7366
M. Guino´, K. K. Hii / Tetrahedron Letters 46 (2005) 7363–7366
4424; (c) Jang, S. B. Tetrahedron Lett. 1997, 38, 1793–
O
(PS-PCy2)Pd{P(t-Bu)3}
O
Cl
1796; (d) Fenger, I.; Le Drian, C. Tetrahedron Lett. 1998,
39, 4287–4290; (e) Inada, K.; Miyaura, N. Tetrahedron
2000, 56, 8661–8664.
(2 mol%)
N
+
t-BuONa, toluene
N
H
Me
80 oC, 48 h
Me
3. (a) Whitcombe, N.; Hii, K. K.; Gibson, S. E. Tetrahedron
2001, 57, 7449–7476; (b) Bedford, R. B.; Cazin, C. S. J.;
Holder, D. Coord. Chem. Rev. 2004, 248, 2283–2321.
4. Hu, Q. S.; Lu, Y.; Tang, Z. Y.; Yu, H. B. J. Am. Chem.
Soc. 2003, 125, 2856–2857.
First run: >95%
Second run: >95%
Scheme 4. Aryl amination of an aryl chloride.
5. Bedford, R. B.; Coles, S. J.; Hursthouse, M. B.; Scordia,
V. J. M. Dalton Trans. 2005, 991–995.
6. Parrish, C. A.; Buchwald, S. L. J. Org. Chem. 2001, 66,
3820–3827.
7. Guino, M.; Hii, K. K. Tetrahedron Lett. 2005, 46, 6911–
6913.
8. The idea of ÔboomerangÕ catalysis was first demonstrated
with polymer-supported ruthenium catalyst for olefin
metathesis: Ahmed, M.; Barrett, A. G. M.; Braddock,
D. C.; Cramp, S. M.; Procopiou, P. A. Tetrahedron Lett.
1999, 40, 8657–8662.
catalyst is effectively encapsulated within the cross-
linked structure of the polymer, thus protected against
atmospheric degradation, for example, during the recov-
ery process, compared to catalysts bound on the surface.
Other effects may also be exerted by the macroporous
structure, such as the Ôconfinement effectÕ,13 which could
control the rate of diffusion of tri-tert-butylphosphine
from the reactive site, thus enhancing stability.
9. (a) Galardon, E.; Ramdeehul, S.; Brown, J. M.; Cowley,
A.; Hii, K. K.; Jutand, A. Angew. Chem., Int. Ed. 2002, 41,
1760–1763; (b) Stambuli, J. P.; Buhl, M.; Hartwig, J. F. J.
Am. Chem. Soc. 2002, 124, 9346–9347.
Despite the great number of solid-supported palladium
catalysts reported in the literature, very few are able to
catalyse the reaction of aryl chlorides. With this in mind,
the most active catalyst identified from the above study
was used to catalyse the addition of morpholine to the
relatively unactivated aryl halide substrate, 4-chlorotolu-
ene (Scheme 4). Gratifyingly, the reaction proceeded
under relatively mild reaction conditions. Furthermore,
the catalyst could be reused, and product yield remained
unaffected over two runs.
10. Method A: PS-PCy2 (1.24 mmol/g, 500 mg, 0.62 mmol),
Pd2(dba)3 (214 mg, 0.207 mmol), P(t-Bu)3 (10 wt% in
hexane, 0.670 mL, 0.33 mmol) and anhydrous THF
(10 mL) were placed in a round bottom flask under an
atmosphere of N2. The mixture was swirled in an orbital
shaker at rt overnight. The beads were filtered off,
transferred to a sintered Alltech tube and washed with
acetone/CH3OH/H2O (1:1:1) (5 mL · 5), acetone/CH3OH
(1:1) (5 mL · 5), acetone (5 mL · 5), ethyl acetate
(5 mL · 5), CH2Cl2 (3 mL · 5) and finally HPLC-grade
pentane (5 mL · 5). The dark-coloured beads were then
dried under vacuum at 50 ꢁC for 2 h.
In summary, we have synthesised a new class of sup-
ported PS-Pd-P(t-Bu)3 catalysts from readily available
phosphine and polymer supports. The catalysts were ac-
tive in the aryl amination reaction, and the stability and
recyclability were dependent on the nature of the poly-
mer-supported phosphine moiety, as well as on the
way they are prepared. The palladium catalyst immobi-
lised with the dicyclohexylphosphine-functionalised sup-
port displayed the best turnovers, and preliminary
studies showed that it can be used to catalyse amination
reactions of aryl bromides and chlorides, and can be re-
used up to three times with no apparent loss in catalyst
activity. We are currently investigating the nature of the
palladium catalyst present in these polymer resins in
greater detail. Further applications in other palladium-
catalysed processes will be reported in due course.
Method B: PS-PCy2 (1.24 mmol/g, 300 mg, 0.372 mmol),
Pd(dba)2 (143 mg, 0.248 mmol) and P(t-Bu)3 (10% wt in
hexane, 400 lL, 0.198 mmol) and anhydrous THF (8 mL)
were placed in a RadleyÕs carousel reaction tube under an
atmosphere of N2. The mixture was heated at 80 ꢁC
overnight. After cooling, the beads were stirred for a
further 2 h and then collected into a sintered (Alltech) tube
and subjected to washings as stated in the previous
method. The dark brown beads were dried under vacuum
at 50 ꢁC for 2 h.
11. During the reviewing process, one referee commented on
some unusual values presented in Table 1—entries 5 (low
P loading), 8 and 9 (high P loadings)—compared to
original loading of the polymer beads (given in footnote
ÔaÕ). We do not have a reasonable explanation for this at
this juncture. Given that the elemental analyses were
carried out, in duplicate, by professional services on the
same batch of resins, we have no reason to doubt their
accuracy. One possibility is that the loading values
provided by the commercial supplier were erroneous.
The coordination sphere of immobilised Pd is currently
being examined by other techniques, and results will be
reported in due course.
Acknowledgements
The authors thank KingÕs College and Imperial College,
for studentship support, and Johnson Matthey plc, for
the provision of Pd salts.
12. Reactions were performed in parallel in a RadleyÕs 12-
placed reaction carousel. Typical catalytic procedure: A
reaction tube was charged with bromobenzene (106 lL,
1.0 mmol), aniline (91 lL, 1.0 mmol), sodium tert-butox-
ide (150 mg, 1.5 mmol) and the appropriate catalyst
(2 mol%). Anhydrous toluene (2 mL) was added and the
reaction mixture was stirred at 80 ꢁC for 24 h. The
progress of the reaction was monitored by GC.
References and notes
1. (a) Uozumi, Y. Top. Curr. Chem. 2004, 242, 77–112; (b)
Leadbeater, N. E.; Marco, M. Chem. Rev. 2002, 102,
3217–3273, and references cited therein.
2. (a) Andersson, C. M.; Karabelas, K.; Hallberg, A.;
Andersson, C. J. Org. Chem. 1985, 50, 3891–3895; (b)
Grigg, R.; York, M. Tetrahedron Lett. 1997, 38, 4421–
13. Li, C. Catal. Rev. 2004, 46, 419–492.