in the synthesis and in subsequent free radical reactions of
the allylstannane reagent.4e Because a single phase is utilized
with non-cross-linked polystyrene, the reactions have rates
up to 100 times faster than with standard cross-linked solid-
phase methods.4d,5 Moreover, the reactions can be conve-
niently monitored by standard 1H NMR spectroscopy without
cleavage from polymer support.3 Intermediate products used
to prepare the allylstannane reagent and the tin halides
obtained after the radical reaction are obtained as white
crystalline solids filtered from cold methanol.
The resulting polymers were then reacted with allyl alcohol
anion (Scheme 2) to obtain 8a-e and the loading capacity
of the soluble polystyrene and the loading efficiency of the
displacement. Through NMR integration analysis, the ef-
ficiency of the displacement was calculated as shown in
Table 1. Up to a maximum of 33% loading capacity on the
Table 1. Increased Loading Capacity of the Non-Cross-Linked
Polystyrene
An optimization study of the loading capacity of the
polymer revealed that a 2:1 ratio of styrene to p-(chloro-
methyl)styrene functioned best in these experiments and
allowed for a concentrated number of reactive sites on the
polymer, exceeding standard SPOC supports. Allyltin reagent
2b reacted with several electronically deficient carbon-
centered free radical centers and was regioselective in
dihalides where two reactive sites were present in the same
substrate. Another important aspect of these studies is that
this work represents the first time an allylstannane has been
covalently linked to a polymer support, to the best of our
knowledge.6
We began these studies by investigating several concentra-
tions and loading capacities for the polymer backbone. It
was our intention to prepare a polymer with the most
concentrated sites for attachment of the allyl tin. Janda’s
previous work with non-cross-linked polystyrene indicated
that a 0.3 mmol/g (3%) loading capacity polymer functioned
well in a total synthesis of prostaglandin F2R.4e,f Although
this loading capacity was sufficient and possibly ideal for
that work, our efforts focused on maximizing the amount of
loading sites in the soluble polymer. This increases the
density of reactive sites available and allows less polymer
to be used in the reactions.
Loading Capacity:
3%
15% 27% 33% 50%
5 (equiv.)
6 (equiv.)
Non-Cross-Linked Polymer
Allyl Alcohol
% displacement
Allyl Ether
32
1
7a
6.5
1
3.2
1
2
1
1
1
7b
7c
7d
7e
>99
8a
93
92
>99
98
8b
8c
8d
8e
polymer backbone, all substrates functioned well; however,
at concentrations greater than 33%, the polymer becomes
gelatinous and intractable and loses its ability to readily
crystallize from cold methanol. It appears that a practical
balance of 33% active sites is struck between trying to
achieve the largest number of reactive sites with the best
crystallization properties of the polymer itself.
The polystyrene-supported allyltin reagent was prepared
by hydrostannylation of the allyl ether in 8d using the method
of Imori in 90% yield, shown in Scheme 2.7 The disappear-
1
ance of the olefin was readily monitored by H NMR. The
polymer-bound tin chloride was then treated with allylmag-
nesium bromide, which afforded the desired allyltin reagent
2b in 85% yield.
Table 2 shows the free radical reaction of 2b with several
alkyl halides. Electron-poor substrates containing an R-bromo
carbonyl functioned best. Electron-rich alkyl halides (i.e.
bromodecane) did not undergo reaction, and only starting
materials were recovered. It is interesting to note that
hindered tertiary bromide 13 does not react at all with
allyltributyltin (2a) but does react with 2b to give 14 in 50%
yield.8 Allyl product 14 formed in this case due to the
increased nucleophilicity of allylstannane 2b.
The precursors for the preparation of 7d are inexpensive
and allow the polymer to be “tailor-made” by the user via
varying the number of reactive sites desired, as shown in
Scheme 2. Thus, a study was conducted to explore the
Scheme 2
Dihalides in entries 5 and 6 were regioselective in the free
radical allylation reaction, producing 18 and 20 in 66 and
68% yields, respectively. No other allylstannane reagents
show this type of regioselectivity, displaying a strong
preference for an electron-deficient radical.
Because free radical reactions often have polarity prefer-
ences, allyltin reagent 2b is electron-rich and prefers to react
(5) Maher, J. B.; Furey, M. E.; Greenberg, L. J. Tetrahedron Lett. 1971,
27.
(6) For examples of tin hydride reagents mounted on insoluble cross-
linked polystyrene, see: (a) Weinshenker, N. M.; Crosby, G. A.; Wong, J.
Y. J. Org. Chem. 1975, 40, 1966. (b) Dumartin, G.; Pourcel, M.; Delmond,
B.; Donard, O.; Pereyre, M. Tetrahedron Lett. 1998, 4663. (c) Gerlach,
M.; Jordens, F.; Kuhn, H.; Neumann, W. P.; Peterseim, M. J. Org. Chem.
1991, 56, 5971.
(7) Imori, T.; Lu, V.; Cai, H. Tilley, T. D. J. Am. Chem. Soc. 1995, 117,
9931.
(8) (a) Bromides 9 and 15 react with 2b to give 10 (85%) and 16 (78%),
respectively. (b) Li, X.; Chen, J. J.; Tanner, D. D. J. Org. Chem. 1996, 61,
4314.
different loading capacities of the non-cross-linked soluble
polymer. A simple free radical reaction was utilized to
prepare 7a-e, by varying the amounts of 5 and 6 and
investigating the increase in the reactive sites on the polymer
backbone (i.e. loading capacity) from 3 to 50%.4d
690
Org. Lett., Vol. 1, No. 5, 1999
Enholm, Eric J.
