Abstract
Thermally activated delayed fluorescent (TADF) molecules undergo efficient intersystem crossing (ISC) and reverse intersystem crossing (RISC) processes, making them as third-generation emitters in organic light-emitting diodes (OLEDs), photodynamic therapy (PDT) and time-resolved luminescence imaging. Apart from these applications, recently, TADF molecules have been used extensively as photocatalysts in light-mediated synthesis. In general, highly expensive complexes of Rh, Ir, Ru and organic dyes (Eosin Y, Rose Bengal, 9-mesityl-10-methylacridinium perchlorate [Acr-Mes]+ClO4−) are commonly used in the photocatalysis process. Organic-TADF based molecules help to avoid these costly metal catalysts and frequently used organic dyes, making the reaction economical and greener. This chapter will briefly summarize the photocatalytic properties of organic-TADF compounds in organic synthesis.
Keywords
- thermally activated delayed fluorescence (TADF)
- photocatalysis
- 4CzIPN
- organo photoredox catalysis
- radical chemistry
- single electron transfer (SET)
- halogen atom transfer (XAT)
- cross dehydrogenative coupling (CDC)
- Minisci reaction
- cyclopropanation
- cyclization reaction
- ring opening reaction
- deuteration reaction
- hydroformylation reaction
1. Introduction
The term ‘photocatalysis’ is derived from the concepts of photochemistry. Previously, ultraviolet (UV) irradiation was commonly applied in classical photochemical reactions. The use of high energy ultraviolet light has selectivity issues and requires a designer reaction setup. However, the recent photochemical reaction uses low energy and selective wavelength of visible light from Light-Emitting Diodes (LED). Due to low energy usage, modern photochemical reactions are highly selective. In general, visible light has low absorptivity, so it can not drive the organic reaction competently. A secondary substrate, usually a photocatalyst is introduced to enhance the light absorptivity. This photocatalyst absorbs visible light and provides stable and long photoexcited states, which induces the substrates or reagents to participate in the chemical reaction. The photoexcited catalyst either donates or removes a single electron from the reacting partners, which triggers further reaction
Polish physicist Aleksander Jabłoński studied the molecular absorbance and emission of light. He developed the famous Jablonski diagram to explain the spectra and kinetics of fluorescence and phosphorescence. This diagram illustrates the excited states energy level of a molecule and their radiative and non-radiative transitions. A typical Jablonski diagram is shown in Figure 1a. Under appropriate light irradiation, the molecules excite to an excited singlet state (Sn), and then the excitons migrate to the lowest excited singlet state (S1)
Followed by Jabłoński, French physicists Jean Baptist Perrin, the winner of 1926 Nobel Prize in Physics, and his son Francis Perrin rationalized a third type of radiative transition known as delayed fluorescence. This occurs when a molecule in the lowest triplet excited state (T1) transitions to the lowest excited singlet state (S1)
The TADF proceeds
Eosin Y is the first organic compound identified to show Thermally Activated Delayed Fluorescence (TADF) property. This inexpensive organic dye is widely used in photocatalysis (PC) due to its moderate redox potentials (in 1:1 ratio of acetonitrile and water ratio the ground oxidation and reduction potentials of Eosin Y are
In 2012, Adachi group prepared a conformationally twisted electron-donor and acceptor TADF material, 2,4,5,6-tetra(carbazol-9-yl)benzene-1,3-dicarbonitrile (4CzIPN) by single-step reaction between 2,4,5,6-tetrafluoroisophthalonitrile and carbazole
In 2016, Ollivier and Fensterbank group used 4CzIPN as a photocatalyst for an organic transformation [3]. Under blue LEDs irradiation, 4CzIPN undergo photoexcitation, the photoexcited 4CzIPN* generated benzyl radical from benzyl
Followed by Ollivier and Fensterbank radical-mediated synthesis [3], various organic transformations were documented using 4CzIPN as a photocatalyst under the irradiation of visible light or blue LEDs. Besides this, many reactions were reported using 4CzIPN in combination with a transition metal. This chapter excludes transition metal assisted (synergic catalysis) synthesis and mainly focuses on 4CzIPN as an independent photocatalyst without any transition metals.
2. Cyclopropanation reactions
In 2018, a group of Gutierrez and Molander demonstrated a redox-neutral photocatalytic cyclopropanation of olefins with triethylammonium
From mechanistic aspects, the photocatalytically generated halomethyl radical is trapped by the alkene and generate a stable tertiary radical. This radical accepts a single electron from the 4CzIPN˙−, to form an anion and regenerate the catalyst. It underwent an anionic
In the same year, the Molander group further extended their aforementioned cyclopropanation methodology [4] to the homoallylic tosylates system (Figure 6) [5]. In their previous report, the leaving group (iodo) is attached to the radical precursor motif itself [4]. In their follow-up work, the Molander group incorporated the leaving group into the alkene core. They treated three different alkyl radical precursors such as
In successive work, the reaction between
Around the same time, Noble and Aggarwal’s group jointly documented 4CzIPN-catalyzed cyclopropane reaction by treating aliphatic carboxylic acids with electron-deficient internal and external chloro alkenes (Figure 8) [7]. The reaction proceeded
Homoallyl chlorides provided good yields of 1,1-disubstituted cyclopropanes. On the other hand, allyl chlorides lead to vicinal substituted cyclopropanes with moderate yields. The slightly lowered yield obtained is due to the formation of an allylic ester by-product
From a mechanistic perspective, the excited photocatalyst 4CzIPN* underwent SET with the carboxylate to form a carbon center radical by reduction of the excited photocatalyst to radical anion (4CzIPN˙−). The carbon center radical underwent Giese-type addition into the homoallyl chloride to generate the stabilized alkyl radical. This stabilized alkyl radical accept a single electron from 4CzIPN˙− leading to a stabilized carbanion. Polar 3-exotet cyclization of stabilized carbanion afforded cyclopropane product (Figure 9) [7].
The above cyclopropanation reactions have considerable advantages over other reagents such as diazomethane (respiratory irritant) and highly pyrophoric diethylzinc (C2H5)2Zn, used in the Simmons-Smith reaction.
Subsequently, various research groups generated 4CzIPN photo catalyzed decarboxylative carbon-centered radicals from a carboxylic acid and added it into alkenes (
For example, Wang group generated a carbon-centered radical (
The authors studied the competitive reaction between aryl and alkyl olefin in both inter and intra-molecular manners. The reaction showed higher chemoselective at the aryl olefin site. Alkyl olefin site remains intact in both continuous flow and batch method (Figure 11) [8].
Schubert group employed 4CzIPN-mediated decarboxylative radical conjugate addition to C〓C bonds of dehydroalanine (Dha) and its derivatives peptides (Figure 12) [9]. This protocol opens up new avenues to a diastereoselective synthesis of unnatural amino acids and the late-stage derivatization of a tripeptide (Figure 12) [9].
3. Three-component C▬C and C▬N bond formation reaction
So far, we discussed 4CzIPN catalyzed two compound reactions [3, 4, 5, 6, 7, 8, 9]. For the first time in the year 2019, the Studer group developed a 4CzIPN photocatalyzed three-component reaction for 1,2-amidoalkynylation of unactivated alkenes (Figure 13) [10]. Photoexcited TADF (4CzIPN*) generated an amidyl radical (
This three-component reaction showed broad substrate scope for mono, di and tri substituted terminal alkene and substituted benziodoxolones. In addition to these, vinyl ethers, esters and enamides are also compatible with these reaction conditions (Figure 13). The reaction provided a high level of chemo-selective product. The polar effect plays a major role in chemo-selective product formation. An amidyl radical is attached at the less substituted site of alkene and the alkyne radical is attached at the more substituted site of alkene (Figure 13) [10]. For a particular note, this is the first transition metal-free alkene aminoalkynylation. Before this report, alkene aminoalkynylation reactions are restricted to disubstituted alkenes.
The author concluded that the reaction proceeded through a radical pathway by performing two different radical clock experiments using 1,6-diene and vinylcyclopropane (Figure 15) [10].
4. Photoinduced C▬Si bond formation via decarboxylation of silacarboxylic acids
All the aforementioned examples deal with photoinduced C▬C bond formation
5. TADF-photocatalyzed Minisci reactions
The addition of nucleophilic radical to electron-deficient nitrogen-containing heteroarenes bases followed by a formal hydrogen atom loss is known as
Sherwood and co-workers employed a 4CzIPN-photocatalyzed Minisci reaction between a variety of electron-deficient
From mechanistic aspects, when blue LEDs light is exposed to organophotocatalyst 4CzIPN and
In the afore-mentioned Minisci protocols (Figures 17 and 18), acid additives were used in the reaction medium [12, 13]. In 2019, Graham and Noonan demonstrated an acid additive-free, large-scale (67 g) photoredox catalyzed Minisci reaction towards the synthesis of 2,4-dichloro-6-[1-(methylsulfanyl)cyclopropyl]pyrimidine (Figure 20) [16]. This protocol reduces four reaction steps in the classical production of cancer’s phase II clinical trials molecule ceralasertib [16]. Compared to 4CzIPN (50% yield), 3-DPA2FBN (70%) is a more effective photocatalyst for the above-mentioned transformation.
In general most of the Minisci reactions proceeds through the decarboxylation (▬CO2) pathway [12, 13, 15, 16]. Large amounts of oxidants are generally required when aldehydes are used as the radical precursors. In 2019, Huang and Zhao groups disclosed a visible-light-induced photoredox decarbonylative (▬CO) Minisci type C▬C bond formation (alkylation) between aldehydes and
This reaction is highly compatible with secondary and tertiary aldehydes. However, primary alkyl aldehydes and aromatic aldehydes failed to deliver decarbonylative Minisci-type alkylated products. The substrate scope of this aerobic photoredox decarbonylative alkylation reaction is decorated by various mono
The author proposed a plausible reaction mechanism, as shown in Figure 22. Visible light-induced photoexcited catalyst 4CzIPN* underwent SET with O2 to form a superoxide radical anion (O2˙−). This superoxide radical anion abstracts a hydrogen atom from aldehyde to produce an acyl radical (
6. Cross-dehydrogenative Minisci type reactions
Cross dehydrogenative coupling (CDC) reaction is step and atom economical reaction. It plays a vital role in the construction of a diverse array of C▬C and C▬heteroatom bonds, by functionalizing C▬H bonds of all types sp, sp2, sp3 [18, 19, 20, 21, 22, 23].
In 2020 Li and An group demonstrated an acid-free, 4CzIPN photocatalyzed, Minisci reaction between diverse Csp3▬H sources and
Sun group developed 4CzIPN and quinuclidine-catalyzed direct C▬H silylation of quinoxalinones or electron-deficient heteroarenes
7. Cyclization reactions
Cai group established a 4CzIPN-photocatalyzed intramolecular cascade oxidative aryl-trifluoromethylations [26] and aryl-methylcyanation [27] of
From a mechanistic perspective, the photoexcited 4CzIPN* catalyst decomposes sodium triflinate (CF3SO2Na) into CF3 radical and SO2. This CF3 radical is added into alkene of
The author proposed a plausible reaction mechanism of aryl-methylcyanation of
Cai group further extended the reaction protocol to
In 2021, Yu group demonstrated a 4CzIPN catalyzed cascade cyclization of
This cyclization reaction proceeds
8. Ring opening reaction
He and co-workers demonstrated a 4CzIPZ catalyzed aerobic oxidative cleavage of unstrained Csp3▬Csp3 bonds of morpholine derivatives using visible light as the energy source and O2 as an oxidant (Figure 31) [29]. The author proposed that the photoexcited 4CzIPN* was reduced by
9. Deuteration reaction
In 2020, Leonori and co-workers incorporated deuterium in unactivated 1°, 2° and 3° alkyl iodide using a combination of synergistic photoredox 4CzIPN catalyst and Bu3N as the halogen atom transfer (XAT)-agent precursor and methyl thioglycolate▬D2O as the D-atom donor (Figure 32) [30].
From mechanistic aspects, the excited photocatalyst 4CzIPN* oxidize Bu3N followed by deprotonation leads to α-aminoalkyl radical (
In addition to deuteration reaction, Leonori and co-workers further utilized the
10. Conclusions
It is well-known that photocatalytic reactions are powerful tools for a wide range of organic transformations. In this regard, visible-light-induced metal complexes have gained huge attention in the last two decades. Recently TADF materials have been used as an alternative for metal photocatalyst. In this chapter, we summarized a few TADF materials, particularly 4CzIPN as photocatalyst for various radical-based organic transformation reactions. This inexpensive TADF photocatalyst is less toxic and greener. A large number of TADF materials are prepared and used in OLEDs applications. However, only very few TADF molecules are explored in visible light promoted organic transformations. This TADF catalyzed organic transformation reactions are still in its infancy. Many new organo photocatalysts should be discovered for milder organic transformation.
Acknowledgments
B.K. Patel. acknowledges the support of this chapter by SERB (EMR/2016/007042) and CSIR 02(0365)/19-EMR-II. R. Suresh acknowledges the support of this chapter by SERB for funding under the National Post-Doctoral Fellowship scheme SERB-NPDF (PDF/2021/002055) and MRC, IISc Bangalore.
Conflict of interest
The authors declare no conflict of interest.
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