Solvent-Controlled C2/C5-Regiodivergent Alkenylation of Pyrroles

Article abstract of DOI:10.1002/chem.201502418

A solvent-controlled C2/C5-selective alkenylation of 3,4-disubstituted pyrroles has been developed. The C3 substituent of pyrroles proved crucial to the regioselectivity. Substrates bearing directing groups at the C3 position exhibited excellent C2-select

Full text of DOI:10.1002/chem.201502418

DOI: 10.1002/chem.201502418
Full Paper
&
Heterocycles
Solvent-Controlled C2/C5-Regiodivergent Alkenylation of Pyrroles
Youla Su, Shang Gao, Yue Huang, Aijun Lin,* and Hequan Yao*[a]
Abstract: A solvent-controlled C2/C5-selective alkenylation
of 3,4-disubstituted pyrroles has been developed. The C3
substituent of pyrroles proved crucial to the regioselectivity.
Substrates bearing directing groups at the C3 position ex-
hibited excellent C2-selectivities in chelation-assisted CÀH
activation in toluene or 1,4-dioxane. However, a DMSO/DMF
solvent system could override the chelation effect of weak
directing groups, such as carboxylate and carbonyl groups,
favoring instead regioselectivity towards the more electron-
rich C5 position. A series of 3-carboxylate and 3-carbonyl
pyrroles were tested and showed moderate to good yields
with good regioselectivities for both C2- and C5-alkenylation
process.
Introduction
Substituted pyrroles represent privileged structural motifs of
medicinal and therapeutic activity that are found in many nat-
ural products[1] and bioactive molecules[2] (Figure 1). Prevalent
strategies[3] for preparing substituted pyrroles typically require
several steps from specific starting materials, rendering the
construction of pyrrole-containing molecular libraries incon-
venient. As an alternative method, employing transition metal-
catalyzed CÀH activation in the synthesis of heteroarenes, in-
cluding pyrroles, has attracted considerable attention over the
last decade.[4] In particular, regioselective CÀH functionalization
has allowed the step-efficient production of structures with di-
verse substituted patterns from unfunctionalized platforms.[5]
In 2006, Gaunt and co-workers developed a switchable C2/C3
alkenylation of simple pyrroles, whereby N-protecting groups
differentiated
the
steric
and
electronic
properties
(Scheme 1a).[6] N-Boc (Boc=tert-butoxycarbonyl) pyrroles led
to C2-alkenylated products, whereas N-TIPS (TIPS=triisopropyl-
silyl) pyrroles gave C3-alkenylated products. In 2014, Itami, Ya-
maguchi and co-workers disclosed a catalyst-controlled switch-
able C2/C3 arylation of pyrroles (Scheme 1b).[7] RhI catalyst led
to the formation of C3-arylation products, whereas opposite
site selectivity (C2 arylation) was obtained with Pd0 catalyst.
For more challenging C2/C5-selective functionalization of pyr-
roles, we reported a solvent-controlled switchable C2/C5 alke-
Figure 1. Natural products and bioactive small molecules containing pyrrole
skeletons.
nylation
of
4-aryl-1H-pyrrole-3-carboxylates
in
2014
(Scheme 1c).[8] Simply changing the solvent from toluene to
[a] Y. Su,+ S. Gao,+ Y. Huang, Dr. A. Lin, Prof. Dr. H. Yao
State Key Laboratory of Natural Medicines (SKLNM) and
Department of Medicinal Chemistry, School of Pharmacy
China Pharmaceutical University, Nanjing, 210009 (P. R. China)
E-mail: hyao@cpu.edu.cn
DMSO/DMF reversed the regioselectivity from C2 to C5 posi-
tion of pyrroles. Our previous results mostly focused on pyr-
roles bearing a carboxylate at C3 and a phenyl group at C4. In
the course of our further study, herein we will explore a series
of 3,4-disubstituted pyrroles in detail to gain insights into the
reaction mechanism and expand the utility of our solvent-con-
trolled regioselective CÀH alkenylation of pyrroles comprehen-
sively (Scheme 1d).
ajlin@cpu.edu.cn
[+] These authors contributed equally to this work.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201502418.
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taining strong ortho-directing
groups at C3, such as CN (1 f)
and CONHnBu (1g), C2-alkenyla-
tion products 2 f and 2g could
be obtained in 67% and 78%
yields with excellent regioselec-
tivities.
Unfortunately,
they
showed poor regioselectivities
for C5-alkenylation (1:1 for 3 f
and 1:1.5 for 3g ), resulting in
an inseparable mixture of C2-,
C5-, and C2,5-alkenylation prod-
ucts. CF3-substituted pyrrole 1h,
without chelating effect, offered
C5-alkenylation product 3h in
24% yield instead of C2-alkeny-
lation product 2h in toluene and
C5-alkenylation product 3h in
67% yield with excellent regiose-
lectivity (3/2=22:1) in DMSO/
DMF. Based on the above obser-
vations, we could conclude that
C2-alkenylation was brought
Scheme 1. Regioselective CÀH functionalization of pyrroles.
about by coordination of the di-
recting group at C3 with PdII. All
of the substrates with directing
Results and Discussion
groups at C3 (1b–g), underwent C2-alkenylation in moderate
to good yields and excellent regioselectivities. DMSO/DMF
could compete with the weak chelating effect[9] of carboxylate,
carbonyl, nitro and methoxymethyl groups, and reverse the re-
gioselectivity towards the more electron-rich position of pyr-
roles (C5 position of pyrroles 1b–d). In the case of substrate
1e, the electron density at C2 and C5 was similar, which led to
Our initial investigation on the olefination of N-methyl-3-
phenyl-1H-pyrrole (1a), utilizing previously reported optimized
conditions,[8] revealed that the C2-alkenylation product 2a was
formed with good regioselectivity in both toluene and DMSO/
DMF, whereas selective alkenylation at the more sterically hin-
dered C5 position failed (Table 1). Both C2- and C5-alkenylation
products could be obtained in good yields and regioselectivi-
ties by using 4-phenyl pyrrole-3-carboxylate 1b as substrate
(2b, 83%, 2/3=93:7; 3b, 73%, 3/2=8:1). Next, other 4-phenyl
pyrroles incorporating different substituents at the C3 position
were designed for further study.
a
mixture of C2, C5, and C2,5-alkenylation products
(Scheme 2).
Next we turned our attention to the C2-alkenylation of vari-
ous 3,4-disubstituted pyrroles in toluene (Table 2). When R2 =
3-Acetyl pyrrole gave C2-alkeny-
lation product 2c in 82% yield
(2/3>95:5) and C5-alkenylation
product 3c in 72% yield (3/2=
8:1), respectively. In addition,
subjecting a substrate with nitro
group at C3 to the standard re-
action conditions led to de-
creased yields in both toluene
and DMSO/DMF (2d in 45% and
3d in 56% yield). C3-methoxy-
methyl-substituted pyrrole 1e
provided C2-alkenylation prod-
uct 2e in 47% yield with good
regioselectivity in toluene. How-
ever, 1e gave poor yield and re-
gioselectivity for C5-alkenylation
(3e in 6% yield, 3/2=1:3.5) in
DMSO/DMF. For substrates con- Scheme 2. Proposed reaction mechanisms
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Table 1. Substrate scope of 4-phenyl pyrroles.[a]
C2-alkenylated products[b]
Yield [%][d]
Ratio (2/3)[e]
>95:5
C5-alkenylated products[c]
Yield [%][d]
trace[f]
Ratio (3/2)[e]
2a
2b
2c
2d
2e
2 f
27
83
3a
3b
3c
3d
3e
3 f
–
93:7
>95:5
84:16
93:7
73
8:1
8:1
4:1
1:3.5
1:1
82
72
45
56
47
6[g,h]
40[g]
26[g]
67
67
>95:5
>95:5
–
2g
2h
78
3g
3h
1:1.5
trace[i]
22:1
[a] Reaction conditions: 1a–h (0.5 mmol), Pd(OAc)2 (10 mol%), AgOAc (1.0 mmol), and acrylate (1.0 mmol) in solvent (2.0 mL), 808C, 20 h; [b] toluene as sol-
vent; [c] DMF/DMSO (4:1 v/v) as solvent; [d] yield of isolated product; [e] ratios were determined by 1H NMR spectroscopy using dibromomethane (d=
4.80 ppm) as the internal standard; [f] C2-alkenylation product 2a and C2,5-dialkenylation product were obtained in 32% and 15% yields, respectively;
[g] yield was determined by 1H NMR spectroscopy; [h] 2e and C2,5-dialkenylation product were obtained in 22% and 21% yields, respectively; [i] 3h was
obtained in 24% yield.
H, the reaction of 1ba with acrylate gave the C2-alkenylation
product 2ba in 35% yield. For 1,4-dimethyl pyrrole-3-carboxyl-
ate (1bb), the corresponding C2-alkenylation product 2bb was
obtained in 43% yield in toluene, and 71% yield in 1,4-diox-
ane, possibly because the 1,4-dioxane coordinated with PdII,[10]
stabilizing the reaction intermediate to improve the reactivity.
Substrates bearing n-butyl, cyclohexyl, or benzyl group at the
C4 position furnished the C2-alkenylation product in moderate
yields (2bc in 50%, 2bd in 69%, and 2be in 51% yield) with
good regioselectivities. As with pyrrole-3-carboxylates, 3-acetyl
pyrroles could also react with acrylate to give the C2-alkenyla-
tion products 2ca and 2cb in 63% and 70% yield, respectively.
Applying 3-propionyl, 3-pivaloyl, or 3-benzoyl pyrroles as sub-
strates, the corresponding C2-alkenylation products 2cc–ce
were obtained in 60%, 85%, and 83% yields. Moreover, elec-
tronically and regionally diverse methyl, methoxy, chloro, and
trifluoromethyl groups on the benzoyl group were all tolerated
under standard reaction conditions. The yields with electron-
withdrawing groups were lower than those with electron-do-
nating groups (60% for CF3 in 2ci vs. 85% for OMe in 2cg).
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Table 2. C2-alkenylation of 3,4-disubstituted pyrroles.[a]
Table 3. C5-alkenylation of 3,4-disubstituted pyrroles.[a]
Yield [%][b] Ratio
C2-alkenylation products
Yield [%][b] Ratio
C5-alkenylation products
(2/3)[c]
(3/2)[c]
R2 =H
2ba 35
3.5:1
>95:5
>95:5
>95:5
>95:5
91:9
R2 =H
R2 =Me
R2 =nBu
R2 =Cy
R2 =Bn
3ba 57[d]
4:1
20:1
10:1
1:1
3bb 72[d]
3bc 42[d]
3bd 35[d]
3be 65[d]
43
R2 =Me 2bb
71[d]
32
R2 =nBu 2bc
50[d]
8:1
R2 =Cy
R2 =Bn
2bd 69
2be 51[d]
R2 =Me
R2 =iPr
3ca 71
3cb 41
5:1
4:1
83:17
R2 =Me
R2 =iPr
2ca 63[d]
2cb 70[d]
95:5
>95:5
3cc 73
3cd 71
3ce 52
9:1
20:1
8:1
2cc 60
2cd 85
2ce 83
>95:5
>95:5
>95:5
R4 =o-Me 3cf 62
R4 =p-OMe 3cg 58
3ch 70
R4 =p-CF3 3ci 71
6:1
7:1
7:1
7:1
R4 =o-Me 2cf 65
R4 =p-OMe 2cg 85
R4 =p-Cl 2ch 69
R4 =p-CF3 2ci 60
>95:5
>95:5
95:5
R4 =p-Cl
94:6
3cj 64
6:1
2cj 92
>95:5
[a] Reaction conditions (unless otherwise stated): 1 (0.5 mmol), Pd(OAc)2
(10 mol%), AgOAc (1.0 mmol), and alkene (1.0 mmol) in DMF/DMSO
(2:1 v/v, 2.0 mL), 808C, 20 h; [b] yield of isolated product; [c] ratios were
determined by 1H NMR spectroscopy using dibromomethane (d=
4.80 ppm) as the internal standard; [d] DMF/DMSO (4:1 v/v, 2.0 mL) as sol-
vent.
[a] Reaction conditions:
1 (0.5 mmol), Pd(OAc)2 (10 mol%), AgOAc
(1.0 mmol), and alkene (1.0 mmol) in toluene (2.0 mL), 808C, 20 h;
[b] yield of isolated product; [c] ratios were determined by 1H NMR spec-
troscopy using dibromomethane (d=4.80 ppm) as the internal standard;
[d] 1,4-dioxane as solvent.
C4-naphthyl pyrrole 1cj was converted into the desired prod-
uct 2cj in 92% yield.
65%, and 3ca in 71% yield. However, for some sterically bulky
substituents, such as iPr (1cb), nBu (1bc), and Cy (1bd), the
yields of C5-alkenylation decreased. Changing the C3-acetyl
group into propionyl or pivaloyl resulted in 3cc and 3 cd in
73% and 71% yields, respectively. In contrast to C2-alkenyla-
tion, substrates containing electron-withdrawing groups on
the phenyl ring of benzoyl groups gave C5-alkenylation prod-
ucts in higher yields than those with electron-donating groups
(71% for CF3 in 3ci vs. 58% for OMe in 3cg).
After the investigation of C2-alkenylation of 3,4-disubstituted
pyrroles in toluene or 1,4-dioxane, we then explored the scope
of C5-alkenylation in DMSO/DMF solvent mixture (Table 3).
Methyl pyrrole-3-carboxylate (1ba) afforded the C5-alkenyla-
tion product 3ba in 57% yield. For most 4-alkyl-substituted
pyrroles, the desired products were obtained in moderate to
good yields and regioselectivities, that is, 3bb in 72%, 3be in
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Combining our solvent-controlled regiodivergent alkenyla-
tion of pyrrole with the van Leusen reaction[11] provided
a straightforward approach for the construction of various
1,2,3,4-tetrasubstituted pyrroles. For example, compounds 2c
and 3c, the C2- and C5-alkenylated products derived from the
same substrate 1c in different solvents, can undergo diverse
cross couplings[12] to give 3,4-dialkenyl-[13] (4 and 6) or aryl-sub-
stituted pyrroles (5)[14] in moderate to good yields (Scheme 3).
CÀH functionalization of the ketoxime derived from 3c with
diazo compounds[15] led to the formation of 2-alkenyl pyrrole-
fused-pyridine N-oxide building block 7, which could not be
obtained by final-step alkenylation of pyrrole-fused-pyridine N-
oxides.
and regioselectivities. Moreover, various 1,2,3,4-tetrasubstituted
pyrroles could be synthesized through our regioselective strat-
egy. Given the importance of pyrrole structural motifs in natu-
ral products and pharmaceutical intermediates, this method
will be useful for the synthesis of the pyrrole-containing com-
pounds.
Experimental Section[12]
General procedure for C2ÀH alkenylation: A suspension of
Pd(OAc)2 (10 mol%), acrylate (1.0 mmol, 2 equiv), AgOAc
(
1.0 mmol, 2 equiv), and pyrrole 1 (0.5 mmol, 1 equiv) in toluene or
1,4-dioxane (2 mL) was introduced to a Schlenk tube. After stirring
at 808C for 20 h under air, the reaction mixture was diluted with
ethyl acetate, and filtered through a pad of celite. Volatiles were re-
moved under reduced pressure to give the crude product, which
was purified by flash column chromatography on silica gel to
afford the C2-alkenylated pyrrole 2.
General procedure for C5ÀH alkenylation: A suspension of
Pd(OAc)2 (10 mol%), acrylate (1.0 mmol, 2 equiv), AgOAc
(1.0 mmol, 2 equiv), and pyrrole
1 (0.5 mmol, 1 equiv) in
DMF:DMSO (v/v, 4:1 or 2:1, 2 mL) was introduced to a Schlenk
tube and vigorously stirred at 808C for 20 h under air inert atmos-
phere. After cooling to room temperature, the reaction mixture
was diluted with ethyl acetate (15 mL) and water (15 mL), and then
filtered through a plug of Celite. The organic phase was separated
and washed with water (10”2 mL). The aqueous layers were fur-
ther extracted with ethyl acetate. The combined organic extracts
were dried, filtered and solvents were removed under reduced
pressure. The crude product was purified by flash chromatography
on silica gel to afford the C5-alkenylated pyrrole 3.
Acknowledgements
Generous financial support from the National Natural Science
Foundation of China (NSFC21272276 and NSFC21572272), the
Natural Science Foundation of Jiangsu Province (BK20140655
and BK20130645), and the Foundation of State Key Laboratory
of Natural Medicines (ZZJQ201306) is gratefully acknowledged.
Scheme 3. Functionalization of the alkenylated products. Reaction condi-
tions: a) n-butyl acrylate, Pd(OAc)2, AgOAc, toluene, 808C, 20 h; b) n-butyl
acrylate, Pd(OAc)2, AgOAc, DMF/DMSO (4:1 v/v), 808C, 20 h; c) acrylamide,
Pd(OAc)2, AgOAc, toluene, 808C, 12 h; d) 1-iodo-4-methoxybenzene, PdCl2,
PPh3, Ag2CO3, DMF, Ar, 808C, 12 h; e) 1,2-bis(4-bromophenyl)ethyne,
[(RhCp*Cl2)2], AgSbF6, Cu(OAc)2, 1208C, 12 h; f) Py, NH2OH·HCl, EtOH, reflux
1 h; diazo compounds, [(RhCp*Cl2)2], NaOAc, MeOH, 808C,12 h.
Keywords: alkenes
·
CÀH activation
·
pyrroles
·
regioselectivity · solvent effects
[1] For representative reviews on pyrrole-containing natural products, see:
a) J. Robertson, K. Stevens, Nat. Prod. Rep. 2014, 31, 1721–1788; b) I. S.
Young, P. D. Thornton, A. Thompson, Nat. Prod. Rep. 2010, 27, 1801–
1839; c) R. Rane, N. Sahu, C. Shah, R. Karpoormath, Curr. Top. Med.
Chem. 2014, 14, 253–273.
[2] a) V. Bhardwaj, D. Gumber, V. Abbot, S. Dhiman, P. Sharma, RSC Adv.
2015, 5, 15233–15266; b) A. Mai, S. Massa, I. Cerbara, S. Valente, R.
Ragno, P. Bottoni, R. Scatena, P. Loidl, G. Brosch, J. Med. Chem. 2004, 47,
1098–1109; c) C. L. Fleming, T. D. Ashton, V. Gaur, S. L. McGee, F. M.
Pfeffer, J. Med. Chem. 2014, 57, 1132–1135; d) M. Nguyen, R. C. Marcel-
lus, A. Roulston, M. Watson, L. Serfass, S. R. Murthy Madiraju, D. Goulet,
J. Viallet, L. BØlec, X. Billot, S. Acoca, E. Purisima, A. Wiegmans, L. Cluse,
R. W. Johnstone, P. Beauparlant, G. C. Shore, Proc. Natl. Acad. Sci. USA
2007, 104, 19512–19517.
Conclusion
In summary, we have reported a solvent-controlled regiodiver-
gent CÀH alkenylation of 3,4-disubstituted pyrroles. The effect
of C3 substituents on the regioselectivity of alkenylation were
investigated in detail. C2-alkenylation was accomplished
through the chelating effects of directing groups at C3 in tolu-
ene or 1,4-dioxane solvents. A DMSO/DMF solvent system
could override the weak coordination effect of carboxylate and
carbonyl groups to favor C5-alkenylation. The strong coordina-
tion of cyano and amide groups could not be completely re-
versed by DMSO/DMF. Electron-withdrawing groups, such as
CF3, only gave C5-alkenylated products. A series of 3-carboxyl-
ate- and 3-carbonyl-substituted pyrroles were tested and gave
C2- and C5-alkenylation products in moderate to good yields
[3] a) V. EstØvez, M. Villacampa, J. C. MenØndez, Chem. Soc. Rev. 2014, 43,
4633–4657; b) V. EstØvez, M. Villacampa, J. C. MenØndez, Chem. Soc.
Rev. 2010, 39, 4402–4421; c) S. D. Joshi, U. A. More, V. H. Kulkarni, T. M.
Aminabhavi, Curr. Org. Chem. 2013, 17, 2279–2304.
Chem. Eur. J. 2015, 21, 15820 – 15825
www.chemeurj.org
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[4] For recent reviews on CÀH activation processes in synthesis of hetero-
cycles, see: a) A. V. Gulevich, A. S. Dudnik, N. Chernyak, V. Gevorgyan,
Chem. Rev. 2013, 113, 3084–3213; b) A. V. Gulevich, V. Gevorgyan,
Chem. Heterocycl. Compd. 2012, 48, 17–20; c) A. S. Dudnik, V. Gevorgy-
an in Catalyzed Carbon-Heteroatom Bond Formation (Ed.: A. K. Yudin),
Wiley-VCH, Weinheim, 2011, chapter 8, pp. 227–316; d) R. Jazzar, J.
Hitce, A. Renaudat, J. Sofack-Kreutzer, O. Baudoin, Chem. Eur. J. 2010,
16, 2654–2672; e) T. Guo, F. Huang, L. Yu, Z. Yu, Tetrahedron Lett. 2015,
56, 296–302.
[5] For selected examples of regioselective CÀH functionalizations of heter-
oarenes, see: a) S. Tani, T. N. Uehara, J. Yamaguchi, K. Itami, Chem. Sci.
2014, 5, 123–135; b) F. Zhao, Y.-F. Zhang, J. Wen, D.-G. Yu, J.-B. Wei, Z.
Xi, Z.-J. Shi, Org. Lett. 2013, 15, 3230–3233; c) L.-C. Campeau, M. Ber-
trand-Laperle, J.-P. Leclerc, E. Villemure, S. Gorelsky, K. Fagnou, J. Am.
Chem. Soc. 2008, 130, 3276–3277; d) D. Lapointe, T. Markiewicz, C. J.
Whipp, A. Toderian, K. Fagnou, J. Org. Chem. 2011, 76, 749–759; e) I.
Sasaki, J. Taguchi, S. Hiraki, H. Ito, T. Ishiyama, Chem. Eur. J. 2015, 21,
9236–9241; f) I. A. Sanhueza, A. M. Wagner, M. S. Sanford, F. Schoene-
beck, Chem. Sci. 2013, 4, 2767–2775; g) S. Yanagisawa, K. Ueda, H. Seki-
zawa, K. Itami, J. Am. Chem. Soc. 2009, 131, 14622–14623; h) J. P. Brand,
J. Charpentier, J. Waser, Angew. Chem. Int. Ed. 2009, 48, 9346–9349;
Angew. Chem. 2009, 121, 9510–9513; i) G. L. Tolnai, S. Ganss, J. P. Brand,
J. Waser, Org. Lett. 2013, 15, 112–115; j) Y. Fall, H. Doucet, M. Santelli,
ChemSusChem 2009, 2, 153–157; k) J. J. Dong, D. Roy, R. J. Roy, M.
Ionita, H. Doucet, Synthesis 2011, 2011, 3530–3546.
[8] Y. Su, H. Zhou, J. Chen, J. Xu, X. Wu, A. Lin, H. Yao, Org. Lett. 2014, 16,
4884–4887.
[9] a) G. Li, L. Wan, G. Zhang, D. Leow, J. Spangler, J.-Q. Yu, J. Am. Chem.
Soc. 2015, 137, 4391–4397; b) J. Kim, S. Chang, Angew. Chem. Int. Ed.
2014, 53, 2203–2207; Angew. Chem. 2014, 126, 2235–2239; c) R. Feng,
W. Yu, K. Wang, Z. Liu, Y. Zhang, Adv. Synth. Catal. 2014, 356, 1501–
1508; d) V. O. Iaroshenko, A. Gevorgyan, O. Davydova, A. Villinger, P.
Langer, J. Org. Chem. 2014, 79, 2906–2915; e) G. Li, D. Leow, L. Wan, J.-
Q. Yu, Angew. Chem. Int. Ed. 2013, 52, 1245–1247; Angew. Chem. 2013,
125, 1283–1285.
[10] J. A. Molina de La Torre, P. Espinet, A. C. AlbØniz, Organometallics 2013,
32, 5428–5434.
[11] D. van Leusen, E. van Echten, A. M. van Leusen, J. Org. Chem. 1992, 57,
2245–2249.
[12] See the Supporting Information for experimental details.
[13] a) Z. Shi, S. Ding, Y. Cui, N. Jiao, Angew. Chem. Int. Ed. 2009, 48, 7895–
7898; Angew. Chem. 2009, 121, 8035–8038; b) F. W. Patureau, T. Besset,
N. Kuhl, F. Glorius, J. Am. Chem. Soc. 2011, 133, 2154–2156; c) Z. Li, L.
Ma, C. Tang, J. Xu, X. Wu, H. Yao, Tetrahedron Lett. 2011, 52, 5643–5647.
[14] a) A. M. Wagner, M. S. Sanford, Org. Lett. 2011, 13, 288–291; b) N. Lai-
daoui, J. Roger, A. Miloudi, D. El Abed, H. Doucet, Eur. J. Org. Chem.
2011, 2011, 4373–4385; c) L. Zhao, Z. Li, L. Chang, J. Xu, H. Yao, X. Wu,
Org. Lett. 2012, 14, 2066–2069.
[15] Z. Shi, D. C. Koester, M. Boultadakis-Arapinis, F. Glorius, J. Am. Chem.
Soc. 2013, 135, 12204–12207.
[6] E. M. Beck, N. P. Grimster, R. Hatley, M. J. Gaunt, J. Am. Chem. Soc. 2006,
128, 2528–2529.
Received: June 22, 2015
Published online on September 17, 2015
[7] K. Ueda, K. Amaike, R. M. Maceiczyk, K. Itami, J. Yamaguchi, J. Am. Chem.
Soc. 2014, 136, 13226–13232.
Chem. Eur. J. 2015, 21, 15820 – 15825
www.chemeurj.org
15825
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