Preparation of α,β-acetylenic ketones by catalytic heterogeneous oxidation of alkynes

Article abstract of DOI:10.1039/b204122g

Covalent grafting of iron phthalocyanines onto silica affords active catalysts for selective oxidation of alkynes and propargylic alcohols to α,β-acetylenic ketones, highly valuable precursors in the preparation of fine chemicals.

Full text of DOI:10.1039/b204122g

Preparation of a,b-acetylenic ketones by catalytic heterogeneous
oxidation of alkynes†
Céline Pérollier and Alexander B. Sorokin*
Institut de Recherches sur la Catalyse, CNRS, 2, avenue A. Einstein, 69626 Villeurbanne Cedex, France.
E-mail: sorokin@catalyse.univ-lyon1.fr; Fax: +(33) 4 72 44 53 99; Tel: +(33) 4 72 44 53 37
Received (in Cambridge, UK) 30th April 2002, Accepted 6th June 2002
First published as an Advance Article on the web 19th June 2002
Covalent grafting of iron phthalocyanines onto silica affords
active catalysts for selective oxidation of alkynes and
propargylic alcohols to a,b-acetylenic ketones, highly valua-
ble precursors in the preparation of fine chemicals.
the diffuse reflectance UV-vis spectroscopy that evidenced the
effective complex grafting. The complex loading was deter-
mined by metal analysis using an inductively coupled plasma-
mass spectrometry method to be 30–40 mmol g21
.
The model substrate, oct-4-yne, was oxidized by TBHP into
oct-4-yn-3-one with 80% conversion and 89% selectivity in the
presence of 2 mol % of 1 (run 1, Table 1). Only trace amounts
of oct-4-yn-3-ol (5%) and oct-4-yn-3,6-dione were found by
GC-MS analysis. Remarkably, the oxidation of oct-4-yne was
very selective, the second a-position being almost inactive. The
main product, oct-4-yn-3-one, was completely stable under
reaction conditions. On the contrary, propargylic alcohols
which could be the initial products of the alkyne oxidation were
rapidly converted into their corresponding ketones. Thus oct-
The quest for efficient clean catalytic methods remains an
important challenge for the preparation of fine and speciality
chemicals. This is especially true for oxidation reactions where
traditional stoichiometric oxidants are usually applied.
For example, a,b-acetylenic ketones are very useful building
blocks for enantioselective total synthesis and for the prepara-
tion of heterocyclic compounds, nucleosides, non-proteino-
genic amino-acids, pheromones and drugs.1 Conjugated ynones
are usually prepared by acylation of metal acetylenides and
multistep synthesis2 and only a few methods have been reported
using direct a-oxidation of alkynes. Chromium complexes have
been used to oxidize alkynes in moderate yields and a large
excess of tert-butyl hydroperoxide (TBHP) was used.3 Ishii et
al. reported an homogeneous catalytic method for oxidation of
alkynes using N-hydroxyphthalimide combined with a transi-
tion metal under aerobic conditions.4 Recently Pei et al.
reported the efficient homogeneous oxidation of alkynes to a,b-
acetylenic ketones by TBHP in the presence of 4 mol % metallic
salt.5 A mechanism of this oxidation is thought to be via an
energetically favorable hydrogen atom abstraction from the a-
CH2 group of alkyne (87.3 kcal mol21 for pent-2-yne4)
followed by the reaction with dioxygen or oxygen-centered
radicals to form a,b-acetylenic ketones.4,5
The catalysts immobilised on solid supports are especially
attractive because they allow easy separation from the reaction
mixture and possible recycling. We have recently showed that
iron tetrasulfophthalocyanine covalently supported onto silica
(FePcS-SiO2, 1) was an efficient catalyst in the oxidation of
aromatic compounds (Fig. 1).6,7 These reactions operate via 1e2
oxidation steps. Additionally, FePcS in combination with H2O2
was shown to be quite inert vis-à-vis double bonds.8 These
properties coupled with availability, chemical stability and easy
grafting of metallophthalocyanines onto silica support make
them good potential heterogeneous catalysts for the oxidation of
alkynes to a,b-acetylenic ketones.
Fig. 1 Catalysts based on metallophthalocyanines.
Scheme 1 Catalytic oxidation of alkynes.
Indeed, homogeneous oxidation of oct-4-yne in the presence
of FePcS having tetrabutylammonium cations to provide a
solubility in organic solvents resulted in 60% conversion with
near 100% selectivity for oct-4-yn-3-one formation. This
promising result prompted us to anchor phthalocyanine com-
plexes onto amino-modified silica. Here we report the first
heterogeneous catalytic oxidation of alkynes to ynones under
mild conditions (Scheme 1).
Table 1 Oxidation of alkynes by TBHP catalyzed by supported metal-
lophthalocyaninesa
Conversion Selectivity
Run Substrate
Product
(%)b
(%)b
1
2
3
4
C3H7C·CC3H7
C3H7C·CC(O)C2H5 80
89
83
38
100
85
47
The heterogeneous catalysts FePcS-SiO2(1) and FePcCl16-
SiO2(2) were prepared as previously described7 and charac-
terized by elemental analysis, surface area determination and
PhC·CC2H5
HC·CC6H13
PhC·CC(O)CH3
HC·CC(O)C5H11
75
38
HC·CC(OH)C5H11 HC·CC(O)C5H11
84
5c C3H7C·CC3H7
C3H7C·CC(O)C2H5 81
CH3C·CC(O)C4H9 64
C3H7C·CC(O)C2H5 79
6
CH3C·CC5H11
† Electronic Supplementary information (ESI) available: details of the
synthesis and characterisation of authentic ynones; kinetic curves of the oct-
4-yne oxidation under air and under argon; mass spectra of oct-4-yn-3-one
and 4-phenylbut-3-yn-2-one obtained in labelling studies; DR UV-vis
spectra of catalyst 2 before and after 3 successive oxidations. See http://
www.rsc.org/suppdata/cc/b2/b204122g/
7d C3H7C·CC3H7
88
93
8d PhC·CC2H5
PhC·CC(O)CH3
86
a The reaction was carried out at 40 ·C for 24 h. b Conversions and
selectivities were deter·ined by GC using 1-chloronaphthalene as an internal
standard. c Under argon. d With FePcCl16-SiO2 2.
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1-yn-3-ol gave rapidly oct-1-yn-3-one with 84% conversion and
100% selectivity (run 4) while oct-1-yne showed only a 38%
conversion (run 3) suggesting that the limiting step is the initial
oxidation of alkyne into propargylic alcohol through an a-
hydrogen atom abstraction. Other substrates were oxidized in
the presence of FePcS-SiO2 and TBHP (Table 1).
1-phenylbut-1-yne was also converted into 4-phenylbut-
3-yn-2-one with high selectivity (run 2). When the reaction was
carried out without catalyst, only 21% and 15% non-selective
conversions were observed for oct-4-yne and 1-phenylbut-
1-yne, respectively. Terminal oct-1-yne and oct-2-yne were less
reactive and selective providing 38 and 64% conversions and 38
and 47% selectivities, respectively.
The perchlorinated catalyst 2 exhibited similar catalytic
activity in the oxidation of oct-4-yne (run 7). Interestingly, 2
was superior to 1 in the oxidation of 1-phenylbut-1-yne
providing 86% conversion along with 93% selectivity (run 8).
When oct-4-yne and 1-phenylbut-1-yne were oxidized in the
presence of 1 mol % of the catalysts 1 or 2 we obtained the same
conversions and selectivities. Further decreasing of the catalyst
1 amount to 0.5 mol % resulted in decreasing of the selectivity
of 15–20% while keeping the same conversion of oct-4-yne. It
is noteworthy that the lower loading of catalyst 2 of 0.5 mol %
provided the same high conversion and selectivity for the
oxidation of 1-phenylbut-1-yne as for 2 mol % demonstrating a
high efficiency of this catalyst.
The good results obtained with catalyst 2 have prompted us to
study recyclability of the catalyst under the conditions of run 8.
After completing the first run new portions of the substrate and
oxidant were directly added to the reaction mixture. Three
successive oxidations of 1-phenylbut-1-yne showed that the
catalytic activity remained high, the conversions being 86, 84
and 73%, respectively. The selectivity of oxidation became
slightly higher in successful oxidations: 93, 100 and 95%. The
catalyst 2 recycled after 3 oxidations exhibited the same DR
UV-vis spectrum as that of the initial supported catalyst
indicating no degradation (see ESI†). A further set of experi-
ments was carried out to examine the reusability of the
phthalocyanine supported catalysts. After the first oxidation of
1-phenylbut-1-yne the catalyst 2 was isolated by filtration,
washed with MeCN and Et2O and dried. On reuse, 83%
conversion and 95% selectivity of 1-phenylbut-1-yne oxidation
were observed proving the high efficiency of the catalyst
recovery.
Sche·e 2 Proposed ·echanis· of the oxidation of alkynes by iron
phthalocyanine-TBHP syste· under air.
incorporation of 18O2 did not depend on the reaction time. The
oxygen atom is thus incorporated into a,b-acetylenic ketone
from both molecular oxygen and FePcS-based active species
(Scheme 2). The proportion of the oxygen incorporated from
these two sources seems to depend on the concentration of 18O2
suggesting that the reaction rates of the two pathways are of the
same order. In accord with this proposal, if the reaction is run
under argon, the oxygen in the product derives from peroxide-
FePcS active species. Since the kinetics of the reaction is
practically the same under Ar as under air we can conclude that
oxygen insertion is not the rate limiting step.
The above results lead us to propose the mechanism of this
reaction (Scheme 2). At the first rate limiting step, iron
phthalocyanine based active species abstract a hydrogen atom
from the a-position. The radical formed reacts either with iron
phthalocyanine active species to give propargylic alcohol or
with O2 to give an intermediate peroxo radical leading to
acetylenic ketones in successive oxidation steps. Intermediate
propargylic alcohol is rapidly converted to final product.‡
In conclusion, we have demonstrated efficient and selective
heterogeneous oxidation of alkynes to give valuable a,b-
acetylenic ketones using phthalocyanine supported catalysts
capable of re-use or continuous operation.
This work was supported by Fonds National de la Science.
CP is indebted to the French Ministry of Education, Research
and Technology for a post-doctoral fellowship.
Notes and references
The evidence for a mechanism involving an a-hydrogen atom
abstraction as a limiting step was gained through a comparison
of the kinetics of the reaction under air and under argon and
through an isotope labelling study with 18O2.
‡ Typical procedure for the oxidation of alkynes (catalyst–alkyne–oxidant
1+50+200): to a solution of alkyne (400 mmol) in t-BuOH (4 mL) was added
FePcS-SiO2 (8 mmol), then six portions of a 3.45 M TBHP solution in
1,2-DCE or PhCl were added to the mixture at reaction times of 0, 1, 2, 3,
5, 7 h (6 3 77.3 mL). The reaction was carried out at 40 °C for 24 h and the
progress of the reaction was monitored by using gas chromatography. The
products were identified by NMR and GC-MS methods and quantified by
GC using authentic samples prepared according published methods.5
Under argon, the oxidation of oct-4-yne was as efficient as
under air (run 5, Table 1) following the same kinetics (see
ESI†). Apparently, this finding suggested that O2 was not
involved in the oxidation. The source of product oxygen has
been examined by a 18O-labelling study to determine whether
the oxygen transfer occurs from FePcS-based active species or
from O2. If a high-valent iron oxo species, which is generated by
the O–O bond cleavage of the iron peroxo complex, is the only
species involved, no 18O incorporated in a,b-acetylenic ketone
formed would be detected. So we performed the oxidation of
oct-4-yne with labelled molecular oxygen (98.5% 18O enrich-
ment) in the presence of TBHP and 1. The mass spectrum of
unlabelled oct-4-yn-3-one exhibits a major ion at m/z = 95
corresponding to the adduct [M 2 C2H5]+ along with weak M+
at m/z = 124. Under an atmosphere containing 27.6% of 18O2
and 72.4% of Ar, the 18O-content of labelled ketone was found
to be 61.7 ± 0.3% as measured by the relative intensities of the
molecular ions (m/z 124/126) and of the base peaks (m/z 95/97).
The oxidation of 1-phenylbut-1-yne by TBHP in the presence of
2 under an atmosphere containing 40.2% of 18O2 and 59.8% of
Ar also produced ketone with 85.1 ± 2.0% labelled oxygen, as
was measured from the relative intensities of the molecular
peaks (m/z 144/146) and of the base peaks (m/z 129/131)
resulting from the loss of methyl radical. In both cases the
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