Redox-economical radical generation from organoborates and carboxylic acids by organic photoredox catalysis

Abstract

A simple generation method of carbon radicals via 1e-oxidation of organotrifluoroborates and carboxylic acids by the action of an organophotoredox catalyst, 9-mesityl-10-methylacridinium perchlorate ([Acr⁺–Mes]ClO₄), has been developed. This organophotocatalytic protocol is amenable to radical C–C bond formation with electron-deficient olefins.

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Over the past few years, photoredox catalysis, which is composed of visible-light-induced single-electron-transfer (SET) processes, has become a powerful tool in the field of synthetic organic chemistry.¹ In particular, a well-defined tris(2,2′-bipyridine) ruthenium(II) complex (1a) and the relevant cyclometalated iridium(III) derivatives (1b and 1c) have been proven to be useful transition metal photocatalysts for invaluable radical transformations. On the other hand, organic photoredox catalysis has also been attracting great interest in terms of the elements strategy initiative and green chemistry.²

Organoboronic acid derivatives and organoborates are regarded as convenient radical precursors in terms of high stability, low toxicity and high compatibility with various functional groups. One-electron oxidation of organoboron compounds smoothly generates reactive carbon-centered radicals through deboronation. Recently, some metal-catalyzed radical reactions using organoboronic acid derivatives have been reported, but they usually require an excess amount of co-oxidants (the upper process in Scheme 1a).³ More recently, our group and the groups of Chen and Molander have developed radical reactions of organoborates designed by Ru or Ir photoredox catalysis (the lower process in Scheme 1a).^4,5

Scheme 1 Generation of C-radicals through catalytic oxidation of organoborons.

In this communication, we describe a simple generation method of carbon-centered radicals from organotrifluoroborates 2 and carboxylic acids 3 by the action of 9-mesityl-10-methylacridinium perchlorate ([Acr⁺–Mes]ClO₄ (1d)), an organophotoredox catalyst developed by Fukuzumi and Ohkubo.^6,7 The photoinduced electron-transfer state of 1d is known as an oxidant (+1.65 V vs. Cp₂Fe) which is stronger than those of the Ru and Ir photoredox catalysts. Thus, 1d enables oxidative transformation, which cannot be promoted by metal photoredox catalysis. We will describe a new and simple protocol for the generation of organic radicals from organoborates 2 and carboxylic acids 3, which is followed by radical C–C bond formation without noble metals and co-oxidants (Scheme 1b).

We initially examined the photocatalytic reaction of potassium phenethyltrifluoroborate (2a) with ethylidenemalonic acid dimethyl ester (4a) in the presence of 1d (2 mol%) in a 1 : 1 acetone-d₆ and CD₃OD mixture under visible light irradiation (blue LEDs: λ_max = 425 nm) for 24 h (entry 1 in Table 1). As a result, the addition product 5aa was obtained in a 64% NMR yield (24 h). An elongated reaction time (48 h) gave a better yield (79%). The acetone–methanol mixed solvent system resulted in the highest yield (entries 1–5). It should be noted that the typical transition metal photoredox catalysts (1a–c) afforded the product in considerably lower yields (entries 6–8). The reactivity of the organocatalyst 1d was superior to that of metal catalysts 1a–c and can be ascribed to the oxidation potentials of the photoactivated species (1a: +0.43 V, 1b: +0.91 V, 1c: +0.80 V, 1d: +1.65 V vs. Cp₂Fe).^1d,f The organoborate 2a (oxidation potential: +1.41 V vs. Cp₂Fe) is readily oxidized by the photoactivated 1d but not by the excited 1a–c. Both the photocatalyst and visible light were essential for the present reaction (entries 9 and 10), strongly supporting the hypothesis that the photoactivated species of the photocatalyst is involved in the reaction.

Table 1 Optimization of the photocatalytic radical reaction of 2a with 4a^a

Entry	Photocatalyst	Solvent	NMR yield of 5aa/%
a Reaction conditions: a reaction mixture of 2a (0.06 mmol), 4a (0.05 mmol), photocatalyst (1.0 μmol), SiEt4 (an internal standard) and solvent (0.50 mL) was irradiated by 3 W blue LEDs (λ = 425 ± 15 nm) at room temperature for 24 h.b Reaction time = 48 h.c The reaction was conducted in the dark.
1	1d	Acetone-d6/CD3OD (1/1)	64, 79^b
2	1d	Acetone-d6	28
3	1d	CD3OD	34
4	1d	CD3CN	53
5	1d	DMSO-d6	0
6	1a	Acetone-d6/CD3OD (1/1)	0
7	1b	Acetone-d6/CD3OD (1/1)	13
8	1c	Acetone-d6/CD3OD (1/1)	3
9^c	1d	Acetone-d6/CD3OD (1/1)	0
10	None	Acetone-d6/CD3OD (1/1)	0

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Next, we examined the scope of the present photocatalytic reaction (Table 2). The reaction of tertiary-alkyltrifluoroborates (2b and 2c) smoothly proceeded with the construction of a quaternary carbon center to give the corresponding products (5bb and 5ca) in 61% and 94% yields, respectively. Secondary-alkyltrifluoroborates (2d–l), regardless of cyclic or acyclic structures, afforded the products (5db–lb) in good yields (58–85%). Primary-alkyltrifluoroborates (2m–o) were also applied to this photocatalytic system (38–93% yields). It is noteworthy that the addition of more substituted alkyl groups is rather efficient in the present C–C bond formation. Tolerance to a variety of functionalities such as Br (2k), ester (2l), Boc-protected amines (2h and 2n) and ethers (2i and 2o) is particularly significant. Furthermore, the reaction of potassium cyclohexyltrifluoroborate (2f) with a range of electron-deficient alkenes, acrylate derivatives (4c and 4d) and alkenes bearing a substituent at the reaction site (4e, 4f and 4g), provided the corresponding C–C coupled products (5fc–5fg: 38–88%). These results reveal that the present photocatalytic system enables the selective generation of various alkyl radicals with/without functionalities from the corresponding organoborates.

Table 2 The scope of the present photocatalytic reaction^a,b

a Reaction conditions: a reaction mixture of 2 (0.36 mmol), 4 (0.30 mmol), 1d (6.1 μmol), acetone (1.5 mL) and MeOH (1.5 mL) was irradiated by 3 W blue LEDs (λ = 425 ± 15 nm) at room temperature for 24 h.b Isolated yields.c Reaction time = 12 h.d Reaction time = 36 h.e Reaction time = 18 h.f Reaction time = 60 h.g Reaction time = 15 h.h Reaction time = 48 h.

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Remarkably, sunlight, which includes visible light as the main component, can be utilized as the light source. To our surprise, the sunlight-driven system was more efficient than the blue LED system. The reaction of 2f with 4b was completed within 18 h under daylight (eqn (1)).

Encouraged by these results, we next investigated the generation of organic radicals from carboxylic acids by the present organophotoredox system. Carboxylic acids are readily available and known to serve as C-radical sources through 1e-oxidation followed by decarboxylation.⁸ We optimized the reaction of pivalic acid (3b) with 4b (see the ESI†). To our delight, the reaction of 3b with 4b in the presence of Na₂CO₃ (0.1 equiv.) and organophotocatalyst 1d (2 mol%) proceeded smoothly to give the corresponding product 5bb in an 81% isolated yield (Scheme 2). However, the efficiency of the reactions of 1-adamantanecarboxylic acid (3c), cyclohexanecarboxylic acid (3f) and 2-methylbutyric acid (3j) declined (60 h).⁹ In addition, the reactions of 3-phenylpropionic acid (3a) and n-pentanoic acid (3m) did not proceed at all. These results show that this organophotoredox catalysis can be applied to the oxidation of carboxylic acids, but the scope of the reaction is rather limited compared to the reaction of organoborates.

Scheme 2 Photocatalytic radical addition of carboxylic acids 3.

On the basis of our study and previous reports,^4,6,7 a plausible reaction scheme through a redox-neutral process is illustrated in Scheme 3. First, visible light irradiation (blue LEDs or sunlight) causes excitation of the organocatalyst 1d into a photoinduced electron-transfer state, Acr˙–Mes˙⁺, which serves as a strong oxidant, through the excited state, *[Acr⁺–Mes]. A carbon-centered radical is generated via the 1e-oxidation of organoborate 2 or carboxylic acid 3 by Acr˙–Mes˙⁺ accompanying the formation of the reduced species, Acr˙–Mes. The organic radical reacts with an electron-deficient alkene 4 to give the radical intermediate 6, subsequent 1e-reduction of which by Acr˙–Mes provides a carboanion intermediate 7. Finally, smooth protonation by the solvent, MeOH, produces the adduct 5. Control experiments in CD₃OH revealed that the α-H atom in the product 5 does not result from hydrogen abstraction from the CD₃ group but from protonation with the OH group (see the ESI†), supporting the involvement of a carboanionic intermediate 7.

Scheme 3 A plausible reaction mechanism.

In conclusion, we have developed a novel redox-economical photocatalytic radical reaction via oxidative generation of carbon radicals from organotrifluoroborates and carboxylic acids by the action of an organophotoredox catalyst, [Acr⁺–Mes]ClO₄. The present organocatalytic strategy turns out to be free of a noble metal catalyst, co-oxidant and toxic/explosive chemicals. In particular, owing to the high oxidation potential of photoinduced electron-transfer state, [Acr⁺–Mes]ClO₄ can generate organic radicals from a variety of organoborates, which cannot be smoothly mediated by the Ru and Ir species. Further development of the synthetically valuable organic photoredox catalysis and redox-economical reaction is a continuing effort in our laboratory.

Acknowledgements

The financial support from the Japanese government (Grant-in-Aid for Scientific Research: no. 26288045) is gratefully acknowledged.

Notes and references

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9. The reactions of 3f and 3j were not completed under these conditions.

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Footnote

† Electronic supplementary information (ESI) available: Experimental details and spectral data. See DOI: 10.1039/c5ra01826a

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