DOI: 10.1039/C3CC45240A
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Hémez is gratefully acknowledged for HRMS analyses.
Notes and references
40 a Université de Nantes, UFR Sciences et Techniques, UMR CNRS 6230,
CEISAM, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3,
b Institut Universitaire de France, 103, Boulevard Saint-Michel, 75005
Paris Cedex 05, France.
45 † Electronic Supplementary Information (ESI) available: Experimental
procedures for all new compounds and computational details are
provided. See DOI: 10.1039/b000000x/
1 For selected references, see : (a) Joucla, L.; Djakovitch, L. Adv. Synth.
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2 (a) Perrier, A.; Maurel, F.; Jacquemin, D. Acc. Chem. Res. 2012, 45,
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Groenendaal, L.; Bruining, M. J.; Hendrickx, E. H. J.; Persoons, A.;
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10, 226. (d) Maeda, H.; Kinoshita, K.; Naritani, K.; Bando, Y. Chem.
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3 For recent examples, see: (a) Hari, D. P.; Schroll, P.; König, B. J. Am.
Chem. Soc. 2012, 134, 2958. (b) Singh, P. P.; Aithagani, S. K.; Yadav,
M.; Singh, V. P.; Vishwakarma, R. A. J. Org. Chem. 2013, 78, 2639.
4 Galli, C. Chem. Rev. 1988, 88, 765.
Scheme 3 Proposed catalytic cycle.
The corresponding imaginary frequency mode that
characterizes the transition state presents a frequency of 384
cm-1 (see ESI). We also note that the 1a+2→D reaction is
exergonic with a ΔG of -24.7 kcal.mol-1. Therefore both
thermodynamic and kinetic criteria go in the same direction
and indicate a preferred C2 attack.
5
5 For recent reviews on the Meerwein arylation, see : (a) Heinrich, M. R.
Chem. Eur. J. 2009, 15, 820; (b) Hari, D. P.; König, B. Angew. Chem. Int.
Ed. 2013, 52, 4734.
6 For recent references, see: (a) Racanè, L.; Tralić-Kulenović, V.; Boykin,
D. W.; Karminski-Zamola, G. Molecules 2003, 8, 342; (b) Obushak, N.
D.; Gorak, Y. I.; Matiichuk, V. S.; Lytvyn, R. Z. Russ. J. Org. Chem.
2008, 44, 1689; (c) Obushak, M. D.; Matiychuk, V. S.; Lytvyn, R. Z.
Chem. Heterocycl. Compd. 2008, 44, 936. (d) Gorak, Y. I.; Obushak, N.
D.; Matiichuk, V. S.; Lytvyn, R. Z. Russ. J. Org. Chem. 2009, 45, 541; (e)
Matiychuk, V. S.; Obushak, N. D.; Lytvyn, R. Z.; Horak, Y. I. Chem.
Heterocycl. Compd. 2010, 46, 50.
7 Pratsch, G.; Anger, C. A.; Ritter, K.; Heinrich, M. R. Chem. Eur. J.
2011, 17, 4104.
10
Scheme 4 Kinetic isotope effect.
8 Wetzel, A.; Pratsch, G.; Kolb, R.; Heinrich, M. R. Chem. Eur. J. 2010,
16, 2547.
The role of CaCO3 was also investigated with labelled
9 For examples of copper-catalyzed arylation of heteroarenes with
iodonium salts, see: (a) Beck, E. M.; Hatley, R.; Gaunt, M. J.; Angew.
Chem. Int. Ed. 2008, 47, 3004; (b) Phipps, R. J.; Grimster, N. P.; Gaunt,
M. J. J. Am. Chem. Soc. 2008, 130, 8172.
10 For examples on large scale, see: (a) Nielsen, M. A.; Nielsen, M. K.;
Pittelkow, T. Org. Process Res. Dev. 2004, 8, 1059; (b) Molinaro, C.;
Mowa, J.; Gosselin, F.; O’Shea, P. D.; Marcoux, J.-F.; Angelaud, R.;
Davies, I. W. J. Org. Chem. 2007, 72, 1856; (c) Maligres, P. E.;
Humphrey, G. R.; Marcoux, J.-F.; Hillier, M. C.; Zhao, D.; Krska, S.;
Grabowski, E. J. J. Org. Process Res. Dev. 2009, 13, 525.
11 a) Le Callonnec, F.; Fouquet, E.; Felpin, F.-X. Org. Lett. 2011, 13,
2646. b) Susperregui, N.; Miqueu, K.; Sotiropoulos, J.-M.; Le Callonnec,
F.; Fouquet, E.; Felpin, F.-X. Chem. Eur. J. 2012, 18, 7210.
12 Honraedt, A.; Le Callonnec, F.; Le Grognec, E.; Fernandez, V.;
Felpin, F.-X. J. Org. Chem. 2013, 78, 4604.
13 For in situ generated diazonium salts, see : (a) Doyle, M. P.; Siegfried,
B.; Elliott, R. C.; Dellaria, J. F. J. Org. Chem. 1977, 42, 2431; (b) Andrus,
M. B.; Song, C.; Zhang, J. Org. Lett. 2002, 4, 2079; (c) Wu, X.-F.;
Neumann, H.; Beller, M. Chem. Commun. 2011, 47, 7959.
14 Rondestvedt, C. S. Org. React. 1976, 24, 225.
experiments (Scheme 4). A kinetic isotope effect (kH/kD
3.16) was observed between pyrrole 2 and its deuterated
15 analogue d4-2, indicating that the C-H bond cleavage could be
involved in a rate limiting step. Thereby, we suggest that
CaCO3 could facilitate the deprotonation of the pyrrolo cation
E which likely follows undesirable pathways decreasing the
=
reaction yield in the absence of
a base. Theoretical
20 calculations of the transition states corresponding to
deprotonation could be found with both OH- and HCO-3
anions (see ESI) but not for MeSO-3, hinting that a sufficiently
efficient base is indeed necessary.
In summary, we have developped a Meerwein-type arylation
25 of pyrroles under very mild conditions. The methodology
features aqueous solvents, room temperature, inexpensive
reagents and catalysts, as well as experimental simplicity.
Experimental and theoritical studies provided mechanistic
insights.
Authors are thankful to the “Université de Nantes”, the
“CNRS”, and the “Région Pays de la Loire” in the framework
of a “Recrutement sur poste stratégique” for funding. D.J.
acknowledges the European Research Council (ERC) for
funding in the framework of a Starting Grant (Marches -
15 Kochi, J. K. J. Am. Chem. Soc. 1955, 77, 5090.
30
16 For the cleavage of the Boc group, see: Basaric, N.; Baruah, M.; Qin,
W.; Metten, B.; Smet, M.; Dehaen, W.; Boens, N. Org. Biomol. Chem.
2005, 3, 2755.
35 278845). This research used resources of the GENCI-
CINES/IDRIS, the CCIPL (Centre de Calcul Intensif des Pays
de Loire) and a local Troy cluster (Nantes University). Julie
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