Thiophene-Alkyne-Based CMPs as Highly Selective Regulators for Oxidative Heck Reaction

Article abstract of DOI:10.1021/acs.orglett.7b01858

Thiophenes containing an adjacent C≡C group as ligands for Pd^II-promoted organic reactions are reported for the first time. These ligands were utilized as catalytic sites and integrated into the skeleton of conjugated microporous polymers. By e

Full text of DOI:10.1021/acs.orglett.7b01858

Letter
pubs.acs.org/OrgLett
Thiophene-Alkyne-Based CMPs as Highly Selective Regulators for
Oxidative Heck Reaction
Ren-Hao Li,† Zong-Cang Ding,† Cun-Yao Li,‡ Jun-Jia Chen,† Yun-Bing Zhou,† Xiao-Ming An,†
Yun-Jie Ding,*,‡ and Zhuang-Ping Zhan*,†
†Department of Chemistry and Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical
Engineering, Xiamen University, Xiamen 361005, China
‡Dalian National Laboratory for Clean Energy, Collaborative Innovation Center of Chemistry for Energy Materials, Dalian Institute of
Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
S
* Supporting Information
ABSTRACT: Thiophenes containing an adjacent CC group as ligands for PdII-
promoted organic reactions are reported for the first time. These ligands were
utilized as catalytic sites and integrated into the skeleton of conjugated
microporous polymers. By employing these CMP materials as selective regulators,
oxidative Heck reactions between arylboronic esters and electronically unbiased
alkenes provide highly selective linear products.
he Heck−Mizoroki reaction provides a versatile strategy
of branched conjugated dienes using the catalyst derived from
palladium and phenanthroline-type ligands.6
1
Tto convert vinylic C−H bonds into C−C bonds.
However, olefins that lack directing groups or electronic biased
groups gave a mixture of Heck isomers with low selectivity.
Most precedents achieve regioselectivity by using substrates
that have an intrinsic electronic bias. Electron-rich vinyl ethers
and vinyl amides favor coupling adjacent to the heteroatom to
give the branched products,2 while electron-poor olefins, such
as acrylates and styrenes, favor coupling at the terminal position
to give the linear products (Figure 1).3 The scope of these
reactions is severely limited, however, by challenges in
controlling the product regioselectivities.
As noted above, linear-selective Heck coupling typically
requires electron-poor substrates. However, Sigman and co-
workers demonstrated that high linear selectivity could be
achieved by submitting electronically unbiased alkene sub-
strates to a catalytic system incorporating a carbene ligand.7
White’s group reported a chelate-controlled intermolecular
oxidative Heck reaction catalyzed by a versatile Pd(OAc)2/
sulfoxide catalyst that proceeds with excellent selectivities for a
wide range of non-resonance-biased α-olefins with proximal
oxygen and nitrogen functionality (Scheme 1, eq 1).8 However,
electronically nonbiased aliphatic alkenes yielded very poor
selectivity.
Scheme 1. PdII/Sulfur-Containing Catalyst for Oxidative
Heck Reaction
Figure 1. Different products of the Heck reaction.
Recent developments have begun to address these limitations
through the identification of catalyst systems. For example,
Zhou and co-workers developed Pd-catalyzed branched-
selective Heck reaction of electronically unbiased alkenes with
bulky bisphosphine.4 Jamison’s group reported Heck-coupling
reactions between benzyl chlorides and electronically unbiased
alkenes using [Ni(cod)2] and PCy2Ph, providing a regiose-
lective access to branched products.5 The Stahl group also
demonstrated high regioselectivity in the Heck-type synthesis
Received: June 21, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b01858
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Organic Letters
Letter
Conjugated microporous polymers (CMPs) are a novel class
of porous materials with an extended π-conjugation in an
amorphous organic framework.9 Owing to the wide-ranging
flexibility in the choice and design of functional units, the
available control of pore parameters, and the advantage of easy
separation, these polymers can be tailored for use in various
applications, such as gas adsorption,10 energy storage,11
sensing,12 light emitting,13 and light harvesting.14 More
recently, specific functionalities were achieved by the
introduction of designed catalytic sites into CMPs, particularly
for heterogeneous catalysis, because these material are
synthetically versatile and have good thermal stability and
excellent chemical robustness to acids, bases, and organic
solvent. For example, Cooper and co-workers have shown that
CMP-CpIr-3 is a highly active catalyst for reductive
amination15a and RP-CMP1 is an effective noble-metal-free
photocatalyst for heterogeneous photocatalytic aza-Henry
reactions.15b Recently, our group also reported a privileged
pyridine-alkyne-based CMPs as a heterogeneous catalytic ligand
for the PdII-catalyzed oxidative Heck reaction with high linear
selectivity.16 The rigid porous structures of CMPs have a
positive effect on controlling the regioselectivity of organic
reactions.
In the past few years, the PdII/sulfur-containing catalyst
system has been reported. Stahl demonstrated that Pd(OAc)2/
DMSO is an effective catalyst for the aerobic oxidation of
alcohols and other organic substrates.17 Shi and co-workers
have shown a Pd(OAc)2/iPr2S-catalyzed oxidative cross-
coupling of electron-deficient polyfluoroarenes with completely
unactivated aromatics.18 Diisopropyl sulfide was indispensable
for promoting the efficacy. The famous White reagent was also
used in chelate-controlled intermolecular oxidative Heck
reaction.8 Thiophene as polymer unit is the hotspot in material
chemistry.19 However, thiophene−Pd complex catalyzed
organic reactions have not been reported. Interestingly, we
found that ligands of thiophene containing an adjacent CC
group promote organic reactions. Herein, we develop a method
for oxidative Heck reaction using novel thiophene−alkyne-
based CMPs as highly selective regulators (Scheme 1, eq 2).
Not only can these units provide catalytic sites, but they also
serve as building blocks in the CMP skeleton.
Aliphatic olefins with electronical unbiasedness are challeng-
ing substrates for selective oxidative Heck reaction.7,8 There-
fore, in our initial screening experiments, 1-hendecene was
investigated by different thiophene-type ligands (Figure 2).
Pd(OAc)2 in the absence of an ancillary ligand led to low
selectivity despite higher conversions. Thiophene (Figure 2,
L1) and bithiophene (Figure 2, L2) inhibit PdII activity leading
to low yield and selectivity. In comparison with thiophene and
bithiophene, the thiophene containing adjacent CC groups
as ligands (Figure 2, L3−L6) showed higher yields and
regioisomeric ratios. The yield was obviously decreased when a
thiophene-type ligand L7 in which the CC bond is too far
from the S sites to coordinate to the palladium center was used.
The ligand 2,5-diphenylthiophene (Figure 2, L8) led to a lower
regioisomeric ratio of linear product compared with L6. Based
on above results, we selected L4 (a bifunctional ligand consists
of CC and thiophene-S sites with proper coordination
geometric angle) as a functional unit and further integrated into
the skeleton of CMP to serve as a heterogeneous catalytic
ligand.
Figure 2. Effect of ligands on the formation of different products of
the model reaction. In addition to the formation of the linear product
(blue bars), branched product (red bars) and other isomers (green
bars) was also observed. Ratio of linear/branched/other isomers as
determined by GC analysis. The model reaction: 1-hendecene (0.5
mmol), phenylboronic ester (1.0 mmol), Pd(OAc)2 (6 mol %),
Cu(OTf)2 (20 mol %), L1-L8 (20 mol %), CMP-A, CMP-B or POL-A
(10 mg), DMA (3 mL), 40 °C, O2 (1 atm), 48 h.
comparison, the thiophene-containing polymer POL-A without
CC bond was also synthesized by free radical polymeri-
zetion (see the Supporting Information, Scheme S1). In the
presence of CMP-B or POL-A, moderate yields and
regioisomeric ratios were obtained. Excitedly, the use of
CMP-A as a heterogeneous ligand gave the product in 73%
yield, excellent ratio of ln/br (ln/br = 30:1) and good
selectivity of linear product (rr = 3.5:1, rr = linear/all other
isomers), which was much better than white’s catalyst (ln/br =
8:1, rr < 1:1).8 In controlling the regioselectivity, porous
polymers (CMP-A, CMP-B) are better than monomeric
thiophene-type ligands (L3, L6), which could be largely
attributed to the confinement effect of the porous structure
of CMP materials.
CMP-A and CMP-B were synthesized by sonogashira
coupling in the presence of PdCl2(PPh3)2 and CuI. In
B
DOI: 10.1021/acs.orglett.7b01858
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Organic Letters
Letter
To explore the structure−activity relationship, CMP-A and
related prepared Pd(OAc)2/CMP-A were characterized by
thermogravimetry (TG), N2 adsorption−desorption analysis,
scanning electron micrograph (SEM), transmission electron
micrograph (TEM) and X-ray photoelectron spectroscopy
(XPS). The TG shows that CMP-A remains intact at
temperatures up to 400 °C, even with only about 8% weight
loss at 800 °C, indicating its good thermal stability (Figure S1).
Nitrogen adsorption−desorption analysis demonstrates that
CMP-A possesses hierarchical porosity, which is further
confirmed by SEM (Figure 3A) and TEM (Figure S2) images.
yields with excellent ln/br selectivity (>15:1 ratio in most
cases) (Table 1, entries 1−8). The straight-chain olefins (Table
a
Table 1. Substrate Scope of Oxidative Heck Reaction
Figure 3. (A) Scanning electron microscopy (SEM) of CMP-A. (B)
Node−strut topology for simulated network fragment for PdII/CMP-
A. Key: H (white ball), C of benzene and thiophene (gray ball), C of
alkyne (dark yellow ball), S (yellow ball), Pd (violet ball), C) N2
adsorption−desorption isotherms. (D) Pore size distribution curves.
The BET surface areas and total pore volumes of CMP-A are
up to 269.8 m2/g and 0.441 cm3/g, respectively. The pore sizes
of CMP-A are mainly distributed between 1 and 4 nm which
was calculated from the method of nonlocal density functional
theory (NLDFT), indicating that the hierarchical porous CMP-
A mainly consists of micropores and mesopores. The
confinement effect of these porous space play an important
role in controlling the regioselectivity for the Heck reaction. No
obvious change in the pore size distribution emerged between
CMP-A and Pd(OAc)2/CMP-A (Figure 3D). Despite the slight
decrease in specific surface area, Pd(OAc)2/CMP-A is still
significantly microporous (Figure 3C). Furthermore, XPS
confirmed the coordination of palladium with sulfur of
thiophene (Figure S3). The network fragments of PdII/CMP-
A have been simulated by node−strut topology (Figure 3B). In
addition, the elemental distribution in the Pd(OAc)2/CMP-A
was determined by using the energy-dispersive X-ray spectros-
copy (EDX) mapping technique in scanning electron
microscopy. The highly dispersed character of all functional
elements (C, S and Pd) demonstrates the excellent integration
of homogeneously distributed active functional sites (Figure
S4).
a
Reaction conditions: olefins (0.5 mmol), arylboronic esters (1.0
mmol), Pd(OAc)2 (6 mol %), Cu(OTf)2 (20 mol %), CMP-A (10
mg), DMA (3 mL), 40 °C, O2 (1 atm), 48 h. The selectivity for
product (rr = linear/all other isomers) was >10:1 unless otherwise
b
c
d
noted. Isolated yield. Recovered starting material. Determined by
e
f
g
h
1H NMR spectroscopy. rr = 3.5:1. rr = 8:1. CMP-A (5 mg). 60 °C
1, entries 1−2) and branched-chain olefin (Table 1, entry 3) all
proceed with good yields and regioselectivities. Vinylcyclohex-
ane yielded excellent regioselectivity with a range of arylboronic
esters (Table 1, entries 4−8). In addition, this oxidative Heck
reaction favors formation of the (E)-linear products and
tolerant various functional groups. The catalyst Pd(OAc)2/
CMP-A promoted the cross-coupling of a doubly protected
allylic amine with a range of arylboronic esters to afford the
linear products with good yields and high selectivities (Table 1,
entries 9−11). The olefins bearing a ketone (Table 1, entry 12)
or ester (Table 1, entries 13 and 14) all proceeded with good
yields and excellent regioselectivity. It should be pointed out
that good yields and excellent selectivities were observed for an
allyl ester, a type of substrate that is prone to undergo oxidative
The Pd(OAc)2/CMP-A system was evaluated by using a
variety of electronically unbiased alkenes and arylboronic esters,
which displayed excellent selectivity toward a broad range of
alkenes. Of note, in the presence of CMP-A, aliphatic olefins
were converted smoothly to the (E)-linear products in good
C
DOI: 10.1021/acs.orglett.7b01858
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Organic Letters
Letter
(5) Tasker, S. Z.; Gutierrez, A. C.; Jamison, T. F. Angew. Chem., Int.
Ed. 2014, 53, 1858; Angew. Chem. 2014, 126, 1889.
addition in the presence of a palladium catalyst (Table 1, entry
15).20 Substrates containing an acetyl- or TBS-protected
homoallylic alcohol also afforded high selectivities and
moderate to good yields with a range of arylboronic esters
(Table 1, entries 16−19). Alkenyl epoxides usually suffered
from nucleophilic attack by organoboron compounds.21
However, the alkene containing a oxirane group was a suitable
substrate for the oxidative Heck reaction in the presence of
Pd(OAc)2/CMP-A, delivering the desired product with good
yield and selectivity (Table 1, entry 20).
In conclusion, we have reported thiophenes containing an
adjacent CC group as ligands with PdII promoting an organic
reaction for the first time. These ligands were utilized as
catalytic sites and integrated into the skeleton of conjugated
microporous polymers. The CMP material with bifunctional
ligand feature (CC and thiophene) and porous structure
could achieve excellent linear-selectivity with electronically
unbiased alkenes in oxidative Heck reaction. This work
developed a way to use CMP as highly selective catalyst in
controlling the regioselectivity of organic reactions.
(6) (a) Zheng, C.; Wang, D.; Stahl, S. S. J. Am. Chem. Soc. 2012, 134,
16496. (b) Zheng, C.; Stahl, S. S. Chem. Commun. 2015, 51, 12771.
(7) Werner, E. W.; Sigman, M. S. J. Am. Chem. Soc. 2010, 132, 13981.
(8) Delcamp, J. H.; Brucks, A. P.; White, M. C. J. Am. Chem. Soc.
2008, 130, 11270.
(9) Jiang, J.; Su, F.; Trewin, A.; Wood, C. D.; Campbell, N. L.; Niu,
H.; Dickinson, C.; Ganin, A. Y.; Rosseinsky, M. J.; Khimyak, Y. Z.;
Cooper, A. I. Angew. Chem., Int. Ed. 2007, 46, 8574.
(10) Xie, Y.; Wang, T.; Liu, X.; Zou, K.; Deng, W. Nat. Commun.
2013, 4, 1960.
(11) Kou, Y.; Xu, Y.; Guo, Z.; Jiang, D. Angew. Chem., Int. Ed. 2011,
50, 8753; Angew. Chem. 2011, 123, 8912.
(12) Gu, C.; Huang, N.; Gao, J.; Xu, F.; Xu, Y.; Jiang, D. Angew.
Chem., Int. Ed. 2014, 53, 4850; Angew. Chem. 2014, 126, 4950.
(13) Xu, Y.; Chen, L.; Guo, Z.; Nagai, A.; Jiang, D. J. Am. Chem. Soc.
2011, 133, 17622.
(14) Chen, L.; Honsho, Y.; Seki, S.; Jiang, D. J. Am. Chem. Soc. 2010,
132, 6742.
(15) (a) Jiang, J.; Wang, C.; Laybourn, A.; Hasell, T.; Clowes, R.;
Khimyak, Y. Z.; Xiao, J.; Higgins, S. J.; Adams, D. J.; Cooper, A. I.
Angew. Chem., Int. Ed. 2011, 50, 1072; Angew. Chem. 2011, 123, 1104.
(b) Jiang, J.; Li, Y.; Wu, X.; Xiao, J.; Adams, D. J.; Cooper, A. I.
Macromolecules 2013, 46, 8779.
(16) Zhou, Y. B.; Wang, Y. Q.; Ning, L. C.; Ding, Z. C.; Wang, W. L.;
Ding, C. K.; Li, R. H.; Chen, J. J.; Lu, X.; Ding, Y. J.; Zhan, Z. P. J. Am.
Chem. Soc. 2017, 139, 3966.
(17) Steinhoff, B. A.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 4348.
(18) Li, H.; Liu, J.; Sun, C.; Li, B.; Shi, Z. Org. Lett. 2011, 13, 276.
(19) (a) Zhang, Z.; Qin, Y. Macromolecules 2016, 49, 3318.
(b) Fronk, S. L.; Shi, Y.; Siefrid, M.; Mai, C. − K.; McDowell, C.;
Bazan, G. C. Macromolecules 2016, 49, 9301.
(20) (a) Ohmiya, H.; Makida, Y.; Tanaka, T.; Sawamura, M. J. Am.
Chem. Soc. 2008, 130, 17276. (b) Ohmiya, H.; Makida, Y.; Li, D.;
Tanabe, M.; Sawamura, M. J. Am. Chem. Soc. 2010, 132, 879.
(21) (a) Kjellgren, J.; Aydin, J.; Wallner, O. A.; Saltanova, I. V.;
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.7b01858.
Experimental details (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: dyj@dicp.ac.cn.
*E-mail: zpzhan@xmu.edu.cn.
ORCID
́
Szabo, K. J. Chem. - Eur. J. 2005, 11, 5260. (b) Nielsen, D. K.; Doyle,
A. G. Angew. Chem., Int. Ed. 2011, 50, 6056; Angew. Chem. 2011, 123,
6180.
Yun-Jie Ding: 0000-0001-8894-9648
Zhuang-Ping Zhan: 0000-0002-6310-8663
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (No. 21272190), the Strategic priority research program
of the Chinese Academy of Sciences (Grant No.
XDB17020400), and NFFTBS (No. J1310024).
REFERENCES
■
(1) (a) Heck, R. F. Acc. Chem. Res. 1979, 12, 146. (b) McCartney, D.;
Guiry, P. J. Chem. Soc. Rev. 2011, 40, 5122. (c) Beletskaya, I. P.;
Cheprakov, A. V. Chem. Rev. 2000, 100, 3009. (d) Cabri, W.; Candiani,
I. Acc. Chem. Res. 1995, 28, 2.
(2) (a) Ruan, J.; Xiao, J. Acc. Chem. Res. 2011, 44, 614. (b) Mo, J.; Xu,
L.; Xiao, J. J. Am. Chem. Soc. 2005, 127, 751. (c) Hansen, A. L.;
Skrydstrup, T. J. Org. Chem. 2005, 70, 5997. (d) Ruan, J.; Iggo, J. A.;
Berry, N. G.; Xiao, J. J. Am. Chem. Soc. 2010, 132, 16689.
(3) (a) Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 6989.
(b) Ruan, J.; Li, X.; Saidi, O.; Xiao, J. J. Am. Chem. Soc. 2008, 130,
2424. (c) Andappan, M. M. S.; Nilsson, P.; Larhed, M. Chem.
Commun. 2004, 218. (d) Lindh, J.; Enquist, P.; Pilotti, Å.; Nilsson, P.;
Larhed, M. J. Org. Chem. 2007, 72, 7957.
(4) (a) Qin, L.; Ren, X.; Lu, Y.; Li, Y.; Zhou, J. Angew. Chem., Int. Ed.
2012, 51, 5915; Angew. Chem. 2012, 124, 6017. (b) Qin, L.; Hirao, H.;
Zhou, J. Chem. Commun. 2013, 49, 10236.
D
DOI: 10.1021/acs.orglett.7b01858
Org. Lett. XXXX, XXX, XXX−XXX