reactions and linking agents, and (general approach 2) soluble
polymer-supported asymmetric radical reactions using em-
bedded carbohydrates as chiral scaffolds. This reaction
represents the first example of diastereoselective radical
reaction on soluble support. We hope these two approaches
will lead to useful studies in the new and promising field of
free radical reactions on soluble support.
Scheme 2
Although showing some success, cross-linked resin sup-
ports for the current state-of-the-art solid-phase organic
chemistry (SPOC) still have many drawbacks to address.
Soluble supports for free radical reactions avoid many of
these difficulties and have several distinct advantages.5 These
include (1) complete organic solubility (EtOAc, benzene,
CHCl3, CH2Cl2, and THF) of compounds, (2) more reactive
sites on the polymer, providing a substantial 2- to 3-fold
increase, (3) ability to stir reactions with a standard stir-bar,
(4) convenient monitoring of radical reactions by standard
1H NMR spectroscopy without cleavage from polymer
support, and (5) virtually quantitative yield of allylated
products after the radical reaction, obtained as tin-free white
crystalline-like solids from cold methanol.2,3
allylated esters 5 and 6 were hydrolyzed to give pentenoic
acid and 4-methyl-4-pentenoic acid, respectively. The loading
of the soluble polymer 3 was near quantitative as determined
1
by H NMR, or a very high 2.7-3.0 mmol/g.
Once we had established that NCPS polymers functioned
well in radical allylations and organotin byproducts could
be removed by precipitation of the products, we turned our
attention to diastereoselective allylations using the protected
D-xylose pentose 7 as a means of asymmetric control
(Scheme 3).6 We reasoned that with a C1-C2 acetonide
Benzyl chloride NCPS polymer 3, prepared by radical
polymerization of styrene (2 equiv) and p-chloromethylsty-
rene (1 equiv) was converted to a benzyl alcohol via an ester
displacement followed by a saponification, as shown in
Scheme 1. Bromoester 4 was then prepared by a coupling
Scheme 3
Scheme 1
reaction with DCC and bromoacetic acid (68% for three
steps). Treatment of 4 with allyltributyltin and methallyl-
tributyltin under free radical conditions, shown in Scheme
2, provided two allylated products 5 (96% yield) and 6 (98%
yield) with near quantitative recovery of the polymer and
complete conversion as determined by 1H NMR. The
effectively blocked the R-face oxygens of 7 for chelation.
The remaining oxygens at C3, C4, and C5 would be available
for a tridentate chelate on the â-face of the ring. An initial
concern was that the sugar would be too far from the reacting
radical center at the C3-carbon would exert almost no control
in an allyl transfer. A second concern was the effect the
polymer backbone would have on the diastereoselectivity of
the reaction. A third concern was the potential for cleavage
of the sugar from the backbone in the presence of strong
Lewis acids.
Because carbohydrates have not been studied as removable
chiral auxiliaries for radical reactions, this reaction had to
be separately investigated off-support, as shown in Scheme
3. Thus, R-bromo ester 8 was prepared from commercially
available xylose derivative 7. Protection of the C5-hydroxyl
in 7 as a benzyl ether, followed by DCC-mediated coupling
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