ORGANIC
LETTERS
2
006
Vol. 8, No. 25
853-5856
Highly Active in Situ Catalysts for
Anti-Markovnikov Hydration of Terminal
Alkynes
5
Aur e´ lie Labonne, Thomas Kribber, and Lukas Hintermann*
Institute of Organic Chemistry, RWTH Aachen UniVersity, Landoltweg 1, D-52074
Aachen, Germany
Received October 5, 2006
ABSTRACT
The anti-Markovnikov hydration of terminal alkynes to give aldehydes is catalyzed by complexes derived in situ from air-stable [CpRu(η6
naphthalene)]PF (C) and 6-aryl-2-diphenylphosphinopyridines (L). Ligands L are readily available from a modular synthesis. Increasing the
-
6
size of the ligand C-6 aryl group in the order R
highest known activity.
)
Ph < mesityl < 2,4,6-triisopropylphenyl < (2,4,6-triphenyl)phenyl gave hydration catalysts of
6
Alkynes have long been known to undergo synthetically
useful metal-catalyzed hydrations to give carbonyl com-
pounds, but only in 1998 did Tokunaga and Wakatsuki find
heterofunctionalization reactions are promising tools for
sustainable synthesis because they generate heterofunction-
7
ality with atom-economy. We have been eager to incorporate
a ruthenium catalyst that selectively produced aldehydes from
the title reaction into synthetic sequences, but progress was
initially hampered by the low activity of the first generation
catalysts 1, and later by availability of sufficient quantities
1
terminal alkynes. Complexes [CpRu(PR
3
)
2
]X (1) (R ) aryl,
5
alkyl, bridging alkyl; Cp ) η -cyclopentadienyl; X ) Cl,
PF ) have since emerged as catalysts for anti-Markovnikov
hydration with almost perfect regioselectivity. A crucial
ligand modification (PR ) L1 ) 6-tert-butyl-2-diphe-
nylphosphanylpyridine) by Grotjahn and Lev gave the
complex [CpRu(L1) (MeCN)]PF (2), which is 3 orders of
8
of complex 2.
6
2-4
These hurdles in the way of a broader synthetic application
9
of anti-Markovnikov hydration of terminal alkynes have
3
5
motivated us to search for more available and easy to handle
catalysts. We can now present in situ catalysts for the title
reaction that combine the advantages of ready availability
and air-stability, and we also report on a surprising ligand
effect that has allowed us to tune the catalyst to highest levels
of activity.
2
6
magnitude more active than 1 and thus paved the way for
synthetic applications under mild conditions.4 Catalytic
(
(
1) Tokunaga, M.; Wakatsuki, Y. Angew. Chem., Int. Ed. 1998, 37, 2867.
2) (a) Suzuki, T.; Tokunaga, M.; Wakatsuki, Y. Org. Lett. 2001, 3, 735.
(
b) Tokunaga, M.; Suzuki, T.; Koga, N.; Fukushima, T.; Horiuchi, A.;
Wakatsuki, Y. J. Am. Chem. Soc. 2001, 123, 11917.
3) (a) Grotjahn, D. B.; Incarvito, C. D.; Rheingold, A. L. Angew. Chem.,
(6) (a) Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. ReV. 2004, 104,
3079. (b) Beller, M.; Seayad, J.; Tillack, A.; Jiao, H. Angew. Chem., Int.
Ed. 2004, 43, 3368. (c) Catalytic Heterofunctionalization; Togni, A.,
Gr u¨ tzmacher, H., Eds.; Wiley-VCH: Weinheim, Germany, 2001.
(7) Trost, B. M. Science 1991, 254, 1471.
(
Int. Ed. 2001, 40, 3884. (b) Chevallier, F.; Breit, B. Angew. Chem., Int.
Ed. 2006, 45, 1599.
(
4) (a) Grotjahn, D. B.; Lev, D. A. J. Am. Chem. Soc. 2004, 126, 12232.
b) Grotjahn, D. B. Chem. Eur. J. 2005, 11, 7146.
5) Baur, J.; Jacobsen, H.; Burger, P.; Artus, G.; Berke, H.; Dahlenburg,
L. Eur. J. Inorg. Chem. 2000, 1411.
(8) Availability of 2 is limited by the synthesis of L1 (6 steps, low overall
yield) and the use of an expensive precursor [CpRu(MeCN)3]PF6. Note,
however, that 2 is now sold in research quantities by Strem Chemicals.
(9) We are not aware of applications of this methodology in synthesis.
(
(
1
0.1021/ol062455k CCC: $33.50
© 2006 American Chemical Society
Published on Web 11/16/2006