Conversion of pentynol to pentanone catalysed by Pd(II) metal centres

Article abstract of DOI:10.1016/j.jorganchem.2006.06.022

The cyclization of 3- or 4-pentyn-1-ol is catalysed by PdCl₂ or trans-[PdCl₂L₂] (L = R-camphorimine; R = Ph; Prⁱ; NMe₂) complexes at room temperature affording heterocyclic compounds, respectively, 2-methyl-2-pent-3-ynyloxy-tetrahydrofuran or 2-methyl-2-pent-4-ynyloxy-tetrahydrofuran which subsequently add water to give selectively 5-(2-methyl-tetrahydrofuran-2-yloxy)-pentan-2-one from both starting materials. By hydrolysis 5-(2-methyl-tetrahydrofuran-2-yloxy)-pentan-2-one undergoes ring cleavage to form 5-hydroxy-2-pentanone. The catalytic activity and selectivity of complexes trans-[PdCl₂L₂] (L = R-camphorimine) depend on the characteristics of the R group (NMe₂ > Prⁱ > Ph). The catalytic activity of PdCl₂ is comparable to that of trans-[PdCl₂L₂] (L = Ph-camphorimine) which is the less efficient catalyst.

Full text of DOI:10.1016/j.jorganchem.2006.06.022

Journal of Organometallic Chemistry 691 (2006) 4124–4127
www.elsevier.com/locate/jorganchem
Conversion of pentynol to pentanone catalysed by Pd(II) metal centres
a,
a
b
M. Fernanda N.N. Carvalho *, Ana S.D. Ferreira , Rudolf Herrmann
a
Centro de Qu´ımica Estrutural, Complexo I, Instituto Superior Te´cnico, Av. Rovisco Pais 1049-001 Lisboa, Portugal
b
Institut fu¨r Physik, Universita¨t Augsburg, Universita¨tsstr. 1, 86159 Augsburg, Germany
Received 12 April 2006; received in revised form 12 June 2006; accepted 16 June 2006
Available online 22 June 2006
Abstract
The cyclization of 3- or 4-pentyn-1-ol is catalysed by PdCl2 or trans-[PdCl2L2] (L = R-camphorimine; R = Ph; Pri; NMe2) complexes
at room temperature affording heterocyclic compounds, respectively, 2-methyl-2-pent-3-ynyloxy-tetrahydrofuran or 2-methyl-2-pent-4-
ynyloxy-tetrahydrofuran which subsequently add water to give selectively 5-(2-methyl-tetrahydrofuran-2-yloxy)-pentan-2-one from both
starting materials. By hydrolysis 5-(2-methyl-tetrahydrofuran-2-yloxy)-pentan-2-one undergoes ring cleavage to form 5-hydroxy-2-pen-
tanone. The catalytic activity and selectivity of complexes trans-[PdCl2L2] (L = R-camphorimine) depend on the characteristics of the R
group (NMe2 > Pri > Ph). The catalytic activity of PdCl2 is comparable to that of trans-[PdCl2L2] (L = Ph-camphorimine) which is the
less efficient catalyst.
ꢀ 2006 Elsevier B.V. All rights reserved.
Keywords: Catalysis; Alkynols; Palladium; Camphor; Heterocycles; Organic synthesis
1. Introduction
In the last decades several transition metals were studied
as catalysts for promotion of cyclization of alkynes [15,16]
due to the relevance of these processes for syntheses of nat-
ural products or biological active species.
The search for more active or/or selective catalysts to
promote the formation of aromatic or heterocyclic systems
continues to be a challenge to fulfil more economical and
environmental friendly synthetic processes.
Catalytic activation of unsaturated molecules by transi-
tion metals is a well-established process for the synthesis of
organic species which may be difficult to prepare with clas-
sical organic strategies [1]. Cascade reactions are of partic-
ular interest since several steps can be accomplished in the
same vessel this accounting for time and atom economy.
Among the unsaturated molecules, alkynes are attrac-
tive versatile species that display high coordinative ability
to most the transition metals forming alkynyl, vinylidene
or other type of complexes [2–5] that in same cases trigger
reactions such as coupling [6] or cyclization [7–12]. The
introduction of an additional alcohol group may modify
well-known reaction paths leading to the syntheses of het-
erocyclic species such as furans [13] or less stable cyclic
ketal-type species [14].
2. Results and discussion
We started to explore the potential of alkynols for the
synthesis of oxygen-containing heterocycles by studying
the reactions of several {PdCl2} metal centres with 3- or
4-pentyn-1-ol. In the absence of a catalyst these pentynols
are stable at room temperature and no cyclization or
hydration occur.
PdCl2 (2–5%) catalysis the dimerization of 4-pentyn-1-ol
affording 2-methyl-2-pent-4-ynyloxy-tetrahydrofuran (1a)
as the first step within a process that undergoes the forma-
tion of 5-(2-methyl-tetrahydrofuran-2-yloxy)-pentan-2-one
(2) followed by 5-hydroxy-2-pentanone (3) in mild
*
Corresponding author.
E-mail addresses: fcarvalho@ist.utl.pt (M. Fernanda N.N. Carvalho),
rudolf.herrmann@physik.uni-augsburg.de (R. Herrmann).
0022-328X/$ - see front matter ꢀ 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2006.06.022

M. Fernanda N.N. Carvalho et al. / Journal of Organometallic Chemistry 691 (2006) 4124–4127
4125
experimental conditions, Scheme 1. In a parallel process
the catalyst also activates 3-pentyn-1-ol towards formation
of 2-methyl-2-pent-3-ynyloxy-tetrahydrofuran (1b) which
can be hydrated to 2 and hydrolysed to 3.
either in dichloromethane or chloroform. Traces of mois-
ture in the reagents account for the hydration process.
Controlled addition of water to 1a, in the presence of
catalytic amounts of PdCl2 (<2%) affords 2 as the only
ketone species. A large excess of H2O leads to hydrolysis
and formation of 5-hydroxy-2-pentanone (3) plus some
starting 4-pentyn-1-ol (due to reverse reaction). A similar,
step by step process is observed in the case of 1b.
The hydration of 4-pentyn-1-ol catalysed by Hg(II) is
known to afford 5-(2-methyl-tetrahydrofuran-2-yloxy)-
pentan-2-one [22]. The process involves a Markovnikov
type mechanism that is very selective in the case of terminal
alkynes. However, the hydration of internal alkynes using
the mercury catalyst is a random non-selective process,
forming different regio-isomers with respect to the position
of the carbonyl group in the chain, unless the alkyne is
symmetric.
The results now reported show that the hydration of 3-
pentyn-1-ol catalysed by PdCl2 is more selective than that
with mercury catalyst leading exclusively to 2 (no other
cyclic ketal-ketone isomer was detected by 13C NMR).
The final 5-hydroxy-2-pentanone forms by hydrolysis of 2
conceivably through a linear ketal species. No experimental
evidence could be obtained by NMR for such a linear spe-
cies which is expected to be unstable and undergo C–O
bond breaking (Scheme 2).
The catalytic process is slow, a fact that is inconvenient
for synthetic purposes but was very useful to get details on
the activation of pentynols by {PdCl2} species. At the pro-
cess, the aprotic solvent (CH2Cl2 or CHCl3) conceivably
plays a key role since former studies [17,18] made in protic
solvents did not allow the identification of species of type 1
in the conversion of 3- or 4-pentyn-1-ol to 5-hydroxy-2-
pentanone.
1
Following by H NMR the reaction of 4-pentyn-1-ol
with PdCl2 we first observed the decrease of intensity fol-
lowed by the disappearance of the signal assigned to the
terminal proton of the alkyne group, in agreement with
coordination through the alkyne such as reported for Pt(II)
[17], Ru [19] or Pd [18] but in contrast with reported for
Rh(I) [20] that was found to involve coordination of the
alcohol group. The different characteristic of the metal cen-
tres conceivably account for different intermediates and
mechanism.
The study of the mechanism of cyclization of 4-pentyn-
1-ol [21] promoted by W(0) showed that the coordination
of the alkyne is followed by the intramolecular attack of
the alcohol group to the exo carbon atom affording a het-
erocyclic species that rearranges to the final furan product.
The results herein show that {PdCl2} catalysts promote
further reactivity, i.e. addition of the alcohol moiety of a
second alkynol molecule to the exo carbon atom of the
coordinated heterocyclic species (conceivably similar to
that in [21]) affording the ketal-alkyne species 1a or 1b that
undergo hydration to 2 followed by hydrolysis to 5-
hydroxy-2-pentanone.
In dichloromethane, at 10 ꢁC, in the absence of added
water, under catalytic conditions, compound 1a is the only
product detected by 13C NMR until consumption of 4-pen-
tyn-1-ol (ca. 50%). Longer reaction times allow addition of
traces of water (in the solvent or alkynol) to the triple bond
of the alkyne moiety of species 1 affording the ketone-ketal
species 2.
In chloroform the formation of 2 accompanies that of 1,
almost since the beginning of the reaction. Increasing the
temperature to 25 ꢁC the formation of 2 becomes faster,
Compounds 1a, 1b and 2 were characterized by NMR
and FT/IR data (see Section 4).
Up to now we demonstrated that the commercially
available PdCl2 catalyses the conversion of terminal or
internal pentynols into 5-hydroxy-2-pentanone by a slow
process that generates two reasonably stable cyclic ketal
species which are hydrolysed to 5-hydroxy-2-pentanone.
In order to try to increase the low reaction rates
induced by PdCl2 we started the evaluation of trans-
[PdCl2(L)2] (L, R = Ph (A); Pri (B); NMe2 (C), see
Fig. 1 for L) as catalysts for the dimerization of 3- or
4-pentyn-1-ol, since the camphorimine derived complexes
trans-[PdCl2(L)2] are known to catalyse the cyclotrimer-
ization of alkynes [7,8].
Following the reaction by NMR, we verify that trans-
[PdCl2L2] (1–2%) react with 3- or 4-pentyn-1-ol affording
species 1 such as observed by reaction with PdCl2. The
selectivity and kinetics of the process depends on L.
10
5
4
3
2
1
O
9
PdCl2
OH
6 O
(i)
8
7
(1a)
(ii)
H 2
O
1
O
H 2
(iii)
O
2
4
OH
O
O
3
5
O
(3)
(2)
Scheme 1.

4126
M. Fernanda N.N. Carvalho et al. / Journal of Organometallic Chemistry 691 (2006) 4124–4127
C
H3
C
O
H
H3
O
H2O
O
O
O
O
C
H3
C
H3
HO
(2)
O
O
H
C
H3
(3)
Scheme 2.
in order to extend this synthetic procedure to other
heterocycles.
NR
3. Conclusions
O
Fig. 1. Camphor type ligands (L).
The conversion of 3- or 4-pentyn-1-ols to 5-hydroxy-2-
pentanone is catalysed by metal centres having in common
the {PdCl2} unit. In the process, cyclization of the alkynol
followed by addition to the coordinated heterocycle of a
second alkynol molecule affords moderate stable cyclic
ketal species (1) that still keep the alkyne function. These
alkyne-ketal species undergo catalytic hydration without
ring cleavage forming selectively a methyl ketal-ketone
(2) that can be hydrolysed to the final ketone product (3).
The process is highly selective in the case of the internal
alkynol which is an advantage compared to former cata-
lysts. The ketal-alkyne and ketal-ketone species are prom-
ising building blocks for organic syntheses.
The {PdCl2} metal centre is necessary to promote the
dimerization of the alkynol to the alkyne-ketal species 1
but camphorimine complexes trans-[PdCl2L2] enhance the
selectivity by enabling higher reaction rates. The activity
and selectivity of the {PdCl2} catalysts are tuned by the elec-
tronic and steric properties of the camphorimine ligands.
At room temperature, in CHCl3 complex A (R = Ph)
takes 5 h to convert 20% of 4-pentyn-1-ol into 1a (75%)
and 2 (25%) the kinetics being comparable to reaction with
PdCl2. In the same experimental conditions, using complex
B (R = Pri) the reaction is ca. two times faster on forma-
tion of 1a and is much more selective (just traces of species
2 were obtained). Increasing the temperature (50 ꢁC) the
catalytic process becomes slightly faster (ca. 1.2·) but less
selective (1a, 70%; 2, 30%).
Complex C (R = NMe2) is the most efficient catalyst,
since, in less than half one hour, it selectively converts
4-pentyn-1-ol (50%) into 1a (no traces of 2). A similar
trend was observed in the reaction with 3-pentyn-1-ol,
i.e. complex C reacts faster and more selectively than B
or A towards formation of 1b. However, in this case the
reaction rate is lower than with 4-pentyn-1-ol, since just
20% of 3-pentyn-1-ol were converted to 1b in half an
hour.
The catalytic properties of poor soluble PdCl2 (in
chlorinated solvents) and high soluble complex A are
identical. Thus, faster kinetics can not be attributed to
higher solubility of the Pd-camphorimine complexes.
Moreover, complexes A, B or C display similar solubility
and rather different reaction rates pointing to being steric
and/or electronic factors responsible for their reactivity
pattern.
4. Experimental section
The experiments were carried out under inert atmo-
sphere by using vacuum and the Schlenck techniques.
Complexes trans-[PdCl2L2] were prepared by published
methods [8]. Solvents were purchased from Aldrich, puri-
fied by conventional techniques and distilled before use.
PdCl2 was purchased from Riedel-de Hae¨n.
The NMR samples were prepared in CD2Cl2 or CDCl3
using screw-cap NMR tubes and spectra were obtained on
a Varian 300 spectrometer. The IR spectra were obtained
in a JASCO FT/IR 4100 spectrometer.
The results herein show that the catalytic activity of
trans-[PdCl2L2] complexes towards heterocyclic dimeriza-
tion of internal or terminal pentynols follows the trend
C > B > A, such as observed in the cyclotrimerization of
3-phenyl-1-propyne [8]. The two sets of results confirm that
the camphor ligand derived from dimethylhydrazine acti-
vates better the {PdCl2} metal centre for catalysis.
Investigations to tune the catalytic properties by modifi-
cation of the characteristics of the coordination sphere of
the catalysts or the experimental conditions are in progress
4.1. Catalysis
The amount of PdCl2 or trans-[PdCl2L2] catalysts varied
from 2% to 5%. The reactions were carried till completion
(confirmed by NMR) typically as follows:

M. Fernanda N.N. Carvalho et al. / Journal of Organometallic Chemistry 691 (2006) 4124–4127
4127
4.2. 2-Methyl-2-pent-4-ynyloxy-tetrahydrofuran (1a) or 2-
methyl-2-pent-3-ynyloxy-tetrahydrofuran (1b)
Further addition of H2O or exposition to air led quanti-
tatively to 3, H NMR, (CDCl3): d = 2.03 (s, 3H, CH3),
1
1,66 (q, 2H, J = 6.6 Hz, H-4), 2.43 (t, 2H, J = 7.1 Hz, H-
3), 3.46 (t, 2H, J = 6.0 Hz H-5) ppm; 13C NMR (CDCl3):
d = 29.54(C-1), 26.26 (C-4), 61.36 (C-5), 209.6 (C-2),
39.98 (C-3) ppm) (see Scheme 1 for labelling).
PdCl2 (5 mg, 0.028 mmol) was added to a solution of 4-
pentyn-1-ol (100 ll, 1.07 mmol) or 3-pentyn-1-ol (100 ll,
1.08 mmol) in CH2Cl2 (10 cm3) and the mixture stirred
for 2 days. After partial evaporation of the solvent fol-
lowed by addition of Et2O (ca. 5 cm3) the catalyst was sep-
arated from the red–brown solution by filtration. Full
evaporation of the solvent afforded yellow oil (1a,
Acknowledgments
This work was partially supported by Fundac¸ao para a
˜
Cieˆncia e Tecnologia – FCT and FEDER under POCI
2010 (Project POCI/QUI/58119/2004).
145 mg; 80% conversion; mC„C = 2119 cmÀ1
;
1H NMR
(CD2Cl2): d = 1,34 (s, 3H, CH3), 1.6–2.0 (m, 10H, H-
2,4,6,7,8), 1.7–1.8 (m, 1H, CH, 1-H), 2.18 (td, 2H,
J = 7.0 and J = 2.2 Hz, H-3), 3.3–3.4 (m, 2H, H-5), 3.7–
3.8 (m, 2H, H-9) ppm; 13C NMR (CD2Cl2): d = 16.11
(C-3), 22.10 (C-10), 25.43 (C-4), 30.15 (C-8), 38.85 (C-7),
59.88 (C-5), 68.24 (C-9), 68.98 (C-1), 85–06 (C-2); 108.1
(C-6) ppm) or (1b, 140 mg; 77% conversion;
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m
C„C = 2061 cmÀ1 ill defined; 1H NMR, (CDCl3):
,
d = 1,38 (s, 3H, CH3), 1.6–2.4 (m, 10H, H-2,4,6,7,8), 1.70
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(2)
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and the mixture stirred for 2 days. Then, H2O (20 ll)
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140 mg; 77% conversion; mCO = 1716 cmÀ1
;
1H NMR
(CD2Cl2): d = 1.32 (s, 3H, CH3), 1.6–2.0 (m, 10H, H-
2,4,6,7,8), 2.04 (s, 1H, CH, 1-H), 2.40 (t, 2H,
J = 7.3 Hz, H-3), 3.3–3.4 (m, 2H, H-5), 3.7–3.8 (m, 2H,
H-9) ppm; 13C NMR (CD2Cl2): d = 22.64 (C-10), 25.38
(C-4), 30.45 (C-8 and C-1), 38.84 (C-7), 41.35 (C-3),
60.66 (C-5), 68.98 (C-9), 108.1 (C-6), 209.1 (C-2) ppm)
(see Scheme 1 for labelling).
´
´
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