Oligoarene strategy for catalyst development. Hydroxylated oligoarene-type phosphines for palladium-catalyzed cross coupling

Article abstract of DOI:10.1246/cl.2007.1302

Various oligoarene-type phosphines having a hydroxy group were synthesized based on a two-step repetitive method that we developed, and these phosphines were used as ligands for palladium in catalytic cross coupling with Grignard reagents. The study revealed that a hydroxylated terphenylphosphine accelerated the rate of the cross coupling of o-bromophenol and exhibited preference for the ortho-isomer over the meta- and para-isomers. Copyright

Full text of DOI:10.1246/cl.2007.1302

1302
Chemistry Letters Vol.36, No.11 (2007)
Oligoarene Strategy for Catalyst Development. Hydroxylated Oligoarene-type
Phosphines for Palladium-catalyzed Cross Coupling
Shunpei Ishikawa and Kei ManabeÃ
RIKEN, 2-1 Hirosawa, Wako 351-0198
(Received August 20, 2007; CL-070883; E-mail: keimanabe@riken.jp)
O
Various oligoarene-type phosphines having a hydroxy group
PCy2
were synthesized based on a two-step repetitive method that we
developed, and these phosphines were used as ligands for palla-
dium in catalytic cross coupling with Grignard reagents. The
study revealed that a hydroxylated terphenylphosphine acceler-
ated the rate of the cross coupling of o-bromophenol and exhib-
ited preference for the ortho-isomer over the meta- and para-iso-
mers.
Br
Pd2(dba)3 (cat.)
P(t-Bu)3•HBF4 (cat.)
20, KF
Pd2(dba)3 (cat.)
10
P(t-Bu)3•HBF4 (cat.)
19, KF
THF
63%
O
THF
84%
O
1) HSiCl3
1) HSiCl3
Et3N
Et3
N
PCy2
PCy2•HBF4
PCy2
•
PCy2
toluene
toluene
HBF4
2) HBF4
CH2Cl2
78%
2) HBF4
CH2Cl2
68%
HO
13
OH
2
11
OH
1
OH
Tf2NPh, NaH
THF, 98%
O
Tf2O, pyridine
CH2Cl2, 98%
Pd(OAc)2
PCy2
HBF4
•
O
(cat.)
1) HSiCl3
Pd(OAc)2 (cat.)
Pd(OAc)2 (cat.)
17 (cat.), 21, KF
17 (cat.)
19, KF
PCy2
Et3N
PCy2
17 (cat.)
21, KF
toluene
1) HSiCl3
Et3
toluene
2) HBF4
CH2Cl2
56%
THF/H2
92%
O
Tf2O, pyridine
CH2Cl2, 81%
THF/H2O
85%
2) HBF4
CH2Cl2
49%
THF/H2O
95%
Development of catalysts that enable highly efficient trans-
formation of organic compounds is a major focus in synthetic
chemistry. Here, we describe a new strategy based on oligoar-
ene-type ligands for metal-catalyzed organic reactions.
Oligoarenes, composed of aromatic rings such as benzene
rings connected through a single bond, provide a useful frame-
work for functional molecules.1 We have developed a synthetic
method of oligoarenes having various functional groups.2 The
method, involving a two-step repetitive technique, includes tri-
flation of a hydroxy group and subsequent Suzuki–Miyaura cou-
pling3 of hydroxyphenylboronic acids or their derivatives
(Figure 1a). Repetition of these two steps affords oligoarenes
containing various functional groups in high yields.
As an application of oligoarenes to catalytic molecules, we
designed hydroxylated oligoarene-type phosphines4 (HOPs,
Figure 1b) as ligands for metals, based on biphenylphosphines
developed mainly by Buchwald et al.5 It was expected that a
HOP library would be readily prepared by the two-step repetitive
method. The OH group of HOP is introduced during the synthe-
sis of the oligoaryl moiety, while it simultaneously functions as
an assisting group in a catalytic reaction in which the HOP is
used as a ligand for a metal. For example, the metal oxido group
(M2–O in Figure 1c), formed from the OH group, would bind a
substrate through a functional group (Y). This binding would
place the reactive group (Z) close to the catalytic metal (M1)
coordinated by the phosphino group, leading to acceleration of
the catalytic reaction. Optimizing linker length and substitution
pattern (ortho-, meta-, para-) of HOPs would give suitable HOPs
N
OH
14
OTf
12
Pd(OAc)2
(cat.)
5
OTf
Pd(OAc)2
(cat.)
Pd(OAc)2 (cat.)
17 (cat.), 20, KF
THF/H2O, 97%
17 (cat.)
21, KF
18 (cat.), 20
O
THF/H2
O
KF
PCy2•HBF4
1) HSiCl3
PCy2
84%
THF/H2O, 81%
Et3
N
PCy2•HBF4
toluene
1) HSiCl3
1) HSiCl3
Et3N
Et3N, toluene
2) HBF4
2) HBF4
CH2Cl2
52%
toluene
2) HBF4
CH2Cl2
27%
OH
CH2Cl2, 53%
15
6
3
OH
Tf2O, pyridine
CH2Cl2, 75%
OH
PCy2•HBF4
Pd(OAc)2 (cat.)
17 (cat.), 20, KF
THF/H2O, 70%
PCy2•HBF4
O
PCy2
HBF4
•
PCy2
1) HSiCl3
OH
4
Et3
N
7
toluene
OH
2) HBF4
CH2Cl2
40%
8
PCy2
16
OH
OH
PCy2
i-Pr
i-Pr
Tf2O, pyridine
CH2Cl2, 67%
CH3
O
OCH3
PCy2•HBF4
Pd(OAc)2 (cat.)
17 (cat.), 21, KF
1) HSiCl3
i-Pr
18
Et3
N
B(OH)2
BO
BO
THF/H2O, 81%
toluene
17
OH
2) HBF4
CH2Cl2
25%
9
HO
OH
n
n
OH
20
21
19
Figure 2. Synthetic scheme of HOPs. Formulas 20 and 21
represent boronic anhydrides.6 Some HOPs contain solvents of
recrystallization.7
for specific reactions and also realize high substrate specificity
and reaction selectivity.
Figure 2 shows the synthetic scheme of a library of HOPs 1–
9.7 The key features of the synthesis include: (1) The two-step
repetitive method mentioned above was used for construction
of the oligoarene frameworks. For the synthesis of HOPs having
the common 2-dicyclohexylphosphinobiphenyl core structure,
this synthetic scheme efficiently produced the HOP library, be-
cause intermediates such as 11–16 were commonly utilized;
(2) Since the PCy2 group is gradually oxidized in an air atmo-
sphere, the phosphino group was protected as a phosphinyl
group throughout the oligoarene elongation. This protection also
facilitates the triflation steps, since Tf2O reacts with the phosphi-
no group to give undesired products. Finally, reduction of the
phosphinyl group gave the corresponding phosphines, which
were purified and stored as the HBF4 salts.8 For convenience,
these HBF4 salts are also called HOPs throughout this paper;
(3) Although HOPs synthesized in the present work have only
phosphino and OH functional groups, the present synthetic strat-
egy can be applied to the synthesis of HOPs having other types
Rn+1
a
Rn
Rn
Rn
Rn+1
X2B
OH
repetition
oligoarene
R
OH
R
OTf
OH
R
OH
triflation
cross-coupling
PR2
Z
b
c
Y
M2
O
M1
R
R
n
P
linker
n
Figure 1. (a) Two-step repetitive method for oligoarene synthe-
sis. (b) HOP. (c) Proposed intermediate of the reaction using an
oligoarene-type metal complex as catalyst.
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.11 (2007)
1303
Pd2(dba)3 (1 mol %)
ligand (2.4 mol %)
PhMgBr (3 equiv.)
PCy2
PCy2
PCy2•HBF4
HO
Br
HO
Pd2(dba)3 (1 mol %)
26 (2.4 mol %)
OH
OH
Br
PhMgBr (3 equiv.)
OCH3
THF
25
24
HO
(2)
o-, m-, p-22
yield (%)
o-, m-, p-23
THF
50 °C, 3 h
o-23
19%
o-22
26
100
80
60
40
20
0
(1 h)
Pd2(dba)3 (1 mol %)
5 (2.4 mol %)
PhMgBr (3 equiv.)
OCH3
OCH3
Br
o-23
(3)
THF
25 °C, 1 h
m-23
p-23
28
17%
27
In conclusion, we have developed a strategy for the develop-
ment of useful catalysts based on oligoarene-type phosphine
ligands having an OH group. The use of these ligands for Pd-
catalyzed cross coupling successfully resulted in identification
of one ligand that drastically accelerated the reaction of o-bro-
mophenol and exhibited substrate specificity. Although the focus
of this study was a specific reaction of the substrate, the concept
presented for finding suitable catalysts is applicable to other
catalytic reactions using various substrates.10
17
24
25
1
2
3
4
5
6
7
8
9
5
25 °C, 1 h
50 °C, 3 h
Figure 3. Cross coupling of a bromophenol with PhMgBr.
of functional groups, according to our previous work.2
To demonstrate the effectiveness of HOPs 1–9, they were
tested in Pd-catalyzed cross coupling of bromoarenes with
Grignard reagents.7,9 Bromophenols as bromoarenes were used,
because the phenolic oxygen of the substrates was expected to
act as the interacting group (Y) as shown in Figure 1c. Figure 3
shows the results of cross coupling of a bromophenol with
PhMgBr in the presence of Pd2(dba)3 and a phosphine ligand.
HBF4 salts 1–9 were directly used for the reaction. As the ligand,
commercially available phosphines 17,5b 24,5a and 255e were al-
so tested. The yields of o-23, m-23, and p-23 were significantly
affected by the ligands. For each ligand, m-22 gave a higher
yield than did o-22 and p-22, except when ligand 1, 5, or 25
was used. In particular, 5 exhibited much greater activity for
o-22 than for m-22 and p-22, and the higher yield of o-23 main-
tained even with a shorter reaction time (1 h). The reaction of o-
22 using 5 proceeded even at 25 ꢀC in good yield (79%), and the
preference for o-22 over m-22 and p-22 was further emphasized.
This high activity for o-22 was observed only for 5, indicating
that 5 is an optimized ligand for the reaction of o-22.
This work was partly supported by a Grant-in-Aid for Scien-
tific Research on Priority Areas ‘‘Advanced Molecular Transfor-
mations of Carbon Resources’’ from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
References and Notes
1
a) J. M. Tour, Chem. Rev. 1996, 96, 537. b) A. J. Berresheim, M.
Muller, K. Mullen, Chem. Rev. 1999, 99, 1747. c) F. J. M. Hoeben,
¨
¨
P. Jonkheijm, E. W. Meijer, A. P. H. J. Schenning, Chem. Rev.
2005, 105, 1491.
2
a) S. Ishikawa, K. Manabe, Chem. Lett. 2006, 35, 164. b) S.
Ishikawa, K. Manabe, Chem. Commun. 2006, 2589. c) H. Shimizu,
K. Manabe, Tetrahedron Lett. 2006, 47, 5927.
3
4
A. Suzuki, H. C. Brown, Organic Synthesis via Boranes, Vol. 3,
Suzuki Coupling, Aldrich Chemical Company, Milwaukee, 2003.
Examples of oligoarene-type phosphines. a) H.-B. Yu, Q.-S. Hu,
L. Pu, J. Am. Chem. Soc. 2000, 122, 6500. b) K. Goto, Y. Ohzu,
H. Sato, T. Kawashima, Phosphorus, Sulfur Silicon 2002, 177,
2179. c) T. Matsumoto, T. Kasai, K. Tatsumi, Chem. Lett. 2002,
346. d) T. Iwasawa, T. Komano, A. Tajima, M. Tokunaga, Y.
Obora, T. Fujihara, Y. Tsuji, Organometallics 2006, 25, 4665.
e) K. Matsui, S. Takizawa, H. Sasai, Synlett 2006, 761.
a) J. P. Wolfe, S. L. Buchwald, Angew. Chem., Int. Ed. 1999, 38,
2413. b) X. Huang, K. W. Anderson, D. Zim, L. Jiang, A. Klapars,
S. L. Buchwald, J. Am. Chem. Soc. 2003, 125, 6653. c) T. E.
Barder, S. D. Walker, J. R. Martinelli, S. L. Buchwald, J. Am.
Chem. Soc. 2005, 127, 4685. d) R. Martin, S. L. Buchwald, J.
Am. Chem. Soc. 2007, 129, 3844. e) C. A. Parrish, S. L. Buchwald,
J. Org. Chem. 2001, 66, 3820.
Next, a competitive experiment using bromophenols was
conducted (eq 1). Under the reaction conditions utilizing HOP
5 and a 1:1:6 mixture of o-22, p-22, and PhMgBr, o-23 was
afforded preferentially over p-23. Thus, substrate specificity
for o-22 was clearly demonstrated.
5
Pd2(dba)3 (1 mol %)
5 (2.4 mol %)
PhMgBr (6 equiv.)
OH
OH
Br
Br
+
+
(1)
THF, 25 °C, 1 h
HO
HO
p-23
5%
p-22
o-23
59%
o-22
6
7
The real aggregation states of the boronic anhydrides are unclear
because of the complexity associated with the phenolic OH
groups.
See Supporting Information for experimental details. The material
is available electronically on the CSJ-Journal web site, http://
www.csj.jp/journals/chem-lett/.
Although the mechanism that allows HOP 5 to catalyze the
reaction of o-22 effectively is unknown, the following experi-
ments strongly suggest that the OH groups of both 5 and o-22
play a major role in the rate acceleration and substrate specificity
observed. First, reference ligand 267 resulted in very low yield
(eq 2). Second, compound 27 in the presence of 5 gave the prod-
uct 28 in very low yield (eq 3). From these results, we assume
that the reaction proceeds via the intermediate as shown in
Figure 1c, in which the Mg oxido group of HOP holds a position
ortho to the oxido group of bromophenoxide close to the Pd atom
coordinated by the phosphine.
8
9
M. R. Netherton, G. C. Fu, Org. Lett. 2001, 3, 4295.
a) J. Tsuji, Palladium Reagents and Catalysts, John Wiley & Sons,
West Sussex, 2004, p. 335. b) T. Takahashi, K.-i. Kanno, in
Modern Organonickel Chemistry, ed. by Y. Tamaru, Wiley-
VCH, Weinheim, 2005, p. 41. c) I. Cepanec, Synthesis of Biaryls,
Elesevier, Oxford, 2004, p. 83.
10 See the following paper: S. Ishikawa, K. Manabe, Chem. Lett.
2007, 36, 1304.
Published on the web (Advance View) October 6, 2007; doi:10.1246/cl.2007.1302