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P. E. Berget et al. / Tetrahedron Letters 48 (2007) 8101–8103
R1
R2
R1
R2
1.
OH
HO
1. LAH, THF, 0 ºC
O
O
2. NaOH, H2O
18-Crown-6, K2CO3,
6b, R1 = H,
3. CBr4, Ph3P, THF
THF, 60 ºC, 2 d
R2 = (CH2C5H4)CpTiCl2
O
O
4a
4. NaCp, THF
5. KH, THF
6. CpTiCl3
6c, R1 = CH2=CH,
2. 4b or 4c, 18-Crown-6,
K2CO3, THF, 60 ºC,1 d
R2 = (CH2C5H4)CpTiCl2
9, R1 = polystyrene,
R2 = (CH2C5H4)CpTiCl2
O
O
5b, R1 = H, R2 = MeO2C
5c, R1 = CH2=CH, R2 = MeO2C
Scheme 1. Synthesis of first-generation titanocene dendrimers.
We had previously employed the multicomponent
butene synthesis described by Watabe et al., Eq. 3,6 as
a test for the catalytic activity of titanocenes such as 1.
We found that in THF solution, monomeric dendrimer
6b functioned identically to Cp2TiCl2, giving butene 7 in
Cl
Ti
O
Cl
O
1
O
96% yield by H NMR as an 87:13 E/Z mixture. The
same results were obtained in isopropylbenzene, indicat-
ing that the reaction is compatible with a polystyrene
framework. The sole byproduct in all applications of
this process is dimethylphenylvinylsilane, which results
from the uncatalyzed reaction that competes with the
Ti-catalyzed butene synthesis.
O
O
Cl
Cl
Ti
O
Cl
Cl
O
Ti
MgBr,
Cp2TiCl2, THF
O
Si
Si Cl
O
Si
0 ºC, 3 h
7
Cl
Cl
O
Ti
ð3Þ
8
A number of styryl-functionalized dendrimers that
function as polymerization monomers are known.7 In
a manner similar to the synthesis of 6b we prepared
first-generation crosslinking bis-titanocene monomer
6c in 44% overall yield from 4c. We also constructed
small amounts of second-generation tetrakis-titanocene
8. We prepared the third-generation octabromo species,
but got no further as subsequent steps gave only intrac-
table material. The intermediates in these syntheses were
stable as solids but sensitive toward polymerization in
solution. The first-, second-, and third-generation
brominated species proved to be easiest to handle and
to obtain pure.
initially gave 80% yield of butene product. Product
removal and addition of more substrate in both cases
gave 75% conversion in a second run and 60% in a third.
A fourth run gave 22% butene using 2 and 8% from 9
(remainder Me2PhSiCH@CH2). As discussed previ-
ously,1 we suspect that the reduction in reactivity derives
from at least two causes: formation of Ti complexes of
unknown structure that cannot reenter the catalytic cycle
and buildup of salts within the polymer that inhibit
substrate-catalyst interaction, allowing the uncatalyzed
solution-phase vinylsilane formation to compete.
Significantly, the lightly loaded disks 9 gave aggregate
turnover numbers four times greater than disks 2:
2.7 mmol substrate was converted to product by
0.017 mmol Ti in 9 (TON = 159) versus 2.9 mmol con-
verted by 0.074 mmol Ti in 2 (TON = 39). Evidently
the lower crosslinking in 9 more than offsets the reduced
Ti loading relative to 2, giving rise to much improved
catalytic efficiency. Indeed, the results from 9 also
exceed the TON reported for the original solution-phase
Cp2TiCl2-based system by nearly a factor of three
(Table 1). In contrast, heavily loaded Wang-derived
titanocene dichloride-containing beads gave very poor
results: <10% in each of the two runs, corresponding
essentially to stoichiometric activity. It is possible that
the monolith polymer environment is protecting the
organometallic from deactivation under the reaction
To evaluate the access of reagents to the interior of poly-
merized dendrimeric disks we polymerized styrene and
brominated dendron 4c in a 5 mm ID test tube. The
resulting disks, 0.85% crosslinked assuming complete
reaction of vinyl groups, swelled nearly twice as much
in THF as did disks of 1% DVB-crosslinked polystyrene.
Polymerization of 6c gave disks of 9 (Scheme 1) contain-
ing 0.113 mmol/g Ti, corresponding to 0.64% crosslink-
ing, much lower than disks 2 (0.312 mmol/g Ti). Yet
disks 9 significantly outperformed disks 2. In our low-tech
batch-flow reactor,1 disks 9 gave significant catalytic
activity, and, like disks 2, could be recycled through three
runs after which reactivity dropped. Both polymers
Berget, Patrick E.
