Suzuki reactions catalyzed by palladium complexes bearing the bulky (2,6-dimesitylphenyl)dimethylphosphine

Article abstract of DOI:10.1016/j.tetlet.2004.09.069

Good yields for coupling of aryl halides with arylboronic acids are achieved utilizing a (m-terphenyl)dialkylphosphine palladium complex. A new bulky and stable phosphine (2,6-dimesitylphenyl)dimethylphosphine, and representative palladium complexes have been prepared and structurally characterized; some of these complexes prove efficient for coupling of aryl chlorides with arylboronic acids.

Full text of DOI:10.1016/j.tetlet.2004.09.069

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8327–8330
Suzuki reactions catalyzed by palladium complexes bearing
the bulky (2,6-dimesitylphenyl)dimethylphosphine
Rhett C. Smith,a Robert A. Woloszynek,a Weizhong Chen,b
Tong Renb and John D. Protasiewicza,*
aDepartment of Chemistry, Case Western Reserve University, Cleveland, OH 44106, USA
bDepartment of Chemistry, University of Miami, Coral Gables, FL 33146, USA
Received 23 July 2004; revised 4 September 2004; accepted 9 September 2004
Available online 28 September 2004
Abstract—A new bulky and stable phosphine (2,6-dimesitylphenyl)dimethylphosphine, and representative palladium complexes
have been prepared and structurally characterized; some of these complexes prove efficient for coupling of aryl chlorides with aryl-
boronic acids.
Ó 2004 Elsevier Ltd. All rights reserved.
Sterically encumbered phosphines are a subject of cur-
rent interest,1 especially for use in catalytic C–C coupling
reactions. In particular, it has been shown that bulky
ortho-biphenyldialkylphosphines (A, Fig. 1) have led to
some spectacular successes in this area of chemistry.2–7
For example, a recent report announced that when
R = Cy and R0 = 2,6-(OMe)2 even palladium catalyzed
Suzuki–Miyaura couplings involving normally unreac-
tive hindered chloroarenes with arylboronic acids can
be highly efficient.2 The success of this hindered biaryl-
phosphine was attributed in part to the increased steric
bulk of the ortho-biphenyl group. Development of phos-
phines based on various meta-terphenyls and quater-
phenyls has also yielded other interesting ligands.8,9,13
als.10,11 One such material, DmpPCl2 (Fig. 1, X = Cl,
Dmp = 2,6-dimesitylphenyl)12 seemed particularly sui-
ted for serving as a precursor to new dialkylphosphines
of the form DmpPR2. Like (biaryl)dialkylphosphines A,
(triaryl)dialkylphosphines might also find applications
as ligands for catalysis. We herein report on the synthe-
sis of DmpPMe2 (1) and of its corresponding palladium
complexes. These materials have been fully character-
ized, and preliminary studies reveal that such palladium
complexes can effect efficient coupling of aryl halides
with arylboronic acids.
Phosphine 1 was readily prepared in 65% yield by reac-
tion of DmpPCl2 with 2.2equiv of MeLi at low temper-
ature in diethyl ether.18 Attesting to the steric protection
afforded by the Dmp unit, crystalline 1 is stable to oxi-
dation even after standing open to the atmosphere at
room temperature for at least one month. Crystallo-
We have previously examined the use of meta-terphenyls
for the development of low coordinate (multiply
bonded) phosphorus centres in pi-conjugated materi-
graphic analysis of
1 (see Supplementary data)
R'
shows it to possess a geometry similar to the related
structurally characterized meta-terphenylphosphine
2,6-(4-tBuC6H4)2C6H3PCl2.14
PX2
PR2
Phosphine 1 was found to yield a variety of complexes
depending upon the particular palladium source used.
Complex 2, trans-[(1)2PdCl2], was readily prepared in
essentially quantitative yield by stirring 2equiv of 1 with
PdCl2(NCPh)2 in CH2Cl2 at room temperature for
30min.18 By contrast, addition of the reagents in a 1:1
ratio led to the isolation of [(1)PdCl(l-Cl)]2 (3) in 92%
yield18 (Scheme 1).
DmpPX2
A
Figure 1.
Keywords: Phosphines; Suzuki reaction; Palladium catalyst.
*
Corresponding author. Tel.: +1 216 368 5060; fax: +1 216 368
3006; e-mail: protasiewicz@case.edu
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.09.069

8328
R. C. Smith et al. / Tetrahedron Letters 45 (2004) 8327–8330
Cl
DmpMe2P
Pd PMe2Dmp
(2)
Cl
0.5 PdCl2(NCPh)2
Pd(OAc)2
1
PdCl2(NCPh)2
OAc
PMe2Dmp
O
O
Cl
PMe2Dmp
Cl
Cl
Pd
Pd
O
Pd
Pd
DmpMe2P
OAc
DmpMe2P
Cl
O
(3)
(4)
Scheme 1.
Figure 2. X-ray structure of 4 (H atoms and cocrystallized THF
˚
molecule have been omitted for clarity). Select bond lengths (A) and
Reaction of 1 with Pd(OAc)2 also led to dimeric com-
plex 4 that was isolated in 85%.18 Compounds 3 and 4
(1:1 Pd:phosphine ratio) are attractive materials, as
under catalytic conditions they might generate highly
active monophosphine Pd species, perhaps stabilized
by interaction of Pd with the p system of a flanking mesi-
tyl group, as has been noted for PdÆA-type complexes.9,15
angles (°): P–Pd 2.2120(13); Pd–O3, 2.025(3); Pd–O2, 2.020(3); Pd–O1,
2.103(3); Pd–Pd(A) 3.427; P–Pd–O1, 173.60(11); O3–Pd–O2,
169.43(15).
most easily discerned by comparison to the related struc-
ture of [PdCl(l-OAc)(PMe2Ph)]2 (B).16
˚
The Pd–P bond length in 4 (2.2120(13)A) is essentially
˚
the same as that in B (2.213A), while the Pd–Pd distance
An X-ray structural analysis of complex 4ÆTHF (see Sup-
plementary data) confirms a dimeric structure (Fig. 2),
and also reveals a number of additional features of note.
The global coordination mode, in which the l-acetato
moieties are distributed cis to one another, is in line with
many other structurally characterized complexes featur-
ing a diacetato-bridged dipalladium core.
˚
in 4 (3.427A) is the longest among structurally charac-
terized complexes featuring the diacetato-bridged dipal-
˚
ladium core (cf. 3.080A for B). This spreading of the
core is likely a response to steric forces imposed by the
convex Dmp groups.
Having confirmed the expected formulation of these
materials, preliminary investigations into the catalytic
efficacy of 3 and 4 were carried out (Table 1). Initial
screening indicated that 3 was a more potent catalyst,
and reactions with this complex were thus more thor-
oughly pursued. These promising early (nonoptimized)
results are comparable to those obtained with catalysts
containing ligands of type A when phenylboronic acid
The phosphines are oriented in the presumably more
sterically favourable (noneclipsed) orientation, with a
nonbridging acetate completing the pseudo-square pla-
nar coordination sphere at each Pd centre. The Pd lies
above the ligand plane by 0.154A as the ligands tilt
slightly away from the dipalladium core. The structural
impact of the bulky phosphine substituent is perhaps
˚
Table 1. Suzuki couplings catalyzed by 1mol% 3
R
R'
R'
R
R'
R'
base
+
B(OH)2
X
R''
R''
dioxane, 100° C
Entry
R
X
R0
R00
H
Base
Yield (%)17
1
2
H
Cl
Br
Cl
Br
Cl
Cl
Br
Cl
Br
Cl
H, H
H, H
Cs2CO3
Cs2CO3
CsF
97
100
72
91
75
46
48
31
48
40
H
CH3
H
3
H
CH3, H
CH3, H
CH3, CH3
H, H
4
H
H
CsF
CsF
5
H
CH3
H
6
CH3
CH3
CH3
CH3
CH3
CsF
CsF
7
H, H
CH3
H
8
H, CH3
H, CH3
CH3, CH3
CsF
CsF
9
10
H
CH3
CsF

R. C. Smith et al. / Tetrahedron Letters 45 (2004) 8327–8330
8329
met. Chem. 1999, 587, 49; (k) Nagata, K.; Takeda, N.;
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is one of the reaction partners. Notably, moderate to
high yields are observed for the coupling of aryl chlo-
rides with phenylboronic acid (97% for chlorobenzene
using 1mol% 3). The successful coupling of phenylbo-
ronic acid with either 2-chlorotoluene (72%) or 2-chlo-
romesitylene (75%) indicates that coupling of bulkier
aryl halides is also accessible despite the bulk of the
phosphine. This finding may reflect the aforementioned
in situ formation of less bulky and more reactive
monophosphine complexes, although this is currently
speculative and additional studies must therefore be car-
ried out.
2. Walker, S. D.; Barder, T. E.; Martinelli, J. R.; Buchwald,
S. L. Angew. Chem., Int. Ed. 2004, 43, 1871.
3. Miura, M. Angew. Chem., Int. Ed. 2004, 43, 2201.
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5455.
10. Smith, R. C.; Protasiewicz, J. D. Eur. J. Inorg. Chem.
2004, 5, 998.
Depressed yields are observed when the bulkier ortho-
tolylboronic acid is employed under the same condi-
tions, however. Optimization of reaction conditions
and/or variation of alkyl/meta-terphenyl combination
may lead to additional improvements.
11. Smith, R. C.; Protasiewicz, J. D. J. Am. Chem. Soc. 2004,
126, 2268.
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Chem. Soc. 2003, 125, 7816.
In conclusion, a bulky meta-terphenyl substituted
dialkylphosphine has been prepared and structurally
characterized. Three palladium complexes of this phos-
phine have been prepared and one has been structurally
characterized. These complexes hold promise for use in
high yield Suzuki coupling of aryl chlorides and boronic
acids, including sterically hindered aryl chlorides. Fur-
ther investigations into catalytic applications employing
1 and other meta-terphenyl phosphines are currently
underway.
16. Wong-Ng, W.; Cheng, P.-T.; Kocman, V.; Luth, H.;
Nyburg, S. C. Inorg. Chem. 1979, 18, 2620.
17. Yields and product identities were determined by GC–MS
analysis of product mixtures using a Hewlett Packard 5890
Series II gas chromatograph coupled to a Hewlett Packard
5971A mass spectroscopic detector. Analysis and calibra-
tion procedures are detailed in: McMaster, M. C.;
McMaster, C. GC/MS: A Practical Userꢀs Guide; John
Wiley and Sons: New York, 1998.
18. Experimental and physical data for 1–4:1: To a solution of
DmpPCl2 (1.0g, 2.5mmol) in diethyl ether (30mL) at
ꢀ78°C was added MeLi (1.6M in diethyl ether, 3.4mL,
5.4mmol) and the resultant was allowed to come to room
temperature. The solution was filtered and volatiles
removed in vacuo to give a light orange solid. The solid
was taken up in a minimum amount of ether and cooled to
ꢀ35°C for 24h, after which time large white crystals had
formed. The crystals were collected and dried to give 1
(0.585g, 65%). 1H NMR (CDCl3): d 0.72 (d, 6H, J = 4Hz),
2.03 (s, 12H), 2.34 (s, 6H), 6.92 (s, 4H), 6.95 (d, 2H,
J = 7Hz), 7.36 (t, 1H, J = 7Hz); 31P NMR (CDCl3): d
ꢀ36.9. Anal. Calcd for C26H31P: C, 83.39; H, 8.34. Found:
C, 83.14; H, 8.11.
Acknowledgements
The authors thank the National Science Foundation
(CHE-0202040) for support.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2004.09.069. The supplementary data is available online
with the paper in ScienceDirect (crystallographic details
in .cif format for 1 and 4).
References and notes
Compound 2: To a mixture of solids 1 (50mg, 0.13mmol)
and PdCl2(NCPh)2 (25mg, 0.067mmol) was added 3mL of
anhydrous dichloromethane. Upon addition of solvent, the
solution became orange in colour, then quickly faded to
yellow. After 30min of stirring at room temperature, the
volatiles were removed in vacuo to give a pale yellow solid.
The solid was rinsed with hexanes and dried to give 2
1. (a) Some recent references: Kataoka, N.; Shelby, Q.;
Stambuli, J. P.; Hartwig, J. F. J. Org. Chem. 2002, 67,
5553; (b) Hartwig, J. F.; Richards, S.; Baranano, D.; Paul,
F. J. Am. Chem. Soc. 1996, 118, 3626; (c) Chen, H.-P.; Liu,
Y.-H.; Peng, S.-M.; Liu, S.-T. Dalton Trans. 2003, 1419;
(d) Bell, N. A.; Coles, S. J.; Constable, C. P.; Hursthouse,
M. B.; Light, M. E.; Mansor, R.; Salvin, N. J. Polyhedron
2002, 21, 1845; (e) Albert, J.; Bosque, R.; Cadena, J. M.;
Delgado, S.; Granell, J.; Muller, G.; Ordinas, J. I.; Bardia,
M. F.; Solans, X. Chem. Eur. J. 2002, 8, 2279; (f) Xu, X.;
Nieuwenhuyzen, M.; James, S. L. Angew. Chem., Int. Ed.
2002, 41, 764; (g) Matsumoto, T.; Kasai, T.; Tatsumi, K.
Chem. Lett. 2002, 3, 346; (h) Stuer, W.; Wolf, J.; Werner,
H. J. Organomet. Chem. 2002, 641, 203; (i) Alyea, E. C.;
Ferguson, G.; Kannan, S. Polyhedron 2000, 19, 2211; (j)
Yamamoto, Y.; Kawasaki, K.; Nishimura, S. J. Organo-
1
(61mg, 98%) as a pale yellow solid. H NMR (CD2Cl2): d
1.13 (virtual t, 12H, J = 3Hz), 2.05 (s, 24H), 2.27 (s, 12H),
6.84 (s, 8H), 6.88 (d, 4H, J = 7Hz), 7.42 (t, 2H, J = 7Hz);
31P NMR (CD2Cl2):
d
ꢀ10.1. Anal. Calcd for
C52H62Cl2P2Pd: C, 67.42; H, 6.75. Found: C, 68.01; H, 6.62.
Compound 3: To a solution of PdCl2(NCPh)2 (51mg,
0.13mmol) in 3mL of anhydrous dichloromethane was
added a dichloromethane (3mL) solution of 1 (50mg,
0.13mmol) over 1.5min. During addition, the solution
became deep orange in colour. The solution was allowed to
stir at room temperature for 3h and solvent volume was

8330
R. C. Smith et al. / Tetrahedron Letters 45 (2004) 8327–8330
then reduced in volume to incipient crystallization. The
dichloromethane (6mL) solution of 1 (100mg, 0.26mmol)
over about 3min at ꢀ35°C. After 1h the mixture was
allowed to come to room temperature and solvent
removed until incipient crystallization. The mixture was
allowed to stand at ꢀ35°C overnight, over which time
brown crystals formed. The crystals were collected and
dried in vacuo, yielding 4 (140mg, 85%). 1H NMR
(CDCl3): d 1.06 (d, 12H, J = 13Hz), 1.76 (s, 12H),
2.10 (s, 24H), 2.35 (s, 12H), 7.01 (s, 8H), 7.06 (dd, 4H,
JHH = 7Hz, JHP = 3Hz), 7.61 (t, 2H, J = 7Hz);
31P NMR (CDCl3): d 3.7. Anal. Calcd for C61H76Cl2O8-
P2Pd2 (4ÆCH2Cl2): C, 57.11; H, 5.97. Found: C, 57.75; H,
5.85.
solution was allowed to stand for 16h, over which time a
microcrystalline orange-brown solid formed, which was
collected and dried in vacuo to give 3 (93mg, 92%).
Analytically pure material was obtained by slow evapora-
tion from a saturated dichloromethane solution. 1H NMR
(CDCl3): d 1.19 (d, 12H, J = 13Hz), 2.12 (s, 24H), 2.43 (s,
12H), 7.01 (s, 8H), 7.05 (dd, 4H, JHH = 8Hz, JHP = 3Hz),
7.42 (t, 2H, J = 8Hz); 31P NMR (CDCl3):d 8.7. Anal.
Calcd for C53H64Cl6P2Pd2 (3ÆCH2Cl2): C, 53.86; H, 5.21.
Found: C, 54.31; H, 5.36.
Compound 4: To a solution of Pd(OAc)2 (60mg,
0.26mmol) in dichloromethane (6mL) was added a