Photoinduced Ligand-to-Metal Charge Transfer in Base-Metal Catalysis

Abstract

The absorption of light by photosensitizers has been shown to offer novel reactive pathways through electronic excited state intermediates, complementing ground state mechanisms. Such strategies have been applied in both photocatalysis and photoredox catalysis, driven by generating reactive intermediates from their long-lived excited states. One developing area is photoinduced ligand-to-metal charge transfer (LMCT) catalysis, in which coordination of a ligand to a metal center and subsequent excitation with light results in the formation of a reactive radical and a reduced metal center. This mini review concerns the foundations and recent developments in ligand-to-metal charge transfer in transition metal catalysis focusing on the organic transformations made possible through this mechanism.

Graphical Abstract

1. Introduction

The photochemistry of transition metal complexes has been studied extensively, especially in earth-abundant metals comprising the 3d block.^1–3 Deeply colored representative complexes from this group are often used as examples in chemical education for their vibrant illustration of photophysical transitions.⁴ Despite a rich history of study, the incorporation of such transitions into catalytic manifolds has thus far been limited. Recent advances in photoredox and photocatalysis have ignited renewed interest in utilizing light energy to enable organic transformations.^5–8 Fundamental to these innovations was the development of various photocatalysis scaffolds, centering around both transition metal complexes as well as organic compounds.⁹ Various electronic transitions are implicated in the production of excited state species with synthetically useful lifetimes in solution. Many of the most well-studied metal-centered photoredox catalysts employ photoinduced metal-to-ligand charge transfer (MLCT), in which an absorption of a photon induces an electron transfer from the metal-centered HOMO to the ligand centered LUMO. Another method of excitation of metal centered photocatalysts is photoinduced ligand to metal charge transfer (LMCT) in which the photoexcitation leads to electron transfer from a ligand centered orbital to a metal centered orbital. The requisite metal centered HOMO and ligand centered LUMO render this transition favorable in the case of high-valent metal centers with low energy d orbitals and electron rich ligands.

Previous studies in metal coordination chemistry have furnished numerous examples of complexes exhibiting LMCT to generate highly reactive charge separated species capable of single electron transfer (SET) and energy transfer (EnT) through outer sphere mechanisms.¹⁰ Although examples of such complexes have been centered on base-metals,¹¹ this mini review will focus on LMCT that results in σ-bond homolysis and the extrusion of a reactive radical and a reduced metal species. This process has been applied in organic chemistry to numerous photooxidation reactions in which the metal species is employed in a stoichiometric fashion. Key examples of stoichiometric reactivity will be discussed as a foundation for later catalytic applications. Employing photoinduced LMCT as a key step in a catalytic cycle has come to prominence in recent years through applications in synthetic methodology. Literature reviews regarding synthetic advances based on photoinduced LMCT have been published previously by Julia and Reiser.^12–14 This mini review provides an update, focusing on the earth-abundant metals Fe, Co, Ni, and Cu, for which significant synthetic contributions are described herein.

LMCT catalysis, besides offering alternative pathways to reactive radicals, maintains numerous advantages over previous photocatalytic platforms. LMCT is more common among earth abundant metals such as first row transition metals and lanthanides, promoting its utility in sustainable methods. Although these complexes typically exhibit short excited state lifetimes relative to other widely employed photocatalysts, the coordination of the substrate prior to excitation enables sufficient quantum yield to promote efficient reactivity. Furthermore, since coordination of the substrate is essential to the mechanism of radical formation, functional groups that form coordination complexes with the metal center can be selectively oxidized regardless of their susceptibility to activation by SET or EnT processes. These advantages demonstrate the ability of LMCT catalysis to provide novel synthetic transformations and more sustainable organic synthesis.

2.1. Iron

Iron LMCT chemistry has been utilized for decades for actinometry in the case of potassium ferrioxalate reduction under irradiation.^15–16 Under visible light, ferrioxalate salts undergo LMCT to furnish a reduced Fe-center and carbon dioxide. Inoue provided the first synthetic application of photoinduced Fe-LMCT reactivity through the oxidation of ethylene glycol as well as the chlorination of toluene, although with little comment on the reactive intermediates produced.^17–20 Later work by Sugimori showed that stoichiometric Fe₂(SO₄)₃ enables Minisci reactions under various forms of irradiation.²¹ Both Sato and Barbier explored stoichiometric photooxidations utilizing FeCl₃ towards the generation of α-Cl-ketones from alkenes and lactones from cyclic ethers respectively.^22–25 Further work by Shul’pin demonstrated that catalytic loadings of FeCl₃ could enable chlorination and oxidation of alkanes under light irradiation and excess O₂ in which the photogeneration of chlorine radical via LMCT was proffered as the mechanism.^26–28 This work has been more thoroughly investigated by Tataki^29–30 and later by Fu and Liu.^31–32

Jin has made significant contributions through the development of a catalytic protocol taking inspiration from previously discussed work from Sugimori.³³ With pyridine and excess sodium bromate, his group has shown various oxidative decarboxylation reactions including Minisci reactions and C-H carboxylation, Scheme 5. The use of bipyridyl-amine ligands enabled the redox neutral decarboxylative alkylation and amination of acids with electron deficient olefins and azodicarboxylates.³⁴ Zhu then showed the halooxidation of styrenes with catalytic FeBr₃, enabled by LMCT to form reactive bromine radicals.³⁵

Scheme 5:

Seminal contributions to catalytic methods involving photoinduced LMCT with Fe.

Work from the Rovis group showed that FeCl₃ LMCT could be used to generate chlorine radicals and enable skeletal rearrangements of carbonyl and aryl compounds through β-selective HAT, Scheme 6.³⁶ Adjusting the reaction conditions was shown to change the selectivity in Giese alkylation reactions between rearranged and unrearranged products. The in-situ generated Fe^II-center is oxidized back to Fe^III via single electron transmetallation of the electrophilic radical followed by protodemetallation. Subsequent work from Duan, Jin, and Rovis showed the ability of FeCl₃ to catalyze C-H Giese and amination reactions of various alkanes, with Jin demonstrating effective catalysis using methane as the pronucleophile.^37–39

Scheme 6:

Leveraging HAT with chlorine radical towards Giese reactions of unactivated C(sp³)-H bonds.

Numerous authors have made significant contributions through the generation of alkoxy radicals through LMCT mechanisms through Fe catalysis, Scheme 7. The intermediacy of metal-alkoxides for direct LMCT has been complicated by conflicting reports from various research groups especially surrounding Ce-LMCT catalysis.^40–44 Recent work has showed reaction conditions to be essential to selectively generate O-centered radicals versus Cl radicals.⁴⁵ However, chlorine free conditions have also been reported to enable alkoxy radical reactivity lending credence that both mechanisms could be operative.⁴⁶ Following precedent from Zuo in his work on Ce LMCT, Hu, Li, and Zeng showed alkoxy radicals to be powerful intermediates to form reactive alkyl radicals via β-scission as well as 1,5 HAT chemistry. Hu showed that various alcohols undergo β-scission and subsequent reduction of the resulting radical through catalytic thiol H-atom donation to generate ketone and aldehyde products.⁴⁷ Li and Zeng showed that alkoxy radicals generated from aliphatic alcohols can promote 1,5 HAT to enable regioselective remote amination with azodicarboxylates using FeCl₃ as a catalyst.⁴⁸ Further work from Zeng under chlorine free conditions showed that Fe-alkoxides can likewise utilize β-scission to furnish remotely aminated product with azodicarboxylates.⁴⁶

Scheme 7:

Catalytic generation of alkoxy radicals through Fe-centered photoinduced LMCT.

Moving Fe-LMCT catalysis outside the purview of metal salts, the Nocera group produced a bisiminopyridine Fe catalyst that could better control HAT from chlorine radicals through ligand design, Scheme 8.⁴⁹ The Stache group showed LMCT catalysis with FeCl₃ to enable chemical upcycling of commercial polystyrene using flow chemistry and O₂.⁵⁰ Photogeneration of chlorine radical from FeCl₃ has been shown by Duan and Jin for the alkynylation of C-H bonds with alkynyl sulfones.³⁷ This mechanism has likewise been utilized towards the C(sp³)-H chalcogenation of alkyl amides with disulfides and diselenides by Lauthé.⁵¹ Li and Zeng have also shown an amide synthesis from aldehydes with nitroarenes providing the amine component.⁵² Work from Mao has demonstrated C-H amidation through FeCl₃ LMCT with excess di-tert-butyl peroxide acting as the terminal oxidant.⁵³ Hu has recently disclosed a decarboxylative fluorination driven by Fe-catalyzed LMCT through electrophilic fluorination of the resulting alkyl radical by Selectfluor.⁵⁴ Wang and Gong have shown a wide variety of radical electrophiles capable of coupling with FeCl₃ as an LMCT photocatalyst.⁵⁵ Zeng has recently disclosed a dual catalytic manifold utilizing Fe-carboxylate LMCT to generate reactive alkyl radicals that can be intercepted by a Cu-cocatalyst to enable an overall decarboxylative amination.⁵⁶ Recent work from Reiser has leveraged photoinduced LMCT from FeCl₃ in concert with organic photocatalysis to enable the C(sp²)-H alkylation of aldehydes with electron deficient olefins.⁵⁷ Further recent work from Yoon has demonstrated the employment of excess FeCl₃ towards the decarboxylative cross-coupling of nucleophiles.⁵⁸

Scheme 8:

Further transformations involving Fe-Cl photoinduced LMCT. Decarboxylative functionalizations of aliphatic acids via photoinduced LMCT of Fe-carboxylates.

2.2. Cobalt

Cobalt also maintains rich LMCT chemistry, including excited states capable of various photooxidations, Scheme 9. Early work by Endicott established the competency of various Co^III complexes to undergo photoinduced LMCT with carboxylate ligands towards the formation of the corresponding Co-alkyl species.^2,59–60 A common motif in Co photochemistry is the homolysis of Co-C bonds under irradiation via LMCT. Vitamin B₁₂ and its derivatives (cobalamines and cobaloximes) have catalyzed various organic transformations in both thermal and photochemical methods.^61–62 Giese demonstrated the use of alkylated cobaloxime reagents as effective nucleophiles with olefins through the in-situ generation of corresponding alkyl radicals via photoinduced LMCT.⁶³ The ability of Co^II cobaloximes to abstract weak C-H bonds has been further leveraged by Carreira towards intramolecular Heck reactions of alkyl iodides, Scheme 10.⁶⁴ Co^I cobaloximes are well documented to undergo S_N2 reactions with alkyl halides to generate Co^III alkyl species. Photoinduced LMCT of this intermediate generates the corresponding alkyl radical which cyclizes and recombines with Co^II to form another Co^III-species. Photoinduced LMCT of this intermediate enables HAT of the α-C-H bond to furnish the eliminated product. Deprotonation of the resultant Co^III-H enables turnover of the catalyst. Further work from the Carreira group showed that a similar transformation could be achieved in an intermolecular fashion with trifluoroethyl iodide and various styrenes.⁶⁵ Later work by Morandi showcased a similar strategy, albeit with epoxides and aziridines as the polar electrophilic component in both an intra- and inter-molecular fashion.⁶⁶ The Gryko lab disclosed a reductive Giese reaction between S-acyl thiopyridines and electron deficient olefins catalyzed by Vitamin B₁₂ derivatives under blue LED irradiation, Scheme 12.⁶⁷ The nucleophilic reactivity of Co^I is leveraged to generate a Co-C bond, in this case a Co-acyl, which upon absorption of a photon homolyzes to generate the corresponding radical. Komeyama later built upon this work to use alkyl tosylates as the polar electrophile for a similar reductive Giese reaction.⁶⁸ The Gryko group later disclosed a dual catalytic approach utilizing Co-LMCT to generate reactive alkyl radicals poised for coupling with in-situ generated Ni-aryl species from aryl halides. A variety of ring opened products including bicyclobutanes, epoxides, and oxetanes proved effective polar electrophiles in this manifold.^69–71

Scheme 9:

Representative Co-catalysts noted for photoinduced LMCT. Key mechanisms in Co-photoinduced LMCT catalysis. Early examples of Co-carboxylate and Co-C photoinduced homolysis.

Scheme 10:

Combining Co^I nucleophilicity with photoinduced LMCT to produce reactive alkyl radicals.

Scheme 12:

Forming alkyl radicals via Co^I nucleophilicity and subsequent Co^III photoinduced LMCT towards Giese reactions and Ni catalyzed arylation.

Whereas previous studies necessitated a photoredox catalyst to promote Co^I formation with spatiotemporal control towards the cyclotrimerization of alkynes,⁷² further work from the Rovis group showed the ability of in-situ generated Co^II acetylides to undergo LMCT to enable arene synthesis, Scheme 11.⁷³ Contemporary innovations in the generation of alkyl radicals have obviated a reaction with an electrophile to generate the desired Co^III intermediate poised for photoinduced LMCT. Work from Sorensen showed that radicals generated via intermolecular HAT with decatungstate could be intercepted by Co^II cobaloxime catalysts and enable a net dehydrogenation of alkanes and alcohols albeit with limited yields and substrate scope.⁷⁴ Similarly, the Ritter group utilized photoredox catalysis to facilitate oxidative decarboxylation of alkyl acids to form alkyl radicals which could then undergo dehydrogenation via HAT from a cobaloxime catalyst.^75–76 Recent work from Leonori has shown that engineering of the cobaloxime can lead to catalyst-controlled selectivity in the olefin form from β-Br-ethers using direct halogen atom transfer to enable initial radical formation.⁷⁷

Scheme 11:

Photoinduced LMCT of Co^II-acetylides enables Co^I catalyzed [2+2+2] cyclizations. Cobaloxime enabled dehydrogenations via alkyl radical intermediates.

2.3. Nickel

Nickel centered LMCT complexes have only recently been the subject of significant study due to their presence as proposed reactive intermediates in photoinduced cross-coupling reactions. Seminal work from Nocera and coworkers showed that isolated Ni^III-Cl complexes can undergo LMCT to extrude chlorine radicals under UV irradiation.^78–79 The Doyle lab demonstrated synthetic utility of Ni-Cl bond homolysis via LMCT through C(sp³)-H arylation and acylation of alkanes through chlorine radical mediated HAT.⁸⁰ The key Ni^III-Cl intermediate is proposed to be generated from oxidation of a Ni^II, chloride complex by a photoredox cocatalyst. Further work showed that using acetals and orthoformates as C(sp³)-H pronucleophiles could promote β-scission to furnish alkyl radicals.^81–82 This mechanism permitted alcohols to be used as synthons in valuable C-C cross coupling reactions via a facile preactivation strategy.⁸³ The Molander group has similarly disclosed a method for C(sp³)-H arylation but with the key HAT agent ascribed a nickel bromide adduct.⁸⁴ Further computational investigations of this mechanism by Gagliardi and Cavallo showed that bromine radical should indeed form via Dexter EnT from the iridium photocatalyst.⁸⁵ The Wu group demonstrated that alkynes could be used as coupling partners with C(sp³)-H pronucleophiles with nickel chloride catalysts.⁸⁶ Work from Huo and coworkers has shown that chiral ligands permit asymmetric arylation reactions of amide derivatives in good yield and high enantioselectivity.⁸⁷ Chu and coworkers leveraged LMCT generated chlorine radicals to difunctionalize alkynes.⁸⁸ The proposed mechanism involves chlorine addition across the alkyne followed by 1,5 HAT transfer from the vinyl radical intermediate to generate a more stable alkyl radical which then intercepts the nickel catalyst again to undergo arylation. Renewed interest in the photochemistry of Ni^II complexes resulting from in-situ oxidative addition has been thoroughly investigated by both Doyle and Hadt.^89–90 The ability for Ni-C bonds to homolyze through an LMCT mechanism was later exploited by Rovis and coworkers towards the demethylation of tertiary methylamines via HAT, metalation, and elimination.⁹¹

2.4. Copper

LMCT chemistry of copper complexes was first disclosed by the Kochi lab in 1962.⁹² They discovered that cupric chloride salts in solution undergo photolysis under mercury lamp irradiation to extrude chlorine radicals, demonstrating numerous examples of alkane and alkene chlorinations with stoichiometric loadings of the copper photooxidant. Later work by Mereshchenko and coworkers confirmed a LMCT mechanism and identified the photophysical transitions involved in the photoreaction.⁹³ Work involving organic transformations with copper that proceed through a LMCT step remained sparse until recently. Igniting renewed interests in the synthetic utility of the intermediates capable of LMCT, Reiser and Rehbein disclosed a Cu photocatalyzed oxy-azidation of olefins involving the homolysis of a Cu-N₃ bond.⁹⁴ Air was used as the terminal oxidant to turn over the Cu catalyst as well as provide an oxygen source for the benzylic oxidation. Further work from the Reiser group demonstrated an atom-transfer radical addition (ATRA) reaction of tosyl chloride with olefins.⁹⁵ Key to the mechanism of this reaction is the formation of chlorine radicals and concomitant reduction to Cu^I to enable photoexcitation and subsequent reduction of the sulfonyl chloride electrophile. Utilizing Cu^II-Cl LMCT as a safe and operationally simple way to generate chlorine radicals in solution was shown by Wan and coworkers in 2020 towards the dichlorination of olefins with excess CuCl₂ or with catalytic loadings of CuCl₂ and air to turn over the catalyst.⁹⁶ Rovis and coworkers then leveraged the HAT ability of chlorine radical to enable C(sp³)-H alkylation of alkanes with electron deficient olefins.⁹⁷ This was achieved with catalytic loadings of CuCl₂ due to a proposed protodemetalation step which enables oxidation of Cu^I back to Cu^II to regenerate the photoactive species to provide a redox neutral reaction. Further work on CuCl2 photocatalysis has shown a variety of valuable organic transformations enabled by a key Cu-Cl photoinduced homolysis. The Wan lab provided a chemodivergent protocol for the selective oxidation or demethylation of the dimethyl amides under an oxygen atmosphere.⁹⁸ Further work from Cai and coworkers showed the chloro oxidation of styrene derviatives.⁹⁹ Under similar conditions, the Hwang group showed that the dichloro oxidation of aryl substituted alkynes was also efficient.¹⁰⁰ The Zhang group also enabled the regioselective C(sp²)-H chlorination of coumarins employing excess loadings of Cu under 460 nm irradiation. ¹⁰¹

Extensive synthetic chemistry has been similarly extracted through the coordination of functional groups to Cu^II salts with readily displaced counterions such as ^-OTf, ^-NTf₂, and ^-BF₄. Although employed with an excess of Cu^II salts to act as oxidants, seminal works from Ritter and Yoon have shown the viability of LMCT of coordinating functional groups to be highly valuable for selective organic transformations of aryl and alkyl carboxylic acids for decaboxylative nucleophilic addition.^102–106 The MacMillan group has made similarly powerful contributions through decarboxylative borylation and halogenation that is catalytic in Cu through the addition of excess halogen electrophile and oxidant.^107–108 The Gong group has enabled the coupling of benzylic trifluoroborate salts with N-sulfonyl imines.¹⁰⁹ Key to the mechanism is LMCT of an in-situ alkyl-Cu species which generates the key alkyl radical. Through the use of chiral ligands they are able to achieve high enantioselectivity for the desired product. Guo and coworkers were able to use ambient air with catalytic Cu(OTf)₂ to afford oxidative cleavage of cyclic ketones via initial LMCT of the enolate with the coordinated Cu^II.¹¹⁰ Reiser has shown LMCT between dapCu^II and dmpCu^II photocatalysts with 1,3 dicarbonyl compounds to couple with electron deficient olefins.¹¹¹ Using the same catalytic system albeit with the catalyst formed in-situ, Reiser was also able to furnish the decarboxylative oxidation of alkyl carboxylic acids.¹¹² Verma and Reiser further showed that N-tosyl-cyclopropyl amines undergo LMCT upon coordination to CuCl and irradiation.¹¹³ They utilized the cyclopropyl ring opening in order to effect the synthesis of cyclopentylamines from a variety of alkenes and alkynes. Reiser and coworkers also accomplished an oxyhalogenation of styrene derivatives via LMCT Cu catalysis.¹¹⁴

3. Future Outlook and Conclusion

Despite a rapid rise in popularity in recent years, work in LMCT catalysis with base-metals is far from exhausting the synthetic transformations available. Many of the methods discussed herein rely on Lewis acidic metal salts or well-established ligand environments to generate photoactive complexes. Further work on refining ligands that can promote elementary organometallic mechanisms as well as photoinduced LMCT would be highly valuable to expanding the synthetic repertoire of this strategy. Developing synthetic methods through base-metal photoinduced LMCT promotes novel organic transformations for a more sustainable future.

Scheme 1:

Photoinduced LMCT, an elementary mechanism in base metal catalysis.

Scheme 2:

Photoinduced LMCT, an elementary mechanism in base metal catalysis.

Scheme 3:

Reactive radicals generated via photoinduced LMCT with Fe complexes.

Scheme 4:

Stoichiometric precedent invoking photoinduced LMCT with Fe to form reactive open shell species.

Scheme 13:

Ni^III chlorides undergo photoinduced LMCT to extrude reactive chlorine radicals. Both Ni^III-Cl and Ni^III-Br complexes can generated under photoredox catalysis to enable C(sp³)-H arylation

Scheme 14:

Synthetic elaboration of Ni-photoredox catalysis involving the extrusion of chlorine radicals.

Scheme 15:

Enantioselective C(sp³)-H arylation of amides via Ni-photoredox catalysis. Selective catalytic demethylation of tertiary alkyl amines via Ni-photoredox catalysis.

Scheme 16:

Reactive radicals generated via photoinduced LMCT with Cu complexes.

Scheme 17:

Seminal report of photoinduced LMCT with cupric chloride salts. Photoinduced LMCT enables formation of azide radicals towards azidooxidation of styrene derivatives.

Scheme 18:

Various transformations utilizing photoinduced formation of chlorine radicals via LMCT

Scheme 19:

Decarboxylative functionalizations of organic acids via photoinduced LMCT with copper salts.

Scheme 20:

Photoinduced LMCT with Cu salts to generate reactive C-centered radicals.