Radical [3 + 2] cycloaddition reaction with various alkenes using iodomethylcyclopropane derivatives as new homoallyl radical precursors

Article abstract of DOI:10.1021/jo010950i

Radical iodine atom transfer [3 + 2] cycloaddition with various alkenes using dimethyl 2-(iodomethyl) cyclopropane-1,1-dicarboxylate and 1,1-bis(phenylsulfonyl)-2-(iodomethyl)cyclopropane as new precursors of a homoallyl radical species smoothly proceeds to give functionalized cyclopentane derivatives in good yields.

Full text of DOI:10.1021/jo010950i

922
J . Org. Chem. 2002, 67, 922-927
Ra d ica l [3 + 2] Cycloa d d ition Rea ction w ith Va r iou s Alk en es
Usin g Iod om eth ylcyclop r op a n e Der iva tives a s New Hom oa llyl
Ra d ica l P r ecu r sor s
Osamu Kitagawa, Yoichiro Yamada, Hiroki Fujiwara, and Takeo Taguchi*
Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, J apan
taguchi@ps.toyaku.ac.jp.
Received September 25, 2001
Radical iodine atom transfer [3 + 2] cycloaddition with various alkenes using dimethyl 2-(iodom-
ethyl)cyclopropane-1,1-dicarboxylate and 1,1-bis(phenylsulfonyl)-2-(iodomethyl)cyclopropane as new
precursors of a homoallyl radical species smoothly proceeds to give functionalized cyclopentane
derivatives in good yields.
Sch em e 1
In tr od u ction
The [3 + 2] cycloaddition reaction of a homoallyl radical
species with an alkene is a powerful means for one-pot
transformation to a cyclopentanoide skeleton from simple
substrates.1,2 Especially, the reaction of electrophilic
homoallyl radicals such as allylated active methine
radicals would be synthetically very useful, because
simple alkyl-substituted alkenes (without any activating
groups such as electron-withdrawing groups) can be used
as the partners.2 As the precursors of such electrophilic
homoallyl radical species, the use of vinylcyclopropane
derivatives having an electron-withdrawing group on the
ring1e,f,2a,c and allylated R-iodo-active methine deriva-
tives2b,d,e has been reported, while there still remain
several problems in these methods. For example, in
Feldman and Oshima’s method using vinylcyclopropane
derivatives, a large excess of alkenes (15-50 equiv) is
required1e,f,2a and there is no description concerning an
application to less reactive 1,2-disubstituted alkenes.1e,f,2a,b
On the other hand, although Curran et al. have succeeded
in reactions with various 1-alkenes and 1,1- and 1,2-
disubstituted alkenes by the use of allyl-R-iodomalono-
nitrile,2d,e it was not applicable to the reaction with
electron-rich alkenes such as enol ethers because of the
nature as an electrophilic iodine source of the unstable
allyl-R-iodo-active methine.3
bis(phenylsulfonyl)-2-(iodomethyl)cyclopropane (2; E )
SO2Ph) as new homoallyl radical precursors. That is,
these iodomethylcyclopropane derivatives 1 and 2 can be
easily prepared through the iodocarbocyclization of al-
lylated active methines previously found by our group4
and may produce electrophilic homoallyl radicals 1A and
2A via the regioselective C(2)-C(1)E2 bond cleavage of
cyclopropylmethyl radicals formed by the reaction with
a radical initiator (Scheme 1).2a,5 Successively, the result-
ing 1A and 2A would possibly give iodoalkylated cyclo-
pentane derivatives 3 and 4 through a radical iodine
atom transfer reaction with alkenes (Scheme 1).6 In
contrast to vinylcyclopropane2a and allyl-R-iodo-active
methine2b,d,e derivatives, the use of radical precursors 1
and 2, which do not have an alkene part, may also lead
to an increase in the chemical yield, because a side
reaction such as the attack of the resulting homoallyl
We have been interested in dimethyl 2-(iodomethyl)-
cyclopropane-1,1-dicarboxylate (1; E ) CO2Me) and 1,1-
* To whom correspondence should be addressed. Fax and tel: +81-
426-76-3257.
(1) The reaction with electron-deficient alkenes: (a) Clive, D. L. J .;
Angoh, J . Chem. Soc., Chem. Commun. 1985, 980. (b) Cekovik, Z.;
Saicic, R. Tetrahedron Lett. 1986, 27, 5893. (c) Curran, D. P.; Chen,
M. J . Am. Chem. Soc. 1987, 109, 6558. (d) Barton, D. H. R.; Zard, S.
Z.; da Silva, E. J . Chem. Soc., Chem. Commun. 1988, 285. (e) Feldman,
K. S.; Romanelli, A. L.; Ruckle, R. E., J r.; Miller, R. F. J . Am. Chem.
Soc. 1988, 110, 3300. (f) Feldman, K. S.; Ruckle, R. E., J r.; Romanelli,
A. L. Tetrahedron Lett. 1989, 30, 5845. (g) Chuang, C. P.; Ngoi, T. H.
J . J . Chin. Chem. Soc. 1991, 38, 379. (h) Curran, D. P. In Compre-
hensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon
Press: New York, 1991; Vol. 4, p 779, and references therein.
(2) The reaction with simple alkenes: (a) Miura, K.; Fugami, K.;
Oshima, K.; Utimoto, K. Tetrahedron Lett. 1988, 29, 5135. (b) Curran,
D. P.; Chen, M.; Spletzer, E.; Seong, C. M.; Chang, C. J . Am. Chem.
Soc. 1989, 111, 8872. (c) Singleton, D. A.; Church, K. M. J . Org. Chem.
1990, 55, 4780. (d) Curran, D. P.; Seong, C. M. Tetrahedron 1992, 48,
2157. (e) Curran, D. P.; Seong, C. M. Tetrahedron 1992, 48, 2175.
(3) Curran D. P.; Eichenberger, E.; Collis, M.; Roepel M. G.; Thoma,
G. J . Am. Chem. Soc. 1994, 116, 4279
(4) For our review in relation to iodocarbocyclization: Kitagawa, O.;
Taguchi, T. Synlett 1999, 1191.
(5) For reviews in relation to the rearrangement of the cyclopropy-
lcarbinyl radical to the homoallyl radical: (a) Motherwell, W. B.; Crich,
D. Free Radical Chain Reactions in Organic Synthesis; Academic
Press: London, 1991. (b) Nonhebel, D. C. Chem. Soc. Rev. 1993, 347.
(c) Dowd, P.; Zhang, W. Chem. Rev. 1993, 93, 2091.
(6) For reviews in relation to the reaction of carbon-centered
radicals: (a) Giese, B. Radicals in Organic Synthesis: Formation of
Carbon-Carbon Bonds; Pergamon Press: New York, 1986. (b) Curran,
D. P. Synthesis 1988, 417. (c) J asperse, C. P.; Curran, D. P.; Fevig, T.
L. Chem. Rev. 1991, 91, 1237. (d) Motherwell, W. B.; Crich, D. Free
Radical Chain Reactions in Organic Synthesis; Academic Press:
London, 1992. (e) Fossey, J .; Lefort, D.; Sorba, J . Free Radicals in
Organic Chemistry; Wiley: New York, 1995. (f) Curran, D. P.; Porter,
N. A.; Giese, B. Stereochemistry of Radical Reactions; VCH: New York,
1996. For a review in relation to radical atom transfer reaction: (g)
Curran, D. P. Synthesis 1988, 489.
10.1021/jo010950i CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/15/2002

New Homoallyl Radical Precursors
J . Org. Chem., Vol. 67, No. 3, 2002 923
Ta ble 1. Ra d ica l Iod in e Atom Tr a n sfer [3 + 2]
Cycloa d d ition of 1 w ith Va r iou s Electr on -Rich Alk en es
Sch em e 2
Sch em e 3
radical at the precursors can be disregarded. In addition,
since the chemically stable 1 and 2, in comparison with
allyl-R-iodo-active methine derivatives, are not electro-
philic iodine sources, reactions with electron-rich alkenes
may be also possible. In this paper, we report radical
iodine atom transfer [3 + 2] cycloaddtion with various
alkenes using 1 and 2 as new homoallyl radical precur-
sors.7,8
a
b
Isolated yield. The ratio was determined on the basis of
isolated yield. c The hydroxycyclopentane 3b was obtained after
d
desilylation by treatment with 5% HCl. 3c and 3c′ were obtained
in a ratio of 3:1. e Other stereoisomers could not be detected by
300 MHz 1H NMR and 75 MHz 13C NMR. f The ratio was
determined by 1H NMR.
Resu lts a n d Discu ssion
[3 + 2] cycloaddition reaction of 1 with various electron-
rich alkenes (2 equiv) such as enol ethers and enamide
smoothly proceeds in the presence of Et3B (1 equiv)12 in
CH2Cl2 to give iodoalkylated cyclopentane derivatives 3
in good yields (Table 1). For example, the reaction of 1
with butyl vinyl ether and silyl enol ether gave function-
alized cyclopentane derivatives 3a and 3b in good yields
(3a , 66%; 3b, 79%), respectively, while the diastereo-
selectivities of these reactions were low (3a , cis/trans )
1.2; 3b, cis/trans ) 1/1.8) (entries 1 and 2).13
In the reaction with 2,3-dihydrofuran, oxygen-contain-
ing bicyclic products 3c and 3c′ were obtained with
almost complete diastereoselectivity (entry 3). In this
reaction, the isomer having an iodomethyl (3c) or a
methyl (3c′) group of endo orientation on the bicyclo-
[3.3.0]octane ring was selectively formed.13 Such prefer-
ential formation of the endo isomer, which is thermo-
dynamically unfavorable relative to the exo isomer, has
also been observed in the reaction of allylated iodo-
malononitrile with cyclopentene reported by Curran et
al.2e,14 Since separation of iodide 3c and reduction product
3c′ formed in a ratio of 3/1 through this reaction was
difficult, the product was isolated after complete conver-
sion to 3c′ by subsequent treatment with (Me3Si)3SiH and
AIBN (59% overall yield).
Syn th esis of Iod om eth ylcyclop r op a n e Der iva -
tives (Hom oa llyl Ra d ica l P r ecu r sor s). To avoid dia-
stereomeric complication in the products, we chose
dimethyl 2-(iodomethyl)cyclopropane-1,1-dicarboxylate
(1) and 1,1-bis(phenylsulfonyl)-2-(iodomethyl)cyclopro-
pane (2), having the same electron-withdrawing groups
at C1 as electrophilic homoallyl radical precursors.
According to our previous report, 1 could be prepared in
good yield through Ti(OR)4-mediated iodocarbocyclization
of allylmalonate (Scheme 2).9 Beckwith’s method using
NaH and I2 was also usable for the efficient preparation
of 1 (Scheme 2).10 The bis(phenylsulfonyl) cyclopropane
derivative 2 could be obtained in 54% yield through the
iodocarbocyclization of allylbis(phenylsulfonyl)methane
using TiCl4-Et3N,11 while Ti(OR)4-mediated iodocarbo-
cyclization did not afford 2 (Scheme 3). Although Beck-
with’s method10 also gave 2 in 49% yield, in this case the
formation of a side product which is difficult to separate
from 2 was observed (Scheme 3).
Ra d ica l Iod in e Atom Tr a n sfer [3 + 2] Cycloa d d i-
tion Rea ction u sin g Dim eth yl 2-(Iod om eth yl)cyclo-
p r op a n e-1,1-d ica r boxyla te (1). Initially, the radical [3
+ 2] cycloaddition reaction with electron-rich alkenes
using dimethyl 2-(iodomethyl)cyclopropane-1,1-dicarbox-
ylate (1) as a homoallyl radical precursor was investi-
gated. It was found that the radical iodine atom transfer
The present reaction can be applied to not only enol
ether derivatives but also an enamide derivative. In this
case, aminocyclopentane derivative 3d was obtained with
high cis selectivity (cis/trans ) 18) in good yield (76%)
(entry 4). The higher diastereoselectivity as compared to
(7) Preliminary communication of this work: Kitagawa, O.; Fuji-
wara, H.; Taguchi, T. Tetrahedron Lett. 2001, 42, 2165.
(8) In relation to the present reaction of (iodomethyl)cyclopropane
derivatives, we have recently succeeded in the development of radical
iodine atom transfer [3 + 2] cycloaddition reactions with alkenes using
N-tosyliodoaziridine as a new aza-homoallyl radical precursor: Kita-
gawa, O.; Yamada, Y.; Fujiwara, H.; Taguchi, T. Angew. Chem., Int.
Ed. 2001, 40, 3865.
(12) Oshima, K.; Uchimoto, K. J . Synth. Org. Chem. J pn. 1989, 47,
40.
(13) The stereochemistries of the products were determined on the
basis of NOESY measurement or comparison of the chemical shift of
the iodomethyl group in the 13C NMR. In general, the chemical shift
of the iodomethyl group in cis isomers appears upfield from that of
trans isomers.
(9) (a) Kitagawa, O.; Inoue, T.; Taguchi, T. Tetrahedron Lett. 1992,
33, 2167. (b) Inoue, T.; Kitagawa, O.; Ochiai, O.; Taguchi, T. Tetrahe-
dron: Asymmetry 1995, 6, 691.
(10) Beckwith, A. L.; Zozer, M. J . Tetrahedron Lett. 1992, 33, 4975.
(11) Kitagawa, O.; Suzuki, T.; Inoue, T.; Watanabe, Y.; Taguchi, T.
J . Org. Chem. 1998, 63, 9470.
(14) The model to rationalize such endo selectivity in the bicyclo-
[3.3.0]octane system has been reported by Curran et al.: Curran, D.
P.; Rakiewicz, D. M. Tetrahedron 1985, 41, 3943.

924 J . Org. Chem., Vol. 67, No. 3, 2002
Kitagawa et al.
F igu r e 2. Additive effect of Yb(OTf)3 in the reaction with 1.
Ta ble 3. Ra d ica l Iod in e Atom Tr a n sfer [3 + 2]
Cycloa d d ition of 1 w ith Va r iou s Alk yl Su bstitu ted
Alk en es
F igu r e 1. Stereochemical model accounting for the cis
selectivity in the reaction of 1 with enamide.
Ta ble 2. Ad d itive Effect in Ra d ica l Iod in e Atom
Tr a n sfer [3 + 2] Cycloa d d ition of 1 w ith 1-Hexen e
yield
cis/
entry
1
additive
conditions
(%)a transb
Et3B (1 equiv)
CH2Cl2,
22
8.8
room temp
C6H6, reflux
(Me3Sn)2 (0.1 equiv), hν C6H6
Et3B (1 equiv), Yb(OTf)3 CH2Cl2,
2
AIBN (0.05 equiv)
4
40
87
3
7.5
8.8
4c
(1 equiv)
room temp
5c
Et3B (1 equiv), Yb(OTf)3 CH2Cl2, 0 °C
(1 equiv)
82
11.2
a
b
Isolated yield. The ratio was determined by 13C NMR. c Air
(20 mL) was introduced with a syringe.
those in the reactions with vinyl ethers may be rational-
ized on the basis of the cyclization model in Figure 1:
that is, in the chairlike cyclization model having an
equatorial olefin part, the more bulky imide group as
compared to the butoxy or siloxy group should prefer
equatorial orientation such as in model B* to avoid 1,3-
diaxial repulsion. Accordingly, the cyclization reaction
should preferentially proceed through model B* over
model A*, having an axial imide group, to give the
product 3d with high cis selectivity.
a
b
Isolated yield. The ratio was determined by 75 MHz 13C
NMR. c Five equivalents of alkene was used. Two stereoisomers
were mainly obtained, while the sterochemistries were not deter-
mined. e The ratio was determined by 1H NMR.
d
The radical [3 + 2] cycloaddition reaction with simple
alkyl-substituted alkenes was further examined. In
contrast to the reaction with electron-rich alkenes, reac-
tion of 1 with 1-hexene gave the product 3e in poor yield
(22%) under the same conditions (Table 2, entry 1). No
remarkable improvement was observed under other
radical iodine atom transfer conditions such as AIBN and
(Me3Sn)2-hν (entries 2 and 3). On the other hand, the
addition of Yb(OTf)3 was found to lead to a remarkable
increase in the chemical yield.15,16 Thus, the reaction with
1-hexene (2 equiv) at room temperature in the presence
of Et3B (1 equiv) and Yb(OTf)3 (1 equiv) gave 3e in good
yield (87%) with high diastereoselectivity (cis/trans ) 8.8)
(entry 4). When the same reaction was performed at 0
°C, further increase in the cis selectivity was observed
(cis/trans ) 11.2) (entry 5).13 The remarkable additive
effect of Yb(OTf)3 may be explained as shown in Figure
2. That is, Yb(OTf)3 may promote the rate of addition of
the malonate radical through the formation of a more
electrophilic radical on the basis of bidentate coordination
with the two ester groups.16b,c In addition, the formation
of a chelate complex with the precursor 1 may also lead
to an increase in the rate of the iodine abstraction.15h,16b
Radical iodine atom transfer [3 + 2] cycloaddition
reactions with various alkyl-substituted alkenes using
Et3B and Yb(OTf)3 are shown in Table 3. The reactions
with other 1-alkenes such as vinylsilane, allylsilane, and
homoallyl alcohol also proceeded with cis selectivity (3f,
(15) Typical reports in relation to Lewis acid mediated radical
reaction: (a) Guindon, Y.; Yoakim, C.; Lemieux, R.; Boisvert, L.;
Delorme, D.; Lavallee, J . F. Tetrahedron Lett. 1990, 31, 2845. (b)
Yamamoto, Y.; Onuki, S.; Yamamoto, M.; Asao, N. J . Am. Chem. Soc.
1994, 116, 421. (c) Renaud, P.; Moufid, N.; Kuo, L. H.; Curran, D. P.
J . Org. Chem. 1994, 59, 3259. (d) Nishida, M.; Ueyama, E.; Hayashi,
H.; Ohtake, Y.; Yamamura, Y.; Yanaginuma, E.; Yonemitsu, O.;
Nishida, A.; Kawahara, N. J . Am. Chem. Soc. 1994, 116, 6455. (e)
Urabe, H.; Yamashita, K.; Suzuki, K.; Kobayashi, K.; Sato, F. J . Org.
Chem. 1995, 60, 3576. (f) Renaud, P.; Gerster, M. J . Am. Chem. Soc.
1995, 117, 6607. (g) Wu, J .; H.; Radinov, R.; Porter, N. A. J . Am. Chem.
Soc. 1995, 117, 11029. (h) Guindon, Y.; Guerin, B.; Chabot, C.; Ogilvie,
W. J . Am. Chem. Soc. 1996, 118, 12528. (i) Sibi, M. P.; J i, J .; Wu, J .
H.; Gu¨rtler, S.; Porter, N. A. J . Am. Chem. Soc. 1996, 118, 2000. (j)
Murakata, M.; J ono, T.; Mizuno, Y.; Hoshino, O. J . Am. Chem. Soc.
1997, 119, 11713. For reviews: (k) Renaud, P.; Gerster, M. Angew.
Chem., Int. Ed. 1998, 37, 2562. (l) Guindon, Y.; J ung, G.; Guerin, B.;
Ogilvie, W. W. Synlett 1998, 213.
(16) Among various Lewis acids examined (TiCl4, SnCl4, ZnCl2,
MgBr2, Sc(OTf)3, Yb(OTf)3), the use of Yb(OTf)3 gave the best result.
Reports in relation to Yb(OTf)3-promoted radical reaction: (a) Sibi, M.
P.; J asperse, C. P.; J i, J . J . Am. Chem. Soc. 1995, 117, 10779. (b) Mero,
C. L.; Porter, N. A. J . Am. Chem. Soc. 1999, 121, 5155. (c) Yang, D.;
Ye, X.; Gu, S.; Xu, M. J . Am. Chem. Soc. 1999, 121, 5579.

New Homoallyl Radical Precursors
J . Org. Chem., Vol. 67, No. 3, 2002 925
cis/trans ) 6; 3g, cis/trans ) 5.6; 3h , cis/trans ) 10.8)13
to give the products in good yields (3f, 67%; 3g, 89%; 3h ,
68%) (entries 1-3). In the reactions with 1-hexene (entry
5 in Table 2), vinylsilane (entry 1 in Table 3), and
allylsilane (entry 2 in Table 3), considerable increase in
the chemical yields or diastereoselectivities was observed
in comparison with those attained by Curran’s method
using allyliodomalonate (3e, 53%, cis/trans ) 4; 3f, 46%,
cis/trans ) 2; 3g, 71%, cis/trans ) 5).2b Similar to the
case for 1-alkenes, 1,1-disubstituted alkenes also gave
the cycloaddition products in good yields (3i, 88%; 3j,
73%) (entries 4 and 5).
Ta ble 4. Ra d ica l Iod in e Atom Tr a n sfer [3 + 2]
Cycloa d d ition of 2 w ith Va r iou s Alk en es
The present reaction is applicable not only to 1-alkenes
and 1,1-disubstituted alkenes but also to less reactive 1,2-
disubstituted alkenes; that is, the reaction with cyclo-
pentene and cis-3-hexene gave the products 3k and 3l
in good yields (70% and 65%, respectively) (entries 6 and
7). Similar to the reaction with 2,3-dihydrofuran (Table
1, entry 3), the reaction with cyclopentene also gave the
isomer 3k , having an endo-iodomethyl group with almost
complete stereoselectivity (entry 6).13,14 These results
should be noteworthy, because it was reported that the
reaction with 1,2-disubstituted alkenes hardly proceeds
under Curran’s conditions using allyliodomalonate as a
homoallyl radical precursor.2b
Thus, we have found that radical iodine atom transfer
[3 + 2] cycloaddition with various alkenes using dimethyl
2-(iodomethyl)cyclopropane-1,1-dicarboxylate (1) effi-
ciently proceeds to give functionalized cyclopentane
derivatives in good yields. In comparison with the reac-
tion systems previously reported by other groups, the
advantages of the present reaction are as follows. (1) A
large excess (15-50 equiv) of alkenes used in Oshima’s
and Feldman’s methods is not required. That is, the [3
+ 2] cycloadducts are obtained in good yields even in the
presence of 2 equiv of alkenes (5 equiv in the cases of
1,2-disubstituted alkenes). (2) The present reaction can
be applied not only to 1-alkenes and 1,1-disubstituted
alkenes but also to less reactive 1,2-disubstituted alkenes.
(3) The reaction with electron-rich alkenes is also possible
because of the chemical stability of 1 in comparison with
Curran’s allylated iodoactive methines.
Ra d ica l Iod in e Atom Tr a n sfer [3 + 2] Cycloa d d i-
tion Rea ction u sin g 1,1-Bis(p h en ylsu lfon yl)-2-(iod o-
m eth yl)cyclop r op a n e (2). The radical iodine atom
transfer [3 + 2] cycloaddition reaction with 1,1-bis-
(phenylsulfonyl)-2-(iodomethyl)cyclopropane (2) as an-
other homoallyl radical precursor was investigated. In
the presence of Et3B (1 equiv), the reaction of 2 with
1-hexene (2 equiv) gave cycloadduct 4a in a moderate
yield (46%). Although the addition of Yb(OTf)3, which
worked well in the reactions of 1 (see Table 2), was
attempted, improvement of the chemical yield was not
observed. This result may indicate that the formation of
the chelate complex between 2 and Yb(OTf)3 does not
efficiently occur. On the other hand, the reaction under
high concentration was found to lead to improvement of
the chemical yield. That is, when the concentration of 2
in CH2Cl2 was changed to 1.0 M from 0.13 M (concentra-
tion of 1-hexene: 2.0 M from 0.26 M), the chemical yield
of 4a increased to 68% from 46% (Table 4, entry 1). Under
the same high concentration conditions, the reaction of
homoallyl alcohol also gave the cycloadduct 4b in good
yield (64%) (entry 2). With these 1-alkenes, moderate cis
selectivities were observed (4a , cis/trans ) 4; 4b, cis/trans
) 2.6).13
a
b
Isolated yield. The ratio was determined by 75 MHz 13C
NMR. c The hydroxycyclopentane 4e was obtained after desilyla-
d
tion by treatment with 5% HCl. The ratio was determined by
1H NMR.
Similar to the case for 1-alkenes, the reaction with 1,1-
disubstituted alkenes such as methylenecyclohexane and
2-ethyl-1-butene also proceeded to give the products 4c
and 4d in good yields (4c, 72%; 4d , 71%) (entries 3 and
4). Electron-rich alkenes such as silyl enol ether and
enamide could be also used (entries 5 and 6). In the
reaction with enamide having a bulky imide group,
higher cis selectivity in comparison with that of the
reaction with silyl enol ether was observed (4f, cis/trans
) 6) (entry 6).
Unfortunately, in contrast to the case for 1, the
reaction of 2 with 1,2-disubstituted alkenes such as
cyclopentene and 2,3-dihydrofuran hardly proceeded,
resulting in the quantitative recovery of 2.
In conclusion, we have succeeded in the development
of radical iodine atom transfer [3 + 2] cycloaddition with
various alkenes using 2-(iodomethyl)cyclopropane-1,1-
dicarboxylate (1) and 1,1-bis(phenylsulfonyl)-2-(iodo-
methyl)cyclopropane (2) as new homoallyl radical precur-
sors. The present reaction should provide an efficient and
practical synthetic methodology of functionalized cyclo-
pentane skeletons from simple substrates.
Exp er im en ta l Section
Melting points were uncorrected. H and 13C NMR spectra
1
were recorded on a 300 MHz spectrometer. In H and 13C NMR
1
spectra, chemical shifts were expressed in δ (ppm) downfield
from CHCl3 (7.26 ppm) and CDCl3 (77.0 ppm), respectively.
Mass spectra were recorded by electron impact or chemical
ionization. Column chromatography was performed on silica
gel (75-150 µm). Medium-pressure liquid chromatography
(MPLC) was performed on a 30 × 4 cm i.d. prepacked column
(silica gel, 50 µm) with a UV detector.
Sta r tin g Ma ter ia ls: Dim eth yl 2-(Iod om eth yl)cyclop r o-
p a n e-1,1-d ica r boxyla te (1).17 1 was prepared in accordance

926 J . Org. Chem., Vol. 67, No. 3, 2002
Kitagawa et al.
with our method (Ti(OR)4-mediated iodocarbocyclization9) or
Beckwith’s method.10
washed with brine, dried over MgSO4, and evaporated to
dryness. Purification of the residue by column chromatography
(4/1 hexane/AcOEt) gave cis-3b (less polar, 146 mg, 28%) and
trans-3b (more polar, 262 mg, 51%). cis-3b: colorless oil; IR
1,1-Bis(ph en ylsu lfon yl)-2-(iodom eth yl)cyclopr opan e (2).
To allylbis(phenylsulfonyl)methane (4.7 g, 14 mmol) in CH2-
Cl2 were added Et3N (2.9 mL, 21 mmol) and TiCl4 (2.8 mL,
25.2 mmol) under an Ar atmosphere at room temperature.
After the mixture was stirred for 10 min, I2 (5.3 g, 21 mmol)
was added, and then the reaction mixture was stirred for 30
min at room temperature. The mixture was poured into 2%
HCl and extracted with Et2O. The Et2O extracts were washed
with aqueous Na2S2O3 solution, dried over MgSO4, and evapo-
rated to dryness. Purification of the residue by column
chromatography (12/1 hexane/AcOEt) gave 2 (3.5 g, 54%). 2:
1
(neat) 3527, 1731 cm-1; H NMR (CDCl3) δ 4.32 (1H, q, J )
4.2 Hz), 3.76 (3H, s), 3.73 (3H, s), 3.29 (1H, t, J ) 9.6 Hz),
3.21 (1H, dd, J ) 6.3, 9.6 Hz), 2.50-2.68 (2H, m), 2.40 (1H,
dd, J ) 4.4, 15.0 Hz), 2.38 (1H, m), 2.00-2.16 (2H, m); 13C
NMR (CDCl3) δ 173.7, 172.5, 74.2, 59.2, 53.2, 53.0, 48.8, 42.9,
37.8, 3.7; MS (m/z) 342 (M+ + 1). Anal. Calcd for C10H15IO5:
C, 35.11; H, 4.42. Found: C, 35.44; H, 4.63. trans-3b: colorless
1
oil; IR (neat) 3502, 1732 cm-1; H NMR (CDCl3) δ 3.99 (1H,
m), 3.76 (3H, s), 3.74 (3H, s), 3.31 (1H, dd, J ) 6.1, 10.0 Hz),
3.23 (1H, dd, J ) 6.8, 10.0 Hz), 2.62 (2H, m), 2.28 (1H, dd, J
) 5.5, 13.7 Hz), 2.14 (1H, dd, J ) 6.2, 13.7 Hz), 1.93 (1H, dd,
J ) 9.4, 13.8 Hz); 13C NMR (CDCl3) δ 172.9, 172.1, 57.1, 53.1,
53.0, 49.1, 42.6, 38.9, 17.5, 8.8; MS (m/z) 342 (M+ + 1). Anal.
Calcd for C10H15IO5: C, 35.11; H, 4.42. Found: C, 35.40; H,
4.57.
white solid; mp 111-113 °C; IR (KBr) 1321, 1147 cm-1 1H
;
NMR (CDCl3) δ 8.00-8.06 (2H, m), 7.91-7.97 (2H, m), 7.65-
7.74 (2H, m), 7.53-7.62 (4H, m), 3.74 (1H, t, J ) 10.0 Hz),
3.53 (1H, dd, J ) 5.9, 10.0 Hz), 2.99 (1H, ddt, J ) 5.9, 8.9,
10.0 Hz), 2.28 (1H, dd, J ) 6.3, 9.9 Hz), 2.12 (1H, dd, J ) 6.3,
8.9 Hz); 13C NMR (CDCl3) δ 139.9, 138.2, 134.4, 129.6, 129.3,
128.9, 67.0, 33.8, 23.1, -1.4; MS (m/z) 462 (M+). Anal. Calcd
for C16H15IO4S: C, 41.57; H, 3.27. Found: C, 41.69; H, 3.37.
The lack of two aromatic carbon resonances in the 13C NMR
of 2 is due to overlap of signals.
Gen er a l P r oced u r e of Ra d ica l Iod in e Atom Tr a n sfer
[3 + 2] Cycloa d d ition Rea ction of 1 w ith Sim p le Alk yl-
Su bstitu ted Alk en es. Under an Ar atmosphere, to a solution
of dimethyl 2-(iodomethyl)cyclopropane-1,1-dicarboxylate (1;
149 mg, 0.5 mmol), 1-hexene (0.13 mL, 1 mmol), and Yb(OTf)3
(310 mg, 0.5 mmol) in CH2Cl2 (4 mL) was added Et3B (0.5 mL,
1 M hexane solution) at 0 °C. A 20 mL of dry air was subse-
quently introduced with a syringe. After being stirred for 5 h
at 0 °C, the mixture was poured into aqueous NH4Cl solution
and extracted with Et2O. The Et2O extracts were washed with
brine, dried over MgSO4, and evaporated to dryness. Purifica-
tion of the residue by column chromatography (20/1 hexane/
AcOEt) gave an inseparatable mixture of cis-3e and trans-3e
Gen er a l P r oced u r e of Ra d ica l Iod in e Atom Tr a n sfer
[3 + 2] Cycloa d d ition Rea ction s of 1 w ith Electr on -Rich
Alk en es. Under an Ar atmosphere, to a solution of dimethyl
2-(iodomethyl)cyclopropane-1,1-dicarboxylate (1; 149 mg, 0.5
mmol) and butyl vinyl ether (0.12 mL, 1 mmol) in CH2Cl2 (3
mL) was added Et3B (0.5 mL, 1 M hexane solution). A 20 mL
amount of dry air was subsequently introduced with a syringe.
After being stirred for 5.5 h at room temperature, the mixture
was poured into aqueous NH4Cl solution and extracted with
Et2O. The Et2O extracts were washed with brine, dried over
MgSO4, and evaporated to dryness. Purification of the residue
by column chromatography (20/1 hexane/AcOEt) gave a mix-
ture of cis-3a and trans-3a . Further purification of the mixture
by MPLC (6/1 hexane/AcOEt) gave cis-3a (less polar, 71 mg,
36%) and trans-3a (more polar, 61 mg, 30%), respectively.
1
(157 mg, 82%, cis/trans ) 11.2). H NMR data of 3e coincided
with those reported in the literature.2b
Dim eth yl 3-n -Bu tyl-4-(iod om eth yl)cyclop en ta n e-1,1-
d ica r boxyla te (3e). 1H NMR data of 3e coincided with those
reported in the literature.2b cis-3e: 13C NMR (CDCl3) δ 173.1,
173.0, 58.5, 52.9 (OCH3 × 2), 45.5, 42.6, 40.1, 38.4, 30.2, 28.3,
22.8, 14.0, 7.8 (CH2I). trans-3e: 13C NMR (CDCl3) δ 11.0
(CH2I).
cis- a n d tr a n s-Dim eth yl 4-n -bu toxy-3-(iod om eth yl)-
cyclop en ta n e-1,1-d ica r boxyla te (cis-3a a n d tr a n s-3a ). cis-
3a : colorless oil; IR (neat) 1737 cm-1; 1H NMR (CDCl3) δ 3.84
(1H, m), 3.72 (3H, s), 3.71 (3H, s), 3.49 (1H, td, J ) 6.3, 9.1
Hz), 3.33 (1H, t, J ) 9.0 Hz), 3.24 (1H, td, J ) 6.3, 9.1 Hz),
3.17 (1H, dd, J ) 5.5, 9.0 Hz), 2.74 (1H, dd, J ) 0.9, 14.5 Hz),
2.36-2.48 (2H, m), 2.14-2.28 (2H, m), 1.42-1.54 (2H, m),
1.26-1.40 (2H, m), 0.90 (3H, t, J ) 7.4 Hz); 13C NMR (CDCl3)
δ 173.0, 171.9, 80.6, 68.3, 59.1, 52.9, 52.7, 48.1, 38.6, 37.8, 31.8,
(3S*,3a S*,6a R*)-Dim et h yl 3-(Iod om et h yl)h exa h yd r o-
1,1-(2H)-p en ta len ed ica r boxyla te (3k ). 3k was prepared
from 1 (149 mg, 0.5 mmol) and cyclopentene (0.22 mL, 2.5
mmol) in accordance with the general procedure for the
reaction with simple alkyl-substituted alkenes. Purification of
the residue by column chlomatography (20/1 hexane/AcOEt)
gave 3k (129 mg, 70%) as a single stereoisomer. 3k : colorless
oil; IR (neat) 1728 cm-1; 1H NMR (CDCl3) δ 3.74 (3H, s), 3.69
(3H, s), 3.30 (1H, q, J ) 9.0 Hz), 3.19 (1H, dd, J ) 6.5, 9.6
Hz), 3.07 (1H, t, J ) 9.6 Hz), 2.64 (1H, m), 2.25 (1H, m), 2.21
(1H, dd, J ) 5.0, 12.4 Hz), 1.99 (1H, dd, J ) 12.4, 13.5 Hz),
1.73-1.87 (2H, m), 1.71 (1H, m), 1.32 (1H, m), 1.11 (1H, m),
0.94 (1H, m); 13C NMR (CDCl3) δ 172.4, 170.7, 63.5, 52.9, 52.3,
47.8, 45.7, 42.9, 37.4, 30.6, 27.2, 26.9, 5.4; MS (m/z) 367 (M+
+ 1). Anal. Calcd for C13H19IO4: C, 42.64; H, 5.23. Found: C,
43.01; H, 5.23.
Gen er a l P r oced u r e of Ra d ica l Iod in e Atom Tr a n sfer
[3 + 2] Cycloa d d ition Rea ction of 2 w ith Alk en es. Under
an Ar atmosphere, to a solution of 1,1-bis(phenylsulfonyl)-2-
(iodomethyl)cyclopropane (2; 231 mg, 0.5 mmol) and methyl-
enecyclohexane (0.13 mL, 1 mmol) in CH2Cl2 (0.5 mL) was
added Et3B (0.5 mL, 1 M hexane solution). A 20 mL portion of
dry air was subsequently introduced with a syringe. After
being stirred for 2 h at room temperature, the mixture was
poured into aqueous NH4Cl solution and extracted with Et2O.
The Et2O extracts were washed with brine, dried over MgSO4,
and evaporated to dryness. Purification of the residue by
column chromatography (12/1 hexane/AcOEt) gave 4c, includ-
ing impurity. Further purification of the mixture by MPLC
(5/1 hexane/AcOEt) gave 4c (201 mg, 72%).
19.3, 13.8, 4.2; MS (m/z) 399 (M+ + 1). Anal. Calcd for C14H23
-
IO5: C, 42.22; H, 5.82. Found: C, 42.34; H, 5.75. trans-3a :
colorless oil; IR (neat) 1736 cm-1; 1H NMR (CDCl3) δ 3.73 (3H,
S), 3.72 (3H, s), 3.57 (1H, q, J ) 6.3 Hz), 3.46 (1H, td, J ) 6.5,
9.2 Hz), 3.36 (1H, td, J ) 6.5, 9.2 Hz), 3.32 (1H, dd, J ) 4.9,
10.0 Hz), 3.23 (1H, dd, J ) 7.0, 10.0 Hz), 2.69 (1H, dd, J )
7.4, 13.8 Hz), 2.67 (1H, dd, J ) 6.4, 13.8 Hz), 2.21 (1H, dd, J
) 6.3, 13.8 Hz), 2.14 (1H, m), 1.77 (1H, dd, J ) 9.5, 13.8 Hz),
1.44-1.56 (2H, m), 1.26-1.40 (2H, m), 0.90 (3H, t, J ) 7.2
Hz); 13C NMR (CDCl3) δ 172.3, 171.9, 83.2, 69.4, 56.8, 52.8,
52.7, 46.5, 39.0, 38.0, 31.9, 19.2, 13.8, 9.7; MS (m/z) 399 (M+
+ 1). Anal. Calcd for C14H23IO5: C, 42.22; H, 5.82. Found: C,
42.55; H, 5.89.
cis- a n d tr a n s-Dim eth yl 3-Hyd r oxy-4-(iod om eth yl)-
cyclop en ta n e-1,1-d ica r boxyla te (cis-3b a n d tr a n s-3b).
Under an Ar atmosphere, to a solution of dimethyl 2-(iodom-
ethyl)cyclopropane-1,1-dicarboxylate (1; 447 mg, 1.5 mmol) and
silyl enol ether (0.45 mL, 3 mmol) in CH2Cl2 (7 mL) was added
Et3B (1.5 mL, 1 M hexane solution). A 20 mL amount of dry
air was subsequently introduced with a syringe. After the
mixture was stirred for 2 h at room temperature, 5% HCl (8
mL) and MeOH (15 mL) was added and then the mixture was
stirred for 15 min. After removal of MeOH by evaporation, the
residue was extracted with Et2O. The Et2O extracts were
2,2-Bis(ph en ylsu lfon yl) 4-(Iodom eth yl)spir o[4.5]decan e-
2,2-d ica r boxyla te (4c). 4c: white solid; mp 166-168 °C; IR
(KBr) 1316, 1146 cm-1; 1H NMR (CDCl3) δ 8.04-8.10 (4H, m),
7.69-7.76 (2H, m), 7.57-7.65 (4H, m), 3.22 (1H, dd, J ) 3.0,
9.6 Hz), 2.75-2.93 (3H, m), 2.44-2.61 (2H, m), 2.15 (1H, m),
(17) Kitagawa, O.; Inoue, T.; Hirano, K.; Taguchi, T. J . Org. Chem.
1993, 58, 3106.

New Homoallyl Radical Precursors
J . Org. Chem., Vol. 67, No. 3, 2002 927
0.90-1.70 (10H, m); 13C NMR (CDCl3) δ 136.8, 135.7, 134.7,
134.6, 131.5, 131.3, 128.9, 128.7, 91.3, 52.7, 46.0, 40.1, 38.1,
37.5, 28.4, 25.8, 23.8, 22.0, 4.5; MS (m/z) 431 (M+ - I); HRMS
calcd for C23H27O4S2 (M+ - I) 431.1350, found 431.1348.
cis- a n d tr a n s-1,1-Bis(p h en ylsu lfon yl)-3-h yd r oxy-4-
(iod om eth yl)cyclop en ta n e (cis-4e a n d tr a n s-4e). Under
anAr atmosphere, to a solution of 1,1-bis(phenylsulfonyl)-2-
(iodomethyl)cyclopropane (2; 231 mg, 0.5 mmol) and silyl enol
ether (0.15 mL, 1 mmol) in CH2Cl2 (0.5 mL) was added Et3B
(0.5 mL, 1 M hexane solution). A 20 mL portion of dry air was
subsequently introduced with a syringe. After being stirred
for 2 h at room temperature, 5% HCl (2.5 mL) and MeOH (2.5
mL) was added and then the mixture was stirred for 30 min
at room temperature. The mixture was extracted with AcOEt.
The AcOEt extracts were washed with brine, dried over
MgSO4, and evaporated to dryness. Purification of the residue
by column chromatography (5/1 hexane/AcOEt) gave a mixture
of cis-4e and trans-4e. Further purification of the mixture by
MPLC (2/1 hexane/AcOEt) gave cis-4e (less polar, 119 mg,
47%) and trans-4e (more polar, 61 mg, 24%), respectively. cis-
4e: white solid; mp 161-163 °C; IR (KBr) 3510, 1307, 1143
cm-1; 1H NMR (CDCl3) δ 8.10 (2H, d, J ) 8.0 Hz), 8.03 (2H, d,
J ) 7.8 Hz), 7.72-7.81 (2H, m), 7.58-7.70 (4H, m), 4.33 (1H,
m), 3.12-3.34 (3H, m), 2.69-2.92 (3H, m), 2.23-2.46 (2H, m);
13C NMR (CDCl3) δ 135.3, 135.2, 135.1, 135.0, 131.5, 131.3,
129.0, 128.9, 93.0, 73.3, 49.5, 40.3, 35.9, 1.9; MS (m/z) 379 (M+
- I). Anal. Calcd for C18H19IO5S2: C, 42.69; H, 3.78. Found:
C, 42.73; H, 4.16. trans-4e: white solid; mp 84-88 °C; IR (KBr)
1
3526, 1317, 1146 cm-1; H NMR (CDCl3) δ 8.10 (2H, d, J )
7.5 Hz), 8.08 (2H, d, J ) 7.5 Hz), 7.74 (2H, t, J ) 7.5 Hz), 7.62
(4H, t, J ) 7.5 Hz), 3.95 (1H, m), 3.36 (1H, dd, J ) 4.0, 10.3
Hz), 3.29 (1H, dd, J ) 6.2, 10.3 Hz), 2.92 (1H, dd, J ) 7.1,
15.1 Hz), 2.64 (1H, dd, J ) 7.7, 15.4 Hz), 2.52 (1H, dd, J )
8.8, 15.1 Hz), 2.44 (1H, brd, J ) 6.3 Hz), 2.29 (1H, dd, J )
11.4, 15.4 Hz), 1.94 (1H, m); 13C NMR (CDCl3) δ 135.5, 134.9,
131.5, 131.4, 128.9, 89.0, 75.3, 47.2, 39.2, 35.6, 8.0; MS (m/z)
506 (M+); HRMS calcd for C18H19O5S2 (M+ - I) 379.0674, found
379.0643. The lack of three aromatic carbon resonances in the
13C NMR of trans-4e is due to overlap of signals.
Su p p or tin g In for m a tion Ava ila ble: Text giving experi-
mental procedures for the preparation and characterization
data of products 3c (3c′), 3d , 3f-3j, 3l (5l), 4a , 4b, 4d , and 4f
and figures giving 1H and 13C NMR spectra of new compounds
(4a (cis/trans mixture), 4b (cis/trans mixture), 4c, trans-4e,
cis-4f) lacking elemental analysis. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O010950I