Hydration of terminal alkynes to aldehydes in aqueous micellar solutions by ruthenium(II) catalysis; first anti-Markovnikov addition of water to propargylic alcohols

Article abstract of DOI:10.1016/S0040-4039(01)01841-X

The hydration of terminal alkynes and of propargylic alcohols to the corresponding aldehyde derivatives is conveniently carried out at 60°C in an aqueous micellar environment, in the presence of 5 mol% of the indenyl ruthenium(II) complex [Ru(η⁵-C₉H₇)Cl(PPh₃) ₂]. Higher yields and improved regioselectivity of aldehyde versus ketone as well as reaction conditions, in particular temperature and catalyst load, are found with respect to a solvent mixture 2-propanol-water, due to the aggregating conditions of the micellar solution. The reactions of the propargylic alcohols indicate the tolerance of the hydroxy functionality by the ruthenium complex.

Full text of DOI:10.1016/S0040-4039(01)01841-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8467–8470
Hydration of terminal alkynes to aldehydes in aqueous micellar
solutions by ruthenium(II) catalysis; first anti-Markovnikov
addition of water to propargylic alcohols
Patricia Alvarez,a Mauro Bassetti,b,* Jose´ Gimenoa,* and Giovanna Mancinib
aInstituto de Qu´ımica Organometa´lica ‘Enrique Moles’ (Unidad Asociada al CSIC),
Departamento de Qu´ımica Orga´nica e Inorga´nica, Facultad de Qu´ımica, Universidad de Oviedo, 33071 Oviedo, Spain
bCentro CNR di Studio sui Meccanismi di Reazione, c/o Dipartimento di Chimica, Universita` ‘La Sapienza’, 00185 Roma, Italy
Received 30 August 2001; revised 27 September 2001; accepted 1 October 2001
Abstract—The hydration of terminal alkynes and of propargylic alcohols to the corresponding aldehyde derivatives is conveniently
carried out at 60°C in an aqueous micellar environment, in the presence of 5 mol% of the indenyl ruthenium(II) complex
[Ru(h5-C9H7)Cl(PPh3)2]. Higher yields and improved regioselectivity of aldehyde versus ketone as well as reaction conditions, in
particular temperature and catalyst load, are found with respect to a solvent mixture 2-propanol–water, due to the aggregating
conditions of the micellar solution. The reactions of the propargylic alcohols indicate the tolerance of the hydroxy functionality
by the ruthenium complex. © 2001 Elsevier Science Ltd. All rights reserved.
Hydration of terminal alkynes catalyzed by metal com-
plexes represents a convenient method for the prepara-
tion of carbonyl compounds. The reaction proceeds by
addition of water to the metal p-alkyne complex,
according to Markovnikov’s rule, to form the corre-
sponding ketone compound.1 In contrast, it has been
recently reported that the reaction can be regioselec-
tively oriented to the formation of aldehydes in alco-
holic aqueous media (ca. 25% water in 2-propanol) by
catalysis of ruthenium(II) complexes, e.g. [RuCl2(h6-
C6H6){PPh2(C6F5)}] (10 mol%), in the presence of a
large excess of fluorinated phosphines.2 The excess of
phosphine can be avoided by the use of cyclopentadi-
enyl complexes bearing bidentate or monodentate phos-
phine ligands, such as [Ru(h5-C5H5)(dppm)Cl] (dppm=
diphenylphosphinomethane), while high temperatures
(100°C) are still required.3 The key species for forma-
tion of aldehyde versus ketone has been proposed to be
a ruthenium vinylidene intermediate, prone to nucleo-
philic attack by water at the a-carbon atom. Such an
effect on the regioselectivity as well as the potential for
the use of water as reagent and reaction medium have
prompted our interest in this subject.
In light of the possibilities offered by surfactants to
perform organic reactions in water,4 and to affect the
regiochemistry,5 we have explored the hydration of
terminal alkynes in aqueous micelles, as well as in
aqueous 2-propanol. The cationic hexadecyltrimethyl-
ammonium bromide (CTAB), or the anionic sodium
dodecylsulfate (SDS), which are both inexpensive com-
mercially available materials, have been used as surfac-
tants.6 We have used the indenyl complex
[Ru(h5-C9H7)Cl(PPh3)2] as catalyst, which is known to
activate terminal alkynes in the stoichiometric forma-
tion of vinylidene and allenylidene complexes,7 as well
as to promote the isomerization of allylic alcohols to
ketones.8 The hydration reaction has been carried using
Keywords: aldehydes; micelles; ruthenium; acqueous reactions; cataly-
sis.
* Corresponding authors.
Scheme 1.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01841-X

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P. Al6arez et al. / Tetrahedron Letters 42 (2001) 8467–8470
Table 1. Product analysisa of the hydration reaction in
2-propanol/water (1.25/0.37, cm3) in the presence of
[Ru(h5-C9H7)Cl(PPh3)2] (5 mol%)b at 90°C (48 h)
as substrates the lipophilic aromatic phenylacetylene (1)
and aliphatic 1-octyne (2), and the propargylic alcohols
1-octyn-3-ol (3), 1-ethynyl-1-cyclohexanol (4) and 2-
propyn-1-ol (5) (Scheme 1).
Alkynec
%
Aldehyde
Ketone (%) By-products
Conversion (%)
The results of the reaction carried out in the mixture
2-propanol/water, at 90°C, in the presence of [Ru(h5-
C9H7)Cl(PPh3)2] (5 mol%) are shown in Table 1.
1
2
3
4
5
\99
89
\99
94
71 (69)
63 (61)
63
17
15
21
13
19
12
11
16
12
31
The reactions did not proceed appreciably below 90°C.
The aliphatic substrates as well as phenylacetylene and
propargylic alcohols were converted into products in
the absence of additives, with larger formation of the
aldehyde than of the ketone species, except for 2-
propyn-1-ol, which showed small conversion and no
selectivity. To the best of our knowledge, this is the first
report of catalytic hydration of propargylic alcohols to
the aldehyde derivatives.
68
74
24
a Gas chromatographic yields (yields of isolated products).
b 0.025 mmol, 0.015 M.
c 0.5 mmol.
With respect to the reactions in aqueous 2-propanol,
yields, selectivity (aldehyde/ketone and carbonyl com-
pounds/by-products), and reaction conditions (temper-
ature) are favored in the presence of surfactants. The
results indicate that the reaction occurs within the
micelle, which aggregates both catalyst and substrate.
One remarkable feature of this aggregation is that the
catalyst operates in the concentration range 1–2×10−3
M, while in aqueous 2-propanol the concentration of
the ruthenium complex is 0.015 M. In the case of
2-propyn-1-ol (5), the solubility of the alkyne in water
yields scarce interaction with the catalyst in the micelle
and hence lower conversions. Nevertheless, the reaction
of 5 proceeds in the micellar aggregate, and not in the
water phase, yielding a selectivity as high as that of the
more lipophilic alkynes.
We have recently shown that the complex [Ru(h5-
C9H7)Cl(COD)] (COD=1,5-cyclooctadiene) catalyzes
the hydration of alkynes (1, 2 and 4) to form ketones in
high yields.9
Since the bis-phosphine and the COD complexes are
characterized by different electron density at the metal,
these results show the role played by the p-alkyne/vinyl-
idene equilibrium (see Scheme 2 for a graphical repre-
sentation of these species) in the regioselectivity. In fact
an electrophilic ruthenium center is expected to favor a
p-alkyne intermediate and direct the addition of water
in a Markovnikov fashion,10 as in the case of the COD
complex with p-acidic properties (E0=0.61 V),11 while
the electron rich bis-phosphine complex (E0=0.07 V)11
is expected to favor the vinylidene form.12
In the case of phenylacetylene, the formation of ace-
tophenone and of phenylacetaldehyde in SDS or CTAB
(0.1 M) solutions was followed at different reaction
times (Fig. 1). The plot confirms higher selectivity for
the aldehyde in the anionic SDS than in the cationic
CTAB surfactant, suggesting that the organometallic
intermediates are cationic species, formed in larger
Homogeneous aqueous solutions of alkyne (0.04 M),
surfactant (0.1 M) and [Ru(h5-C9H7)Cl(PPh3)2] (5
mol%) were heated at 60°C for the appropriate time.13
Reaction conditions and yields are reported in Table 2.
Table 2. Product analysisa of the hydration reaction in aqueous micellar solutions in the presence of [Ru(h5-C9H7)Cl(PPh3)2]
(5 mol%) at 60°Cb
Alkyne
Surfactant (M)
T (h)
Conversion
Aldehyde
Ketone
1
1
1
1
1
2
2
2
3
3
3
4
4
5
5
SDS (0.1)
SDS (0.1)
SDS (0.5)c
CTAB (0.1)
CTAB (0.1)
SDS (0.1)
CTAB (0.1)
SDS (0.5)c
SDS (0.1)
SDS (0.1)
CTAB (0.1)
SDS (0.1)
CTAB (0.1)
SDS (0.1)
CTAB (0.1)
12
24
24
24
48
24
24
24
12
24
30
36
48
36
48
80
99
\99
79
\99
99
\99
\99
85
95
98
92
98
77
3
9
7
9
10
6
12
3
1
1.4
4
4
91 (89)
93 (91)
70
90
93
88
97 (95)
84
93
93
88
87
25
25
5
1.5
1
27
27
a Gas chromatographic yields (isolated products).
b 0.5 mmol of surfactant (0.1 M), 0.20 mmol of alkyne (0.04 M), 0.01 mmol (8 mg) of ruthenium complex (2×10−3 M) in 5 cm3 of water solution.
c 12.5 mmol of surfactant (0.5 M), 5 mmol of alkyne (0.2 M), 0.25 mmol (200 mg) of ruthenium complex (2×10−3 M) in 25 cm3 of water solution.

P. Al6arez et al. / Tetrahedron Letters 42 (2001) 8467–8470
8469
Figure 1. Yield (% from gas chromatographic analysis) of
phenylacetaldehyde versus time, from the hydration reaction
of phenylacetylene (0.04 M) in aqueous SDS (ꢀ) or CTAB
(ꢁ) (0.1 M), at 60°C, in the presence of complex [Ru(h5-
C9H7)Cl(PPh3)2] (5 mol%, 2×10−3 M).
Scheme 2.
halide and accelerate the reaction in 2-propanol–water
has caused larger formation of by-products.
quantities and stabilized in the surfactant with an
anionic head group.
Interaction with the alkyne in the micelle yields a
p-adduct, which rearranges in a favored equilibrium
toward the vinylidene species, due to the donor proper-
ties of the phosphine ligands. The following steps
involve addition of water to the cationic vinylidene
complex to give an a-hydroxy carbene species, forma-
tion of an acyl complex,15 and release of free aldehyde
and catalyst. The fact that conjugated unsaturated alde-
hydes were not detected in the reactions of the propar-
gylic alcohols 3–5 indicates that dehydration of the
Ru–vinylidene intermediate to form allenylidene spe-
cies, as in the stoichiometric activation of these sub-
strates, is disfavored in the aqueous medium of this
procedure.
A
31P{1H} NMR investigation of the reaction in the
presence of SDS showed a signal at l=38.5 ppm,
corresponding to [Ru(h5-C9H7)(ꢀCꢀCHPh)(PPh3)2]+
(l=38.9 ppm for [Ru(h5-C9H7)(ꢀCꢀCHPh)(PPh3)2]-
[PF6] in CDCl3), and later a signal at l=51 ppm, due
to [Ru(h5-C9H7)(CO)(CH2Ph)(PPh3)]. This carbonyl
complex, which has been obtained independently by
reaction of [Ru(h5-C9H7)(ꢀCꢀCHPh)(PPh3)2][PF6] with
water in methanol,14 forms by attack of water to the
a-vinylidene carbon atom and subsequent phosphine
dissociation and decarbonylation. This sequence of
reaction steps in ruthenium complexes has already been
described.15 The complex [Ru(h5-C9H7)(CO)(CH2Ph)-
(PPh3)] did not show activity as catalyst in the hydra-
tion reaction, therefore the decarbonylation of [Ru(h5-
The comparison between two different ruthenium com-
plexes shows that the ligand effects which modulate the
equilibrium p-alkyne/vinylidene can also be oriented to
the desired regiochemistry in the hydration reaction,
versus either ketone or aldehyde, in aqueous 2-
propanol. The neutral indenyl complex [Ru(h5-
C9H7)Cl(PPh3)2] can be used effectively for anti-
Markovnikov addition of water to alkynes by inclu-
sion in aqueous micellar aggregates, with signifi-
cant improvements of yields, regioselectivity and reaction
conditions. Further tuning of the reaction can be ob-
tained by structural changes of the surfactant.
C9H7)(COCH2Ph)(PPh3)2] represents
a pathway in
competition with the productive release of aldehyde.
When the counteranion of complex [Ru(h5-C9H7)-
(ꢀCꢀCHPh)(PPh3)2][PF6] was exchanged with sodium
docecyl sulfate to obtain [Ru(h5-C9H7)(ꢀCꢀCHPh)-
(PPh3)2][C12H25OSO3], the new salt displayed poor
activity in the hydration of ethynylcyclohexanol in
water (48 h, 9% of conversion and 7% of aldehyde),
which confirms the key role played by the micellar
aggregate.
This work represents the first report of catalytic hydra-
tion of propargylic alcohols to aldehydes, which implies
the tolerance of the ruthenium catalyst to the hydroxyl
functional group. Substitution reactions17 and the
dimerization18 of propargylic alcohols catalyzed by
ruthenium complexes have been reported recently, indi-
cating the versatility of this class of compounds as
substrates in ruthenium catalysis.
A plausible reaction pathway is depicted in Scheme 2.
Complex 1 in the micellar aggregate dissociates a chlo-
ride ion to give a cationic species, the same step which
precedes interaction with the alkyne in the synthesis of
vinylidene complexes.16 The extrusion of chloride is
favored in the anionic SDS micelle. On the other hand,
the use of a silver salt, AgBF4, in order to abstract the

8470
P. Al6arez et al. / Tetrahedron Letters 42 (2001) 8467–8470
Reference electrode:aqueous saturated calomel electrode
Acknowledgements
(SCE) separated from the solution by a porous septum.
Working electrode: platinum disk. Electrolite: NBu4PF6.
12. Bruce, M. I. Chem. Rev. 1998, 98, 2797.
Support from NATO (Collaborative Research Grant
950794) and COST CHEMISTRY Action D12, Project
D12/0025/99 ‘Ruthenium Catalysts for Fine Chemistry’
is gratefully acknowledged.
13. Solutions of surfactant (0.1 M, 0.5 M) were prepared by
dissolving CTAB or SDS in deionized water. The alkyne
([surfactant]/[alkyne]=2.5 or 5) was added to 5 cm3 of
the solution (25 cm3 under preparative conditions), in a
vessel sealed by a Teflon stopper, and the mixture stirred
in a ultrasound bath (30 min). The ruthenium complex
was added (5 mol% with respect to the alkyne), the
mixture stirred (30 min) and then heated (60°C). The
reaction was monitored by gas chromatography, until
consumption of the substrate. Petroleum ether (5 cm3)
was then added to the aqueous solution, the organic
phase was extracted, dried over anhydrous magnesium
sulfate, and analyzed (GC–MS). Under preparative con-
ditions, the organic solvent, after filtration, was removed
under vacuum, and the oily residue was purified by
chromatography (hexane/silica), or vacuum distilled, to
give the product. The organic products described in this
work are known. Characterization was obtained by 1H
NMR and by GC–MS.
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