Investigation of bis(tributyltin)-initiated free radical cyclization reactions of 4-pentenyl iodoacetates

Article abstract of DOI:10.1021/jo0109568

Bis(tributyltin)-initiated atom transfer cyclization reactions of 4-pentenyl iodoacetates (1) at 80°C led to the formations of 5-(3-iodopropyl)-substituted dihydro-2(3H)-furanones (3) in high yield. With BF₃·Et₂O as the catalyst, the

Full text of DOI:10.1021/jo0109568

J . Org. Chem. 2002, 67, 1271-1276
1271
In vestiga tion of Bis(tr ibu tyltin )-In itia ted F r ee Ra d ica l Cycliza tion
Rea ction s of 4-P en ten yl Iod oa ceta tes
J unhua Wang and Chaozhong Li*
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road,
Shanghai 200032, P. R. China
clig@pub.sioc.ac.cn
Received September 27, 2001
Bis(tributyltin)-initiated atom transfer cyclization reactions of 4-pentenyl iodoacetates (1) at 80 °C
led to the formations of 5-(3-iodopropyl)-substituted dihydro-2(3H)-furanones (3) in high yield. With
BF3‚Et2O as the catalyst, the reactions were run at room temperature to afford the corresponding
γ-iodoheptanolactones (2), which could be further transformed into 3-(tetrahydro-2-furyl)propanoic
acids (6) upon treatment with aqueous NaHCO3. The reaction mechanism was postulated to be
the 8-endo free radical cyclization to generate γ-iodoheptanolactones which easily underwent
intramolecular nucleophilic substitution to form bicyclic acylium species (7) as the key intermediate.
Subsequent attack by iodide ion furnished γ-lactones while attack by hydroxide ion gave the
tetrahydrofuran derivatives.
Sch em e 1
In tr od u ction
The past two decades have witnessed a rapid growth
in free radical reactions and their applications in organic
synthesis.1 Among them, cyclizations of R-carbonyl radi-
cals leading to the formations of lactones, lactams, and
cycloalkanones are of primary interests due to their great
potential in natural product synthesis. Several methods
have been developed to carry out the cyclization reac-
tions, including the standard tributylstannane method,
a halogen atom transfer method2 with bis(tributyltin) or
triethylborane, and the organomercurial method.3 The
halogen atom transfer annulation method developed by
Curran et al., in particular, has been demonstrated to
be a unique tool in the investigations of R-carbonyl
radical cyclization reactions. For example, sunlamp ir-
radiation of allyl iodoacetate with 10 mol % of bis-
(tributyltin) at 80 °C led to the formation of 4-iodo-
methyltetrahydrofuran-2-one in 41% yield (Scheme 1),
while reaction of allyl bromoacetate with tributyltin
hydride gave only the direct reduction product allyl
acetate.2 More recently, triethylborane-initiated iodine
atom transfer annulation reactions in water have been
reported by Oshima et al.4
While the initial attempts in the cyclization of R-car-
bonyl radicals were concentrated mainly in the prepara-
tions of γ- and δ-lactones,5 recent efforts6 have been put
into the formations of medium and large size lactones
which are difficult to synthesize via traditional lactone-
forming reactions starting from ω-halo- or ω-hydroxy-
carboxylic acids.7 Among them, heptanolactones are the
least accessible ones and only a few examples have been
reported.8 Investigations in the cyclization of (4-pen-
tenoxycarbonyl)methyl radicals in an 8-endo mode have
shown its potential in the preparations of heptano-
lactones.3e,9,10 Russell and Li employed tert-butylmercury
iodide and diphenyl disulfide to react with 4-pentenyl
acrylates to afford the heptanolactones in moderate
(5) (a) Belletire, J . L.; Mahmoodi, N. O. Tetrahedron Lett. 1989, 30,
4363. (b) Clough, J . M.; Pattenden, G.; Wight, P. G. Tetrahedron Lett.
1989, 30, 7469. (c) Hanessian, S.; Di Fabio, R.; Marcoux, J .-F.;
Prud’homme, M. J . Org. Chem. 1990, 55, 3436.
(6) For a review on the synthesis of medium-sized rings via free
radical processes, see: Yet, L. Tetrahedron 1999, 55, 9349.
(7) For reviews, see: (a) Back, T. G. Tetrahedron 1977, 33, 3041.
(b) Rousseau, G. Tetrahedron 1995, 51, 2777.
(8) (a) Funk, R. L.; Abelman, M. M. J . Org. Chem. 1986, 51, 3247.
(b) Buszek, K. R.; Sato, N.; J eong, Y. J . Am. Chem. Soc. 1994, 116,
5511. (c) Andrus, M. B.; Argade, A. B. Tetrahedron Lett. 1996, 37, 5049.
(d) Shiina, I.; Fujisawa, H.; Ishii, T.; Fukuda, Y. Heterocycles 2000,
52, 1105.
(1) For review articles, see: (a) Curran, D. P. Synthesis 1988, 417,
489. (b) J asperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991,
91, 1237. (c) Melikyan, G. G. Synthesis 1993, 833. (d) Iqbal, J .; Bhatia,
B.; Nayyar, N. K. Chem. Rev. 1994, 94, 519. (e) Snider, B. B. Chem.
Rev. 1996, 96, 339. (f) Curran, D. P.; Porter, N. A.; Giese, B.
Stereochemistry of Radical Reactions; VCH: Weinheim, 1996. (g)
Gansauer, A.; Bluhm, H. Chem. Rev. 2000, 100, 2771.
(2) (a) Curran, D. P.; Chang, C.-T. Tetrahedron Lett. 1987, 28, 2477.
(b) Curran, D. P.; Chang, C.-T. J . Org. Chem. 1989, 54, 3140. (c)
Curran, D. P.; Chen, M.-H.; Kim, D. J . Am. Chem. Soc. 1989, 111,
6265. (d) Curran, D. P.; Chang, C.-T. Tetrahedron Lett. 1990, 31, 933.
(e) Curran, D. P.; Tamine, J . J . Org. Chem. 1991, 56, 2746.
(3) (a) Russell, G. A. Acc. Chem. Res. 1989, 22, 1. (b) Russell, G. A.;
Li, C.; Chen, P. J . Am. Chem. Soc. 1995, 117, 3645. (c) Russell, G. A.;
Li, C.; Chen, P. J . Am. Chem. Soc. 1996, 118, 9831. (d) Russell, G. A.;
Li, C. Synlett 1996, 699. (e) Russell, G. A.; Li, C. Tetrahedron Lett.
1996, 37, 2557.
(4) (a) Yorimitsu, H.; Nakamura, T.; Shinokubo, H.; Oshima, K. J .
Org. Chem. 1998, 63, 8604. (b) Yorimitsu, H.; Nakamura, T.; Shi-
nokubo, H.; Oshima, K.; Omoto, K.; Fujimoto, H. J . Am. Chem. Soc.
2000, 122, 11041.
(9) (a) Pirrung, F. O. H.; Steeman, W. J . M.; Hiemstra, H.;
Speckamp, W. N.; Kaptein, B.; Boesten, W. H. J .; Schoemaker, H. E.;
Kamphuis, J . Tetrahedron Lett. 1992, 33, 5141. (b) Pirrung, F. O. H.;
Hiemstra, H.; Kaptein, B.; Martinez Sobrino, M. E.; Petra, D. G. I.;
Schoemaker, H. E.; Speckamp, W. N. Synlett 1993, 739. (c) Pirrung,
F. O. H.; Hiemstra, H.; Speckamp, W. N.; Kaptein, B.; Schoemaker,
H. E. Tetrahedron 1994, 50, 12415. (d) Pirrung, F. O. H.; Hiemstra,
H.; Speckamp, W. N.; Kaptein, B.; Schoemaker, H. E. Synthesis 1995,
458. (e) De Campo, F.; Lastecoueres, D.; Verlhac, J .-B. Chem. Commun.
1998, 2117. (f) De Campo, F.; Lastecoueres, D.; Verlhac, J .-B. J . Chem.
Soc., Perkin Trans. 1 2000, 575.
(10) (a) Lee, E.; Yoon, C. H.; Lee, T. H. J . Am. Chem. Soc. 1992,
114, 10981. (b) Lee, E.; Yoon, C. H.; Lee, T. H.; Kim, S. Y.; Ha, T. J .;
Sung, Y.; Park, S.-H.; Lee, S. J . Am. Chem. Soc. 1998, 120, 7469.
10.1021/jo0109568 CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/17/2002

1272 J . Org. Chem., Vol. 67, No. 4, 2002
Wang and Li
Sch em e 2
Sch em e 3
yield.3e Speckamp and Verlhac treated 4-pentenyl di- or
trichloroacetates with Cu(I) or Fe(II) complexes to give
the corresponding 8-endo cyclization products which
could be transferred to heptanolactones by Bu3SnH/AIBN
reduction.9 Lee et al. used tributyltin hydride and AIBN
to carry out the reaction of 4-pentenyl bromoacetates at
80 °C and obtained the 8-endo cyclization products.
However, the yields were moderate because of the
contamination of the direct reduction products (Scheme
2).10
Compared to the tin hydride method, halogen atom
transfer annulation with bis(tributyltin) or triethylborane
as initiator could be a more efficient way to conduct the
8-endo cyclization. However, to our surprise, the atom
transfer annulation method using bis(tributyltin) or
triethylborane has never been employed in the 8-endo
radical cyclizations of R-carbonyl radicals and sometimes
was omitted from published studies with no clear rea-
sons.4 We were lured to the field by our curiosity of the
above situation.
Sch em e 4
Resu lts a n d Discu ssion
faster isomerization than 2a . For compounds 1g-i,
however, no rearrangement products 3 could be detected
while the corresponding γ-iodoheptanolactones 2g-i
were isolated in high yields (Table 2, method A).
To obtain γ-iodoheptanolactones 2 without contamina-
tion of the rearrangement products 3, we carried out the
cyclization reaction of 1a at lower temperature. The
reaction was very slow at 20 °C and more than half of
1a remained unchanged after 24 h. To accelerate the
reaction, we turned to Lewis acids for help as they were
used to enhance radical reactivity and to improve product
selectivity in many examples.11,12
Among the Lewis acids screened (Yb(OTf)3, Zn(OTf)2,
Mg(OTf)2, BF3‚OEt2), BF3‚OEt2 gave the best result.
When the reaction was carried out with the catalysis of
3 equiv of BF3‚OEt2 at room temperature, all starting 1a
was smoothly consumed within 6 h. TLC monitoring
showed that only 2a was formed while no 3a could be
detected. The usual workup followed by flash chroma-
tography on silica, however, failed to give 2a in pure
form. Careful examination revealed that the cyclization
product was very sensitive to moisture. Thus, when the
purification was performed under strict anhydrous condi-
Tributyltin hydride/AIBN-initiated reaction of 4-pen-
tenyl iodoacetate (1a ) gave mainly the direct reduction
product 4-pentenyl acetate (70%) while less than 15% of
the cyclized product heptanolactone could be isolated.
When 1a was irradiated with the aid of a 300 W sunlamp
in the presence of 10 mol % of bis(tributyltin) in benzene
at 80 °C, it was consumed within 3 h and two products
were formed as indicated by TLC monitoring. GC analy-
sis showed the ratio of the two products to be 80:20. After
usual workup and column chromatography on silica, the
minor product was isolated in 15% yield and its structure
was characterized to be 5-(3-iodopropyl)dihydro-2(3H)-
furanone 3a . However, the major product underwent
decomposition in the column and could not be obtained
in pure form. To get more information on the structure
of the major product, we treated the two products,
without isolation, with 1.5 equiv of tributyltin deuteride
and 5 mol % of AIBN at 80 °C in benzene for 1 h and two
deuterated compounds, 4 and 5, were isolated and
identified. The formation of 4 clearly indicated the major
product to be the expected 8-endo cyclization product 2a
(Scheme 3).
To understand the instability of 2a as well as the
mechanism for the formation of 3a , we carried out the
reaction of 1a at 80 °C for a longer time and TLC and
GC monitoring showed that 2a was converted to 3a
smoothly. After 7 h, 2a was completely consumed and
3a was isolated in 80% yield (Scheme 4).
To gain more information on the isomerization reac-
tion, we tested various substrates, 1b-i. Compounds
1b-f afforded the corresponding 3b-f under the same
reaction conditions (Table 1). In the cases of 1d -f, no
corresponding intermediates 2d -f could be detected by
GC or TLC throughout the reaction, implying their much
(11) For a review article, see: Renaud, P.; Gerster, M. Angew.
Chem., Int. Ed. 1998, 37, 2562.
(12) For more recent examples, see: (a) Sibi, M. P.; J i, J .; Sausker,
J . B.; J aspersse, C. P. J . Am. Chem. Soc. 1999, 121, 7517. (b) Iserloh,
U.; Curran, D. P.; Kanemasa, S. Tetrahedron: Asymmetry 1999, 10,
2417. (c) Dakternieks, D.; Dunn, K.; Tamara Perchyonok, V.; Schiesser,
C. H. Chem. Commun. 1999, 1665. (d) Mero, C. L.; Porter, N. A. J .
Am. Chem. Soc. 1999, 121, 5155. (e) Porter, N. A.; Feng, H.; Kavrakova,
I. Tetrahedron Lett. 1999, 40, 6713. (f) Sibi, M. P.; Rheault, T. R. J .
Am. Chem. Soc. 2000, 122, 8873. (g) Friestad, G. K.; Qin, J . J . Am.
Chem. Soc. 2000, 122, 8329. (h) Munakata, R.; Totani, K.; Takao, K.-
I.; Tadano, K.-I. Synlett 2000, 979. (i) Hayen, A.; Koch, R.; Metzger, J .
O. Angew. Chem., Int. Ed. 2000, 39, 2758. (j) Porter, N. A.; Zhang, G.;
Redd, A. D. Tetrahedron Lett. 2000, 41, 5773. (k) Yang, D.; Ye, X.-Y.;
Xu, M.; Pang, K.-W.; Cheung, K.-K. J . Am. Chem. Soc. 2000, 122, 1658.

Bis(tributyltin)-Initiated Cyclization of 4-Pentenyl Iodoacetates
J . Org. Chem., Vol. 67, No. 4, 2002 1273
Ta ble 1. Com p ou n d s 3 Syn th esized a
Ta ble 2. Com p ou n d s 2 Syn th esized
a
Photostimulation of 1 with 10 mol % of bis(tributyltin) in
benzene at 80 °C for 3-10 h until TLC monitoring showed that
b
the reaction was complete. Isolated yield based on the starting
1. c Determined by 1H NMR.
tions with care, the product 2a was isolated in 80% yield
(Scheme 5). Substrates 1b-d ,g,h ,j,k showed similar
behavior. For compound 1i, the cyclization was slower
probably because of steric hindrance. However, when the
reaction was run at 30 °C for 14 h, an almost quantitative
yield of product 2i was obtained. In the case of 1e,f, no
corresponding product 2 could be isolated in pure form,
which might be ascribed to the steric hindrance or the
very low stability of the products. The results are
summarized in Table 2 (method B). The reactions showed
remarkable regioselectivity and no corresponding 7-exo
cyclization products could be detected.
Although no detailed work was done to elucidate the
function of BF3‚OEt2 in the cyclization reactions, we
presume that the effect of BF3‚OEt2 might be attributed
to its effective coordination with the carbonyl oxygen of
1, which made the R-ester radicals more reactive toward
electron-rich alkenes because of the polar effect. The
ineffectiveness of other Lewis acids screened might be
ascribed to their poor coordination to 1 owing to their
very low solubility in benzene.
a
Method A: photostimulation of 1 with 10 mol % of bis(tribu-
tyltin) in benzene at 80 °C for 3 h. Method B: photostimulation
of 1 with 3 equiv of BF3‚OEt2 and 10 mol % of bis(tributyltin) in
benzene at 20 °C for 3-10 h until TLC showed that the reaction
was complete. Isolated yield based on 1. c Determined by 1H
b
d
NMR. The reaction was run at 30 °C for 14 h.
of 2a under neutral condition showed that one of the
decomposition products was 3-(tetrahydro-2-furyl)pro-
panoic acid (6a ). In light of the above result, we treated
2a with aqueous NaHCO3 in acetone at room tempera-
ture and a high yield of 6a was isolated. Thus, after the
cyclization of 1a was complete, an excess amount of
aqueous NaHCO3 was added and the solution was stirred
at room temperature overnight. After the usual workup,
6a was isolated in 72% yield in this one-pot, two-stage
manner (Scheme 6). The results are summarized in Table
3.
Among the products 2 prepared, 2g-i were relatively
stable and the structure of 2g was further confirmed by
its X-ray diffraction analysis. However, in all other cases,
the products 2 were very sensitive to moisture and
sometimes decomposed within hours at room tempera-
ture. Careful identification of the decomposition products

1274 J . Org. Chem., Vol. 67, No. 4, 2002
Wang and Li
Sch em e 5
Sch em e 7
Sch em e 6
Ta ble 3. Com p ou n d s 6 Syn th esized
Sch em e 8
pot formations of 3 resulted from radical atom transfer
annulation followed by ionic reaction.14 For compounds
2g-i, iodide attack at the C-7 of 7 (C-10a of 2g-i) was
unfavorable because of the phenyl substitution and no
corresponding rearrangement product 3 could be de-
tected. However, hydroxide attack at the carbonyl to form
6 was not affected by the phenyl substitution and 6g was
thus obtained.
To provide further evidence for the mechanism, we
designed the following experiments. Direct reflux of the
cis isomer of 2c in benzene in the dark for 4 h led to the
exclusive formation of the cis isomer of 3c. Treatment of
the trans isomer of 2b in acetone with aqueous NaHCO3
afforded the trans isomer of 6b as the only product
(Scheme 8). Similarly, trans-2c gave trans-3c and cis-
2b gave cis-6b only. The results indicated the reversion
of configuration at the C-5 center of 2, which was
consistent with the proposed mechanism. When 2a was
treated with 4 equiv of NaI in dry acetone at 45 °C for 8
h, it was smoothly consumed to give the rearrangement
a
b
Isolated yield based on the starting 1. Mixture of two
stereoisomers in approximately 1:1 ratio determined by 1H NMR.
c Mixture of two stereoisomers in 25:75 ratio determined by 13C
NMR.
On the basis of the above results, a plausible mecha-
nism could be drawn as depicted in Scheme 7. First,
iodoacetate 1a underwent free radical iodine atom trans-
fer cyclization reaction to afford γ-iodoheptanolactone 2a ,
which might be in equilibrium with the bicyclic acylium
intermediate 713 via intramolecular nucleophilic substi-
tution of the γ-iodide by the “ether” oxygen atom. Upon
heating, the iodide ion attacked the C-7 of 7 to generate
3a (path a). Treatment with aqueous NaHCO3 led to the
hydrolysis of 7 to give 6a (path b). Therefore, the one-
(13) The intermediate 7 was also postulated in the reaction of 6a
with trifluoroacetic anhydride: Grayson, D. H.; Roycroft, E. D. J . Chem.
Soc., Chem. Commun. 1992, 1296.
(14) For radical atom transfer reactions followed by irreversible ionic
reactions, see: (a) Yorimitsu, H.; Wakabayashi, K.; Shinokubo, H.;
Oshima, K. Tetrahedron Lett. 1999, 40, 519. (b) Curran, D. P.; Ko, S.-
B. Tetrahedron Lett. 1998, 39, 6629. (c) J oung, M. J .; Ahn, J . H.; Lee,
D. W.; Yoon, N. M. J . Org. Chem. 1998, 63, 2755. (d) Nagahara, K.;
Ryu, I.; Komatsu, M.; Sonoda, N. J . Am. Chem. Soc. 1997, 119, 5465.

Bis(tributyltin)-Initiated Cyclization of 4-Pentenyl Iodoacetates
J . Org. Chem., Vol. 67, No. 4, 2002 1275
Sch em e 9
indicating the boat conformation of the ester group. NOE
was also observed between the C-3 proton (δ 2.47) and
one of the C-6 protons (δ 1.61). The NOESY spectrum
along with the coupling constants observed in proton
NMR (600 MHz) could be best analyzed according to
conformation 8. For cis-2c, strong NOE between the C-3
product 3a in 68% yield, while less than 5% of 3a could
be achieved under similar experimental conditions with-
out NaI (Scheme 9). This experiment clearly showed the
faster isomerization of 2 catalyzed by iodide ion, indicat-
ing the nucleophilic nature in the rearrangement step.
The above results unambiguously demonstrated that
8-endo cyclization of R-ester radicals is a highly efficient
process and atom transfer annulation is so far the best
method to carry out the transformations. The cyclization
reactions were significantly accelerated by the catalysis
of BF3‚OEt2. Although in the cases of 1e and 1f the
corresponding heptanolactones were not obtained, the
further rearrangement products 3e and 3f could be
achieved in high yield, indicating not only the efficiency
of 8-endo ester cyclization process but also the instability
of heptanolactone products. Our results are in good
agreement with Lee’s calculation that 8-endo ester cy-
clization is the fundamentally preferred mode of reaction
for (alkoxycarbonyl)methyl radicals which might be at-
tributed to the low-energy s-trans conformations of the
radicals in the transition states.10
proton (δ 2.10-2.15) and one of the C-8 protons (δ 3.53)
was observed in its NOESY spectrum, indicating the boat
conformation of the ester group. Strong NOEs were also
observed between the C-3 proton (δ 2.10-2.15) and the
C-5 proton (δ 4.13) and between the C-5 proton (δ 4.13)
and one of the C-8 protons (δ 3.53). These NOEs clearly
showed that cis-2 possessed the boat-chair conformation
9. The conformations 8 and 9 are consistent with Noe’s
calculation in heptanolactone.16 Thus, the “ether” oxygen
(O-1) lying at the backside of the C(5)-I bond readily
attacks C-5 based on the above conformations. Unfortu-
nately, our attempts to grow single crystals of cis-2c and
trans-2c were unsuccessful. Nevertheless, the X-ray
crystal structure of the (5R,6aR,10aâ) isomer of 2k clearly
showed that it possessed the boat-chair conformation as
9. 2g also existed in the boat-chair conformation in the
solid state, which was only slightly distorted from 9 due
to phenyl substitution (Scheme 10).
The easy formation of acylium intermediate 7 should
be associated with the conformations of γ-iodoheptano-
lactones 2. The dipole moment for heptanolactone in the
nonpolar solvent benzene indicates that the major con-
formation of heptanolactone is E (s-cis).15 Noe et al.’s
study16 showed that heptanolactone has two stable
conformations, both possessing the Z conformation and
in boat-chair shape. On the other hand, s-trans confor-
mation in a chair-chair shape was also reported for a
substituted heptanolactone by Speckamp et al.9a To have
a better picture of the conformations of substituted
heptanolactones, we chose 2c for 2D NOESY experi-
ments.
The above halogen atom transfer annulation reactions
provided a convenient and efficient route to the synthesis
of γ-iodoheptanolactones 2, 3-iodopropyl-substituted γ-lac-
tones 3, and tetrahydrofuran derivatives 6. A number of
naturally occurring heptanolactones have been reported
and the free radical pathway should be of potential
application in their synthesis. Furthermore, the rear-
rangement products 3 can be utilized to prepare γ-hy-
droxycycloheptanones by treatment with SmI2 as dem-
onstrated by Molander and co-workers.17
Con clu sion
The two stereoisomers of 2c could be separated by
careful column chromatography on silica. The NOESY
spectrum of trans-2c showed strong NOE between C-3
proton (δ 2.47) and one of the C-8 protons (δ 3.78-3.85),
8-Endo cyclization of R-ester radicals is an intrinsically
favored process and halogen atom transfer annulation
is a highly effective method to carry out the transforma-
tion. The cyclization reactions can be significantly ac-
Sch em e 10. Cr ysta l Str u ctu r es of 2g a n d th e (5r,6a r,10a â) Isom er of 2k

1276 J . Org. Chem., Vol. 67, No. 4, 2002
Wang and Li
removed under reduced pressure. The crude product was
purified by column chromatography on silica gel with hexane-
ethyl acetate (1:1, v:v) as the eluent to obtain pure product 3a
as a colorless oil. Yield: 204 mg (80%). 1H NMR (400 MHz,
CDCl3) δ 1.77-1.84 (2H, m), 1.86-1.97 (2H, m), 1.98-2.08 (1H,
m), 2.32-2.41 (1H, m), 2.55 (2H, dd, J ) 7.1, 9.5 Hz), 3.19-
3.29 (2H, m), 4.48-4.55 (1H, m). 13C NMR (CDCl3) δ 5.9, 27.9,
28.6, 29.2, 36.3, 79.6, 176.7. EIMS: m/z (relative intensity)
255 (M+ + 1, 59), 127 (100), 109 (10), 85 (32), 55 (8), 41 (11).
Anal. Calcd for C7H11IO2: C, 33.09; H, 4.36. Found: C, 33.30;
H, 4.26. The structure was confirmed by its 2D COSY and
HETCOR spectra.
celerated by boron trifluoride etherate. The products,
γ-iodoheptanolactones 2, can be rearranged in high yield
to 3-iodopropyl-substituted γ-lactones 3 upon heating,
while treatment of 2 with aqueous NaHCO3 leads to the
formation of tetrahydrofuran derivatives 6. The mecha-
nism is postulated to be the formation of bicyclic acylium
intermediate 7 via intramolecular nucleophilic substitu-
tion.
Exp er im en ta l Section
NMR spectra were recorded in CDCl3 or C6D6 (1H at 300 or
400 MHz and 13C at 75.47 MHz) using TMS as the internal
standard. All melting points were uncorrected. Most products
were isolated by column chromatography on silica gel with
hexane-ethyl acetate or acetone in the appropriate ratio as
the eluent. Photostimulated reactions utilized a 300 W fluo-
rescent sunlamp. Benzene was dried over CaH2 and freshly
distilled prior to use. Boron trifluoride etherate was distilled
and stored under nitrogen. The preparation of substrates that
were not commercially available is summarized in the Sup-
porting Information.
5-Iod o-2-oxoca n on e (2a ). Typ ica l P r oced u r e. Boron
trifluoride etherate (0.37 mL, 3 mmol) was added to a benzene
(33 mL) solution of 4-pentenyl iodoacetate (1a , 254 mg, 1.0
mmol) in a dry, 50 mL three-necked flask under nitrogen at
room temperature. Bis(tributyltin) (0.050 mL, 0.1 mmol) was
added and the mixture was irradiated at 20 °C with the aid of
a 300 W sunlamp. The reaction was monitored by TLC. After
the substrate 1a disappeared (6 h), the resulting mixture was
concentrated under reduced pressure. The crude product was
purified by flash chromatography on silica gel with dry
hexane-ethyl acetate (2:1, v:v) as the eluent to afford the
product 2a as a colorless oil. Yield: 203 mg (80%). 1H NMR
(300 MHz, C6D6) δ 1.12-1.20 (2H, m), 1.43-1.59 (2H, m),
1.78-1.86 (1H, m), 1.92-1.99 (2H, m), 2.02-2.10 (1H, m), 3.53
(1H, dt, J ) 12.1, 5.4 Hz), 3.76-3.89 (2H, m). 13C NMR (C6D6)
δ 30.8, 31.4, 32.0, 35.2, 39.8, 66.5, 174.7. EIMS: m/z (relative
intensity) 255 (M+ + 1, 27), 237 (4), 209 (1), 127 (100), 109
(8), 85 (33), 81 (13). HRMS calcd for C7H11IO2: 253.9804.
Found: 253.9833.
3-(Tet r a h yd r o-2-fu r yl)p r op a n oic Acid (6a ). Typ ica l
P r oced u r e. Boron trifluoride etherate (0.37 mL, 3 mmol) was
added to a benzene (33 mL) solution of 4-pentenyl iodoacetate
(1a , 254 mg, 1.0 mmol) in a dry, 50 mL three-necked flask
under nitrogen at room temperature. Bis(tributyltin) (0.050
mL, 0.1 mmol) was added and the mixture was irradiated at
20 °C for 6 h with the aid of a 300 W sunlamp. A saturated
aqueous NaHCO3 solution (12 mL) was added and the result-
ing mixture was stirred vigorously for 10 min. The mixture
was evaporated under reduced pressure to allow most of the
solvent benzene to be removed. Acetone (30 mL) was added to
the residue and the mixture was stirred in dark at room
temperature overnight. The resulting solution was concen-
trated in vacuo, washed with CH2Cl2 (2 × 10 mL), and then
acidified with aqueous HCl (1 N). The solution was extracted
with ether (6 × 30 mL) and the combined organic phase was
dried over anhydrous MgSO4. After removal of the solvent, the
crude product was purified by flash chromatography on silica
gel with hexane-acetone (2:1, v:v) as the eluent to give pure
1
6a 13,14a as a colorless oil. Yield: 104 mg (72%). H NMR (300
MHz, CDCl3) δ 1.41-1.53 (1H, m), 1.77-2.04 (5H, m), 2.35-
2.53 (2H, m), 3.68-3.76 (1H, m), 3.80-3.92 (2H, m), 9.89 (1H,
br). 13C NMR (CDCl3) δ 25.7, 30.4, 31.0, 31.2, 67.8, 78.3, 178.9.
EIMS: m/z (relative intensity) 145 (M++1, 0.9), 144 (M+, 0.4),
127 (4), 116 (10), 98 (7), 85 (16), 71 (100), 55 (11), 43 (53).
HRMS calcd for C7H10O2 (M - H2O): 126.0681. Found:
126.0634.
Ack n ow led gm en t. This project is supported by the
Hundreds of Talent program of the Chinese Academy
of Sciences, by the National Natural Science Foundation
of China (No. 20002006 and No. 29832050), and by the
QiMingXing Program of the Shanghai Municipal Sci-
entific Committee. We also thank Dr. Xicheng Dong and
Ms. Weiqi Zhang for their help in theoretical calcula-
tions.
5-(3-Iod op r op yl)d ih yd r o-2(3H)-fu r a n on e (3a ). Typ ica l
P r oced u r e. Bis(tributyltin) (0.050 mL, 0.1 mmol) was added
to a benzene (33 mL) solution of 4-pentenyl iodoacetate (1a ,
254 mg, 1.0 mmol) in a dry, 50 mL three-necked flask under
nitrogen at room temperature. The reaction mixture was
heated to reflux and irradiated with the aid of a 300 W
sunlamp. The reaction was monitored by TLC. After the
substrate 1a disappeared (3 h), the sunlamp was turned off
and the reaction mixture was kept at reflux for an additional
7 h. The resulting mixture was cooled and the solvent was
Su p p or tin g In for m a tion Ava ila ble: General procedure
for the preparations of 1a -k . Characterization data for
compounds 1a -k , 2b-k , 3b-f, 4, and 6b,c,d ,g,j. X-ray crystal
structural data for 2g and the (5R,6aR,10aâ) isomer of 2k . This
material is available free of charge via the Internet at
http://pubs.acs.org.
(15) Huisgen, R.; Ott, H. Tetrahedron 1959, 6, 253.
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64, 4586.
(17) (a) Molander, G. A.; Alonso-Alija, C. J . Org. Chem. 1998, 63,
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(18) Agorrody, M.; Montaudon, E.; Maillard, B. Can. J . Chem. 1987,
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