Photo-induced copper-catalyzed C-H chalcogenation of azoles at room temperature

Article abstract of DOI:10.1039/c7cc03107f

Inexpensive copper catalysts enabled direct C-H chalcogenations at ambient temperature by means of photo-induced catalysis. The expedient copper catalysis set the stage for C-S and C-Se bond formation from readily accessible non-volatile elemental chalcogens. The photo-assisted copper catalysis manifold proved suitable for a wide range of substrates with good functional group tolerance and exhibited high catalytic efficacy even at a reaction temperature of 25 °C.

Full text of DOI:10.1039/c7cc03107f

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: G. Parthasarathy,
J. Mo and L. Ackermann, Chem. Commun., 2017, DOI: 10.1039/C7CC03107F.
This is an Accepted Manuscript, which has been through the
Volume 52 Number
1 4 January 2016 Pages 1–216
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Accepted Manuscripts are published online shortly after
Chemical Communications
www.rsc.org/chemcomm
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
=
3
rsc.li/chemcomm

Please do not adjust margins
Page 1 of 5
ChemComm
View Article Online
DOI: 10.1039/C7CC03107F
ChemComm
COMMUNICATION
Photo-induced Copper-Catalyzed C–H Chalcogenation
of Azoles at Room Temperature
Received 00th January 20xx,
Accepted 00th January 20xx
Parthasarathy Gandeepan, Jiayu Mo and Lutz Ackermann*
DOI: 10.1039/x0xx00000x
www.rsc.org/
Inexpensive copper catalysts enabled direct C–H chalcogenations transformations are largely restricted to rather harsh reaction
at ambient temperature by means of photo-induced catalysis. The conditions. In contrast, photo-mediated cross-couplings of
expedient copper catalysis set the stage for C–S and C–Se bond thiols were recently achieved.15 Hence, photo-induced copper-
formation from readily accessible non-volatile elemental catalyzed cross-couplings of aryl iodides/bromides proved
chalcogens. The photo-assisted copper catalysis manifold proved viable,15a,d,g while a nickel-catalyzed photoredox process was
suitable for a wide range of substrates with good functional group exploited for C–S forming cross-couplings in the presence of a
tolerance and exhibited a high catalytic efficacy even at a reaction precious iridium photo catalysts (PCs).15b In spite of these
temperature of 25 C.
considerable advances, the necessity for prefunctionalized
substrates in these cross-coupling approaches represents a
considerable obstacle. Furthermore, synthetically useful
selenides have as of yet proven elusive in photo-induced cross-
couplings. Within our program on sustainable C–H activation
by base-metal catalysis,16 we herein report on first C–H
chalcogenations at 25 C by sustainable copper catalysis (Fig.
1). Notable features of our report include a) base metal-
catalysis at room temperature, as well as b) copper-catalyzed
C–H thiolations and selenations with c) non-volatile elemental
chalcogens, being d) devoid of any expensive iridium or
ruthenium catalyst.
Methods for the direct functionalization of C–H bonds by base
metal catalysis are in high demand, due to their low toxicity,
natural abundance, and cost effectiveness as compared to
typically used precious transition metals.1 Recently, significant
advances have been accomplished in copper-catalyzed C–C and
C–heteroatom bond formation via C–H activation.2 While the
use of cost-effective and environmentally-friendly copper
catalysts is thus highly attractive, major disadvantages are
represented by the requirement of stoichiometric quantities of
copper, the need for strong silver(I) or peroxide oxidants, the
limitation to specific ligands, and/or rather harsh reaction
conditions with typical reaction temperatures of 100-140 °C.3
In recent years, photocatalysis has emerged as a powerful
tool in organic synthesis.4 Thus, enabling photoredox
transformations were developed with transition metals,
including iridium,5 ruthenium,6 gold,7 nickel,8 and copper.9
Particularly, the possibility of merging photocatalysis with
noble palladium, rhodium, and ruthenium catalyzed C–H
functionalization has been highlighted,10,11 albeit at elevated
reaction temperatures of 100-120 °C. In sharp contrast, our
group recently disclosed the photo-induced copper-catalyzed
C–H arylation, proceeding at ambient temperature.12
Fig. 1 Photo-induced copper-catalyzed C–H chalcogenation at 25 °C.
Despite of notable progress in thiolation and selenation
We initiated our studies by probing reaction conditions for
the envisioned C–H thiolation of benzothiazole (1a) with 3-
iodotoluene (2a), employing elemental sulphur (Table 1).
Various ligands failed to improve the yield of desired product
3aa (Table 1, entries 1-7). Furthermore, the catalytic efficiency
was not significantly altered when the reaction was performed
under an atmosphere of oxygen or nitrogen (entries 8 and 9).
While different copper salts provided comparable results,
chemistry,13,14
transition
metal-catalyzed
thermal
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität,
Tammannstraße 2, 37077 Goettingen, Germany.
E-mail: Lutz.Ackermann@chemie.uni-goettingen.de
Homepage: http://www.org.chemie.uni-goettingen.de/ackermann/
†Electronic Supplementary Information (ESI) available: Experimental procedures,
characterization data, and 1H and 13C NMR spectra for products. See
DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 5
COMMUNICATION
Journal Name
copper(I) thiophene-2-carboxylate (CuTc) displayed the best selenium at room temperature were also viable under otherwise
View Article Online
performance for the catalytic C–H thioarylation at room identical reaction conditions (Scheme 2).DTOhI:u1s0,.10a3v9/aCri7eCtCy0o31f027F-
temperature. A reaction conducted in DMSO as the solvent arylselanylbenzothiazoles
4 were obtained within the three-
proceeded less efficiently (entry 15), and other reaction media, component C–H activation regime. The robustness of the
including toluene, THF, Et2O, 1,4-dioxane or CH3CN, gave photo-induced copper-catalyzed C–H activation was further
inferior results. Finally, control experiments verified that the C– reflected by the C–H chalcogenation of benzothiazole 1a with
H thioarylation did not occur in the absence of the copper both elemental sulphur and selenium and aryl bromides
5 at
complex or without irradiation (entries 17 and 18). The mass ambient temperature (Scheme 3). It is particularly noteworthy
balance of the photo-induced C–H chalcogenation was that challenging heteroaryl bromides derived from quinoline
accounted for by unreacted starting material 1a
.
and isoquinoline were effectively transformed into the desired
2-thionylbenzothiazoles and 2-selanylbenzothiazoles with
high levels of chemo and positional selectivities.
3
4
Table 1 Optimization of copper-catalyzed C–H thioarylation at room temperaturea
Entry
1
Cu Salt
CuI
Ligand
Solvent
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
PhMe
DMF
DMF
DMF
DMF
Yield (%)
26
30
28
35
28
26
44
47b
42c
41
43
19
50
35
40
6
1,10-Phen
2
CuI
bpy
3
CuI
DMEDA
4
CuI
TMEDA
5
CuI
L-Proline
6
CuI
Me2NCH2CO2H
7
CuI
--
--
--
--
--
--
--
--
--
--
--
--
--
--
8
CuI
9
CuI
10
11
12
13
14
15
16
17
18
19
20
CuCl
CuBr
CuOAc
CuTc
Cu(OAc)2
CuTc
CuTc
CuTc
--
Scheme 1 Photo-induced copper-catalyzed C–H thioarylation at 25 °C.
0d
0
5e
0f
CuTc
CuTc
a Reaction conditions: 1a (0.40 mmol), 2a (1.20 mmol), S (0.80 mmol), Cu salt (20
mol %), ligand (30 mol %), 254 nm, LiOtBu (1.20 mmol), DMF (2.0 mL), under air,
b
c
d
yield of isolated product. Under O2. Under N2. Reaction performed in the
e
f
dark. 22 W CFL. 5 W blue LED. Phen = phenanthroline, bpy = 2,2’-bipyridine,
DMEDA N,N’-dimethylethylenediamine, TMEDA N,N,N’,N’-
tetramethylethylenediamine, CuTc = copper(I) thiophene-2-carboxylate.
=
=
We next explored the scope of the photo-assisted C–H
thioarylation of heteroarenes by probing diversely substituted
aryl iodides (Scheme 1). Thus, the optimized copper catalyst
performed well with good functional group tolerance to deliver
the desired C–H thioarylation products . Moreover, a thiazole
also provided the desired C–H thiolation product 3eb
1
Scheme 2 Photo-induced copper-catalyzed C–H selenation at 25 °C.
2
In consideration of the unique versatility of the photo-
induced copper catalysis, we became attracted by rationalizing
its mode of action. To this end, intermolecular competition
3
.
The catalytic system was not restricted to the C–H
thiolation manifold. Indeed, C–H selenations with elemental
experiments revealed electron-deficient aryl iodides
2 to be
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 5
ChemComm
Please do not adjust margins
Journal Name
COMMUNICATION
preferentially converted (Scheme 4a). Further, we probed a diphenyl disulfide (7a) afforded product 3ab in VhieiwgAhrticyleieOlndl.in1e8
SET-type reaction regime by the use of the typical radical Finally, we treated iodobenzene 2b wiDthOI:e1le0m.10e3n9t/aCl7CsCu0lp3h10u7rF,
scavenger galvinoxyl (Scheme 4b), which resulted in a delivering diphenyl disulfide (7a) and diphenyl sulfide (8a).
significant inhibition of the catalytic efficacy.
These results provided strong evidence for the in-situ formation
of diaryl disulfides as the key intermediates.
Scheme 3 Photo-induced C–H chalcogenation with aryl bromides 5.
Scheme 5 Probing a reaction intermediate.
In summary, we have developed the unprecedented photo-
induced copper-catalyzed C–H chalcogenation at room
temperature. The C–H functionalization of azoles19 with
(hetero)aryl electrophiles and elemental sulphur/selenium
enabled C–H arylchalcogenations of aromatic heterocycles with
ample scope. The characteristic features of these
transformations include an operationally-simple copper
catalysis, user-friendly elemental chalcogens, sustainable base-
metal catalysis, and ambient reaction temperature under aerobic
reaction conditions.
Generous support by the Alexander von Humboldt-
foundation (fellowship to P.G.), the CSC (fellowship to J.M.),
and the European Research Council under the Seventh
Framework Program of the European Community
(FP720072013; ERC Grant Agreement No. 307535) is
gratefully acknowledged.
References
1
Recent reviews: (a) T. Yoshino and S. Matsunaga, Adv. Synth. Catal.,
2017, DOI: 10.1002/adsc.201700042; (b) M. Moselage, J. Li and L.
Ackermann, ACS Catal., 2016,
Muto and K. Itami, Top. Curr. Chem., 2016, 374, 55; (d) W. Liu and
L. Ackermann, ACS Catal., 2016, , 3743–3752; (e) D. Wei, X. Zhu,
J.-L. Niu and M.-P. Song, ChemCatChem, 2016, , 1242–1263; (f) G.
Cera and L. Ackermann, Top. Curr. Chem., 2016, 374, 57; (g) L. C.
M. Castro and N. Chatani, Chem. Lett., 2015, 44, 410–421; (h) P.
Gandeepan and C.-H. Cheng, Acc. Chem. Res., 2015, 48, 1194–1206.
For representative reviews, see: (a) X. Zhu and S. Chiba, Chem. Soc.
Rev., 2016, 45, 4504–4523; (b) O. Daugulis, J. Roane and L. D. Tran,
Acc. Chem. Res., 2015, 48, 1053–1064; (c) K. Hirano and M. Miura,
6, 498–525; (c) J. Yamaguchi, K.
Scheme 4 Key mechanistic studies.
6
To further elucidate the nature of the thiolating reagent, we
performed a series of additional experiments (Scheme 5).
Under otherwise identical reaction conditions, the use of the
thiophenol PhSH (6a) in place of the aryl electrophile and
elemental sulphur did not provide the desired product 3ab
(Scheme 5a).17 However, the reaction of substrate 1a with
8
2
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 5
COMMUNICATION
Journal Name
Chem. Lett., 2015, 44, 868–873; (d) X.-X. Guo, D.-W. Gu, Z. Wu
and W. Zhang, Chem. Rev., 2015, 115, 1622–1651; (e) K. Hirano and
Nishihara, Chem. Eur. J., 2014, 20, 2459–2462; (j)VLiew. DAr.ticTlerOann,linIe.
Popov and O. Daugulis, J. Am. Chem. Soc., 2012, 134, 18237–18240.
DOI: 10.1039/C7CC03107F
M. Miura, Chem. Commun., 2012, 48, 10704–10714; (f) A. E. 15 (a) M. Jiang, H. Li, H. Yang and H. Fu, Angew. Chem. Int. Ed., 2017,
Wendlandt, A. M. Suess and S. S. Stahl, Angew. Chem. Int. Ed.,
2011, 50, 11062–11087.
For selected examples, see: (a) M. Nishino, K. Hirano, T. Satoh and
M. Miura, Angew. Chem. Int. Ed., 2013, 52, 4457–4461; (b) P.-C.
56, 874–879; (b) M. S. Oderinde, M. Frenette, D. W. Robbins, B.
Aquila and J. W. Johannes, J. Am. Chem. Soc., 2016, 138, 1760–
1763; (c) S. Mukherjee, B. Maji, A. Tlahuext-Aca and F. Glorius, J.
Am. Chem. Soc., 2016, 138, 16200–16203; (d) M. W. Johnson, K. I.
3
Huang, P. Gandeepan and C.-H. Cheng, Chem. Commun., 2013, 49
8540–8542; (c) R. Jeyachandran, H. K. Potukuchi and L. Ackermann,
Beilstein J. Org. Chem., 2012, , 1771–1777; (d) M. Kitahara, N.
,
Hannoun, Y. Tan, G. C. Fu and J. C. Peters, Chem. Sci., 2016, 7,
4091–4100; (e) R. Honeker, R. A. Garza-Sanchez, M. N. Hopkinson
and F. Glorius, Chem. Eur. J., 2016, 22, 4395–4399; (f) L. Candish,
8
Umeda, K. Hirano, T. Satoh and M. Miura, J. Am. Chem. Soc., 2011,
133, 2160–2162; (e) H.-Q. Do and O. Daugulis, J. Am. Chem. Soc.,
2011, 133, 13577–13586; (f) Q. Shuai, G. Deng, Z. Chua, D. S.
Bohle and C.-J. Li, Adv. Synth. Catal., 2010, 352, 63–636; (g) H.-Q.
L. Pitzer, A. Gómez-Suárez and F. Glorius, Chem. Eur. J., 2016, 22,
4753–4756; (g) C. Uyeda, Y. Tan, G. C. Fu and J. C. Peters, J. Am.
Chem. Soc., 2013, 135, 9548–9552. See also: (h) N. Ishida, Y.
Masuda, S. Uemoto and M. Murakami, Chem. Eur. J., 2016, 22
,
Do, R. M. K. Khan and O. Daugulis, J. Am. Chem. Soc., 2008, 130
,
6524-6527.
15185–15192; (h) L. Ackermann, H. K. Potukuchi, D. Landsberg and 16 Selected recent examples: (a) Z. Ruan, N. Sauermann, E. Manoni and
R. Vicente, Org. Lett., 2008, 10, 3081–3084; (i) X. Chen, X.-S. Hao,
C. E. Goodhue and J.-Q. Yu, J. Am. Chem. Soc., 2006, 128, 6790–
6791.
L. Ackermann, Angew. Chem. Int. Ed., 2017, 56, 3172–3176; (b) S.
Nakanowatari, R. Mei, M. Feldt and L. Ackermann, ACS Catal.,
2017,
7, 2511–2515; (c) G. Cera, T. Haven and L. Ackermann,
4
For select recent reviews, see: (a) K. L. Skubi, T. R. Blum and T. P.
Chem. Eur. J., 2017, 23, 3577–3582.
Yoon, Chem. Rev., 2016, 116, 10035–10074; (b) M. H. Shaw, J. 17 (a) C. Dai, Z. Xu, F. Huang, Z. Yu and Y.-F. Gao, J. Org. Chem.,
Twilton and D. W. C. MacMillan, J. Org. Chem., 2016, 81, 6898– 2012, 77, 4414–4419; (b) A.-X. Zhou, X.-Y. Liu, K. Yang, S.-C.
6926; (c) N. A. Romero and D. A. Nicewicz, Chem. Rev., 2016, 116 Zhao and Y.-M. Liang, Org. Biomol. Chem., 2011, , 5456–5462; (c)
,
9
10075–10166; (d) D. Ravelli, S. Protti and M. Fagnoni, Chem. Rev.,
2016, 116, 9850–9913; (e) D. C. Miller, K. T. Tarantino and R. R.
S. Ranjit, R. Lee, D. Heryadi, C. Shen, J. E. Wu, P. Zhang, K.-W.
Huang and X. Liu, J. Org. Chem., 2011, 76, 8999–9007.
Knowles, Top. Curr. Chem., 2016, 374, 30; (f) M. D. Kärkäs, J. A. 18 (a) A. R. Rosario, K. K. Casola, C. E. S. Oliveira and G. Zeni, Adv.
Porco and C. R. J. Stephenson, Chem. Rev., 2016, 116, 9683–9747;
Synth. Catal., 2013, 355, 2960–2966; (b) I. Popov, H.-Q. Do and O.
(g) I. Ghosh, L. Marzo, A. Das, R. Shaikh and B. König, Acc. Chem.
Daugulis, J. Org. Chem. 2009, 74, 8309–8313.
Res., 2016, 49, 1566–1577; (h) G. Zhang, C. Bian and A. Lei, Chin. 19 Under otherwise identical reaction conditions, the use of
J. Catal., 2015, 36, 1428–1439.
benzimidazoles led thus far to less satisfactory results.
5
K. Teegardin, J. I. Day, J. Chan and J. Weaver, Org. Process Res.
Dev., 2016, 20, 1156–1163.
6
7
T. P. Yoon, M. A. Ischay and J. Du, Nat. Chem., 2010, 2, 527–532.
M. N. Hopkinson, A. Tlahuext-Aca and F. Glorius, Acc. Chem. Res.,
2016, 49, 2261–2272.
8
9
L. N. Cavalcanti and G. A. Molander, Top. Curr. Chem., 2016, 374,
39.
(a) O. Reiser, Acc. Chem. Res., 2016, 49, 1990–1996; (b) A. C.
Hernandez-Perez and S. K. Collins, Acc. Chem. Res., 2016, 49
,
,
1557–1565; (c) S. Paria and O. Reiser, ChemCatChem, 2014,
2477–2483.
6
10 (a) D. Kalyani, K. B. McMurtrey, S. R. Neufeldt and M. S. Sanford,
J. Am. Chem. Soc., 2011, 133, 18566–18569; (b) for metal-free
reactions: D. P. Hari, P. Schroll and B. König, J. Am. Chem. Soc.,
2012, 134, 2958–2961.
11 (a) D. C. Fabry, M. A. Ronge, J. Zoller and M. Rueping, Angew.
Chem. Int. Ed., 2015, 54, 2801–2805; (b) J. Zoller, D. C. Fabry, M.
A. Ronge and M. Rueping, Angew. Chem. Int. Ed., 2014, 53, 13264–
13268; (c) D. C. Fabry, J. Zoller, S. Raja and M. Rueping, Angew.
Chem. Int. Ed., 2014, 53, 10228–10231.
12 F. Yang, J. Koeller and L. Ackermann, Angew. Chem. Int. Ed., 2016,
55, 4759–4762.
13 For reviews, see: (a) S. Shaaban, S. Liang, N.-W. Liu and G.
Manolikakes, Org. Biomol. Chem., 2017, 15, 1947–1955; (b) I. P.
Beletskaya and V. P. Ananikov, Chem. Rev., 2011, 111, 1596–1636;
(c) J. F. Hartwig, Acc. Chem. Res., 2008, 41, 1534–1544; (d) T.
Kondo and T. Mitsudo, Chem. Rev., 2000, 100, 3205–3220.
14 For selected recent examples, see: (a) P. Gandeepan, J. Koeller and L.
Ackermann, ACS Catal., 2017, 7, 1030–1034; (b) W. Xie, B. Li and
B. Wang, J. Org. Chem., 2016, 81, 396–403; (c) T. Müller and L.
Ackermann, Chem. Eur. J., 2016, 22, 14151–14154; (d) T. Gensch,
F. J. R. Klauck and F. Glorius, Angew. Chem. Int. Ed., 2016, 55
11287–11291; (e) G. Cera and L. Ackermann, Chem. Eur. J., 2016,
22, 8475–8478; (f) S. Yu, B. Wan and X. Li, Org. Lett., 2015, 17
,
,
58–61; (g) V. P. Reddy, R. Qiu, T. Iwasaki and N. Kambe, Org.
Biomol. Chem., 2015, 13, 6803–6813; (h) R. Qiu, V. P. Reddy, T.
Iwasaki and N. Kambe, J. Org. Chem., 2015, 80, 367–374; (i) M.
Iwasaki, M. Iyanaga, Y. Tsuchiya, Y. Nishimura, W. Li, Z. Li and Y.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 5
ChemComm
View Article Online
DOI: 10.1039/C7CC03107F
TOC:
Photo-induced copper-catalyzed C–H chalcogenation at 25 °C
Parthasarathy Gandeepan, Jiayu Mo, Lutz Ackermann*
Copperꢀcatalyzed C−H chalcogenations of heteroarenes were achieved at room temperature of 25 °C
by photoꢀinduced catalysis within a threeꢀcomponent C–S and C–Se forming regime.