Gallium-catalyzed reductive lactonization of γ-keto acids with a hydrosilane

Article abstract of DOI:10.1039/c6ra19286f

Described herein is the GaCl₃-catalyzed lactonization of γ-keto carboxylic acids in the presence of PhSiH₃ leading to the direct preparation of γ-lactone derivatives. This reducing system showed a relatively wide functional group tolerance.

Full text of DOI:10.1039/c6ra19286f

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Gallium-Catalyzed Reductive Lactonization of
Hydrosilane
γ
-Keto Acids with a
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
Norio Sakai, * Shuhei Horikawa and Yohei Ogiwara
DOI: 10.1039/x0xx00000x
www.rsc.org/
1
0
11
Described herein is the GaCl
3
-catalyzed lactonization of
leading to the direct embedded in a ring structure was treated with trifluoroacetic
-lactone derivatives. This reducing system showed acid (TFA)-Et SiH or TFA-PhMe SiH to form a trisubstituted
a relatively wide functional group tolerance. lactone (eq c in Scheme 1). Although the reductive cyclization
of a -keto carboxylic acid derivative with a Lewis acid, BF and
Et SiH was reported by Nordlander and co-workers, the
γ-keto Doyle and Rovis disclosed that a cyclic γ-keto acid
carboxylic acids in the presence of PhSiH
preparation of
3
γ
3
2
γ-
γ
3
Since γ-lactone derivatives constitute a central and ubiquitous
3
structure in valuable natural products and biologically active
substances, the development of a facile approach to these
skeletons has attracted the interest of a number of organic,
example reported in this paper is the only one example of its
kind, and a systematic investigation has not yet been
1
2
conducted. In addition, as an example of a two-step
transformation, the combination of an initial reduction of 3-
1
pharmaceutical and material chemists. Thus far, a typical
1
3
approach to the
achieved through cyclization of a carboxylic acid bonding an
alcohol moiety ( -hydroxy acid) in the presence of a variety of
condensation reagents. Also, the lactonization of
acid by a sole metal triflate, Hf(OTf) , has been reported.
γ-lactone skeleton has been generally
2
benzoylpropanoic acid by either a chiral borane or ZnCl -
i
14
Bu
corresponding
In this context, we reported the indium-catalyzed annulation
of LA with aromatic/aliphatic amines in the presence of PhSiH
2
AlH and subsequent cyclization with TFA led to the
γ
γ
-lactone.
2
ω
-hydroxy
3
11
4
3
1
5
Moreover, a cyclization of 1,4- or 1,5-keto alcohols using a
leading to the preparation of
that a GaCl -TMDS (1,1,3,3-tetrahydrosiloxane)-CuCl
undertook the reductive chlorination of carboxylic acids. We
report herein a gallium(III)-catalyzed reductive cyclization of
keto carboxylic acids with PhSiH smoothly leading to -lactone
derivatives (eq (d) in Scheme 1). This procedure using the
novel association of a metallic Lewis acid, GaCl , and a
hydrosilane, PhSiH , presents a new entry to a lactone skeleton
from a keto carboxylic acid.
γ
-lactam derivatives, and found
Noyori hydrogen transfer catalyst led to the asymmetrical
4
synthesis of γ-lactone.
3
2
system
1
6
On the other hand, as a recent interesting extension, the
preparation of a -lactone skeleton through a reductive
lactonization from a biomass-derived -keto carboxylic acid,
such as levulinic acid (LA), to -valerolactone (GVL), has been
disclosed gradually. For example, as with cases involving a
γ
-
γ
3
γ
γ
γ
3
3
5
1
7
homogenous metal catalyst, a RuCl
3
7
-PPh
3
system or a
6
complex, the Shvo complex, and an Iridium pincer
Ru(acac)
3
8
complex with an additive, these have efficiently reduced LA to
GVL in the presence of H or HCO H as a reducing reagent (eq
2
2
a in Scheme 1). Also, the same transformation with
heterogeneous complexes such as Ni, Raney-Ni, Cu, Ru, and Pd
2 2 3
supported on either activated carbon, SiO , or Al O , under
9
hydrogen gas has been developed (eq b in Scheme 1).
Moreover, as an alternative reducing reagent, the use of
easily-handled hydrosilanes has been reported. For example,
a.
Department of Pure and Applied Chemistry, Faculty of Science and Technology,
Tokyo University of Science (RIKADAI), Noda, Chiba 278-8510, Japan.
E-mail: sakachem@rs.noda.tus.ac.jp
Electronic Supplementary Information (ESI) available: Spectral data and H- and
Scheme 1 Diverse approaches to γ-lactones from γ-keto acids
1
†
1
3
C-NMR charts of γ-lactones prepared by the present method. See
DOI: 10.1039/x0xx00000x
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To achieve this concept, the reaction conditions were initially
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5
Table 2 Scope of an aryl group in keto acids
1
examined (Table 1). On the basis of our previous results,
when keto acid 1a was treated with In(OAc) (5 mol %) in the
presence of PhSiH (3 equiv) in toluene at 80 ˚C, the reductive
cyclization slightly proceeded to produce 4-phenyl-
3
3
γ
-
butyrolactone (2a) in a 23% yield (entry 1). Thus, although the
effect of a counter anion on the indium compound was
examined, a remarkable improvement in the product yield was
Entry
product
Yield (%)
1
2
3
2b (o-Me)
86
95
90
3
not observed (entries 2-5). Interestingly, GaCl , instead of an
2c (m-Me)
2d (p-Me)
indium compound, efficiently catalyzed the reductive
cyclization (entry 6). On the other hand, other Lewis acids,
3 2 3
such as AlCl , ZnCl , and BiCl , did not show an effect for this
cyclization (entries 7-9). Thus, with a gallium halide in hand,
when several examinations for solvents and temperatures
4
5
2e
2f
78
97
1
8
were performed, the heating conditions at 60 ˚C in the
presence of GaCl showed the best results (entries 10 and 11).
Also, the use of a stronger Lewis acid, GaBr
GaCl
3).
3
3
3
and GaI , than
3
caused a decrease in the chemical yield (entries 12 and
1
Table 1 Examinations of reaction conditions
2g
0
6
2
g’
21
Entry
Cat.
Solvent
Temp
Yield
b
(%)
2
2
h
72
4
a
(
˚C)
80
80
80
80
80
80
80
80
80
80
60
60
60
1
2
3
4
5
6
7
8
9
In(OAc)
3
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
benzene
benzene
benzene
benzene
23
28
7
In(OTf)
InI
InBr
InCl
GaCl
AlCl
ZnCl
3
h’
3
31
3
20
3
34
3
59
8
9
2i
84
3
0
2
0
b
2j (X = F)
76
63
BiCl
3
0
b
b
1
1
0
1
2k (X = Cl)
10
11
12
13
GaCl
3
82
2l (X = Br)
67
GaCl
GaBr
GaI
3
99 (94)
74
3
3
69
12
2m
63
72
a
b
Bath temperature. NMR (Isolated) yield.
1
1
1
3
4
5
2n
2o
2p
Then, the effect of an aryl group on the keto acid was
examined under the optimal conditions (Table 2). Regardless
of location and number, the cases with a methyl-substituted
aryl group gave lactones 2b-f in relatively good yields. In
contrast, keto acid 1g having a para-MeO group did not cyclize,
and instead, led to a formation (21%) of the carboxylic acid
derivative 2g’, the ketone moiety of which was reduced. This
may be due to the fact that the indium compound would
prefer to activate the methoxy group than the carbonyl
moiety. Also, this result is not in complete agreement with the
78
0
a
b
Isolated yield. Reaction time = 7 d.
result shown by Nordlander et al, in which the TFA-Et SiH
3
system selectively reduced only the ketone moiety of the keto
1
acid.
2
2
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In contrast, the substrate having a para-PhO group afforded a 59% NMR yield as a major product (Eq d in Scheme 2).
the corresponding lactone 2h in a 72% yield with a by-product, Although there is no clear reason for the over-reduction at this
1
9
the carboxylic acid 2h’ (4%). Moreover, the keto acid with a stage, the reducing system could be applied to the 6-
meta-MeO group successfully produced lactone 2i in a good membered lactone construction.
yield. Keto acids with a halogen substituent also gave the
corresponding lactones 2j-2l in relatively good yields, but a
quite longer reaction time (> 7 days) was required to complete
the cyclization. Consequently, a typical halogen atom in the
aromatic ring shows a tolerance to the reducing system. On
3
the other hand, the substrates with a CF , a biphenyl, and a 1-
naphthyl group were mostly complete after 24 h, affording
lactones 2m-2o in 63, 72, and 78% yields. Unfortunately,
instead of a benzene ring, the keto acid with a thiophene ring
did not produce the expected lactone.
Scheme 3 Plausible mechanism for the lactonization
Scheme 3 shows a plausible mechanism for the reductive
lactonization from keto acids. As an initial step, the formation
of silyl ester
A via dehydrogenation between a carboxylic acid
moiety activated by the indium catalyst and a hydrosilane
2
0
occurred. The second step is the hydrosilylation of the
ketone moiety of the intermediate to produce the
anticipative intermediate (or ). Subsequent intramolecular
cyclization of the intermediate finally leads to the production
A
B
C
2
1
of the expected γ-lactone. In the cases with a strong electro-
donating group, such as a 4-MeO or a 4-PhO substituent, on
the aryl group, it seems that an electron-donating effect of
these groups would promote the facile release of the silyl
ether moiety activated by the gallium catalyst on B, and then
Scheme 2. Extension to various
γ
-keto carboxylic acids
the benzyl position was again reduced to produce the
corresponding carboxylic acid.
We have developed a novel gallium(III)-catalyzed lactonization
As an extension, the present reducing procedure was applied of
to the lactonization of various
-keto acids. For example, when production of
keto acid
with an alkyl ketone moiety was treated with the substituents, and showed that unlike a GaBr
optimal conditions, the expected cyclization proceeded cleanly system
to produce -phenethyl-substituted lactone
in a nearly reducing system involving GaCl
quantitative yield (Eq a in Scheme 2). Then, when the retained the formed ester moiety. The present lactonization
cyclization was attempted with 2-benzoylbenzoic acid (
), 3- cleanly proceeds under relatively mild and neutral conditions.
phenylphthalide (
) was obtained in a 50% isolated yield (Eq b This work was partially supported by JSPS KAKENHI Grant
in Scheme 2). To expand the ring size of the lactone skeleton, Number JP25410120. We deeply thank Shin-Etsu Chemical Co.,
the similar lactonization with -keto carboxylic acids
was Ltd., for the gift of hydrosilanes.
γ
-keto acids in the presence of PhSiH
3
, which led to the
variety of
-TMDS reducing
γ
γ
-lactone derivatives with
a
3
3
1
7a
22
and an In(III)-hydrosilane reducing system, this
and PhSiH in benzene
γ
4
3
3
5
6
δ
7
examined with the above optimal conditions. However,
contrary to our expectation, the lactonization did not proceed
cleanly, and, instead, the result was the production of
Notes and references
carboxylic acid
8
with a trans-alkene portion (J = 16 Hz) in a
1
(a) I. T. Horvath, H. Mehdi, V. Fabos, L. Boda and L. T. Mika,
Green Chem., 2008, 10, 238; (b) D. M. Alonso, S. G. Wettstein
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low yield (Eq c in Scheme 2) and a complex mixture. Thus,
when the same reaction was treated with Et SiH, the
3
Yang, J. Chai and Y. Lu, Appl. Catal. B Environ., 2015, 179
92.
,
formation of δ-lactone 9 was isolated in a rather low yield, and
an over-reduced 2-phenyltetrahydropyran (9’) was obtained in
2
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2
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1
1
8 Other solvents, such as 1,4-dioxane, DMF and 1,2-
dichloroethane, were ineffective for the lactonization, which
led to the decrease in the product yield.
9 Biermann et al. reported that a combination of GaBr
1
3
(0.5 -
.0 mol %) and TMDS in the absence of a solvent successfully
reduced the carbonyl moiety in fatty esters, triglycerides,
and lactones. See ref 17a.
2
0 For selected examples of
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O
GaCl3 (5 mol %)
OH PhSiH3 (Si-H: 3 equiv)
R
C6H6, 60 ˚C
R
O
O
O
1
6 examples
up to 97% yield
R = aryl and alkyl
Gallium chloride efficiently catalyzes cyclization of γ-keto carboxylic acids
in the presence of PhSiH3 to produce the corresponding γ-lactone derivatives.