Zwitterionic Acridinium Amidate for Photocatalytic Acceptorless Dehydrogenation

Abstract

The development of catalytic systems that facilitate simple yet valuable molecular transformations in a sustainable manner is of fundamental importance in the field of synthetic organic chemistry. Herein, we report the expedient application of a zwitterionic acridinium amidate, a recently developed direct hydrogen-atom-transfer catalyst, in catalytic acceptorless dehydrogenation (CAD). The combined use of the acridinium amidate with a cobaloxime complex and a protic additive as a catalyst system enables the CAD of hydrocarbons to proceed with high efficiency under mild reaction conditions.

Catalytic acceptorless dehydrogenation (CAD) of aliphatic compounds, which proceeds with the release of molecular hydrogen, is one of the most straightforward and sustainable methods for constructing olefinic and aromatic molecular frameworks.[1] [2] [3] [4] [5] These transformations commonly require a strong external driving force, primarily because they are thermodynamically unfavorable endergonic processes. To circumvent this problem, a combination of photocatalytic hydrogen-atom transfer (HAT)[6] with catalytic hydrogen evolution has emerged as a promising strategy for promoting CAD under mild reaction conditions. The first example of such a system, elaborated by Sorensen and co-workers, was based on the combined use of tetrabutylammonium decatungstate (TBADT) as a direct HAT (d-HAT)[7] catalyst and a cobaloxime pyridine chloride[8] as a hydrogen-evolution catalyst (Figure [1a]).[9] Later, Xu, Huang, and their co-workers established CAD of a broad range of aliphatic compounds by using a photoexcited anthraquinone derivative and a cobaloxime formed in situ.[10] As an alternative, the Kanai group developed an efficient visible-light-induced CAD of N-heterocycles and tetrahydronaphthalenes to produce fused aromatic compounds by employing an acridinium photoredox catalyst, a thiol-based HAT catalyst, and a Pd(II) or Ni(II) metal catalyst.[11] [12] Whereas these pioneering studies, along with recent seminal contributions that have expanded the scope of photocatalytic CAD, underscore the importance of identifying suitable photocatalysts for this mode of dehydrogenation, the options are restricted to a library of well-known catalysts.[13] [14] [15] [16] [17] [18]

We recently introduced the zwitterionic acridinium amidate 1 as a novel organic molecular photocatalyst that undergoes intramolecular charge transfer in the excited state with the aid of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) to generate the corresponding amidyl radical in the form of a radical pair capable of homolytically cleaving various C–H bonds, including those of structurally unbiased aliphatic compounds (Figure [1b]).[19] Considering the remarkable ability of amidate 1 to serve as a d-HAT catalyst for promoting C–H bond functionalization under light irradiation, we became interested in the possibility of combining 1 with an appropriate transition-metal-based hydrogen-evolution catalyst to develop a unique dehydrogenation protocol (Figure [1c]). Here, we report a hybrid catalytic system consisting of 1 and a cobaloxime complex for facilitating the HAT-mediated CAD of hydrocarbons.

Initially, we attempted CAD of 1,2,3,4-tetrahydronaphthalene in the presence of amidate 1 (3 mol %) and the cobaloxime complex 2a [Co(dmgBF₂)₂(H₂O)₂] (5 mol %) in HFIP under blue-light irradiation; however, this did not show any detectable formation of the fully dehydrogenated product 3a (Table [1], entry 1). This outcome led us to examine other common solvents instead of HFIP, and we found that 3a was formed, albeit in a low yield, when 1,2-dichloroethane (DCE) was used (entry 2). Subsequent trials with other cobaloxime complexes resulted in no significant improvement in the reactivity (entries 3–5). We therefore evaluated the effect of various hydrogen-bond-donor additives on the reactivity profile, considering the critical relevance of the noncovalent interaction to the facile generation of the reactive triplet state of 1 upon photoexcitation.[19] The addition of a catalytic amount of HFIP slightly enhanced the reaction efficiency, and 3a was produced in higher yield with 2,4,6-collidinium tosylate as an additive (entries 6–9). Further optimization of the reaction conditions allowed us to obtain 3a in a satisfactory yield when the reaction was carried out for 48 hours under the influence of 1, 2a, and 2,4,6-collidinium tosylate (entry 10). This ternary catalyst combination was revealed to be optimal through a screening of various collidinium salts (entries 11–13). Control experiments confirmed that the presence of 1 and light irradiation were both essential for CAD (entries 14 and 15).

Table 1 Optimization of the Reaction Conditions for CAD of 1,2,3,4-Tetrahydronaphthalene.^a

Entry	Co complex	Time (h)	Additive	Yieldb (%)
1c	2a	24	–	–
2	2a	24	–	20
3	2b	24	–	23
4	2c	24	–	8
5	2d	24	–	18
6	2a	24	HFIP	25
7	2a	24	2,4,6-collidine	20
8	2a	24	2,4,6-collidine + HFIP	25
9	2a	24	2,4,6-collidine·TsOH	32
10	2a	48	2,4,6-collidine·TsOH	81
11	2a	48	2,4,6-collidine·AcOH	65
12	2a	48	2,4,6-collidine·H3PO4	24
13	2a	48	2,4,6-collidine·TFA	67
14d	2a	24	2,4,6-collidine·TsOH	–
15e	2a	24	2,4,6-collidine·TsOH	–

^a Unless otherwise noted, the reactions were performed in a flame-dried Schlenk tube with 1,2,3,4-tetrahydronaphthalene (0.1 mmol), 1 (3 mol %), cobalt complex 2 (5 mol %), and additive (50 mol %) in dry degassed DCE under argon with blue LED irradiation with a fan to maintain the temperature.

^b By NMR analysis with 1,3,5-trimethoxybenzene as the internal standard.

^c In HFIP instead of DCE.

^d Without 1.

^e In darkness.

The substrate scope under the optimized reaction conditions was then explored (Figure [2a]). A range of benzene-fused carbocycles reliably underwent dehydrogenation to afford the corresponding unsaturated compounds 3b–e. Nitrogen-containing carbocycles were also amenable to this hybrid catalysis, providing indoles 3f–i, the isoquinoline 3j, and the 2-pyridone 3k in good to high yields. Furthermore, benzylic alcohols were successfully converted into the ketone 3l and aldehyde 3m. To assess the feasibility of CAD of complex molecules, we examined the reaction of (+)-estrone 3-methyl ether (4; Figure [2b]). Although a higher catalyst loading was required to ensure sufficient substrate conversion, the 4b,5-dehydro product 5 was formed and isolated in 35% yield as a single regioisomer.[20] [21] [22] [23]

Based on the behavior of zwitterionic acridinium amidate 1 [19] and previous reports on the photocatalyzed acceptorless dehydrogenation of alkanes,[9] [10] [11] [12] a plausible mechanism is proposed, as shown in Figure [3]. Upon photoexcitation and complexation with the hydrogen-bond-donor salt 2,4,6-collidinium tosylate, the catalytically active triplet state A is formed. This species can then undergo a HAT with the alkane substrate via its N-centered radical, leading to the amide acridinyl radical B and the corresponding C-centered radical. The resulting carbon radical reacts with the cobaloxime co-catalyst [Co] to afford the desired desaturated product and a cobalt–hydride species [Co-H]. Finally, a single-electron transfer and proton transfer events between B and [Co-H] take place, regenerating 1 and the cobaloxime catalyst with concomitant evolution of a hydrogen molecule.

In conclusion, we have introduced a hybrid catalytic system that is effective in facilitating CAD of benzene-fused carbocycles, nitrogen-containing carbocycles, and benzylic alcohols by properly combining a zwitterionic acridinium amidate, a cobaloxime complex, and a protic additive.[24] The potential applicability of this catalytic system for the direct transformation of complex molecules was demonstrated by the site-selective dehydrogenation of an estrone derivative. Further efforts to expand the utility of CAD and to unveil unique photocatalysis by acridinium amidates are underway.

Conflict of Interest

The authors declare no conflict of interest.

• References and Notes

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• 24 Acceptorless Dehydrogenation of 1,2,3,4-Tetrahydronaphthalene; Typical Procedure A flame-dried Schlenk tube equipped with a stirrer bar was charged with acridinium amidate 1 (1.6 mg, 0.003 mmol, 3 mol %), Co complex 2a (2.1 mg, 0.005 mmol, 5 mol %), and 2,4,6-collidinium tosylate (14.7 mg, 0.05 mmol). The tube was sealed with a rubber septum, evacuated, and backfilled with Ar five times, then DCE (500 μL) and 1,2,3,4-tetrahydronaphthalene (13.2 mg, 0.1 mmol, 1.0 equiv) were successively introduced into the Schlenk tube. The rubber septum was replaced with a glass stopper under a steady flow of Ar, and the tube was quickly evacuated and backfilled with Ar five times. The mixture was then stirred for 48 h under irradiation by two Kessil H150 Blue lamps, with fan cooling to maintain the temperature below 40 °C. The mixture was concentrated, and the yield of naphthalene was determined by GC-FID with 1,3,5-trimethoxybenzene as an internal standard [yield: 0.080 mmol (80%)].

Corresponding Authors

Publication History

Received: 11 March 2025

Accepted after revision: 29 April 2025

Accepted Manuscript online:
29 April 2025

Article published online:
10 June 2025

© 2025. Thieme. All rights reserved

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

• References and Notes

• 1 Dobereiner GE, Crabtree RH. Chem. Rev. 2010; 110: 681
  Search in Google Scholar
• 2 Armaroli N, Balzani V. ChemSusChem 2011; 4: 21
  Search in Google Scholar
• 3 Gunanathan C, Milstein D. Science 2013; 341: 1229712
  Search in Google Scholar
• 4 Verma PK. Coord. Chem. Rev. 2022; 472: 214805
  Search in Google Scholar
• 5 Zhou M.-J, Liu G, Xu C, Huang Z. Synthesis 2022; 55: 547
  Search in Google Scholar
• 6 Capaldo L, Ravelli D. Eur. J. Org. Chem. 2017; 2017: 2056
  Search in Google Scholar
• 7 Capaldo L, Ravelli D, Fagnoni M. Chem. Rev. 2022; 122: 1875
  Search in Google Scholar
• 8 Dam P, Zuo K, Azofra LM, El-Sepelgy O. Angew. Chem. Int. Ed. 2024; 63: e202405775
  Search in Google Scholar
• 9 West JG, Huang D, Sorensen EJ. Nat. Commun. 2015; 6: 10093
  Search in Google Scholar
• 10 Zhou M.-J, Zhang L, Liu G, Xu C, Huang Z. J. Am. Chem. Soc. 2021; 143: 16470
  Search in Google Scholar
• 11 Kato S, Saga Y, Kojima M, Fuse H, Matsunaga S, Fukatsu A, Kondo M, Masaoka S, Kanai M. J. Am. Chem. Soc. 2017; 139: 2204
  Search in Google Scholar
• 12 Fuse H, Kojima M, Mitsunuma H, Kanai M. Org. Lett. 2018; 20: 2042
  Search in Google Scholar
• 13 Ritu Ritu, Das S, Tian Y.-M, Karl T, Jain N, König B. ACS Catal. 2022; 12: 10326
  Search in Google Scholar
• 14 Zuo K, Zhu J, Akhtar F, Dam P, Azofra LM, El-Sepelgy O. Org. Lett. 2025; 27: 30
  Search in Google Scholar
• 15 Yi P, Wu Y, Wang J, Liu Q, Xing Y, Lu Y, Ma C, Duan L, Zhao J, Meng Q. Org. Biomol. Chem. 2025; 23: 1574
  Search in Google Scholar
• 16 Yuan Y, Zhang Y, Menzel JP, Santoro J, Dolack M, Wang H, Batista V, Wang D. ACS Catal. 2024; 14: 17445
  Search in Google Scholar
• 17 Gu X, Zhang Y.-A, Zhang S, Wang L, Ye X, Occhialini G, Barbour J, Pentelute BL, Wendlandt AE. Nature 2024; 634: 352
  Search in Google Scholar
• 18 Ritu Ritu, Kolb D, Jain N, König B. Adv. Synth. Catal. 2023; 365: 605
  Search in Google Scholar
• 19 Entgelmeier L.-M, Mori S, Sendo S, Yamaguchi R, Suzuki R, Yanai T, García Mancheño O, Ohmatsu K, Ooi T. Angew. Chem. Int. Ed. 2024; 63: e202404890
  Search in Google Scholar
• 20 Stéphan E, Zen R, Authier L, Jaouen G. Steroids 1995; 60: 809
  Search in Google Scholar
• 21 Kürti L, Czakó B, Corey EJ. Org. Lett. 2008; 10: 5247
  Search in Google Scholar
• 22 Yue T, Li H.-P, Ding K. Tetrahedron Lett. 2016; 57: 4850
  Search in Google Scholar
• 23 Alsayari A, Kopel L, Ahmed MS, Pay A, Carlson T, Halaweish FT. Steroids 2017; 118: 32
  Search in Google Scholar
• 24 Acceptorless Dehydrogenation of 1,2,3,4-Tetrahydronaphthalene; Typical Procedure A flame-dried Schlenk tube equipped with a stirrer bar was charged with acridinium amidate 1 (1.6 mg, 0.003 mmol, 3 mol %), Co complex 2a (2.1 mg, 0.005 mmol, 5 mol %), and 2,4,6-collidinium tosylate (14.7 mg, 0.05 mmol). The tube was sealed with a rubber septum, evacuated, and backfilled with Ar five times, then DCE (500 μL) and 1,2,3,4-tetrahydronaphthalene (13.2 mg, 0.1 mmol, 1.0 equiv) were successively introduced into the Schlenk tube. The rubber septum was replaced with a glass stopper under a steady flow of Ar, and the tube was quickly evacuated and backfilled with Ar five times. The mixture was then stirred for 48 h under irradiation by two Kessil H150 Blue lamps, with fan cooling to maintain the temperature below 40 °C. The mixture was concentrated, and the yield of naphthalene was determined by GC-FID with 1,3,5-trimethoxybenzene as an internal standard [yield: 0.080 mmol (80%)].

• Supplementary Material