ORGANIC
LETTERS
2011
Vol. 13, No. 4
660–663
Chemoselectivities in the Platinum-
Catalyzed Hydrative Carbocyclizations
of Oxo-Alkyne-Nitrile Functionalities
Anupam Mukherjee and Rai-Shung Liu*
Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan, ROC
Received December 1, 2010
ABSTRACT
Two new hydrative carbocyclizations of oxa-alkyne-nitrile functionalities are reported to produce distinct nitrogen-containing heterocycles.
Protracted heating of oxoalkynyl nitrile substrates with PtCl2/CO/H2O in hot 1,4-dioxane gave 2,3-dihydro-1H-pyrido[1.2-b]-isoquinolin-4(6H)-
ones. In this hydration reaction, dicarbonyl nitrile intermediates were isolated efficiently after a brief period, and they were subjected to an NHC-
based crossed benzoin coupling to give spiro alcohols that further reacted with TfOH to give spiro[indene-2,20-piperidine]-1,60(3H)-diones.
Regiocontrolled metal-catalyzed hydrations of alkynes
to form carbonyl derivatives are of prime interest in organic
synthesis.1,2 Hydrative coupling of an alkyne with another
functionality is particularly interesting because it not only
introduces a carbonyl group but also allows formation of a
C-C bond. Metal-catalyzed three-component couplings
are powerful tools to access complicated frameworks,3 but
hydrative carbocyclizations of alkynes are exclusively focused
on two-component coupling reactions, including 1,n-diynes,4
1-yne-5-enones,5 1-en-5-ynes,6 and 1-allen-n-ynes (n=5-7),7
with rare examples for three-component coupling reactions.8
WithPtCl2 catalysts, we found that the neighboring ketone
of 2-ketonyl-alkynylbenzenes 1 selectively controlled the
hydration regioselectivity of the tethered alkyne to produce
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(b) Trost, B. M.; Rudd, M. T. J. Am. Chem. Soc. 2005, 127, 4763. (c)
Odedra, A.; Wu, C.-J.; Pratap, T. B.; Huang, C.-W.; Ran, Y. F.; Liu, R.-
S. J. Am. Chem. Soc. 2005, 127, 3406. (d) Zhang, C.; Cui, D.-M.; Yao, L.-
Y.; Wang, B.-S.; Hu, Y.-Z.; Hayashi, T. J. Org. Chem. 2008, 73, 7811. (e)
Cui, D.-M.; Ke, Y.-N.; Zhaung, D.-W.; Wang, Q.; Zhang, C. Tetra-
hedron Lett. 2010, 51, 980.
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(2) Selected examples for Au- and Pt-catalyzed alkyne hydrations: (a)
Marion, N.; Ramon, R. S.; Nolan, S. P. J. Am. Chem. Soc. 2009, 131,
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€
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10.1021/ol1029047
Published on Web 01/19/2011
2011 American Chemical Society