Radical Carbonylation/Reductive Cyclization for the Construction of Tetrahydrofuran-3-ones and Pyrrolidin-3-ones

Article abstract of DOI:10.1021/jo030153f

β-Hydroxyalkyl aryl chalcogenides obtained by regioselective ring-opening of epoxides with benzeneselenolate or -tellurolate were found to undergo efficient hetero-Michael addition when treated with ethyl propiolate. Subsequent carbonylation/reductive cyclization of the resulting vinylogous carbonates in the presence of AIBN/TTMSS and carbon monoxide (80 atm) afforded 2,5-disubstituted tetrahydrofuran-3-ones, predominantly as cis isomers (cis/trans = 4/1-9/1). Starting from a polymer-supported diaryl diselenide, the methodology was also successfully extended to solid-phase synthesis. Vinylogous carbamates prepared by hetero-Michael addition of aziridines to electron-deficient alkynes were regioselectively ring-opened with benzeneselenolate from the sterically least hindered side. Radical carbonylation/reductive cyclization of the resulting N-vinyl-β-amino-alkyl phenyl selenides afforded 2,5-disubstituted pyrrolidin-3-ones, predominantly as cis isomers (cis/trans = 3/1-12/1).

Full text of DOI:10.1021/jo030153f

Ra d ica l Ca r bon yla tion /Red u ctive Cycliza tion for th e Con str u ction
of Tetr a h yd r ofu r a n -3-on es a n d P yr r olid in -3-on es
Stefan Berlin, Cecilia Ericsson, and Lars Engman*
Uppsala University, Institute of Chemistry, Department of Organic Chemistry,
Box 599, SE-751 24, Uppsala, Sweden
lars.engman@kemi.uu.se
Received May 5, 2003
â-Hydroxyalkyl aryl chalcogenides obtained by regioselective ring-opening of epoxides with
benzeneselenolate or -tellurolate were found to undergo efficient hetero-Michael addition when
treated with ethyl propiolate. Subsequent carbonylation/reductive cyclization of the resulting
vinylogous carbonates in the presence of AIBN/TTMSS and carbon monoxide (80 atm) afforded
2,5-disubstituted tetrahydrofuran-3-ones, predominantly as cis isomers (cis/trans ) 4/1-9/1).
Starting from a polymer-supported diaryl diselenide, the methodology was also successfully extended
to solid-phase synthesis. Vinylogous carbamates prepared by hetero-Michael addition of aziridines
to electron-deficient alkynes were regioselectively ring-opened with benzeneselenolate from the
sterically least hindered side. Radical carbonylation/reductive cyclization of the resulting N-vinyl-
â-amino-alkyl phenyl selenides afforded 2,5-disubstituted pyrrolidin-3-ones, predominantly as cis
isomers (cis/trans ) 3/1-12/1).
In tr od u ction
amides,11 lactams,12 and acyl selenides.13 Atom or group
transfer, inter- or intramolecular radical addition, cas-
cade reactions, radical translocation, one-electron oxida-
tion, or ionic chemistry are involved in some of these
transformations.
Acyl radicals1 take part in a large variety of inter- and
intramolecular reactions and are therefore useful syn-
thetic intermediates.2 These species are commonly gener-
ated by homolysis of an acyl-X bond, where X could be
hydrogen, halogen, chalcogen, or a metal. Since most of
these derivatives suffer from certain shortcomings in
radical processes (inefficient chain transfer, over-reduc-
tion, or poor reactivity toward stannyl or silyl radicals),
selenol esters have become the most versatile precursors
for acyl radicals.3 As demonstrated by Ryu and co-
workers, acyl radicals can also be readily formed by
reaction of alkyl radicals with carbon monoxide.1,4,5 These
carbonylation reactions are commonly performed as one-
pot reactions with 60-80 atm of CO, conditions that can
easily be obtained by using an ordinary autoclave.
Primary, secondary, and tertiary radicals can be ef-
ficiently carbonylated and further transformed in more
or less elaborate ways into carbonyl derivatives such as
aldehydes,6 ketones,7 esters,8 lactones,9 thiolactones,10
It occurred to us that radical carbonylation/reductive
cyclization could provide easy access to tetrahydrofuran-
3-one and pyrrolidin-3-one derivatives from readily avail-
(6) Ryu, I.; Kusano, K.; Ogawa, A.; Kambe, N.; Sonoda, N. J . Am.
Chem. Soc. 1990, 112, 1295.
(7) (a) Ryu, I.; Kusano, K.; Yamazaki, H.; Sonoda, N. J . Org. Chem.
1991, 56, 5003. (b) Ryu, I. Yamazaki, H.; Kusano, K.; Ogawa, A.;
Sonoda, N. J . Am. Chem. Soc. 1991, 113, 8558. (c) Ryu, I.; Yamazaki,
H.; Ogawa, A.; Kambe, N.; Sonoda, N. J . Am. Chem. Soc. 1993, 115,
1187. (d) Brinza, I. M.; Fallis, A. G. J . Org. Chem. 1996, 61, 3580. (e)
Nagahara, K.; Ryu, I.; Yamazaki, H.; Kambe, N.; Komatsu, M.; Sonoda,
N.; Baba, A. Tetrahedron 1997, 53, 14615.
(8) Nagahara, K.; Ryu, I.; Komatsu, M.; Sonoda, N. J . Am. Chem.
Soc. 1997, 119, 5465.
(9) (a) Tsunoi, S.; Ryu, I.; Okuda, T.; Tanaka, M.; Komatsu, M.;
Sonoda, N. J . Am. Chem. Soc. 1998, 120, 8692. (b) Kreimerman, S.;
Ryu, I.; Minakata, S.; Komatsu, M. Org. Lett. 2000, 2, 389.
(10) Ryu, I.; Okuda, T.; Nagahara, K.; Kambe, N.; Komatsu, M.;
Sonoda, N. J . Org. Chem. 1997, 62, 7550.
(11) Ryu, I.; Nagahara, K.; Kambe, N.; Sonoda, N.; Kreimerman,
S.; Komatsu, M. Chem. Commun. 1998, 1953.
(12) Ryu, I.; Matsu, K.; Minakata, S.; Komatsu, M. J . Am. Chem.
Soc. 1998, 120, 5838.
(13) Ryu, I.; Muraoka, H.; Kambe, N.; Komatsu, M.; Sonoda, N. J .
Org. Chem. 1996, 61, 6396.
(1) Chatgilialoglu, C.; Crich, D.; Komatsu, M.; Ryu, I. Chem. Rev.
1999, 99, 1991.
(2) For representative examples of acyl radical cyclizations, see: (a)
Boger, D. L.; Mathvink, R. J . J . Am. Chem. Soc. 1990, 112, 4003. (b)
Boger, D. L.; Mathvink, R. J . J . Am. Chem. Soc. 1990, 112, 4008. (c)
Boger, D. L.; Mathvink, R. J . J . Org. Chem. 1992, 57, 1429. (d) Crich,
D.; Chen, C.; Hwang, J .-T.; Yuan, H.; Papadatos, A.; Walter, R. I. J .
Am. Chem. Soc. 1994, 116, 8937. (e) Crich, D.; Yao, Q. J . Org. Chem.
1996, 61, 3566. (f) Crich, D.; Hao, X. J . Org. Chem. 1997, 62, 5982. (g)
Chen, L.; Gill, G. B.; Pattenden, G.; Simonian, H. J . Chem. Soc., Perkin
Trans. 1 1996, 31. (h) Batsanov, A.; Chen, L.; Gill, G. B.; Pattenden,
G. J . Chem. Soc., Perkin Trans. 1 1996, 45. (i) Pattenden, G.; Roberts,
L.; Blake, A. J . J . Chem. Soc., Perkin Trans. 1 1998, 863.
(3) Renaud, P. In Topics in Current Chemistry; Wirth, T., Ed.;
Springer-Verlag: Berlin, 2000; Vol 208, p 81.
(4) (a) Ryu, I.; Sonoda, N. Angew. Chem., Int. Ed. Engl. 1996, 35,
1050. (b) Ryu, I.; Sonoda, N.; Curran, D. P. Chem. Rev. 1996, 96, 177.
(5) Ryu, I. Chem. Soc. Rev. 2001, 30, 16.
10.1021/jo030153f CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/02/2003
8386
J . Org. Chem. 2003, 68, 8386-8396

Construction of Tetrahydrofuran-3-ones and Pyrrolidin-3-ones
SCHEME 1
SCHEME 2
pure (E)-isomers (Table 1). Attempts to vinylate ring-
opened isobutylene oxide failed, and the starting material
was recovered unchanged.
Carbonylation/radical cyclization was conducted in an
autoclave. To elucidate the optimal reaction conditions,
selenide 2a was carbonylated/cyclized under various
conditions (Table 2). The use of tri-n-butyltin hydride as
a hydrogen atom donor was found to cause formation of
substantial amounts of reduced product 4. Better results
were obtained using tris(trimethylsilyl)silane (TTMSS).
With carbon monoxide at 80 atm, an 86% yield of
compound 3a was obtained as a 9:1 mixture of cis and
trans isomers. At lower pressures (60 atm), reduction of
the starting material again started to become an un-
wanted side-reaction. Tri-n-butylgermane was also tried
as a hydrogen atom donor but found to be inferior to
TTMSS. Thus, subsequent carbonylation/reductive cy-
clization of the remaining compounds 2 (Scheme 2) was
carried out using TTMSS as a hydrogen atom donor and
CO at 80 atm.
As shown in Table 1 (entries 1-4), organotellurium
radical precursors 2b and 2d performed almost as well
as their organoselenium counterparts in the chemistry
developed. The unexpectedly low yield of compound 3c
(40%) was due to competing 1,5 hydrogen atom shift/6-
exo-cyclization (Scheme 3). This gave rise to dioxane 5,
which was isolated in 32% yield starting from compound
2c and 30% yield starting from 2d . Only one diastere-
omer of the compound was isolated with all three
substituents occupying equatorial positions. In a separate
experiment carried out in the absence of CO, the dioxane
derivative 5 was isolated in 82% yield along with 3%
reduced starting material.
It is also noteworthy that the benzylic radical formed
from compound 2e (Table 1, entry 5) failed to undergo
carbonylation/5-exo-cyclization. Only reduced starting
material was isolated in 56% yield. However, this is in
accord with previous observations that carbonylated
stabilized radicals (benzylic, allylic, tertiary) decarbony-
late more rapidly than other acyl radicals.1 Carbonyla-
tion/cyclization of radical precursors 2f-i afforded 2,5-
disubstituted tetrahydrofuran-3-ones in moderate to good
yields (59-82%). Small amounts (6-14%) of reduced
starting material were formed in the reactions. The
â-hydroxyalkyl phenyl selenides originating from 1,2-
disubstituted epoxides (Table 1, entries 10-11) furnished
2,4,5-trisubstituted tetrahydrofuran-3-ones as insepa-
rable mixtures of diastereomers. It seems that carbony-
lation of the secondary alkyl radical produces both of the
possible diastereomeric acyl radicals (cis/trans), which
then undergo 5-exo-cyclization.
able organochalcogen precursors. Some time ago, we
showed that epoxides can be regioselectively ring-opened
by benzeneselenolate or benzenetellurolate. The resulting
â-hydroxyalkyl phenyl chalcogenides were readily O-
allylated by treatment with allyl bromide and base.
Subsequent reductive cyclization with AIBN initiation
then provided 2,4-disubstituted tetrahydrofurans in high
yields as mixtures of diastereomers (eq 1).14 In a similar
fashion, N-tosyl aziridines were regioselectively ring-
opened by benzeneselenolate and, following N-allylation,
cyclized to give N-tosyl-2,4-disubstituted pyrrolidines (eq
2).15 Evans and co-workers have already shown that 2,5-
disubstituted tetrahydrofuran-3-ones can be efficiently
prepared by intramolecular acyl radical cyclization
(Scheme 1; X ) O, lower left).16,17 By generating acyl
radicals directly from alkyl radicals and carbon monoxide
(Scheme 1; lower right), we thought we could approach
these systems, as well as the corresponding pyrrolidin-
3-ones (X ) NH) in a different way, using more readily
available starting materials.18
Resu lts a n d Discu ssion
Con str u ction of Tetr a h yd r ofu r a n -3-on es. For the
preparation of 2,5-disubstituted tetrahydrofuran-3-ones
by radical carbonylation/reductive cyclization, â-hydroxy-
alkyl phenyl selenides 1 were allowed to undergo hetero-
Michael addition to ethyl propiolate16a-c,17b,19 or to act as
nucleophiles in the vinylogous substitution of (E)-1,2-bis-
(phenylsulfonyl)ethylene16d,17a (Scheme 2). The O-viny-
lation proceeded smoothly at room temperature to give
radical precursors 2a -k in 64-95% isolated yields as
(14) (a) Engman, L.; Gupta, V. J . Org. Chem. 1997, 62, 157. (b)
Ericsson, C.; Engman, L. Org. Lett. 2001, 3, 3459.
(15) (a) Gupta, V.; Besev, M.; Engman, L. Tetrahedron Lett. 1998,
39, 2429. (b) Besev, M.; Engman, L. Org. Lett. 2000, 2, 1589.
(16) (a) Evans, P. A.; Roseman, J . D. Tetrahedron Lett. 1995, 36,
31. (b) Evans, P. A.; Roseman, J . D. J . Org. Chem. 1996, 61, 2252. (c)
Evans, P. A.; Murthy, V. S.; Roseman, J . D.; Rheingold, A. L. Angew.
Chem., Int. Ed. 1999, 38, 3175. (d) Evans, P. A.; Manangan, T. J . Org.
Chem. 2000, 65, 4523.
(17) (a) Evans, P. A.; Roseman, J . D. Tetrahedron Lett. 1997, 38,
5249. (b) Evans, P. A.; Roseman, J . D.; Garber, L. T. J . Org. Chem.
1996, 61, 4880.
(18) For a communication of part of the present work, see: Berlin,
S.; Ericsson, C.; Engman, L. Org. Lett. 2002, 4, 3.
(19) (a) Tiecco, M.; Testaferri, L.; Tingoli, M.; Marini, F. J . Org.
Chem. 1993, 58, 1349. (b) Mitsudera, H.; Kakehi, A.; Kamimura, A.
Tetrahedron Lett. 1999, 40, 7389. (c) Leeuwenburgh, M. A.; Litjens,
R. E. J . N.; Code´e, J . D. C.; Overkleeft, H. S.; van der Marel, G. A.;
van Boom, J . H. Org. Lett. 2000, 2, 1275.
The stereochemistry of the 2,5-disubstituted tetrahy-
drofuran-3-ones 3 prepared was assigned by using two-
J . Org. Chem, Vol. 68, No. 22, 2003 8387

Berlin et al.
TABLE 2. Op tim iza tion of Ca r bon yla tion Con d ition s
TABLE 1. O-Vin yla ted â-Hyd r oxya lk yl P h en yl
Ch a lcogen id es a n d Th eir Con ver sion to
Tetr a h yd r ofu r a n -3-on es via Ra d ica l Ca r bon yla tion /
Red u ctive Cycliza tion
entry
H-atom donor
PCO (atm)
3a a
4a
1
2
3
4
n-Bu3SnH
TTMSS
TTMSS
60
60
80
80
20
81
86
86
66
6
0
n-Bu3GeH
6
a
Isolated yield in percent.
SCHEME 3
disubstituted tetrahydrofuran-3-ones. However, by treat-
ment of compound 3a with 0.1 equiv of DBU in refluxing
benzene, the cis/trans ratio could only be increased to 1:2.
Solid -P h a se Syn t h esis of Tet r a h yd r ofu r a n -3-
on es. Polymer-supported selenium linkers were intro-
duced by Nicolaou21 in 1998. They have already found
extensive use in combinatorial chemistry,22 as well as in
natural product synthesis.23 Although an increasing
number of radical reactions on solid support24 have been
(20) (a) Beckwith, A. L. J .; Easton, C. J .; Serelis, A. K. J . Chem.
Soc., Chem. Commun. 1980, 482. (b) Beckwith, A. L. J .; Lawrence, T.;
Serelis, A. K. J . Chem. Soc., Chem. Commun. 1980, 484. (c) Beckwith,
A. L. J .; Schiesser, C. H. Tetrahedron 1985, 41, 3925. (d) Spellmeyer,
D. C.; Houk, K. N. J . Org. Chem. 1987, 52, 959.
(21) Nicolaou, K. C.; Pastor, J .; Barluenga, S.; Winssinger, N. J .
Chem. Soc., Chem. Commun. 1998, 1947.
a
b
Isolated yields (%). Isolated yield of reduced uncyclized
material (%). c Inseparable mixture of diastereomers.
(22) (a) Nicolaou, K. C.; Mitchell, H. J .; Fylaktakidou, K. C.; Suzuki,
H.; Rodr´ıguez, R. M. Angew. Chem., Int. Ed. 2000, 39, 1089. (b)
Nicolaou, K. C.; Pfefferkorn, J . A.; Cao, G.-Q. Angew. Chem., Int. Ed.
2000, 39, 734. (c) Nicolaou, K. C.; Roecker, A. J .; Pfefferkorn, J . A.;
Cao, G.-Q. J . Am. Chem. Soc. 2000, 122, 2966. (d) Nicolaou, K. C.;
Pfefferkorn, J . A.; Roecker, A. J .; Cao, G.-Q.; Barluenga, S.; Mitchell,
H. J . J . Am. Chem. Soc. 2000, 122, 9939. (e) Nicolaou, K. C.;
Pfefferkorn, J . A.; Mitchell, H. J .; Roecker, A. J .; Barluenga, S.; Cao,
G.-Q.; Affleck, R. L.; Lillig, J . E. J . Am. Chem. Soc. 2000, 122, 9954.
(f) Nicolaou, K. C.; Pfefferkorn, J . A.; Barluenga, S.; Mitchell, H. J .;
Roecker, A. J .; Cao, G.-Q. J . Am. Chem. Soc. 2000, 122, 9968.
dimensional NOESY experiments. A 1,3 NOE was always
seen for the cis isomer. The selective formation of cis-
2,5-disubstituted tetrahydrofuran-3-ones follows from the
Beckwith-Houk rules for ring-closure, assuming that the
2,5-substituents are both pseudoequatorial in the chair-
like transition state.20 Some attempts were made to
epimerize the diastereomeric mixture of cis-/trans-2,5-
8388 J . Org. Chem., Vol. 68, No. 22, 2003

Construction of Tetrahydrofuran-3-ones and Pyrrolidin-3-ones
SCHEME 4
SCHEME 5
carbonate 4 (yields were calculated over three steps).
Attempts to further increase the concentration of TTMSS
(0.3 M) resulted in lower product yields (37%) and
formation of more reduced material (42%).
desribed, they have, to the best of our knowledge, never
been applied to radical carbonylation/reductive cycliza-
tion reactions. We therefore thought it would be interest-
ing to try to extend the methodology developed for the
preparation of tetrahydrofuran-3-ones to the solid phase.
Con str u ction of P yr r olid in -3-on es. For extending
the methodology developed to the preparation of 2,5-
disubstituted pyrrolidin-3-ones, we envisioned a reaction
sequence involving benzenselenol ring-opening of an
aziridine,26 Michael addition27 of the resulting â-ami-
noalkyl phenyl selenide to a propiolate ester, and carbon-
ylation/reductive28 cyclization (Scheme 5, upper path-
way). However, it turned out that the conjugate addition
products from primary amines were labile and more
difficult to isolate than those from the corresponding
alcohols. Thus, ring-opened 2-benzylaziridine (10, R )
Bn) reacted only sluggishly with methyl propiolate/NMM
when heated in DMF at 80 °C to give a complex mixture
of products. The corresponding N-tosylated compound
was found to be even less reactive. Spurred by the early
finding by Vessiere and co-workers29 that electron-
deficient aziridines undergo efficient Michael addition to
electron-deficient alkynes by gentle heating in polar
solvents, we tried to add aziridines to methyl propiolate.
The idea was to regiospecifically ring-open the resulting
N-vinylated aziridine 11 from the sterically least hin-
dered side to obtain the desired radical precursor 12 for
carbonylation/radical cyclization (Scheme 5, lower part).
Simple stirring of neat 2-benzylaziridine with a slight
excess of methyl propiolate provided a quantitative yield
of adduct 11a as a 6/1 mixture of (E)- and (Z)-isomers
(Table 3). Other mono- and disubstituted aziridines
reacted similarly. Dimethyl acetylene dicarboxylate (en-
try 5) and ethynyl p-tolyl sulfone (entry 6) could also be
A diselenide resin 6 was prepared in a few steps from
cross-linked (1%) polystyrene as described in the litera-
ture.25 The loading of selenium, based on elemental
analysis for nitrogen after treatment of the polymer with
NaBH4/N,N-dimethyl carbamoyl chloride, was 2.25 mmol/g
resin.
Benzyloxirane was added to an ethanolic suspension
of resin 6, which had been treated with NaBH4 (Scheme
4). The resulting â-hydroxyalkyl phenyl selenide resin 7
was then purified by washing and filtration. To show that
the reaction had proceeded well, the resin was treated
in refluxing benzene with a large excess of TTMSS/AIBN.
On the basis of the loading of selenium on the resin, the
alcohol 8 was isolated in near quantitative yield (97%).
The Michael addition of alcohol resin 7 was carried out
with ethyl propiolate in neat NMM at 60° C. Reductive
cleavage of resin 9 as described above provided vinylo-
gous carbonate 4 in excellent yield (91%). The resin
bound radical precursor was finally subjected to radical
carbonylation/reductive cyclization. Initial attempts with
a low concentration (0.01 M) of hydrogen atom donor
resulted in poor conversion. When a more concentrated
solution (0.1 M) was used, tetrahydrofuran-3-one 3a was
isolated in 55% yield, along with 12% of vinylogous
(23) (a) Nicolaou, K. C.; Winssinger, N.; Hughes, R.; Smethurst, C.;
Cho, S. Y. Angew. Chem., Int. Ed. 2000, 39, 1084. (b) Zaragoza, F.
Angew. Chem., Int. Ed. 2000, 39, 2077. (c) Nicolaou, K. C.; Pfefferkorn,
J . A.; Cao, G.-Q.; Kim, S.; Kessabi, J . Org. Lett. 1999, 1, 807.
(24) For a review on radical reactions on solid support, see: (a)
Radicals in Organic Synthesis; Renaud, P., Sibi, M., Eds.; Wiley:
Weinheim, 2001; Vol. 2, Chapter 1.5, p 81. (b) Enholm, E. J .; Gallagher,
M. E.; J iang, S.; Batson, W. A. Org. Lett. 2000, 2, 3355. (c) Sibi, M. P.;
Chandramouli, S. V. Tetrahedron Lett. 1997 38, 8929. (d) Miyabe, H.;
Konishi, C.; Naito, T. Org. Lett. 2000, 2, 1443. (e) J ia, G. F.; Iida, H.;
Lown, J . W. Synlett 2000, 603. (f) Wendeborn, S.; De Mesmaeker, A.;
Brill, W. K. D.; Berteina, S. Acc. Chem. Res. 2000, 215. (g) J eon, G.
H.; Yoon, J . Y.; Kim, S.; Kim, S. S. Synlett 2000, 128. (h) Miyabe, H.;
Ueda, M.; Yoshioka, N.; Yamakawa, K.; Naito, T. Tetrahedron 2000,
56, 2413. (i) Miyabe, H.; Tanaka, H.; Naito, T. Tetrahedron Lett. 1999,
40, 8387. (j) Caddick, S.; Hamza, D.; Wadman, S. N. Tetrahedron Lett.
1999, 40, 7285. (k) Berteina, S.; De Mesmaeker, A.; Wendeborn, S.
Synlett 1999, 1121. (l) Yim, A. M.; Vidal, Y.; Viallefont, P.; Martinez,
J . Tetrahedron Lett. 1999, 40, 4535. (m) Miyabe, H.; Fujishima, Y.;
Naito, T. J . Org. Chem. 2000, 64, 2174. (n) Watanabe, Y.; Ishikawa,
S.; Takao, G.; Toru, T. Tetrahedron Lett. 1999, 40, 3411-3414.
(25) (a) Farrall, M. J .; Fre´chet, M. J . J . Org. Chem. 1976, 24, 3877.
(b) Ruhland, T.; Andersen, K.; Pedersen, H. J . Org. Chem. 1998, 63,
9204.
(26) (a) Besev, M.; Engman, L. Org. Lett. 2002, 4, 3023. (b) Katagiri,
T.; Takahashi, M.; Fujiwara, Y.; Ihara, H.; Uneyama, K. J . Org. Chem.
1999, 64, 7323.
(27) See for example: Grigg, R.; Savic, V. Chem. Commun. 2000,
873.
(28) Radical cyclization onto derivatives of vinylogous carbamates
has been frequently used in heterocycle construction.28a However,
additions of acyl radicals are scarce.28b (a) Navarro-Va´zquez, A.; Garcia,
A.; Dominguez, D. J . Org. Chem. 2002, 67, 3213 and references therein.
(b) Evans, P. A.; Manangan, T.; Rheingold, A. L. J . Am. Chem. Soc.
2000, 122, 11009.
(29) Gelas-Mialhe, Y.; Touraud, E.; Vessiere, R. Can. J . Chem. 1982,
60, 2830.
J . Org. Chem, Vol. 68, No. 22, 2003 8389

Berlin et al.
TABLE 3. Vin yl Azir id in es: Th eir Rin g-Op en in g w ith Ben zen eselen ola te a n d Con ver sion to P yr r olid in -3-on es
a
b
Isolated yield (%). Crude yield (%) after NaBH4/BrCH2CO2H treatment. c Isolated yield (%) after flash chromatography on Al2O3
d
(neutral). Stereochemistry not determined.
used as Michael acceptors. Except for sulfone 11f, the
addition products were always enriched in the (E)-isomer.
The N-vinyl aziridines 11 were then subjected to ring-
opening (Scheme 5). Whereas N-unsubstituted aziridines
have to be protonated before they can be ring-opened by
chalcogen nucleophiles, aziridines carrying electron-
withdrawing N-substituents react in the unprotonated
form. After treatment of the aziridine with benzene-
selenolate at ambient temperature in ethanol, complete
and regiospecific ring-opening was usually seen after 2-3
h (Table 3). The only exception was the 8-azabicyclo[5.1.0]-
octane-derived N-vinylaziridine 11g, which required
heating at reflux in methanol for 3 h to undergo ring-
position of the materials. Purification on neutral alumina
worked better, producing pure enamines. Treatment of
the crude product with sodium borohydride in ethanol
until colorlessness was achieved and addition of excess
bromoacetic acid as a trapping agent for benzeneseleno-
late turned out to be a more practical way of removing
the diphenyl diselenide.30 After final extraction with base,
crude vinylogous carbamates 12 were obtained in 92-
98% yields (Table 3). Ring-opening was accompanied by
double-bond isomerization of the enamine moiety. Thus,
compound 11a as a 6/1 E/Z mixture afforded enamine
12a as a 4/5 E/Z mixture. Ring-opening of both the pure
(E)- and (Z)-isomers of compound 11a produced the same
mixture (E/ Z ) 4/5) of compound 12a , suggesting that
the product ratio is thermodynamically controlled. As
1
opening. J udging from the H NMR spectra of the crude
product, the vinylogous carbamates 12 were only con-
taminated by some diphenyl diselenide. However, at-
tempted purification on silica caused extensive decom-
(30) Clive, D. L. J .; Daigneault, S. J . Org. Chem. 1991, 56, 3801.
8390 J . Org. Chem., Vol. 68, No. 22, 2003

Construction of Tetrahydrofuran-3-ones and Pyrrolidin-3-ones
1132, 1629, 1705 cm-1. Anal. Calcd for C20H22O3Se: C, 61.70;
H, 5.70. Found: C, 61.60; H, 5.63.
Spectral data for compounds 2 prepared are shown below.
seen in Table 3, the E/ Z ratios of vinylaziridines varied
dramatically for the compounds prepared (e.g., E/ Z )
9/1 for vinylic sulfone 12f and E/ Z ) 1/>25 for acrylate
12d ).
For yields, see Table 1.
(E)-3-(1-Ben zyl-2-ph en yltellu r en yl-eth oxy)-acr ylic Acid
Eth yl Ester (2b): 1H NMR (CDCl3) δ 1.27 (t, J ) 7.1, 3H),
3.00-3.12 (several peaks, 4H), 4.14 (q, J ) 7.1, 2H), 4.32 (m,
1H) 5.14 (d, J ) 12.4, 1H), 7.13-7.33 (several peaks, 8H), 7.36
(d, J ) 12.4, 1H), 7.75 (m, 2H); 13C NMR (CDCl3) δ 12.3, 14.4,
41.3, 59.7, 84.6, 97.9, 111.1, 126.8, 128.1, 128.6, 129.4, 129.5,
Radical carbonylation/reductive cyclization was con-
ducted at 80 °C with carbon monoxide at 80 atm. In terms
of avoiding formation of reduced starting material,
TTMSS again proved to be superior to n-Bu3SnH as a
hydrogen atom donor. Pyrrolidin-3-ones 13 were isolated
in 65-85% yields, often as a mixture of cis and trans
isomers (Table 3). For some reason, radical precursor 12f,
carrying a vinyl sulfone acceptor, failed to give a pyrro-
lidin-3-one on attempted radical carbonylation/reductive
cyclization. Except for compound 13e (cis/trans ) 12/1),
cis/trans ratios were in many cases close to 3/1 for 2,5-
disubstituted compounds. Thus, the selectivity is lower
than that seen above in the preparation of 2,5-disubsti-
tuted tetrahydrofuran-3-ones 2 (Table 1, entries 1, 6, 7).
Evans and co-workers28b have recently reported the
formation of a trans-2,5-disubstituted pyrrolidin-3-one as
the major diastereomer (cis/trans ) 1/2) in the intramo-
lecular addition of an acyl radical to a vinylogous car-
bamate. However, this change in diastereoselectivity can
probably be ascribed to an additional N-substituent
(benzyl), which could change the diastereoselectivity
predicted assuming a chairlike Beckwith-Houk transi-
tion state.31 Some of the pyrrolidin-3-ones prepared were
surprisingly unstable (13a -c). Significant decomposition
was observed already when the compounds were kept for
a few days in the refrigerator. N-Tosylation was found
to significantly improve their stability and allow for
proper characterization.
136.4, 138.8, 161.3, 167.7; IR (neat) 1129, 1637, 1701 cm-1
.
Anal. Calcd for C20H22O3Te: C, 54.85; H, 5.06. Found: C, 54.66;
H, 5.25.
(E)-3-(1-Ben zyloxym eth yl-2-p h en ylselen en yl-eth oxy)-
a cr ylic Acid Eth yl Ester (2c): 1H NMR (CDCl3) δ 1.26 (t, J
) 7.1, 3H), 3.08 (dd, J ) 13.1, 6.5, 1H), 3.15 (dd, J ) 13.1, 6.3,
1H), 3.64 (dd, J ) 10.5, 6.5, 1H), 3.69 (dd, J ) 10.5, 4.0, 1H),
4.15 (q, J ) 7.1, 2H), 4.19 (m, 1H), 4.49 (s, 2H), 5.18 (d, J )
12.3, 1H), 7.26-7.36 (several peaks, 8H), 7.48 (d, J ) 12.3,
1H), 7.51 (m, 2H); 13C NMR (CDCl3) δ 14.4, 28.1, 59.7, 70.5,
73.4, 81.8, 98.0, 127.6, 127.7, 128.4, 129.1, 129.3, 133.3, 137.5,
161.8, 167.7; IR (neat) 1132, 1369, 1641, 1703 cm-1. Anal.
Calcd for C21H24O4Se: C, 60.14; H, 5.77. Found: C, 60.06; H,
5.65.
(E)-3-(1-Ben zyloxym eth yl-2-p h en yltellu r en yl-eth oxy)-
a cr ylic Acid Eth yl Ester (2d ): 1H NMR (CDCl3) δ 1.25 (t, J
) 7.1, 3H), 3.07 (dd, J ) 12.6, 6.1, 1H), 3.13 (dd, J ) 12.6, 3.9,
1H), 3.65 (dd, J ) 10.4, 5.4, 1H), 3.86 (dd, J ) 10.4, 4.4, 1H),
4.14 (q, J ) 7.1, 2H), 4.27 (m, 1H), 4.48 (s, 2H), 5.17 (d, J )
12.4, 1H), 7.17-7.37 (several peaks, 8H), 7.48 (d, J ) 12.4,
1H), 7.74 (m, 2H); 13C NMR (CDCl3) δ 8.7, 14.3, 59.7, 71.6,
73.4, 82.7, 98.0, 127.7, 127.8, 128.1, 128.3, 128.4, 129.4, 137.5,
138.8, 161.6, 167.7; IR (neat) 1133, 1640, 1705 cm-1. Anal.
Calcd for C21H24O4Te: C, 53.89; H, 5.17. Found: C, 53.71; H,
5.18.
(E)-3-(2-P h en yl-2-ph en ylselen en yl-eth oxy)-acr ylic Acid
Eth yl Ester (2e): 1H NMR (CDCl3) δ 1.27 (t, J ) 7.1, 3H),
4.16 (q, J ) 7.1, 2H), 4.25 (m, 1H), 4.39 (dd, J ) 10.4, 9.2,
1H), 4.56 (dd, J ) 9.2, 5.5, 1H), 5.16 (d, J ) 12.7, 1H), 7.23-
7.38 (several peaks, 8H), 7.49 (d, J ) 12.7, 1H), 7.53 (m, 2H);
13C NMR (CDCl3) δ 14.3, 45.3, 59.7, 73.0, 96.9, 127.6, 127.7,
128.1, 128.4, 128.6, 128.7, 129.1, 135.5, 161.5, 167.4; IR (neat)
1133, 1625, 1708 cm-1. Anal. Calcd for C19H20O3Se: C, 60.80;
H, 5.37. Found: C, 60.71; H, 5.42.
(E)-3-(1-P h en ylselen en ylm eth yl-pen tyloxy)-acr ylic Acid
Eth yl Ester (2f): 1H NMR (CDCl3) δ 0.89 (m, 3H), 1.27 (t, J
) 7.1, 3H), 1.20-1.40 (several peaks, 4H), 1.71 (m, 2H), 3.03
(dd, J ) 12.9, 6.1, 1H), 3.09 (dd, J ) 12.9, 6.3, 1H), 4.01 (m,
1H), 4.15 (q, J ) 7.1, 2H), 5.14 (d, J ) 12.3, 1H), 7.25-7.31
(several peaks, 3H), 7.45 (dd, J ) 12.3, 0.5, 1H), 7.53 (m, 2H);
13C NMR (CDCl3) δ 13.8, 14.4, 22.4, 27.2, 31.8, 33.9, 59.7, 83.2,
97.4, 127.5, 129.2, 129.4, 133.3, 162.0, 168.0; IR (neat) 1138,
1639, 1702 cm-1. Anal. Calcd for C17H24O3Se: C, 57.46; H, 6.81.
Found: C, 57.25; H, 6.89.
(E)-3-(2-P h en oxy-1-p h en ylselen en ylm et h yl-et h oxy)-
a cr ylic Acid Eth yl Ester (2g): 1H NMR (CDCl3) δ 1.30 (t, J
) 7.2, 3H), 3.20 (dd, J ) 13.3, 6.1, 1H), 3.26 (dd, J ) 13.3, 6.6,
1H), 4.13-4.24 (several peaks, 4H), 4.40 (m, 1H), 5.23 (d, J )
12.3, 1H), 6.87 (m, 2H), 7.01 (m, 1H), 7.27-7.32 (several peaks,
5H), 7.55 (d, J ) 12.3, 1H), 7.58 (m, 2H); 13C NMR (CDCl3) δ
14.3, 27.8, 59.7, 68.3, 80.9, 98.2, 114.5, 121.3, 127.6, 129.3,
129.4, 133.3, 157.9, 161.5, 167.5; IR (neat) 1133, 1642, 1707
cm-1; HRMS calcd for C20H22O4Se 406.0683, found 406.0695.
(E)-3-(1-P h en yl-2-ph en ylselen en yl-eth oxy)-acr ylic Acid
Eth yl Ester (2h ): 1H NMR (CDCl3) δ 1.24 (t, J ) 7.1, 3H),
3.22 (dd, J ) 13.0, 5.2, 1H), 3.40 (dd, J ) 13.0, 8.2, 1H), 4.10
(dq, J ) 10.8, 7.1, 1H), 4.14 (dq, J ) 10.8, 7.1, 1H), 5.02 (ddm,
J ) 8.2, 5.2, 1H), 5.19 (d, J ) 12.5, 1H), 7.26-7.40 (several
peaks, 8H), 7.48 (dd, J ) 12.5, 0.4, 1H), 7.51 (m, 2H); 13C NMR
(CDCl3) δ 14.3, 34.4, 59.7, 83.7, 98.9, 126.2, 127.4, 128.7, 128.8,
129.2, 129.5, 133.3, 138.9, 160.9, 167.5; IR (neat) 1131, 1642,
In conclusion, novel methodology for the preparation
of tetrahydrofuran-3-ones and pyrrolidin-3-ones from
readily available starting materials was developed, using
radical carbonylation/reductive cyclization in the key
step. The required radical precursors were obtained
either from epoxides via regioselective benzenselenolate
ring-opening and O-vinylation (for tetrahydrofuran-3-
ones) or from aziridines via N-vinylation and regioselec-
tive benzeneselenolate ring-opening (for pyrrolidin-3-
ones).
Exp er im en ta l Section
Coupling constants given below are in hertz (Hz).
Typ ica l P r oced u r e for Con ju ga te Ad d ition of â-Hy-
d r oxyla lk yl P h en yl Ch a lcogen id es to Eth yl P r op iola te:
P r epar ation of (E)-3-(1-Ben zyl-2-ph en ylselen en yl-eth oxy)-
a cr ylic Acid Eth yl Ester (2a ). To a stirred solution of
2-hydroxy-3-phenylpropyl phenyl selenide (0.965 g, 3.3 mmol)
in CH2Cl2 (10 mL) was added N-methyl morpholine (NMM)
(0.546 mL, 5.0 mmol). Ethyl propiolate (0.503 mL, 5.0 mmol)
was then added, and the resulting mixture was stirred for 6 h
at room temperature. The solvent was removed in vacuo, and
the residue was purified by flash chromatography (5-10%
ethyl acetate/pentane) to afford 1.23 g (95%) of the title
compound as a yellowish oil: 1H NMR (CDCl3) δ 1.25 (t, J )
7.1, 3H), 2.97-3.10 (several peaks, 4H), 4.12 (q, J ) 7.1, 2H),
4.22 (m, 1H), 5.12 (d, J ) 12.4, 1H), 7.14 (m, 2H), 7.21-7.31
(several peaks, 6H), 7.34 (d, J ) 12.4, 1H), 7.48 (m, 2H); 13C
NMR (CDCl3) δ 14.3, 30.9, 40.2, 59.7, 83.5, 97.7, 126.9, 127.5,
128.6, 129.1, 129.3, 129.5, 133.2, 136.3, 161.6, 167.8; IR (neat)
(31) For other examples of diastereocontrol by the N-substitutent,
see ref 15b.
J . Org. Chem, Vol. 68, No. 22, 2003 8391

Berlin et al.
1708 cm-1. Anal. Calcd for C19H20O3Se: C, 60.80; H, 5.37.
Found: C, 60.66; H, 5.21.
Spectral data for compounds 3 prepared are shown below.
For yields and isomeric ratios, see Table 1.
(E)-3-(1-Eth yl-2-p h en ylselen en yl-bu toxy)-a cr ylic Acid
Eth yl Ester (2j): 1H NMR (CDCl3) δ 0.91 (t, J ) 7.4, 3H),
1.12 (t, J ) 7.3, 3H), 1.28 (t, J ) 7.1, 3H), 1.58 (m, 1H), 1.78-
1.89 (several peaks, 3H), 3.17 (m, 1H), 3.93 (m, 1H), 4.17 (q, J
) 7.1, 2H), 5.22 (d, J ) 12.2, 1H), 7.27-7.31 (several peaks,
3H), 7.42 (d, J ) 12.2, 1H), 7.56 (m, 2H); 13C NMR (CDCl3) δ
9.8, 12.7, 14.4, 23.9, 25.6, 51.9, 59.6, 88.3, 97.1, 129.1, 127.7,
[(2R*,5R*)-5-Ben zyloxym eth yl-3-oxo-tetr a h yd r o-fu r a n -
2-yl]-a cetic Acid Eth yl Ester (3c, cis): H NMR (CDCl3) δ
1
1.23 (t, J ) 7.1, 3H), 2.52 (dd, J ) 17.9, 6.9, 1H), 2.58 (dd, J
) 18.0, 9.3, 1H), 2.75 (dd, J ) 16.9, 5.5, 1H), 2.83 (dd, J )
16.9, 4.2, 1H), 3.65 (dd, J ) 10.5, 5.3, 1H), 3.69 (dd, J ) 10.5,
3.9, 1H), 4.09 (dd, J ) 4.2, 5.5, 1H), 4.12 (q, J ) 7.1, 2H), 4.43
(m, 1H), 4.59 (s, 2H), 7.27-7.36 (several peaks, 5H); 13C NMR
(CDCl3) δ 14.1, 36.1, 38.8, 60.9, 71.6, 73.5, 75.2, 77.4, 127.7,
127.7, 128.4, 137.7, 169.9, 213.9. [(2S*,5R *)-5-Ben zyloxy-
m eth yl-3-oxo-tetr a h yd r o-fu r a n -2-yl]-a cetic Acid Eth yl
Ester (3c, tr a n s): 1H NMR (CDCl3) δ 1.25 (t, J ) 7.1, 3H),
2.51 (ddd, J ) 17.9, 4.8, 0.8, 1H), 2.73-2.84 (several peaks,
3H), 3.54 (dd, J ) 10.3, 4.0, 1H), 3.72 (dd, J )10.3, 3.2, 1H),
4.14 (q, J ) 7.1, 2H), 4.29 (m, 1H), 4.53 (d, J ) 12.1, 1H), 4.60
(d, J ) 12.1, 1H), 4.63 (m, 1H), 7.26-7.36 (several peaks, 5H);
13C NMR (CDCl3) δ 15.2, 37.0, 38.1, 65.7, 73.0, 73.5, 75.2, 76.1,
127.5, 128.5, 129.1, 137.6, 170.1, 214.5. 3c (mixture of dia-
stereomers): IR (neat) 1028, 1096, 1378, 1735, 1758, 2982
cm-1; HRMS calcd for C16H20O5 292.1311, found 292.1274.
129.1, 134.9, 163.0, 168.1; IR (neat) 1141, 1637, 1698 cm-1
.
Anal. Calcd for C17H24O3Se: C, 57.46; H, 6.81. Found: C, 57.30;
H, 6.74.
(E )-3-(t r a n s -2-P h e n y ls e le n e n y l-c y c lo h e x y lo x y )-
a cr ylic Acid Eth yl Ester (2k ): 1H NMR (CDCl3) δ 1.27 (t, J
) 7.1, 3H), 1.29-1.36 (several peaks, 3H), 1.45-1.78 (several
peaks, 5H), 2.08-2.19 (several peaks, 2H), 3.25 (ddd, J ) 10.0,
8.4, 4.3, 1H), 3.95 (ddd, J ) 12.6, 8.6, 4.0, 1H), 4.15 (q, J )
7.1, 2H), 5.15 (d, J ) 12.4, 1H), 7.25-7.31 (several peaks, 3H),
7.48 (d, J ) 12.5, 1H), 7.56 (m, 2H); 13C NMR (CDCl3) δ 14.4,
23.1, 25.1, 31.1, 31.7, 46.2, 59.7, 80.1, 97.3, 126.7, 128.4, 129.4,
137.0, 161.6, 168.0; IR (neat) 1133, 1639, 1707 cm-1; HRMS
calcd for C17H22O3Se 354.0734, found 354.0748.
In the preparation of tetrahydrofuran-3-one 3c (Table 1,
entries 3 and 4), compound 5 was isolated as a byproduct in
32 and 30% yields. A control experiment conducted under the
same conditions as in the typical procedure for carbonylation/
reductive radical cyclization, but in the absence of CO, afforded
compound 5 as a colorless oil in 82% yield: [(2R*,3R*,6S*)-
6-Meth yl-3-p h en yl-[1,4]d ioxa n -2-yl]-a cetic Acid Eth yl Es-
ter (5): 1H NMR (CDCl3) δ 1.13 (d, J ) 6.2, 3H), 1.18 (t, J )
7.1, 3H), 2.19 (dd, J ) 15.3, 3.9, 1H), 2.35 (dd, J ) 15.3, 8.6,
1H), 3.42 (dd, J ) 10.2, 11.4, 1H), 3.88 (dd, J ) 11.3, 2.7, 1H),
3.93 (m, 1H), 4.02 (q, J ) 7.1, 2H), 4.04 (m, 1H), 4.19 (d, J )
9.1, 1H), 7.28-7.38 (several peaks, 5H); 13C NMR (CDCl3) δ
14.1, 16.7, 37.2, 60.5, 71.8, 72.4, 77.2, 81.9, 127.7, 128.5, 128.6,
137.6, 170.6; IR (neat) 1094, 1157, 1740, 2978 cm-1; HRMS
calcd for C15H20O4 264.1362, found 264.1346.
P r ep a r a tion of (E)-3-(1-Ben zyl-2-p h en ylselen en yl-eth -
oxy)-p h en ylsu lfon yl Eth ylen e (2i). To a stirred solution of
2-hydroxy-3-phenylpropyl phenyl selenide (412 mg, 1.4 mmol)
in THF (13 mL) was added NaH (60% in mineral oil, 85 mg,
2.1 mmol) in small portions. The resulting suspension was
stirred for 15 min. (E)-1,2-Bis-(phenylsulfonyl)ethylene (567
mg, 1.8 mmol) was then added, and the mixture was stirred
for an additional 6 h at rt. The solvent was removed in vacuo,
and the residue was purified using flash chromatography (5-
10% ethyl acetate/pentane) to afford the title compound (512
mg, 79%) as a yellowish oil: 1H NMR (CDCl3) δ 2.96 (dd, J )
14.1, 7.5, 1H), 3.04 (d, J ) 6.1, 2H), 3.08 (dd, J ) 14.1, 5.0,
1H), 4.21 (ddt, J ) 7.4, 6.1, 5.0, 1H), 5.48 (d, J ) 12.0, 1H),
7.11 (m, 2H), 7.19-7.31 (several peaks, 7H), 7.42-7.60 (several
peaks, 5H), 7.74 (m, 2H); 13C NMR (CDCl3) δ 30.7, 40.2, 84.8,
107.1, 126.4, 126.4, 127.1, 128.1, 128.4, 128.2, 128.8, 128.9,
131.9, 132.9, 135.6, 142.7, 159.9; IR (neat) 1084, 1142, 1217,
1305, 1625, 2928, 3065 cm-1; HRMS calcd for C23H22O3SSe
458.0455, found 458.0494.
[(2R*,5S*)-5-Bu t yl-3-oxo-t et r a h yd r o-fu r a n -2-yl]-a ce-
tic Acid Eth yl Ester (3f, cis): 1H NMR (CDCl3) δ 0.89-0.95
(m, 3H), 1.26 (t, J ) 7.1, 3H), 1.28-1.48 (several peaks, 4H),
1.61 (m, 1H), 1.79 (m, 1H), 2.33 (dd, J ) 17.9, 10.7, 1H), 2.53
(dd, J ) 17.9, 5.7, 1H), 2.72 (dd, J ) 16.8, 5.4, 1H), 2.81 (dd,
J ) 16.8, 4.3, 1H), 4.01 (dd, J ) 5.4, 4.3, 1H), 4.14 (m, 1H),
4.15 (q, J ) 7.1, 2H); 13C NMR (CDCl3) δ 14.0, 14.1, 22.6, 27.4,
35.1, 36.0, 42.5, 60.9, 76.3, 77.6, 170.0, 215.5. [(2S*,5S*)-5-
Bu tyl-3-oxo-tetr a h yd r o-fu r a n -2-yl]-a cetic Acid Eth yl Es-
ter (3f, tr a n s): 1H NMR (CDCl3) δ 0.86-0.97 (m, 3H), 1.26
(t, J ) 7.1, 3H), 1.26-1.47 (several peaks, 4H), 1.54 (m, 1H),
1.72 (m, 1H), 2.24 (ddd, J ) 18.0, 6.6, 1.0, 1H), 2.75 (m, 2H),
2.76 (ddd, J ) 18.0, 7.2, 0.5, 1H), 4.15 (q, J ) 7.1, 2H), 4.20
(m, 1H), 4.43 (m, 1H); 13C NMR (CDCl3) δ 14.0, 14.1, 22.5, 27.6,
35.6, 36.7, 42.2, 61.0, 75.3, 43.1, 170.3, 215.5. 3f (mixture of
diastereomers): IR (neat) 1027, 1099, 1159, 1192, 1377, 1741,
1763, 2863 cm-1; HRMS calcd for C12H20O4 228.1362, found
228.1342.
Typ ica l P r oced u r e for Ca r bon yla tion /Red u ctive Ra d i-
ca l Cycliza tion . P r ep a r a tion (5-Ben zyl-3-oxo-tetr a h yd r o-
fu r a n -2-yl)-a cetic Acid Eth yl Ester (3a ). To a solution of
compound 2a (0.143 g, 0.36 mmol) in dry benzene (50 mL) were
added AIBN (0.018 g, 0.11 mmol) and tris(trimethylsilyl)silane
(TTMSS) (0.192 mL, 0.62 mmol). The solution was then purged
once with 20 atm of carbon monoxide and then pressurized to
80 atm and heated to 80 °C. After 12 h, the reaction mixture
was cooled and the solvent removed in vacuo. The residue, on
purification by flash chromatography (20-25% ethyl acetate/
pentane), afforded the title compound 3a (0.083 g, 86%) as a
9:1 mixture of cis and trans isomers. [(2R*,5S*)-5-Ben zyl-3-
oxo-tetr a h yd r o-fu r a n -2-yl]-a cetic Acid Eth yl Ester (3a ,
1
cis): H NMR (CDCl3) δ 1.28 (t, J ) 7.1, 3H), 2.44 (dd, J )
[(2R*,5R*)-3-Oxo-5-p h en oxym eth yl-tetr a h yd r o-fu r a n -
2-yl]-a cetic Acid Eth yl Ester (3g, cis): 1H NMR (CDCl3) δ
1.24 (t, J ) 7.2, 3H), 2.65 (dd, J ) 18.1, 7.2, 1H), 2.69 (dd, J
) 18.0, 9.2, 1H), 2.79 (dd, J ) 17.0, 5.4, 1H), 2.88 (dd, J )
17.0, 4.3, 1H), 4.13 (q, J ) 7.2, 2H), 4.14-4.18 (several peaks,
3H), 4.64 (m, 1H), 6.90-6.99 (several peaks, 3H), 7.26-7.31
(m, 2H); 13C NMR (CDCl3) δ 14.0, 36.1, 38.6, 60.8, 69.5, 74.3,
77.3, 114.4, 121.1, 129.4, 158.3, 169.8, 213.3. [(2S*,5R*)-3-
Oxo-5-ph en oxym eth yl-tetr ah ydr o-fu r an -2-yl]-acetic Acid
Eth yl Ester (3g, tr a n s): 1H NMR (CDCl3) δ 1.26 (t, J ) 7.2,
3H), 2.64 (ddd, J ) 18.0, 4.7, 0.8, 1H), 2.80 (dd, J ) 17.0, 4.5,
1H), 2.85 (dd, J ) 17.0, 4.5, 1H), 2.94 (dd, J ) 18.0, 8.6, 1H),
4.05 (dd, J ) 10.1, 3.6, 1H), 4.14 (q, J ) 7.2, 2H), 4.16 (m,
1H), 4.24 (dd, J ) 10.1,3.1, 1H), 4.83 (m, 1H), 6.89-6.97
(several peaks, 3H), 7.26-7.31 (m, 2H); 13C NMR (CDCl3) δ
14.1, 37.0, 38.0, 61.0, 74.5, 76.1, 114.5, 121.3, 129.5, 158.4,
170.2, 214.4. 3g (mixture of diastereomers): IR (neat) 1033,
17.9, 9.5, 1H), 2.49 (dd, J ) 17.9, 6.9, 1H), 2.74 (dd, J ) 16.8,
5.3, 1H), 2.84 (dd, J ) 16.8, 4.3, 1H), 2.97 (dd, J ) 13.7, 6.6,
1H), 3.14 (dd, J ) 13.7, 6.0, 1H), 4.05 (dd, J ) 5.3, 4.4, 1H),
4.16 (m, 2H), 4.44 (m, 1H), 7.23-7.29 (several peaks, 3H),
7.30-7.35 (m, 2H); 13C NMR (CDCl3) δ 14.1, 36.0, 41.5, 41.8,
60.9, 76.7, 77.6, 126.6, 128.4, 129.3, 136.9, 169.8, 214.4.
[(2S*,5S*)-5-Ben zyl-3-oxo-t et r a h yd r o-fu r a n -2-yl]-a cet ic
1
Acid Eth yl Ester (3a , tr a n s): H NMR (CDCl3) δ 1.25 (t, J
) 7.2, 3H), 2.34 (ddd, J ) 18.1, 6.6, 1.0, 1H), 2.71 (ddd, J )
18.1, 7.3, 0.7, 1H), 2.72 (dd, J ) 16.7, 5.2, 1H), 2.77 (dd, J )
16.7, 4.7, 1H), 2.88 (dd, J ) 13.8, 6.9, 1H), 3.05 (dd, J ) 13.8,
6.0, 1H), 4.14 (q, J ) 7.2, 2H), 4.21 (m, 1H), 4.73 (m, 1H), 7.20-
7.26 (several peaks, 3H), 7.30 (m, 2H); 13C NMR (CDCl3) δ 14.1,
36.8, 41.3, 42.0, 61.0, 75.7, 76.9, 126.7, 128.6, 129.4, 137.0,
170.2, 214.6. 3a (mixture of diastereomers): IR (neat) 1095,
1156, 1189, 1375, 1735, 1758, 2917, 2981 cm-1; HRMS calcd
for C15H18O4 262.1205, found 262.1173.
8392 J . Org. Chem., Vol. 68, No. 22, 2003

Construction of Tetrahydrofuran-3-ones and Pyrrolidin-3-ones
1156, 1195, 1234, 1735, 1763, 2929 cm-1; HRMS calcd for
(E)-3-(1-Met h yl-p en t yloxy)-a cr ylic Acid E t h yl E st er :
1H NMR (CDCl3) δ 0.90 (m, 3H), 1.26 (d, J ) 6.2, 3H), 1.26 (t,
J ) 7.2, 3H), 1.25-1.40 (several peaks, 2H), 1.45-1.72 (several
peaks, 4H), 4.03 (m, 1H), 4.15 (q, J ) 7.2, 2H), 5.22 (d, J )
12.4, 1H), 7.54 (dd, J ) 12.4, 0.5, 1H); 13C NMR (CDCl3) δ
13.9, 14.4, 20.0, 22.5, 27.4, 36.0, 59.6, 79.8, 97.0, 162.0, 168.3.
C
15H18O5 278.1154, found 278.1168.
[(2R*,5R*)-3-Oxo-5-p h en yl-tetr a h yd r o-fu r a n -2-yl]-a ce-
tic Acid Eth yl Ester (3h , cis): 1H NMR (CDCl3) δ 1.26 (t, J
) 7.2, 3H), 2.76 (dd, J ) 18.0, 10.6, 1H), 2.84 (dd, J ) 18.0,
6.3, 1H), 2.87 (dd, J ) 17.0, 4.7, 1H), 2.94 (dd, J ) 17.0, 4.3,
1H), 4.18 (dd, J ) 4.7, 4.3, 1H) 4.18 (dq, J ) 10.8, 7.2, 1H),
4.19 (dq, J ) 10.8, 7.2, 1H), 5.16 (dd, J ) 10.6, 6.3, 1H), 7.29-
7.45 (several peaks, 5H); 13C NMR (CDCl3) δ 14.1, 35.8, 44.6,
61.0, 77.8, 77.9, 126.3, 128.4, 128.6, 139.9, 169.9, 214.2.
[(2S*,5R*)-3-Oxo-5-p h en yl-t et r a h yd r o-fu r a n -2-yl]-a ce-
tic Acid Eth yl Ester (3h , tr a n s): 1HNMR (CDCl3) δ 1.30 (t,
J ) 7.2, 3H), 2.69 (ddd, J ) 18.1, 7.0, 1.1, 1H), 2.90 (d, J )
4.7, 2H), 3.15 (ddd, J ) 18.1, 7.7, 0.6, 1H), 4.20 (q, J ) 7.2,
2H), 4.39 (tdd, J ) 4.7, 1.1, 0.6, 1H), 5.56 (dd, J ) 7.7, 7.0,
1H), 7.24-7.55 (several peaks, 5H); 13C NMR (CDCl3) δ 14.1,
36.8, 44.0, 61.1, 75.9, 77.6, 125.7, 128.0, 128.7, 141.2, 170.4,
214.5. 3h (mixture of diastereomers): IR (neat) 1026, 1094,
1151, 1192, 1375, 1735, 1758, 2929 cm-1; HRMS calcd for
(E)-3-(1-Meth yl-2-p h en oxy-eth oxy)-a cr ylic Acid Eth yl
1
Ester : H NMR (CDCl3) δ 1.27 (t, J ) 7.2, 3H), 1.40 (d, J )
6.4, 3H), 3.99 (dd, J ) 10.1, 4.2, 1H), 4.05 (dd, J ) 10.1, 6.3,
1H), 4.17 (q, J ) 7.2, 2H), 4.43 (ddd, J ) 6.4, 6.3, 4.2, 1H),
5.30 (d, J ) 12.4, 1H), 6.90 (m, 2H), 6.97 (m, 1H), 7.28 (m,
2H), 7.61 (d, J ) 12.4, 1H); 13C NMR (CDCl3) δ 14.3, 16.9, 59.7,
70.8, 77.5, 98.0, 114.8, 121.4, 129.5, 158.4, 161.7, 167.8.
(E)-3-(1-P h en yl-eth oxy)-a cr ylic Acid Eth yl Ester : 1H
NMR (CDCl3) δ 1.25 (t, J ) 7.2, 3H), 1.61 (d, J ) 6.5, 3H),
4.12 (dq, J ) 10.9, 7.2, 1H), 4.13 (dq, J ) 10.9, 7.2, 1H), 5.06
(dq, J ) 6.5, 0.5, 1H), 5.25 (d, J ) 12.5, 1H), 7.29-7.41 (several
peaks, 5H), 7.54 (dd, J ) 12.5, 0.5, 1H); 13C NMR (CDCl3) δ
14.3, 23.3, 59.6, 80.4, 98.5, 125.7, 128.1, 128.7, 141.3, 161.2,
167.7.
P r ep a r a tion of Resin -Bou n d 2-Hyd r oxy-3-p h en ylp r o-
p yl P h en yl Selen id e (7). To a suspension of polymer-
supported diaryl diselenide 6 (300 mg, 0.675 mmol) in ethanol
(5 mL) was added NaBH4 (51 mg, 1.35 mmol). The suspension
was gently stirred for 6 h after which benzyloxirane (450 mg,
3.38 mmol) was added. The mixture was stirred overnight. HCl
(2 mL, 2 M) was added, and the reaction was stirred for
another 2 h. The filtered resin was washed successively with
water, ethanol, water, ethanol, ether, and ethanol to afford
title resin 7.
P r ep a r a tion of Resin -Bou n d (E)-3-(1-Ben zyl-2-p h e-
n ylselen en yl-eth oxy)-a cr ylic Acid Eth yl Ester (9). To a
preheated (60 °C) suspension of resin 7 from the previous
experiment in NMM (10 mL) was added ethyl propiolate (342
µl, 3.38 mmol). The suspension was gently stirred for 6 h. The
resin was then filtered and washed successively with water,
CH2Cl2, ethanol, water, ethanol, ether, and ethanol to afford
the title resin 9.
C
14H16O4 248.1049, found 248.1026.
(2S*,5S*)-2-Ben zen esu lfon ylm eth yl-5-ben zyl-d ih yd r o-
1
fu r a n -3-on e (3i, cis): H NMR (CDCl3) δ 2.24 (dd, J ) 18.3,
10.3, 1H), 2.50 (dd, J ) 18.3, 5.7, 1H), 2.90 (dd, J ) 14.1, 6.0,
1H), 2.98 (dd, J ) 14.1, 6.0, 1H), 3.33 (dd, J ) 14.8, 8.2, 1H),
3.57 (dd, J ) 14.8, 2.6, 1H), 4.23 (dd, J ) 8.2, 2.6, 1H), 4.40
(m, 1H), 7.01-7.08 (m, 2H), 7.19-7.35 (m, 3H), 7.53-7.60 (m,
2H), 7.64-7.70 (m, 1H), 7.93-7.98 (m, 2H); 13C NMR (CDCl3)
δ 40.8, 40.8, 57.4, 76.3, 76.9, 126.7, 128.2, 128.4, 129.1, 129.4,
133.8, 136.3, 140.0, 211.7. (2R*,5S*)-2-Ben zen esu lfon yl-
m eth yl-5-ben zyl-d ih yd r o-fu r a n -3-on e (3i, tr a n s): 1H NMR
(CDCl3) δ 2.36 (ddd, J ) 18.3, 6.6, 0.9, 1H), 2.59 (dd, J ) 18.3,
7.2, 1H), 2.85 (dd, J ) 14.0, 6.5, 1H), 2.97 (dd, J ) 14.0, 6.1,
1H), 3.37 (dd, J ) 14.7, 8.1, 1H), 3.49 (dd, J ) 14.7, 3.0, 1H),
4.13 (m, 1H), 4.61 (m, 1H), 7.14-7.34 (several peaks, 5H),
7.47-7.53 (m, 2H), 7.63 (m, 1H), 7.86-7.93 (m, 2H); 13C NMR
(CDCl3) δ 40.5, 41.2, 57.3, 74.2, 76.6, 126.8, 128.1, 128.6, 129.2,
129.4, 134.2, 136.4, 139.8, 212.1. 3i (mixture of diastereomers):
IR (neat) 1084, 1144, 1308, 1448, 1762, 2918 cm-1; HRMS calcd
for C18H18O4S 330.0926, found 330.0930.
Typ ica l P r oced u r e for Ra d ica l Ca r bon yla tion /Red u c-
tive Cycliza tion of P olym er -Bou n d Resin : P r ep a r a tion
of (5-Ben zyl-3-oxo-tetr ah ydr o-fu r an -2-yl)-acetic Acid Eth -
yl Ester (3a ). To resin 9 from the previous experiment swelled
in benzene (114 mL) were added AIBN (33 mg, 0.2 mmol) and
TTMSS (354 µL, 1.14 mmol, 0.01 M). The suspension was
pressurized with CO at 80 atm and heated to 80 °C for 12 h.
After filtration and washing with diethyl ether, the combined
filtrate was concentrated and purified by column chromatog-
raphy to afford the title compound (97 mg, 55% over three
steps) as a 9:1 mixture of cis and trans isomers.
Typ ica l P r oced u r e for Red u ctive Clea va ge of Resin -
Bou n d Selen id es. To a preheated (80 °C) suspension of resin
9 from the above experiment in benzene (10 mL) were added
AIBN (11 mg, 0.06 mmol) and TTMSS (1.04 mL, 3.38 mmol).
The suspension was heated at reflux for 8 h, after which the
reaction was filtered and the solid washed with diethyl ether.
The combined filtrate was concentrated and purified by flash
chromatography to afford vinyl ether 4 (144 mg, 91% over
three steps).
(4,5-Dieth yl-3-oxo-tetr a h yd r o-fu r a n -2-yl)-a cetic Acid
Eth yl Ester (3j): Characteristic peaks in 1H NMR (CDCl3) δ
1.26 (t, J ) 7.1, 3H), 2.19 (dt, J ) 9.7, 6.0, 1H), 2.70 (dd, J )
16.5, 5.6, 1H), 2.81 (dd, J ) 16.5, 4.4, 1H), 3.79 (ddd, J ) 9.7,
7.1, 3.9, 1H), 3.96 (dd, J ) 5.5, 4.3, 1H), 4.15 (q, J ) 7.1, 2H);
MS m/e 229 (M + 1), 213, 201, 149, 139; IR (neat) 1033, 1161,
1188, 1376, 1466, 1740, 1758, 2937 cm-1; HRMS calcd for
C
12H20O4 228.1362, found 228.1345.
(3-Oxo-octa h yd r o-ben zofu r a n -2-yl)-a cetic Acid Eth yl
Ester (3k ): Characteristic peaks in 1H NMR (CDCl3) δ 1.23
(t, J ) 7.1, 3H), 2.73 (dd, J ) 16.8, 5.8, 1H), 2.81 (dd, J )
16.8, 4.1, 1H), 3.45 (dt, J ) 11.3, 3.9, 1H), 3.97 (dd, J ) 5.8,
4.1, 1H), 4.13 (q, J ) 7.1, 2H); MS m/e 227 (M + 1), 213, 185,
149, 139; IR (neat) 1132, 1187, 1264, 1376, 1448, 1740, 1762,
2863 cm-1; HRMS calcd for C12H18O4 226.1205, found 226.1182.
Below are spectroscopic data for reduced, uncyclized prod-
ucts isolated in the preparation of compounds 3a and 3e-h ,
respectively.
(E)-3-(1-Meth yl-2-p h en yl-eth oxy)-a cr ylic Acid Eth yl
1
Ester (4): H NMR (CDCl3) δ 1.26 (t, J ) 7.1, 3H), 1.28 (d, J
Reductive cleavage of resin 7 similarly afforded 1-phenyl-
2-propanol 8 (89 mg, 97% over two steps) with spectral data
in accordance with literature.32
) 6.2, 3H), 2.80 (dd, J ) 13.8, 6.3, 1H), 2.98 (dd, J ) 13.8, 6.6,
1H), 4.14 (q, J ) 7.1, 2H), 4.22-4.30 (m, 1H), 5.24 (d, J )
12.5, 1H), 7.16-7.32 (m, 5H), 7.47 (d, J ) 12.5, 1H); 13C NMR
(CDCl3) δ 14.4, 19.6, 42.5, 59.7, 80.1, 97.3, 126.7, 128.4, 129.4,
137.0, 161.6, 168.0; IR (neat) 1130, 1622, 1642, 1708, 2980,
3029 cm-1; HRMS calcd for C14H18O3 + H+ 235.1334, found
235.1346.
2-Am in o-3-p h en ylp r op yl P h en yl Selen id e (10, R
)
Bn ): 1H NMR (CDCl3) δ 1.46 (br s, 2H), 2.67 (dd, J ) 7.9,
13.3, 1H), 2.86 (dd, J ) 8.0, 12.4, 1H), 2.88 (dd, J ) 5.4, 13.3,
1H), 3.14 (dd, J ) 4.3, 12.4, 1H), 3.22 (m, 1H) 7.18 (m, 2H),
7.21-7.34 (several peaks, 6H), 7.47-7.52 (several peaks, 2H);
13C NMR (CDCl3) δ 36.6, 44.0, 52.5, 126.4, 126.9, 128.5, 129.1,
129.2, 130.1, 132.6, 138.8; IR (neat) 1437, 1478, 1578, 2920,
(E)-3-P h en eth yloxy-a cr ylic Acid Eth yl Ester : 1H NMR
(CDCl3) δ 1.28 (t, J ) 7.1, 3H), 3.04 (t, J ) 6.9, 2H), 4.07 (t, J
) 6.9, 2H), 4.18 (q, J ) 7.1, 2H), 5.23 (d, J ) 12.5, 1H), 7.21-
7.39 (several peaks, 5H), 7.60 (d, J ) 12.5, 1H); 13C NMR
(CDCl3) δ 14.3, 35.3, 59.8, 71.3, 96.7, 126.7, 128.6, 128.8, 137.2,
162.1, 167.7.
(32) Hayashi, T.; Matsumoto, Y.; Ito, Y. Tetrahedron: Asymmetry
1991, 2, 601.
J . Org. Chem, Vol. 68, No. 22, 2003 8393

Berlin et al.
3025, 3058, 3366 cm-1; HRMS calcd for C15H17NSe + H+
J ) 3.9, 1H), 3.66 (s, 3H), 3.87 (s, 3H), 5.27 (s, 1H); 13C NMR
(CDCl3) δ 26.1, 30.4, 30.7, 49.2, 51.4, 52.6, 101.9, 160.3, 166.2,
166.4. (Z)-11e: 1H NMR (CDCl3) δ 0.97 (s, 9H), 1.73 (dd, J )
6.3, 1.0, 1H), 2.24 (dd, J ) 6.4, 4.0, 1H), 2.60 (dd, J ) 4.0, 1.0,
1H), 3.72 (s, 3H), 3.79 (s, 3H), 6.08 (s, 1H); 13C NMR (CDCl3)
δ 26.7, 31.0, 35.4, 50.3, 51.3, 52.4, 106.8, 154.9, 164.4, 165.3.
11e (mixture of diastereomers): IR (neat) 1171, 1261, 1437,
1608, 1714, 1744, 2953 cm-1. Anal. Calcd for C12H19NO4: C,
59.73; H, 7.94. Found: C, 59.51; H, 8.12.
292.0605, found 292.0610.
Typ ica l P r oced u r e for N-Vin yla tion of Azir id in es.
Syn th esis of 3-(2-Ben zyl-a zir idin -1-yl)-a cr ylic Acid Meth -
yl Ester (11a ). Methyl propiolate (0.775 mL, 8.7 mmol) was
slowly added to 2-benzyl-aziridine (1.10 g, 8.3 mmol), and the
reaction mixture was stirred at room temperature for 2 h. After
in vacuo removal of excess methyl propiolate, the pure title
compound was obtained in quantitative yield as a colorless oil.
For the synthesis of N-vinyl aziridines 11e and 11f, stoichio-
metric amounts of ethynyl p-tolyl sulfone and dimethyl acetyl-
enedicarboxylate, respectively, were used instead of methyl
2-Ben zyl-1-[2-(tolu en e-4-su lfon yl)-vin yl]-azir idin e (11f).
(Z)-11f: 1H NMR (CDCl3) δ 2.33 (d, J ) 3.7, 1H), 2.37 (d, J )
5.9, 1H), 2.43 (s, 3H), 2.58 (m, 1H), 2.70 (dd, J ) 6.7, 14.3,
1H), 3.17 (dd, J ) 5.4, 14.3, 1H), 5.57 (d, J ) 8.9, 1H), 6.51 (d,
J ) 8.9, 1H), 7.20-7.33 (several peaks, 7H), 7.86-7.88 (several
peaks, 2H); 13C NMR (CDCl3) δ 21.5, 37.7, 38.2, 42.6, 113.3,
126.5, 126.8, 128.4, 128.8, 129.5, 137.8, 140.0, 143.6, 151.0;
IR (neat) 1142, 1300, 1596, 2922, 3062 cm-1; HRMS calcd for
1
propiolate. (E)-11a : H NMR (CDCl3) δ 2.02 (dt, J ) 5.9, 0.4,
1H), 2.10 (dm, J ) 3.4, 1H), 2.27 (m, 1H), 2.78 (dd, J ) 14.3,
6.8, 1H), 2.78 (dd, J ) 14.3, 5.5, 1H), 3.67 (s, 3H), 5.24 (d, J )
13.4, 1H), 7.22-7.37 (several peaks, 5H), 7.50 (d, J ) 13.4,
1H); 13C NMR (CDCl3) δ 33.8, 38.5, 40.3, 51.1, 105.2, 126.6,
128.6, 128.6, 138.2, 157.2, 168.0. (Z)-11a : 1H NMR (CDCl3) δ
2.12 (dt, J ) 5.7, 0.4, 1H), 2.10 (dm, J ) 3.6, 1H), 2.42 (m,
1H), 2.75 (dd, J ) 14.3, 6.5, 1H), 3.15 (dd, J ) 14.3, 5.7, 1H),
3.72 (s, 3H), 5.15 (d, J ) 8.9, 1H), 6.61 (d, J ) 8.9, 1H), 7.22-
7.34 (several peaks, 5H); 13C NMR (CDCl3) δ 37.2, 38.3, 42.5,
50.8, 102.3, 126.4, 128.5, 128.6, 138.4, 155.0, 165.8. 11a
(mixture of diastereomers): IR (neat) 1154, 1266, 1621, 1709,
2949 cm-1. Anal. Calcd for C13H15NO2: C, 71.87; H, 6.96.
Found: C, 71.85; H, 6.97.
C
18H19NO2S + H+, 314.1215, found 314.1218.
3-(8-Aza -bicyclo[5.1.0]oct-8-yl)-a cr ylic Acid Meth yl Es-
ter (11g). (E)-11g: 1H NMR (CDCl3) δ 1.25-1.63 (several
peaks, 6H), 1.73-1.85 (several peaks, 2H), 1.88-1.96 (several
peaks, 2H), 2.13-2.19 (several peaks, 2H), 3.67 (s, 3H), 5.27
(d, J ) 13.4, 1H), 7.53 (d, J ) 13.4, 1H); 13C NMR (CDCl3) δ
25.6, 29.2, 31.5, 43.8, 51.0, 103.9, 158.5, 168.3. (Z)-11g: 1H
NMR (CDCl3) δ 1.25-1.63 (several peaks, 6H), 1.73-1.85
(several peaks, 2H), 2.00-2.09 (several peaks, 2H), 2.24-2.30
(several peaks, 2H), 3.67 (s, 3H), 5.03 (d, J ) 9.0, 1H), 6.60 (d,
J ) 9.0, 1H); 13C NMR (CDCl3) δ 25.7, 29.2, 31.7, 46.5, 50.7,
101.4, 155.9, 166.2. 11g (mixture of diastereomers): IR (neat)
1147, 1620, 1714, 2925 cm-1; HRMS calcd for C11H17NO2Se +
H+, 196.1338, found 196.1366.
Spectral data for compounds 11 prepared are shown below.
For yields and E/ Z ratios, see Table 3.
3-(2-P h en oxym eth yl-a zir id in -1-yl)-a cr ylic Acid Meth yl
Ester (11b). (E)-11b: 1H NMR (CDCl3) δ 2.11 (dt, J ) 6.1,
0.5, 1H), 2.20 (dd, J ) 3.4, 0.5, 1H), 2.50 (m, 1H), 3.70 (s, 3H),
3.94 (dd, J ) 10.5, 6.7, 1H), 4.13 (dd, J ) 10.5, 4.2, 1H), 5.14
(d, J ) 13.4, 1H), 6.89-7.00 (several peaks, 3H), 7.26-7.32
(several peaks, 2H), 7.54 (dm, J ) 13.4, 1H); 13C NMR (CDCl3)
δ 31.4, 37.6, 51.2, 68.8, 106.3, 114.6, 121.1, 129.5, 156.4, 158.3,
3-(2,2-Dim eth yl-a zir id in -1-yl)-a cr ylic Acid Meth yl Es-
1
ter (11h ). (E)-11h : H NMR (CDCl3) δ 1.26 (s, 6H), 1.91 (s,
2H), 3.68 (s, 3H), 5.28 (d, J ) 13.4, 1H), 7.50 (d, J ) 13.4,
1H); 13C NMR (CDCl3) δ 21.9, 39.3, 40.5, 50.5, 104.1, 155.0,
1
1
167.6. (Z)-11h : H NMR (CDCl3) δ 1.30 (s, 6H), 2.06 (s, 2H),
167.8. (Z)-11b: H NMR (CDCl3) δ 2.20 (d, J ) 5.8, 1H), 2.40
3.68 (s, 3H), 5.16 (d, J ) 8.9, 1H), 6.58 (d, J ) 8.9, 1H); 13C
NMR (CDCl3) δ 21.9, 41.6, 43.4, 50.1, 101.5, 152.7, 165.7. 11h
(mixture of diastereomers): IR (neat) 1158, 1312, 1618, 1711
cm-1; HRMS calcd for C8H14NO2+H+, 156.1025, found 156.1032.
Typ ica l P r oced u r es (A a n d B) for Rin g-Op en in g of
Vin yla ted Azir id in es w ith Ben zen eselen ola te. Syn th esis
of 3-(2-P h en yl-1-p h en ylselen en ylm et h yl-et h yla m in o)-
a cr ylic Acid Met h yl E st er (12a ): P r oced u r e A. NaBH4
(0.149 g, 3.94 mmol) was added to a solution of diphenyl
diselenide (1.12 g, 3.59 mmol) in ethanol (20 mL). To the
colorless reaction mixture was added dropwise 3-(2-benzyl-
aziridin-1-yl)-acrylic acid methyl ester 11a (1.30 g, 5.98 mmol),
and the solution was stirred for 6 h. R-Bromoacetic acid was
added, and the reaction mixture was stirred for an additional
hour. The white suspension was diluted with diethylether (50
mL) and then extracted with NaHCO3 (saturated aqueous) and
NaCl (saturated). After drying of the mixture over MgSO4 and
in vacuo removal of solvent, the title compound (2.19 g, 98%)
was obtained as a 4/5 mixture of (E)- and (Z)-isomers.
P r oced u r e B. NaBH4 (0.149 g, 3.94 mmol) was added to a
solution of diphenyl diselenide (1.12 g, 3.59 mmol) in ethanol
(20 mL). To the colorless reaction mixture was added dropwise
3-(2-benzyl-aziridin-1-yl)-acrylic acid methyl ester 11a (1.30
g, 5.98 mmol), and the solution was stirred for 6 h. The solvent
was evaporated and the residue diluted with diethyl ether (50
mL). The organic phase was extracted with H2O and NaCl
(saturated) and then dried over MgSO4. After in vacuo removal
of the solvent, the residue was purified by column chroma-
tography on neutral alumina (3-10% EtOAc in pentane) to
afford the title compound (1.87 g, 84%) as a 4/5 mixture of
(d, J ) 3.5, 1H), 2.64 (m, 1H), 3.70 (s, 3H), 4.06 (dd, J ) 10.5,
5.2, 1H), 4.32 (dd, J ) 10.5, 5.3, 1H), 5.19 (d, J ) 9.0, 1H),
6.67 (d, J ) 9.0, 1H), 6.91-6.98 (several peaks, 3H), 7.24-
7.31 (several peaks, 2H); 13C NMR (CDCl3) δ 34.7, 40.0, 50.8,
68.6, 103.0, 114.5, 120.9, 129.3, 154.3, 158.4, 165.7. 11b
(mixture of diastereomers): IR (neat) 1158, 1245, 1272, 1496,
1625, 1708, 2949, 2994 cm-1. Anal. Calcd for C13H15NO3: C,
66.94; H, 6.48. Found: C, 66.76; H, 6.47.
3-(2-Hexyl-azir idin -1-yl)-acr ylic Acid Meth yl Ester (11c).
1
(E)-11c: H NMR (CDCl3) δ 0.88 (m, 3H), 1.24-1.54 (several
peaks, 10H), 1.93-1.96 (several peaks, 2H), 2.01 (m, 1H), 3.69
(s, 3H), 5.31 (d, J ) 13.3, 1H), 7.52 (d, J ) 13.3, 1H); 13C NMR
(CDCl3) δ 14.0, 22.5, 27.3, 29.0, 31.7, 32.2, 33.9, 39.8, 51.1,
105.0, 157.7, 168.1. (Z)-11c: 1H NMR (CDCl3) δ 0.88 (m, 3H),
1.24-1.54 (several peaks, 10H), 1.76 (m, 1H), 2.08 (m, 1H),
2.15 (m, 1H), 3.69 (s, 3H), 5.12 (d, J ) 8.9, 1H), 6.64 (d, J )
13.3, 1H); 13C NMR (CDCl3) δ 14.0, 22.6, 26.8, 29.0, 31.8, 32.1,
32.7, 41.8, 50.8, 102.2, 155.3, 165.9. 11c (mixture of diaster-
eomers): IR (neat) 1152, 1266, 1623, 1714, 2929 cm-1. Anal.
Calcd for C12H21NO2: C, 68.21; H, 10.02. Found: C, 68.24; H,
10.00.
3-(2-ter t-Bu tyl-a zir id in -1-yl)-a cr ylic Acid Meth yl Ester
(11d ). (E)-11d : 1H NMR (CDCl3) δ 0.91 (s, 9H), 1.76 (dt, J )
6.2, 0.7, 1H), 1.81 (ddd, J ) 6.2, 3.5, 0.5, 1H), 2.11 (dd, J )
3.6, 0.7, 1H), 3.68 (s, 3H), 5.29 (d, J ) 13.4, 1H), 7.51 (dt, J )
13.4, 0.6, 1H); 13C NMR (CDCl3) δ 26.3, 30.4, 36.3, 49.3, 51.1,
1
104.5, 158.7, 168.2. (Z)-11d : H NMR (CDCl3) δ 0.92 (s, 9H),
1.86 (dd, J ) 6.0, 3.7, 1H), 1.91 (dt, J ) 6.0, 0.6, 1H), 2.53 (dt,
J ) 3.7, 0.5, 1H), 3.68 (s, 3H), 5.10 (d, J ) 8.8, 1H), 6.64 (dm,
J ) 8.8, 1H); 13C NMR (CDCl3) δ 26.1, 30.4, 30.5, 49.6, 50.8,
101.7, 156.6, 165.9. 11d (mixture of diastereomers): IR (neat)
1
(E)- and (Z)-isomers. (Z)-12a : H NMR (CDCl3) δ 2.79-3.10
(several peaks, 4H), 3.43 (m, 1H), 3.65 (s, 3H), 4.40 (d, J )
8.1, 1H), 6.38 (dd, J ) 12.9, 8.1, 1H), 7.07-7.18 (several peaks,
1154, 1255, 1624, 1714, 2956 cm-1. Anal. Calcd for C10H17
NO2: C, 65.54; H, 9.35. Found: C, 65.44; H, 9.42.
-
2-(2-ter t-Bu t yl-a zir id in -1-yl)-b u t -2-en ed ioic Acid Di-
m eth yl Ester (11e).33 (E)-11e: 1H NMR (CDCl3) δ 0.88 (s,
9H), 1.95 (d, J ) 6.5, 1H), 2.07 (dd, J ) 6.5, 3.9, 1H), 2.19 (d,
(33) Configuration was assigned in analogy with compounds pre-
pared in ref 29.
8394 J . Org. Chem., Vol. 68, No. 22, 2003

Construction of Tetrahydrofuran-3-ones and Pyrrolidin-3-ones
2H), 7.21-7.31 (several peaks, 6H), 7.43-7.52 (several peaks,
2H), 7.92 (br m, 1H). Characteristic peaks in 13C NMR (CDCl3)
δ 33.9, 42.2, 50.1, 60.8, 82.0, 126.6, 127.1, 128.5, 129.1, 129.3,
peaks, 2H), 8.27 (d, J ) 11.2, 1H); 13C NMR (CDCl3) δ 26.5,
32.0, 35.9, 50.7, 52.5, 62.9, 86.8, 126.7, 129.0, 130.7, 132.1,
147.1, 152.5, 170.9; IR (neat) 1193, 1230, 1270, 1605, 1661,
1735, 1961, 3272 cm-1; HRMS calcd for C18H25NO4Se + H+,
400.1028, found 400.1016.
1
132.8, 137.2, 150.7, 170.8. (E)-12a : H NMR (CDCl3) δ 2.81-
3.07 (several peaks, 4H), 3.66 (s, 3H), 3.67 (m, 1H), 4.66 (br
m, 1H), 4.69 (d, J ) 13.4, 1H), 7.05-7.20 (several peaks, 2H),
7.21-7.31 (several peaks, 6H), 7.36 (dd, J ) 13.1, 9.1, 1H),
7.43-7.52 (several peaks, 2H). Characteristic peaks in 13C
NMR (CDCl3) δ 34.8, 40.6, 50.6, 58.6, 86.6, 126.8, 127.5, 128.9,
129.2, 129.3, 133.2, 136.7, 169.7. 12a (mixture of diastereo-
mers): IR (neat) 1196, 1478, 1615, 1669, 2944, 3023, 3059,
3316 cm-1; HRMS calcd for C19H21NO2Se + H+, 376.0817,
found 376.0977.
(1-Ben zyl-2-p h en ylselen en yl-eth yl)-[2-(tolu en e-4-su lfo-
n yl)-vin yl]-a m in e (12f). (Z)-12f: 1H NMR (CDCl3) δ 2.40 (s,
3H), 2.69-3.12 (several peaks, 4H), 3.37 (m, 1H), 4.50 (d, J )
8.6, 1H), 6.22 (dd, J ) 8.6, 13.4, 1H), 7.05 (m, 1H), 7.12 (m,
2H), 7.15-7.31 (several peaks, 8H), 7.48 (m, 2H), 7.68 (m, 2H);
13C NMR (CDCl3) δ 31.4, 33.9, 42.0, 61.0, 89.8, 125.8, 127.4,
128.1, 128.3, 128.8, 129.0, 129.4, 132.1, 133.0, 136.9, 141.5,
142.8, 145.7. (E)-12f: 1H NMR (CDCl3) δ 2.40 (s, 3H), 2.82
(dd, J ) 6.8, 14.0, 1H), 2.93 (dd, J ) 6.3, 14.0, 1H), 2.94 (m,
2H), 3.49 (m, 1H), 4.86 (d, J ) 12.7, 1H), 4.92 (t, J ) 9.0, 1H),
7.06 (m, 2H), 7.20 (m, 1H), 7.15-7.31 (several peaks, 8H), 7.42
(m, 2H), 7.63 (m, 2H); 13C NMR (CDCl3) δ 31.4, 31.8, 38.8, 61.0,
94.8, 126.2, 126.8, 127.6, 128.6, 129.1, 129.3, 129.3, 129.9,
133.3, 136.6, 141.6, 142.2, 146.2. 12f (mixture of diastereo-
mers): IR (neat) 1081, 1133, 1281, 1616, 2923, 3060, 3335
cm-1; HRMS calcd for C24H25NO2SSe + Na+ 494.0670, found
494.0630.
3-(t r a n s -2-P h e n y ls e le n e n y l-c y c lo h e p t y la m i n o )-
a cr ylic Acid Meth yl Ester (12g). (Z)-12g: 1H NMR (CDCl3)
δ 1.37-2.17 (several peaks, 10H), 3.27-3.40 (several peaks,
2H), 3.64 (s, 3H), 4.45 (d, J ) 7.9, 1H), 6.54 (dd, J ) 7.9, 13.0,
1H), 7.23-7.32 (several peaks, 3H), 7.51-7.56 (several peaks,
2H), 8.15 (br m, 1H); 13C NMR (CDCl3) δ 23.0, 26.4, 28.3, 32.1,
33.6, 50.2, 52.5, 64.0, 81.7, 127.7, 129.1, 129.4, 134.9, 150.8,
171.1. (E)-12g: 1H NMR (CDCl3) δ 1.37-2.17 (several peaks,
10H), 3.19 (m, 1H), 3.33 (m, 1H), 3.66 (s, 3H), 4.59 (d, J )
13.4, 1H), 4.66 (br m, 1H), 7.23-7.32 (several peaks, 3H), 7.39
(dd, J ) 9.0, 13.4, 1H), 7.51-7.56 (several peaks, 2H); 13C NMR
(CDCl3) δ 23.5, 26.1, 28.2, 32.8, 33.6, 50.5, 52.5, 64.0, 86.6,
128.0, 129.2, 129.4, 135.3, 150.8, 169.8. 12g (mixture of
diastereomers): IR (neat) 1207, 1477, 1615, 1667, 2930, 3320
cm-1; HRMS calcd for C17H23NO2Se + H, 354.0972, found
354.0973.
Spectral data for compounds 12 prepared are shown below.
For yields and E/ Z ratios, see Table 3.
3-(2-P h en oxy-1-p h en ylselen en ylm et h yl-et h yla m in o)-
a cr ylic Acid Meth yl Ester (12b). (Z)-12b: 1H NMR (CDCl3)
δ 3.16 (dd, J ) 13.0, 6.7, 1H), 3.27 (dd, J ) 13.0, 6.5, 1H), 3.60
(m, 1H), 3.65 (s, 3H), 4.02 (dd, J ) 9.3, 4.9, 1H), 4.09 (dd, J )
9.3, 5.0, 1H), 4.54 (d, J ) 8.1, 1H), 6.65 (dd, J ) 12.9, 8.2,
1H), 6.68-6.88 (several peaks, 2H), 6.98 (m, 1H), 7.19-7.31
(several peaks, 5H), 7.48-7.58 (several peaks, 2H), 8.10 (dd,
J ) 11.8, 9.7, 1H); 13C NMR (CDCl3) δ 28.7, 50.3, 58.4, 67.3,
87.1, 114.6, 121.3, 127.4, 129.1, 129.2, 129.4, 133.0, 147.8,
1
158.1, 170.7. (E)-12b: H NMR (CDCl3) δ 3.18 (dd, J ) 12.9,
7.6, 1H), 3.23 (dd, J ) 12.9, 5.4, 1H), 3.66 (s, 3H), 3.67 (m,
1H), 3.99 (dd, J ) 9.3, 4.5, 1H), 4.18 (dd, J ) 9.3, 3.6, 1H),
4.65 (d, J ) 13.4, 1H), 6.68-6.88 (several peaks, 2H), 6.96 (m,
1H), 7.19-7.31 (several peaks, 5H), 7.43 (dd, J ) 13.4, 9.0,
1H), 7.48-7.58 (several peaks, 2H), 8.10 (dd, J ) 11.8, 9.7,
1H); 13C NMR (CDCl3) δ 30.7, 50.6, 60.4, 69.5, 83.2, 114.4,
121.5, 127.7, 128.7, 129.4, 129.5, 133.3, 150.7, 158.0, 169.6.
12b (mixture of diastereomers): IR (neat) 1201, 1242, 1478,
1495, 1618, 1671, 2946, 3401 cm-1; HRMS calcd for C19H21
-
NO3Se + H+, 388.0792, found 388.0789.
3-(1-P h en ylselen en ylm eth yl-h eptylam in o)-acr ylic Acid
Meth yl Ester (12c). (Z)-12c: 1H NMR (CDCl3) δ 0.86 (m, 3H),
1.18-1.72 (several peaks, 10H), 2.99 (dd, J ) 7.3, 12.6, 1H),
3.04 (dd, J ) 5.6, 12.7, 1H), 3.18 (m, 1H), 3.64 (s, 3H), 4.46 (d,
J ) 8.1, 1H), 6.58 (dd, J ) 8.1, 13.0, 1H), 7.23-7.28 (several
peaks, 3H), 7.48-7.53 (several peaks, 2H), 7.81 (br m, 1H);
13C NMR (CDCl3) δ 14.0, 22.5, 25.9, 28.9, 31.6, 35.2, 35.7, 50.1,
59.5, 81.6, 127.1, 129.1, 129.8, 132.9, 151.2, 171.1. (E)-12c:
1H NMR (CDCl3) δ 0.87 (m, 3H), 1.18-1.72 (several peaks,
10H), 3.03 (dd, J ) 5.7, 11.5, 1H), 3.06 (dd, J ) 5.2, 11.5, 1H),
3.36 (m, 1H), 3.65 (s, 3H), 4.47 (br m, 1H), 4.63 (d, J ) 13.3,
1H), 7.23-7.28 (several peaks, 3H), 7.38 (dd, J ) 9.4, 13.3,
1H), 7.48-7.53 (several peaks, 2H); 13C NMR (CDCl3) δ 14.0,
22.5, 25.8, 28.9, 31.7, 34.9, 35.6, 50.4, 57.0, 86.0, 127.4, 129.0,
129.2, 133.2, 148.7, 169.9. 12c (mixture of diastereomers): IR
(neat) 1194, 1478, 1615, 1670, 2856, 2929, 3324 cm-1; HRMS
calcd for C18H29NO2Se + H+, 372.1443, found 372.1450.
3-(2,2-Dim eth yl-1-p h en ylselen en ylm eth yl-p r op yla m i-
n o)-a cr ylic Acid Meth yl Ester (12h ). (Z)-12h : 1H NMR
(CDCl3) δ 1.33 (s, 6H), 3.07 (s, 2H), 3.62 (s, 3H), 4.47 (d, J )
8.2, 1H), 6.74 (dd, J ) 8.2, 13.5, 1H), 7.16-7.25 (several peaks,
3H), 7.47-7.53 (several peaks, 2H), 8.17 (d, J ) 13.5, 1H); 13
C
NMR (CDCl3) δ 27.6, 43.1, 50.0, 54.4, 82.1, 126.9, 128.9, 129.2,
1
132.9, 147.1, 170.7. (E)-12h : H NMR (CDCl3) δ 1.32 (s, 6H),
3.07 (s, 2H), 3.62 (s, 3H), 4.72 (d, J ) 1.92, 1H), 4.94 (d, J )
13.6, 1H), 7.43 (dd, J ) 12.9, 13.6, 1H), 7.16-7.25 (several
peaks, 3H), 7.47-7.53 (several peaks, 2H); 13C NMR (CDCl3)
δ 27.7, 42.8, 50.3, 54.7, 87.7, 127.2, 129.1, 128.7, 132.9, 146.6,
169.5. 12h (mixture of diastereomers): IR (neat) 1081, 1133,
1281, 1616, 2923, 3060, 3335 cm-1; HRMS calcd for C14H20
-
NO2Se + H+, 314.0659, found 314.0662.
3-(2,2-Dim eth yl-1-p h en ylselen en ylm eth yl-p r op yla m i-
n o)-a cr ylic Acid Meth yl Ester (12d ). (Z)-12d : 1H NMR
(CDCl3) δ 0.93 (s, 9H), 2.82-2.86 (several peaks, 2H), 3.27 (m,
1H), 3.64 (s, 3H), 4.45 (d, J ) 7.9, 1H), 6.57 (dd, J ) 7.9, 12.8,
1H), 7.23-7.27 (several peaks, 3H), 7.46-7.50 (several peaks,
2H), 7.92 (m, 1H); 13C NMR (CDCl3) δ 26.5, 31.0, 35.9, 50.1,
69.8, 80.6, 127.1, 129.1, 130.0, 132.9, 152.9, 171.3; IR (neat)
1188, 1477, 1612, 1666, 2960, 3307 cm-1; HRMS calcd for
Typ ica l P r oced u r e for Ca r bon yla tion /Red u ctive Ra d i-
ca l Cycliza tion : P r ep a r a tion of (5-Ben zyl-3-oxo-p yr r o-
lid in -2-yl)-a cetic Acid Meth yl Ester (13a ). To a solution
of compound 12a (109 mg, 0.29 mmol) in dry benzene (49 mL)
were added AIBN (14 mg, 0.09 mmol) and tris(trimethylsilyl)-
silane (TTMSS) (0.153 mL, 0.5 mmol). The solution was then
purged once with 20 atm of carbon monoxide and then
pressurized to 80 atm and heated to 80 °C. After 12 h, the
reaction mixture was cooled and the solvent removed in vacuo.
The residue, on purification by flash chromatography (20-40%
ethyl acetate/pentane), afforded the title compound (57 mg,
79%) as a 4:1 mixture of cis and trans isomers. Due to the
poor stability of the material, it was characterized in the
N-tosylated form. This was also true for compounds 13b and
13c. Thus, to a stirred solution of 13a (57 mg, 0.23 mmol) in
CH2Cl2 (10 mL) were added TsCl (89 mg, 0.46 mmol), DMAP
(2 mg, 0.02 mmol), and Et3N (0.032 mL, 0.23 mmol). After 12
h, the solvent was removed in vacuo and the residue purified
by flash chromatography to afford (74 mg, 80%) of N-tosylated
material. [(2R*,5S*)-5-Ben zyl-3-oxo-1-(tolu en e-4-su lfon yl)-
C
16H23NO2Se + H+, 342.0973, found 342.0985.
2-(2,2-Dim eth yl-1-p h en ylselen en ylm eth yl-p r op yla m i-
n o)-bu t-2-en ed ioic Acid Dim eth yl Ester (12e). Min or
isom er : 1H NMR (CDCl3) δ 0.98 (s, 9H), 2.81 (dd, J ) 10.9,
12.6, 1H), 3.32 (dd, J ) 2.5, 12.6, 1H), 3.66 (s, 3H), 3.72 (s,
3H), 3.90 (m, 1H), 5.07 (s, 1H), 7.18-7.27 (several peaks, 3H),
7.40-7.45 (several peaks, 2H), 8.27 (d, J ) 11.2, 1H); 13C NMR
(CDCl3) δ 26.5, 32.0, 35.9, 50.7, 52.5, 61.7, 86.6, 126.7, 129.0,
130.7, 132.1, 147.1, 152.5, 170.9. Ma jor isom er : 1H NMR
(CDCl3) δ 0.99 (s, 9H), 2.80 (dd, J ) 10.9, 12.6, 1H), 3.32 (dd,
J ) 2.5, 12.6, 1H), 3.66 (s, 3H), 3.72 (s, 3H), 3.90 (m, 1H), 5.07
(s, 1H), 7.18-7.27 (several peaks, 3H), 7.40-7.45 (several
J . Org. Chem, Vol. 68, No. 22, 2003 8395

Berlin et al.
p yr r olid in -2-yl]-a cetic Acid Meth yl Ester (13a , cis): 1H
NMR (CDCl3) δ 2.23 (ddd, J ) 18.8, 9.9, 1.4, 1H), 2.43 (s, 3H),
2.49 (ddm, J ) 18.8, 3.8, 1H), 2.91 (dd, J ) 13.3, 10.2, 1H),
2.92 (dd, J ) 16.9, 4.2, 1H), 2.97 (dd, J ) 16.9, 5.0, 1H), 3.38
(ddm, J ) 13.3, 3.7, 1H), 3.72 (s, 3H), 3.85 (m, 1H), 4.21 (m,
1H), 7.17-7.42 (several peaks, 8H), 7.77 (m, 2H); 13C NMR
(CDCl3) δ 21.5, 38.0, 40.5, 43.5, 52.0, 58.3, 61.0, 126.8, 127.7,
128.7, 129.5, 130.1, 133.2, 137.1, 144.5, 170.8, 209.1. [(2S*,5S*)-
5-Ben zyl-3-oxo-1-(t olu en e-4-su lfon yl)-p yr r olid in -2-yl]-
3H), 3.07 (m, 1H), 2.95 (dd, J ) 17.8, 3.3, 1H), 3.10 (dd, J )
17.8, 4.5, 1H), 3.66 (s, 3H), 3.81 (m, 1H), 4.45 (m, 1H), 7.29
(m, 2H), 7.72 (m, 2H); 13C NMR (CDCl3) δ 14.0, 21.5, 22.5, 25.2,
29.0, 31.6, 34.2, 35.8, 42.1, 51.7, 58.3, 59.3, 127.7, 129.6, 138.3,
143.5, 170.1, 211.1. 13c (mixture of diastereomers): IR (neat)
1160, 1350, 1739, 1762, 2857, 2926 cm-1; HRMS calcd for
C
20H29NO5Se + Na+ 418.1664, found 418.1658.
[(2R*,5R*)-5-ter t-Bu tyl-3-oxo-pyr r olidin -2-yl]-acetic Acid
Meth yl Ester (13d , cis): 1H NMR (CDCl3) δ 0.90 (s, 9H), 2.09
(ddd, J ) 18.3, 10.8, 0.4, 1H), 2.27 (ddd, 18.3, 6.4, 0.7, 1H),
2.42 (br s, 1H), 2.52 (dd, J ) 17.1, 8.2, 1H), 2.81 (dd, J ) 17.1,
3.3, 1H), 3.10 (dd, J ) 10.8, 6.4, 1H), 3.54 (ddm, J ) 8.1, 3.3,
1H), 3.68 (s, 3H); 13C NMR (CDCl3) δ 25.8, 32.7, 36.2, 38.4,
51.8, 61.6, 63.6, 172.4, 215.6. [(2S*,5R*)-5-ter t-Bu tyl-3-oxo-
p yr r olid in -2-yl]-a cetic Acid Meth yl Ester (13d , tr a n s): 1H
NMR (CDCl3) δ 0.90 (s, 9H), 2.24 (ddd, J ) 18.4, 8.0, 1.2, 1H),
2.38 (ddd, J ) 18.4, 7.2, 0.6, 1H), 2.43 (br s, 1H), 2.52 (dd, J )
16.2, 8.5, 1H), 2.65 (dd, J ) 16.2, 3.8, 1H), 3.26 (dd, J ) 8.0,
7.3, 1H), 3.69 (s, 3H), 3.74 (m, 1H); 13C NMR (CDCl3) δ 25.9,
34.0, 36.7, 38.7, 51.9, 59.9, 62.9, 171.9, 216.9. 13d (mixture of
diastereomers): IR (neat) 1175, 1245, 1747, 1752, 2957, 3364
cm-1; HRMS calcd for C11H20NO3, 214.1443, found 214.1393.
(2R*,5R*)-5-ter t-Bu t yl-2-m et h oxyca r b on ylm et h yl-3-
oxo-p yr r olid in e-2-ca r boxylic Acid Meth yl Ester (13e,
tr a n s): 1H NMR (CDCl3) δ 0.90 (s, 9H), 2.22 (dd, J ) 18.7,
10.3, 1H), 2.36 (dd, 18.7, 7.2, 1H), 2.69 (d, J ) 16.6, 1H), 2.88
(br s, 1H), 3.14 (d, J ) 16.6, 1H), 3.43 (dd, J ) 10.3, 7.1, 1H),
3.66 (s, 3H), 3.74 (s, 3H); 13C NMR (CDCl3) δ 25.6, 33.0, 37.5,
41.8, 51.9, 53.2, 62.1, 71.9, 170.4, 170.9, 209.1; IR (neat) 1205,
1
a cetic Acid Meth yl Ester (13a , tr a n s): H NMR (CDCl3) δ
2.43 (s, 3H), 2.43 (dd, J ) 17.7, 1.6, 1H), 2.66 (dd, J ) 13.1,
10.0, 1H), 2.89 (dd, J ) 18.0, 3.3, 1H), 2.95 (dd, J ) 17.7, 9.5,
1H), 3.06 (dd, J ) 18.0, 4.5, 1H), 3.36 (s, 3H), 3.42 (dd, J )
13.1, 3.2, 1H), 3.71 (m, 1H), 4.71 (m, 1H), 7.18-7.45 (several
peaks, 8H), 7.85 (m, 2H); 13C NMR (CDCl3) δ 21.5, 35.2, 41.5,
51.6, 59.1, 59.4, 60.4, 127.0, 127.1, 128.8, 129.7, 130.4, 131.5,
136.4, 143.7, 169.9, 210.6. 13a (mixture of diastereomers): IR
(neat) 1161, 1348, 1736, 1762, 2923, 3024 cm-1; HRMS calcd
for C21H23NO5S + Na+, 424.1195, found 424.1183.
Spectral data for compounds 13 (in the case of compounds
13b and 13c, the N-tosylated derivatives) prepared are shown
below. For yields and isomeric ratios, see Table 3.
[(2R*,5R*)-5-P h en oxym eth yl-3-oxo-1-(tolu en e-4-su lfo-
n yl)-p yr r olid in -2-yl]-a cetic Acid Meth yl Ester (13b, cis):
1H NMR (CDCl3) δ 2.43 (ddd, J ) 18.3, 10.0, 1.4, 1H), 2.45 (s,
3H), 2.61 (ddd, 18.3, 2.7, 0.9, 1H), 2.98 (dd, J ) 16.7, 4.6, 1H),
3.11 (dd, J ) 16.7, 5.4, 1H), 3.74 (s, 3H), 4.00 (m, 1H), 4.20
(dd, J ) 9.3, 3.5, 1H), 4.24 (dd, J ) 9.3, 5.6, 1H), 4.41 (m, 1H),
6.87 (m, 2H), 6.98 (m, 1H), 7.29 (m, 2H), 7.37 (m, 2H), 7.78
(m, 2H); 13C NMR (CDCl3) δ 21.6, 38.2, 39.4, 52.1, 55.3, 60.7,
71.1, 114.4, 121.4, 127.6, 129.6, 130.2, 133.3, 144.7, 157.9,
171.2, 208.4. [(2S*,5R*)-5-P h en oxym eth yl-3-oxo-1-(tolu en e-
4-su lfon yl)-pyr r olidin -2-yl]-acetic Acid Meth yl Ester (13b,
1736, 1766, 2956, 3368 cm-1; HRMS calcd for C13H21NO5
+
H+, 272.1498, found 272.1475.
(3-Oxo-decah ydr o-cycloh epta[b]pyr r ol-2-yl)-acetic Acid
1
Meth yl Ester 13g: Characteristic peaks in H NMR (CDCl3)
1
tr a n s): H NMR (CDCl3) δ 2.05 (s, 3H), 2.56 (dm, J ) 17.5,
δ 2.40 (m, 1H), 2.49 (dd, J ) 8.3, 17.2, 1H), 2.58 (dd, J ) 8.3,
17.4, 1H), 2.85 (dd, J ) 2.9, 17.2, 1H), 2.86 (dd, J ) 3.5, 17.4,
1H), 3.08 (dt, J ) 4.1, 10.2, 1H), 3.46 (dd, J ) 3.2, 8.3, 1H),
3.57 (dd, J ) 3.4, 8.3, 1H), 3.69 (s, 3H); IR (neat) 1162, 1739,
2927, 3344 cm-1; HRMS calcd for C12H19NO3 + H+, 226.1443,
found 226.1446.
(5,5-Dim eth yl-3-oxo-p yr r olid in -2-yl)-a cetic Acid Meth -
yl Ester 13h : 1H NMR (CDCl3) δ 1.24 (s, 3H), 1.33 (s, 3H),
2.25 (s, 2H), 2.36 (br s, 1H), 2.55 (dd, J ) 17.0, 7.9, 1H), 2.79
(dd, J ) 17.0, 3,5, 1H), 3.66 (s, 3H), 3.68 (m, 1H); 13C NMR
(CDCl3) δ 27.7, 30.1, 36.2, 50.6, 51.8, 54.8, 59.4, 172.1, 217.0;
IR (neat) 1174, 1203, 1739, 2960, 3339 cm-1; HRMS calcd for
C9H15NO3 + H+, 186.1130, found 186.1159.
1H), 3.02 (dd, 17.6, 3.2, 1H), 3.23 (dd, J ) 17.6, 4.7, 1H), 3.26
(dd, J ) 17.5, 9.7, 1H), 3.56 (s, 3H), 3.89 (dd, J ) 9.9, 1.5, 1H),
3.99 (m, 1H), 4.51 (dd, J ) 9.9, 2.7, 1H), 4.76 (m, 1H), 6.90
(m, 2H), 7.06 (m, 1H), 7.16 (m, 2H), 7.43 (m, 2H), 7.85 (m,
2H); 13C NMR (CDCl3) δ 21.6, 36.3, 40.4, 51.8, 56.7, 60.4, 69.7,
114.1, 121.3, 126.7, 129.2, 130.4, 133.0, 148.0, 158.0, 170.3,
209.8. 13b (mixture of diastereomers): IR (neat) 1163, 1244,
1350, 1599, 1737, 1765, 2952 cm-1; HRMS calcd for C21H23
-
NO6S + Na+, 440.1144, found 440.1111.
[(2R*,5S*)-5-Hexyl-3-oxo-1-(tolu en e-4-su lfon yl)-p yr r o-
lid in -2-yl]-a cetic Acid Meth yl Ester (13c, cis): 1H NMR
(CDCl3) δ 0.88 (m, 3H), 1.13-1.36 (several peaks, 8H), 1.61
(m, 1H), 1.88 (m, 1H), 2.33-2.36 (several peaks, 2H), 2.44 (s,
3H), 2.91 (dd, J ) 16.5, 4.5, 1H), 3.01 (dd, J ) 16.5, 5.6, 1H),
3.71 (s, 3H), 3.90 (dd, J ) 5.6, 4.5, 1H), 3.95 (m, 1H), 7.35 (m,
2H), 7.74 (m, 2H); 13C NMR (CDCl3) δ 14.0, 21.6, 22.6, 25.8,
28.9, 31.7, 37.4, 38.4, 41.5, 52.1, 57.3, 60.7, 127.7, 130.0, 133.6,
144.4, 170.7, 209.9. [(2S*,5S*)-5-Hexyl-3-oxo-1-(tolu en e-4-
su lfon yl)-p yr r olid in -2-yl]-a cetic Acid Meth yl Ester (13c,
Ack n ow led gm en t. We thank the Swedish Research
Council for financial support.
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal methods. This material is available free of charge via the
Internet at http://pubs.acs.org.
1
tr a n s): H NMR (CDCl3) δ 0.85 (m, 3H), 1.13-1.36 (several
peaks, 8H), 1.52 (m, 1H), 1.90 (m, 1H), 2.36 (m, 1H), 2.42 (s,
J O030153F
8396 J . Org. Chem., Vol. 68, No. 22, 2003