Efficient transformation of propargylic alcohols to α,β-unsaturated aldehydes catalyzed by ruthenium/water under neutral conditions

Article abstract of DOI:10.1016/S0040-4039(02)01821-X

α,β-Unsaturated aldehydes were selectively obtained in high yields from propargylic alcohols in aqueous solutions using RuCpCl(PR₃)₂ (Cp=η⁵-C₅H₅) as a catalyst. Of the tert-phosphine ligands examined, PMe₃ gave the most satisfactory results. Typically, RuCpCl(PMe₃)₂ (5 mol%) catalyzed the transformation of oct-1-yn-3-ol at 100°C to give 2-octenal in an isolated yield of 85% (E/Z=80/20).

Full text of DOI:10.1016/S0040-4039(02)01821-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7531–7533
Efficient transformation of propargylic alcohols to
a,b-unsaturated aldehydes catalyzed by ruthenium/water under
neutral conditions
Toshiaki Suzuki,a Makoto Tokunagab and Yasuo Wakatsukia,*
aRIKEN (The Institute of Physical and Chemical Research), Wako, Saitama 351-0198, Japan
bPRESTO (Japan Science and Technology Corporation), Kawaguchi, Saitama 332-0012, Japan
Received 15 July 2002; revised 14 August 2002; accepted 23 August 2002
Abstract—a,b-Unsaturated aldehydes were selectively obtained in high yields from propargylic alcohols in aqueous solutions using
RuCpCl(PR3)2 (Cp=h5-C5H5) as a catalyst. Of the tert-phosphine ligands examined, PMe3 gave the most satisfactory results.
Typically, RuCpCl(PMe3)2 (5 mol%) catalyzed the transformation of oct-1-yn-3-ol at 100°C to give 2-octenal in an isolated yield
of 85% (E/Z=80/20). © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
CH=C(R)(R%) was achieved at 50–100°C by a two-step
but one-pot reaction via ruthenium(II)-catalyzed anti-
Markovnikov addition of benzoic acid to the alkyne
moiety and subsequent acid-catalyzed cleavage of the
resulting enol esters (Eq. (1)).9 Although one equiv. of
benzoic acid is required, this route provides easy access
to a,b-unsaturated aldehydes, where the presumed key
step is the attack of the a-carbon of the Ru–vinylidene
intermediate by PhCOO(−) anion. We previously
reported the highly regioselective, efficient, and sub-
stituent-tolerant anti-Markovnikov hydration of termi-
nal alkynes to give n-aldehyde using a catalytic amount
of readily available cyclopentadienylruthenium com-
plexes bearing appropriate bidentate or monodentate
phosphine ligands.10 We report here a reaction system
that yields directly and selectively a,b-unsaturated alde-
hydes when propargylic alcohols (HCꢀC-CH(R)OH)
are treated with water/alcohol under neutral conditions
in the presence of ruthenium catalyst (Eq. (2)). Since
benzoic acid/Ru-assisted rearrangement has only been
reported for tert propargylic alcohols while our water/
Ru-assisted reaction is best suited for sec-alcohols, the
two systems appear complementary.
The Meyer–Schuster-1 and Rupe-type2 rearrangements
of propargylic alcohols to a,b-unsaturated ketones and
aldehydes, which are versatile organic intermediates in
the manufacture of natural products of biological or
pharmaceutical importance,3 have been the subject of a
large number of investigations. Such transformation is
achieved by carrying out the reaction in acidic medium
or by using strong acid as a catalyst,4 which often gives
rise to unselective regioproducts. The reaction can be
better catalyzed by a variety of transition metal oxides,
such as Ti(IV)/CuCl/organic acid,5 oxovanadium,6 and
Bu4NReO4/p-TsOH.7 However, these systems need ele-
vated reaction temperatures and/or acidic conditions.
In 1996, the rearrangement reaction was reported to
proceed at 100°C under neutral conditions using
MoO2(acac)/dibutylsulfoxide, but could be applied only
to tertiary propargylic alcohols since the use of sec-
ondary alcohols results in simple oxidation of the alco-
hol
unit.8
Such
oxo-metal
complex-catalyzed
isomerization has been believed to take place via a
[3,3]-sigmatropic rearrangement of the oxo-propargy-
lox–metal intermediate. More recently, a completely
different route has been developed by Dixneuf and
co-workers to obtain a,b-unsaturated aldehydes: the
formal isomerization of HCꢀC-C(R)(R%)OH to OHC-
2. Results and discussion
The reaction of but-1-yn-3-ol (1a) in 2-propanol/H2O at
100°C for 12 h in the presence of 5 mol% of
RuCpCl(PMe3)2 (Cp=h5-cyclopentadienyl)11 led to
complete conversion of the starting material with the
selective formation of 2-butenal (2a) in 96% yield
Keywords: hydration; propargylic alcohol; aldehyde; ruthenium cata-
lyst.
* Corresponding author. Tel./fax: +81-48-4685063; e-mail: waky@
postman.riken.go.jp
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01821-X

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T. Suzuki et al. / Tetrahedron Letters 43 (2002) 7531–7533
(Table 1, entry 1). Reducing the amount of catalyst to
2 mol% did not lower the yield of 2a, but a longer
reaction time was necessary (entry 3). The addition of
NH4PF6 or an elevated temperature did not improve
the activity of the catalyst. With respect to the phos-
phine ligand, RuCpCl(PMe3)2 gave the highest activity:
PMe2, Et2PCH2CH2PEt2, and Ph2P(CH2)nPPh2 (n=2–
4)), were not effective and resulted in poor yields (0–
5%) of 2a, thus demonstrating the importance of the
choice of phosphine ligands in the present catalytic
reactions.
RuCpCl(dppm)
(dppm=bis(diphenyl-phosphino)-
Using RuCpCl(PMe3)2 as a catalyst, the scope of the
present transformation reaction of propargylic alcohol
derivatives was examined (Table 1, entries 4–8). Pent-1-
yn-3-ol (1b) was converted to 2b in 94% yield (entry 4).
Likewise, other alkyl-substituted propargylic alcohols
1c–e gave the corresponding a,b-unsaturated aldehydes
2c–e in high yields under similar reaction conditions
and the (E)-forms were always obtained as the major
stereoisomer (entries 5–7). Cinnamyl aldehyde (2f) was
methane), which was the best catalyst for anti-
Markovnikov hydration of various terminal alkynes
examined previously, lowered the reaction rate (68%)
under the same conditions, probably due to greater
steric hindrance (entry 2). Similarly, RuCpCl(PMe2Ph)2
gave 2a in only 25% yield while other cyclopentadienyl-
ruthenium complexes with different phosphine ligands,
RuCpCl(L)2 (L=PMePh2 and PPh3, (L)2=Me2PCH2-
(1)
(2)
Table 1. Formal isomerization of propargylic alcohols catalyzed by ruthenium complexesa

T. Suzuki et al. / Tetrahedron Letters 43 (2002) 7531–7533
7533
formed from 3-phenyl-prop-1-yn-3-ol (1f), again with
the E isomer as the predominant form, but the reaction
was slow and a longer reaction time (60 h) was required
(entry 8). Tertiary propargylic alcohols, 3-methyl-but-1-
yn-3-ol, and 3-phenyl-but-1-yn-3-ol, were scarcely
transformed to a,b-unsaturated aldehydes, and
remained unreacted under these conditions: elevated
reaction temperatures (e.g. 140°C) caused formation of
side products.
hydes in high yields in the presence of water and a
catalytic amount of ruthenium complex. This reaction
is remarkably clean and proceeds under neutral condi-
tions. In general, the reaction mixture simply consists of
solvent, water, unreacted reactants, and the a,b-unsatu-
rated aldehydes formed regardless of the conversion,
while few if any by-products are detected throughout
the reaction. Further applications of this reaction, as
well as detailed mechanistic investigations, are now in
progress.
The reaction is formally a 1,3-shift isomerization of the
hydroxy group, but does not proceed without the pres-
ence of adequate water. To confirm that the present
process does not involve the concerted 1,3-migration of
the alcoholic OH group, the reaction of 1c was carried
out in a mixture of H218O and 2-propanol. The
obtained aldehyde exclusively contained 18O, n-
C5H11CHꢁCHC(ꢁ18O)H (2c−18O), as was obvious by
the red-shift of the stretching vibration of the carbonyl
group compared to that of 2c [n(CO): 1695 cm−1 in 2c,
1662 cm−1 in 2c−18O]. Therefore, it is obvious that the
net reaction is anti-Markovnikov hydration at the ter-
minal alkyne carbon with concomitant dehydration of
the original OH group. The established reaction mecha-
nism for the previously reported anti-Markovnikov
hydration of 1-alkynes12 may be applied to the present
hydration of propargylic alcohols, although it is not yet
clear when the dehydration takes place. Early-stage
dehydration should give Ru–allenylidene intermediate
(A) followed by nucleophilic attack of the a-carbon of
the allenylidene unit by OH(−): the ability of Ru–
allenylidene complexes to react with weak nucleophiles,
such as alcohol and amine, at C(a) has been reported.13
Alternatively, the dehydration could occur after the
attack of C(a) of g-hydroxyvinylidene intermediate (B)
by water and successive formation of a g-hydroxyacyl
complex. In any case, the key-intermediate should have
a Ru(IV) metal center which bears a hydride and an
allenylidene (or (hydroxy)vinylidene) units. Interest-
ingly, Bassetti and co-workers very recently applied the
anti-Markovnikov hydration of 1-alkynes to propar-
gylic alcohols in micellar solutions at 60°C and
obtained saturated b-hydroxyaldehydes.14
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In summary, we have found a highly selective transfor-
mation of propargylic alcohols to a,b-unsaturated alde-