ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Versatile Pyrrole Synthesis through
Ruthenium(II)-Catalyzed Alkene CÀH
Bond Functionalization on Enamines
Lianhui Wang and Lutz Ackermann*
€
Institut fu€r Organische und Biomolekulare Chemie, Georg-August-Universitat,
€
Tammannstrasse 2, 37077 Gottingen, Germany
Received November 22, 2012
ABSTRACT
An efficient ruthenium(II) catalyst enabled broadly applicable oxidative alkyne annulations with electron-rich enamines to provide diversely
decorated pyrroles, even in an aerobic fashion with air as the ideal oxidant.
Pyrroles are among the most abundant heterocycles and
represent indispensable structural motifs for instance in
bioactive natural products or material sciences.1À5 There-
fore, there is a continued strong demand for methods
that give broad access to this important heteroaromatic
scaffold. Despite significant recent advances through
transition-metal catalysis, the majority of available meth-
ods for pyrrole syntheses capitalized upon preactivation
of the N-containing substrates.1 Yet, considerable recent
progress was represented by Fagnou’s elegant pyrrole6 syn-
thesis via rhodium-catalyzed oxidative C(sp2)ÀH7 bond
functionalization8 on enamides.9À11 Unfortunately, the
high costs of the required rhodium(III) catalyst were,
among others, identified as a limitation of this approach.
In contrast, significantly less expensive ruthenium(II)
complexes12,13 were only very recently identified as viable
catalysts for oxidative alkyne annulations.14 Unfortu-
nately, these CÀH/NÀH bond functionalizations were
hitherto restricted to electron-deficient alkenes displaying
electron-withdrawing carbonylgroups. Inconsiderationof
(1) Bergman, J.; Janosik, T. In Modern Heterocyclic Chemistry;
Alvarez-Builla, J., Vaquero, J. J., Barluenga, J., Eds.; Wiley-VCH: Wein-
heim, 2011; Vol. 1, p 269.
(2) (a) Bauer, I.; Knoelker, H.-J. Top. Curr. Chem. 2012, 309, 203. (b)
Furstner, A. Angew. Chem., Int. Ed. 2003, 43, 3582.
€
(3) Ulrich, G.; Ziessel, R.; Harriman, A. Angew. Chem., Int. Ed. 2007,
47, 1184.
(4) Brothers, P. J. Inorg. Chem. 2011, 50, 12374.
(5) Gonc-alves, M. S. T. Chem. Rev. 2009, 109, 190.
(6) For progress in the oxidative synthesis of indoles, see: (a) Stuart,
D. R.; Bertrand-Laperle, M.; Burgess, K. M. N.; Fagnou, K. J. Am.
(9) Stuart, D. R.; Alsabeh, P.; Kuhn, M.; Fagnou, K. J. Am. Chem.
Soc. 2010, 132, 18326.
(10) Huestis, M. P.; Chan, L.; Stuart, D. R.; Fagnou, K. Angew.
Chem., Int. Ed. 2011, 50, 1338.
(11) Besset, T.; Kuhl, N.; Patureau, F. W.; Glorius, F. Chem.;Eur.
J. 2011, 17, 7167.
(12) Recent reviews on ruthenium-catalyzed CÀH bond functionali-
zations: (a) Kozhushkov, S. I.; Ackermann, L. Chem. Sci. 2013, DOI:
10.1039/C2SC21524. (b) Arockiam, A. P. B.; Bruneau, C.; Dixneuf, P. H.
Chem. Rev. 2012, 112, 5879. (c) Ackermann, L. Pure Appl. Chem. 2010,
82, 1403. (d) Ackermann, L.; Vicente, R. Top. Curr. Chem. 2010,
292, 211. For examples of cross-dehydrogenative alkenylations with
alkenes, see: (e) Ackermann, L.; Pospech, J. Org. Lett. 2011, 13, 4153.
(f) Ueyama, T.; Mochida, S.; Fukutani, T.; Hirano, K.; Satoh, T.;
Miura, M. Org. Lett. 2011, 13, 706. (g) Weissman, H.; Song, X.; Milstein,
D. J. Am. Chem. Soc. 2001, 123, 337 and references cited therein.
1100, Pd: 669, and Ru: 110 US$/troy oz.
€
Chem. Soc. 2008, 130, 16474. (b) Wurtz, S.; Rakshit, S.; Neumann, J. J.;
€
Droge, T.; Glorius, F. Angew. Chem., Int. Ed. 2008, 47, 7230. (c) Shi, Z.;
Zhang, C.; Li, S.; Pan, D.; Ding, S.; Cui, Y.; Jiao, N. Angew. Chem., Int.
Ed. 2009, 48, 4572. (d) Wei, Y.; Deb, I.; Yoshikai, N. J. Am. Chem. Soc.
2012, 134, 9098 and references cited therein.
(7) A rhodium-catalyzed functionalization of C(sp3)ÀH bonds: Rakshit,
S.; Patureau, F. W.; Glorius, F. J. Am. Chem. Soc. 2010, 132, 9585.
(8) Selected reviews on CÀH bond functionalization: (a) Neufeldt,
S. R.; Sanford, M. S. Acc. Chem. Res. 2012, 45, 936. (b) Engle, K. M.;
Mei, T.-S.; Wasa, M.; Yu, J.-Q. Acc. Chem. Res. 2012, 45, 788. (c)
€
Wencel-Delord, J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011,
40, 4740. (d) Ackermann, L.; Potukuchi, H. K. Org. Biomol. Chem. 2010,
8, 4503. (e) Daugulis, O. Top. Curr. Chem. 2010, 292, 57. (f) Sun, C.-L.;
Li, B.-J.; Shi, Z.-J. Chem. Commun. 2010, 46, 677. (g) Colby, D. A.;
Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (h) Satoh, T.;
Miura, M. Chem.;Eur. J. 2010, 16, 11212. (i) Ackermann, L.; Vicente,
R.; Kapdi, A. Angew. Chem., Int. Ed. 2009, 48, 9792. (j) Thansandote, P.;
Lautens, M. Chem.;Eur. J. 2009, 15, 5874.
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10.1021/ol303224e
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