Advantage of Radical Oligomers in Organic Synthesis
SCHEME 6
Con clu sion
The chemistry detailed above represents a considerable
extension in scope of the novel deoligomerization meth-
5
odology disclosed in our preliminary reports. The unique
characteristic of radical oligomeric mixtures as synthetic
intermediates is that they are self-protected, making
their reactions clean and atom-economical. Complete
oligomerization in a condensation mode appears to be the
condition for deoligomerization.
Exp er im en ta l Section
Typ ica l P r oced u r e for th e Oligom er iza tion . Trieth-
ylborane (0.2 mL, 0.2 mmol, 1 M solution in hexane) was added
to allyl iodoacetate (1, 452 mg, 2.0 mmol) in CH Cl (4 mL)
2 2
and the mixture was stirred at room temperature for 2 h. TLC
1
monitoring showed that 1 was totally consumed. H NMR
monitoring indicated that no vinylic proton signals could be
observed. The resulting solution, which contained the oligo-
meric mixture 5, was then directly used in the following
relatively high reaction temperature. For example, when
copper was used as the radical initiator according to
Metzger’s procedure,13 its reaction with 1a at 140 °C
afforded 2 and 4-iodomethyltetrahydro-2(3H)-furanone as
the normal 5-exo cyclization product in a 3:1 ratio in an
overall 45% yield. Apparently the high temperature
required for the initiation also facilitates the intramo-
lecular cyclization.
1
deoligomerization reactions. Characterization of 5: H NMR
(
4
3
300 MHz, CDCl
3
) δ 1.91-2.26 (2H, m), 2.44-2.68 (2H, m),
.19-4.58 (3H, m). Anal. Calcd for (C IO : C, 26.57; H,
.12. Found: C, 26.82; H, 3.18. The oligomeric mixture 5 was
5
H
7
2 n
)
5a
also characterized by HPLC analysis.
Typ ica l P r oced u r e for th e Syn th esis of P en ten oic
Acid s 6a -e via Deoligom er iza tion . The oligomeric mixture
5
prepared from 1 (2 mmol) as outlined above was concentrated
The other important factor is that the oligomers should
be the condensation oligomers rather than the addition
oligomers (Scheme 6).14 This requires that the adduct
radical 27 generated from the addition of a substarte
radical 26 to a CdC double bond of another substrate
should be quenched by an iodine atom (to give 28) rather
than add to another CdC double bond (to give 29). The
iodoacetates such as 1 meet this requirement because,
in their oligomerization, the trapping rate of the adduct
radicals by an iodine atom is significantly faster than that
by a CdC double bond. Curran and co-workers measured
the rate constants for the halogen atom or aryl chalcogen
in vacuo and the residue was dissolved in THF (20 mL). Zinc
powder (196 mg, 3 mmol) was added to the solution and the
mixture was refluxed for 4 h. The resulting mixture was cooled
to room temperature and hydrochloric acid (2 N) was added
until the pH of the solution was close to 3. The solution was
then extracted with ether (20 mL × 3) and the combined
2 4
organic phase dried over anhydrous Na SO . After removal of
the solvent, the crude product was purified by flash chroma-
tography on silica gel with ethyl acetate/hexane (1/4, v/v) as
the eluent to give the pure product 6a as a colorless liquid.
Yield: 170 mg (85%).
2
,2-Dip h en yl-5-h yd r oxym eth yltetr a h yd r ofu r a n (14a ).
Typ ica l P r oced u r e. The oligomeric mixture 5 prepared from
a (2 mmol) as outlined above was concentrated in vacuo and
(
2 2
X) transfer from XCH CO Et to a primary alkyl radical
1
4
5
in benzene at 50 °C to be about 7 × 10 (for Br), 1 × 10
the residue was dissolved in THF (10 mL). Phenylmagnesium
bromide prepared from PhBr (1.26 g, 8 mmol) and magnesium
powder (0.20 g, 8 mmol) in THF (20 mL) was added dropwise
to the solution at rt and the mixture was further stirred at rt
for 4 h. Hydrochloric acid (2 N) was added until the solution
was slightly acidic. The resulting mixture was then extracted
with ether (20 mL × 3) and the combined organic phase dried
7
7
-1
(
s
for PhSe), 2.3 × 10 (for PhTe), and 2.6 × 10 (for I) M
-
1
15
, respectively. In the meantime, the rate constant
for the addition of a primary radical to a simple alkene
3
4
-1 -1 16
at 50 °C is roughly in the range of 10 to 10 M
s .
On the basis of these kinetic data, iodo and phenyltelluro
acetates should be excellent choices for the condensation
oligomerization. On the other hand, one has to be careful
in planning to use the bromo or phenylseleno analogues,
while chloro derivatives are unlikely to be suitable in the
condensation oligomerization.
2 4
over anhydrous Na SO . After removal of the solvent, the crude
product was purified by flash chromatography on silica gel
with ethyl acetate/hexane (1/4, v/v) as the eluent to give the
pure product 14a as a white solid. Yield: 305 mg (60%).
Ack n ow led gm en t. This project was supported by
the National Natural Science Foundation of China (No.
20002006).
(
(
13) Metzger, J . O.; Mahler, R.; Francke, G. Liebigs Ann. 1997, 2303.
14) For their definitions, see: (a) Carothers, W. H. Chem. Rev. 1931,
8
, 353. (b) Hiemenz, P. C. Polymer Chemistry; Marcel Dekker: New
York, 1984.
(15) (a) Curran, D. P.; Bosch, E.; Kaplan, J . A.; Newcomb, M. J .
Org. Chem. 1989, 54, 1826. (b) Curran, D. P.; Martin-Esker, A. A.;
Ko, S.-B.; Newcomb, M. J . Org. Chem. 1993, 58, 4691.
Su p p or tin g In for m a tion Ava ila ble: Characterizations
of 10 and 14b-g, preparations and characterizations of 25a -
c. This material is available free of charge via the Internet at
http://pubs.acs.org.
(
16) (a) Curran, D. P. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, UK, 1991; Vol. 4, p 715.
b) Curran, D. P.; van Elbury, P. A.; Giese, B.; Gilges, S. Tetrahedron
Lett. 1990, 31, 2861. (c) Fischer, H.; Paul, H. Acc. Chem. Res. 1987,
0, 200.
(
2
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J . Org. Chem, Vol. 69, No. 1, 2004 145