Dearomative Cycloadditions Utilizing an Organic Photosensitizer: An Alternative to Iridium Catalysis

Letter

Dearomative Cycloadditions Utilizing an Organic Photosensitizer:

An Alternative to Iridium Catalysis

Alessa B. Rolka and Burkhard Koenig*

Cite This: https://dx.doi.org/10.1021/acs.orglett.0c01622

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sı Supporting Information

ABSTRACT: A highly eﬃcient, cheap, and organic alternative to the

commonly used iridium photosensitizer (Ir[dF(CF )ppy] (dtbpy))PF

(

[Ir−F]) is presented for visible-light energy transfer catalysis. The

organic dye 2CzPN surpasses [Ir−F] in selectivity while at the same

time being easily accessible in one step. The catalyst is recyclable and,

due to its uncharged nature, soluble in nonpolar solvents such as

toluene. Furthermore, the scope of molecular scaﬀolds that are

compatible substrates for visible-light catalyzed dearomative cyclo-

additions is expanded.

ver the past few years, energy transfer catalysis has

correspondingly high price that can make the cost of the

gained signiﬁcant attention and has emerged as a

catalyst prohibitively expensive. Furthermore, the presence of

transition metals in pharmaceuticals is highly regulated, and

use of an iridium photocatalyst in late stage steps is undesirable

in regards to industrial applications of these complexity

powerful synthetic tool. The reasons for this are manifold,

but of particular signiﬁcance is the methodology’s ability to

1a,2

rapidly generate high levels of molecular complexity. This is

elegantly highlighted by the works of Glorius et al. and You et

generating processes. Finally, the charged nature of the

8d,12

al. that demonstrate the generation of polycyclic cores by

intramolecular dearomative cycloadditions of naphthol

Scheme 1A) and indole derivatives (Scheme 1B). The

expensive catalyst complicates its recyclability

as well as

limits the catalyst’s solubility in many common nonpolar

10a

solvents.

(

This work aims to address these problems by avoiding

iridium and oﬀers a highly eﬀective, cheap, neutral, and organic

alternative for the widely utilized [Ir−F] photosensitizer.

resulting molecular scaﬀolds often map onto natural product

frameworks and are challenging to synthesize via other means.

One alternative to accessing these structures is the direct

excitation of substrates by UV light. However, this method

Based upon OLED research and reports about the

photochemical and photophysical properties of organic dyes,

we were drawn to 1,2-bis(carbazol-9-yl)-4,5-dicyanobenzene

often leads to unwanted side reactions and poor selectivity. By

utilizing visible light and suitable photosensitizers to indirectly

activate molecules, the need for UV light and/or other harsh

reaction conditions can be avoided.

(

2CzPN) (Scheme 1D) as a promising candidate for this

task. Speciﬁcally, the high triplet energy of this system at 60.6

kcal/mol (corresponding to T = 2.63 eV)

prior use of this catalyst for photochromism led us to explore

its performance in the dearomatization reactions of afore-

mentioned naphthol and indole derivatives.

14d

as well as the

Key to the success of such a mild visible-light catalyzed

process is the careful selection of a photosensitizer whose

triplet energy upon excitation with visible light and intersystem

crossing matches the targeted molecules. In the past,

photocatalysts (PCs) with suﬃciently high triplet energies

for challenging dearomative processes of the type depicted in

Scheme 1 have been largely limited to iridium-based systems

utilizing (Ir[dF(CF )ppy] (dtbpy))PF ([Ir−F]) (Scheme

The dearomative cycloaddition of naphthol 1a was used as a

model reaction to investigate the organic catalyst 2CzPN

(

Table 1). To begin, 1a and 5 mol % 2CzPN were irradiated

with 455 nm light in 1,4-dioxane at room temperature. Under

,4,7

C) and its derivatives.

This catalyst, which has also been

Received: May 12, 2020

shown to be eﬀective in other catalytic energy transfer

processes, beneﬁts from a long-lived excited triplet state and

,8,9

a high triplet energy.

Despite these desirable traits, iridium

catalysis has several signiﬁcant drawbacks that limit its

widespread use. On the economic side, iridium has the

distinction of being the rarest of the rare earth metals and has a

XXXX American Chemical Society

Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters

Letter

Scheme 1. Previously Reported Dearomatizations of

furnishes 2a. The ultimate ratio of 2a:3a is inﬂuenced by the

triplet energy of the catalyst and the rate of energy transfer. For

the complete mechanism, see Supporting Information 5.1.

Lowering the wavelength from 455 to 405 nm did not

inﬂuence selectivity (entry 2). After a brief screening of

solvents, it was found that chloroform was ideal, leading to

formation of 2a with a high selectivity of 16:1 (entry 4). We

were able to lower both the reaction time to 14 h and the

catalyst loading to 1 mol % without impacting the reaction

Naphthol Derivatives (A) and Indole Derivatives (B) and

Structure of the Organic Alternative 2CzPN (D) to ([Ir−

F]) (C)

(

entry 5). Further lowering the catalyst loading resulted in

worse selectivity (entries 6 and 7). Through the addition of a

Lewis acidic additive, the reaction could be directed toward the

selective formation of 3a (entry 8). However, this observed

eﬀect proved not to be general to other substrates.

Therefore, 1 mol % 2CzPN in chloroform irradiated at 455

nm for 14 h were chosen as the optimized conditions, giving 2a

in 94% isolated yield as a single diastereomer and with a 2a:3a

ratio of 16:1 (entry 5). In comparison, the optimized

conditions of Glorius utilizing 1 mol % [Ir−F] (1,4-dioxane;

.04 M; 18 h; 455 nm) achieved a ratio of 6:1 with a yield of

6%, showing that 2CzPN is able to improve the selectivity of

the reaction. Control experiments utilizing the organic

photosensitizer thioxanthone (TX), which absorbs at lower

wavelengths (entry 9), and irradiation without any catalyst

entry 10) resulted in no conversion, proving the necessity of

(

CzPN.

With optimized conditions in hand, tailored to the organic

dye 2CzPN, the substrate scope was investigated to better

compare 2CzPN with [Ir−F]. To do so, ﬁve substrates were

selected with diﬀerent electronic and steric properties at the

Table 1. Optimization Studies for the Organocatalytic

Dearomatization of Naphthol 1a

activating group R as well as at the naphthyl ring R (Scheme

). For ease of comparison, the already reported yields with 1

mol % of the iridium catalyst [Ir−F] are included in brackets.

Based upon these yields, it is evident that 2CzPN is able to

catalyze the dearomatization of naphthols in a highly eﬃcient

fashion that is comparable or superior to [Ir−F].

Scheme 2. Substrate Scope of Naphthols

entry

time (h)

solvent

ratio 2a:3a

2CzPN

1,4-dioxane

PhMe

CHCl₃

1.2:1

1.8:1

16:1

16 (94%) :1

3:1

0.5

0.2

1:1.6

1:20

N/A

1,4-dioxane

N/A

Reactions were run at a 0.2 mmol scale. Determined by H-crude

NMR ratio. Entries with a ratio showed no other proton signals and

full conversion with isolation of a mixture of 2a and 3a in near

quantitative yield. 0.04 M λ = 405 nm light was used instead of

max

λ_m_a_x= 455 nm. 94% isolated yield conﬁrms the use of the NMR ratio

is a reliable indication of yield. 0.1 equiv of Sc(OTf)₃. Not

applicable. No conversion of starting material.

these conditions, we were pleased to see full conversion of the

starting material but with poor selectivity, as measured by the

ratio of 2a:3a (entry 1). This reaction proceeds via two

sequential triplet energy excitation processes. First, excitation

of 1a results in a [2 + 2] cycloaddition to form 3a, while

subsequent excitation of 3a followed by rearrangement

Yields are isolated yields. Yields in brackets are isolated yields of the

originally reported reactions with 1 mol % [Ir−F]. Reactions were

run on a 0.2 mmol scale at 0.1 M. Two mol % 2CzPN, 42 h.

Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters

Letter

Reactions with 2CzPN readily scale and could be performed

equally eﬀectively in multiple gram quantities with only 1 mol

To demonstrate the eﬃciency of our conditions, a scope of

indoles was investigated (Scheme 4). Just as with [Ir−F],

catalyst (Scheme 3A). We were also able to take advantage

Scheme 4. Substrate Scope of Indoles

Scheme 3. Scale-up of the Reaction with Recycling of

Catalyst (A) and Subsequent Reaction with Recycled

Catalyst (B)

Yields are isolated yields. Yields in brackets are isolated yields of the

originally reported reactions with [Ir−F]. Reactions run on a 0.05

mmol scale at 0.0125 M. Nineteen hours. Originally reported

of 2CzPN’s neutral charge to readily recycle the catalyst by

means of column chromatography in 88% yield, and the

recycled catalyst shows no change in activity upon reuse

reaction with 8 mol % [Ir−F].

substitution at the 2-position was well-tolerated (5a, 5d, 5e,

and 5f), as was the use of a more sterically hindered 1,1-

disubstituted alkene (5e). The reaction proceeds utilizing

substrates bearing the free indole N−H or an N-acetyl group,

with the highest yields observed with the acetylated substrates

(

Scheme 3B).

Motivated by the positive results, we explored the

compatibility of 2CzPN with the dearomatization of indole

derivates. This class of compounds represents a more

challenging test due to their increased triplet energy. While

the optimized conditions for naphthol dearomatization

resulted in very poor conversion of 4a, it was found that

utilization of toluene as solvent allowed the reaction to proceed

in high yields (Supporting Information 3.1). It is thought that

the use of the less polar toluene solvent inhibits electron

transfer from the indole substrate to the excited photocatalyst

that preferentially occurs over triplet sensitization in polar

solvents.

(

5b, 5c). These nearly quantitative yields are thought to be

attributed to the electron-withdrawing nature of the acetyl

group, which lowers the triplet energy of the substrates while at

the same time increasing their oxidation potential to limit

redox events with the catalyst. Using an N-acetylated substrate,

we were especially delighted to ﬁnd that high levels of

reactivity could be obtained without the bulky diester linker

which facilitates ring closure via the Thorpe−Ingold−Eﬀect

(

5c). Once again, for all substrates tested, the organic

The ability to utilize nonpolar solvents with 2CzPN

highlights another advantage of this organic photosensitizer

over the [Ir−F] system, which is only minimally soluble in

photosensitizer proved to be comparable or superior to [Ir−F]

at equivalent catalyst loadings.

10a

Having established that the organic catalyst is an eﬀective

replacement for [Ir−F], we sought to test the organic

photocatalyst on more challenging cases containing allene

cycloaddition partners that have the potential to form highly

strained methylencyclobutane products. This class of

substrates is particularly intriguing due to the presence of an

oleﬁn in the product that can serve as a functional group

handle for further structural elaboration.

toluene (100−1000 ppm) and other nonpolar solvents due

to its charged nature (Table 2). A comparison of the maximum

solubility in a range of diﬀerent solvents revealed a more than

00 times higher solubility of 2CzPN in toluene. It is

noteworthy that the organic catalyst retains high solubility in

polar solvents.

Table 2. Maximum Solubilities of [Ir−F] and 2CzPN in

Whereas the direct UV excitation of aromatic rings followed

by their trapping with allenes has been reported, little has been

done within the ﬁeld of visible-light triplet-sensitized

Common Organic Solvents

solvent

[Ir−F]

2CzPN

₇_.₀_×₁₀−

−2

−4

−2

chemistry. A rare example of triplet-sensitized chemistry

involving allenes is the work of Arai and Ohkuma, where 50

mol % of 3′,4′-dimethoxyacetophenone sensitizer was required

PhMe

,4-dioxane

DCM

1.3 × 10

1.6 × 10

8.3 × 10

9.2 × 10

1.6 × 10

−4

2.2 × 10

5.6 × 10

7.0 × 10

1.6 × 10

−

18d,e

in the dearomative cycloaddition of indole derivatives.

methyl tert-butyl ether

However, in addition to the high catalyst loading, a high-

pressure mercury lamp was necessary (Supporting Information

5.2 ). Inspired by their work, we synthesized allene 6 to

investigate whether 2CzPN can overcome these signiﬁcant

DMSO

Maximum solubility given as concentration (Molar). As reported by

10a c

the group of Weaver.

See Supporting Information 3.4.

Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters

The Supporting Information is available free of charge at

Letter

limitations. Applying the same optimized conditions as for 4b,

we were pleased to see full conversion of 6 to the dearomatized

products 7 and 8 in high yield and with a ratio of 5.3:1

or outperformed the iridium catalyst in dearomative cyclo-

additions. The organic dye was furthermore applied in the

previously not reported visible-light induced photocycloaddi-

tion of naphthol and indole allenes, giving rise to complex

polycyclic frameworks. The catalyst itself is readily synthesized

in gram quantities in one step from cheap and commercial

starting materials and is bench-stable. Its uncharged nature

allows for solubility in a broad range of polar and nonpolar

solvents and for easy recovery and reuse of the catalyst via

column chromatography. Finally, reactions performed with

(Scheme 5).

Scheme 5. Formation of Methylencyclobutane Products

from Allene Substituted Indole 6

CzPN have proven to be readily amenable to large, multigram

scales. We believe that the presented work will facilitate a

broader use of visible-light mediated triplet-sensitized reactions

through the identiﬁcation of a cheap organic replacement for

the previously utilized iridium catalyst.

Isolated yield. Reaction has previously not been reported with [Ir−

ASSOCIATED CONTENT

sı Supporting Information

■

F]. The reaction was run on a 0.05 mmol scale at 0.0125 M.

https://pubs.acs.org/doi/10.1021/acs.orglett.0c01622.

We next explored the previously unreported visible-light

photochemistry of naphthol allene derivatives. When treating

naphthol ketone 9a with slightly modiﬁed conditions described

above for the dearomatization of naphthols, we were surprised

to obtain the aromatic cyclic acetal 10a as the main product in

Experimental details, characterization data, and spectra

(PDF )

Accession Codes

1% yield. The product was con ﬁ rmed by a single crystal X-ray

CCDC 1998653 −1998654 , 1998663 , and 2000974 contain the

supplementary crystallographic data for this paper. These data

can be obtained free of charge via www.ccdc.cam.ac.uk/

data_request/cif , or by emailing data_request@ccdc.cam.ac.

uk , or by contacting The Cambridge Crystallographic Data

Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44

analysis (Supporting Information 7.3) and supported by the

literature-known UV-photochemistry of allenyl salicylaldehy-

8b,c

des.

We believe that 10a is formed via dearomatized

intermediate 12 that upon 1,3-allylic transposition yields

product 10a. As a minor side product under these conditions,

dihydrofuran 11a was also obtained via a 1,4-cycloaddition. By

exchanging the acetyl group (9a) with a phenyl ester (9b),

only the dearomatized product 11b was observed in 81% yield

1223 336033.

AUTHOR INFORMATION

Corresponding Author

■

(Scheme 6).

Burkhard Koenig − Institute of Organic Chemistry, University

of Regensburg, 93053 Regensburg, Germany; orcid.org/

Scheme 6. Dearomative Cycloaddition of Allene-Substituted

Naphthol Derivatives

000-0002-6131-4850 ; Email: burkhard.koenig@

chemie.uni-regensburg.de

Author

Alessa B. Rolka − Institute of Organic Chemistry, University of

Regensburg, 93053 Regensburg, Germany

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.orglett.0c01622

Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

This work was supported by the German Science Foundation

DFG, KO 1537/18-1). We would like to thank the Fonds der

■

(

Chemischen Industrie (FCI) and the Studienstiftung des

deutschen Volkes for ﬁnancial support. Furthermore, we would

like to thank Anamitra Chatterjee (University of Regensburg)

for the synthesis of compound 4d. We are also grateful to

Birgit Hischa (University of Regensburg) for X-ray crystallo-

graphic analysis.

Yields are isolated yields. Reaction has previously not been reported

with [Ir−F]. Reactions were run on a 0.1 mmol scale at 0.05 M.

In conclusion, we have shown 2CzPN to be a highly

eﬀective and general triplet sensitizer that can serve as an

eﬀective replacement for the expensive [Ir−F] catalyst that has

until now been the preferred sensitizer to activate substrates

with high triplet energies via visible light. Through a series of

direct comparisons, the organic catalyst consistently matched

REFERENCES

■

(1) For a recent review on energy transfer mediated reactions, see:

(a) Zhou, Q.-Q.; Zou, Y.-Q.; Lu, L.-Q.; Xiao, W.-J. Visible-Light-

Induced Organic Photochemical Reactions through Energy-Transfer

Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters

L.; Glorius, F. Energy transfer catalysis mediated by visible light:

Letter

Pathways. Angew. Chem., Int. Ed. 2019, 58, 1586−1604. For a tutorial

review covering the principles and applications of energy transfer

catalysis, see: (b) Strieth-Kalthoff, F.; James, M. J.; Teders, M.; Pitzer,

principles, applications, directions. Chem. Soc. Rev. 2018, 47, 7190−

2020, 142, 3094−3103. Recently, an example of gadolinium

photocatalysis was published: (b) Ma, J.; Schafers, F.; Daniliuc, C.;

Bergander, K.; Strassert, C. A.; Glorius, F. Gadolinium Photocatalysis:

Dearomative [2 + 2] Cycloaddition/Ring-Expansion Sequence with

Indoles. Angew. Chem., Int. Ed. 2020, 59, 2−9. For an example of

rhodium-catalyzed deraomatization of benzofuranes and benzothio-

phenes, see: (c) Hu, N.; Jung, H.; Zheng, Y.; Lee, J.; Zhang, L.; Ullah,

Z.; Xie, X.; Harms, K.; Baik, M.-H.; Meggers, E. Catalytic Asymmetric

Dearomatization by Visible-Light-Activated [2 + 2] Photocycloaddi-

tion. Angew. Chem., Int. Ed. 2018, 57, 6242−6246. For an example of

dearomatization of molecules with a lower degree of aromaticity

202.

2) For selected reviews, see: (a) Sarkar, D.; Bera, N.; Ghosh, S. [2 +

] Photochemical Cycloaddition in Organic Synthesis. Eur. J. Org.

259 −1273. (c) Roche, S. P.; Porco, J. A. Dearomatization Strategies

Chem. 2020 , 2020 , 1310 −1326. (b) Okumura, M.; Sarlah, D. Visible-

Light-Induced Dearomatizations. Eur. J. Org. Chem. 2020 , 2020 ,

in the Synthesis of Complex Natural Products. Angew. Chem., Int. Ed.

011, 50, 4068−4093.

3) James, M. J.; Schwarz, J. L.; Strieth-Kalthoff, F.; Wibbeling, B.;

utilizing an organic sensitizer, see: (d) Troster, A.; Alonso, R.; Bauer,

(

A.; Bach, T. Enantioselective Intermolecular [2 + 2] Photo-

cycloaddition Reactions of 2(1 H )-Quinolones Induced by Visible

Light Irradiation. J. Am. Chem. Soc. 2016, 138, 7808−7811.

Glorius, F. Dearomative Cascade Photocatalysis: Divergent Synthesis

through Catalyst Selective Energy Transfer. J. Am. Chem. Soc. 2018,

(8) For selected examples utilizing [Ir-F] as an energy transfer

catalyst, see: (a) Becker, M. R.; Richardson, A. D.; Schindler, C. S.

4) Zhu, M.; Zheng, C.; Zhang, X.; You, S.-L. Synthesis of

40, 8624−8628.

Functionalized azetidines via visible light-enabled aza Paterno-Buchi

Cyclobutane-Fused Angular Tetracyclic Spiroindolines via Visible-

Light-Promoted Intramolecular Dearomatization of Indole Deriva-

tives. J. Am. Chem. Soc. 2019, 141, 2636−2644.

reactions. Nat. Commun. 2019, 10, 5095. (b) Soni, V. K.; Lee, S.;

Kang, J.; Moon, Y. K.; Hwang, H. S.; You, Y.; Cho, E. J. Reactivity

Tuning for Radical −Radical Cross-Coupling via Selective Photo-

catalytic Energy Transfer: Access to Amine Building Blocks. ACS

Catal. 2019, 9, 10454−10463. (c) Patra, T.; Mukherjee, S.; Ma, J.;

Strieth-Kalthoff, F.; Glorius, F. Visible-Light-Photosensitized Aryl and

Alkyl Decarboxylative Functionalization Reactions. Angew. Chem., Int.

Ed. 2019, 58, 10514−10520. (d) Ma, J.; Strieth-Kalthoff, F.; Dalton,

T.; Freitag, M.; Schwarz, J. L.; Bergander, K.; Daniliuc, C.; Glorius, F.

Direct Dearomatization of Pyridines via an Energy-Transfer-Catalyzed

Intramolecular [4 + 2] Cycloaddition. Chem. 2019 , 5 , 2854 −2864.

(5) For a review covering natural cyclobutane-containing alkaloids,

see (a) Dembitsky, V. M. Bioactive cyclobutane-containing alkaloids.

J. Nat. Med. 2007, 62, 1−33. For selected reviews featuring the

alternative synthesis of complex molecular scaffolds, see: (b) Zheng,

C.; You, S.-L. Catalytic asymmetric dearomatization (CADA)

reaction-enabled total synthesis of indole-based natural products.

Nat. Prod. Rep. 2019 , 36 , 1589 −1605. (c) Sebren, L. J.; Devery, J. J.;

Stephenson, C. R. J. Catalytic Radical Domino Reactions in Organic

Synthesis. ACS Catal. 2014 , 4 , 703 −716. (d) Pape, A. R.; Kaliappan,

(e) Chatterjee, A.; Ko

and Heteroarenes by Sensitized Electron Transfer. Angew. Chem., Int.

Ed. 2019, 58, 14289−14294. (f) Teders, M.; Henkel, C.; Anhauser,

L.; Strieth-Kalthoff, F.; Gomez-Suarez, A.; Kleinmans, R.; Kahnt, A.;

nig, B. Birch-Type Photoreduction of Arenes

K. P.; Kundig, E. P. Transition-Metal-Mediated Dearomatization

Reactions. Chem. Rev. 2000, 100, 2917−2940. For selected papers

featuring natural products related to the scaffolds accessed by energy

transfer catalysis, see: (e) Hara, H.; Maruyama, N.; Yamashita, S.;

Hayashi, Y.; Lee, K. H.; Bastow, K. F.; Marumoto, C. R.; Imakura, Y.

Elecanacin, a Novel New Naphthoquinone from the Bulb of

Eleutherine americana. Chem. Pharm. Bull. 1997, 45, 1714 −1716.

Rentmeister, A.; Guldi, D.; Glorius, F. The energy-transfer-enabled

biocompatible disulfide-ene reaction. Nat. Chem. 2018 , 10 , 981 −988.

(g) Sun, Z.; Kumagai, N.; Shibasaki, M. Photocatalytic α -Acylation of

Ethers. Org. Lett. 2017, 19 , 3727 −3730. (h) Bagal, D. B.; Park, S.-W.;

Song, H.-J.; Chang, S. Visible light sensitization of benzoyl azides:

cascade cyclization toward oxindoles via a non-nitrene pathway.

Chem. Commun. 2017, 53, 8798−8801. (i) Pagire, S. K.; Hossain, A.;

Traub, L.; Kerres, S.; Reiser, O. Photosensitised regioselective [2 +

2]-cycloaddition of cinnamates and related alkenes. Chem. Commun.

2017, 53, 12072−12075. (j) Zhao, J.; Brosmer, J. L.; Tang, Q.; Yang,

Z.; Houk, K. N.; Diaconescu, P. L.; Kwon, O. Intramolecular Crossed

[2 + 2] Photocycloaddition through Visible Light-Induced Energy

Transfer. J. Am. Chem. Soc. 2017 , 139 , 9807 −9810. (k) Heitz, D. R.;

Tellis, J. C.; Molander, G. A. Photochemical Nickel-Catalyzed C-H

Arylation: Synthetic Scope and Mechanistic Investigations. J. Am.

Chem. Soc. 2016, 138, 12715−12718. (l) Xia, X.-D.; Ren, Y.-L.; Chen,

J.-R.; Yu, X.-L.; Lu, L.-Q.; Zou, Y.-Q.; Wan, J.; Xiao, W.-J.

Phototandem Catalysis: Efficient synthesis of 3-Ester-3-hydroxy-2-

oxindoles by a Visible Light-Induced Cyclization of Diazoamides

through an Aerobic Oxidation Sequence. Chem. - Asian J. 2015 , 10 ,

124 −128. (m) Hurtley, A. E.; Lu, Z.; Yoon, T. P. [2 + 2]

Cycloaddition of 1,3-Dienes by Visible Light Photocatalysis. Angew.

Chem., Int. Ed. 2014 , 53 , 8991 −8994. (n) Lu, Z.; Yoon, T. P. Visible

Light Photocatalysis of [2 + 2] Styrene Cycloadditions by Energy

Transfer. Angew. Chem., Int. Ed. 2012, 51, 10329−10332. For

selected examples utilizing other iridium-based catalysts for energy

transfer catalysis, see: (o) Nicastri, M. C.; Lehnherr, D.; Lam, Y.-H.;

DiRocco, D. A.; Rovis, T. Synthesis of Sterically Hindered Primary

Amines by Concurrent Tandem Photoredox Catalysis. J. Am. Chem.

(f) Jamart-Gregoire, B.; Fort, Y.; Zouaoui, M. A.; Caubere, P. Efficient

́ ̀

Synthesis of New Benzocyclobutenic Phenethylamines. Synth.

Commun. 1993, 23, 885−894. (g) Carre, M. C.; Youlassani, A.;

Caubere, P.; Saint-Aubin-Floch, A.; Blanc, M.; Advenier, C. Synthesis

of a Novel Series of (Aryloxy)propanolamines: New Selective Beta 2-

blocking Agents. J. Med. Chem. 1984, 27, 792−799.

(

6) For selected reviews, see: (a) Poplata, S.; Tro

Bach, T. Recent Advances in the Synthesis of Cyclobutanes by Olefin

2 + 2] Photocycloaddition Reactions. Chem. Rev. 2016 , 116 , 9748 −

815. (b) Yoon, T. P.; Ischay, M. A.; Du, J. Visible light photocatalysis

as a greener approach to photochemical synthesis. Nat. Chem. 2010 ,

, 527 −532. (c) Hoffmann, N. Photochemical Cycloaddition between

Benzene Derivatives and Alkenes. Synthesis 2004 , 4 , 481 −495.

d) Bach, T. Stereoselective Intermolecular [2 + 2]-Photocycloaddi-

tion Reactions and Their Application in Synthesis. Synthesis 1998,

ster, A.; Zou, Y.-Q.;

[

Photochemical Cycloadditions. Org. React. 1993 , 44 , 297. (g) Baus-

998, 683−705. (e) Fleming, S. A.; Bradford, C. L.; Gao, J. J.

Regioselective and Stereoselective [2 + 2] Photocycloadditions. In

Organic Photochemistry, Molecular and Supramolecular Photochemistry;

Ramamurthy, V., Schanze, K. S., Eds.; Dekker: New York, 1997; Vol.

, p 187. (f) Crimmins, M. T.; Reinhold, T. L. Enone Olefin [2 + 2]

laugh, P. G. Photochemical Cycloaddition Reactions of Enones to

Alkenes; Synthetic Applications. Synthesis 1970, 1970, 287−300. For

an example of a UV-light induced dearomatization of naphthol

derivatives, see: (h) Wagner, P. J. Photoinduced Ortho [2 + 2]

Cycloaddition of Double Bonds to Triplet Benzenes. Acc. Chem. Res.

Soc. 2020, 142, 987−998. (p) Hormann, F. M.; Chung, T. S.;

(

001, 34, 1−8.

Rodriguez, E.; Jakob, M.; Bach, T. Evidence for Triplet Sensitization

in the Visible-Light-Induced [2 + 2] Photocycloaddition of

Eniminium Ions. Angew. Chem., Int. Ed. 2018, 57, 827−831.

(q) Zhu, S.; Pathigoolla, A.; Lowe, G.; Walsh, D. A.; Cooper, M.;

Lewis, W.; Lam, H. W. Sulfonylative and Azidosulfonylative

Cyclizations by Visible-Light-Photosensitization of Sulfonyl Azides

7) (a) Oderinde, M. S.; Mao, E.; Ramirez, A.; Pawluczyk, J.; Jorge,

C.; Cornelius, L. A. M.; Kempson, J.; Vetrichelvan, M.; Pitchai, M.;

Gupta, A.; Gupta, A. K.; Meanwell, N. A.; Mathur, A.; Dhar, T. G. M.

Synthesis of Cyclobutane-Fused Tetracyclic Scaffolds via Visible-Light

Photocatalysis for Building Molecular Complexity. J. Am. Chem. Soc.

Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters

Kidd, J. B.; Jung, H.; Guzei, I. A.; Baik, M.-H.; Yoon, T. P.

Letter

in THF. Chem. - Eur. J. 2017, 23, 17598−17604. (r) Skubi, K. L.;

Enantioselective Excited-State Photoreactions Controlled by a Chiral

Hydrogen-Bonding Iridium Sensitizer. J. Am. Chem. Soc. 2017, 139,

Theory Comput. 2013, 9, 3872−3877. For a recent example of an

organic sensitizer with a triplet energy lower than that of 2CzPN used

in a not-dearomative process, see: (e) Chen, D.-F.; Chrisman, C. H.;

Miyake, G. M. Bromine Radical Catalysis by Energy Transfer

Photosensitization. ACS Catal. 2020, 10, 2609−2614.

(15) Zhang, Z.; Zhang, J.; Wu, B.; Li, X.; Chen, Y.; Huang, J.; Zhu,

L.; Tian, H. Diarylethenes with a Narrow Singlet-Triplet Energy Gap

Sensitizer: a Simple Strategy for Efficient Visible-Light Photo-

chromism. Adv. Opt. Mater. 2018, 6, 1700847.

17186−17192. (s) Lei, T.; Zhou, C.; Huang, M.-Y.; Zhao, L.-M.;

Yang, B.; Ye, C.; Xiao, H.; Meng, Q.-Y.; Ramamurthy, V.; Tung, C.-

H.; Wu, L.-Z. General and Efficient Intermolecular [2 + 2]

Photodimerization of Chalcones and Cinnamic Acid Derivatives in

Solution through Visible-Light Catalysis. Angew. Chem., Int. Ed. 2017,

6, 15407−15410. (t) Scholz, S. O.; Farney, E. P.; Kim, S.; Bates, D.

(16) Iyer, A.; Clay, A.; Jockusch, S.; Sivaguru, J. Evaluating

brominated thioxanthones as organo-photocatalysts. J. Phys. Org.

Chem. 2017, 30, No. e3738.

(17) Beesley, R. M.; Ingold, C. K.; Thorpe, J. F. The formation and

stability of spiro-compounds. J. Chem. Soc., Trans. 1915, 107, 1080−

1106.

(18) For a review about photochemical cycloadditions of allenes,

see: (a) Alcaide, B.; Almendros, P.; Aragoncillo, C. Exploiting [2 + 2]

cycloaddition chemistry: achievements with allenes. Chem. Soc. Rev.

M.; Yoon, T. P. Spin-Selective Generation of Triplet Nitrenes: Olefin

Aziridination through Visible-Light Photosensitization of Azidofor-

mates. Angew. Chem., Int. Ed. 2016, 55, 2239−2242.

(

9) Triplet lifetime: τ = 2300 ns; E = 60.1 kcal/mol, see: (a) Day, J.

I.; Teegardin, K.; Weaver, J.; Chan, J. Advances in Photocatalysis: A

Microreview of Visible Light Mediated Ruthenium and Iridium

Catalyzed Organic Transformations. Org. Process Res. Dev. 2016, 20,

1156−1163. (b) Singh, A.; Teegardin, K.; Kelly, M.; Prasad, K. S.;

2010, 39, 783−816. For UV-light mediated dearomative cyclo-

Krishnan, S.; Weaver, J. D. Facile synthesis and complete character-

ization of homoleptic and heteroleptic cyclometalated Iridium(III)

complexes for photocatalysis. J. Organomet. Chem. 2015 , 776 , 51 −59.

addition of allenes to saliyclaldehydes, see: (b) Streit, U.; Birbaum, F.;

Quattropani, A.; Bochet, C. G. Photocycloaddition of Arenes and

Allenes. J. Org. Chem. 2013 , 78 , 6890 −6910. (c) Birbaum, F.; Neels,

A.; Bochet, C. G. Photochemistry of Allenyl Salicylaldehydes. Org.

Lett. 2008, 10, 3175−3178. For triplet sensitized dearomative

cycloaddition of allenes to indoles, see: (d) Arai, N.; Ohkuma, T.

Stereoselective preparation of methylenecyclobutane-fused angular

tetracyclic spiroindolines via photosensitized intramolecular [2 + 2]

cycloaddition with allene. Tetrahedron Lett. 2019 , 60 , 151252.

Photoredox Catalysis with Transition Metal Complexes: Applications

in Organic Synthesis. Chem. Rev. 2013, 113, 5322−5363. (d) Lowry,

M. S.; Hudson, W. R.; Pascal, R. A.; Bernhard, S. Accelerated

Luminophore Discovery through Combinatorial Synthesis. J. Am.

Chem. Soc. 2004, 126, 14129−14135.

(

10) (a) Jespersen, D.; Keen, B.; Day, J. I.; Singh, A.; Briles, J.;

e) Arai, N.; Ohkuma, T. Stereoselective Construction of Methyl-

Mullins, D.; Weaver, J. D. Solubility of Iridium and Ruthenium

Organometallic Photoredox Catalysts. Org. Process Res. Dev. 2019 , 23 ,

enecyclobutane-Fused Indolines through Photosensitized [2 + 2]

Cycloaddition of Allene-Tethered Indole Derivatives. Org. Lett. 2019,

087 −1095. (b) Hans Wedepohl, K. The composition of the

continental crust. Geochim. Cosmochim. Acta 1995, 59, 1217−1232.

11) (a) Hermann, J. C.; Chen, Y.; Wartchow, C.; Menke, J.; Gao,

1, 1506−1510. For a recent example of visible-light triplet sensitized

allene chemistry, see: (f) Li, X.; Jandl, C.; Bach, T. Visible-Light-

Mediated Enantioselective Photoreactions of 3-Alkylquinolones with

(

L.; Gleason, S. K.; Haynes, N.-E.; Scott, N.; Petersen, A.; Gabriel, S.;

Vu, B.; George, K. M.; Narayanan, A.; Li, S. H.; Qian, H.; Beatini, N.;

Niu, L.; Gan, Q.-F. Metal Impurities Cause False Positives in High-

Throughput Screening Campaigns. ACS Med. Chem. Lett. 2013, 4,

4-O -Tethered Alkenes and Allenes. Org. Lett. 2020, 22, 3618−3622.

97−200. (b) Abernethy, D. R.; Destefano, A. J.; Cecil, T. L.; Zaidi,

K.; Williams, R. L. Metal Impurities in Food and Drugs. Pharm. Res.

010, 27, 750−755.

12) Recently, a few approaches focused on immobilizing the

(

iridium catalyst on polymers to recycle the catalyst and make iridium

catalysis more sustainable, underlining the need for alternatives:

(a) Xu, Z.-Y.; Luo, Y.; Zhang, D.-W.; Wang, H.; Sun, X.-W.; Li, Z.-T.

Iridium complex-linked porous organic polymers for recyclable,

broad-scope photocatalysis of organic transformations. Green Chem.

020, 22, 136−143. (b) Zhi, P.; Xi, Z.-W.; Wang, D.-Y.; Wang, W.;

Liang, X.-Z.; Tao, F.-F.; Shen, R.-P.; Shen, Y.-M. Vilsmeier −Haack

reagent mediated synthetic transformations with an immobilized

iridium complex photoredox catalyst. New J. Chem. 2019, 43, 709−

717.

(13) Uoyama, H.; Goushi, K.; Shizu, K.; Nomura, H.; Adachi, C.

Highly efficient organic light-emitting diodes from delayed

fluorescence. Nature 2012, 492, 234−238.

Liu, Q.; Yang, S.; Shi, W.; Li, S.; Huang, J.; Zhang, J. Donor-Acceptor

14) For a summary of selected properties, see Supporting

Information 2. For key references, see: (a) Lu, J.; Pattengale, B.;

Fluorophores for Energy-Transfer-Mediated Photocatalysis. J. Am.

Chem. Soc. 2018 , 140 , 13719 −13725. (b) Luo, J.; Zhang, J. Donor −

Acceptor Fluorophores for Visible-Light-Promoted Organic Syn-

thesis: Photoredox/Ni Dual Catalytic C(sp )−C(sp ) Cross-Cou-

pling. ACS Catal. 2016 , 6 , 873 −87. (c) Lee, K.; Kim, D. Local-

Excitation versus Charge-Transfer Characters in the Triplet State:

Theoretical Insight into the Singlet −Triplet Energy Differences of

Carbazolyl-Phthalonitrile-Based Thermally Activated Delayed Fluo-

rescence Materials. J. Phys. Chem. C 2016, 120, 28330−28336.

(d) Huang, S.; Zhang, Q.; Shiota, Y.; Nakagawa, T.; Kuwabara, K.;

Yoshizawa, K.; Adachi, C. Computational Prediction for Singlet- and

Triplet-Transition Energies of Charge-Transfer Compounds. J. Chem.