Selectivity Controlled Palladium-Catalyzed Carbonylative Synthesis of Propiolates and Chromenones from Phenols and Alkynes

Article abstract of DOI:10.1021/acs.orglett.8b01368

An interesting selectivity-controlled palladium-catalyzed oxidative carbonylation procedure for the synthesis of propiolates and chromenones has been developed. Starting from phenols and alkynes, under slightly different conditions, various propiolates an

Full text of DOI:10.1021/acs.orglett.8b01368

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Selectivity Controlled Palladium-Catalyzed Carbonylative Synthesis
of Propiolates and Chromenones from Phenols and Alkynes
Fengxiang Zhu and Xiao-Feng Wu*
Leibniz-Institut fur Katalyse e.V. an der Universitat Rostock, Albert-Einstein-Str. 29a, Rostock, 18059, Germany
̈
̈
S
* Supporting Information
ABSTRACT: An interesting selectivity-controlled palladium-catalyzed oxida-
tive carbonylation procedure for the synthesis of propiolates and chromenones
has been developed. Starting from phenols and alkynes, under slightly different
conditions, various propiolates and chromenones can be isolated in moderate
to good yields. Additionally, this also presents the first example of direct
carbonylative annulation of nonpreactivated phenols and terminal alkynes to
produce chromenones.
Such types of methodologies can increase the diversity of the
ne of the key goals in organic chemistry is the
Odevelopment of new and selective catalytic processes products obtained and also enrich the knowledge in reactivity
tuning and new catalysts design.1
for the synthetic toolkit. It is even more interesting that
Among all the organic transformation methods, palladium-
catalyzed carbonylative reactions have now emerged as a
powerful platform in organic chemistry.2 Various carbonyl-
containing compounds can be easily prepared by choosing the
proper substrates. In the case of using terminal alkynes as the
starting materials, valuable propiolic products can be prepared.3
Concerning the coupling partners with terminal alkynes,
arylboronic acids,4 amines,5 and aliphatic alcohols6 have been
achieved in recent years. However, the use of phenols as the
coupling partner has not been achieved yet. The main reason is
the low nucleophilicity of phenols as well as the potential to be
easily oxidized. To date, the corresponding propiolates are
mainly prepared by the reaction of arylpropyolic acids with
phenols in the presence of an excess amount of activating
reagents.
different types of products can be selectively produced from the
same substrates under slightly different reaction conditions.
a
Table 1. Optimization of the Reaction Conditions
Additionally, chromenone is an important class of hetero-
cycles with broad applications in pharmaceutical and agro-
chemical industries.7 Without surprise, carbonylative proce-
dures have successfully been explored in the synthesis of
chromenones.8 These methodologies require the use of 2-
iodophenols, 2-alkynylphenols, 2-alkenylphenols, or o-hydroxy-
acetophenones as the starting materials. More recently, we
reported an iridium-catalyzed carbonylative cyclization of
simple phenols with internal alkynes to produce chromenones.9
The selectivity can be tuned by choosing the proper phosphine
ligand. However, only disubstituted products can be obtained
and we failed with terminal alkynes.
Based on our continuous interest in carbonylative reactions,
we became interested in studying the challenges discussed
above. With the success of carbonylation of phenols and
terminal alkynes, propiolates and chromenones can be
produced.
a
Phenol (0.2 mmol), alkyne (0.4 mmol), Pd(OAc)2 (5 mol %),
additive (50 mol %), PPh3 (10 mol %) other ligand (5 mol %), oxidant
(0.3 mmol), DCE (2 mL), CO (20 bar), 70 °C, 24 h, GC yield.
b
Pd(dppf)Cl2 (5 mol %) instead of Pd(OAc)2 (5 mol %) and DPPF
c
d
(5 mol %). Pd(TFA)2 (5 mol %). Pd(CH3CN)4(CF3SO3)2 (5 mol
%).
Received: April 30, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b01368
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Organic Letters
Letter
Table 2. Pd-Catalyzed Carbonylative Propiolate Synthesis:
Substrate Scope of Alkynes
Table 3. Pd-Catalyzed Carbonylative Propiolate Synthesis:
Substrate Scope of Phenols
a
a
a
Phenol (0.2 mmol), alkynes (0.4 mmol), Pd(dppf)Cl2 (5 mol %), BQ
(0.3 mmol), DCE (2 mL), CO (20 bar), 70 °C, 24 h, isolated yield.
checked (Table 1, entries 13−19), and 10% of the 6-
methoxy-4-phenyl-2H-chromen-2-one (4aa) can be achieved
when using BF3·Et2O as the additive (Table 1, entry 19). Based
on these conditions, we also tested the influence of palladium
catalysts (Table 1, entries 20−22) and found the yield can be
increased to 61% when using Pd(TFA)2 as the catalyst (Table
1, entry 20). Fine-tuning loadings of catalyst and acid could not
further improve the yield of the desired produced. The choice
of solvent and CO pressure is critical as well. Dramatically
decreased yields of the products were observed when using
DMF, DMSO, toluene, or 1,4-dioxane as the solvent or under
lower or higher CO pressure. Here, it is also important to
mention that hydration of the alkyne could occur in the
presence of acid when the desired reaction did not proceed.
With the optimum conditions in hand, the carbonylative
oxidative cross-coupling of different terminal alkynes with 4-
methoxyphenol to construct the corresponding propiolates
were first explored. As depicted in Table 2, different aromatic
alkynes can be effectively transformed with 4-methoxyphenol
and afford the corresponding products in moderate to good
yields. 3-Ethynylthiophene can be applied as well and gave the
corresponding propiolate derivative in good yield (Table 2,
3ai). Ethynylcyclohexane as an example of an aliphatic alkyne
can be reacted successfully as well with good results under our
standard conditions (Table 2, 3aj). Subsequently, different
phenols were also tested (Table 3). Phenols with electron-
donating or -withdrawing functional groups are all suitable
substrates for this methodology. Good yields of the desired
products can be achieved in all the tested cases.
a
Phenol (0.2 mmol), alkynes (0.4 mmol), Pd(dppf)Cl2 (5 mol %), BQ
(0.3 mmol), DCE (2 mL), CO (20 bar), 70 °C, 24 h, isolated yield.
Initially, 4-methoxyphenol (1a) and phenylacetylene (2a)
were chosen as the model substrates using Pd(OAc)2 as the
catalyst and DCE as the solvent to establish this carbonylation
procedure (Table 1). The reaction was totally ineffective when
different commonly applied oxidants such as Cu(OAc)2,
AgOAc, and K2S2O8 were employed (Table 1, entries 1−3).
To our delight, 4-methoxyphenyl 3-phenylpropiolate (3aa) can
be detected with BQ as the oxidant and PPh3 as the ligand
(Table 1, entry 4). Encouraged by this exciting result, we then
tested DDQ and DMBQ (DMBQ, 2,5-dimethyl-1,4-benzoqui-
none) as the oxidant, but could not find any of the desired
product (Table 1, entries 5−6). Then variations of ligands were
carried out subsequently (Table 1, entries 7−11; XantPhos, 4,5-
bis(diphenylphosphino)-9,9-dimethylxanthene; DPEPhos, bis-
(2-diphenylphosphinophenyl)ether; Phen, 1,10-phenanthrolin;
DPPF, 1,1′-bis(diphenylphosphino)ferrocene; XPhos, 2-
dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl). The
yields can be improved by using DPPF as the ligand (Table
1, entry 11), and 68% of propiolate can be formed with
Pd(dppf)Cl2 as the catalyst (Table 1, entry 12). In order to
obtain the chromenone product, different additives were
Inspired by the good results of propiolates synthesis, we
turned our attention to the substrate scope of oxidative
carbonylation with phenols and alkynes to synthesize different
chromenones (Table 4). Alkynes with electron-donating or
B
DOI: 10.1021/acs.orglett.8b01368
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Organic Letters
Letter
a
Table 4. Pd-Catalyzed Carbonylative Coumarins Synthesis
Scheme 2. Plausible Reaction Mechanistic
cases. Different phenols were also tested, and except for the
electron-withdrawing functional groups, good yields can be
achieved. However, in the case of meta-substituted phenol
being applied, a mixture of two isomers was obtained (Table 4,
entry 9). It is also important to mention that a 1 mmol scale
experiment was carried out as well and 49% of the desired
product was obtained (Table 4, entry 1).
In order to gain insight into the reaction pathway, control
experiments were performed (Scheme 1). Under identical
conditions, but in the absence of carbon monoxide, no reaction
of phenol with phenylacetylene could be observed (Scheme 1,
eq 1). No cyclization product could be detected in the presence
of only BF3·Et2O (Scheme 1, eq 2). To our delight, propiolates
can be cyclized with the addition of a palladium catalyst and
good yields of chromenones can be achieved in the absence of
BQ (Scheme 1, eq 3).
Based on the above mechanistic studies and according to the
existing knowledge on palladium-catalyzed oxidative carbon-
ylation of alkynes, we propose the reaction pathway, as shown
in Scheme 2. Initially, phenol with PdII generated PhOPdII
species A, and then the CO insertion into the Pd−O bond
allowing the formation of complex B. Intermediate B then
reacted with alkyne, to give the intermediate C which
eliminates the terminal propiolate product D. The formed
Pd(0) will be oxidized back to Pd(II) by BQ. While in the
presence of BF3·Et2O, palladium hydride will be generated and
added to the propiolate to give intermediate E, which will give
the final chromenone product. However, for the cyclization
step, an electrophilic addition mechanism can not be excluded.
In conclusion, an interesting selectivity controlled reaction
for the direct synthesis of propiolates and chromenones from
simple phenols and alkynes has been developed. With
palladium as the catalyst, various desired propiolates and
chromenones were prepared in moderate to good yields.
Remarkably, these represent the first examples of oxidative
carbonylation of phenols and terminal alkynes to propiolates
and also the direct carbonylative annulation of simple phenols
and terminal alkynes to produce chromenones.
a
Phenol (0.2 mmol), alkynes (0.4 mmol), Pd(TFA)2 (5 mol %),
DPPF (5 mol %), BF3·Et2O (50 mol %), BQ (0.3 mmol), DCE (2
b
c
mL), CO (20 bar), 70 °C, 24 h, isolated yield. 1 mmol scale. Phenols
(0.2 mmol), alkyne (0.4 mmol), Pd(TFA)2 (5 mol %), DPPF (5 mol
%), BQ (0.3 mmol), DCE (2 mL), CO (20 bar), 70 °C, 24 h, then
BF3·Et2O (50 mol %), 70 °C, 24 h, isolated yield.
Scheme 1. Control Experiments
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b01368.
Additional experimental results and procedures and
characterization data (PDF)
AUTHOR INFORMATION
Corresponding Author
■
-withdrawing functional groups are all suitable substrates for
this methodology. Good yields can be achieved in all the tested
*E-mail: Xiao-Feng.Wu@catalysis.de.
C
DOI: 10.1021/acs.orglett.8b01368
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Organic Letters
ORCID
Letter
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(f) Hughes, N. L.; Brown, C. L.; Irwin, A. A.; Cao, Q.; Muldoon, M. J.
Palladium(II)-Catalysed Aminocarbonylation of Terminal Alkynes for
the Synthesis of 2-Ynamides: Addressing the Challenges of Solvents
and Gas Mixtures. ChemSusChem 2017, 10, 675−680.
Xiao-Feng Wu: 0000-0001-6622-3328
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
The authors thank the Chinese Scholarship Council for
financial support. The analytic support of Dr. W. Baumann,
Dr. C. Fisher, S. Buchholz, and S. Schareina in LIKAT is
gratefully acknowledged. We also appreciate the general
support from Professors Matthias Beller and Armin Borner in
LIKAT.
̈
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