Direct Photocatalyzed Hydrogen Atom Transfer (HAT) for Aliphatic C-H Bonds Elaboration

Abstract

Direct photocatalyzed hydrogen atom transfer (d-HAT) can be considered a method of choice for the elaboration of aliphatic C-H bonds. In this manifold, a photocatalyst (PC_HAT) exploits the energy of a photon to trigger the homolytic cleavage of such bonds in organic compounds. Selective C-H bond elaboration may be achieved by a judicious choice of the hydrogen abstractor (key parameters are the electronic character and the molecular structure), as well as reaction additives. Different are the classes of PCs_HAT available, including aromatic ketones, xanthene dyes (Eosin Y), polyoxometalates, uranyl salts, a metal-oxo porphyrin and a tris(amino)cyclopropenium radical dication. The processes (mainly C-C bond formation) are in most cases carried out under mild conditions with the help of visible light. The aim of this review is to offer a comprehensive survey of the synthetic applications of photocatalyzed d-HAT.

Scheme 1. Homolytic Cleavage of a C–H Bond via a Hydrogen Atom Transfer Step

Scheme 2. Factors Affecting C–H Bond Cleavage

Different factors operating in the selective HAT-based C–H functionalization in organic compounds. In violet the reactive site where the hydrogen is preferentially cleaved during the functionalization (for the explanation of the effects, see the text).

Scheme 3. Bond Dissociation Energies (BDEs) in kcal/mol of Representative Compounds

Bond dissociation energies (BDEs) in kcal/mol of the X–H bonds (in red) in representative compounds. Values taken from ref (53) except where otherwise noted. Value taken from ref (54). Value taken from ref (55).

Scheme 4. Common Hydrogen Abstractors Used in Synthetic Planning

Scheme 5. Photocatalyzed Indirect Hydrogen Atom Transfer (i-HAT) vs Direct Hydrogen Atom Transfer (d-HAT)

Figure 1

Main photocatalysts (PCs_HAT) used in photocatalyzed HAT: BP, benzophenone; ABP, aminobenzophenone; DMBP, 4,4′-dimethoxybenzophenone; BPSS, disodium benzophenonedisulfonate; DCBP, 4,4′-dichlorobenzophenone; AP, acetophenone; FL, 9-fluorenone; DBS, dibenzosuberenone; DTX, 3,6-dimethoxy-9H-thioxanthen-9-one; PQ, 9,10-phenanthrenequinone; XA, xanthone; TX, thioxanthone; AQ, anthraquinone; ClAQ, 2-chloroanthraquinone; tBAQ, 2-tert-butylanthraquinone; AQ-2-COOH, anthraquinone-2-carboxylic acid; AQ-2-SO₃Na, anthraquinone-2-sulfonic acid sodium salt; PT, 5,7,12,14-pentacenetetrone; AQ-2,3-diCOOH, anthraquinone-2,3-dicarboxylic acid; PGA, phenylglyoxylic acid; PYD, 1,6-pyrenedione; EY, Eosin Y; DT, decatungstate anion (TBADT, tetrabutylammonium decatungstate; NaDT, sodium decatungstate); Ur, uranyl cation (UrN, uranyl nitrate hexahydrate; UrP, uranyl perchlorate); Sb-Oxo, antimony-oxo tetra-(p-methoxyphenyl)porphyrin.

Scheme 6. Photoaddition of Isopropanol onto Maleic Acid

Scheme 7. Photocatalyzed Functionalization of an α-Enone

Scheme 8. Photocatalyzed Synthesis of 1,5-Dioxaspiro[5.5]undecane-2-ones

Scheme 9. Photocatalyzed Functionalization of Furanones under Flow Conditions

Scheme 10. Synthesis of Homoallyl Alcohols

Scheme 11. Photocatalyzed Incorporation of a Masked Formyl Group

Scheme 12. Dual-Catalytic Asymmetric Formation of Quaternary Carbons

Scheme 13. Cyclic Ethers as H-Donors in the Functionalization of Butendioate Esters

Scheme 14. Different PCs_HAT for the Photocatalyzed Cleavage of the C–H Bond in THF

Scheme 15. Photocatalyzed Addition of THF onto Cyclohexa-2,5-dien-1-ones

Scheme 16. TBADT-Mediated Derivatization of Cyclic Carbonates

Scheme 17. Selective C–H Cleavage in Ketones and Esters

Scheme 18. Allylation of Tetrahydrothiophene

Scheme 19. Amides, Carbamates, and Amines as H-Donors

Scheme 20. Photocatalyzed C(sp³)–H Alkylation of Amines

Scheme 21. Metallaphotoredox Strategy for the Trifluoromethylation of Amines

Scheme 22. Regioselective Photocatalyzed C–H Cleavage in (a) Aliphatic Nitriles and (b) Alkylpyridines

Scheme 23. Functionalization of (a) Benzylic and (b,c) Allylic Hydrogens

Scheme 24. Photocatalyzed C–H Cleavage in (Cyclo)alkanes

Scheme 25. Photocatalyzed Derivatization of Methane under Flow Conditions

Scheme 26. Photocatalyzed Three-Component Difunctionalization of Alkenes

Scheme 27. Photocatalyzed Derivatization of Electron-Rich Olefins

Scheme 28. Photocatalyzed Addition of Hydrocarbons onto Imine Derivatives

Scheme 29. Multicomponent Synthesis of Secondary Amines

Scheme 30. Photocatalyzed Functionalization of C=O Bonds

Scheme 31. Photocatalyzed Addition of Cycloalkanes onto Alkynes

Scheme 32. Photocatalyzed Alkenylation of Amides

Scheme 33. Dual-Catalyzed Dehydrogenative (E)-Alkenylation of Cycloalkanes

Scheme 34. Photocatalyzed Arylation of Five-Membered Heterocycles

Scheme 35. Arylation of Strong C–H Bonds via a TBADT/Nickel Dual-Catalyzed Strategy

Scheme 36. Photocatalyzed Cross-Dehydrogenative Coupling between Amides and Heteroarenes

Scheme 37. Electrophotocatalytic Arylation of Ethers Mediated by the Trisaminocyclopropenium (TAC⁺) Ion

Scheme 38. Three-Component Photocatalyzed Synthesis of Unsymmetrical Ketones

Scheme 39. Photocatalyzed Alkynylation of Ethers by Bromoalkynes

Scheme 40. BP-Photocatalyzed Cyanation of Nitrogen-Containing Heterocycles

Scheme 41. Photocatalyzed Acetylation of Crotonic Acid

Scheme 42. Cyclohexenone Acylation by Addition of Aliphatic (Upper Part) and Aromatic (Lower Part) Aldehydes

Scheme 43. Preparation of Homoallyl Ketones from Cyclopentanones via a Two-Step Photochemical Norrish Type-I Cleavage/Photocatalyzed Hydroacylation Sequence

Scheme 44. Hydroacylation of Benzylidene Malononitrile Triggered by Different PCs_HAT

Scheme 45. Photocatalyzed Preparation of Isothiazolidin-3-one 1,1-Dioxides

Scheme 46. Photocatalyzed Hydroacylation of Vinyl (Hetero)aromatics

Scheme 47. Asymmetric Acyl-Carbamoylation of Alkenes

Scheme 48. Synthesis of 1,3-Dicarbonyl Derivatives via a Dual-Catalytic Strategy

Scheme 49. TBADT-Photocatalyzed Carbamoylation of Electron-Poor Olefins

Scheme 50. Photocatalyzed Acylation of 1,4-Naphthoquinone

Scheme 51. Photocatalyzed Acylation of Ynoates on the Route to Coumarin Scaffolds

Scheme 52. Photocatalyzed Preparation of Pyridyl Ketones

Scheme 53. Photocatalyzed Preparation of Aromatic Ketones and Benzamides

Scheme 54. Dual-Catalytic Cross-Dehydrogenative Coupling between Aldehydes and Aryl Alkenes

Scheme 55. TBADT-Photocatalyzed Alkynylation of Aldehydes

Scheme 56. Functionalization of Fullerene-C60 via Addition of Photogenerated Acyl Radicals

Scheme 57. TBADT-Photocatalyzed Synthesis of Hydrazides

Scheme 58. TBADT-Photocatalyzed Formation of a C–N Bond in Flow

Scheme 59. One-Pot Synthesis of Hydroxamic Acids from Aldehydes

Scheme 60. Azidation of the Methine Site of Leucine

Scheme 61. Electrophotocatalytic Azidation via a DMBP/Mn Dual-Catalytic System

Scheme 62. C(sp³)–H Heteroarylation via Radical-Polar Crossover

Scheme 63. Photocatalyzed Benzylic Hydroperoxidation under Visible Light Irradiation

Scheme 64. Molecular Oxygen as the Oxidant in the Selective CH₂ to C=O Conversion

Scheme 65. Gram-Scale Remote Oxidation of Pyrrolidine

Scheme 66. Heterogenized NaDT-Photocatalyzed Oxidation of Benzylic Alcohols

Scheme 67. One-Pot Asymmetric Aldol Reaction Starting from Benzyl Alcohols under Aerobic Conditions

Scheme 68. EY-Photocatalyzed Synthesis of Alkyl Quinazolinones via Oxidation of Primary Alcohols

Scheme 69. Anthraquinone-Photocatalyzed Benzylic Oxidation of Methylarenes

Scheme 70. Photocatalyzed Thioesterification of Aldehydes

Scheme 71. Difluoromethylthiolation of Aldehydes

Scheme 72. Trifluoromethylthiolation of Aldehydes

Scheme 73. Three-Component Asymmetric Sulfonylation via HAT

Scheme 74. Diarylketone-Photocatalyzed Selective Benzylic Mono- and Difluorinations

Scheme 75. One-Pot Arylation of Unactivated Benzylic C–H Bonds

Scheme 76. Photocatalyzed Benzylic Fluorination under Flow Conditions

Scheme 77. TBADT-Photocatalyzed Benzylic Fluorination in Flow

Scheme 78. Photocatalyzed Preparation of Fluorocycloalkanes

Scheme 79. Photocatalytic Fluorination of Unactivated C–H Bonds

Scheme 80. TBADT-Photocatalyzed Fluorination of Leucine in Flow

Scheme 81. Visible Light Fluorination of Cyclooctane

Scheme 82. Synthesis of Acyl Fluorides from Aldehydes

Scheme 83. Chlorination of Benzyl MIDA Boronates

Scheme 84. Chlorination of (+)-Sclareolide via a Schlenk-in-Flow Approach

Scheme 85. Photocatalyzed Hydrogen Isotope Exchange (HIE)

Scheme 86. Enantioselective Formation of a P–C Bond

Scheme 87. Photocatalyzed Synthesis of Chlorosilanes

Scheme 88. TBADT-Photocatalyzed Hydrosilylation of Electron-Poor Olefins

Scheme 89. BP-Photocatalyzed S–C Bond Formation

Scheme 90. TBADT/Cobaloxime Dual-Catalytic Approaches for the (a) Dehydrogenation of Alkanes and (b) Dehydroformylation of Aldehydes

Scheme 91. Aerobic Photooxidative Cleavage of (a) 1,3-Diketones and (b) 1,3-Dioxolanes