J. Am. Chem. Soc. 2001, 123, 11917-11924
11917
Ruthenium-Catalyzed Hydration of 1-Alkynes to Give Aldehydes:
Insight into anti-Markovnikov Regiochemistry
Makoto Tokunaga,‡ Toshiaki Suzuki,† Nobuaki Koga,§ Tomoaki Fukushima,¶
Akira Horiuchi,¶ and Yasuo Wakatsuki*,†
Contribution from RIKEN (The Institute of Physical and Chemical Research),
Wako-shi, Saitama 351-0198, Japan, PRESTO (Japan Science and Technology Corporation), Kawaguchi,
Saitama 332-0012, Japan, Graduate School of Human Informatics, Nagoya UniVersity, Chikusa,
Nagoya 464-8601, Japan, and Faculty of Science, Rikkyo UniVersity, Toshima, Tokyo 171-8501, Japan
ReceiVed August 9, 2001
Abstract: The mechanism of the selective conversion of 1-alkynes to aldehydes by hydration was investigated
by isolating organic and organometallic byproducts, deuterium-labeling experiments, and DFT calculations.
The D-labeled acetylenic hydrogen of 1-alkyne was found exclusively in the formyl group of the resulting
aldehydes. After the reaction, the presence of metal-coordinated CO was confirmed. All of the experimental
results strongly suggest the involvement of a metal-acyl intermediate with the original acetylenic hydrogen
also bound to the metal center as a hydride, with the next step being release of aldehyde by reductive elimination.
Theoretical analyses suggest that the first step of the catalytic cycle is not oxidative addition of acetylene
C-H or tautomerization of η2-alkyne to a vinylidene complex, but rather protonation of the coordinated 1-alkyne
at the substituted carbon to form a metal-vinyl intermediate. This cationic intermediate then isomerizes to
Ru(IV)-hydride-vinylidene via R-hydride migration of the vinyl group to the metal center, followed by attack
of the vinylidene R-carbon by OH- to give the metal-hydride-acyl intermediate.
Previously reported addition reactions of water to 1-alkynes
catalyzed by acids, mercuric salt,1 NaAuCl4,2 Ru(III),3 RhCl3,4
[PtCl2(CH2dCH2)]2,5 PtCl4,6 and other metals7 have all followed
Markovnikov’s rule and furnished ketones, until we reported
the first anti-Markovnikov hydration in 1998. This hydration
was catalyzed by a RuCl2/phosphine mixture (system-1), where
the phosphine had to be rather special, although they are
commercially available, i.e., P(C6H5)2(C6F5) or P(C6H4-3-SO3-
Na)3 (TPPTS).8a The activity of system-1 was not very high,
since ca. 10 mol % of catalyst was required and a small amount
of the conventional Markovnikov product, i.e., ketone, was
always present in the reaction products. However, we later found
that complexes of the type RuCpCl(PR3)2 (system-2) are
excellent catalysts that show both high activity and perfect
selectivity for the anti-Markovnikov hydration of 1-alkynes.8b
Our next goal has been to clarify the mechanism and to elucidate
the controlling factor of this completely reversed regioselectivity.
Closely related stoichiometric reactions of 1-alkynes and water
assisted by iron-group metal complexes have been reported to
result in C-C triple bond cleavage.9 Reactions of metal-
vinylidene complexes, tautomers of metal-(1-alkyne) com-
plexes, with water have been known to lead to a similar C-C
bond cleavage.10 Summarizing these 1-alkyne/water/metal or
metal-vinylidene/water reactions, Bianchini et al. reported their
detailed “final chapter” study on the stoichiometric Ru(II)-
assisted C-C fission of phenylacetylene by water into toluene
and a Ru(II)-CO complex, which demonstrated the participation
of a Ru(II)-vinylidene intermediate and successive generation
of a metal-acyl intermediate (Scheme 1).11 Therefore, it seemed
likely that our catalytic reaction also involves isomerization of
η2-coordinated 1-alkyne to a vinylidene form prior to attack by
water. Unlike the known cases based on coordination chemistry
as described above, the resulting metal-acyl intermediate
formed in our catalytic cycle was thought to take up a proton
to release an aldehyde rather than undergo competitive decar-
bonylation to carbonyl-metal complex (C-C fission type
reaction). Unexpectedly, deuterium-labeling experiments in our
systems have clearly indicated that the reaction mechanism in
water solvent is not so straightforward, i.e., not the catalytic
version of modified Bianchini-type reactions shown in lower
part of Scheme 2. We report here the full details of a mechanistic
† RIKEN
‡ PRESTO
§ Nagoya University
¶ Rikkyo University
(1) (a) Larock, R. C.; Leong, W. W. In ComprehensiVe Organic
Synthesis; Trost, B. M., Flemming, I., Semmelhock, M. F., Eds.; Perga-
mon: Oxford, UK, 1991; Vol. 4, p 269. (b) March, J. AdVanced Organic
Chemistry; Wiley: New York, 1992; p 762.
(2) Fukuda, Y.; Utimoto, K. J. Org. Chem. 1991, 56, 3729.
(3) (a) Halpern, J.; James, B. R.; Kemp, A. L. W. J. Am. Chem. Soc.
1961, 83, 4097. (b) Halpern, J.; James, B. R.; Kemp, A. L. W. J. Am. Chem.
Soc. 1966, 88, 5142. (c) Khan, T. M. M.; Halligudi, S. B.; Shukla, S. J.
Mol. Catal. 1990, 58, 299.
(4) Blum, J.; Huminer, H.; Alper, H. J. Mol. Catal. 1992, 75, 153.
(5) (a) Hiscox, W.; Jennings, P. W. Organometallics 1990, 9, 1997. (b)
Hartman, J. W.; Hiscox, W. C.; Jennings, P. W. J. Org. Chem. 1993, 58,
7613.
(6) Baidossi, W.; Lahav, M.; Blum, J. J. Org. Chem. 1997, 62, 669.
(7) (a) Hu, N. X.; Aso, Y.; Otsubo, T.; Ogura, F. Tetraheron Lett. 1986,
27, 6099. (b) Meier, I. K.; Marsella, J. A. J. Mol. Catal. 1993, 78, 31.
(8) (a) Tokunaga, M.; Wakatsuki, Y. Angew. Chem., Int. Ed. Engl. 1998,
37, 2867. (b) Suzuki, T.; Tokunaga, M.; Wakatsuki, Y. Org. Lett. 2001, 3,
735.
(9) Sullivan, B. P.; Smythe, R. S.; Kober, E. M.; Meyer, T. J. J. Am.
Chem. Soc. 1982, 104, 4701.
(10) (a) Bruce, M. I.; Swincer, A. G. Aust. J. Chem. 1980, 33, 1471. (b)
Bruce, M. I. Pure Appl. Chem. 1986, 58, 553. (c) Knaup, W.; Werner, H.
J. Organomet. Chem. 1991, 411, 471.
(11) Bianchini, C.; Casares, J. A.; Peruzzini, M.; Romerosa, A.; Zanobini,
F. J. Am. Chem. Soc. 1996, 118, 4585.
10.1021/ja0119292 CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/06/2001