Visible-light-induced [4 + 2] cycloaddition of pentafulvenes by organic photoredox catalysis

Kenta Tanaka *a, Yosuke Asada b, Yujiro Hoshino *b and Kiyoshi Honda *b
aFaculty of Pharmaceutical Science, Tokyo University of Science, 2641 Yamazaki, Noda-city, Chiba 278-8510, Japan. E-mail:
bGraduate School of Environment and Information Sciences, Yokohama National University, Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan. E-mail:;

Received 3rd June 2020 , Accepted 5th August 2020

First published on 6th August 2020

We have developed thioxanthylium photoredox catalyzed [4 + 2] cycloaddition of pentafulvenes at room temperature under green light irradiation, which affords tetrahydrocyclopenta[b]chromenes with high regioselectivities. The present reaction provides a sustainable approach to carry out the cycloaddition of pentafulvenes without the use of transition metal catalysts or high-temperature conditions. This procedure enables a mild and straightforward access to 1,3a,9,9a-tetrahydrocyclopenta[b]chromenes. The quantum yield of the reaction (Φ = 0.15) indicates that the reaction would mainly proceed via photocatalytic pathways.

The cycloaddition of pentafulvenes is a powerful approach to obtain various polycyclic compounds.1 In the past few decades, a variety of cycloaddition reactions such as [2 + 2], [3 + 2], [4 + 2], [6 + 2], [6 + 3] and [6 + 4] cycloadditions have been successfully developed due to their ability to exhibit multiple cycloaddition profiles.2 More recently, a chiral scandium-complex-catalyzed asymmetric [4 + 2] cycloaddition with fulvenes was also reported.3 However, previously reported cycloaddition reactions of fulvenes were mainly carried out by using transition metal catalysts or high temperature conditions (Scheme 1(a));4 hence, the development of more efficient and milder methods is highly desirable.
image file: d0ob01151g-s1.tif
Scheme 1 Cycloaddition reaction of pentafulvene.

Being one such efficient protocol, the photochemical reaction is an attractive method in organic synthetic chemistry, and especially, the visible-light-induced photoredox reaction has become a powerful tool in organic synthesis over the past few decades.5 However, only a few examples of UV light-induced cycloaddition reactions of pentafulvenes have been developed.6

In the course of our study on [4 + 2] cycloaddition reactions,7 we recently synthesized thioxanthylium organic photoredox catalysts, which have high excited state reduction potentials and are able to be used under irradiation with green light.8 Compared with transition-metal photoredox catalysts, organic photoredox catalysts have some merits that their use represents a more cost-effective and sustainable approach.9,10 In 2019, we reported that thioxanthylium photoredox catalysts efficiently promoted oxa-[4 + 2] cycloaddition of ortho-quinone methides with styrenes to furnish chromanes.11 Based on the aforementioned background, we assumed that photocatalytic systems can be applied to not only styrenes, but also other various dienophiles such as fulvenes. Moreover, only a few hetero-[4 + 2] cycloaddition reactions of fulvenes have so far been reported.3,12 Therefore, in order to expand the utility of the reaction of fulvenes, herein, we report thioxanthylium organic photoredox catalyzed [4 + 2] cycloaddition of pentafulvene under green light irradiation at room temperature (Scheme 1(b)).

Initially we screened the reaction of ortho-quinone methide (1a) with pentafulvene (2a) in the presence of thioxanthylium photoredox catalyst using various solvents at room temperature under green light irradiation (Table 1). When medium to non-polar solvents such as THF and toluene were used, the reaction did not afford any of the target product (3a) (entries 1 and 2). On the other hand, while polar solvents such as DMF and CH3CN were not suitable for the reaction (entries 3 and 4), reactions with CF3CH2OH, CH3NO2 and CH2Cl2 furnished the desired [4 + 2] cycloadduct (entries 5–7), whereby especially CH2Cl2 effectively increased the product yield to 98% (dr = 1.4[thin space (1/6-em)]:[thin space (1/6-em)]1). These solvents were often used for radical cation cycloadditions, and they would stabilize radical cation intermediates, suggesting that this reaction system may proceed through the radical cation pathway.13 Fortunately, single crystals of each diastereomer 3a, which are suitable for an X-ray diffraction analysis, could be obtained by recrystallization. Therefore, the relative stereochemistry of endo- and exo-chromanes 3a could be determined by single crystal X-ray diffraction analysis. From the blank experiments, the reaction effectively proceeds in the only case of using a photocatalyst, a light source, and air (entries 8–10). Finally, the photocycloaddition reactions using the representative organo-photocatalysts under otherwise identical reaction conditions were examined (see the ESI, page S5). As a result, miserable outcomes were obtained, and it was found that for the present photoredox catalysis the TXT catalyst specifically works well.

Table 1 Optimization of the reaction conditionsa

image file: d0ob01151g-u1.tif

Entry Solvent Yield (%) drb
a All reactions were carried out with 1a (0.250 mmol), 2a (0.125 mmol), catalyst (1.0 mol%) in solvent (2.0 mL) at room temperature for 4 h under irradiation with green light. b 1H NMR yield. The ratio is endo/exo. c No catalyst. d No light. e Under Ar. PMP: p-methoxyphenyl.
1 THF 0
2 Toluene 0
3 DMF 0
4 CH3CN 0
5 CF3CH2OH 15 1[thin space (1/6-em)]:[thin space (1/6-em)]1
6 CH3NO2 78 1[thin space (1/6-em)]:[thin space (1/6-em)]1
7 CH2Cl2 98 1.4[thin space (1/6-em)]:[thin space (1/6-em)]1
8c CH2Cl2 0
9d CH2Cl2 0
10e CH2Cl2 6 1.4[thin space (1/6-em)]:[thin space (1/6-em)]1

With the optimized conditions in hand, the scope of pentafulvenes was examined (Table 2). When diarylfulvenes bearing halogen functionalities such as chloro, bromo and fluoro groups were used as a dienophile, excellent yields of the desired products were obtained (3a–3c). 6,6-Diphenyl fulvene was well tolerated in the reaction (3d). Diarylfulvene bearing electron donating groups furnished the corresponding products in moderate to good yields (3e–3g). Next, we investigated fulvenes bearing aliphatic groups. When 6,6-dipropylfulvene was used, the reaction smoothly proceeded under the same reaction conditions leading to the formation of the desired cycloadduct in good yield (3h). Pentafulvenes bearing cyclopentyl, cyclohexyl and cycloheptyl groups were also good substrates for the formation of the desired cycloadducts (3i–3k). In addition, the stereoselectivity of the product was effectively improved when 5-cyclopentylidenecyclopenta-1,3-diene was used as a substrate. ortho-Quinone methide bearing dimethoxy groups furnished the desired product in high yield (3l). When the reaction was carried out with ortho-quinone methide bearing the p-tolyl group instead of PMP, the corresponding cycloadduct was also obtained in good yields (3m–3o). Finally, monosubstituted fulvene at the C-6 position was examined. When the photocycloaddition reaction of 6-phenylfulvene was carried out in EtOAc at rt for 24 h in the presence of TXT (5.0 mol%), the corresponding cycloadduct 3p was obtained in 44% yield. Unfortunately, cistrans isomers were also produced as a non-separable mixture along with low diastereoselectivity, giving a complex mixture of isomers that were hard to accurately analyze the structure and selectivity of them. These results indicate that the reaction can be applied to various 6,6-disubstituted pentafulvenes bearing both aromatic and aliphatic groups.

Table 2 [4 + 2] Cycloaddition reaction of ortho-quinone methides with pentafulvenes
a 8 h. b TXT (5.0 mol%) was used. c Reaction conditions: TXT (5.0 mol%), EtOAc, rt, 24 h.
image file: d0ob01151g-u2.tif

A plausible reaction mechanism for the reaction of pentafulvene with ortho-quinone methide is presented in Scheme 2. The photoredox catalyst (PC+*; E1/2 (C*/C) = + 1.76 V vs. SCE)11 which can be activated by irradiation with green light enables the oxidation of ortho-quinone methide 1a (Ep/2 = +1.19 V vs. SCE). Based on the Stern–Volmer experiments (Fig. 1), the single electron transfer from ortho-quinone methide 1a to the photoredox catalyst should occur. Since the reaction seems to require oxygen to promote the catalytic cycle (Table 1, entry 10), the reduced photocatalyst (PC˙) would be regenerated into the photoredox catalyst (PC+) via single-electron transfer to O2. To support the generation of O2˙, a control experiment in the presence of benzoquinone, which is known as a trap agent of O2˙, was carried out under the same reaction conditions (see the ESI, page S5). As expected, no reaction occurred, suggesting the important role of O2˙ in the catalytic cycle. Pentafulvene 2a could undergo an [4 + 2] cycloaddition with the resulting radical cation A providing radical cation B.14 To confirm the radical chain processes in the catalysis, we determined the quantum yield of the reaction (Φ = 0.15),15 which suggests that the reaction mainly proceeds via photocatalytic pathways. Thus, single electron transfer from the superoxide radical (O2˙) to radical cation intermediate B would occur to afford the cycloadduct 3a.

image file: d0ob01151g-s2.tif
Scheme 2 Proposed reaction mechanism. PMP: p-methoxyphenyl.

image file: d0ob01151g-f1.tif
Fig. 1 Stern–Volmer plots for ortho-quinone methide 1a (red line) and pentafulvene 2a (blue line).

In conclusion, we have developed organic photoredox catalyzed [4 + 2] cycloaddition of pentafulvenes under visible light irradiation. The various pentafulvenes reacted with ortho-quinone methides in the presence of thioxanthylium organic photoredox catalyst (TXT) under green light irradiation to furnish the corresponding [4 + 2] cycloadducts in good yields. Pentafulvenes bearing aromatic and aliphatic groups could be successfully applied to the reaction. Based on the quantum yield of the reaction (Φ = 0.15), the reaction mainly proceeds via photocatalytic pathways. We hope that the reaction system provides an efficient and sustainable method for the cycloaddition reaction of fulvenes.

Conflicts of interest

There are no conflicts to declare.


We thank Prof. Mahito Atobe of Yokohama National University for cyclic voltammetry measurements. Funding for this research was provided by Yokohama National University (kyodo kenkyu suishin program B) and Nakatsuji Foresight Foundation (Nakatsuji Foresight Foundation Research Grant).

Notes and references

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  15. The detailed reaction quantum yield is shown in the ESI..


Electronic supplementary information (ESI) available: Experimental details and supporting characterization. CCDC 1978128 and 1978129. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/d0ob01151g

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