Graphene oxide as a catalyst for the diastereoselective transfer hydrogenation in the synthesis of prostaglandin derivatives

Article abstract of DOI:10.1039/c7cc05105k

Modification of GO by organic molecules changes its catalytic activity in the hydrogen transfer from i-propanol to enones, affecting the selectivity to allyl alcohol and diastereoselectivity to the resulting stereoisomers. It is noteworthy the system does not contain metals and is recyclable.

Full text of DOI:10.1039/c7cc05105k

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Graphene oxide as a catalyst for the
diastereoselective transfer hydrogenation
Cite this:DOI: 10.1039/c7cc05105k
in the synthesis of prostaglandin derivatives†
Received 2nd July 2017,
Accepted 16th August 2017
a
a
a
a
Simona M. Coman, Iunia Podolean, Madalina Tudorache, Bogdan Cojocaru,
a
b
b
Vasile I. Parvulescu, * Marta Puche and Hermenegildo Garcia
*
DOI: 10.1039/c7cc05105k
rsc.li/chemcomm
7
8
5
Modification of GO by organic molecules changes its catalytic aza-Michael addition, polymerization, oxidation and gas phase
9
activity in the hydrogen transfer from i-propanol to enones, affecting C–C multiple bond hydrogenations.
the selectivity to allyl alcohol and diastereoselectivity to the resulting
Aimed at extending the applicability of such versatile materials
stereoisomers. It is noteworthy the system does not contain metals also in the area of pharmaceutical syntheses, herein we report on
and is recyclable.
the performance of graphene oxide (GO, 48.6 wt% oxygen and 1.8 S
content) in the hydrogen transfer reduction of lactonic enone 1
The unprecedented development of pharmaceutical industries, ([3aa,4a(E),5b,6aa]-(Æ)-4-[4-(3-chlorophenoxy)-3-oxo-1-butenyl]-hexa-
currently based mostly on multi-step organic syntheses, came hydro-5-hydroxy-2H-cyclopenta[b]furan-2-one) (Scheme 1) used
with the unwanted price of the huge amounts of harmful wastes in the synthesis of commercial cloprostenol. The use of metal-
produced with high environmental impact due to their biological free catalysts other than GO for the hydrogen transfer reduction
activity. This situation entailed the need to apply green chemistry of carbonyl compounds by isopropanol has been reported in the
1
0–12
principles and, particularly, heterogeneous catalysis as an alter- literature.
native to stoichiometric reactions. Thus, many of the modern Between the two possible diastereomers shown in Scheme 1, only
syntheses in today’s pharmaceutical industry are based on catalytic the 15R form of the allylic alcohol 2 exhibits biological activity and
reactions, but unfortunately many of them use precious metals as has practical importance (the atom numbers 11 and 15 are in
1
active components. As a consequence, due to their limited agreement with the structure of PGF2a). Therefore, the synthesis
abundance and low reserves, the use of noble or critical metals should be chemoselective to the allylic alcohol and diastereoselective
can become a bottleneck for the pharmaceutical industry, to its 15R form. However, as indicated in Scheme 1, other products
therefore it is of interest to find alternative catalysts.
besides the desired 15R diastereomer can also be formed.
Particularly, the high interest in the production of synthetic
Table 1 lists some results of the transfer hydrogenation of
prostaglandins, with a wide range of medicinal applications, enone 1 with i-PrOH as the transferring agent and GO as the
made us to develop not long ago noble metal (e.g., Ru, Ir, Pt) catalyst. No enone 1 conversion was detected using blank
catalysts for their synthesis. The hydrogenation of the lactonic controls under the same conditions in the absence of catalyst.
enone intermediate in the synthesis of commercial cloprostenol,
a more stable structural analogue with a more specific effect
compared to natural PGF ‘’s, can be promoted efficiently and in
2a
2
a highly stereoselective manner by these metallic catalysts.
In the context of the development of sustainable alternatives
to precious or critical metal catalysts, carbon materials are
increasingly attractive as metal-free catalysts for a large variety of
3,4
5
6
organic reactions, such as hydration, Michael-type Friedel–Crafts
a
Department of Organic Chemistry, Biochemistry and Catalysis, Chemistry,
University of Bucharest, Bdul Regina Elisabeta 4-12, Bucharest 030016, Romania.
E-mail: vasile.parvulescu@chimie.unibuc.ro
b
Instituto Universitario de Tecnolog ´ı a Qu ´ı mica CSIC-UPV, Universitat Politecnica
de Valencia, Av. de los Naranjos s/n, 46022 Valencia, Spain.
E-mail: hgarcia@qim.upv.es
Scheme 1 The possible products of the prostaglandin intermediate 1
†
Electronic supplementary information (ESI) available. See DOI: 10.1039/c7cc05105k
reduction.
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Table 1 Catalytic performance of GO as a catalyst in transfer hydrogena-
a
tion of enone 1
Entry Reaction time, h Conv., %
Sallylic alhohol 2, % d.e., %/conf.
1
2
3
4
5
6
6
12
24
36
6
39.6
51.0
62.1
94.2
21.7
9.1
17.5
29.3
48.0
50.4
27.5
31.5
13.4/(11R, 15R)
Racemic
Racemic
Racemic
Racemic
12
b
c
Fig. 1 Functional groups on the surface of GO.
24
77.8/(11R, 15S)
a
b
Reaction conditions: 30 mg GO, 28 mg enone, 5 mL i-PrOH, 80 1C. of GO as hydrogen transfer catalysts would be the existence on the
c
7
mg GO, 14 mg enone, 2.5 mL i-propanol 80 1C. 7 mg GO, 14 mg
GO layer of a similar type of frustrated Lewis acid–base pair
located at an adequate distance to promote the i-propanol
enone, 2.5 mL i-PrOH, r. t.
+
dehydrogenation with the simultaneous formation of H -like
À
and H -like sites (Scheme 2). NH -TPD measurements of the GO
3
In contrast to the results of the blank experiment, Table 1
catalyst confirmed the presence of the strong acidic sites
shows that for an enone/catalyst ratio of ca. 1/1 wt% after 36 h
(Fig. S1, ESI†). Based on prior studies showing the catalytic
(entry 4) more than 90% of the enone is converted. Even more
activity of hydrogensulfate and sulfonic groups introduced in
the GO by sulfuric acid in the formation of graphite oxide from
important, for this high conversion, the selectivity to allylic
alcohol 2 reached 50.4%. Upon increasing the enone/catalyst
ratio to 2/1, the conversion decreased from 39.6 to 21.7%
1
9,20
graphite,
it is proposed also that these S containing groups
are the ones contributing to the observed catalytic activity.
Accordingly, it seems that the reaction mechanism should
(
2
Table 1, entries 1 and 5), while the selectivity to allylic alcohol
increased from 17.5 to 27.5%. Room temperature improved
the selectivity to 31.5% in detriment to the enone conversion
9.1%, entry 6). A lower reaction temperature had also a
involve the uptake of H from i-propanol on GO, probably as
2
À
+
H
and H that subsequently would transfer to the enone 1.
(
Evidence for the existence of such sites is detailed in ref. 9.
beneficial effect in increasing the d.e. selectivity value.
The stereospecificity of the CQO group reduction would
require a preferential direction of attack of nucleophilic H
The chemoselectivity to product 2 increases with time
À
(Table 1, entries 1–4), a fact that might reflect alteration of
(
axis a or b) present on the catalyst surface and the existence of
GO active sites during the reaction due to the reductive conditions
of the hydrogenation reaction. This phenomenon, also known as
2
21
a single enone conformation (Scheme 3). Corey demonstrated
that in order to observe a preferential direction of the attack of
hydride to the carbonyl group, leading to the formation of (11R,
15R) – a natural type configuration, a large steric hindrance to
avoid the hydrogen attack on the ‘‘b’’ direction is not sufficient
and a preferential cis enone conformation is also necessary.
To gain some information about the possible role of acids
and bases, a series of control experiments were carried out. By
adding acetic acid or pivalic acid into the liquid phase, the
enone conversion was highly improved while the selectivity to 2
highly decreased. However, while acetic acid led to a racemic
mixture of the two stereoisomers, the steric hindrance generated
by the pivalic acid–enone interaction controls the stereoselectivity
in favor of the natural-like configuration (d.e. = 100%, Table 2,
entries 3 and 4). However, the increase of the reaction time from
‘‘reaction-induced selectivity improvement’’, has previously been
1
3
described in the literature and also observed and reported by
1
4
some of us in the Meerwein–Ponndorf–Verley reaction using
PtSnx alloys as catalysts. A lower reaction temperature has also an
effect in increasing the diastereoselectivity from racemic to 77.8%
(epi-like diastereomer).
There exist on the surface of GO (see ESI†) different functional
groups, including epoxide, OH and ether groups on the basal
plane and –CO H, and quinones at the edges, all these groups
2
amounting to 42.1 wt% oxygen. Besides these, aromatic C–H at
the edges or defects and small isolated aromatic domains (2–3 nm)
within the sp C matrix (Fig. 1) are also present. While CO
OH groups display acidic properties, ethers and carbonyls are
neutral or may form basic structures, such as quinone groups. In
addition, the p-electron system of the basal planes contributes to
9
3
15
2
H and
16
6
to 24 h led to a depletion of the selectivity to allylic alcohol from
1
7
29% to only 3.5%, due to the subsequent hydrogenation of the
CQC double bond.
the carbon basicity. The GO surface picture is completed by
taking also into consideration the possible existence of
metal impurities in trace amount levels, particularly of Mn
In contrast, the butylamine–enone interactions do not influence
significantly the interaction of substrate 1 with the GO surface, the
catalytic efficiency being more or less similar with that in the
absence of butylamine (Table 2, entries 1 and 5). However, replacing
(
150 Æ 23 ppm) and Fe (8 Æ 2 ppm), as determined by
9
quantitative chemical analysis.
The conversion of alcohols on carbon catalysts has been
18
studied most extensively. Clearly, i-propanol suffers simultaneous
dehydration and dehydrogenation, due to the presence of CO H
2
groups and Lewis acid–base pairs on the GO surface, the catalytic
activity being controlled by the number and strength of the
functional groups. On the basis of this known activity of Lewis
acid–base pairs acting as metal-free hydrogenation/dehydro-
Scheme 2 Proposed dehydrogenation mechanism of secondary alcohols
genation catalysts, a reasonable proposal to rationalize the activity due to the presence of frustrated Lewis acid–base pairs.
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Àd
Scheme 3 Possible directions ‘‘a’’ or ‘‘b’’ of the H attack to the pros-
taglandin precursor.
Table 2 Influence of different organic acid and base molecules added in
the liquid phase on the catalytic performance of GO in the transfer
a
hydrogenation of enone 1
Organic molecule Conv., % Sallylic alhohol 2, % d.e., %/conf.
1
2
3
4
5
6
7
8
9
1
1
—
9.1
64.0
83.2
88.0
2.2
2.1
78.8
2.0
31.5
1.0
28.9
3.5
46.0
95.6
2.0
81.3
79.2
58.8
23.4
77.8/(11R, 15S)-epi
Racemic
100/(11R, 15R)-nat.
100/(11R, 15R)-nat.
64.4/(11R, 15S)-epi
49.5/(11R, 15S)-epi
Racemic
86.7/(11R, 15R)-nat.
91.1/(11R, 15R)-nat.
90.0/(11R, 15S)-epi
100/(11R, 15S)-epi
Acetic acid
Pivalic acid
Pivalic acid
Butylamine
Acetic acid
Butylamine
Pivalic acid
Pyridine
b
Fig. 2 IR spectra of GO (a), and GO after the addition of pivalic acid (b),
acetic acid (c), butylamine (d), and pyridine (e).
c
c
c
89.1
d
e
0
1
Pyridine and TsOH 96.1
TsOH 1.7
pyridine with the acidic groups creates a balance of acidic and
basic sites necessary for the generation on the catalyst surface
+d
Àd
a
H
and H pairs. The IR spectra shown in Fig. 2 evidenced
Reaction conditions: 7 mg GO, 14 mg enone, 0.5 mL organic compound,
b
c
2
.5 mL i-propanol, room temperature, 24 h. 6 h. Pre-modified catalyst the differences between the functional groups in GO and the
d
with 0.5 mL of organic molecule, room temperature. 7 mg p-toluene-
modification introduced by the addition of organic acids
and bases.
sulfonic acid, 14 mg enone, 0.5 mL pyridine, 2.5 mL i-propanol, room
temperature, 24 h. Pre-modified GO with p-toluenesulfonic acid, room
temperature.
e
5,22
GO exhibits a typical DRIFT spectrum
with bands attributed
to various oxygen functional groups as OH (a broad band at
À1
À1
À1
3
200–3500 cm and a maximum at 3148 cm , a band at
À1
butylamine by pyridine produced remarkable results both in terms 1348 cm , and a band of C–OH at 1038–1175 cm ), carbonyl
of activity and selectivity to allylic alcohols and also in terms of (CQO) and carboxyl (COOH) groups (bands at 1613 cm and
diastereoselectivity (Table 2, entry 9). Accordingly, the chemo- 1713 cm , 3000–3600 cm and 1176 cm ), epoxides (C–O–C) and
selectivity to allylic alcohol 2 increased to 79.2% for an enone ethers (C–O) (800–1200 cm , an intense band at ca. 1340 cm ).
conversion of 89%, while the d.e. value increased to 91.1%. The band at about 1580 cm is attributed to CQC in plane
Then, replacing the GO catalyst by p-toluenesulfonic acid vibrations.
TsOH) afforded an increase of both enone conversion and As expected in view of its basicity, the chemisorption of
À1
À1
À1
À1
À1
À1
À1
2
2
(
allylic alcohol selectivity from 9.1% (Table 2, entry 10) to 96.1% butylamine on GO modified the DRIFT spectrum, the most
and from 31.5% (Table 1, entry 1) to 93.6% (7 mg TsOH, 14 mg remarkable variations being the decrease in intensity of the
À1
enone, 2.5 mL i-propanol, room temperature, 24 h). However the 1713 cm band due to carboxylic acids, accompanied by the
À1
d.e. value with TsOH was only 73.6%.
appearance of a new band at about 1623 cm attributable to
23
Since TsOH is insoluble in i-propanol, the enhancement of amides formed by the reaction of butylamine and CO
2
H groups.
the catalytic performance is exclusively due to the presence Other peaks ascribed to the presence of C–N and N–H bonds were
24
of the Brønsted acid onto the catalytic system. The addition of also observed. In the case of pyridine chemisorption, besides the
pyridine to TsOH led to a decrease of the selectivity to allylic disappearance of CO H groups, new bands associated with the
alcohol 2 to 58.8% for a conversion of enone of 96.1% (Table 2, CQN stretching vibrations were also observed.
2
25,26
entry 10), while the d.e. value increased to 90.0% in favor of the
epi-like configuration (i.e., (11R, 15S)). It is noteworthy that the bands at about 1746, 1623 and 1047 cm increased due to the
presence of pyridine in the TsOH based system provokes its reprotonation of the COO groups. Overall, FTIR spectroscopy
Chemisorption of acetic acid led to a different pattern. The
À1
À
17
solubilization, and the catalytic system becomes in this case confirms the disappearance and growth of the CQO stretching
À
homogeneous.
associated with CO H/CO groups depending on the acidic/
2
2
An explanation of the activity data could be that an excess of basic nature of the additive.
carboxylic acid groups and acid groups favors dehydration vs.
According to this pattern, i-propanol will undergo the reaction
dehydrogenation of i-propanol providing in this way a too low via a different reactivity pattern with the GO surface depending
dÀ
concentration of H nucleophiles for transfer hydrogenation. on the nature of the groups. Also, the CQO group of the substrate
In contrast, the interaction of butylamine and even more of 1 will have a different interaction with the surface modified by
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and basic additives, pyridine produced remarkable positive effects
in the hydrogen transfer of the investigated enone providing high
activity, selectivity to allylic alcohols and diastereoselectivity in the
synthesis of an important prostaglandin product. Also, pivalic acid
swaps the diastereoselectivity totally. Also, GO is able to hydrogenate
a,b-unsaturated ketones such as b-ionone or methoxynaphthyl-2-
butanone to the corresponding allylic or saturated alcohols with
excellent yields. It is noteworthy that the system does not contain
metals and is recyclable.
Conflicts of interest
There are no conflicts to declare.
Notes and references
Scheme 4 Hydrogenation of b-ionone (3, A) and 4-(6-methoxy-2-
naphthyl)-3-butenone (8, B).
1
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a,b-unsaturated ketones, namely, b-ionone (3) and 4-(6-methoxy-2-
naphthyl)-3-buten-2-one (8) (Scheme 4A and B), were hydrogenated.
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the isolated double bond in b-ionone (3) is only a minor reaction,
and a selectivity of 81% for the allylic alcohol (i.e., b-ionol 6) was
obtained at a high conversion (490%). However, by association
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1
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2
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