Organic Letters
Letter
4-trifluoromethylphenylacetylene was used as the substrate.25
With basic reaction sites (such as −NH2 and −CN) in the
substrates (2e, 2j), apart from the 20% acid catalyst, another
equivalent of acid was necessary to quench the basicity. Most
organic functional groups, including ester (2b), −CO2H (2c),
−OH (2d), −NH2 (2e), alkyl group (2f), −Cl (2g), −Br (2i),
−CN (2j), −CF3 (2k), −OMe (2l), and −F (2m), could
survive the reaction conditions, and they all delivered the
products in excellent yields (80−100%). This broad functional
group compatibility and mild conditions would provide
enormous potential to further functionalize the hydration
products, especially in complex natural product synthesis.
Besides aryl alkynes, aliphatic alkyne can also deliver the
Markovnikov-type hydration product with good yield (76%),
although a higher temperature (70 °C) was necessary (2n).
Unfortunately, the protocol is not applicable to the function-
alized aliphatic alkynes including propargylic alcohol and
methyl propiolate. However, our reaction procedure is
applicable to the internal arylalkynes (2o, 2p) by using the
standard conditions.
ACKNOWLEDGMENTS
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We are grateful to the Canada Research Chair (Tier 1)
foundation, FQRNT (CCVC), CFI, and NSERC for their
support of our research. W.L. is thankful for McGill Drug
Development Training Program (DDTP) for a fellowship.
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we also conducted a gram scale reaction by choosing
phenylacetylene (1.4 g, 14 mmol) as the substrate (Scheme
3). Under our standard conditions, the desired hydration
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Scheme 3. Gram Scale Reaction under Our Standard
Conditions
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In summary, we have developed an extremely mild protocol
to accomplish alkyne hydration. Our reaction operates at low
temperature with broad functional group compatibility, is
applicable to various alkynes, and only requires slightly more
than a stoichiometric amount of water in the absence of any
transition metals. Moreover, the reaction conditions are also
applicable for the large-scale reaction. The success of our
reaction lies in the use of TFE as the solvent. Exploration of
other nucleophiles to attack the vinyl carbocation is underway
in our laboratory and will be reported in due course.
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ASSOCIATED CONTENT
* Supporting Information
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(26) Olivi, N.; Thomas, E.; Peyrat, J.-F.; Alami, M.; Brion, J.-D.
Synlett 2004, 2004, 2175−2179.
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The Supporting Information is available free of charge on the
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1
Experimental section, spectroscopic data, and H, 13C,
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and 19F NMR spectra (PDF)
(30) Beg
18−29.
́ ́
ue, J.-P.; Bonnet-Delpon, D.; Crousse, B. Synlett 2004, 2004,
AUTHOR INFORMATION
Corresponding Author
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(32) Noyce, D. S.; Schiavelli, M. D. J. Am. Chem. Soc. 1968, 90,
1020−1022.
Notes
(33) Allen, A. D.; Chiang, Y.; Kresge, A. J.; Tidwell, T. T. J. Org.
Chem. 1982, 47, 775−779.
The authors declare no competing financial interest.
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Org. Lett. XXXX, XXX, XXX−XXX