Benzene-1,3,5-triyl triformate (TFBen): a convenient, efficient, and non-reacting CO source in carbonylation reactions

Article abstract of DOI:10.1016/j.tetlet.2016.06.071

Benzene-1,3,5-triyl triformate (TFBen) as a kind of convenient and efficient CO source has been prepared for the first time. The character of TFBen as potent and non-reacting CO source has been proven by the successful synthetic applications in carbonylation reactions. Phloroglucinol (1,3,5-trihydroxybenzene) is abundant and naturally occurring has been applied as the reusable material for TFBen synthesis.

Full text of DOI:10.1016/j.tetlet.2016.06.071

Tetrahedron Letters 57 (2016) 3368–3370
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Tetrahedron Letters
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Benzene-1,3,5-triyl triformate (TFBen): a convenient, efficient, and
non-reacting CO source in carbonylation reactions
a
a
a,b,
⇑
Li-Bing Jiang , Xinxin Qi , Xiao-Feng Wu
a
Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, People’s Republic of China
Leibniz-Institut für Katalyse e.V. an der Universit Rostock, Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Benzene-1,3,5-triyl triformate (TFBen) as a kind of convenient and efficient CO source has been prepared
for the first time. The character of TFBen as potent and non-reacting CO source has been proven by the
successful synthetic applications in carbonylation reactions. Phloroglucinol (1,3,5-trihydroxybenzene)
is abundant and naturally occurring has been applied as the reusable material for TFBen synthesis.
Ó 2016 Elsevier Ltd. All rights reserved.
Received 25 May 2016
Revised 14 June 2016
Accepted 16 June 2016
Available online 17 June 2016
Keywords:
Palladium catalyst
Carbonylation
Aryl formates
Benzene-1,3,5-triol
CO surrogate
Recently, the development of new carbon monoxide-free car-
bonylative procedures becomes an interesting research topic in
carbonylation chemistry.1 Strategically, the methodology estab-
lishment can be cataloged in two directions based on where the
CO generated: ex situ and in situ. The ex situ CO generation proce-
dures usually refer to the two-chamber system. That is one cham-
ber for CO generation which is connected to the other chamber for
of phenol, depending on the other nucleophiles applied, phenol
might react with acylpalladium intermediate to give phenyl ben-
zoates or related derivatives (Scheme 1). Hence carbonylative pro-
7
cedure with phenyl formate as CO source should be well designed.
Phloroglucinol (1,3,5-trihydroxybenzene) is a non-expensive
1
0
and abundant chemical which was originally found in fruit trees.
Because of the unique symmetric arene substitution pattern of
phloroglucinol, it is in equilibrium with its keto form (1,3,5-cyclo-
hexanetrione; phloroglucin) in solution which has ketone-like
character (Scheme 2). This distinctive property attracted our inter-
est. The three hydroxyl groups allow the formation of the trifor-
mate compound which is more efficient as the CO source. After
CO release, the ketone form of the phloroglucinol formed makes
it less or not reactive with metal catalyst intermediates. Addition-
ally, formic acid as the reaction partner here can be produced by
2
carbonylation transformations. The in situ CO generation systems
are based on the producing of CO from CO surrogates in the same
reaction tube. In this manner, the manipulation of CO gas with
autoclave can be avoided. For the CO surrogates, many metal car-
bonyl complexes and organic compounds have been developed
3
4
as suitable CO sources which including Mo(CO)
6
,
formamides,
5
formic acid, aryl formates,7 etc. However, each candi-
6
8
(
CH O) ,
2 n
dates has their own advantages and disadvantages. Concerning
the shortcomings, a large amount metal waste generation or speci-
fic activator requirement is the most obvious character. Taking
consideration of atom efficiency and sustainable chemistry, and
considered the importance of carbonylation chemistry, more
efforts are required for its further development and also deserved.
On the other hand, phenyl formate has been proven to be an
interesting and practical CO surrogate.7 Phenyl formate is ready
to decompose to CO and phenol by heating or in the presence of
a small amount of base. However, due to the good nucleophilicity
2
reduction of CO which is even more abundant. For these reasons,
the newly produced benzene-1,3,5-triyl triformate (TFBen) can be
used as a solid, stable, efficient, cheap, convenient, and efficient but
non-reacting CO surrogate for CO chemistry.
In order to verify our hypotheses, we started with the synthesis
1
1
of benzene-1,3,5-triyl triformate (TFBen). At room temperature,
82% isolated yield of TFBen can be achieved by reacting phloroglu-
cinol with formic acid in the presence of palladium catalyst.6 As a
white solid, it’s stable at room temperature under air (Scheme 3).
After the successful preparation of TFBen, the synthetic applica-
tions and non-reacting proven becomes the main target
,9
i
⇑
Corresponding author.
E-mail address: xiao-feng.wu@catalysis.de (X.-F. Wu).
1
2
(
Scheme 4). We chose bromobenzene and phenylboronic acid
http://dx.doi.org/10.1016/j.tetlet.2016.06.071
040-4039/Ó 2016 Elsevier Ltd. All rights reserved.
0

L.-B. Jiang et al. / Tetrahedron Letters 57 (2016) 3368–3370
3369
O
O
2 3
Pd(OAc) , NEt
[
Pd]
O
ArBr
TFBen
.4 equiv.
Ar'OH
ArX
Ph
Ph
Xantphos, 100 o
C
O
H
Ar
R
O
Ar
OAr'
Ph
0
O
O
O
O
O
[
Pd]/[Ru]
Ph
Ph
O
R
Ph
Ph
O
O
O
H
O
F3C
NC
Scheme 1. Carbonylations based on phenyl formate.
80%
82%
O
7
5%
O
O
Ph
Ph
O
Ph
OH
O
O
O
O
2
N
N
O
78%
65%
CF
41%
HO
OH
O
O
3
O
Scheme 2. Equilibrium between phloroglucinol and phloroglucin.
O
70%
O
OH
Scheme 5. Pd-catalyzed alkoxycarbonylation with TFBen as the CO source.
Pd(PPh
NaOAc (1 equiv.)
Ac O (10 equiv.)
HCOOH (4 mL), rt
3
)
4
(2 mol%)
H
O
O
O
O
2
HO
OH
I
CHO
H
O
H
Pd(OAc)
2
(3 mol%)
(6 mol%)
PCy
3
8
2% yield
TFBen
TFBen
5
9 % a)
HCOOH (2.5 equiv.)
0
.4 equiv.
o
Et
3
N, DMF, 100 C
tBu
I
tBu
Scheme 3. Synthesis of TFBen.
Ph
5 % b)
as the starting materials, with the combination of Pd(OAc)
BuPAd as the catalyst system and only using 0.4 equiv of TFBen
as the CO source, 75% of benzophenone was isolated (Scheme 4,
Eq. a). The non-reacting nature of phloroglucinol obtained from
TFBen by loss of CO was demonstrated carrying out the reaction
2
and
Pd(OAc)2 (3 mol%)
O
PPh (6 mol%)
3
2
TFBen
0.4 equiv.
8
PhCCH (2 equiv.)
o
Et
3
N, toluene, 60
C
Scheme 6. Pd-catalyzed reductive carbonylation and Sonogashira carbonylation
with TFBen as the CO source.
2
in the absence of PhB(OH) (Scheme 4, Eq. b). Even with 1 equiva-
lent of TFBen, none of possible benzoates derived from alkoxycar-
bonylation of PhBr with phloroglucinol were formed. Only traces of
benzoic acid (resulting from the reaction of trace amount of water
with acylpalladium intermediate) were detected. Remarkably, as
the starting material 1,3,5-trihydroxybenzene can be recycled in
the purification process and reused.
With this promising information in hand, and continually
strength the efficient but non-reacting characters, alkoxycarbony-
lation transformations were performed. In the presence of palla-
dium catalyst and 0.4 equiv of TFBen, good yields of esters can be
produced from aryl bromides and phenols (Scheme 5). These
results strongly supported our hypotheses and confirmed the
non-reacting character. Electron-withdrawing substituted aryl
halides usually challenge substrates in palladium-catalyzed car-
bonylative coupling transformations, as they trend more towards
dehalogenation. However, in our system, good yields can be
achieved without further optimization. Remarkably, nitro group
can be well tolerated as well which is not possible in CO gas based
carbonylation chemistry. Notably, in all the experiments per-
formed here, the 1,3,5-trihydroxybenzene can be easily recovered
during the product purification process.
The applications of this new CO source in other carbonylation
reactions have been explored as well. With formic acid as the
reductant, 59% of 4-(tert-butyl)benzaldehyde can be produced
1
3
14
from the corresponding iodide (Scheme 6, Eq. a). Efficient car-
bonylative Sonogashira coupling for alkynone synthesis can be
realized as well. Excellent yield was achieved under mild condi-
1
5
tions (Scheme 6, Eq. b).
In conclusion, benzene-1,3,5-triyl triformate (TFBen) as a kind
of convenient and efficient CO source has been prepared for the
O
Br
Pd(OAc)2 (3 mol%), BuPAd2 (6 mol%)
NEt3 (2 equiv.), THF (4 mL), 100 oC, 16h
TFBen
PhB(OH)2
a)
b)
1
mmol
mmol
0.4 equiv.
2 mmol
Conv.: 100%
Yield: 75 %
O
Ph
O
Br
Pd(OAc)2 (3 mol%), BuPAd2 (6 mol%)
NEt3 (2 equiv.), THF (4 mL), 100 oC, 24h
TFBen
O
O
1
1 equiv.
Ph
O
O
Ph
Conv.: 10%
Yield: 0%
Scheme 4. Carbonylative Suzuki coupling and non-reacting proven.

3
370
L.-B. Jiang et al. / Tetrahedron Letters 57 (2016) 3368–3370
first time. The character of TFBen as a potent and non-reacting CO
source has been proven by the numerous synthetic applications in
carbonylation reactions. Phloroglucinol (1,3,5-trihydroxybenzene),
the starting material for TFBen synthesis, is an abundant and nat-
urally occurring substance which is recovered during the product
purification process.
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Acknowledgments
5628; (c) Wieckowska, A.; Fransson, R.; Odell, L. R.; Larhed, M. J. Org. Chem.
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The authors thank the financial supports from NSFC (21472174)
and Zhejiang Natural Science Fund for Distinguished Young
Scholars (LR16B020002). X.-F. Wu appreciates the general support
from Professor Matthias Beller in LIKAT.
803, 9–12; (e) Chen, J.; Feng, J. B.; Natte, K.; Wu, X.-F. Chem. Eur. J. 2015, 21,
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9
Konishi, H.; Manabe, K. Synlett 2014, 1971–1986.
10. 500 g, 170$, TCI America (04.21.2016).
11. TFBen synthesis: Pd(PPh (2 mol %), benzene-1,3,5-triol (1.0 mmol), and
NaOAc (1.0 equiv) were transferred into an oven-dried pressure tube which
was filled with nitrogen and equipped with a string bar. Then Ac O (10 equiv)
3 4
)
Supplementary data
2
and HCOOH (4.0 mL) were added into the reaction tube. The mixture was
stirred at RT for 12 h. After the reaction was complete, the reaction mixture
was filtered and concentrated, then column chromatography on silica gel
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.06.
(
petroleum ether/ethyl acetate 3:1) to give the pure product in 82% yield as a
1
1
3
0
71.
white solid. H NMR (400 MHz, CDCl
3
) d 8.20 (s, 3H), 6.91 (s, 3H). C NMR
) d 158.27, 150.22, 112.60. GC–MS (EI, 70 ev): m/z(%) = 210.0
[M]+, 13), 210.0 (23), 182.0 (15), 154.0 (12), 126.1 (100), 110.0 (10), 97.0 (11),
5.0 (19), 80.0 (12), 69.0 (27), 52.1 (11).
2. Suzuki carbonylation: Pd(OAc) (3 mol %), BuPAd
(
(
8
101 MHz, CDCl
3
References and notes
1
2
2
(6 mol %), phenylboronic
1
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acid (2 mmol) and TFBen (0.4 equiv) were transferred into an oven-dried
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6
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(2 mmol) and TFBen (0.4 equiv) were transferred into an oven-dried pressure
tube which was filled with nitrogen and equipped with a string bar. Then
bromobenzene (1 mmol), NEt3 (2 mmol), and DMF (4.0 mL) were added into
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2
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reaction was complete, the reaction mixture was filtered and concentrated,
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(0.4 equiv) were transferred into an oven-dried pressure tube which was filled
with nitrogen and equipped with a string bar. Then iodobenzene (1 mmol),
phenylacetylene (2 mmol), NEt3 (2 mmol), and toluene (2.0 mL) were added
into the reaction tube. The mixture was stirred at 60 °C for 16 h. After the
reaction was complete, the reaction mixture was filtered and concentrated,
then column chromatography on silica gel (petroleum ether/ethyl acetate) to
give the pure product.
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