Chiral Photocatalyst Structures in Asymmetric Photochemical Synthesis

Abstract

Asymmetric catalysis is a major theme of research in contemporary synthetic organic chemistry. The discovery of general strategies for highly enantioselective photochemical reactions, however, has been a relatively recent development, and the variety of photoreactions that can be conducted in a stereocontrolled manner is consequently somewhat limited. Asymmetric photocatalysis is complicated by the short lifetimes and high reactivities characteristic of photogenerated reactive intermediates; the design of catalyst architectures that can provide effective enantiodifferentiating environments for these intermediates while minimizing the participation of uncontrolled racemic background processes has proven to be a key challenge for progress in this field. This review provides a summary of the chiral catalyst structures that have been studied for solution-phase asymmetric photochemistry, including chiral organic sensitizers, inorganic chromophores, and soluble macromolecules. While some of these photocatalysts are derived from privileged catalyst structures that are effective for both ground-state and photochemical transformations, others are structural designs unique to photocatalysis and offer insight into the logic required for highly effective stereocontrolled photocatalysis.

Figure 1.

Selected Examples of Chiral Benzenecarboxylate Sensitizers

Figure 2.

Chiral Thioxanthone-Derived Sensitizers

Figure 3.

Photocatalysts with Chiral Counteranions

Figure 4.

Chiral Bis(acetonitrile) Rh(III) Complexes

Figure 5.

Selected Aryl-Sensitizer Derived βCDs

Figure 6.

Representative Examples of Primary Face Modifications of γCD. Note that under reaction conditions the amine groups are protonated making the γCDs cationic.

Figure 7.

Representative examples of rigid γCD primary face and secondary face or core γCD modifications

Figure 8.

Photosensitizer-derived γCDs

Scheme 1.

General Mechanisms of Enantiocontrol by Chiral Chromophores in Asymmetric Photocatalysis

Scheme 2.

Primary Versus Secondary Photoreactions

Scheme 3.

Exciplex Formation and Deactivation Pathways

Scheme 4.

Cyclopropane Isomerization Catalyzed by a Naphthylamide Sensitizer

Scheme 5.

Sulfoxide Deracemization Catalyzed by a Naphthylamide Sensitizer

Scheme 6.

Allene Deracemization Catalyzed by a Steroid Sensitizer

Scheme 7.

Mechanism of Cyclooctene Isomerization Catalyzed by Benzenecarboxylate Sensitizers

Scheme 8.

Effect of Temperature on Photosensitized Cyclooctene Isomerization

Scheme 9.

Effect of Solvent on Photosensitized Cyclooctene Isomerization

Scheme 10.

Cyclooctadiene Isomerization Catalyzed by a Cyclophane Sensitizer

Scheme 11.

Cycloheptene Isomerization and Cycloaddition Catalyzed by Benzenecarboxylate Sensitizers

Scheme 12.

Cyclohexene Isomerization and Cycloaddition Catalyzed by Benzenecarboxylate Sensitizers

Scheme 13.

Polar Photoaddition of Alcohols to Alkenes Catalyzed by Naphthalenecarboxylate Sensitizers

Scheme 14.

Diels–Alder Cycloaddition Catalyzed by a Cyanoarene Sensitizer

Scheme 15.

Cyclopropane Isomerization Catalyzed by a Cyanoarene Sensitizer

Scheme 16.

Excited-State Protonation Catalyzed by a VANOL-derived Sensitizer

Scheme 17.

Polar Photoaddition Catalyzed by an Acridinium Sensitizer

Scheme 18.

Intramolecular [2+2] Cycloaddition Catalyzed by an Atropisomeric Thiourea Sensitizer

Scheme 19.

Cyclopropane Isomerization Catalyzed by an Aryl Ketone Sensitizer

Scheme 20.

Oxa-di-π-methane Rearrangement Catalyzed by an Aryl Ketone Sensitizer

Scheme 21.

Intramolecular [2+2] Cycloaddition Catalyzed by a Hydrogen-Bonding Ketone Sensitizer

Scheme 22.

Intramolecular [2+2] Cycloaddition via a Hydrogen-Bonding Amide Template

Scheme 23.

Intramolecular Cyclization Catalyzed by a Hydrogen-Bonding Benzophenone Sensitizer

Scheme 24.

Intramolecular [2+2] Cycloaddition Catalyzed by a Xanthone Sensitizer

Scheme 25.

Intermolecular [2+2] Cycloaddition Catalyzed by a Xanthone Sensitizer

Scheme 26.

Intermolecular [2+2] Cycloaddition Catalyzed by a Thioxanthone Sensitizer

Scheme 27.

Aza-Paternò–Büchi Reaction Catalyzed by a Thioxanthone Sensitizer

Scheme 28.

Allene Deracemization Catalyzed by a Thioxanthone Sensitizer

Scheme 29.

Primary Allene Amide Deracemization Catalyzed by a Thioxanthone Sensitizer

Scheme 30.

Sulfoxide Deracemization Catalyzed by a Xanthone Sensitizer

Scheme 31.

Di-π-Methane Rearrangement–Cyclopropane Deracemization Cascade Catalyzed by a Thioxanthone Sensitizer

Scheme 32.

Cyclopropane Deracemization Catalyzed by a Thioxanthone Sensitizer

Scheme 33.

Intermolecular [2+2] Cycloaddition Catalyzed by a BINOL-Derived Thioxanthone Sensitizer

Scheme 34.

Intermolecular [2+2] Cycloaddition of Iminium Ions Catalyzed by a BINOL-Derived Thioxanthone Sensitizer

Scheme 35.

1,2-Diamine Synthesis Catalyzed by a BINOL-Derived Thioxanthone Sensitizer

Scheme 36.

Electron Donor–Acceptor Complex Formation and Excitation

Scheme 37.

Aldehyde α-Alkylation via EDA Complex Excitation

Scheme 38.

Photoinitiated Enamine Catalysis Mechanisms

Scheme 39.

Ketone α-Alkylation via EDA Complex Excitation

Scheme 40.

Aldehyde α-Alkylation via Direct Enamine Excitation

Scheme 41.

Aldehyde α-Alkylation Promoted by a Bifunctional Photoaminocatalyst

Scheme 42.

Enal β-Alkylation via Direct Iminium Ion Excitation

Scheme 43.

Enal β-Alkylation Mechanism

Scheme 44.

Cyclopentanol Synthesis via Iminium Ion Catalysis

Scheme 45.

Cascade Reaction via Iminium Ion Catalysis

Scheme 46.

C–H Functionalization of Toluene Derivatives via Iminium Ion Catalysis

Scheme 47.

EDA Complex Formation with Iminium Electron Acceptors

Scheme 48.

Intermolecular [2+2] Cycloaddition via a Chiral Iminium Chromophore

Scheme 49.

Hydroetherification via Chiral Ion-Pairing Catalysis

Scheme 50.

[3+2] Cycloaddition via Chiral Ion-Pairing Catalysis

Scheme 51.

Diels–Alder Cycloaddition Catalyzed by an Oxopyrylium Sensitizer

Scheme 52.

Dicarbofunctionalization of Enamides via Ion-Pairing Catalysis

Scheme 53.

Toluene Functionalization via Excitation of Benzopyrylium Intermediates

Scheme 54.

Perfluoroalkylation of Enolates via Ion-Pairing Catalysis

Scheme 55.

Aerobic Oxidation of β-Ketoesters via Ion-Pairing Catalysis

Scheme 56.

Bathochromic Shift of α,β-Unsaturated Carbonyls upon Lewis Acid Coordination

Scheme 57.

Enantioselective [2+2] Photocycloadditions of Coumarins with a Chiral Oxazaborolidine Catalyst

Scheme 58.

Enantioselective [2+2] Photocycloadditions of 5,6-Dihydro-4-pyridones

Scheme 59.

Application of Chromophore Activation to the [2+2] cycloaddition of 3-Alkenyloxy-2-cycloalkenones

Scheme 60.

Intermolecular Enantioselective [2+2] Cycloaddition Between Cyclohexenones and Terminal Alkenes

Scheme 61.

Enantioselective ortho-Photocycloaddition with Low Catalyst Loadings of Chiral Oxazaborolidine Lewis Acids

Scheme 62.

Enantioselective Oxa-di-π-methane Rearrangement via a Singlet Excited State

Scheme 63.

ON/OFF Photooxygenation Catalysis

Scheme 64.

Helical Chirality of Octahedral Transition-Metal Complexes

Scheme 65.

Enantioselective PET to Co(acac)₃ from Δ-Ru(bpy)₃²⁺

Scheme 66.

Stereoselective PET to Co(acac)₃ with Chiral Ru(bpy)₃²⁺ Photocatalysts

Scheme 67.

Effect of Helical Chirality on Enantioselective PET and Photoderacemization of Co(acac)₃

Scheme 68.

Stereoselective PET to Chiral Methyl Viologens

Scheme 69.

Atroposelective Synthesis of Binapthols

Scheme 70.

Stereoselective Energy Transfer

Scheme 71.

Enantioselective [2+2] Photocycloadditions Using Chiral N,N’-dioxide-Tb(III) Complexes

Scheme 72.

Chiral-at-Metal Ir(III) Photocatalysts Used in Asymmetric Secondary Photoreactions

Scheme 73.

Proposed Catalytic Cycle of Asymmetric Radical Additions with Chiral Bis(acetonitrile) Ir(III) Complexes

Scheme 74.

Enantioselective Net-oxidative Mannich Reaction of 2-Acylimidazoles

Scheme 75.

Enantioselective Radical–Radical Couplings of Trifluoromethyl Ketyl Radicals and α-Aminoradicals

Scheme 76.

Stereoselective PET and Energy Transfer Reactions using a Chiral Hydrogen-Bonding Ligand

Scheme 77.

Enantioselective Alkylation of Aldehydes using Supramolecular Bifunctional Iridium Photoaminocatalyst

Scheme 78.

Enantioselective Intramolecular [2+2] Photocycloaddition with a Chiral Hydrogen-Bonding Iridium Photosensitizer

Scheme 79.

Enantioselective Intermolecular [2+2] Photocycloaddition via an Energy Transfer Rebound Mechanism

Scheme 80.

Asymmetric Photocatalysis Using Iridium-Chiral Borate Ion Pairs

Scheme 81.

Asymmetric C–C Cross-Couplings Enabled by (η³-allyl)Iridium(III) Photocatalyst

Scheme 82.

Enantioselective α-Amination using Chiral-at-Metal Rhodium Photocatalysts

Scheme 83.

Asymmetric Radical Additions Catalyzed by Chiral Rhodium Catalysts

Scheme 84.

Lewis Acid Effects and Mode of Enantioinduction

Scheme 85.

Enantioselective Radical–Radical Coupling Reaction of 2-Acyl-Imidazoles/Pyrazoles and α-Ketoesters

Scheme 86.

Enantioconvergent Coupling of Racemic α-Chloroketones and N-Arylglycines

Scheme 87.

Photocatalytic α-Deracemization of 2-Pyridylketones

Scheme 88.

Enantioselective [3+2] Cycloaddition of Cyclopropyl Ketones with Alkenes and Alkynes

Scheme 89.

Enantioselective Excited-State [2+2] Cycloaddition with Chiral Rhodium Complexes via Chromophore Activation

Scheme 90.

Regio- and Enantioselective Formation of Head-to-Tail Cyclobutanes

Scheme 91:

Enantioselective [2+2] Photocycloaddition of α,β-Unsaturated Sulfones

Scheme 92:

Enantioselective [3+2] Photocycloaddition Between N-Cinnamoylpyrazoles and Vinylazides

Scheme 93.

Enantioselective Hetero-Diels–Alder Reaction via Chromophore Activation

Scheme 94.

Stereoselective Oxidation of β-Ketoesters by a Thioxanthone-Tethered Nickel Lewis Acid

Scheme 95.

Asymmetric Radical Addition Enabled by Bifunctional Nickel Catalyst

Scheme 96.

Enantioselective PET Using Chiral Cu(I) Complexes

Scheme 97.

Asymmetric PET to Cobalt Complexes Using Chiral Cu(I) Complexes

Scheme 98.

Application of Chromophore Activation to an Enantioselective 6π-Photoelectrocyclization

Scheme 99.

Enantioconvergent Ullman C–N Coupling with a Chiral Phosphine–Cu(I) Catalyst

Scheme 100.

Enantioselective Three-Component Coupling Using a Chiral Copper Photocatalyst

Scheme 101.

Enantioselective Dual Carbofunctionalization of Styrenes

Scheme 102.

Asymmetric Decarboxylative Alkynylation with Terminal Alkynes

Scheme 103.

Visible Light Induced Enantioselective C(sp³)-alkylation of Glycine Ester Derivatives

Scheme 104.

Stereoselective Radical Addition Using a Dual-Purpose Copper Photocatalyst

Scheme 105.

Stereoselective Radical Addition into Imines by a Bifunctional Copper Catalyst.

Scheme 106.

Asymmetric Aerobic Cross-Dehydrogenative Coupling

Scheme 107.

Photoinduced Copper-Catalyzed Asymmetric C–O Cross-Coupling

Scheme 108.

General Mechanism for Asymmetric Photocatalysis by Macromolecular Hosts

Scheme 109.

Structure and Nomenclature of Native CDs

Scheme 110.

[4+4] Photodimerization of Substituted Anthracenes

Scheme 111.

Inclusion Complexes of Substituted Anthracenes and βCD or γCD

Scheme 112.

Anthracene Derivatives

Scheme 113.

γCD Mediated Photodimerization of Anthracene Carboxylate

Scheme 114.

Wavelength Dependance of γCD-Mediated Anthracene Dimerization

Scheme 115.

Native γCD-Mediated 2,6-Anthracenecarboxylate Dimerization

Scheme 116.

βCD-Mediated Slipped Dimer Formation

Scheme 117.

Sequential Asymmetric Dimerization of Naphthoate

Scheme 118.

Other Native CD Catalyzed Photoreactions

Scheme 119.

Hydroperoxidation of Linoleic Acid Mediated by a βCD-Derived Porphyrin Photosensitizer

Scheme 120.

Selection of Asymmetric βCD Mediated Cyclooctene Isomerizations

Scheme 121.

Anti-Markovnikov Hydrofunctionalization of 1,1-Diphenylpropene

Scheme 122.

Norish–Yang Photocyclization of Adamantyl Acetophenone

Scheme 123.

Non-Sensitizing Primary and Secondary Face βCD Structural Modifications

Scheme 124.

Selected Examples of Anthracene [4+4] Photodimerization Mediated by Cation Functionalized γCDs.

Scheme 125.

Anthracene Photodimerization Catalyzed by a γCD–Cu²⁺ Complex

Scheme 126.

2,6-Anthracenedicarboxylate Photodimerization with Primary Face Modified γCDs.

Scheme 127.

Selected Examples Anthracene [4+4] Photodimerization Mediated by Rigid-Capped and Secondary-Face Modified γCDs

Scheme 128.. Anthracene Photodimerization Catalyzed by Tethered βCDs.

Reproduced from Ref. . Copyright 2019 American Chemical Society.

Scheme 129.. Anthracene Photodimerization Catalyzed by Tethered βCDs.

Adapted with permission from Ref. . Copyright 2020 The Royal Society of Chemistry.

Scheme 130.

Photoisomerization of Cyclooctadiene Catalyzed by a Naphthalene Curdlan

Scheme 131.

CNN Photosensitized Asymmetric Isomerization of Cyclooctene

Scheme 132.. [2+2] Photodimerization Catalyzed by a Ru-Pd MOC.

Adapted from Ref. . Copyright 2008 American Chemical Society.

Scheme 133.. MOC Photoredox-Catalyzed Dimerization of Bromonaphthol.

Adapted with permission from Ref. . Copyright 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Scheme 134.

Enantioselective Dimerization of Bromoacenaphthylene.

Scheme 135.

Asymmetric Cyclooctene Isomerization Catalyzed by Nucleosides or Single and Double Stranded DNA

Scheme 136.

Photosensitized [2+2] Cycloaddition Catalyzed by an Artificially Modified DNA Three-Way Junction

Scheme 137.

Anthracene Photodimerization in the Presence of BSA

Scheme 138.

HSA Directed Asymmetric Photoisomerization of DTE Derivatives

Scheme 139.

Asymmetric Photocatalytic Dehalogenation by Unnatural Photoactive Enzymes

Scheme 140.

Dehalogentation–Cyclization Photocatalyzed by ‘Ene’-Reductases

Scheme 141.

Intermolecular Dehalogenation–Radical Addition Promoted by a Quaternary Charge-Transfer Complex

Scheme 142.

Photoenzymatic Redox-Neutral Cyclization of α-Halo-β-Amidoesters

Scheme 143.

Hydrogenation and Defluorination by Photoexcitation of FMN

Scheme 144.

Enantioselective Reduction of Cyclohexenone by a Rose Bengal Associated Enzyme

Scheme 145.

Enantioselective Hydroxylation by a Ru-Polypyridyl Derived P450 Enzyme