Properties and Synthetic Performances of Phenylamino Cyanoarenes under One-Photon Excitation Manifolds

In memory of Blas Flores Pérez (1963–2021)

Abstract

The synthesis of a set of new organic photocatalysts (PCs) with a donor-acceptor carbazolyl dicyanobenzene structure is reported. The PCs developed have fine-tailored redox potentials from –1.62 V (PC^•+/PC*) to 1.36 V (PC*/PC^•–) and were accessed through a straightforward two-step synthesis. The potential of these PCs was demonstrated in synthetically relevant reactions with mechanistically opposite thermodynamic requirements, previously reported only in the presence of precious Ir-based PCs. In addition, the PCs outperformed the yields promoted by the well-established 4CzIPN organic dye in both type of reactions.

Biographical Sketch

Luca Dell’Amico completed his Ph.D. at the University of Parma (Italy), under the supervision of Prof. Franca Zanardi, in 2014. He spent a research period­ with Prof. Karl Anker Jørgensen­ at Århus University (Denmark), where he was introduced to the field of organocatalysis. From 2014 to 2016, he was a Marie Curie fellow in Prof. Paolo Melchiorre’s group at ICIQ (Spain). In 2017, he started his independent career at the University of Padova. He was awarded the G. Ciamician Medal 2019 by the Italian Chemical Society and the Thieme Chemistry Journals Award 2020. In 2022, Luca received an ERC-Starting Grant to undertake new research in photoredox catalysis. His current research deals with the development and mechanistic investigation of novel photochemical processes.

In recent decades, photoredox catalysis has been at the vanguard of an intense research effort to develop more efficient synthetic methods and novel mechanistic patterns.[1] On one hand, photoredox catalysis has unlocked unprecedented activation modes in synthetic organic chemistry. This is because excited states can react in completely different modes compared to the ground states, enabling formerly challenging or even impossible transformations.[2] On the other hand, photoredox catalysis is a promising synthetic strategy towards the development of sustainable processes, by employing visible light as an environmentally benign energy source.[3] Additionally, the lack of absorption of most organic molecules in the visible-light region minimizes the activity of side reactions and product decomposition often promoted by higher-energy UV photons. Another advantage is that the use of readily available light sources, such as CFLs or LEDs, has made photochemical synthetic protocols highly practical, safe, and cost-effective.[4] Seminal advancements in the field have involved the use of metal complexes as photocatalysts (PCs) mainly Ru, Ir, or Cu derivatives.[1] [2] However, new directions are pointing towards the identification of more sustainable purely organic molecules as PCs.[5] Organic PCs are generally cheaper and less toxic due to the absence of precious metal atoms while maintaining or even outperforming the photophysical properties of well-established metal-based PCs. Moreover, organic PCs offer an increasing number of modular scaffolds that are characterized by tunable physicochemical features. In this sense, the structure-property relationships and rational design of organic PCs are highly simplified compared to metal complexes.[5]

In this scenario, 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) has recently emerged as a powerful organic PC due to its wide-balanced redox window, chemical stability, and versatility.[6] 4CzIPN is a donor-acceptor fluorophore with carbazolyl substituents as the electron donor moieties and dicyanobenzene as the electron acceptor unit. 4CzIPN, initially identified as an OLED candidate in 2012, exhibits an efficient thermally activated delayed fluorescence (TADF)[7] and excellent redox and photochemical properties, (E _1/2(PC^•+/PC*)= –1.04 V vs SCE, E _1/2 (PC*/PC^•)= 1.35 V vs SCE, λ max: 435 nm).[6] In 2016, Luo and Zhang reported the first application of 4CzIPN as a photoredox catalyst.[8] Since then, 4CzIPN has been applied in a wide variety of transformations such as Giese decarboxylative additions,[9] proton-coupled electron transfer reactions,[10] energy-transfer (EnT) processes,[11] dual catalytic coupling reactions[12] and to promote radical chain propagations,[13] just to mention a few.[6]

An attractive feature of 4CzIPN is its straightforward structural modification.[5] [6] In terms of frontier molecular orbitals, the HOMO is mainly delocalized over the four carbazolyl moieties (red in Figure [1]) while the LUMO is centered on the dicyanobenzene ring (blue in Figure [1]). This feature reflects in a charge transfer (CT) character of its excited state, where significant electron density is transferred from the electron donor units to the electron acceptor core. Moreover, this spatial separation of the HOMO and LUMO allows independent fine-tuning of both orbital energies. Furthermore, by tailoring the number and type of electron-donating units on the central ring, the photophysical properties and photoredox potentials can be adjusted for specific catalytic purposes.

We herein disclose the synthetic application of a set of carbazolyl dicyanobenzenes derivatives, with an ethyl(phenyl)amino group replacing one of the carbazolyl units, as metal-free photocatalysts. The identification of new carbazolyl dicyanobenzenes derivatives as organic PCs was inspired by the recent studies of Zhou, Wu, and co-workers.[14] In their work, they replaced one of the carbazole moieties of 4CzIPN with N-alkylanilines. Interestingly, this small structural modification not only alleviated photocatalyst decomposition but also increased the radical anion lifetime. In fact, the reported PC 3CzEPAIPN can undergo efficiently consecutive photoinduced electron transfer (ConPET) processes with exceedingly high reducing power (Scheme [1a]). However, investigation of such a scaffold under one-photon excitation manifold is still lacking to date. We thus envisaged to explore the PCs potentials under one-photon excitation manifolds (Scheme [1b]). Additionally, further modifying the 3CzEPAIPN scaffold, we aimed at defining new versatile organic PCs with wider redox windows and higher stability for light-triggered single electron transfer reactions. The PCs developed in this present work have fine-tailored redox potentials and have been accessed through a straightforward two-step synthesis. Their structure–photoredox­ property relationships were assessed in terms of the absorption/emission spectra and ground/excited state redox potentials allowing their rational selection for the intended synthetic goal. The potential of these bimodal PCs was benchmarked in synthetically relevant reactions with mechanistically opposite thermodynamic requirements, previously reported only in the presence of more precious Ir-based PCs. Remarkably, these novel organic PCs can promote both types of reactions with high yields and outperform the well-established 4CzIPN organic photocatalyst as well as the originally used Ir-complexes.

We initiate the synthesis of a group of dicyanobenzenes derivatives through a straightforward two-step procedure (Scheme [2]). As reported, the aromatic nucleophilic substitution reaction between 4,5,6-tetrafluoroisophthalonitrile (1) and N-ethylaniline (2) afforded intermediate 3 in 88% yield.[14] Then, through a second synthetic operation, diverse carbazole derivatives bearing methoxy or halogen (Br and Cl) groups were introduced in 58%, 66%, and 67% yields for compounds 4a, 4b, and 4c, respectively. With these novel organic PCs in hand, we next examined their photoredox properties.

We first investigated the absorption and emission spectra of PCs 4a–c (Figure [2]). Compound 4a showed a distinctive absorption spectrum with a peak centered at 360 nm (ε = 28000 M^–1cm^–1) and a shoulder at 400 nm, tailing up to 510 nm as well as a distinct peak at 310 nm (Figure [2], black line). As expected, due to the presence of electron-donating groups, 4a has the most red-shifted absorption from the present compound library,[5] including the previously reported 3CzEPAIPN photocatalyst (Figure [2], green line). In the cases of compounds 4b,c, their absorption spectra are practically identical (Figure [2], red and blue lines). The spectra of 4b,c present a peak centered at 300 nm, which is more red-shifted compared with the peak at 285 nm from 3CzEPAIPN. They also present a peak at 350 nm with a shoulder at 430 nm, tailing up to 490 nm.

As expected, the carbazolyl dicyanobenzene derivatives 4a–c have the potential to promote chemical transformations under visible light irradiation. We determined the ground-state redox potential values of 4a–c by cyclic voltammetry (CV). On one hand, PC 4a undergoes reversible reduction at 1.01 V vs. SCE (PC^•+/PC) and oxidation (PC/PC^•–) at –1.52 V vs. SCE (Table [1]). The resulting estimated potentials of the excited states of –1.49 V (PC^•+/PC*) and 0.98 V (PC*/PC^•–) are well suited for photoreactions requiring demanding reductive power. On the other hand, compounds 4b and 4c present identical redox properties, with a reversible reduction and an irreversible oxidation wave (Table [1]). The excited-state redox potentials were estimated to be –1.62 V (PC^•+/PC*) and 1.36 V (PC*/PC^•–) in both cases. In principle, these wide redox windows can engage in both oxidative and reductive quenching mechanisms, allowing the potential implementation of 4b,c in a variety of photoredox transformations.

Table 1 Excited- and Ground-State Photoredox Properties of 4a–c

Properties	4a	4b	4c
λ (nm)	up to 496	up to 460	up to 460
E 0,0 (eV)	2.50	2.70	2.70
E(PC • +/PC) (V)	1.01	1.08	1.08
E(PC/PC • –) (V)	–1.52	–1.34	–1.34
E(PC • +/PC*) (V)	–1.49	–1.62	–1.62
E(PC*/PC • –) (V)	0.98	1.36	1.36

After having established general structure-property relationships of the PCs 4a–c, we evaluated their photocatalytic performance in two different classes of benchmark reactions involving oxidative and reductive quenching mechanisms. Also, we compared their catalytic activity with the established 4CzIPN and 3CzEPAIPN organic PCs. Our initial study targeted the photoredox-catalyzed intermolecular C–H functionalization of tertiary amines through a reductive quenching mechanism (Scheme [3]).[15] Here, the reaction between N,N,4-trimethylaniline (5) with 2-benzylidenemalononitrile (6) was tested using compounds 4a–c, 4CzIPN, and 3CzEPAIPN as PCs. The redox potentials of 5 (E ₀(5 ^•+/5) ≈ +0.80 V vs. SCE) and O₂ (E ₀(O₂/O₂ ^•–) = –0.64 V vs. SCE)[16] are within the operational windows of the developed PCs. The Rueping group reported that different classes of compounds can be obtained depending on the reaction conditions, using the metal-based PC [Ir(ppy)₂bpy]PF₆.[15] According to the Rueping group, when the reaction is carried out in the presence of oxygen the tetrahydroquinoline derivative 8 is the only product formed, while under oxygen-free conditions the conjugate addition derivative 7 is produced (Scheme [3]). Replacing the Ir complex with our new class of organic PCs, we obtained combined yields of 64%, 70%, and 61% using 4a, 4b, and 4c, respectively, under aerobic conditions (Scheme [3]). Interestingly, in our case, the main product was always 7, either under aerobic or oxygen-free conditions and using the entire set of carbazolyl dicyanobenzene derivatives 4a–c, 3CzEPAIPN, and 4CzIPN as PCs (see SI, Table 2).[17] In this regard, PCs 4a–c furnished product 7 in good yields spanning from 41% to 54% after 15 h of reaction under 456 nm light irradiation in the presence of oxygen. For comparison purposes, we also carried out the reactions with 4CzIPN and 3CzEPAIPN. Interestingly, PCs 4a,b outperformed the yields for 7 achieved with these well-known cyanoarene-based fluorophores. The formation of the tetrahydroquinoline product 8 was also observed in all cases, spanning from 14% to 20% yields. However, PC 4a provided a higher selectivity (81:19) in favor of compound 7.

The presence of oxygen and hydrogen peroxide has been reported to be detrimental to the stability of different PCs.[18] With this in mind, we evaluated the stability of 3CzEPAIPN in this photochemical process. Four parallel reactions (0.2 mmol) were carried out under the optimized reactions conditions. Gratifyingly, 3CzEPAIPN was quantitatively recovered (>98% yield) from the reaction mixture after 15 hours of light irradiation. This high stability of the PC is in line with that reported by Zhou, Wu, and co-workers.[14]

To further evaluate the generality of the PCs, we study a reaction that proceeds under an oxidative quenching mechanism. For this objective, a visible-light-mediated protocol for the deaminative generation of alkyl radicals from Katritzky­ salts was chosen. This process was reported by Glorius and co-workers using [Ir(ppy)₂(dtbbpy)]PF₆ as PC.[19] In principle, the photoinduced reduction of the Katritzky salt 10 (E _1/2 (10/10 ^•–) = –0.93 V vs. SCE in DMF)[19] is thermodynamically feasible with the entire family of PCs developed in this work. In fact, the reaction between isoquinoline 9 and cyclohexyl Katritzky salt 10 afforded the alkylated product 11 after 40 h of light irradiation in presence of PCs 4b,c (Scheme [4]). The reactions yields were high giving 76% and 85% employing PCs 4b and 4c, respectively. These results are significantly superior in comparison with the well-established 4CzIPN PC (59% yield). Quite unexpectedly, PC 4a was not able to promote the reaction, probably because of the oxidative power required to close the catalytic cycle. The PC 3CzEPAIPN, reported by Zhou, Wu, and co-workers, gave the best result of the whole series with 90% yield. It is worth mentioning that the yields with 4c (85%) and 3CzEPAIPN (90%) are comparable or better to the iridium PC (88%) used by Glorius and co-workers, with the advantage of using cheaper and more environmentally benign PCs compared to the metal complex employed in the original study.

In conclusion, we have reported a novel set of carbazolyl dicyanobenzenes derivatives as versatile organic PCs with wide excited-state potentials ranging from –1.62 V (PC^•+/PC*) to 1.36 V (PC*/PC^•–) for one-photon excitation processes. Because of their properties, both mechanistically oxidative and reductive light-driven transformations can be catalyzed by these compounds. Specifically, the developed PCs can promote thermodynamically opposite visible-light-mediated functionalization of tertiary amines and the alkylation of isoquinoline with yields up to 70% and 90%, respectively. These processes had previously been reported using classical transition-metal-based PCs. The implementation of novel organic PCs advanced these relevant synthetic methods to more cost-effective and sustainable settings. We believe that this new class of molecules will expand the repertoire of organic PCs available to the community, defining a new sustainable tool to the construction of synthetically useful building blocks.

Conflict of Interest

The authors declare no conflict of interest.

• References and Notes

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Corresponding Author

Publication History

Received: 08 December 2021

Accepted after revision: 18 February 2022

Accepted Manuscript online:
18 February 2022

Article published online:
19 April 2022

© 2022. Thieme. All rights reserved

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• References and Notes

• 1a Prier CK, Rankic DA, MacMillan DW. C. Chem. Rev. 2013; 113: 5322
  Search in Google Scholar
• 1b Shaw MH, Twilton JD. A, MacMillan DW. C. J. Org. Chem. 2016; 81: 6898
  CrossrefPubMedSearch in Google Scholar
• 2a Silvi M, Melchiorre P. Nature 2018; 554: 41
  CrossrefPubMedSearch in Google Scholar
• 2b Chan AY, Perry IB, Bissonnette NB, Buksh BF, Edwards GA, Frye LI, Garry OL, Lavagnino MN, Li BX, Liang Y, Mao E, Millet A, Oakley JV, Reed NL, Sakai HA, Seath CP, MacMillan DW. C. Chem. Rev. 2022; 122: 1485
  CrossrefPubMedSearch in Google Scholar
• 3 Schultz DM, Yoon TP. Science 2014; 343: 1239176
  CrossrefPubMedSearch in Google Scholar
• 4 McAtee RC, McClain EJ, Stephenson CR. J. Trends Chem. 2019; 1: 111
  CrossrefPubMedSearch in Google Scholar
• 5a Romero NA, Nicewicz DA. Chem. Rev. 2016; 116: 10075
  CrossrefPubMedSearch in Google Scholar
• 5b Vega-Peñaloza A, Mateos J, Companyó X, Escudero-Casao M, Dell’Amico L. Angew. Chem. Int. Ed. 2021; 60: 1082
  CrossrefPubMedSearch in Google Scholar
• 5c Amos SG. E, Garreau M, Buzzetti L, Waser J. Beilstein J. Org. Chem. 2020; 16: 1163
  CrossrefPubMedSearch in Google Scholar
• 5d Mateos J, Rigodanza F, Vega-Peñaloza A, Sartorel A, Natali M, Bortolato T, Pelosi G, Companyó X, Bonchio M, Dell’Amico L. Angew. Chem. Int. Ed. 2020; 59: 1302
  CrossrefPubMedSearch in Google Scholar
• 5e Costa P, Vega-Peñaloza A, Cognigni L, Bonchio M. ACS Sustainable Chem. Eng. 2021; 9: 15694
  CrossrefSearch in Google Scholar
• 6 Shang TY, Lu LH, Cao Z, Liu Y, He WM, Yu B. Chem. Commun. 2019; 55: 5408
  Search in Google Scholar
• 7 Uoyama H, Goushi K, Shizu K, Nomura H, Adachi C. Nature 2012; 492: 234
  Search in Google Scholar
• 8 Luo J, Zhang J. ACS Catal. 2016; 6: 873
  Search in Google Scholar
• 9 Speckmeier E, Fischer TG, Zeitler K. J. Am. Chem. Soc. 2018; 140: 15353
  Search in Google Scholar
• 10 Liu Y, Chen X.-L, Li X.-Y, Zhu S.-S, Li S.-J, Song Y, Qu L.-B, Yu B. J. Am. Chem. Soc. 2021; 143: 964
  Search in Google Scholar
• 11 Lu J, Pattengale B, Liu Q, Yang S, Shi W, Li S, Huang J, Zhang J. J. Am. Chem. Soc. 2018; 140: 13719
  CrossrefPubMedSearch in Google Scholar
• 12 Badir SO, Dumoulin A, Matsui JK, Molander GA. Angew. Chem. Int. Ed. 2018; 57: 6610
  CrossrefPubMedSearch in Google Scholar
• 13a Duhail T, Bortolato T, Mateos J, Anselmi E, Jelier B, Togni A, Magnier E, Dagousset G, Dell’Amico L. Org. Lett. 2021; 23: 7088
  CrossrefPubMedSearch in Google Scholar
• 13b Singh VK, Yu C, Badgujar S, Kim Y, Kwon Y, Kim D, Lee J, Akhter T, Thangavel G, Park LS, Lee J, Nandajan PC, Wannemacher R, Milian-Medina B, Lüer L, Kim KS, Gierschner J, Kwon MS. Nat. Catal. 2018; 1: 794
  CrossrefSearch in Google Scholar
• 14 Xu J, Cao J, Wu X, Wang H, Yang X, Tang X, Toh RW, Zhou R, Yeow EK. L, Wu J. J. Am. Chem. Soc. 2021; 143: 13266
  CrossrefPubMedSearch in Google Scholar
• 15 Zhu S, Das A, Bui L, Zhou H, Curran DP, Rueping M. J. Am. Chem. Soc. 2013; 135: 1823
  CrossrefPubMedSearch in Google Scholar
• 16 Singh PS, Evans DH. J. Phys. Chem. B 2006; 110: 637
  CrossrefPubMedSearch in Google Scholar
• 17 In our catalytic system, the removal of oxygen from the reaction medium causes a detriment in the overall reaction yields (see SI, Table 2).
• 18a Oster G, Wotherspoon N. J. Chem. Phys. 1954; 22: 157
  CrossrefSearch in Google Scholar
• 18b Majek M, Filace F, Jacobi von Wangelin A. Beilstein J. Org. Chem. 2014; 10: 981
  CrossrefPubMedSearch in Google Scholar
• 19 Klauck FJ. R, James MJ, Glorius F. Angew. Chem. Int. Ed. 2017; 56: 12336
  CrossrefPubMedSearch in Google Scholar

• Supplementary Material