Scheme 2
Table 1. Catalyst Comparison in the Hydrophosphinylation of
1-Octene with H3PO2
a
aq H3PO2/
concd
50% aq
H3PO2
CH3CN/H2O
10:1
H3PO2
catalyst
rt
reflux
rt
reflux rt
reflux
64
xantphos/Pd2dba3
88
100
79
97
68
0
(62)
(86)
nixantphos/Pd2dba3 91
dppf/Pd2dba3
hydroformylation reactions.3 They have also reported a
powerful catalyst based on the xantphos motif immobilized
on a silicate matrix 3.4 To our knowledge, their immobilized
catalyst has never been tested in hydrophosphinylation
reactions. We have focused on a different approach, which
relies on a single step for the synthesis of a robust
polystyrene-supported ligand 4 from commercially available
reagents (Scheme 2). Reaction of excess polystyryl isocy-
anate (Aldrich or Chemtech) with nixantphos 2 (Strem) in
refluxing toluene directly produces the desired urea-linked
ligand. As expected, the phenoxazine nitrogen in 2 is quite
unreactive and conversions are relatively low (ca. 40%). The
use of refluxing mesitylene does not significantly improve
the yield. The remaining isocyanate functionalities are reacted
with diisopropylamine. Unreacted nixantphos is recovered
essentially pure by washing the polymer and removing the
volatile components, and it can be recycled. Loadings of
0.10-0.33 mmol/g are typically achieved, and no significant
differences between batches are observed in the subsequent
reactions. The active catalyst 5 is then obtained by treating
polymer 4 with Pd2dba3 and washing, if it is not prepared in
situ (Scheme 2). The catalyst is air-stable and does not
require particular handling precautions.
0
10% Pd-C
xantphos/10% Pd-C 83
ligand 4/Pd2dba3
0
0
78
100
(85)
69
82
58
99
0
89
35
78
93
(73)
(61) (100)
77
(64) 80
ligand 4/10% Pd-C
ligand 4/5% Pd-C
ligand 4/Pd(OAc)2
64
93
89
95
(92)
a All yields are NMR yields which are determined by integration of all
the resonances in the 31P NMR spectra. The yields are accurate within 10%
of the value indicated, reproducible, and representative of at least two runs.
Numbers in parentheses correspond to runs conducted in air. Reactions were
conducted with 1.5-2.0 equiv of H3PO2. Reactions at room temperature
require 12-18 h. Reactions at reflux are usually complete in 2-3 h. Runs
conducted in 10:1 CH3CN/H2O require extended reaction times.
for the reaction, but catalyst 5 gives comparable results with
1-octene. The use of 10% Pd-C with xantphos also gives
satisfactory results although the yields are 10-20% lower
than with the homogeneous system, high amounts of water
significantly suppress the reaction, and the reaction time
increases. As expected, the P-C bond-forming reaction does
not take place in the absence of ligand, and transfer
hydrogenation occurs instead. Dppf is completely unsatisfac-
tory to conduct hydrophosphinylation with H3PO2 (Table 1),
whereas it was a good ligand with alkyl phosphinates.1
Catalyst 5 uniformly gives good yields of addition and
appears significantly more water-tolerant than its homoge-
neous counterpart 1/Pd2dba3 (Table 1). Hydrophosphinylation
of 1-octene with catalyst 5 also takes place with BuOP(O)-
H2 in refluxing acetonitrile (100% NMR yield) or with
PhNH3OP(O)H2 (100% in CH3CN, 81% in DMF at 85 °C).5
In addition, the hydrophosphinylation can even be conducted
in air (yields in parentheses in Table 1). Overall, the results
shown in Table 1 for 1-octene indicate that the polymer-
supported catalyst 4/Pd2dba3 is at least as good as the
homogeneous system under a variety of conditions and that
it is significantly more air and water tolerant.
As shown in Table 1, catalyst 5 successfully catalyzes the
hydrophosphinylation of 1-octene with commercial 50 wt
% aqueous H3PO2. When concentrated H3PO2 is employed,
it is prepared by removing the water in vacuo for 20-30
min. Xantphos 1 and even nixantphos 2 are excellent ligands
(1) Depre`le, S.; Montchamp, J.-L. J. Am. Chem. Soc. 2002, 124, 9386.
(2) For example: (a) Bra¨se, S.; Lauterwasser, F.; Ziegert, R. E. AdV.
Synth. Catal. 2003, 345, 869. (b) Leadbeater, N. E.; Marco, M. Chem. ReV.
2002, 102, 3217. (c) van Heerbeek, R.; Kamer, P. C. J.; van Leeuwen, P.
W. N. M.; Reek, J. N. H. Chem. ReV. 2002, 102, 3717. (d) Clapham, B.;
Reger, T. S.; Janda, K. D.Tetrahedron 2001, 57, 4637. (e) Chiral Catalyst
Immobilization and Recycling; De Vos, D. E., Vankelecom, I. F. J., Jacobs,
P. A., Eds.; Wiley-VCH: Weinheim, 2000.
(3) (a) Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Acc.
Chem. Res. 2001, 34, 895. (b) van Leeuwen, P. W. N. M.; Kamer, P. C. J.;
Reek, J. N. H.; Dierkes, P. Chem. ReV. 2000, 100, 2741. (c) van Leeuwen,
P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H. Pure Appl. Chem. 1999, 71,
1443. (c) van der Veen, L.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.
Organometallics 1999, 18, 4765. (d) Kranenburg, M.; van der Burgt, Y. E.
M.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Organometallics 1995, 14,
3081.
As expected, various substrates reacted successfully under
the influence of 5 (Table 2). More importantly, catalyst 5
can be used directly in multiple runs without further addition
of palladium (Table 2), except when DMF is used as the
reaction solvent. With DMF, extensive leaching of the
palladium apparently occurs, and the recovered polymer 4
(4) (a) van Leeuwen, P. W. N. M.; Sandee, A. J.; Reek, J. N. H.; Kamer,
P. C. J. J. Mol. Catal. A 2002, 182-183, 107. (b) Sandee, A. J.; Reek, J.
N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. J. Am. Chem. Soc.
2001, 123, 8468. (c) Sandee, A. J.; van der Veen, L. A.; Reek, J. N. H.;
Kamer, P. C. J.; Lutz, M.; Spek, A. L.; van Leeuwen P. W. N. M. Angew.
Chem., Int. Ed. 1999, 38, 3231.
(5) Results not shown.
3806
Org. Lett., Vol. 6, No. 21, 2004