitriles
Scheme 119
Scheme 119
Mn(I)-Catalyzed C–H Bond Additions to Nitriles
Scheme 120
Scheme 120
General Scheme for Additions to C=C π-Bonds followed by Cyclization upon Polarized π-Bond Directing Group
Scheme 121
Scheme 121
Re(I)-Catalyzed Alkyne Addition/Cyclization Cascade with Aldimines
Scheme 122
Scheme 122
Re(I)-Catalyzed Alkyne Addition/Cyclization Cascade with Free N–H Ketimines
Scheme 123
Scheme 123
Ru(II)-Catalyzed Alkyne Addition/Cyclization with N-Sulfonyl Imines
Scheme 124
Scheme 124
Ru-Catalyzed Alkyne Addition/Cyclization with Free N–H Ketimines
Scheme 125
Scheme 125
Ru(II)-Catalyzed Synthesis of Amino Indenes from N-Sulfonyl Imines and Alkynes
Scheme 126
Scheme 126
Rh(I)-Catalyzed Alkyne Addition/Cyclization with Free N–H Ketimines
Scheme 127
Scheme 127
Asymmetric Rh(I)-Catalyzed Alkyne Addition/Cyclization with Free N–H Ketimines
Scheme 128
Scheme 128
Rh(III)-Catalyzed Alkyne Addition/Cyclization with Azomethine Ylides
Scheme 129
Scheme 129
Rh(III)-Catalyzed Synthesis of Indenones from Aryl Nitrones and Alkynes
Scheme 130
Scheme 130
Rh(III)-Catalyzed Annulation of O-Methyl Oximes and Alkynes
Scheme 131
Scheme 131
Rh(III)-Catalyzed Annulation of Cyclic Ketimines and Alkynes
Scheme 132
Scheme 132
Rh(III)-Catalyzed Three-Component Coupling of Alkynes and Aldehydes
Scheme 133
Scheme 133
Co(III)-Catalyzed Annulation of Cyclic Ketimines and Alkynes
Scheme 134
Scheme 134
Re(I)-Catalyzed Annulation of Aryl Ketones and Enoates
Scheme 135
Scheme 135
Re(I)-Catalyzed Annulation of Aryl Ketimines and Enones/Enoates
Scheme 136
Scheme 136
Mn-Catalyzed Annulation of N-Aryl Ketimines and Enoates
Scheme 137
Scheme 137
Rh(I)-Catalyzed Allene Addition/Cyclization with Free N–H Ketimines
Scheme 138
Scheme 138
Re-Catalyzed Allene Addition/Cyclization with Aryl Ketimines
Scheme 139
Scheme 139
Ir(I)-Catalyzed Annulation of Cyclic Ketimines and Dienes
Scheme 140
Scheme 140
Ir(I)-Catalyzed Annulation of N-Sulfonyl Ketimines and Dienes
Scheme 141
Scheme 141
Rh(III)-Catalyzed Synthesis of Indolines from N-Aryl Nitrones and Alkynes
Scheme 142
Scheme 142
Rh(III)-Catalyzed Synthesis of Indenols
Scheme 143
Scheme 143
Rh(III)-Catalyzed Synthesis of Indenes Using Ketones with α-Hydrogens
Scheme 144
Scheme 144
Rh(III)-Catalyzed Synthesis of Indenes Using Alkynes with Propargylic Hydrogens
Scheme 145
Scheme 145
Rh(III)-Catalyzed Annulation of Aryl Ketones and Alkynes
Scheme 146
Scheme 146
Ru(II)-Catalyzed Annulation of Aryl Ketones and Alkynes
Scheme 147
Scheme 147
Rh(III)-Catalyzed Enone Addition/Cyclization with Aryl Ketones
Scheme 148
Scheme 148
Rh(III)-Catalyzed Allylic Alcohol Addition/Cyclization with Aryl Ketones
Scheme 149
Scheme 149
Co(III)-Catalyzed Annulation of Anilides and Alkynes
Scheme 150
Scheme 150
Co(III)-Catalyzed Synthesis of Quinolines
Scheme 151
Scheme 151
Co(III)-Catalyzed Synthesis of Quinolines
Scheme 152
Scheme 152
Rh(III)-Catalyzed Annulation of Imides and Alkynes
Scheme 153
Scheme 153
Co(III)-Catalyzed Annulation of Aryl Esters and Alkynes
Scheme 154
Scheme 154
Co(III)-Catalyzed Synthesis of Indenones from Aryl Esters and Alkynes
Scheme 155
Scheme 155
Co(III)-Catalyzed Synthesis of Pyrroloindolones
Scheme 156
Scheme 156
Rh(III)-Catalyzed Synthesis of Pyrroloquinolinones
Scheme 157
Scheme 157
Rh(III)-Catalyzed Cascade Addition of Enone Tethered Aldehydes
Scheme 158
Scheme 158
Synthesis of a Cationic Rh(III)-Enolate
Scheme 159
Scheme 159
Rh(III)-Catalyzed Three-Component Addition of Enones and Aldehydes
Scheme 160
Scheme 160
Co(III)-Catalyzed Diastereoselective Three-Component Coupling
Scheme 161
Scheme 161
Mechanistic Experiments for Co(III)-Catalyzed Three-Component Coupling
Scheme 162
Scheme 162
Proposed Mechanism for the Co(III)-Catalyzed Three-Component Coupling
Scheme 163
Scheme 163
Asymmetric Co(III)-Catalyzed Three-Component Additions to N-tert-Butanesulfinyl Imines
Scheme 164
Scheme 164
Ni/Cu-Catalyzed Aerobic C(sp2)–H Carbonylation using DMF as Carbonyl Source
Scheme 165
Scheme 165
Ni/Cu-Catalyzed Aerobic C(sp3)–H Carbonylation using DMF as Carbonyl Source
Scheme 166
Scheme 166
Pd/Ag-Catalyzed Aerobic C(sp2)–H Carbonylation using DMF as Carbon Source
Scheme 167
Scheme 167
Re-Catalyzed Synthesis of 1,3-Diiminoisoindolines by C(sp2)–H Bond Insertion into Carbodiimides
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