Palladium-catalyzed P(O)R2 directed C-H arylation to synthesize electron-rich polyaromatic monophosphorus ligands

Article abstract of DOI:10.1039/c3cc49050e

Palladium-catalyzed arylation of (diisopropylphosphoryl)biphenyl skeleton derivatives by the P(O)R₂ directed C-H functionalization was reported. The related products were obtained in high regioselectivity and good functional group tolerance was observed. This reaction provided a new and efficient pathway for the synthesis of polyaromatic monophosphorus ligands. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3cc49050e

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Palladium-catalyzed P(O)R2 directed C–H
arylation to synthesize electron-rich polyaromatic
monophosphorus ligands†
Rong-Bin Hu,a Heng Zhang,a Xiao-Yu Zhanga and Shang-Dong Yang*ab
Cite this: Chem. Commun., 2014,
50, 2193
Received 27th November 2013,
Accepted 19th December 2013
DOI: 10.1039/c3cc49050e
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Palladium-catalyzed arylation of (diisopropylphosphoryl)biphenyl C–H olefination and hydroxylation.12 In particular, R2(O)P is
skeleton derivatives by the P(O)R2 directed C–H functionalization not only acting as the directing group, but also the useful
was reported. The related products were obtained in high regio- composition of the product in our case. Herein, we report a
selectivity and good functional group tolerance was observed. This R2(O)P directed palladium-catalyzed C–H arylation to synthesize
reaction provided a new and efficient pathway for the synthesis of a series of polyaromatic monophosphorus compounds, and this
polyaromatic monophosphorus ligands.
directing group can be easily reduced to trivalent phosphorus
by trichlorosilane, which are useful ligands for transition-metal-
Transition-metal-catalyzed C–H functionalization of directing- catalyzed cross-coupling reactions.13 Moreover, instead of forming
group-containing substrates has emerged as a promising strategy a five-membered cyclopalladium pretransition state, the reaction
in synthetic reactions.1 By assisting chelation and subsequently may go through a seven-membered cyclopalladium pretransition
promoting further C–H functionalization, directing groups provide state, and shows high regioselectivity (Scheme 1 path b).
a whole new way for the valuable structural frameworks and the
We began our optimization with [1,10-biphenyl]-2-yldiisopropyl-
improvement of the overall synthetic efficiency and regioselectivity. phosphine oxide (1a) and diphenyliodonium trifluoromethane-
Because biphenyl derivatives are important structural units in sulphonate (2) as template substrates. After a series of screens, the
numerous functional molecules relevant to medicinal chemistry optimized reaction conditions were obtained (Table S1, entry 32;
and materials science,2 so many directing groups such as hetero- see ESI†). Subsequently, various substrates which have been used
cycles,3 anilides,4 amides,5 oximes,6 benzylamines,7 carboxylic to determine the scope and limitations of present methodology
acids8 and ketones9 have been successfully applied in transition were investigated (Table 1). Firstly, different directing groups were
metal-catalyzed direct C–H arylation of arenes to construct these examined, when R is cyclohexyl or t-butyl, we could obtain the
skeletons. However, in spite of tremendous progress, the applica- arylated product in moderate yields. With 2-diphenylphosphino
tion of innovative directing groups with improved directing oxide as the directing group, 3d and 3e could be obtained in
qualities, representing useful functional groups that are tunable moderate yields. When diisopropylphenyl phosphorous oxide
and show increased levels of reactivity and selectivity, should be (non-biphenyl skeleton) was used as a substrate, the product 3f
beneficial. Our ongoing interest is focused on finding new was not detected, this suggested that the five-membered cyclo-
organophosphorus transformations,10 which also prompts us to palladium transition state was unfavourable. Next, the scope of
examine the utilization of the phosphorus as the directing group different substituted 2-(diisopropylphosphoryl)biphenyl derivatives
for selective C–H functionalization reaction. Phosphorous acid
and phosphate ester have already been used as directing groups to
access C–H functionalization through a five- or six-membered
cyclopalladium pretransition state.11 Very recently, our group has
also developed the process of R2(O)P directed palladium-catalyzed
a State Key Laboratory of Applied Organic Chemistry, Lanzhou University,
Lanzhou 730000, P. R. China. E-mail: yangshd@lzu.edu.cn;
Fax: +86-931-8912859; Tel: +86-931-8912859
b State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute
of Chemical Physics, Lanzhou 730000, P. R. China
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
Scheme 1 Regioselective C–H activation by cyclopalladium.
c3cc49050e
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Table 1 Highly regioselective monophenylation of various biphenyl skeletonsa,b
Scheme 2 Reduction of phosphorous oxides to monophosphorus
ligands.
a
Reaction conditions: 1a–1p (0.2 mmol),
2 (2.5 equiv.), PdCl2
(10 mol%), Ag2CO3 (0.2 equiv.), PivOH (2.0 equiv.), DMF (4.0 mL), air
b
c
atmosphere, 80 1C, 36 h. Isolated yields. PdCl2 (20 mol%) and
Ag2CO3 (0.4 equiv.) were used.
was evaluated. The arylation of diisopropylphosphoryl biphenyl
substituted by an electron-donating group, such as methyl or
methoxy, on the ortho-, meta- or para-position of the aromatic ring
Ar1 proceeded smoothly to give the corresponding products.
Remarkably, the phenylnaphthalene skeleton was also further
arylated and yielded 3l in 63% yield under standard conditions.
Scheme 3 Plausible mechanism of Pd(II)-catalyzed C–H arylation.
For electron-deficient substrates, the chloride or trifluoromethyl yields, which also provided the possibility for further functional
substituent was also well tolerated, and gave 3m and 3n in transformation.
63% and 55% yields. When substituted by methyl or methoxy on
The polyaromatic monophosphorus ligand may be an impor-
aromatic ring Ar2, the products were obtained in moderate yield. tant ligand in transition-metal-catalyzed cross-coupling reactions,
Next, different hypervalent iodines as arylation reagents14 so we used the classical reduction system for our arylated product,
were evaluated in this transformation (Table 2), this kind of and obtained the reduction product by flash chromatography
skeleton was also further functionalized. The ortho-position (Scheme 2).15 Therefore, our report provided a new and efficient
substituted aryl iodine reagent was ineffective in this system. pathway for the synthesis of the polyaromatic monophosphorus
The substrate which was substituted by fluoride, chlorine ligand.
and bromine was successfully arylated in moderate to good
According to the previously reported literature16 and the
preliminary mechanistic studies, we proposed the catalytic cycle as
shown in Scheme 3; firstly, PdCl2 combined with PivOH and Ag2CO3
generated the higher activity Pd(PivO)2 A as a pre-activated state.
Then PQO-directed C–H activation occurred and generated the
seven-membered cyclopalladium intermediate B; next, subsequent
oxidative addition of the Pd(II) complex to a Pd(IV) intermediate C by
Ph2IOTf occurred. Finally, the desired product 3a was formed by
reductive elimination and released the Pd(II), which regenerated the
species A. Furthermore, the Pd(0) also could prompt this reaction, so
we couldn’t exclude the cycling of Pd(0)–Pd(II)–Pd(0).
Table 2 Arylation of the biphenyl skeleton with MesArIOTfa,b
In conclusion, we have developed a synthesis approach for
preparation of the terphenyl electron-rich phosphorus compounds
by palladium-catalyzed P(O)R2 directed C–H arylation. It is note-
worthy that the terphenyl products were obtained in high regio-
selectivity and good functional group tolerance was observed.
a
Reaction conditions: 1 (0.2 mmol), 2 (2.5 equiv.), PdCl2 (20 mol%),
Ag2CO3 (0.4 equiv.), PivOH (2.0 equiv.), DMF (4.0 mL), air atmosphere,
80 1C, 36 h. Isolated yields of products.
b
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6 C.-L. Sun, N. Liu, B.-J. Li, D.-G. Yu, Y. Wang and Z.-J. Shi, Org. Lett.,
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These products can be reduced easily to monophosphorus ligands.
In addition, a seven-membered cyclopalladium intermediate may
be involved in this transformation. Investigation of the detailed
mechanism is underway in our laboratory.
We are grateful to the NSFC (No. 21272100), Program for
Changjiang Scholars and Innovative Research Team in University
(PCSIRT: IRT1138) and Research Fund for the Doctoral Program
of Higher Education of China (No. 20100211120014) for finan-
cial support.
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