Visible-Light-Induced Direct Photocatalytic Carboxylation of Indoles with CBr4/MeOH

Article abstract of DOI:10.1002/chem.201503787

Photocatalysis enables the cascade reactions of indoles and CBr₄ in MeOH through a C(sp²)-H functionalization/methanolysis sequence. The title reaction provides an efficient access to indole 2- and 3-carboxylates in a single operation (no preinstallation of protecting as well as directing groups was required) with good yields under mild reaction conditions. Shedding light on indole: The regioselective alkoxycarboxylation of indoles and heteroarenes using the CBr₄/MeOH couple was accomplished through visible-light-induced photoredox catalysis. The described photocatalytic strategy features operational simplicity as well as high functional-group tolerance and represents a direct procedure to access indole carboxylates in generally moderate to good yields (see scheme).

Full text of DOI:10.1002/chem.201503787

DOI: 10.1002/chem.201503787
Communication
&
Photocatalysis
Visible-Light-Induced Direct Photocatalytic Carboxylation of
Indoles with CBr4/MeOH
Qing-Qing Yang,[a, b] Marianna Marchini,[a] Wen-Jing Xiao,[b] Paola Ceroni,*[a] and
Marco Bandini*[a]
Accordingly, the development of highly efficient methods to
Abstract: Photocatalysis enables the cascade reactions of
access direct carboxylation of this pharmacophore, under pro-
indoles and CBr4 in MeOH through a C(sp2)ÀH functionali-
tecting-group/prefunctionalization-free conditions, still remains
zation/methanolysis sequence. The title reaction provides
an unsolved challenge in organic synthesis. As a matter of fact,
an efficient access to indole 2- and 3-carboxylates in
besides the Fisher indole synthesis,[3] the direct C(2)-carboxyl-
a single operation (no preinstallation of protecting as well
ation of indolyl cores frequently involves multiple-step sequen-
as directing groups was required) with good yields under
ces based on aggressive reagents (i.e., organolithium com-
mild reaction conditions.
pounds)[4] with consequent limitation of substrate scope and
moderate yields (Scheme 1A).[5,6] A straightforward and atom-
Indoles and their derivatives have been widely recognized as
a pivotal structural component of a diverse array of natural
products and pharmacological agents of various therapeutic
actions.[1] Among them, indole C(2)-carboxylates are present as
privileged cores in numerous biologically active molecules and
still represent pivotal building blocks for the synthesis of natu-
rally occurring compounds (Figure 1).[2]
Scheme 1. Synthesis of indole 2-carboxylates: A) traditional protecting-
group-based approach; B) present study.
economic route to this structural motif would deal with the
direct CÀH functionalization of the indole nucleus.[7] In this
context, we drove our attention to the visible-light-induced
photoredox catalysis that continues to receive a considerable
amount of attention due to its inherent features of sustainabili-
ty, operational simplicity, and selectivity.[8] In this scenario, visi-
Figure 1. Representative indole C(2)-carboxylate-based natural products and
ble photocatalysis already found elegant applications in both
biologically active compounds.
the synthesis[9] and peripheral functionalization of indoles[10] by
means of metal/organic photosensitizers and electron-donor–
acceptor complexes.[11] However, despite this blooming
[a] Q.-Q. Yang, M. Marchini, Prof. Dr. P. Ceroni, Prof. Dr. M. Bandini
scenario, no example of photoassisted regioselective carboxy-
Department of Chemistry „G. Ciamician“, Alma Mater Studiorum
lative CÀH activation of arenes has been documented so far.[12]
University of Bologna, Via Selmi 2, 40126 Bologna (Italy)
In this context we recognized in the tetrahalogenated meth-
E-mail: paola.ceroni@unibo.it
anes CX4 (X=Cl, Br) potential carboxylating agents for arenes,
marco.bandini@unibo.it
Homepage: http://www.mbandini-group.com
C
due to their intrinsic attitude of generating electrophilic CX3
radicals (CCl4 =À0.78 V vs. SCE and CBr4 =À0.30 V vs. SCE)[13]
by oxidative quenching of photoexcited photosensitizers.[14]
The intercepting of these radical species by aromatic nucleus,
followed by alcoholysis,[15] would deliver a rapid entry to mild
CÀH-type carboxylating events (Scheme 1B).
[b] Q.-Q. Yang, Prof. Dr. W.-J. Xiao
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education
College of Chemistry, Central China Normal University (CCNU)
152 Luoyu Road, Wuhan, Hubei 430079 (China)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201503787.
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Communication
It is worth mentioning that despite their wide use as stoi-
chiometric sacrificial oxidative quenchers, their incorporation in
the final target, by means of visible-light-induced photocatalyt-
ic tools has never been fully exploited so far. Indeed, besides
the elegant photoinduced-ATRA (atom-transfer radical addi-
tion) to alkenes and alkynes reported by Stephenson[14a,c,16a]
and Melchiorre,[16b] tetrahalomethanes found applications
solely in the photochemical activation of oxygenated moieties
such as: 1) halogenation of alcohols,[14a] 2) activation of carbox-
ylic acids,[14b] 3) Losson and Beckmann rearrangements[14e,f]
Table 1. Optimization of reaction conditions.[a]
Entry
Photocatalyst/2
Base
Time [h] Yield [%][b]
1
[Ir(diFppy)2(dtb-bpy)]PF6/2a DTBP
24
12
72
48
12
NR
32
50
trace
42
2
3
[Ru(bpy)3]Cl2·6H2O/2b DTBP
[Ir(diFppy)2(dtb-bpy)]PF6/2b DTBP
4
5
6
7
8
9
fluorescein/2b
DTBP
DTBP
NaHCO3 24
C
( CBr3 is trapped by the solvent—DMF—during the reaction
[Ru(bpy)3](PF6)2/2b
[Ru(bpy)3](PF6)2/2b
[Ru(bpy)3](PF6)2/2b
[Ru(bpy)3](PF6)2/2b
[Ru(bpy)3](PF6)2/2b
[Ru(bpy)3](PF6)2/2b
[Ru(bpy)3](PF6)2/2b
[Ru(bpy)3](PF6)2/2b
–/2b
course) or 4) halogenation of arenes and alkenes (CBr4 is em-
ployed as the source of Br2).[14d,g] The use of CX4 as the latent
source of „carboxylic groups“ under light-driven conditions is
still unknown.
33
Et3N
24
48
24
48
24
6
25
66
73
79
81
90
Cy2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
iPr2NH
10[c]
11[c,d]
12[c,d,e]
13[c,d,e]
14[c,d,f]
As part of our ongoing research program on the functionali-
zation of indole derivatives,[17] we present here the direct and
regioselective synthesis of indole carboxylates by site-selective
photocatalytic CÀH functionalization in the presence of CBr4
and MeOH. The protecting-group-free methodology enables
a range of functionalized C(2)- or C(3)-indolyl esters to be ob-
tained under extremely mild conditions (Scheme 1B). In this di-
rection, it should be mentioned that CBr4 and MeOH have
been already employed by Mukminov in the iron-catalyzed
C(2)-carboxylation of benzofuran.[18] However, in addition to
the limited scope (only one substrate was reported), optimal
reaction conditions involved 130 or 1008C, in the absence or
in the presence of radical initiator, respectively.
24
24
6
NR
trace
81
[Ru(bpy)3](PF6)2/2b
15[c,d, g] [Ru(bpy)3](PF6)2/2b
[a] Unless noted, reactions were performed on 0.2 mmol scale of 1a (1a/
2 1:3 ratio), in degassed reagent-grade MeOH. [b] Isolated yield. [c] CBr4
(1.5 equiv) was used. [d] 1a: 0.05m in MeOH. [e] 7 W blue-LEDs was used.
[f] In the dark. [g] In the sunlight. bpy=2,2’-bipyridine; diFppy=2-(2,4-di-
fluorophenyl)pyridine; dtb-bpy=di-tert-butylbipyridine; DTBP=2,6-di-
tert-butylpyridine. NR=no reaction.
To explore the feasibility of our working plan, we initially in-
vestigated the reaction of 3-methylindole (1a) and CX4 2 (2a:
CCl4, 2b: CBr4, 3 equiv) in the presence of metal photosensitiz-
er (1 mol%), DTBP (2.0 equiv), blue LEDs (3 W) irradiation, and
MeOH as the reaction media.[19] Interestingly, while no reaction
was observed with CCl4 (Table 1, entry 1),[20] the use of more
easily reducible 2b furnished the desired 3a in 32% yield
(entry 2).
Next, we further optimized the reaction conditions by per-
forming a survey of parameters involving: nature of the photo-
sensitizer, light source, concentration, and base, identifying the
following: [Ru(bpy)3](PF6)2 (1 mol%), 7 W blue LEDs, 0.05m,
iPr2NH (2 equiv) as the optimal reaction conditions. Here, com-
pound 3a was isolated in 90% yield as a single regioisomer
upon 6 h irradiation (Table 1, entry 12). Additionally, a sunlight-
induced process was also carried out (entry 15), delivering 3a
in comparable extents (yield: 81%).
With the optimal conditions in hand, we probed the scope
of this photocatalytic carboxylation reaction. As summarized in
Scheme 2, a series of C(3)-substituted indoles (1b–l) were suc-
cessfully applied to this reaction. The 3-substituted indoles
containing linear and branched alkyl groups (i.e. ethyl, cyclo-
pentyl, cyclohexyl) were observed to react smoothly with CBr4
delivering products 3b–d in good yields (70–84%). Focusing
on functional-group tolerance, we also subjected N-protected
tryptamines (1e, 1 f) and tryptophol 1g to best operating con-
ditions. Gratifyingly, in all cases, the desired acyclic products
were recorded in a satisfying manner (yield: 70–82%). It is
worth noting that the present carboxylative process does not
Scheme 2. Generality of the method towards C(3)-substituted indoles (isolat-
ed yields are reported for each example). [a] N-Boc-protected tryptamine 1 f
was used as the starting material.
suffer brominating side events (both on the arene and alcohol-
ic moiety 1g) and that the N-Boc (Boc=tert-butoxycarbonyl)
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group is also selectively cleaved during irradiation (N-free
tryptamine 3 f was isolated as the major compound).
indole C(2)- and C(3)-carboxylates could also be easily accessi-
ble by the use of EtOH as the solvent (5k–l, 49–67% yields).
Last but not least, preliminary encouraging results on different
electron-rich heterocycles (i.e., pyrrole, benzofuran, phenol,
and thiophene, 5m–r) were achieved in moderate to good
yields (33–77%).[18a]
Besides amino and alcohol moieties, a wide range of differ-
ent functional groups proved tolerance of the working condi-
tions. Indoles carrying ketone (1h), ester (1i, 1j), alkene (1k),
and alkyne (1l) substituents were proved competent in our
protocol (yield: 51–77%). Furthermore, the impact of the elec-
tronic properties of the benzene ring on the final chemical
outcome was assessed. To this aim, substrates containing elec-
tron-deficient and -donating groups at the C(4)-, C(5)-, C(6)-,
and C(7) arene-position were tested, furnishing the corre-
sponding C(2)-carboxyl-indoles (3m–t) in good yields (60–
83%).
Preliminary insights into the reaction mechanism are provid-
ed by the additional experiments described in Equations (1)
and (2). In particular, the isolation of the bromo derivative 6a
when ethylene glycohol was used as the solvent [Eq. (1)]
allows some conclusions to be drawn: 1) the carbon atom of
the final carboxylic group comes from CBr4 that exerts the ini-
tial indole CÀH activation; 2) the alternative carbene-like mech-
anism can be excluded.[21]
Next, the generality of the process was further substantiated
by subjecting a range of C(2)-substituted or-unsubstituted in-
doles and azaindoles to the best conditions. As highlighted in
Scheme 3, 2-substituted indoles carrying Me, Ph, and CO2Et
In addition, the comparable results obtained by treating 6a
under standard conditions ([Ru(bpy)3](PF6)2 (1 mol%), 7 W blue
LEDs, 0.05m (6a) in MeOH, iPr2NH (2 equiv)) or simply by stir-
ring 6a in iPr2NH (2 equiv), MeOH at RT for 24 h [3a: 31 and
32% conversion, respectively, Eq. (2)] account for a classic
methanolysis reaction as the conclusive chemical event of the
cascade process.[13]
The reaction completely stopped in the dark and restarted
when the light source was switched on once again (Figure S1,
Supporting Information): this experiment clearly emphasized
the pivotal role played by visible light in promoting the pro-
cess.[22]
Scheme 3. Substrate scope. For reaction conditions see Scheme 2.[a] Com-
plete trans-esterification occurred starting from ethyl indole 2-carboxylate
4c.[b] EtOH was used as the solvent.
As shown in Scheme 4, a plausible mechanism is proposed
using methoxycarboxylation of 3-methylindole (1a) as an ex-
ample of this novel photocatalytic process. Visible-light excita-
units (4a–d) successfully partici-
pated in the process, providing
the corresponding products 5a–
d in 48–62% yields. Analogously,
substrates without substituents
at C(2)- and C(3)-positions were
suitable in this reaction to fur-
nish indole 3-carboxylates 5e–h
(43–64%). In contrast, the intro-
duction of a substituent at the
C(4)-position (i.e. Br) led to the
carboxylation of the C(2) carbon
atom exclusively (yield: 50–60%)
probably due to the steric hin-
drance (5i–j). In addition, ethyl Scheme 4. Hypothesis of reaction mechanism.
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Communication
istry III (Eds.: A. R. Katritzky, C. A. Ramsden, E. F. V. Scriven, R. J. K. Taylor),
Elsevier, Oxford, 2008, Vol. 3, pp. 353–388; c) M. Bandini, A. Eichholzer,
Angew. Chem. Int. Ed. 2009, 48, 9608–9644; Angew. Chem. 2009, 121,
9786–9824; d) A. J. Kochanowska-Karamyan, M. T. Hamann, Chem. Rev.
2010, 110, 4489–4497; e) C.-X. Zhuo, Q.-F. Wu, Q. Zhao, Q.-L. Xu, S.-L.
You, J. Am. Chem. Soc. 2013, 135, 8169–8172.
tion of the reaction mixture yields its lowest energy triplet ex-
cited state of [Ru(bpy)3]2+, *[Ru(bpy)3]2+, since none of the
other reagents is absorbing visible light (Figure S2, Supporting
Information). *[Ru(bpy)3]2+ is quenched by CBr4 (2b) with
a quenching constant of 5.3”106 mÀ1 sÀ1 (see Figure S5, Sup-
porting Information). The quenching process is the oxidation
[2] a) L. Khurana, H. I. Ali, T. Olszewska, K. H. Ahn, A. Damaraju, D. A. Ken-
dall, D. Lu, J. Med. Chem. 2014, 57, 3040–3052; b) N. Ramkumar, R. Na-
garajan, J. Org. Chem. 2014, 79, 736–741; c) M.-Z. Zhang, Q. Chen, G.-F.
Yang, Eur. J. Med. Chem. 2015, 89, 421–441.
of *[Ru(bpy)3]2+ and the reduction of CBr4, which generates
À [14a,23]
C
CBr3 (I) and Br .
Trapping of the electron-deficient radical
[3] a) E. Fischer, F. Jourdan, Ber. Dtsch. Chem. Ges. 1883, 16, 2241–2245;
b) E. Fischer, O. Hess, Ber. Dtsch. Chem. Ges. 1884, 17, 559–568; c) M.
Inman, C. J. Moody, Chem. Sci. 2013, 4, 29–41.
[4] A. R. Katritzky, K. Akutagawa, R. A. Jones, Synth. Commun. 1988, 18,
1151–1158.
by 3-methylindole formed a new benzyl radical II, which can
be oxidized by [Ru(bpy)3]3+ to provide the intermediate III, re-
generating the photocatalyst [Ru(bpy)3]2+. Rearomatization of
the intermediate III followed by methanolysis furnished the ob-
served product. The photoreaction quantum yield upon mono-
chromatic excitation at 450 nm is approximately 2% (see the
Supporting Information for more details), much lower than
100%. This result rules out a chain reaction mechanism, as
supported also by the light on–off experiment described
above. It is worth noting that at the end of the photoreaction
no significant change in the absorption spectrum of the pho-
tosensitizer is observed (Figure S4, Supporting Information),
meaning that [Ru(bpy)3]2+ does not decompose and can be
reused.
[5] For selected examples: a) K. Yamazaki, Y. Nakamura, Y. Kondo, J. Org.
Chem. 2003, 68, 6011–6019; b) A. García-Rubia, B. Urones, R. Gómez Ar-
rayµs, J. C. Carretero, Angew. Chem. Int. Ed. 2011, 50, 10927–10931;
Angew. Chem. 2011, 123, 11119–11123; c) Q.-Q. Yang, C. Xiao, L.-Q. Lu, J.
An, F. Tan, B.-J. Li, W.-J. Xiao, Angew. Chem. Int. Ed. 2012, 51, 9137–
9140; Angew. Chem. 2012, 124, 9271–9274.
[6] Pd-catalyzed carbonylation of pre-functionalized indoles represents an
alternative synthetic strategy to such indole derivatives: J. M. Herbert,
A. H. McNeill, Tetrahedron Lett. 1998, 39, 2421–2424. See also: J. Peng,
L. Liu, Z. Hu, J. Huang, Q. Zhu, Chem. Commun. 2012, 48, 3772–3774.
[7] For selected reviews, see: a) G. W. Gribble, J. Chem. Soc. Perkin Trans.
1 2000, 1045–1075; b) G. R. Humphrey, J. T. Kuethe, Chem. Rev. 2006,
106, 2875–2911; c) L. Ackermann, Synlett 2007, 0507–0526; d) K. Krüger
nØe Alex, A. Tillack, M. Beller, Adv. Synth. Catal. 2008, 350, 2153–2167;
e) A. Brancale, R. Silvestri, Med. Res. Rev. 2007, 27, 209–238; f) S. Cacchi,
G. Fabrizi, Chem. Rev. 2011, 111, PR215–PR283; g) G. Abbiati, F. Marinelli,
E. Rossi, A. Arcadi, Isr. J. Chem. 2013, 53, 856–868; h) N. Yoshikai, Y. Wei,
Asian J. Org. Chem. 2013, 2, 466–478; i) R. Dalpozzo, Chem. Soc. Rev.
2015, 44, 742–778.
In conclusion, we have developed a visible-light-induced
site-selective carboxylation reaction of indoles by direct CÀH
functionalization, in the presence of CBr4 and MeOH as the sol-
vent. The mild conditions requested (RT, few hours, 7 W Blue
LEDs) enable a wide functional-group tolerance. Further stud-
ies on photoredox-mediated carboxylation of different organic
compounds are currently underway in our laboratory.
[8] For selected reviews on visible light photocatalysis, see: a) T. P. Yoon,
M. A. Ischay, J. Du, Nat. Chem. 2010, 2, 527–532; b) J. M. Narayanam,
´
C. R. Stephenson, Chem. Soc. Rev. 2011, 40, 102–113; c) F. Teply, Collect.
Czech. Chem. Commun. 2011, 76, 859–917; d) L. Shi, W. Xia, Chem. Soc.
Rev. 2012, 41, 7687–7697; e) S. Maity, N. Zheng, Synlett 2012, 1851–
1856; f) J. Xuan, W.-J. Xiao, Angew. Chem. Int. Ed. 2012, 51, 6828–6838;
Angew. Chem. 2012, 124, 6934–6944; g) C. K. Prier, D. A. Rankic, D. W. C.
MacMillan, Chem. Rev. 2013, 113, 5322–5363; h) D. Ravelli, M. Fagnoni,
A. Albini, Chem. Soc. Rev. 2013, 42, 97–113; i) D. M. Schultz, T. P. Yoon,
Science 2014, 343, 1239176; j) E. Meggers, Chem. Commun. 2015, 51,
3290–3301.
Experimental Section
Representative procedure
To a 10 mL Schlenk flask equipped with a magnetic stirrer bar was
added MeOH (4 mL), which was bubbled with N2. 3-Methylindole
(1a) (0.2 mmol), CBr4 (2) (0.3 mmol), [Ru(bpy)3(PF6)2] (0.002 mmol),
and iPr2NH (0.4 mmol). The resulting solution was stirred at room
temperature under irradiation of 7 W blue LEDs at a distance of ap-
proximately 5 cm. Upon completion of the reaction, as monitored
by TLC, the solvent was removed under reduced pressure. The
crude residue was subjected to flash chromatography on silica gel
(silica: 240–400; eluent: cyclohexane/ethyl acetate=20:1) to pro-
vide pure methyl 3-methylindole 2-carboxylate (3a) as a white
solid; yield: 90%.
[9] a) S. Maity, N. Zheng, Angew. Chem. Int. Ed. 2012, 51, 9562–9566;
Angew. Chem. 2012, 124, 9700–9704; b) S.-Q. Zhu, A. Das, L. Bui, H.-J.
Zhou, D. P. Curran, M. Rueping, J. Am. Chem. Soc. 2013, 135, 1823–
1829; c) E. P. Farney, T. P. Yoon, Angew. Chem. Int. Ed. 2014, 53, 793–797;
Angew. Chem. 2014, 126, 812–816; d) X.-D. Xia, J. Xuan, Q. Wang, L.-Q.
Lu, J.-R. Chen, W.-J. Xiao, Adv. Synth. Catal. 2014, 356, 2807–2812; e) J.
Zoller, D. C. Fabry, M. A. Ronge, M. Rueping, Angew. Chem. Int. Ed. 2014,
53, 13264–13268; Angew. Chem. 2014, 126, 13480–13484.
[10] a) J. W. Tucker, J. M. R. Narayanam, S. W. Krabbe, C. R. J. Stephenson,
Org. Lett. 2010, 12, 368–371; b) L. Furst, B. S. Matsuura, J. M. R. Naraya-
nam, J. W. Tucker, C. R. J. Stephenson, Org. Lett. 2010, 12, 3104–3107;
c) L. Furst, J. M. R. Narayanam, C. R. J. Stephenson, Angew. Chem. Int. Ed.
2011, 50, 9655–9659; Angew. Chem. 2011, 123, 9829–9833; d) Z.-Q.
Wang, M. Hu, X.-C. Huang, L.-B. Gong, Y.-X. Xie, J.-H. Li, J. Org. Chem.
2012, 77, 8705–8711; e) S. Zhu, M. Rueping, Chem. Commun. 2012, 48,
11960–11962; f) X. Li, X. Gu, Y. Li, P. Li, ACS Catal. 2014, 4, 1897–1900;
g) S. R. Kandukuri, A. Bahamonde, I. Chatterjee, I. D. Jurberg, E. C. Escu-
dero-Adan, P. Melchiorre, Angew. Chem. Int. Ed. 2015, 54, 1485–1489;
Angew. Chem. 2015, 127, 1505–1509; h) J. J. Devery III, J. J. Douglas,
J. D. Nguyen, K. P. Cole, R. A. Flowers II, C. R. J. Stephenson, Chem. Sci.
2015, 6, 537.
Acknowledgements
We are grateful to the University of Bologna, Q.-Q.Y. thanks the
China Scholarship Council for financial support. M.M. and P.C.
acknowledge the European Commission ERC Starting Grant
(PhotoSi, 278912).
Keywords: carboxylation
methanolysis · photocatalysis · visible light
·
indole functionalization
·
[11] E. Arceo, I. D. Jurberg, A. lvarez-Fernµndez, P. Melchiorre, Nat. Chem.
2013, 5, 750–756.
[12] a) W. Guo, L.-Q. Lu, Y. Wang, Y.-N. Wang, J.-R. Chen, W.-J. Xiao, Angew.
Chem. Int. Ed. 2015, 54, 2265–2269; Angew. Chem. 2015, 127, 2293–
2297; b) M. Majek, A. Jacobi von Wangelin, Angew. Chem. Int. Ed. 2015,
[1] a) T. Kawasaki, K. Higuchi, Nat. Prod. Rep. 2005, 22, 761–793; b) M.
d’Ischia, A. Napolitano, A. Pezzella, in Comprehensive Heterocyclic Chem-
Chem. Eur. J. 2015, 21, 18052 – 18056
www.chemeurj.org
18055
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
54, 2270–2274; Angew. Chem. 2015, 127, 2298–2302; c) Q.-Q. Zhou, W.
Guo, W. Ding, X. Wu, X. Chen, L.-Q. Lu, W.-J. Xiao, Angew. Chem. Int. Ed.
2015, 54, 11196–11199; Angew. Chem. 2015, 127, 11348–11351.
[13] a) K. Mitani, T. Kiriyama, T. Kuratate, J. Org. Chem. 1994, 59, 1279–1282;
b) K. Fukui, K. Morokuma, H. Kato, T. Yonezawa, Bull. Chem. Soc. Jpn.
1963, 36, 217–222.
[14] a) C. Dai, J. M. R. Narayanam, C. R. J. Stephenson, Nat. Chem. 2011, 3,
140–145; b) M. D. Konieczynska, C. Dai, C. R. J. Stephenson, Org. Biomol.
Chem. 2012, 10, 4509–4511; c) C.-J. Wallentin, J. D. Nguyen, P. Fink-
beiner, C. R. J. Stephenson, J. Am. Chem. Soc. 2012, 134, 8875–8884;
d) Y. Zhao, Z. Li, C. Yang, R. Lin, W. Xia, Beilstein J. Org. Chem. 2014, 10,
622–627; e) V. P. Srivastava, A. K. Yadav, L. D. S. Yadav, Synlett 2014,
665–670; f) A. K. Yadav, V. P. Srivastava, L. D. S. Yadav, RSC Adv. 2014, 4,
24498–24503; g) R. Lin, H. Sun, C. Yang, Y. Yang, X. Zhao, W. Xia, Beil-
stein J. Org. Chem. 2015, 11, 31–36.
Mancinelli, M. Bandini, Org. Lett. 2012, 14, 1350–1353; g) M. Chiarucci,
E. Matteucci, G. Cera, G. Fabrizi, M. Bandini, Chem. Asian J. 2013, 8,
1776–1779; h) M. Chiarucci, R. Mocci, L.-D. Syntrivanis, G. Cera, A. Maz-
zanti, M. Bandini, Angew. Chem. Int. Ed. 2013, 52, 10850–10853; Angew.
Chem. 2013, 125, 11050–11053; i) C. Romano, M. Jia, M. Monari, E.
Manoni, M. Bandini, Angew. Chem. Int. Ed. 2014, 53, 13854–13857;
Angew. Chem. 2014, 126, 14074–14077; j) M. Jia, M. Monari, Q.-Q. Yang,
M. Bandini, Chem. Commun. 2015, 51, 2320–2323.
[18] R. I. Khusnutdinov, A. R. Baiguzina, R. R. Mukminov, Russ. J. Org. Chem.
2011, 47, 437–441. For other contributions of the team on the same
topic see: a) R. I. Khusnutdinov, A. R. Baiguzina, R. R. Mukminov, U. M.
Dzhemilev, Russ. J. Appl. Chem. 2009, 82, 340–342; b) R. I. Khusnutdi-
nov, A. R. Baiguzina, R. R. Mukminov, Russ. J. Org. Chem. 2010, 46,
1399–1402; c) R. I. Khusnutdinov, A. R. Baiguzina, R. R. Mukminov, I. V.
Akhmetov, I. M. Gubaidullin, S. I. Spivak, U. M. Dzhemilev, Russ. J. Org.
Chem. 2010, 46, 1053–1059; d) R. I. Khusnutdinov, A. R. Bayguzina, R. R.
Mukminov, Russ. Chem. Bull. 2013, 62, 93–97.
[15] G. N. Gururaja, S. M. Mobin, I. N. N. Namboothiri, A. R. Baiguzina, Eur. J.
Org. Chem. 2011, 2048–2052.
[16] a) J. D. Nguyen, J. W. Tucker, M. D. Konieczynska, C. R. J. Stephenson, J.
Am. Chem. Soc. 2011, 133, 4160–4163; b) E. Arceo, E. Montroni, P. Mel-
chiorre, Angew. Chem. Int. Ed. 2014, 53, 12064–12068; Angew. Chem.
2014, 126, 12260–12264.
[19] The base was added as a scavenger of the HX delivered during the re-
action cycle.
[20] See the Supporting Information for a complete list of screening of reac-
tion conditions.
[17] a) M. Bandini, A. Eichholzer, Angew. Chem. Int. Ed. 2009, 48, 9533–9537;
Angew. Chem. 2009, 121, 9697–9701; b) M. Bandini, A. Gualandi, M.
Monari, A. Romaniello, D. Savoia, M. Tragni, J. Organomet. Chem. 2011,
696, 338–347; c) G. Cera, P. Crispino, M. Monari, M. Bandini, Chem.
Commun. 2011, 47, 7803–7805; d) M. Bandini, Angew. Chem. Int. Ed.
2011, 50, 994–995; Angew. Chem. 2011, 123, 1026–1027; e) G. Cera, S.
Piscitelli, M. Chiarucci, G. Fabrizi, A. Goggiamani, R. S. Ramån, S. P.
Nolan, M. Bandini, Angew. Chem. Int. Ed. 2012, 51, 9891–9895; Angew.
Chem. 2012, 124, 10029–10033; f) G. Cera, M. Chiarucci, A. Mazzanti, M.
[21] E. LØonel, M. Lejaye, S. Oudeyer, J. P. Paugam, J.-Y. NØdØlec, Tetrahedron
Lett. 2004, 45, 2635–2638 (see also ref. [14a]).
[22] M. A. Cismesia, T. P. Yoon, Chem. Sci. 2015, 6, 5426–5434.
[23] Q. Kong, M. Wulff, J. H. Lee, S. Bratos, H. Ihee, J. Am. Chem. Soc. 2007,
129, 13584–13591.
Received: September 21, 2015
Published online on October 28, 2015
Chem. Eur. J. 2015, 21, 18052 – 18056
www.chemeurj.org
18056
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