One-pot transformation of Me3Si-/Ph2P(O)-protected ethynes to unsymmetrical arylethynes

Article abstract of DOI:10.3184/174751918X15269925671284

Me₃Si-/Ph₂P(O)-protected ethynes were successfully transformed to unsymmetrical arylethynes via a one-pot Ph₂P(O)-deprotection/ [Pd(dppf)Cl₂]-catalysed coupling and one-pot Me₃Si-deprotection/Sonogash

Full text of DOI:10.3184/174751918X15269925671284

JOURNAL OF CHEMICAL RESEARCH 2018
VOL. 42 MAY, 271–273
RESEARCH PAPER 271
One-pot transformation of Me3Si-/Ph2P(O)-protected ethynes to
unsymmetrical arylethynes
Li-fen Penga, Jia-ying Leia, Li Wua, Zi-long Tanga*, Zhi-peng Luoa, Yin-chun Jiaoa and Xin-hua Xub
aKey Laboratory of Theoretical Organic Chemistry and Functional Molecule of Ministry of Education, Hunan Provincial Key Laboratory of Controllable Preparation and
Functional Application of Fine Polymers, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, P.R. China.
bState Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082,
P.R. China.
Me Si-/Ph2P(O)-protected ethynes were successfully transformed to unsymmetrical arylethynes via a one-pot Ph2P(O)-deprotection/
[Pd3(dppf)Cl2]-catalysed coupling and one-pot Me3Si-deprotection/Sonogashira coupling under mild conditions and in high yield.
Unsymmetrical phenylethynes, unsymmetrical extended phenylene ethynylenes and unsymmetrical anthrylethynes were successfully
synthesised in good to excellent yields.
Keywords: one-pot, unsymmetrical ethynes, protecting group, deprotection, Sonogashira coupling
Highly π-conjugated unsymmetrical arylethynes, which have
rigid structures and highly extended π-systems, are important
organic materials used in organic field-effect transistors,1 organic
light-emitting diodes,2–4 liquid crystals5 and dye-sensitised solar
cells6,7. The Sonogashira coupling is a powerful method for
synthesising arylethynes from the corresponding aryl halide and
terminal ethynes as starting materials. The traditional synthesis of
unsymmetrical arylethynes often suffers from severe drawbacks,
such as the difficult separation of the products that have similar
Rf values to the starting materials and by-products as well as low
overall yields and long synthetic steps.8 Althoughtrialkylsilylgroups
such as trimethylsilyl (TMS) and t-butyldimethylsilyl (TBDMS)
and the 2-hydroxy-2-propyl group are routinely used as protecting
groups for terminal ethynes, the phosphoryl group (Ph2P(O)) has
been developed as a new protecting group.9–13 The high polarity
of the phosphoryl group enables the easy separation of the desired
products from the less-polar hydrocarbon by-products.10,12 Recently,
a short one-pot synthesis of unsymmetrical arylethynes has been
developed involving dephosphorylation followed by Sonogashira
couplings. However, the isolation of products was tedious because
of the similar Rf values of the products and by-products, and the
yields of products required improvement.10
Therefore, a more efficient procedure leading to unsymmetrical
arylethynes under mild reaction conditions, with easy purification
and high yields was required. We now report our work on developing
an efficient route to unsymmetrical arylethynes from Me3Si-/
Ph2P(O)-protected arylethynes via a one-pot Ph2P(O)-deprotection
[Pd(dppf)Cl2]-catalysed coupling followed by a one-pot Me3Si-
deprotection/Sonogashira coupling under mild conditions, with
easy purification and in high yield.
Results and discussion
First, we tried a selective Ph2P(O)-deprotection/[Pd(dppf)Cl2]-
catalysed coupling and Me3Si-deprotection/Sonogashira coupling
of the Me3Si-/Ph2P(O)-protected phenylethyne 1. When 1 was
treated successively with MeMgBr and then with the phenyl halide
2 and Pd catalyst, the corresponding Sonogashira coupling product
3 was obtained. The crude product 3 was subjected to a KOH-
catalysed desilylation/[Pd, Cu]-catalysed Sonogashira coupling to
afford product 5 as shown in Table 1. In the above procedure,
Table 1 Synthesis of unsymmetrical phenylethynes
aIsolated yields.
bThe temperature of [Pd(dppf)Cl2]-catalysed coupling was 0–80 (refers only to entry 1).
* Correspondent. E-mail: 1060137@hnust.edu.cn

272 JOURNAL OF CHEMICAL RESEARCH 2018
a filtration of 3 through a thin pad of silica gel was required.
Otherwise, the residual oxidised transition metal catalyst(s)
affected the second one-pot step and produced a low yield of
5. m-, p- and o-substituted unsymmetrical phenyl ethynes were
successfully synthesised in excellent yields, and the products
were easily isolated (Table 1, 5a–c).
We succeeded in the synthesis of the unsymmetrical phenylene
ethynylene 8 with an extended π-system using Ph2P(O)-
deprotection/[Pd(dppf)Cl2]-catalysed coupling and a Me3Si-
deprotection/Sonogashira coupling procedure. Treatment
of 6 with MeMgBr, 1-bromo-4-methoxybenzene and a Pd
catalyst afforded the intermediate 7. After filtration, the crude
intermediate 7 was subjected to a KOH-catalysed desilylation/
[Pd, Cu]-catalysed Sonogashira coupling with 4-iodobenzonitrile
to afford product 8 in 78% yield as shown in Scheme 1.
a KOH-catalysed desilylation/[Pd, Cu]-catalysed Sonogashira
coupling (Scheme 2).
Conclusion
We have developed an efficient procedure for the synthesis of
unsymmetrical arylethynes from Me3Si-/Ph2P(O)-protected
arylethynes through a one-pot Ph2P(O)-deprotection/[Pd(dppf)Cl2]-
catalysed coupling and one-pot Me3Si-deprotection/Sonogashira
coupling. Unsymmetrical phenylethynes, unsymmetrical extended
phenylene ethynylenes and unsymmetrical anthrylethynes were
synthesised successfully in good to excellent yields. The mild
reaction conditions, short synthetic route, facile isolation of
products and excellent yields provide a convenient method to
prepare these important unsymmetrical arylethynes.
Experimental
The Ph2P(O)-deprotection/[Pd(dppf)Cl2]-catalysed coupling
and Me3Si-deprotection/Sonogashira coupling protocol was
also applied to synthesise unsymmetrical anthrylethynes as
well as phenylethynes. Unsymmetrical anthryl ethynes 10a
and 10b were obtained in good yields from Me3Si-/Ph2P(O)-
Dry solvents, reagents and catalysts were purchased as analytical
grade and were used without further purification. Me3Si-/Ph2P(O)-
protected arylethynes 1a–c, 6 and 9 were synthesised according to
literature procedures.11 Analytical TLC was performed with silica
gel 60 F254 plates. Column chromatography was carried out using
silica gel 60 (200–300 mesh). Melting points were measured on a
protected anthrylethyne
9
through MeMgBr-catalysed
dephosphination/[Pd(dppf)Cl2]-catalysed coupling followed by
Scheme 1 Synthesis of unsymmetrical extended phenylene ethynylene.
Scheme 2 Synthesis of unsymmetrical anthrylethynes.

JOURNAL OF CHEMICAL RESEARCH 2018 273
1
SGW X-4 (INESA) melting point apparatus and are uncorrected.
All NMR spectra were recorded on a Bruker AV-II 500 MHz NMR
spectrometer operating at 500 MHz for 1H and 125 MHz for 13C.
10a: White powder; m.p. 235–236 °C (lit.12 234–235 °C); H NMR
(500 MHz, CDCl3): δ 3.88 (s, 3H), 6.97 (d, J = 8.8 Hz, 2H), 7.61–7.66
(m, 4H), 7.69–7.73 (m, 4H), 7.81 (d, J = 8.2 Hz, 2H), 8.56–8.62 (m, 2H),
8.66–8.71 (m, 2H); 13C NMR (125 MHz, CDCl3): δ 55.35, 85.18, 91.01,
100.18, 103.42, 111.56, 114.22, 115.28, 116.36, 118.58, 120.28, 126.73,
127.17, 127.48, 128.27, 131.76, 131.97, 132.18, 132.26, 133.25, 160.12.
1
Tetramethylsilane (TMS) was used as internal reference for H and
13C chemical shifts and CDCl3 was used as solvent. Mass spectra (MS)
were obtained using EI mass spectrometer on a Bruker MicroTof II
mass spectrometer.
1
10b: White powder; m.p. 192–193 °C (lit.12 190–191 °C); H NMR
(500 MHz, CDCl3): δ 7.08–7.11 (m, 4H), 7.19 (d, J = 7.6 Hz, 4H), 7.33 (t,
J = 7.9 Hz, 4H), 7.57–7.68 (m, 8H), 7.96 (d, J = 7.6 Hz, 1H), 8.01 (s, 1H),
8.66–8.67 (m, 2H), 8.69–8.71 (m, 2H); 13C NMR (125 MHz, CDCl3):
δ 85.76, 88.08, 100.29, 103.43, 115.85, 116.82, 119.72, 122.16, 122.21,
123.76, 123.76 (q, J = 272.3 Hz), 124.39, 125.12 (q, J = 2.1 Hz), 126.66,
126.93, 127.04, 127.42, 128.26 (q, J = 3.6 Hz), 129.06, 129.46 (m), 131.12
(d, J = 32.5 Hz), 132.79, 132.20, 132.68, 134.69, 147.05, 148.38.
Synthesis of unsymmetrical arylethynes 5a–c, 8, 10a and 10b; general
procedure (representative procedure for 5a)
A THF solution (10.0 mL) of 1a (1.0 mmol) was treated with
MeMgBr (1.0 mmol). After the mixture had been stirred for
30 min under nitrogen at 0 °C, 2a (1.0 mmol) and Pd(dppf)
Cl2–CH2Cl2 (0.05 mmol) were added at 0 °C. The mixture was
stirred under nitrogen at 80 °C for 6 h. After workup with CH2Cl2
and aqueous NH4Cl, the organic layer was washed with brine and
dried over MgSO4. After filtration, the solvents were evaporated.
The crude product was filtered through a thin pad of silica gel to
give the product 3 in sufficiently pure form for further reaction.
A THF solution (10.0 mL) of the crude product 3 was treated with
TBAF (1.0 mmol) at 0 °C. After the mixture had been stirred
for 4 h under nitrogen at room temperature, 4a (0.95 mmol),
Pd(PPh3)4 (0.05 mmol), CuI (0.05 mmol), toluene (15.0 mL) and
diisopropylamine (0.5 mL) were added sequentially. The mixture
was stirred under nitrogen at 60 °C for 15 h. After workup with
CH2Cl2 and aqueous NH4Cl, the organic layer was washed with brine
and dried over MgSO4. After filtration, the solvents were evaporated.
The crude product was subjected to column chromatography on silica
gel (hexane/CH2Cl2, 3:1) to afford 5a in a pure form (yield 86%).
5a: Pale yellow powder; m.p. 170–172 °C (lit.9 169–171 °C); 1H NMR
(500 MHz, CDCl3): δ 3.86 (s, 3H), 6.89 (d, J = 9.0 Hz, 2H), 7.35 (t,
J = 8.0 Hz, 1H), 7.47–7.53 (m, 4H), 7.601–7.67 (m, 4H), 7.71 (s, 1H);
13C NMR (125 MHz, CDCl3): δ 55.29, 86.97, 88.09, 90.37, 92.96,
111.59, 114.00, 114.07, 114.85, 118.48, 122.46, 124.18, 127.97, 128.58,
131.04, 131.95, 132.09, 133.13, 134.56, 159.81.
Acknowledgements
This work was supported by the Natural Science Fund Youth
Project of Hunan Province (No. 2018JJ3145), the General
Project of Hunan Education Department (17C0629), the
Doctoral Foundation of Hunan University of Science and
Technology (No. E51693), the Open Foundation of Key
Laboratory of Theoretical Organic Chemistry and Functional
Molecule of Ministry of Education, Hunan University of
Science and Technology (No. E21630) and the National Natural
Science Foundation of China (No. 21402048).
Received 24 April 2018; accepted 2 May 2018
Paper 1805397
https://doi.org/10.3184/174751918X15269925671284
Published online: 30 May 2018
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