Metal and acid-free visible light-mediated Friedel-Crafts alkylation reactions of indole with anilines

Article abstract of DOI:10.1016/j.tetlet.2018.06.046

Metal and acid-free visible light-induced Friedel-Crafts C3-alkylation reactions of indole derivatives were developed using N,N-dimethylanilines as the carbon source. A cheap and readily available organic dye, Rose Bengal, was applied as the photocatalyst. This environmentally friendly transformation afforded C3-alkylated indoles in moderate to good yields under mild conditions.

Full text of DOI:10.1016/j.tetlet.2018.06.046

Accepted Manuscript
Metal and Acid-Free Visible Light-Mediated Friedel-Crafts Alkylation Reac-
tions of Indole with Anilines
Xiao-Qiang Dai, Wen-Xiu Xu, Ya-Long Wen, Xing-Hai Liu, Jian-Quan Weng
PII:
S0040-4039(18)30812-8
https://doi.org/10.1016/j.tetlet.2018.06.046
TETL 50084
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
13 May 2018
14 June 2018
19 June 2018
Please cite this article as: Dai, X-Q., Xu, W-X., Wen, Y-L., Liu, X-H., Weng, J-Q., Metal and Acid-Free Visible
Light-Mediated Friedel-Crafts Alkylation Reactions of Indole with Anilines, Tetrahedron Letters (2018), doi:
https://doi.org/10.1016/j.tetlet.2018.06.046
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Tetrahedron Letters
Metal and Acid-Free Visible Light-Mediated Friedel-Crafts Alkylation Reactions of
Indole with Anilines
Xiao-Qiang Dai, Wen-Xiu Xu, Ya-Long Wen, Xing-Hai Liu, and Jian-Quan Weng*
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China
ARTICLE INFO
ABSTRACT
Metal and acid-free visible light-induced Friedel-Crafts C3-alkylation reactions of indole derivatives
were developed using N,N-dimethylanilines as the carbon source. A cheap and readily available organic
dye, Rose Bengal, was applied as the photocatalyst. This environmentally friendly transformation
afforded C3-alkylated indoles in moderate to good yields under mild conditions.
Article history:
Received
Received in revised form
Accepted
Available online
2018 Elsevier Ltd. All rights reserved.
Keywords:
Friedel-Crafts alkylation
Indoles
Rose Bengal
N,N-dimethylanilines
Introduction
In recent years, visible light photoredox catalysis applied in
organic transformations has received considerable attention
because mild and environmentally friendly conditions are
normally achieved by utilizing such catalysts.1a-d Ruthenium and
iridium polypyridyl complexes are commonly employed as
visible light photocatalysts with a relatively long excited state
and favorable redox potentials.2-5 However, such compounds are
expensive, rare, and potentially toxic. In contrast,
environmentally benign and cheap organic dyes have been used
as substitutes of those transition metal complexes in photoredox
catalysis.6,7 In this context, Eosin B,8a-b Eosin Y,9a-h Rhodamine
B,10a-c Methylene blue,11a-c and Rose Bengal12a-j have been
reported as photocatalysts to promote photoredox reactions. For
examples, Eosin Y was reported to promote direct C-H arylation
of heteroarenes with diazonium salts13 and vinylation of
tetrahydrofurans with alkynes;14 Scaiano group11a reported an
aryl boronic acid oxidation by Methylene blue catalysis.
Friedel-Crafts alkylation reaction represents one of the
most significant approaches to synthesize alkylated aromatic
compounds.15a-b As popular aromatic substrates, indoles and
their analogues have attracted considerable attention,16a-d and
many efficient reactions have been developed to synthesize
indole derivatives.17a-c Friedel-Crafts alkylation of indoles were
recently realized through acid mediated,18a-b,19a-g transition metal-
catalyzed18a-b,20a-j and visible light-mediated alkylation
reactions.21a-c Among them, Stephenson group21a reported Ru-
catalyzed visible light-mediated C2-alkylation of indoles with
malonates (Scheme 1, (1)). In 2013, Wu group21b reported a
visible light-mediated C3-alkylation of indoles by combining
Eosin Y and graphene-supported RuO2 nanocomposite as the
photosensitizer (Scheme 1, (2)). To date, in those documented
examples for visible light-mediated alkylation of indoles, either
transition metal salt or acid was necessary to promote the
reactions. Herein, we report a metal and acid-free visible light-
mediated alkylation of indoles with tertiary amines by using
Rose Bengal as the photocatalyst, which gave C3-alkylated
indoles in moderate to good yields.
Visible light-mediated indole alkylation
previous reports (transition-metal catalyst involved)
(1) Ru-catalyzed (Stephenson, 2010)21a
Ru(bpy)3Cl2 (1 mol%)
R
R
CO2Et
CO2Et
CO2Et
CO2Et
DMF, blue LED, rt
Et3N or
Br
+
X
X
NPh2
X=O, NH
MeO
(2) Eosin Y/G-RuO2-catalyzed (Wu, 2013)21b
Eosin Y, G-RuO2
H2O, Visible Light, rt
N
+
Ph
N
N
Ph
H
N
Current work (metal-free)
H
N
Rose bengal (1.5 mol%)
R3
+
R4
N
R1
15 W LED
N
R2
R1
N
R3
CH3CN/H2O, r.t
R4
R2
.metal-free
up to 79% yield
in situ generated HCHO
Friedel-Crafts mechanism
no acid catalyst
Scheme 1. Different protocols for alkylation of indoles

2
Tetrahedron Letter
Results and discussion
Table 1. Optimization of Reaction Conditions a
N
visible light
solvent, air
+
N
H
N
N
photocatalyst
H
1a
2a
3a
entry
catalyst
solvent
yield(%)b
1
2
Eosin Y
Eosin B
DMF
DMF
54
n.r.
3
4
Rose Bengal
Rhodamine B
Rose Bengal
Rose Bengal
Rose Bengal
Rose Bengal
Rose Bengal
Rose Bengal
Rose Bengal
Rose Bengal
Rose Bengal
Rose Bengal
Rose Bengal
Rose Bengal
Rose Bengal
--
DMF
DMF
H2O
62
n.r.
n.r.
20
5
6
CH3CH2OH
DMSO
CHCl3
7
trace
60
8
9
THF
46
10
11
12
13
14c
15d
16e
17f
18
CH3CN
65
66
CH3CN：H2O=3：1
CH3CN：H2O=5：1
CH3CN：H2O=4：1
CH3CN：H2O=4：1
CH3CN：H2O=4：1
CH3CN：H2O=4：1
CH3CN：H2O=4：1
CH3CN：H2O=4：1
70
71
69
52
trace
n.r.
n.r.
aReaction conditions: 1H-indole (1a, 0.5 mmol), N,N-dimethylaniline (2a, 5 equiv., 2.5 mmol), catalyst (1.5
mol%), solvent (5 mL), open to the air, 15 W LED, 24 h. bIsolated yields. cFor 12 h. d5 mol% catalyst. eN2
atmosphere. fIn the dark.
Initially, we selected 1H-indole (1a) and N,N-dimethylaniline (2a) as the model substrate under photochemical conditions toward
synthesis of C3-alkylated product 3a (Table 1). To our delight, using Eosin Y as the photocatalyst upon irradiation of 15 W light-
emitting diode (LED) bulb, 3a was obtained in 54% yield at room temperature in DMF after 24 h (entry 1). Inspired by this result, we
screened other parameters. The Eosin B and Rhodamine B catalysts were no product generated in DMF (entry 2, entry 4), and Rose
Bengal gave a moderate yield (62%, Table 1, entry 3). The transition-metal-free nature of Rose Bengal motivated us to optimize the
reaction conditions using Rose Bengal as the photocatalyst. Thus, a series of different solvents, such as H2O, C2H5OH, DMSO, CHCl3,
THF and CH3CN were screened (entries 5-10). Delightfully, 3a was obtained in moderate yield (65%) in CH3CN after 24 h (entry 10).
In order to achieve a fast demethylation of tertiary amines, the mixed solvents of CH3CN/H2O with different volume ratios were tested
and one with a 4:1 ratio gave an improved yield (entry 13, 71%). The appropriate amount of the photocatalyst was 1.5 mol%. Increasing
it to 5 mol% did not result in yield enhancement (entry 15). Compared with that of the reaction in the air, the yield of the reaction under
N2 atmosphere was sharply reduced (entry 16). Moreover, no conversion could be observed when the reactions were conducted in the
dark and no catalyst (entries 17-18). These results indicate that light, Rose Bengal and air are all essential to achieve the reaction.
With the optimized reaction conditions in hand, the reactions with a range of indoles and N,N-dimethylanilines were extended, and
totally 18 C3-alkylated indole products were obtained, of which 10 were not previously reported. As shown in Table 2, this reaction

was compatible with many functional groups. Generally, the indoles bearing an electron-donating group (methoxyl, methyl) had higher
yield than those bearing an electron-withdrawing group (halogen). 5-Methoxyl indole and 5-methoxyl-N-methyl indole reacted with
N,N-dimethylaniline smoothly affording the corresponding products in 73% and 79% yields, respectively (Table 2, 3k and 3l). The
reactions of methyl-substituted indoles (Table 2, 3b-d, 3i, 3j) and halo-substituted indoles (Table 2, 3e-h) with N,N-dimethylaniline
gave moderate yields. It is also shown in Table 2, the introduction of substituents to the 3-position of N,N-dimethylaniline decreased
yields (3m-r), probably due to the higher steric hindrance caused by 3-position substitutions.
Table 2. Rose Bengal catalyzed synthesis of C3-alkylated indole derivativesa,b
N
N
Rose bengal(1.5 mol%)
+
R4
R3
CH3CN/H2O, air,24 h
15 W LED, r.t
N
R3
R1
N
R2
R4
R1
2
1
R2
3
N
N
N
N
N
H
N
N
H
N
3a, 71%
3c, 61%
3b, 70%
3d, 67%
N
N
N
N
Br
Cl
Br
Cl
N
H
N
N
H
N
3h, 51%
3e, 54%
3g, 51%
3f, 63%
N
N
N
N
H3CO
H3CO
N
H
N
N
H
N
3i, 65%
Br
3k, 73%
3l, 79%
3j, 68%
N
N
N
N
N
H
N
H
N
H
N
3o, 58%
3m, 45%
3p, 62%
3n, 60%
N
N
H3CO
H3CO
N
N
H
3r, 66%
3q, 65%
aReaction conditions: indoles (1, 0.5 mmol), anilines (2, 5 equiv, 2.5 mmol), Rose Bengal (1.5 mol%),
CH3CN/H2O (4:1 mL), open to the air, irradiation under a 15 W LED at room temperature for 24 h.
bIsolated yield.
A plausible mechanism was proposed on the basis of the literature reports (Scheme 2).22,24,25 Under visible-light irradiation, Rose
Bengal was converted to the excited RB*, reductive quenching of RB* by N,N-dimethylaniline resulted in the formation of Rose Bengal
radical anion (RB•−) and radical cation 4. The photoredox cycle is completed by the O2 oxidation of RB•− to the ground state Rose
Bengal.24 On the other hand, the radical cation 4 losing a proton, presumably to the O2•− to afford hydrogen peroxide anion and iminium
ion 5. Then, 5 was oxidized or hydrolyzed to give a-hydroxylated amine, which subsequently decomposed to afford formaldehyde (7)
and the N-methylaniline (6).25 Finally, the target product 3a was formed by the three-component reaction of indole with formaldehyde
and N,N-dimethylaniline involving a intermediate 3-methylidene-3H-indolium cation 8, which may be generated by Rose Bengal
catalyzed condensation of indole with formaldehyde.22 To support the postulation, the byproduct N-methylaniline (6) was isolated from
the reaction mixture and confirmed by NMR and mass spectrometry, and the target product 3a was obtained as expected by a three-
component reaction of indole with formaldehyde and N,N-dimethylaniline using Rose Bengal as the photocatalyst under standard

4
Tetrahedron Letter
conditions (Scheme 3). In addition, another control reaction of indole, formaldehyde and N,N-dimethylaniline was performed without
visible light and photocatalyst under otherwise same conditions (Scheme 4).
N
N
H
3a
N
2a
N
visible-light
RB*
N
H
8
2a
H2O
Photoredox
Catalysis
RB
N
O2
RB
N
-H
O2 or H2O
CH2O
4
N
H
O2
7
1a
5
NH
6
Scheme 2. Plausible Mechanism
N
Rose Bengal
(1.5 mol%)
+
+
CH2O
3 eq.
N
N
CH3CN:H2O, air
visible light,24 h
N
H
H
1eq.
yield 80%
2 eq.
Scheme 3. Rose Bengal catalyzed three-component coupling reaction
of indole, formaldehyde and N,N-dimethylaniline
N
CH3CN:H2O
+
+
CH2O
3 eq.
N
N
air, 24 h
N
H
H
1eq.
2 eq.
yield 35%
Scheme 4. Three-component coupling reaction of indole, formaldehyde and
N,N-dimethylaniline without visible light and photocatalyst
Conclusion
In summary, we have successfully developed the metal and acid-free visible light-mediated C3-alkylation reactions of indole
derivatives with tertiary amines. Rose Bengal, a cheap and readily available organic dye, was applied as the photocatalyst. The reaction
provides a straightforward access to the synthesis of C3-alkylated indoles.
Acknowledgments
We are grateful for the financial support by the National Natural Science foundation of China (No.30900959) and the Natural
Science foundation of Zhejiang Province (LY17C140003).
References and notes
1. (a) Narayanam, J. M. R.; Stephenson, C. R. J. Chem. Soc. Rev. 2011, 40, 102. (b) Prier, C. K.; Rankic, D. A.; Macmillan, D. W. C.
Chem. Rev. 2013, 113, 5322. (c) Xuan, J.; Xiao, W. J. Angew. Chem. Int. Ed. 2012, 51, 6828. (d) Xi, Y. M.; Yi, H.; Lei, A. W. Org.
Biomol. Chem. 2013, 11, 2387.
2. (a) Nicewicz, D. A.; Nguyen, T. M. ACS Catal. 2014, 4, 355. (b) Ravelli, D.; Fagnoni, M. ChemCatChem. 2012, 4, 169. (c) Sun, C.
L.; Shi, Z. J. Chem. Rev. 2014, 114 , B. Chem. Commun. 2014, 50, 6688. (e) Chen, J. R.; Yan, D. M.; Wei,
Q.; Xiao, W. J. ChemPhotoChem. 2017, 1, 148. (f) Shaw, M. H.; Twilton, J.; MacMillan, W. C. J. Org. Chem. 2016, 81, 6898.
3. Ravelli, D.; Fagnoni, M.; Albini, A. Chem. Soc. Rev. 2013, 42, 97.
4. Prier, C. K.; Rankic, D. A.; Macmillan, D. W. Chem. Rev. 2013, 113, 5322.

5. Huang, L. Zhao, J. Z. RSC Adv. 2013, 3, 23377.
6. Guo, S.; Zhang, H. L.; Huang, L.; Guo, Z. D.; Xiong, G.; Zhao, J. Z. Chem.Commun. 2013, 49, 8689.
7. Zhao, J. Z.; Wu, W. H.; Sun, J. F.; Guo, S. Chem. Soc. Rev. 2013, 42, 5323.
8. Eosin B: (a) Hussein, F. H.; Alkhateeb, A. N. Desalination. 2007, 209, 350. (b) Luo, K.; Chen, Y. Z.; Yang, W. C.; Zhu, J.; Wu, L.
Org. Lett. 2016, 18, 452.
9. Eosin Y: (a) Huang, F. Q.; Dong, X.; Qi, L. W.; Zhang, B. Tetrahedron Letters. 2016, 57, 1600. (b) Sagir, H.; Rai, P.; Ibad, A.; Ibad,
F.; Siddiqui, I. R. Catal. Commun. 2017, 100 , B. Acc. Chem. Res. 2016, 49,
1566. (d) Liu, X.; Cong, T. T.; Liu, P.; Sun, P. P. J. Org. Chem. 2016, 81, 7256. (e) Wang, K.; Meng, L. G.; Wang, L. J. Org. Chem.
2016, 81, 7080. (f) Rohokale, R. S.; Koenig, B.; Dhavale, D. D. J. Org. Chem. 2016, 81, 7121. (g) Cai, S. Y.; Xu, Y. H.; Chen, D. L.;
Li, L. H.; Chen, L. H.; Chen, Q. F.; Huang, M. Q.; Weng, W. Org. Lett. 2016, 18, 2990. (h) Yi, H.; Niu, L. B.; Wang, S. C.; Liu, T. Y.;
Singh, A.K.; Lei, A. W. Org. Lett. 2017, 19, 122.
10. Rhodamine B: (a) Guo, W.; Lu, L. Q.; Wang, Y.; Wang, Y. N.; Chen, J. R.; Xiao, W. J. Angew. Chem. Int. Ed. 2015, 54, 2265. (b)
Yoshioka, E.; Kohtani, S.; Jichu, T.; Fukazawa, T.; Nagai, T.; Kawashima, A.; Takemoto, Y.; Miyabe, H. J. Org. Chem. 2016, 81,
7217. (c) Yoo, W. J.; Kobayashi, S. Green Chem. 2013, 15, 1844.
11. Methylene blue: (a) Pitre, S. P.; McTiernan, C. D.; Ismaili, H.; Scaiano, J. C. J. Am. Chem. Soc. 2013, 135, 13286. (b) Zhang, H.;
Trout, W. S.; Liu, S.; Andrade, G. A.; Hudson, D. A.; Scinto, S. L.; Dicker, K. T.; Li, Y.; Lazouski, N.; Rosenthal, J.; Thorpe, C.; Jia,
X. Q.; Fox, J. M. J. Am. Chem. Soc. 2016, 138, 5978. (c) Aguirre-Soto, A.; Lim, C. H.; Hwang, A. T.; Musgrave, C. B.; Stansbury, J.
W. J. Am. Chem. Soc. 2014, 136, 7418.
12. Rose Bengal: (a) Gu, X. Y.; Li, X.; Chai, Y. H.; Yang, Q.; Li, P. X.; Yao, Y. M. Green Chem. 2013, 15, 357. (b) Wu, L. L.; Yang,
G. H.; Guan, Z.; He, Y. H. Tetrahedron. 2017, 73, 1854. (c) Kumar, G.; Verma, S.; Ansari, A.; Khan, N. H.; Kureshy, R. I. Catal.
Commun. 2017, 99, 94. (d) Vila, C.; Lau, J.; Rueping, M. Beilstein. J. Org. Chem. 2014, 10, 1233. (e) Gu, X. Y.; Li, X.; Chai, Y. H.;
Yang, Q.; Li, P. X.; Yao, Y. M. Green Chem. 2013, 15, 357. (f) Kovvuri, J.; Nagaraju, B.; Kamal, A.; Srivastava, A. K. ACS Comb. Sci.
2016, 18, 644. (g) Liu, H. J.; Feng, W.; Kee, C. W.; Zhao, Y. J.; Leow, D. S.; Pan, Y. H.; Tan, C. H. Green Chem. 2010, 12, 953. (h)
Cao, S.; Zhong, S. S.; Xin, L. T.; Wan, J. P.; Wen, C. P. ChemCatChem. 2015, 7, 1478. (i) Li, X.; Gu, X. Y.; Li, Y. J.; Li, P. X. ACS.
Catal. 2014, 4, 1897. (j) Fan, W. G.; Yang, Q.; Xu, F. S.; Li, P. X, J. Org. Chem. 2014, 79, 10588.
13. , B. J. Am. Chem. Soc. 2012, 134, 2958.
14. Li, J.; Zhang, J.; Tan, H. B.; Wang, Z. G. Org. Lett. 2015, 17, 2522.
15. (a) Somei, M.; Yamada, F. Nat. Prod. Rep. 2005, 22, 73. (b) Degterev, A.; Huang, Z. H.; Boyce, M.; Li, Y. Q.; Jagtap, P.;
Mizushima, N.; Cuny, G. D.; Mitchison, T. J.; Moskowitz, M. A.; Yuan, J. Y. Nat. Chem. Biol. 2005, 1, 112.
16. (a) You, S. L.; Cai, Q.; Zeng, M. Chem. Soc. Rev. 2009, 38, 2190. (b) Outlaw, V. K.; Zhou, J. W.; Bragg, A. E.; Townsend, C. A.
RSC Adv. 2016, 6, 61249. (c) Martinez-Ariza, G.; Mehari, B. T.; Pinho, L. A. G.; Foley, C.; Day, K.; Jewett, J. C.; Hulme, C. Org.
Biomol. Chem. 2017, 15, 6076. (d) Mahesh, S.; Anand, R. V. Eur. J. Org. Chem. 2017, 2698.
17. (a) Taylor, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 10558. (b) Muratore, M. E.; Holloway, C. A.; Pilling, A. W.; Storer,
R. I.; Trevitt, G.; Dixon, D. J. J. Am. Chem. Soc. 2009, 131, 10797. (c) Gregory, A. W.; Jakubec, P.; Turner, P.; Dixon, D. J. Org. Lett.
2013, 15, 4330.
18. For general reviews, see (a) Bandini, M.; Eichholzer. A. Angew. Chem. Int. Ed. 2009, 48, 9608. (b) Bartoli, G. Melchiorre, P.
Synlett. 2008, 12, 1759.
19. (a) Dujardin. G.; Poirer, J. M.; Bull. Soc. Chim. Fr. 1994, 131, 900. (b) Liu, Z.; Wang, D.; Wu, Y. C.; Chen, Y. J. Synth. Commun.
2012, 42, 1813. (c) Sanap, A. K.; Shankarling, G. S. RSC Adv. 2014, 4, 34938. (d) Dolman, D.; Sainsbury, M. Tetrahedron Lett. 1981,
22, 2119 . (e) Nunomoto, S.; Kawakami, Y.; Yamashita, Y.; Takeuchi, H.; Eguchi, S. J. Chem. Soc., Perkin Trans. 1990, 1, 111. (f)
Ganesan, S. S.; Ganesan, A. Tetrahedron Lett. 2014, 55, 694. (g) Kona, C. N.; Shinde, M. H.; Ramana, C. V. Org. Biomol. Chem. 2015,
13, 5358.
20. (a) Liu, W. B.; He, H.; Dai, L. X.; You, S. L. Org. Lett. 2008, 10, 1815. (b) Detz, R. J.; Abiri, Z.; Griel, R.; Hiemstra, H.; van
Maarseveen, J. H. Chem. Eur. J. 2011, 17, 5921. (c) Kiyotaka, O.; Chhiaki, K.; Hiroaki, S. Chem. Lett. 2009, 38, 444. (d) Das, D.; Roy,
S. Adv. Synth. Catal. 2013, 355, 1308. (e) Zhou, Z. J.; Li, Y. J.; Gong, L.; Meggers, E. Org. Lett. 2017, 19, 222. (f) Weng, J. Q.; Deng,
Q. M.; Wu, L.; Xu, K.; Wu, H.; Liu, R. R.; Gao, J. R.; Jia, Y. X. Org. Lett. 2014, 16, 776. (g) Siddiki, S. M. A. H.; Kon, K.; Shimizu,
K. I. Chem. Eur. J. 2013, 19, 14416. (h) Wong, M. Y.; Yamakawa, T.; Yoshikai, N. Org. Lett. 2015, 17, 442. (i) Weng, J. Q.; Fan, R. J.;
Deng, Q. M.; Liu, R. R.; Gao, J. R.; Jia, Y. X. J. Org. Chem. 2016, 81, 3023.
21. (a) Furst, L.; Matsuura, B. S.; Narayanam, J. M. R.; Tucker J. W.; Stephenson, C. R. J. Org. Lett. 2010, 12, 3104. (b) Meng, Q. Y.;
Zhong, J. J.; Liu, Q.; Gao, X. W.; Zhang, H. H.; Lei, T.; Li, Z. J.; Feng, K.; Chen, B.; Tung, C. H.; Wu, L. Z. J. Am. Chem. Soc. 2013,
135, 19052. (c) Ye, L.; Cai, S. H.; Wang, D. X.; Wang, Y. Q.; Lai, L. J.; Feng, C.; Loh, T. P. Org. Lett. 2017, 19, 6164.
22. Wang, M. Z.; Zhou, C. Y.; Wong, M. K.; Che, C. M. Chem. Eur. J. 2010, 16, 5723.
23. Shinde, V. V.; Jeong, Y. T. C. R. Chimie. 2015, 18, 449.
24. Li, X.; Gu, X. Y.; Li, Y. J.; Li, P. X. ACS Catal. 2014, 4, 1897.
25. Groves, J. T.; McClusky, G. A. J. Am. Chem. Soc. 1976, 98, 859.

6
Tetrahedron Letter
Highlights



Transition metal-free visible light-induced C3-
alkylation of indoles developed.
Indoles undergo Friedel-Crafts C3-alkylation
without acid catalyst.
The in situ-generated HCHO acts as the carbon
source.

Graphical Abstract
Metal and Acid-Free Visible Light-Mediated Friedel
-Crafts Alkylation Reactions of Indole with Anilines
Xiao-Qiang Dai, Wen-Xiu Xu, Ya-Long Wen, Xing-Hai Liu,
and Jian-Quan Weng*
Leave this area blank for abstract info.
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China
N
Rose bengal (1.5 mol%)
R3
+
R4
N
R1
15 W LED
N
R2
R1
N
R3
CH3CN/H2O, r.t
R4
R2
.metal-free
up to 79% yield
in situ generated HCHO
Friedel-Crafts mechanism
no acid catalyst