Synthesis of novel bisphosphine-containing polymers and their applications as bidentate ligands for nickel(0)-catalyzed cross-coupling reactions

Article abstract of DOI:10.1002/adsc.200606002

The efficient synthesis of two examples of a new type of ferrocene-based bisphosphine-containing polymers and their application as bidentate ligands for Ni(0)-catalyzed cross-coupling reactions of aryl chlorides with arylboronic acids, and aryl fluorides with Grignard reagents are described. Our study may provide a new family of bisphosphine-containing polymers that are readily accessible and potentially useful in transition metal catalysis.

Full text of DOI:10.1002/adsc.200606002

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DOI: 10.1002/adsc.200606002
Synthesis of Novel Bisphosphine-Containing Polymers and Their
Applications as Bidentate Ligands for Nickel(0)-Catalyzed
Cross-Coupling Reactions
Yong Lu, Elizabeth Plocher, Qiao-Sheng Hu*
Department of Chemistry, College of Staten Island and the Graduate Center of the City University of New York,
Staten Island, NY 10314, U.S.A.
Fax: (þ1)-718-982-3910, e-mail: qiaohu@mail.csi.cuny.edu
Received: January 3, 2006; Accepted: March 18, 2006
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The efficient synthesis of two examples of
a new type of ferrocene-based bisphosphine-contain-
ing polymers and their application as bidentate li-
gands for Ni(0)-catalyzed cross-coupling reactions
of aryl chlorides with arylboronic acids, and aryl flu-
orides with Grignard reagents are described. Our
study may provide a new family of bisphosphine-
containing polymers that are readily accessible and
potentially useful in transition metal catalysis.
Keywords: aryl chlorides; cross-coupling; immobili-
zation; nickel; phosphane ligands; Suzuki–Miyaura
reaction
containing polymers could have vs. the limited number
of bisphosphine-containing polymers developed and
studied likely resulted from deficiencies associated
with their synthesis and/or catalysis. The synthesis of
Bisphosphines such as 1,n-diphenylphosphinoalkanes previously reported bisphosphine-polymers is often
(DPPA) and derivatives, 2,2’-bis(diphenylphosphino)- characterized by long synthetic steps and/or not readily
1,1’-binaphthyl (BINAP), 1,1’-bis(diphenylphosphino)- available starting materials. In addition, the perform-
ferrocene (DPPF), and 2,2’-bis(diphenylphosphino)- ance of many of the reported bisphosphine-containing
1,1’-biphenyl (BIPHEP) represent a large group of bi- polymers is not as good as that of the monomeric coun-
dentate ligands in transition metal catalysis.[1,2] They terparts for chosen transformations. It is thus of great in-
have been demonstrated as very useful ligands in an ar- terest to develop new types of bisphosphine-containing
ray of bond-forming reactions including catalytic hydro- polymers that meet the following criteria: (a) starting
genations and transition metal-catalyzed cross-coupling materials are readily available, (b) the synthetic elabo-
reactions.[1,2] Since the 1970s, studies have been carried ration is short, (c) their electronic and steric properties
out to immobilize bidentate bisphosphines in polymer are tunable, and (d) they should perform equally well
networks.[3] However, despite the fact that polymer-sup- as or (e) better than their monomeric counterparts for
ported bisphosphines possess advantages such as easy chosen transformations.
recovery and reuse, and sometimes higher catalytic ac-
In our laboratory, we are interested in developing new,
tivities for derived catalysts compared to their mono- readily accessible ligands for transition metal catalysis.
meric counterparts, only a limited number of polymer- We have initialized a project to synthesize ferrocenyl-
supported bisphosphines has been developed and their methyl-containing ligands from ferrocenylmethyl alco-
applications as ligands in transition metal catalysis hols based on the following considerations:[4] (a) ferro-
have not reached a level that parallels that of their mon- cenylmethyl alcohols including optically active forms
omeric counterparts.
are readily available, and (b) the unique retentive SN1
Careful examination suggested that the unbalanced reaction at the a-position of ferrocene would allow
phenomenon of potential advantages bisphosphine- easy access to a family of ferrocenylmethyl-containing
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841

Yong Lu et al.
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ligands with tunable steric and electronic properties. We
have developed a protocol to directly convert ferroce-
nylmethyl alcohols to monodentate ferrocenylmethyl-
phosphines (Scheme 1),[5] and have also successfully ap-
plied it for the preparation of ferrocenylmethylphos-
phine-containing polymers 3 in very few steps (Scheme
1).[6] Since 1,1’-bis(hydroxymethyl)ferrocenes such as 4
are readily available via a one-step reaction from ferro-
cene and aldehydes and the hydroxy groups of 4 are
structurally similar to that of ferrocenylmethyl alcohol
1, we reasoned that the hydroxy groups in 4 should be-
have similarly to that of 1 and should also be capable
of directly conversion to diphenylphosphosphino moiet-
ies. We believed that successfully realizing this could
lead us to the development of a new family of ferro-
cene-based, bisphosphine-containing polymers from
readily available starting materials in very few synthetic
Scheme 2. Direct conversion of 1,1’-bis(1-hydroxy-1-phenyl-
methyl)ferrocene to bisphosphine 7.
Having established that the feasibility to directly con-
steps. In this communication, we report the efficient syn- vert 1,1’-bis(hydroxymethyl)ferrocenes to 1,1’-bis(di-
thesis of two examples of this new type of ferrocenyl- phenylphosphosphinomethyl)ferrocenes, we were set-
methyl-based bisphosphine-containing polymers, 5 and tled to extend this protocol for the preparation of ferro-
6, and their applications as bidentate ligands in Ni(0)- cene-based bisphosphine-containing polymers. As
catalyzed cross-couplings of aryl chlorides with arybor- shown in Scheme 3, starting from inexpensive ferrocene,
onic acids, and aryl fluorides with Grignard reagents.
reaction with n-BuLi and N,N,N’,N’-tetramethylethyl-
We began our study by testing the reaction of HPPh2 enediamine (TMEDA) followed by treatment with 4-
with diol 4a, which was readily prepared from ferrocene bromobenzaldehyde generated dibromide 4b in 75%
and benzaldehyde.[4,7,8] We were pleased to find that bis- yield.[7] Pd(0)-catalyzed Suzuki cross-coupling polymer-
phosphine 7 was indeed formed directly from 4a under ization with diboronic acid 8 generated polymer 9 in
the conditions that are similar to the preparation of 2 96% yield.[9] By following the procedure described
(100% conversion, 47% isolated yield) (Scheme 2).
above, we were pleased to find that treatment of poly-
mer 9 with HPPh2 smoothly generated polymer 5. Poly-
mer 5 is soluble in common organic solvents such as
THF, toluene, dichloromethane and can be precipitated
out from methanol. GPC (polystyrene standards, THF)
analysis shows its molecular weight is Mw ¼4,300, Mn ¼
ꢀ
3,100 (PDI¼1.41). The complete conversion of OH
1
ꢀ
to PPh2 was confirmed by H NMR.
Polymer 6 was prepared in a similar manner by start-
ing from ferrocene and 3-bromobenzaldehyde
(Scheme 4). Polymer 6 is also soluble in common organ-
ic solvents such as THF, toluene, dichloromethane. The
ꢀ
ꢀ
complete conversion of OH to PPh2 was also con-
firmed by 1H NMR.
Transition metal-catalyzed Suzuki coupling of deacti-
vated aryl chlorides with arylboronic acids has only been
realized recently and represents a notable advance in
transition metal-catalyzed chemistry.[10–12] Although a
number of ligands can now achieve this objective, truly
recoverable and reusable ligands are rare.[13] We have
employed 5 as a ligand for Ni(0)-catalyzed Suzuki cou-
pling reactions of aryl chlorides and arylboronic acids.
As shown in Table 1, Ni(COD)2/5 complexes (3 mol
%/9 mol%) smoothly catalyzed the coupling reaction
between aryl chlorides, including electron-rich ones,
and arylboronic acids. The polymer ligands exhibited
similar catalytic efficiency as bisphosphine 7 (Table 1,
entries 15, 16), and can be readily recovered and reused
(Table 1, entries 2, 8, 11).
Scheme 1. Direct conversion of ferrocenylmethyl alcohols to
ferrocenylmethylphosphines.
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Bisphosphine-Containing Polymers and Their Applications as Bidentate Ligands
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Scheme 3. Preparation of bisphosphine-containing polymer 5.
Scheme 4. Preparation of bisphosphine-containing polymer 6.
To establish the coordination nature of the new type of omeric counterpart 7 (Table 3). Polymer 5 has also been
bisphosphine-containing polymers in Ni(0)-catalyzed demonstrated to be recoverable and reusable.
cross-couplings of aryl chlorides with arylboronic acids,
In summary, the synthesis of two examples of a new
we have compared the catalytic behavior of different li- type of ferrocene-based bisphosphine-containing poly-
gands using the cross-coupling reaction of p-chloroani- mers and their application as bidentate ligands for
sole with phenylboronic acid as the model reaction. Ni(0)-catalyzed cross-coupling reactions are described.
We found that monodentate ferrocenylmethylphos- Our study showed that (a) this new family of ferro-
phine 2, as well as its polymeric form 3, was an efficient cene-based bisphosphine-containing polymers could
ligand for room temperature Ni(0)-catalyzed cross-cou- be readily accessible in very few steps from readily avail-
pling of aryl chlorides with arylboronic acids (Table 2, able starting materials, (b) the catalytic properties of the
entries 1, 2). On the other hand, the same reactions new ferrocene-based bisphosphine polymers exhibited
only take place at elevated temperature when bidentate in Ni(0)-catalyzed cross-coupling reactions of aryl chlor-
DPPF and 1,2-bis(diphenylphosphino)ethane (DPPE) ides with arylboronic acids, and aryl fluorides with
are used as ligands (Table 2, entries 3–5).[12] We found Grignard reagents were comparable to those of their
that the catalytic property of polymer 5 was very similar monomeric counterparts, and (c) the polymer could be
to that of DPPFand DPPE (Table 2, entries 6–9). These recovered and reused. Our future work will be focused
results suggested that the phosphine moieties in poly- on the preparation of other related polymers including
mers 5 and 6 most likely functioned as bidentate ligands optically active ones and exploration of their applica-
rather than monodentate ones.
tions for other Pd(0)- and Ni(0)-catalyzed cross-cou-
We also briefly examined another type of challenging pling reactions.
cross-coupling reaction that involves bidentate ligands
such as DPPP/DPPE as ligands: the cross-coupling of
fluoroarenes with Grignard reagents.[14,15] We found
that polymer 5 behaved similarly as DPPE and its mon-
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Yong Lu et al.
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Table 1. Ni(0)-catalyzed cross-coupling reactions of aryl
Table 2. Ni(0)-catalyzed Suzuki cross-coupling of p-chloro-
chlorides with arylboronic acids.[a]
anisole with phenylboronic acid.[a]
[a]
Reaction conditions: p-chloroanisole (1.0 equiv.), phenyl-
boronic acid (1.5 equivs.), K3PO4 (3 equivs.), THF
(2 mL).
[b]
Yield of isolated products.
Ref.[12a]
[c]
[d]
Ref.[12c]
Table 3. Ni(0)-catalyzed cross-coupling reactions of aryl
fluorides with Grignard reagents.[a]
[a]
Reaction conditions (not optimized): aryl chlorides
[a]
(1.0 mmol.), arylboronic acids (1.5 equivs.), K3PO4
(3 equivs.), 3 mol % Ni(COD)2, ligand (9 mol % based
on repeat unit), THF (2 mL).
Reaction conditions (not optimized): fluoride (1.0 mmol),
Grignard reagent (1.5–2.0 equivs.), 1: 1 ratio of Ni-
(acac)2/ligand (based on repeat unit), THF (2 mL).
[b]
[b]
Yields of isolated products.
Yield of isolated products.
[c]
[c]
[d]
1
Recovered polymer was used.
Based on H NMR.
[d]
1
Conversion based on H NMR.
Recovered polymer was used.
Experimental Section
flask. The mixture was stirred overnight at room temperature.
The solvents were evaporated under vacuum. The residue was
dissolved in a small amount of degassed CH2Cl2 and precipitat-
ed from degassed MeOH. The process was repeated four more
times. The precipitate was obtained by syringing out the sol-
vent. After drying under vacuum, 5 was obtained as a yellow
solid; yield: 0.534 g (53%).
Preparation of Polymer 5
To a solution of polymer 9 (0.67 g, 1 mmol based on repeating
unit) in CH2Cl2 (5 mL), HOAc (2 ml) was added under N2.
HPPh2 (1.64 mL, 10 wt % in hexanes) was syringed into the
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[4] For reviews of ferrocenes: a) A. Togni, T. Hayashi, Ferro-
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[5] Z.-Y. Tang, Y. Lu, Q.-S. Hu, Org. Lett. 2003, 5; 297–300.
[6] Q.-S. Hu, Z.-Y. Tang, Y. Lu, H.-B. Yu, J. Am. Chem. Soc.
2003, 125, 2856–2857.
General Procedure for Ni(COD)2/Polymer Ligand-
Catalyzed Suzuki Cross-Coupling Reactions of Aryl
Chlorides with Arylboronic Acids
To a vial containing 5 or 6 (45 mg, 0.0045 mmol), Ni(COD)2
(4.12 mg, 0.0015 mmol), arylboronic acid (91 mg, 0.75 mmol),
K3PO4 (318 mg, 1.5 mmol) was added THF (2.0 mL). After
the mixture was stirred at room temperature for ca. 5 min,
aryl chloride (0.5 mmol) was added by a syringe. The reaction
mixture was allowed to reflux for 24 h. The reaction was
quenched by water and extracted with diethyl ether. The or-
ganic layer was washed with brine. Evaporation of solvents
and purification of the residue by column chromatography
on silica gel with ethyl acetate/hexane as eluent afforded the bi-
phenyl products.
[7] T. Sammakia, H. A. Latham, J. Org. Chem. 1996, 61,
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[9] Q.-S. Hu, in: Synthetic Methods for Step-Growth Poly-
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For detailed procedures and characterization data, see Sup-
porting Information.
[10] For a recent review on Pd(0)-catalyzed cross-couplings
of aryl chlorides, see: A. F. Littke, G. C. Fu, Angew.
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[11] For recent reviews on nickel-catalyzed Suzuki cross-cou-
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Gozzi, E. Schulz, M. Lemaire, Chem. Rev. 2002, 102,
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Acknowledgements
We gratefully thank the NIH (GM69704) for their generous
funding. Partial support from the PSC-CUNY Research Award
Programs, and GRTI(The Graduate Research and Technology
Initiative) grants are also gratefully acknowledged. We thank
Frontier Scientific for its generous gifts of boronic acids. This
work also benefited from the NSF-REU program at CSI.
[12] a) V. Percec, G. M. Golding, J. Smidrkal, O. Weichold, J.
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[13] Ligand-containing polymers for aryl chlorides cross-cou-
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