Isomerization of propargylic alcohols into α,β-unsaturated carbonyl compounds catalyzed by the sixteen-electron allyl-ruthenium(II) complex [Ru(η3-2-C3H4Me)(CO)(dppf)] [SbF 6]

Article abstract of DOI:10.1002/adsc.200505294

The 16-e^- (η³-allyl)-ruthenium(II) complex [Ru(η³-2-C₃H₄Me)(CO)(dppf)][SbF ₆] is an efficient catalyst for the regioselective isomerization of terminal propargylic alcohols HC≡CCR¹R²(OH) into α,β-unsaturated aldehydes R¹R²C=CHCHO or ketones R³R⁴C=C(R¹)COMe (if R² = CHR³R⁴) under mild conditions. This complex has been also used as catalyst for the preparation of conjugated 1,3-enynes via dehydration of propargylic alcohols.

Full text of DOI:10.1002/adsc.200505294

FULL PAPERS
DOI: 10.1002/adsc.200505294
Isomerization of Propargylic Alcohols into a,b-Unsaturated
Carbonyl Compounds Catalyzed by the Sixteen-Electron
Allyl-Ruthenium(II) Complex [Ru(h3-2-C3H4Me)(CO)(dppf)]
[SbF6]
´
Victorio Cadierno,* Sergio E. García-Garrido, Jose Gimeno*
´
´
´
Departamento de Química Organica e Inorganica, Instituto Universitario de Química Organometalica “Enrique Moles”
(Unidad Asociada al CSIC), Facultad de Química, Universidad de Oviedo, 33071 Oviedo, Spain
Fax: þ(34)985103446; e-mail: vcm@uniovi.es, jgh@uniovi.es
Received: July 25, 2005; Accepted: November 10, 2005
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The 16-eÀ (h3-allyl)-ruthenium(II) complex lyst for the preparation of conjugated 1,3-enynes via
[Ru(h3-2-C3H4Me)(CO)(dppf)][SbF6] is an efficient dehydration of propargylic alcohols.
catalyst for the regioselective isomerization of termi-
1
2
ꢀ
nal propargylic alcohols HC CCR R (OH) into a,b-
1
2
¼
unsaturated aldehydes R R C CHCHO or ketones Keywords: allenylidene ligands; isomerization; prop-
3
4
1
2
3
4
¼
R R C C(R )COMe (if R ¼ CHR R ) under mild argylic alcohols; ruthenium; a,b-unsaturated carbonyl
conditions. This complex has been also used as cata- compounds; vinylidene ligands
Introduction
atom to the C(1) carbon atom of the alkyne ([3,3]-sigma-
tropic rearrangement).
The concept of atom economy, i.e., all atoms of the reac-
It has been reported that ruthenium(II) complexes are
tant end up in the final product, has emerged as a major able to catalyze the isomerization of terminal propargyl-
goal in synthetic organic chemistry in recent years.[1] Iso- ic alcohols into a,b-unsaturated aldehydes (Meyer–
merization processes are typical examples of atom eco- Schuster rearrangement) through completely different
nomical reactions since no by-products are generated. reaction pathways, i.e., the formation of vinylidene- or
In this context, the isomerization of easily accessible allenylidene-ruthenium intermediates resulting from
ꢀ
propargylic alcohols into the valuable raw materials the selective coordination of the C C bond of the alky-
a,b-unsaturated carbonyl compounds (aldehydes or ke- nols to the metal.[9] Thus, Bruneau, Dixneuf and co-
tones) is a desired synthetic goal. Early achievements in workers have developed a one-pot but two-step catalytic
this field are the well-known Meyer–Schuster[2] and procedure based on the anti-Markovnikov addition of
Rupe[3] rearrangements (Scheme 1). Both type of reac- benzoic acid to the carbon-carbon triple bond of tertiary
tions are generally carried out in acidic medium or using alkynols catalyzed by [Ru(h3-2-C3H4Me)2(dppe)]. The
strong acids as catalysts, which often give rise to non-re- final enals are obtained after acidic cleavage with
gioselective transformations.[4] Although more efficient PTSA or HBF4 of the resulting enol esters which can
and selective catalytic systems based on transition be isolated and characterized (Method
A
in
metal complexes, such as Ti(OR)4/CuCl/RCO2H,[5]
Bu4NReO4/p-MeC6H4SO3H,[6]
MoO2(acac)2/R2SO/
ArCO2H[7] and vanadium(V) oxides,[8] have been devel-
oped, elevated temperatures (>1008C) and/or acidic
conditions are still needed. With all these oxo-metal cat-
alysts, the suggested key step in the catalytic cycle in-
volves the formation of an allenyloxy intermediate gen-
erated by O-coordination of the propargylic alcohol to
¼
Scheme 1. The Meyer–Schuster and Rupe rearrangement of
the metal and subsequent addition of the [M] O oxygen propargylic alcohols.
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Scheme 2. Ru-catalyzed isomerization of propargylic alcohols into enals.
Scheme 2).[10] Formation of these enol esters involves
the nucleophilic attack of the benzoate anion at the a-
carbon
of
hydroxy-vinylidene
intermediates
1
2
¼ ¼
[Ru] C C(H)C(OH)R R . A more direct route has
been reported by Wakatsuki and co-workers using the
cyclopentadienyl complex [RuCl(h5-C5H5)(PMe3)2],
which is able to catalyze the isomerization process in
only one step and under neutral conditions (Method B
in Scheme 2).[11] In this case the proposed key-inter-
¼ ¼ ¼
mediate is an allenylidene derivative [Ru] C C CHR,
generated by dehydration of the propargylic alcohol
upon coordination to the metal,[9] which probably under-
goes the nucleophilic attack of the previously eliminated
molecule of water at the electrophilic a-carbon atom of
the allenylidene chain.[9] We note that, while method A
has been exclusively applied to the isomerization of ter-
Scheme 3. Ru-catalyzed propargylic substitution reactions of
1,1-diphenyl-2-propyn-1-ol with alcohols.
tiary propargylic alcohols (R1 and R2 = H), method B is respect to the previously reported Ru-based catalytic
only operative when secondary alkynols are used, the systems[10,11] since, depending on the nature of the prop-
tertiary ones remaining unreactive. Moreover, both argylic alcohol, enals (Meyer–Schuster rearrangement)
methodologies are not stereoselective since enals are or enones (Rupe rearrangement) can be selectively ob-
in all cases obtained as mixtures of the corresponding tained.
E and Z isomers.[12]
Recently, we have reported that the cationic 16-eÀ (h3-
allyl)-ruthenium(II) complex [Ru(h3-2-C3H4Me)- Results and Discussion
(CO)(dppf)][SbF6] [dppf¼1,1’-bis(diphenylphosphi-
no)ferrocene] (1) is able to catalyze the propargylic sub-
Isomerization of Propargylic Alcohols into a,b-
stitution reaction of 1,1-diphenyl-2-propyn-1ol with a
Unsaturated Aldehydes (Meyer–Schuster
large variety of alcohols to afford propargylic ethers
Rearrangement)
[13]
ꢀ
HC CCPh2(OR) in good yields (Scheme 3).
Re-
markably, the formation of minor amounts of 3,3-di-
phenyl-2-propen-1-al, resulting from the formal isomer- Since the favoured formation of the propargylic ethers
ization of the alkynol, was observed by GC/MS in almost vs. the enals (Scheme 3) is due to the presence of alco-
all of the reactions. This fact prompted us to investigate hols, which act both as solvents and nucleophiles, we
the potential of complex 1 as a catalyst for the isomeri- have explored the catalytic activity of the allyl-Ru(II)
zation of propargylic alcohols into a,b-unsaturated car- complex [Ru(h3-2-C3H4Me)(CO)(dppf)][SbF6] (1) in
bonyl compounds. Thus, herein we describe the success- THFas solvent to form the enals selectively. The isomer-
ful application of 1 to the isomerization of a large variety ization of 1,1-diphenyl-2-propyn-1-ol (2a) into 3,3-di-
terminal alkynols. The present paper brings novelty with phenyl-2-propen-1-al (3a) was used as a model reaction.
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Isomerization of Propargylic Alcohols into a,b-Unsaturated Carbonyl Compounds
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Table 1. Isomerization of propargylic alcohols 2a–h into a,b-unsaturated aldehydes 3a–h catalyzed by complex 1 in the pre-
sence of CF3CO2H.[a]
Entry
1
Substrate
Product
Time
Yield[b]
95%
2a
2b
3a
3b
10 min
2
3
30 min
15 min
96%
96%
2c
3c
4
5
2d
2e
3d
3e
30 min
3.5 h
91%
95%
6
7
2f
3f
2.5 h
1.5 h
93%
94%
2g
3g
8
2h
3h
45 min
92%
[a]
Reaction conditions: reactions were carried out in refluxing THF (wet; undistilled) using 1 mmol of the corresponding pro-
pargylic alcohol (1.0 M solution). [Substrate]:[Ru]:[CF3CO2H] ratio¼20: 1: 2.
[b]
Isolated yield (quantitative yields were observed by GC in all cases).
Thus, we have found that when a 1.0 M solution of 2a in for a number of other propargylic alcohols (Scheme 4;
distilled THF was refluxed for 24 h in the presence of a results are summarized in Table 1). Thus, as observed
catalytic amount of 1 (5 mol %), enal 3a was selectively for 1,1-diphenyl-2-propyn-1-ol (2a), other tertiary alky-
obtained in 78% yield (determined by GC). Remarka- nols (2b–d) undergo a fast (ꢁ30 min) and efficient iso-
bly, a dramatic rate enhancement was observed when merization into the corresponding enals (3b–d) (ꢂ91%
wet THF (undistilled) was used as solvent under the isolated yields; quantitative yields were in all cases ob-
same reaction conditions, resulting in the quantitative served by GC) regardless the presence of aryl (entries 2
transformation of 2a into 3a in 1.5 h. Nevertheless, and 3) or alkyl (entry 4) substituents. Secondary alky-
the addition of different acidic co-catalysts including nols (2e–h; entries 5–8 in Table 1) can also be effi-
NH4Cl, NH4PF6, (CH3CO)2O, (CF3CO)2O, CH3CO2H ciently isomerized (ꢂ92% isolated yields within
and CF3CO2H, resulted in an improved catalytic activity. 3.5 h), demonstrating the generality of this catalytic
The best results were obtained using trifluoroacetic acid transformation.[15] Remarkably, the resulting enals
(1.0 M solution in wet THF; [2a]:[1]:[CF3CO2H] ra- 3e–h are in all cases stereoselectively formed as the
tio¼20:1:2; reflux) allowing the quantitative formation thermodynamically more stable E isomer. This fact
of 3,3-diphenyl-2-propen-1-al (3a) in only 10 min (95% contrasts with the results previously reported by Bru-
isolated yield; see entry 1 in Table 1).[14]
neau, Dixneuf and Wakatsuki using the related Ru-
Under these optimized reaction conditions (1.0 M sol- based catalytic systems [Ru(h3-2-C3H4Me)2(dppe)]/
ution in wet THF; [substrate]:[1]:[CF3CO2H] ratio¼ PhCO2H and [RuCl(h5-C5H5)(PPh3)2],[10,11] from which
20:1:2; reflux) the catalytic activity of complex enals are generated as mixtures of the corresponding E
[Ru(h3-2-C3H4Me)(CO)(dppf)][SbF6] (1) was tested and Z stereoisomers.
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Synthesis of Terminal 1,3-Enynes via Catalytic
Dehydration of Propargylic Alcohols
Monitoring the catalytic isomerization of propargylic al-
cohols 4 into enones 5 by GC/MS the intermediate for-
mation of the terminal 1,3-enynes 6 is observed
(Scheme 6).
Scheme 4. The Meyer–Schuster rearrangement catalyzed by
complex 1.
An example of the reaction profile for the isomeriza-
tion of 1-ethynylcyclopentanol (4d) into 1-acetylcyclo-
pentene (5d) is shown in Figure 1. The overall transfor-
mation involves two well-separated steps, i.e., the initial
formation of the terminal enyne 1-ethynylcyclopentene
Isomerization of Propargylic Alcohols into a,b-
Unsaturated Ketones (Rupe Rearrangement)
The catalytic isomerization of propargylic alcohols bear- (6d) after ca. one hour (87% yield), which slowly evolves
À
ing a C H bond in the b-position with respect to the al- into the final product 1-acetylcyclopentene (quantita-
cohol group proceeds in a different way, giving instead tive yield after 20 hours). Taking into account that the
a,b-unsaturated methyl ketones as the result of a formal first step is considerably faster than the second one, we
Rupe-type rearrangement of the alkynol (see Scheme 5 envisaged the possibility to use the catalyst [Ru(h3-2-
and Table 2). Thus, enones 5a–g have been selectively C3H4Me)(CO)(dppf)][SbF6] (1) not only for the isomer-
obtained in 78–94% yield (quantitative transformations ization of propargylic alcohols 4 into ketones 5 but also
by GC) starting from the alkynols 3-isopropyl-4-methyl- for the catalytic synthesis of 1,3-enynes 6 which are im-
1-pentyn-3-ol (4a; entry 1), 3-ethyl-1-pentyn-3-ol (4b; portant synthetic intermediates in organic chemis-
entry 2), 3-methyl-1-pentyn-3-ol (4c; entry 3) and the try.[18,19]
1-ethynylcycloalkanols 4d–g (entries 4–7), using the
Such a transformation has been achieved efficiently at
optimized conditions described above (1.0 M solution 608C by using anhydrous THF (distilled) as solvent. Se-
in wet THF; [substrate]:[1]:[CF3CO2H] ratio¼ lected results are summarized in Table 3 (all reactions
20:1:2; reflux).[16] In contrast to the stereoselective for- performed using 1.0 M solutions of 4; [4]:[1]:[CF3CO2H]
mation of aldehydes 3e–h, the ketones 5b–c are ob- ratio¼20:1:2).[20] Among the different alkynols used,
tained as a 1:1 mixture of the E and Z stereoisomers the dehydration of the hormonal steroids ethisterone
(see entries 2 and 3), suggesting that different inter- (4h; entry 3) and mestranol (4j; entry 4) is noteworthy,
mediates are now involved in the catalytic cycle.
the corresponding conjugated enynes 6h and 6j being
obtained in pure form in excellent yields (96–97%).
Moreover, in accord with the absence of stereoselectiv-
ity observed in the formation of enone 5c (entry 3 in Ta-
ble 2), we have found that the dehydration of propargyl-
ic alcohol 4c (entry 1 in Table 3) does not proceed in a
stereoselective manner, the enyne 6c being obtained as
1:1 mixture of the corresponding E and Z isomers (see
also entry 7). As expected, when the catalytic reactions
are performed in undistilled THF the hydration of the in
situ formed 1,3-enynes 6 generates enones 5. The ability
of complex [Ru(h3-2-C3H4Me)(CO)(dppf)][SbF6] (1) to
Scheme 5. The Rupe rearrangement catalyzed by complex 1.
This catalytic transformation can be also successfully catalyze the direct hydration of 1,3-enynes has been con-
applied to more elaborate substrates such as the hormo- firmed in the transformation of 1-ethynylcyclohexane
nal steroids ethistherone (4h; entry 8), 17a-ethynyles- into 1-acetylcyclohexene.[21]
tradiol (4i; entry 9) and mestranol (4j; entry 10). The re-
sulting enones 5h–j, which are important building
blocks in the chemistry of steroids,[17] have been ob- Mechanistic Proposal for the Isomerization and
tained in pure form in excellent yields (96–97% Dehydration Reactions
yields).
It is worthy of note that no transformations were ob- Schemes 7 and 8 show plausible mechanisms for the for-
served when internal propargylic alcohols such as mation for enals 3a–h and enones 5a–j, respectively, as
ꢀ
ꢀ
MeC CCH2(OH) and (HO)MeHCC CCHMe(OH) well as for the dehydration process yielding 1,3-enynes 6
were used as substrates. The absence of catalytic activity (Scheme 8). Although no catalytically active species
with these particular alkynes is based on their lack of could be isolated or in situ characterized by NMR
ability to undergo tautomerization to form vinylidene techniques, we assume that the key intermediate is
species, a process which is well-documented for terminal in all the cases an hydroxyvinylidene complex
alkynes (see mechanistic proposal below).[9]
[Ru]þ C C(H)C(OH)R R (A). This species results
1
2
¼ ¼
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Isomerization of Propargylic Alcohols into a,b-Unsaturated Carbonyl Compounds
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Table 2. Isomerization of propargylic alcohols 4a–j into a,b-unsaturated ketones 5a–j catalyzed by complex 1 in the presence
of CF3CO2H.[a]
Entry
1
Substrate
Product
Time
2 h
Yield[b]
93%
4a
4b
4c
5a
5b
5c
2[c]
6.5 h
11 h
81%
78%
3[c]
4
5
6
7
4d
4e
4f
5d
5e
5f
20 h
2 h
94%
93%
89%
91%
1.25 h
1.5 h
4g
5g
8
9
4h
4i
5h
5i
26 h
5 h
97%
96%
96%
10
4j
5j
4 h
[a]
Reaction conditions: reactions were carried out in refluxing THF (wet; undistilled) using 1 mmol of the corresponding pro-
pargylic alcohol (1.0 M solution). [Substrate]:[Ru]:[CF3CO2H] ratio¼20: 1: 2.
Isolated yield (quantitative yields were observed by GC in all cases).
[E]:[Z] ratio¼1: 1.
[b]
[c]
from the initial formation of an unstable h2-alkyne com- nium-stabilized propargylic cations in these isomeriza-
plex (via p-coordination of the C C bond of the propar- tion reactions.[22]
ꢀ
gylic alcohol to the metal) which tautomerizes into the
Then, the fate of the catalytic cycle is depending on the
thermodynamically more stable vinylidene isomer A.[9] nature of the propargylic alcohol substituents R1 and R2:
The proposed formation of hydroxyvinylidene A is in i. If no C H bonds are present in the b-position with
accord with the absence of catalytic activity observed
when internal propargylic alcohols are used as sub-
À
respect to the alcohol group (R1 and R2 = CHR3R4;
propargylic alcohols 2a– h), dehydration of A gen-
erates an allenylidene complex B (see Scheme 7).
The electrophilicity of the Ca carbon of the unsatu-
rated chain in B, typical of allenylidene com-
plexes,[9] favours the re-addition of water to give
ꢀ
strates
[i.e.,
MeC CCH2(OH)
or
(HO)Me-
ꢀ
HCC CCHMe(OH)] since they are not able to undergo
the required tautomerization into a vinylidene species.[9]
This fact seems to discard also the involvement of ruthe-
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Victorio Cadierno et al.
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Scheme 6. The two steps in the isomerization of propargylic
alcohols into enones.
the hydroxy-carbene derivative C. Finally, the de-
metallation of carbene C takes place, involving
probably an acyl intermediate D, affording the cor-
responding enals 3a–h and regenerating the 16-eÀ
catalyst. The stereoselectivity observed in the for-
mation of aldehydes 3e–h, starting from the secon-
dary alkynols 2e–h, strongly supports the involve-
ment of an allenylidene intermediate since it is
À
well-documented that the addition of RO H bonds
¼
(water or alcohols) across the Ca Cb unit of mono-
¼ ¼ ¼
substituted allenylidenes [M] C C C(H)R usually
generates Fischer-type alkenyl-carbene complexes
[M] C(OR)-C(H) C(H)R with E stereochemis-
¼
¼
try.[23]
À
ii. If a C H bond is present in the b-position with re-
Scheme 7. Reaction pathway for Ru-catalyzed Meyer–Schus-
spect to the alcohol group (R2 ¼CHR3R4; propar- ter rearrangement.
gylic alcohols 4a–m) the reaction proceeds in a dif-
ferent way since no allenylidene B is formed. The
dehydration of hydroxyvinylidene A leads instead
to the thermodinamically favoured alkenyl-vinyli-
dene tautomer E (see Scheme 8),[24] which is in
equilibrium with its p-enyne isomer F.[9] Provided
that an excess of water is present in the reaction
media, complex F can undergo the Markovnikov
mation of complexes of type G and H (such inter-
mediates are commonly proposed on metal-cata-
lyzed alkyne hydrations).[25] The alternative deme-
tallation of the p-enyne complex F explains the for-
mation of the terminal 1,3-enynes 6c–d, h, j–m. In
accord with this, the catalytic process performed in
distilled THF yield selectively the 1,3-enynes since
the absence of water precludes the addition reac-
tion to give the ketones.
ꢀ
addition of water to the coordinated C C bond to
afford the corresponding enones 5a–j. This final
step most probably involves the intermediate for-
Concerning the role of the co-catalyst, it is well-known
that dehydration of hydroxyvinylidene derivatives to
form both allenylidene or alkenyl-vinylidene complexes
can be promoted by Brønsted or Lewis acids.[26] Thus,
the rate enhancement observed in our catalytic reac-
tions upon addition of CF3CO2H can be explained by as-
suming that the dedydration of intermediate A into B
(Scheme 7) or E (Scheme 8) is favoured in the presence
of acid.[27]
Conclusion
In this work it has been shown that the sixteen-electron
allyl-ruthenium(II)
(CO)(dppf)][SbF6] (1), in the presence of acid, is a high-
complex
[Ru(h3-2-C3H4Me)
Figure 1. Product distribution as a function of time for the
isomerization of 4d.
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FULL PAPERS
Table 3. Dehydration of propargylic alcohols catalyzed by complex 1 in the presence of CF3CO2H.[a]
Entry
Substrate
Product
Time
5 h
Yield[b]
91%
1[c]
4c
6c
2
3
4d
6d
5 h
7 h
94%
97%
4h
4j
6h
6j
4
2.5 h
96%
5
6
4k
4l
6k
6l
6 h
3 h
2 h
75%
97%
92%
7[c]
4m
6m
[a]
Reaction conditions: reactions were carried out in THF (dry; distilled) at 608C using 1 mmol of the corresponding pro-
pargylic alcohol (1.0 M solution). [Substrate]:[Ru]:[CF3CO2H] ratio¼20: 1: 2.
Isolated yield (quantitative yields were observed by GC in all cases).
[E]:[Z] ratio¼1: 1.
[b]
[c]
ly efficient catalyst for the isomerization of terminal served in our group using the indenyl-ruthenium(II) cat-
propargylic alcohols into a,b-unsaturated carbonyl alyst [RuCl(h5-C9H7)(PPh3)2] which, in the presence of
compounds, which can be obtained in excellent yields water, leads to the selective formation of hydroxy-alde-
(78–97%). This complex has also proven to promote hydes R1R2C(OH)CH2CHO.[28] Although the formation
chemoselective transformations giving rise to enals of a hydroxyvinylidene-ruthenium complex as key inter-
(Meyer–Schuster rearrangement) or enones (Rupe mediate in the catalytic cycle is in both cases proposed,
rearrangement) depending on the nature of the propar- its subsequent dehydration to generate allenylidene or
gylic alcohol. To the best of our knowledge, complex alkenyl-vinylidene species seems to be strongly depend-
[Ru(h3-2-C3H4Me)(CO)(dppf)][SbF6] (1) represents ent on the electronic properties of the ruthenium moiet-
the first example of a ruthenium catalyst for the Rupe- ies, being favoured in the case of 1.
type rearrangement of propargylic alcohols. Moreover,
In summary, the catalytic procedure for the synthesis
1 has also proven to be highly stereoselective in the iso- of a,b-unsaturated carbonyl compounds reported here
merization of secondary propargylic alcohols yielding represents a very simple, efficient and selective method-
E-enals exclusively. Although it has been described ology, involving readily available propargylic alcohols as
that complexes [Ru(h3-2-C3H4Me)2(dppe)]/PhCO2H precursors and proceeding in an overall atom economi-
and [RuCl(h5-C5H5)(PPh3)2] are also active in the syn- cal manner.
thesis of enals,[10,11] in contrast to catalyst 1, they always
lead to mixtures of E and Z stereoisomers.
We also note that the catalytic behaviour towards
1
2
Experimental Section
All reagents were obtained from commercial suppliers and
ꢀ
propargylic alcohols HC CCR R (OH) shown by the
allyl-ruthenium(II) complex
[Ru(h3-2-C3H4Me)-
(CO)(dppf)][SbF6] (1) contrasts with that previously ob- used without further purification with the exception of com-
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Victorio Cadierno et al.
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Scheme 8. Reaction pathway for Ru-catalyzed Rupe rearrangement.
plex [Ru(h3-2-C3H4Me)(CO)(dppf)][SbF6] (1)[13] and propar-
General Procedure for the Catalytic Isomerization of
Propargylic Alcohols 4a–j into a,b-Unsaturated
Ketones 5a–j
gylic alcohols 2c, d, f, g, h[29] which were prepared by following
the methods reported in the literature. Gas chromatographic
measurements were made on a Hewlett-Packard HP6890
equipment using an HP-INNOWAX cross-linked polyethy-
lene glycol (30 m, 250 mm) or a Supelco Beta-DexTM 120
(30 m, 250 mm) column.
In
a
Schlenk tube, the catalyst [Ru(h3-2-C3H4Me)-
(CO)(dppf)][SbF6] (1) (0.049 g, 0.05 mmol), the corresponding
propargylic alcohol 4a–h (1 mmol) and CF3CO2H (7.4 mL,
0.1 mmol) were dissolved, under a nitrogen atmosphere, in un-
distilled THF (1 mL) and the reaction mixture was refluxed for
the indicated time (see Table 2; the course of the reaction was
monitored by regular sampling and analysis by GC). After re-
moval of the solvent under vacuum, flash chromatography
(silica gel) of the residue using a mixture of EtOAc/hexane
(1/5) as eluent afforded enones 5a–h.
General Procedure for the Catalytic Isomerization of
Propargylic Alcohols 2a–h into a,b-Unsaturated
Aldehydes 3a–h
General Procedure for the Catalytic Dehydration of
Propargylic Alcohols
In
a
Schlenk tube, the catalyst [Ru(h3-2-C3H4Me)-
(CO)(dppf)][SbF6] (1) (0.049 g, 0.05 mmol), the corresponding
propargylic alcohol 2a–h (1 mmol) and CF3CO2H (7.4 mL,
0.1 mmol) were dissolved, under a nitrogen atmosphere, in un-
distilled THF (1 mL) and the reaction mixture was refluxed for
the indicated time (see Table 1; the course of the reaction was
monitored by regular sampling and analysis by GC). After re-
moval of the solvent under vacuum, flash chromatography
(silica gel) of the residue using a mixture of EtOAc/hexane
(1/5) as eluent afforded enals 3a–h.
In
a
Schlenk tube, the catalyst [Ru(h3-2-C3H4Me)-
(CO)(dppf)][SbF6] (1) (0.049 g, 0.05 mmol) and the corre-
sponding propargylic alcohol 4d, h, j, l, m (1 mmol) were dis-
solved, under a nitrogen atmosphere, in dry THF (1 mL) and
the reaction mixture was refluxed for the indicated time (see
Table 3; the course of the reaction was monitored by regular
sampling and analysis by GC). After removal of the solvent un-
der vacuum, flash chromatography (silica gel) ofthe residue us-
108
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ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 101 – 110

Isomerization of Propargylic Alcohols into a,b-Unsaturated Carbonyl Compounds
FULL PAPERS
ing a mixture of EtOAc/hexane (1/10) as eluent afforded 1,3-
enynes 6d, h, j, l, m. The synthesis of enynes 6c and 6k was per-
formed in a sealed tube and the product isolated from the reac-
tion mixture by fractional distillation (bp 59 and 348C/760 mm
Hg, respectively).
Characterization data for compounds 3a–h, 5a–j and 6c, d,
h, j–m can be found in the Supporting Information.
[10] a) M. Picquet, C. Bruneau, P. H. Dixneuf, Chem. Com-
´
mun. 1997, 1201–1202; b) M. Picquet, A. Fernandez, C.
Bruneau, P. H. Dixneuf, Eur. J. Org. Chem. 2000,
2361–2366.
[11] T. Suzuki, M. Tokunaga, Y. Wakatsuki, Tetrahedron Lett.
2002, 43, 7531–7533.
[12] It should be noted that the redox isomerization (not in-
volving transposition of the oxygen atom) of both termi-
nal and internal propargylic alcohols into enals and
enones catalyzed by [RuCl(h5-C9H7)(PPh3)2]/InCl3/
Et4NPF6 (C9H7 ¼indenyl) has been also reported:
a) B. M. Trost, R. C. Livingston, J. Am. Chem. Soc.
1995, 117, 9586–9587; b) B. M. Trost, Chem. Ber. 1996,
129, 1313–1322.
Acknowledgements
We are indebted to the Ministerio de Ciencia y Tecnología
(MCyT) of Spain (Project BQU2003–00255) for financial sup-
port. S. E. G. G. and V. C. thank the MCyT for the award of a
´
Ph.D. grant and a “Ramon y Cajal” contract, respectively.
[13] V. Cadierno, J. Díez, S. E. García-Garrido, J. Gimeno,
Chem. Commun. 2004, 2716–2717.
[14] We note that, in the absence of complex 1, the trifluoro-
acetic acid is not able to catalyze the isomerization of 2a
into 3a (0% of conversion after 1 h; 1.0 M solution of 2a
in wet THF; [2a]:[CF3CO2H] ratio¼20:2; reflux). This
fact clearly indicates the crucial role of the ruthenium
complex in the catalytic system.
References and Notes
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[15] Although the sixteen-electron complex [Ru(h3-C3H5)-
(CO)(dppf)][SbF6] is also an active catalyst for these iso-
merization reactions, its efficiency is lower when com-
pared to complex 1. As an example, using [Ru(h3-C3H5)-
(CO)(dppf)][SbF6] only 62% of conversion was achieved
in the isomerization reaction of 1,1-diphenyl-2-propyn-1-
ol (2a) (1.0 M solution in wet THF; [2a]:[Ru]:
[CF3CO2H] ratio¼20:1:2; reflux) into 3,3-diphenyl-2-
propen-1-al (3a) after 4 hours (to be compared with en-
try 1 in Table 1). Moreover, it should be noted that the
presence of the 1,1’-bis(diphenylphosphino)ferrocene
(dppf) ligand in the catalyst seems to be crucial since
the closely related complexes [Ru(h3-2-C3H4Me)(CO)-
(dippf)][SbF6] and [Ru(h3-C3H5)(CO)(dippf)][SbF6]
(dippf¼1,1’-bis(diisopropylphosphino)ferrocene) have
found to be completely inactive.
[16] Likewise, as observed in the formation of enals, longer
reaction times are required if the catalytic reactions are
performed in the absence of CF3CO2H. As an example,
quantitative isomerization of 3-isopropyl-4-methyl-1-
pentyn-3-ol (4a) (1.0 M solution in wet THF; [4a]:[1] ra-
tio¼20:1; reflux) into 3-isopropyl-4-methyl-3-penten-2-
one (5a) was achieved only after 22 h (to be compared
with entry 1 in Table 2).
[17] See, for example: a) A. V. Kamernitskii, I. S. Levina, H.
Kasch, Z. Chem. 1986, 26, 374–375; b) M. Lokos, T. Ba-
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co, L. Previtera, A. Fiorentino, F. Giordano, C. Mattia, J.
Org. Chem. 1999, 64, 8976–8978.
[9] For general reviews on the chemistry of transition metal
vinylidenes and allenylidenes see: a) M. I. Bruce, Chem.
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meno, Eur. J. Inorg. Chem. 2001, 571–591; g) Coord.
Chem. Rev. 2004, 248, 1531–1715 (special issue devoted
to the chemistry of vinylidenes, allenylidenes and related
metallacumulenes).
[18] See, for example: C. Aubert, O. Buisine, M. Malacria,
Chem. Rev. 2002, 102, 813–834, and references cited
therein.
Adv. Synth. Catal. 2006, 348, 101 – 110
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
109

Victorio Cadierno et al.
FULL PAPERS
[19] To the best of our knowledge, only one ruthenium com-
plex, i. e., the thiolate-bridged diruthenium(III) deriva-
tive [Cp*RuCl(m2-SMe)2RuCp*Cl], has been previously
used as catalyst for such a transformation: Y. Nishibaya-
shi, M. D. Milton, Y. Inada, M. Yoshikawa, I. Wakiji, M.
Hidai, S. Uemura, Chem. Eur. J. 2005, 11, 1433–1451.
[20] Dehydration of propargylic alcohols 4a, b, e, f, g, i has
also been checked under these reaction conditions. Al-
though the corresponding enynes are readily formed
(yields up to 70%; GC determined), the re-addition of
2137–2147; e) C. Bianchini, N. Mantovani, A. Marchi, L.
Marvelli, D. Masi, M. Peruzzini, R. Rossi, A. Romerosa,
Organometallics 1999, 18, 4501–4508; f) C. Bianchini, N.
Mantovani, L. Marvelli, M. Peruzzini, R. Rossi, A. Ro-
merosa, J. Organomet. Chem. 2001, 617–618, 233–241.
[24] We note that the absence of steroselectivity found in the
formation of enones 5b, c and 1,3-enynes 6c, m is also in
accord with the formation of the hydroxyvinylidene in-
1
3
4
¼ ¼
termediate [Ru] C C(H)-CR (OH)-CHR R (A), since
it is well-known that dehydration of hydroxy-alkanes
into alkenes is usually a non-stereoselective process,
see, for example: H. Knçzinger, in: The Chemistry of
the Hydroxyl Group, (Ed.: S. Patai), Interscience Pub-
lishers, London, 1971, pp. 641–718.
ꢀ
water to the C C bond cannot be completely suppressed
in these cases (see mechanism in Scheme 8) and concom-
itant formation of enones 5a, b, e, f, g, i is also observed.
[21] Quantitative transformation of commercially available 1-
ethynylcyclohexene (6e) (1.0 M solution in wet THF;
[6e]:[1]:[CF3CO2H] ratio¼20:1:2; reflux) into 1-acetyl-
cyclohexene (5e) was achieved after ca. 2.5 h (to be com-
pared with entry 5 in Table 2).
[25] For reviews on transition-metal catalyzed alkyne hydra-
tion, see: a) F. Alonso, I. P. Beletskaya, M. Yus, Chem.
Rev. 2004, 104, 3079–3160; b) M. Beller, J. Seayad, A.
Tillack, H. Jiao, Angew. Chem. Int. Ed. 2004, 43, 3368–
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[26] See, for example: a) H. Werner, T. Rappert, R. Weide-
mann, J. Wolf, N. Mahr, Organometallics 1994, 13,
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38.
[27] a) Formation of intermediate enol esters, analogous to
those proposed in ref.[10] (see Method A in Scheme 2),
can be discarded since our catalytic reactions proceed
in the absence of CF3CO2H (see ref.[16]); b) release of
the h3-allyl ligand as isobutene by protonation with
CF3CO2H cannot be discarded.
[22] Such types of intermediates have been recently proposed
in propargylic substitution reactions of internal alkynols
catalyzed by mononuclear ruthenium(II) complexes:
a) T. Kondo, Y. Kanda, A. Baba, K. Fukuda, A. Naka-
mura, K. Wada, Y. Morisaki, T. Mitsudo, J. Am. Chem.
Soc. 2002, 124, 12960–12961; b) E. Bustelo, P. H. Dix-
neuf, Adv. Synth. Catal. 2005, 347, 393–397; c) C. Fisch-
meister, L. Toupet, P. H. Dixneuf, New J. Chem. 2005, 29,
765–768.
[23] See, for example: a) D. Pilette, K. Ouzzine, H. Le Bozec,
P. H. Dixneuf, C. E. F. Rickard, W. R. Roper, Organome-
tallics 1992, 11, 809–817; b) C. Cosset, I. del Rio, H. Le
Bozec, Organometallics 1995, 14, 1938–1944; c) C. Cos-
´
set, I. del Rio, V. Peron, B. Windmüller, H. Le Bozec,
Synlett 1996, 435–436; d) V. Cadierno, M. P. Gamasa, J.
[28] P. Alvarez, M. Bassetti, J. Gimeno, G. Mancini, Tetrahe-
dron Lett. 2001, 42, 8467–8470.
´
Gimeno, M. Gonzalez-Cueva, E. Lastra, J. Borge, S. Gar-
´
˜
cía-Granda, E. Perez-Carreno, Organometallics 1996, 15,
[29] M. M. Midland, J. Org. Chem. 1975, 40, 2250–2252.
110
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Adv. Synth. Catal. 2006, 348, 101 – 110