ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Ruthenium-Catalyzed Alkyne Annulations
with Substituted 1H‑Pyrazoles by
CÀH/NÀH Bond Functionalizations
Wenbo Ma, Karolina Graczyk, and Lutz Ackermann*
€
Institut fu€r Organische und Biomolekulare Chemie, Georg-August-Universitat,
€
Tammannstrasse 2, 37077 Gottingen, Germany
Received November 9, 2012
ABSTRACT
Cationic ruthenium(II) complexes allowed for highly efficient oxidative annulations of aryl- and alkyl-substituted alkynes by 5-aryl-1H-pyrazoles.
The CÀH/NÀH bond functionalization strategy furthermore proved applicable to the high-yielding activation of heteroaryl as well as alkenyl CÀH
bonds.
Oxidative metal-catalyzed CÀH bond functionalization
reactions1 have emerged as versatile tools for the step-
economical assembly and functionalization of heterocycles.2
Particularly, domino reactions3 that involve the sequential
functionalization of CÀH and NÀH bonds are highly
desirable, which have as of yet mostly relied on the use
of Cp*-rhodium complexes.4 Conversely, significantly less
expensive ruthenium(II) complexes were only very recently
identified as catalysts for annulations of alkenes5 and
alkynes via oxidative CÀH bond functionalizations of
arenes.6 As part of our research program on the streamlining
(5) Selected examples: (a) Li, J.; Kornhaass, C.; Ackermann, L.
Chem. Commun. 2012, 48, 11343–11345. (b) Li, B.; Devaraj, K.; Darcel,
C.; Dixneuf, P. H. Green Chem. 2012, 14, 2706–2709. (c) Li, B.; Ma, J.;
Wang, N.; Feng, H.; Xu, S.; Wang, B. Org. Lett. 2012, 14, 736–739. (d)
Hashimoto, Y.; Ortloff, T.; Hirano, K.; Satoh, T.; Bolm, C.; Miura, M.
Chem. Lett. 2012, 41, 151–153. (e) Graczyk, K.; Ma, W.; Ackermann, L.
Org. Lett. 2012, 14, 4110–4113. (f) Kishor, P.; Jeganmohan, M. Org.
Lett. 2012, 14, 1134–1137. (g) Hashimoto, Y.; Ueyama, T.; Fukutani, T.;
Hirano, K.; Satoh, T.; Miura, M. Chem. Lett. 2011, 40, 1165–1166. (h)
Ackermann, L.; Pospech, J. Org. Lett. 2011, 13, 4153–4155. (i) Ueyama,
T.; Mochida, S.; Fukutani, T.; Hirano, K.; Satoh, T.; Miura, M. Org.
Lett. 2011, 13, 706–708. (j) A review: Kozhushkov, S. I.; Ackermann, L.
Chem. Sci. 2013, DOI:10.1039/C2SC21524A, and references cited
therein.
(1) Recent reviews: (a) Neufeldt, S. R.; Sanford, M. S. Acc. Chem.
Res. 2012, 45, 936–946. (b) Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q.
Acc. Chem. Res. 2012, 45, 788–802. (c) Arockiam, P. B.; Bruneau, C.;
Dixneuf, P. H. Chem. Rev. 2012, 112, 5879–5918. (d) Ackermann, L.;
Potukuchi, H. K. Org. Biomol. Chem. 2010, 8, 4503–4513. (e) Daugulis,
O. Top. Curr. Chem. 2010, 292, 57–84. (f) Colby, D. A.; Bergman, R. G.;
Ellman, J. A. Chem. Rev. 2010, 110, 624–655. (g) Ackermann, L.;
Vicente, R.; Kapdi, A. Angew. Chem., Int. Ed. 2009, 48, 9792–9826
and references cited therein.
(2) Selected reviews: (a) Mei, T.-S.; Kou, L.; Ma, S.; Engle, K. M.;
Yu, J.-Q. Synthesis 2012, 44, 1778–1791. (b) Thansandote, P.; Lautens,
M. Chem.;Eur. J. 2009, 15, 5874–5883. (c) Seregin, I. V.; Gevorgyan, V.
Chem. Soc. Rev. 2007, 36, 1173–1193.
(3) Tietze, L. F.; Brasche, G.; Gericke, K. M. Domino Reactions in
Organic Synthesis; Wiley-VCH: Weinheim, 2006.
(4) Reviews: (a) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41,
3651–3678. (b) Patureau, F. W.; Wencel-Delord, J.; Glorius, F. Aldri-
chimica Acta 2012, 45, 31–41. (c) Wencel-Delord, J.; Droege, T.; Liu, F.;
Glorius, F. Chem. Soc. Rev. 2011, 40, 4740–4761. (d) Satoh, T.; Miura,
M. Chem.;Eur. J. 2010, 16, 11212–11222 and references cited therein.
Selected examples: (e) Umeda, N.; Hirano, K.; Satoh, T.; Shibata, N.;
Sato, H.; Miura, M. J. Org. Chem. 2011, 76, 13–24. (f) Patureau, F. W.;
Besset, T.; Glorius, F. Angew. Chem., Int. Ed. 2011, 50, 1064–1067. (g)
Stuart, D. R.; Bertrand-Laperle, M.; Burgess, K. M. N.; Fagnou, K.
J. Am. Chem. Soc. 2008, 130, 16474–16475. (h) Ueura, K.; Satoh, T.;
Miura, M. J. Org. Chem. 2007, 72, 5362–5367.
(6) Illustrative examples: (a) Zhao, P.; Wang, F.; Han, K.; Li, X. Org.
Lett. 2012, 14, 5506–5509. (b) Kornhaass, C.; Li, J.; Ackermann, L.
J. Org. Chem. 2012, 77, 9190–9198. (c) Li, B.; Feng, H.; Wang, N.; Ma,
J.; Song, H.; Xu, S.; Wang, B. Chem.;Eur. J. 2012, 18, 12873–12879. (d)
Parthasarathy, K.; Senthilkumar, N.; Jayakumar, J.; Cheng, C.-H. Org.
Lett. 2012, 14, 3478–3481. (e) Thirunavukkarasu, V. S.; Donati, M.;
Ackermann, L. Org. Lett. 2012, 14, 3416–3419. (f) Chinnagolla, R. K.;
Jeganmohan, M. Chem. Commun. 2012, 48, 2030–2032. (g) Ackermann,
L.; Pospech, J.; Graczyk, K.; Rauch, K. Org. Lett. 2012, 14, 930–933. (h)
Ackermann, L.; Lygin, A. V. Org. Lett. 2012, 14, 764–767. (i) Ackermann,
L.; Wang, L.; Lygin, A. V. Chem. Sci. 2012, 3, 177–180. (j) Li, B.; Feng, H.;
Xu, S.; Wang, B. Chem.;Eur. J. 2011, 17, 12573–12577. (k) Ackermann,
L.; Fenner, S. Org. Lett. 2011, 13, 6548–6551. (l) Ackermann, L.; Lygin,
A. V.; Hofmann, N. Org. Lett. 2011, 13, 3278–3281. (m) Ackermann, L.;
Lygin, A. V.; Hofmann, N. Angew. Chem., Int. Ed. 2011, 50, 6379–6382.
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See also: (n) Ackermann, L.; Novak, P.; Vicente, R.; Pirovano, V.;
Potukuchi, H. K. Synthesis 2010, 2245–2253.
r
10.1021/ol303083n
XXXX American Chemical Society