An Approach toward Azacycles Using Photochemical and Radical Cyclizations of N-Alkenyl Substituted 5-Thioxopyrrolidin-2-ones

Article abstract of DOI:10.1021/jo035127w

The photochemical reactions of a series of cyclic N-alkenyl-substituted thioimides have been examined. Irradiation of N-3-methylbut-3-enyl-5-thioxo-pyrrolidin-2-one (16) results in intramolecular [2 + 2] cycloaddition to give the highly strained thietane

Full text of DOI:10.1021/jo035127w

An Ap p r oa ch tow a r d Aza cycles Usin g P h otoch em ica l a n d Ra d ica l
Cycliza tion s of N-Alk en yl Su bstitu ted 5-Th ioxop yr r olid in -2-on es
Albert Padwa,* Martin N. J acquez, and Andreas Schmidt
Department of Chemistry, Emory University, Atlanta, Georgia 30322
chemap@emory.edu
Received J uly 31, 2003
The photochemical reactions of a series of cyclic N-alkenyl-substituted thioimides have been
examined. Irradiation of N-3-methylbut-3-enyl-5-thioxo-pyrrolidin-2-one (16) results in intramo-
lecular [2 + 2] cycloaddition to give the highly strained thietane 17, whose structure was confirmed
on the basis of its X-ray analysis. Treatment of cycloadduct 17 with dimethyl(methylthio)sulfonium
tetrafluoroborate gave 2,5,6,7-tetrahydropyrrolizin-3-one (20) in good yield. Further reduction of
20 with Raney-Ni afforded 5,5-dimethylhexahydro-pyrrolizin-1-one (21). This sequence of reactions
demonstrates the facility with which the 2 + 2 photoadduct can be converted into the pyrrolizidine
alkaloid core skeleton. The photochemistry of the closely related N-butenyl thioxopyrrolidin-one
(22) proceeded in a slightly different fashion and produced 7-mercaptomethyl tetrahydropyrrolizin-
3-one (24) in 68% yield. In contrast to the above results, irradiation of the thioxaphthalimido system
containing an N-cycloalkenyl group in the side chain gave rise to products derived by γ-hydrogen
abstraction from the n-π* triplet excited state. The photobehavior of the related N-3-alkenyl
pyrrolidine-2,5-dithione system (62) was also studied and found to give products derived from both
a 2 + 2 cycloaddition (63) and hydrogen atom transfer (64). Finally, the reaction of several N-alkenyl
substituted thioimides (71-73) with tributylstannane in the presence of AIBN gave cyclized products
derived from transient radical intermediates.
In tr od u ction
pare 2,3-disubstituted indoles.12 Other cyclization reac-
tions include electrophile-induced additions to olefins13
and the Rh(II)-catalyzed reaction of thioamido-substi-
tuted R-diazomethyl vinyl ketones.14 As a consequence
of their broad synthetic utility, it is not surprising that
there are numerous procedures for the preparation of
thioamides from amides and lactams.15
Thiocarboxamides are widely used in both agriculture
and medicine1 and represent useful precursors for the
preparation of a variety of organic compounds.2 This
functional group undergoes an assortment of chemical
transformations that makes it attractive for synthetic
applications.3 Thioenolate anions of thioamides have been
employed in a variety of condensation reactions,4 and
stereoselective Michael additions to R,â-unsaturated
ketones are also known to occur.5 Numerous heterocycles
have been generated from thioamides by virtue of their
dipolar nature.6 Thiocarboxamides have been oxidized to
carbonyl compounds,7 reduced to amines,8 and converted
to nitriles,9 thioimidates,10 and amidines.11 Radical cy-
clization of 2-alkenylthioanilides has been used to pre-
(7) (a) Fukuyama, T.; Dunkerton, L. V.; Aratani, M.; Kishi, Y. J .
Org. Chem. 1975, 40, 2011. (b) Kochhar, K. S.; Cottrell, D. A.; Pinnick,
H. W. Tetrahedron Lett. 1983, 24, 1323. (c) Olah, G. A.; Arvanaghi,
M.; Ohannesian, L.; Surya Prakash, G. K. Synthesis 1984, 785. (d) Kim,
Y. H.; Chung, B. C.; Chang, H. S. Tetrahedron Lett. 1985, 26, 1079.
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Ed.; Interscience: New York, 1970; pp 383-475.
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M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 6, pp 419-
434.
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Fukuyama, T. J . Am. Chem. Soc. 1999, 121, 3791.
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54, 4812.
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Lett. 1989, 30, 3625.
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J . Org. Chem. 1990, 55, 132.
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1981, 22, 3305. (b) Gasteiger, J .; Herzig, C. Tetrahedron 1981, 37, 2607.
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Chim. Belg. 1978, 87, 229. (b) Thomsen, I.; Clausen, K.; Scheibye, S.;
Lawesson, S.-O. Org. Synth. 1984, 62, 158 and references therein. (c)
For a comprehensive review of Lawesson’s reagent, see: Cava, M. P.;
Levinson, M. I. Tetrahedorn 1985, 41, 5061. (d) Wakabayashi, T.; Kato,
Y. J pn. Kokai Tokkyo Koho 78 56,662, 1978; Chem. Abstr. 1979, 90,
22818h. (e) Paquer, D.; Smadja, S.; Vialle, J . C. R. Hebd. Seances Acad.
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Commun. 1982, 12, 787. (g) Pedersen, B. S.; Lawesson, S.-O. Bull. Soc.
Chim. Belg. 1977, 86, 693. (h) Ishi, Y.; Hirabayashi, T.; Imaeda, H.;
Ito, K. J apan Patent 1074, 40, 441; Chem. Abstr. 1975, 82, 156074f.
10.1021/jo035127w CCC: $27.50 © 2004 American Chemical Society
Published on Web 12/11/2003
J . Org. Chem. 2004, 69, 33-45
33

Padwa et al.
SCHEME 1
SCHEME 2
Photochemical cyclizations of nitrogen-containing thio-
carbonyl compounds have also been studied in some
detail16 and represent a potentially important method for
the synthesis of various heterocyclic ring systems. Most
simple thioamides were found to be inert to both the
Norrish type I (R-cleavage) and Norrish type II (hydrogen
abstraction) reactions17 in contrast to the behavior of
their oxygen and nitrogen counterparts.18 However, many
aliphatic and aromatic monothioimides of type 1a (X )
H) undergo both inter- and intramolecular Paterno-
Bu¨chi-like photocycloadditions with olefins19 to give
various imido-thietanes 2a (X ) H) as primary products
that can undergo further fragmentation (Scheme 1).
Simple aminothietanes of type 2a (X ) H) are generally
too labile to be isolated, except for one example in the
literature.20 The facility with which the subsequent
fragmentation occurs can be ascribed to the participation
of the lone pair of electrons on the nitrogen atom that
facilitates C-S cleavage in the thietane ring leading to
the formation of a zwitterionic intermediate (3). This
transient species can give rise to a plethora of photo-
products. The [2 + 2] photocycloaddition of various
thioimides,21 thiouracils,22 and 2-thioparabanic acids23
(i.e., 1b or 1c) furnishes isolable thietanes (2b or 2c) since
the availability of the lone-pair electrons on the nitrogen
atom is reduced by conjugation with the second carbonyl
group. Most thioimides of type 1b (X ) O) react from
their n-π* triplet excited state, whereas it is known that
thioketones react from both their n-π* triplet and long-
lived upper singlet excited state (π-π* singlet).24 For
thiocarboxamides 1a (X ) H), π donation by a nitrogen
atom is more efficient than σ withdrawal and thus they
are predicted to have nucleophilic n-π* states. Simple
resonance theory suggests that the addition of a second
carbonyl or thiocarbonyl group to the nitrogen atom
should lead to delocalization of the nitrogen lone-pair
electrons, making the chromophore more reactive during
photochemical excitation. Indeed, introduction of another
carbonyl group onto the thioamide renders the thiocar-
bonyl group quite reactive toward photochemical hydro-
gen abstraction from the â-, γ-, and δ-positions and leads
to nitrogen-containing heterocycles such as lactams and
rearranged amides (Scheme 2).25,26
Work by the Kanaoka and Machida groups has also
shown that, in contrast to thiocarboxamides, photochemi-
cal excitation of aromatic thioimides possessing a benzylic
hydrogen at the δ- and ꢀ-positions of the N-alkyl side
chain gives rise to photocyclization products (i.e., 9 f 10,
Scheme 3).27 Certain cyclic thioimides that contain an
N-ω-(phenylalkyl) substituent also undergo the Norrish
type II cyclization. For example, the photolysis of the
monothioimide 11 resulted in the formation of bicyclic
γ-lactams 13 (27-84% yield) and enethiols 14 and 15
(37-51% yield), which are formed by disproportionation
of the initially generated biradical intermediate 12.28
(16) (a) Machida, M.; Oda, K.; Yoshida, E.; Kanaoka, Y. J . Org.
Chem. 1985, 50, 1681. (B) Machida, M.; Oda, K.; Kanaoka, Y. Chem.
Pharm. Bull. 1985, 33, 3552. (c) Oda, K.; Machida, M.; Kanaoka, Y.
Synthesis 1986, 768. (d) Machida, M.; Ohkura, K.; Seki, M.; Terashima,
M.; Kanaoka, Y. Heterocycles 1990, 31, 1833.
(17) Kanaoka, Y. Acc. Chem. Res. 1978, 11, 407.
(18) Couture, A.; Gomez, J .; de Mayo, P. J . Org. Chem. 1981, 46,
2010.
(19) (a) Coyle, J . D. Tetrahedron 1985, 41, 5395. (b) de Mayo, P.;
Sydnes, L. K.; Wenska, G. J . Org. Chem. 1980, 45, 1549. (c) Couture,
A.; Dubiez, R.; Lablanche-Combier, A. J . Chem. Soc., Chem. Commun.
1982, 842; J . Org. Chem. 1984, 49, 714. (d) Sato, E.; Ikeda, Y.;
Kanaoka, Y. Chem. Pharm. Bull. 1990, 38, 1205. (e) Nishio, T. J . Chem.
Soc., Perkin Trans. 1 1987, 1225. (f) Nishio, T.; Fujisawa, M.; Omote,
Y. J . Chem. Soc., Perkin Trans. 1 1987, 2523. (g) Nishio, T.; Okuda,
N. J . Org. Chem. 1992, 57, 4000. (h) Sato, E.; Hasebe, M.; Nishio, T.;
Ikeda, Y.; Kanaoka, Y. Liebigs Ann. Chem. 1988, 733. (i) Oda, K.;
Machida, M.; Kanaoka, Y. Tetrahedron Lett. 1989, 30, 4421.
(20) Nishio, T.; Okuda, N.; Omote, Y. J . Chem. Soc., Perkin Trans.
1 1998, 1663.
(21) (a) Sakamoto, M.; Omote, Y.; Aoyama, H. J . Org. Chem. 1984,
49, 396. (b) Coyle, J . D.; Rapley, P. A. Tetrahedron Lett. 1984, 25, 2247;
J . Chem. Soc., Perkin Trans. 1 1986, 2173. (c) Machida, M.; Oda, K.;
Kanaoka, Y. Tetrahedron Lett. 1984, 25, 1837; J . Org. Chem. 1985,
40, 1681. (d) Machida, M.; Oda, K.; Yoshida, E.; Kanaoka, Y. Tetra-
hedron 1986, 42, 4691.
(22) (a) Fourrey, J . L.; J ouin, P.; Moron, J . Tetrahedron Lett. 1974,
3005. (b) J ouin, P.; Fourrey, J . L. Tetrahedron Lett. 1975, 1329.
(23) (a) Yonezawa, T.; Matsumoto, M.; Matsuura, Y.; Kato, H. Bull.
Chem. Soc. J pn. 1969, 42, 2323. (b) Gotthardt, H.; Nieberl, S. Chem.
Ber. 1976, 109, 2871.
(24) Ramamurthy, V. In Organic Photochemistry; Padwa, A., Ed.;
Marcel Dekker: New York; Vol. 7, pp 231-338.
(25) Sakamoto, M.; Aoyama, H.; Omote, Y. J . Org. Chem. 1984, 49,
1837.
(26) (a) Sakamoto, M.; Aoyama, H.; Omote, Y. Tetrahedron Lett.
1985, 26, 4475. (b) Sakamoto, M.; Watanabe, S.; Fujita, T.; Tohnishi,
M.; Aoyama, H.; Omote, Y. J . Chem. Soc., Perkin Trans. 1 1988, 2203.
(27) (a) Machida, M.; Oda, K.; Kanaoka, Y. Tetrahedron Lett. 1985,
26, 5173. (b) Machida, M.; Oda, K.; Kanaoka, Y. Chem. Pharm. Bull.
1989, 37, 642. (c) Oda, K.; Machida, M.; Kanaoka, Y. Chem. Pharm.
Bull. 1986, 34, 4406.
34 J . Org. Chem., Vol. 69, No. 1, 2004

Photochemical and Radical Cyclizations
SCHEME 3
SCHEME 4
SCHEME 5
In the course of our own studies dealing with the
cyclization chemistry of thiocarboxamides,29 we became
interested in using the intramolecular [2 + 2] photocy-
cloaddition as a method for preparing various azabicyclic
ring systems commonly found in pyrrolizidine alkaloids.
We reasoned that loss of sulfur from the initially formed
thietane cycloadduct (i.e., 2) might represent an efficient
approach for the synthesis of fused heterocycles. In this
paper, we report an account of our efforts dealing with
the intramolecular photocycloaddition reactions of several
cyclic thioimides.30
nium tetrafluoroborate (DMTSF).32 The ease with which
the S-S bond of (dimethylthio)sulfonium salts are cleaved
by nucleophilic reagents was first documented by Helmka-
mp and co-workers in their work on the preparation of
DMTSF and its addition to alkenes and alkynes.33 These
reactions, and related studies by Meerwein,34 indicate
that reagents such as DMTSF may be regarded as
sulfanyl derivatives and can function as a potential
source of alkylsulfanyl ions.35 It was known from earlier
work in the literature that carbon-sulfur bonds of
sulfides become labile on alkylsulfanylation and that the
sulfonium ions so formed are highly reactive intermedi-
ates that seldom can be isolated.36 It follows, therefore,
that the conversion of 17 to 20 upon treatment with
DMTSF proceeds by the pathway outlined in Scheme 4.
Methylthiolation of the thietane sulfur with DMTSF
produces a transient alkylthiosulfonium salt that easily
dissociates to N-acyliminium ion 19. Once formed, 19
readily undergoes loss of a proton to give 20. Subjection
of 20 to Raney-Ni afforded hexahydropyrrolizinone 21 in
good yield. The above transformations clearly demon-
strate the facility with which the resulting photoadduct
17 can be converted into the pyrrolizidine core skeleton.
The photochemistry of the closely related N-butenyl
thioxopyrrolidinone (22) (R ) H) proceeded in a slightly
different fashion and produced 7-mercaptomethyl-1,2,5,6-
tetrahydropyrrolizin-3-one (24) in 68% yield (Scheme 5).
Resu lts a n d Discu ssion
A series of N-alkenyl-substituted thioxopyrrolidinones
were easily prepared by an N-alkylation reaction of
succinimide followed by thiation using Lawesson’s re-
agent.15 We began our investigation of their photochemi-
cal behavior by first irradiating a sample of N-3-
methylbut-3-enyl-5-thioxopyrrolidin-2-one (16) in benzene
using a 450-W Hanovia medium-pressure lamp under an
argon atmosphere with a Pyrex filter sleeve for 2 h
(Scheme 4). Silica gel chromatography of the crude
reaction mixture afforded the highly strained thietane
17 in 73% yield whose structure was assigned on the
basis of its spectral and analytical data. The assignment
of structure 17 was further validated by single-crystal
X-ray analysis.31 Compound 17 was treated with Raney-
Ni in ethanol for 2 h to give the ethoxy substituted
hexahydropyrrolizin-3-one (18).
We also carried out a ring-opening reaction on cycload-
duct 17 by treating it with dimethyl(methylthio)sulfo-
(32) (a) Trost, B.; Murayama, E. J . Am. Chem. Soc. 1981, 103, 6529.
(b) Trost, B. M.; Saito, T. J . Am. Chem. Soc. 1985, 107, 719.
Commercially available from Aldrich Chemical Co.
(33) (a) Helmkamp, G. K.; Pettitt, D. J . J . Org. Chem. 1963, 28, 2932.
(b) Helmkamp, G. K.; Olsen, B. A.; Pettitt, D. J . J . Org. Chem. 1965,
30, 676. (c) Helmkamp, G. K.; Owsley, D. C. Barnes, W. M.; Cassey,
H. N. J . Am. Chem. Soc. 1968, 90, 1635.
(34) Meerwein, H.; Zenner, K. F.; Gipp, R. J ustus Liebigs Ann. 1965,
688, 67.
(35) (a) Kice, J .; Favstritsky, N. J . Am. Chem. Soc. 1969, 91, 1751.
(b) Benesch, R. E.; Benesch, R. J . Am. Chem. Soc. 1958, 80, 1666.
(36) (a) Smallcombe, S.; Caserio, M. J . Am. Chem. Soc. 1971, 3, 5826.
(b) Kim, J .; Pau, J .; Caserio, M. J . Org. Chem. 1979, 44, 1544.
(28) Sakamoto, M.; Tohnishi, M.; Fujita, T.; Watanabe, S. J . Chem.
Soc., Perkin Trans. 1 1991, 347.
(29) Padwa, A.; Beall, L. S.; Heidelbaugh, T. M.; Liu, B.; Sheehan,
S. M. J . Org. Chem. 2000, 65, 2684.
(30) Padwa, A.; J acquez, M. N.; Schmidt, A. Org. Lett. 2001, 3, 1781.
(31) We have deposited atomic coordinates for compounds 17 and
47b with the Cambridge Data Centre. The coordinates can be obtained
on the request from the Director, Cambridge Crystallographic Data
Centre, 12 Union Road, CB2 1EZ, U.K.
J . Org. Chem, Vol. 69, No. 1, 2004 35

Padwa et al.
SCHEME 6
SCHEME 7
triplet state of the thioxaphthalimido chromophore.38 The
adjacent phthalimido ring apparently enhances the abil-
ity of the n-π* excited state to abstract a γ-hydrogen
relative to undergoing [2 + 2] cycloaddition across the
tethered π bond.
More than likely, the photoreaction also proceeds by a
Paterno-Bu¨chi-like cycloaddition. With this system,
however, the initially formed cycloadduct readily under-
goes ring opening followed by a subsequent deprotonation
to give 24 as a consequence of the available hydrogen
atom (i.e., R ) H). This ring-opening reaction does not
occur with the related 3-methylbutenyl system 17 (i.e.,
R ) Me).
Photolysis of the N-cyclopentenyl derivative 25 was
also carried out and, in a similar fashion, produced the
tetracyclic thietane 26 as the major photoproduct in 68%
yield based on recovered starting material (Scheme 6).
The 1H NMR and 13C NMR spectra indicate that the
cycloadduct was obtained as a single stereoisomer. As
was the case with photoadduct 17, treatment of 26 with
DMTSF afforded the related tetrahydropyrrolizinone 27
in 92% yield. Further reduction of 27 with Raney-Ni gave
spiro pyrrolizinone 28 in 95% yield. The direct reduction
of cycloadduct 26 with Raney-Ni also afforded 28, but in
this case lesser quantities (7%) of the ethoxy-substituted
spiro pyrrolizinone 29 were also formed. Compound 29
is presumably derived by the trapping of an initially
produced N-acyliminium ion with ethanol.
In contrast to the above results, irradiation of the
thioxaphthalimide systems 30 and 31 containing an
N-cycloalkenylalkyl group in the side chain produced the
mercapto-substituted pyridoisoindolones 32 and 33
as a 1:1 mixture of diastereomers in 64 and 73% yields,
respectively. Further treatment of 33 with p-toluene-
sulfonic acid resulted in the loss of H2S and afforded
dihydropyridine 34 in 91% yield. Photolysis of the
closely related N-but-3-enyl thioxaphthalimide (35) fur-
nished the analogous pyridoisoindolone 36 in 73% yield
(Scheme 7).
In an earlier report,37 Oda had suggested that in
certain cases, apparent Norrish type II products such as
32 (or 36) are actually derived from a Paterno-Bu¨chi
photocycloaddition reaction, which is subsequently con-
verted into the mercapto pyridoisoindolone system. How-
ever, we were unable to detect such an intermediate in
the photolysis of 30, 31, or 35. The fact that 36 is the
major product formed from the irradiation of 35 may be
rationalized by γ-hydrogen abstraction from the n-π*
Over a period of years, several research groups have
worked on the photochemistry of phthalimide systems.
These molecules exhibit diverse photochemical behavior,
including electron-transfer reactions,39 photoreductions,40
Paterno-Bu¨chi cycloadditions,41 and the addition of
alkenes to form benzazepine-diones42 (i.e., 37 f 38). In
related studies, Booker-Millburn and co-workers showed
that the photolysis of a number of N-alkenyl-substituted
maleimide derivatives also led to the formation of com-
plex perhydroazaazulenes in excellent yield (i.e., 39 f
41).43 Some of the polycyclic ring systems that were
prepared by this method constitute the core skeleton of
a number of complex alkaloids.44 The overall process has
been considered as a formal intramolecular [5 + 2]
cycloaddition.43 Although the mechanism of this novel
cycloaddition is not known with certainty, it has been
postulated43 from the earlier work of Mazzocchi45 that
the reaction proceeds by a direct [2 + 2] cycloaddition
(38) It is also conceivable that 36 is formed by a mechanism similar
to that outlined in path B, Scheme 11 for the conversion of thiomale-
imide 46 to 47.
(39) (a) Mazzocchi, P. H. In Organic Photochemistry; Padwa, A., Ed.;
Marcel Dekker: New York, 1981; Vol. 5, p 421. (b) Mazzocchi, P. H.;
Minamikawa, S.; Wilson, P. Tetrahedron Lett. 1978, 4361. (c) Maruya-
ma, K.; Kubo, Y. Chem. Lett. 1978, 851. (d) Maruyama, K.; Kubo, Y.;
Machida, M.; Oda, K.; Kanaoka, Y.; Fukuyama, K. J . Org. Chem. 1978,
43, 2302. (e) Maruyama, K.; Kubo, Y. J . Org. Chem. 1981, 46, 3612.
(40) Kanaoka, Y.; Hatanaka, Y. Chem. Pharm. Bull. 1974, 22, 2205.
(41) (a) Mazzocchi, P. H.; Minamikawa, S.; Bowen, M. Heterocycles
1978, 9, 1713. (b) Machida, M.; Takechi, H.; Kanaoka, Y. Tetrahedron
Lett. 1982, 23, 4981.
(42) (a) Mazzocchi, P. H.; Bowen, M. J .; Narain, N. K. J . Am. Chem.
Soc. 1977, 99, 7063. (b) Mazzocchi, P. H.; Minamikawa, S.; Bowen, M.
J . Org. Chem. 1978, 43, 3079. (c) Maruyama, K.; Kubo, Y. Chem. Lett.
1978, 769.
(43) (a) Booker-Milburn, K. I.; Costin, N. J .; Dainty, R. F.; Patel,
D.; Sharpe, A. Tetrahedron Lett. 1998, 39, 7423. (b) Booker-Milburn,
K. I.; Anson, C. E.; Clissold, C.; Costin, N. J .; Dainty, R. F.; Murray,
M.; Patel, D.; Sharpe, A. Eur. J . Org. Chem. 2001, 1473. (c) Booker-
Milburn, K. I.; Cowell, J . K.; Sharpe, A.; Delgado J ime´nez. F. Chem.
Commun. 1996, 249. (d) Booker-Milburn, K. I.; Gulten, S.; Sharpe, A.
Chem. Commun. 1997, 1385.
(44) Booker-Milburn, K. I.; Dudin, L. F.; Anson, C. E.; Guile, S. D.
Org. Lett. 2001, 3, 3005.
(45) (a) Mazzocchi, P. H.; Khachik, F.; Wilson, P. J . Am. Chem. Soc.
1981, 103, 6498. (b) Mazzocchi, P. H.; Wilson, P.; Khachik, F.; Klingler,
L.; Minamikana, S. J . Org. Chem. 1983, 48, 2981. (c) Mazzocchi, P.
H.; Minamikana, S.; Wilson, P.; Bowen, M.; Narain, N. J . Org. Chem.
1981, 46, 4846.
(37) (a) Oda, K.; Machida, M.; Kanaoka, Y. Chem. Pharm. Bull.
1992, 40, 585. (b) Coyle, J . D.; Rapley, P. A. J . Chem. Res. 1986, 142.
36 J . Org. Chem., Vol. 69, No. 1, 2004

Photochemical and Radical Cyclizations
SCHEME 8
SCHEME 10. P a th A
SCHEME 9
A involves γ-hydrogen abstraction from the n-π* triplet
state of the thiomaleimide chromophore and is analogous
to that suggested to occur with the thiophthalimido
systems 30 and 31. The initially formed diradical inter-
mediate 48 undergoes subsequent coupling at the remote
allylic site to preferentially afford the thermodynamically
more stable six-membered ring rather than the more
highly strained four-membered azetidine ring. Although
this pathway seems reasonable, we believe that the
formation of a 3:1 mixture of diastereomers is inconsis-
tent with the hydrogen transfer mechanism (path A,
Scheme 10). A stepwise abstraction-coupling mechanism
would be more likely to produce a 1:1 mixture of diaster-
eomers since the activation energy associated with
diradical coupling is less than 3 kcal. Consequently, there
should be little selectivity encountered in the coupling
step and the diastereomeric ratio would only depend on
whether the amido radical attacks the top or bottom face
of the allylic π radical. The alternate mechanistic pos-
sibility (path B, Scheme 11) differs in its timing from path
A and proceeds by initial addition of the electronically
excited carbon atom of the n-π* excited state of the
thiocarbonyl group onto the adjacent cyclohexenyl π bond.
The resulting diradical intermediate (49 or 50) would
then undergo a subsequent transannular 1,5-hydrogen
abstraction46 to give the diastereomeric photoproducts
47a or 47b. The fact that a 3:1 mixture of stereoisomers
is obtained would certainly support this type of mecha-
nism. Stepwise addition to the π bond will result in two
distinctly different diradical intermediates (i.e., 49 vs 50),
which in turn would deliver the cis (47a ) and trans (47b)
tricyclic diastereomers. Furthermore, one would expect
that the preferred diastereomer would reflect the strain
energy of the resulting tricyclic ring systems.47 In recent
years, molecular mechanics calculations have developed
into an important technique for calculation of molecular
properties.48a The stability of the diastereomeric tricyclic
compounds 47a and 47b can be determined by calcula-
onto the excited amide resonance structure to give a
zwitterionic tricyclic species (i.e., 40), which then under-
goes a spontaneous fragmentation to the product (Scheme
8).
As part of our studies in this area, we thought it would
be of interest to determine whether the photochemistry
of the related thiomaleimide system would undergo an
analogous [5 + 2] cycloaddition or possibly proceed by
some alternate photochemical pathway. We found that
the irradiation of the parent thiomaleimide 42 resulted
in the complete disappearance of the starting material
after 2.5 h, and after chromatographic purification, a new
product was obtained in 62% yield. The structure of this
compound was assigned as the mercapto-substituted
indolizinone 43 on the basis of its spectral properties.
Similarly, photolysis of the related N-3-methyl-but-3-enyl
thiomaleimide (44) gave the analogous product 45 in 64%
yield after 2.5 h of irradiation using a 450-W Hanovia
medium-pressure lamp (Scheme 9). We then turned our
attention to the investigation of the more complex cyclo-
hexenyl substituted system 46 with a view to testing the
limits of the photoreaction. Irradiation of a sample of 46
for 2.5 h afforded a 72% yield of 47 as a 1:3 mixture of
two diastereomers which could be separated by column
chromatography. The structure of the major diastereomer
47b was established as the trans stereoisomer on the
basis of an X-ray crystal structure analysis.31
(46) Serebryakov, E. P. Bull. Acad. Sci. USSR 1984, 33, 120.
(47) Another possibility to account for the preference of the trans
diastereomer was suggested by one of the referees. The trans product
could form from an exo approach of the cycloalkene ring to the
electronically excited heterocyclic ring and the cis product from an endo
approach of the two reacting sites. The difference in energy of the
respective transition states would also explain the preference for the
trans diastereomer.
We considered two mechanistic possibilities to account
for the observed transformation with these systems. Path
J . Org. Chem, Vol. 69, No. 1, 2004 37

Padwa et al.
SCHEME 11. P a th B
SCHEME 12
tion of their steric energies, the direct sum of the force-
field increments.48b We assume that the relative energy
differences of the lowest-energy conformation of com-
pounds 47a and 47b will parallel the energy differences
of the diradical intermediates 49 and 50 and also the
energy differences in the transition state for their forma-
tion. The MMX calculations reveal a 2.1 kcal difference
between the two diastereomeric products but only a 0.1
kcal difference between the conformations of the starting
thiomaleimides. The lower-energy tricyclic diastereomer
(47b) corresponds to the trans isomer, which was the
major product formed. Thus, path B successfully predicts
the observed stereochemistry of the obtained major
(trans) isomer of 47 and lends further weight to this
mechanistic interpretation.
of our investigations, encountered some interesting dif-
ferences. Thus, the irradiation of the straight chain N-3-
butenyl dithione 53 afforded a 4:1 mixture (64%) of
thietane 54 and pyrrolizine-3-thione 55
(Scheme 13). It would appear that the excited thioa-
mido group undergoes [2 + 2] cycloaddition and partial
fragmentation of thioformaldehyde from 54 to give 55.
Treatment of a sample of 54 with a trace of acid gave
the ring-opened mercaptan 56 in high yield. An analo-
gous photocycloaddition reaction also occurred with
dithione 57, which gave the novel 3-thione 58 as well as
1H-pyrrolizine 59 in 72 and 10% yield, respectively.
Irradiation of the N-2-cyclopentenyl-ethyl pyrrolidine
dithione (60) afforded the Paterno-Bu¨chi cycloadduct 61.
Interestingly, when the homologous cyclohexenyl system
62 was used, bicyclic azetidine 64 (30%) was obtained in
addition to the expected [2 + 2] photoadduct 63 (28%).
We suspect that 64 is derived from a competitive hydro-
gen transfer reaction. No signs of a photoproduct related
to 64 were observed with the cyclopentenyl thione 60. It
is well known that [2 + 2] photocycloaddition of the n-π*
state of a carbonyl compound to an unsaturated substrate
proceeds via a biradical intermediate.50 Presumably the
formation of thietane 61 (or 63) also proceeds by a related
biradical intermediate (i.e., 65) derived by addition of the
As a logical extension of our photochemical program
dealing with intramolecular thietane formation, the
photoreaction of several N-3-alkenyl pyrrolidine-2,5-
dithiones was investigated. The change of an oxygen to
a sulfur atom in the cyclic imide chromophore is known
to result in unique photochemistry.16 For example, the
excited state of dithiosuccinimides reacts with olefins only
by photoaddition.49 Other photoreactions such as the
Norrish type I and type II reactions, which are common
to the parent thione and imide families,38 are less
important with dithioimides. The inertness of dithioim-
ides to the undesired Norrish I reaction suggests that
these substrates may have some interesting synthetic
capabilities. For example, thiosuccinimides such as 51
have been reported to undergo smooth intramolecular
cycloaddition to give the highly strained thietane 52
(Scheme 12).49
We opted to study the photochemistry of the related
N-alkenyl dithio-succinimide system and, in the course
(48) (a) For a review, see: Burkert, U.; Allinger, N. L. Molecular
Mechanics; American Chemical Society: Washington, DC, 1982. (b)
We have used the UNIX version of PCModel operating on a G4-
Macintosh computer (OSX 10.2) for these calculations.
(49) Oda, K.; Machida, M.; Aoe, K.; Nisibata, K.; Sato, Y.; Kanaoka,
Y. Chem. Pharm. Bull. 1986, 34, 1411.
(50) Turro, N. J . Modern Molecular Photochemistry; The Benjamin/
Cummings Publishing Co., Inc.: Menlo Park, CA, 1978; p 432.
38 J . Org. Chem., Vol. 69, No. 1, 2004

Photochemical and Radical Cyclizations
SCHEME 13
addition of tri-butylstannyl radical to a thiocarbonyl
group and intramolecular addition of the resulting radical
to a carbon-carbon multiple π bond.12,55 Bachi and co-
workers’ attempts to induce radical cyclizations of thioa-
mides 66-68 by reaction with tri-n-butylstannyl radical
failed, however, to give cyclized products.56 The inert
nature of these compounds was attributed to the radical
stabilizing power of the nitrogen atom.56 Apparently, the
initially formed adduct radical 70 derived from thioamide
69 is not sufficiently reactive to maintain a viable chain
reaction by addition to the neighboring double bond. In
an earlier report we had demonstrated that the radical
stabilizing effect of the nitrogen atom can be significantly
reduced by the incorporation of an electron-withdrawing
substituent and that it becomes possible to induce radical
cyclization under these conditions.57
excited n-π* state of the thiocarbonyl group onto the
terminal position of the tethered alkene.51
Since we had a supply of various N-alkenyl-substituted
5-thioxopyrrolidinones on hand from our photochemical
studies, we decided to investigate their radical cyclization
behavior. For our initial exploratory work, thioimide 71
was chosen as the substrate. Treatment of this compound
with 1.1 equiv of n-Bu3SnH in boiling benzene under the
standard conditions afforded 7-methyl-tetrahydropyr-
rolizin-3-one (77) but in only 28% yield (Scheme 14). More
than likely this reaction proceeds by an initial and
reversible addition of n-Bu3Sn• onto the thiono sulfur
atom. The resulting adduct radical 74 undergoes a
subsequent 5-exo trig addition to the tethered π bond to
give the cyclic radical 75, which then abstracts a hydro-
gen atom from n-Bu3SnH to furnish the cyclized lactam
76. On elimination of tributylstannyl mercaptan, tet-
rahydro-pyrrolizinone 77 is obtained.
As a further continuation of our studies in this area,
we thought it worthwhile to use the N-alkenyl 5-thiox-
opyrrolidinone ring system as a precursor for radical
cyclizations. During the past decade, the synthesis of
heterocyclic rings by radical cyclization has been exten-
sively investigated and this trend is showing no sign of
abating.52 Most of the effort in this area has focused on
carbon centered radicals,53 but oxygen54a and especially
nitrogen radicals54b are attracting an increasing amount
of attention since these species can provide access to a
variety of important heterocyclic systems. Recently, there
have been several examples of radical cyclizations of
various thionoesters and thioamides, which involve the
(51) We assume that the conversion of 25 to 26 also occurs via a
similar diradical intermediate.
Incorporating an electron withdrawing group (R ) SO2-
Me or CO2Me) on the π bond did not significantly enhance
the cyclization process. Thus, the tin-mediated reaction
was not particularly efficient in these two cases since the
(52) (a) Curran, D. P. Synthesis 1988, 489. (b) Cid, M. M.; Domingu-
ez, D.; Castedo, L.; Vazquez-Lopez, E. Tetrahedron 1999, 55, 5599. (c)
Fallis, A. G.; Brinza, I. M. Tetrahedron 1997, 53, 17543. (d) Boivin, J .;
Schiano, A. M.; Zard, S. Z.; Zhang, H. Tetrahedron Lett. 1999, 40, 4531.
(e) Lin, X.; Stien, D.; Weinreb, S. M. Org. Lett. 1999, 4, 637.
(53) (a) Giese, B. Radicals in Organic Synthesis: Formation of
Carbon-Carbon Bonds; Pergamon Press: Oxford, 1986. (b) Curran,
D. P. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Eds.; Pergamon Press: Oxford, 1991; Vol. 4, pp 715-831.
(54) (a) Russell Bowman, W.; Stephenson, P. T.; Young, A. R.
Tetrahedron Lett. 1995, 36, 5623 and references therein. (b) Boivin,
J .; Callier-Dublauchet, A. C.; Quiclet-Sire, B.; Schiano, A. M.; Zard, S.
Z. Tetrahedron 1995, 51, 6517.
(55) (a) Reding, M. T.; Fukuyama, T. Org. Lett. 1999, 7, 973. (b)
Feldman, K. S.; Schildknegt, K. J . Org. Chem. 1994, 59, 1129. (c) Bachi,
M. D.; Bosch, E. J . Org. Chem. 1992, 57, 4696.
(56) Bachi, M. D.; Bosch, E.; Denenmark, D.; Girsh, D. J . Org. Chem.
1992, 57, 6803.
(57) Padwa, A.; Nimmesgern, H.; Wong, G. S. K. J . Org. Chem. 1985,
50, 5620.
J . Org. Chem, Vol. 69, No. 1, 2004 39

Padwa et al.
(m, 1H), 1.94-2.00 (m, 1H), 2.28-2.43 (m, 3H), 2.61-2.70 (m,
1H), 2.77 (d, 1H, J ) 9.1 Hz), 2.90 (d, 1H, J ) 9.1 Hz), 3.51-
3.59 (m, 1H), and 4.00-4.13 (m, 1H); 13C NMR (CDCl3, 75
MHz) δ 23.1, 30.7, 31.3, 32.9, 40.2, 41.4, 56.6, 82.4, and 172.7.
Anal. Calcd for C9H13NOS: C, 58.98; H, 7.15; N, 7.64. Found:
C, 58.77; H, 7.18; N, 7.45.
SCHEME 14
7a-Eth oxy-7,7-dim eth yl-h exah ydr opyr r olizin -3-on e (18).
To a stirred suspension containing 1.0 g of Raney-Ni in 3 mL
of ethanol was added 0.16 g (0.9 mmol) of thietane 17 in one
portion. The reaction mixture was heated at reflux for 6 h,
cooled to room temperature, and filtered over Celite. The
solvent was removed under reduced pressure, and the crude
residue was purified by flash silica gel chromatography to give
0.13 g (74%) of pyrrolizidinone 18 as a colorless oil: IR (neat)
1711, 1468, 1395, and 1157 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 0.81 (s, 3H), 1.06 (s, 3H), 1.16 (dt, 3H, J ) 7.0 and 0.6 Hz),
1.68-1.73 (m, 1H), 1.87-1.94 (m, 1H), 2.05-2.11 (m, 1H),
2.20-2.32 (m, 1H), 2.38-2.46 (m, 1H), 2.72-2.76 (m, 1H), 3.05
(dd, 1H, J ) 11.7 and 10.3 Hz), and 3.37-3.49 (m, 3H); 13C
NMR (CDCl3, 75 MHz) δ 15.6, 20.5, 21.6, 24.1, 34.2, 39.1, 39.5,
43.7, 57.0, 103.6, and 172.1. HRMS Calcd for C11H19NO2:
197.1416. Found: 197.1416.
7-Meth yl-7-m eth yld isu lfa n ylm eth yl-2,5,6,7-tetr a h yd r o-
p yr r olizin -3-on e (20). A 0.33 g (1.8 mmol) sample of thietane
17 in 6 mL of acetonitrile was cooled to -40 °C and was treated
with 0.36 g (1.8 mmol) of DMTSF. After the solution was
stirred for 10 min at -40 °C, 1.3 mL (9.1 mmol) of triethy-
lamine was added dropwise. After the solution was warmed
to 0 °C, the reaction mixture was diluted with ether and a
saturated sodium bicarbonate solution was added. The layers
were separated, and the aqueous layer was extracted with
ether. The combined organic layer was dried over MgSO4 and
concentrated under reduced pressure. The residue was purified
by flash silica gel column chromatography to give 0.27 g (65%)
of disulfide 20 as a colorless oil: IR (neat) 1699, 1380, 1270,
and 958 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.33 (s, 3H), 2.05-
2.14 (m, 1H), 2.34-2.45 (m, 1H), 2.42 (s, 3H), 3.02 (s, 2H), 3.14
(d, 2H, J ) 2.4 Hz), 3.49-3.54 (m, 2H), and 4.85 (t, 1H, J )
2.4 Hz); 13C NMR (CDCl3 100 MHz) δ 23.6, 24.1, 39.2, 40.4,
resulting pyrrolizinones 78 and 79 were only obtained
in 50% yield. These experiments do demonstrate the
feasibility of radical cyclizations using N-alkenyl-substi-
tuted thioimides and opens the way to the construction
of various pyrrolizidine alkaloids.
In conclusion, the photolysis of various thioxapyrroli-
dinones and thiophthal-imides affords novel [2 + 2]
cycloadducts as well as cyclized photoadducts derived
from hydrogen transfer chemistry. Ring opening to
relieve angle strain occurs readily, and this [2 + 2]
photocycloaddition/ring cleavage sequence should prove
useful for the preparation of various azapolycyclic rings.
The preliminary radical cyclizations also show the po-
tential of using N-alkenyl thioimides for the synthesis
of five-membered nitrogen heterocycles. Further varia-
tions and synthetic applications of this methodology will
be reported in due course.
41.9, 43.0, 49.8, 93.4, 154.4, and 174.8; HRMS Calcd for C10H15
NOS2: 229.0595. Found: 229.0599.
-
7,7-Dim eth yl-h exa h yd r o-p yr r olizin -3-on e (21). To a
stirred suspension containing 1.0 g of Raney-Ni in 3 mL of
ethanol was added 0.16 g (0.9 mmol) of disulfide 11 in one
portion. The mixture was heated at reflux for 6 h, cooled to
room temperature, and filtered over Celite. The solvent was
removed under reduced pressure, and the crude residue was
purified by flash silica gel chromatography to give 0.14 g of
pyrrolizin-3-one 21: IR (neat) 2958, 2871, 1690, 1142, and 1280
Exp er im en ta l Section
1-(3-Meth yl-bu t-3-en yl)-5-th ioxo-p yr r olid in -2-on e (16).
A 6.0 g (36 mmol) sample of 1-(3-methyl-but-3-enyl)-pyrroli-
dine-2,5-dione58 and 7.3 g (18 mmol) of Lawesson’s reagent
were suspended in 120 mL of toluene, and the mixture was
heated at reflux for 30 min. The solvent was removed under
reduced pressure, and the resulting residue was purified by
flash silica gel chromatography to give 4.2 g (63%) of thiosuc-
cinimide 16 as a yellow oil: IR (neat) 1753, 1441, and 1397
cm-1; 1H NMR (CDCl3, 400 MHz) δ 1.79 (s, 3H), 2.33 (t, 2H, J
) 7.4 Hz), 2.67-2.72 (m, 2H), 3.09-3.15 (m, 2H), 4.00 (t, 2H,
J ) 7.4 Hz), 4.68 (s, 1H), and 4.76 (s, 1H); 13C NMR (CDCl3,
100 MHz) δ 22.5, 28.9, 34.4, 38.9, 40.8, 112.8, 142.3, 178.8,
and 210.8. Anal. Calcd for C9H13NOS: C, 58.98; H, 7.15; N,
7.64. Found: C, 58.89; H, 7.18; N, 7.60.
1
cm-1; H NMR (CDCl3, 300 MHz) δ 0.77 (s, 3H), 1.00 (s, 3H),
1.72-2.07 (m, 4H), 2.40-2.44 (m, 1H), 2.59-2.2.62 (m, 1H),
3.10-3.11 (m, 1H), 3.37-3.43 (m, 1H), and 3.60 (t, 1H, J )
7.2 Hz); 13C NMR (CDCl3, 75 MHz) δ 19.3, 20.2, 24.7, 34.6,
38.5, 39.9, 41.9, 70.2, and 175.0. Anal. Calcd for C9H14NO: C,
71.02; H, 9.27; N, 9.20. Found: C, 70.78; H, 9.11; N, 9.06.
1-Bu t-3-en yl-5-th ioxo-p yr r olid in -2-on e (22). To a solu-
tion of 5.5 g (36 mmol) of 1-but-3-enyl-pyrrolidine-2,5-dione59
in 120 mL of toluene was added 8.1 g (20 mmol) of Lawesson’s
reagent, and the suspension was heated at reflux for 45 min.
The solvent was removed under reduced pressure, and the
orange residue was purified by flash silica gel chromatography
to give 4.2 g (68%) of thiosuccinimide 22 as a yellow oil: IR
(neat) 1748, 1439, 1397, and 1197 cm-1; 1H NMR (CDCl3, 300
MHz) δ 2.35-2.43 (m, 2H), 267-2.72 (m, 2H), 3.08-3.13 (m,
2H), 3.95 (t, 2H, J ) 7.4 Hz), 5.00-5.07 (m, 2H), and 5.78-
5.81 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ 28.8, 30.9, 38.8,
4-Meth yl-2-th ia -7-a za -tr icyclo[5.3.0.01,4]d eca -8-on e (17).
A 1.1 g (1.8 mmol) sample of thiosuccinimide 16 was dissolved
in 100 mL of benzene, and the mixture was deoxygenated by
bubbling argon through the solution for 15 min. The solution
was irradiated through a Pyrex filter with a 450-W Hanovia
high-pressure Hg lamp for 1 h. The solvent was removed under
reduced pressure, and the residue was purified by flash silica
gel chromatography to give 0.82 g (74%) of thietane 17 as a
white solid: mp 49-51 °C; IR (neat) 2953, 1700, and 1398
41.5, 117.6, 134.4, 178.8, and 210.8. HRMS Calcd for C8H11
NOS: 169.0561. Found: 169.0568.
-
7-Me r ca p t om e t h yl-1,2,5,6-t e t r a h yd r o-p yr r olizin -3-
on e (24). A 0.28 g (6.2 mmol) sample of thiosuccinimide 22
cm-1 1H NMR (CDCl3, 300 MHz) δ 1.31 (s, 3H), 1.53-1.61
;
(58) Burnett, D. A.; Choi, J .-K.; Hart, D. J .; Tsai, Y.-M. J . Am. Chem.
Soc. 1984, 106, 8201.
(59) Gesson, J . P.; J acquesy, J . C.; Rambaud, D. Bull. Soc. Chim.
Fr. 1992, 129, 227.
40 J . Org. Chem., Vol. 69, No. 1, 2004

Photochemical and Radical Cyclizations
was dissolved in 20 mL of benzene, and the mixture was
deoxygenated by bubbling argon through the solution for 15
min. The solution was irradiated in a Pyrex test tube with a
450-W Hanovia high-pressure Hg lamp for 1 h. The solvent
was removed under reduced pressure, and the orange residue
was purified by flash silica gel column chromatography to give
0.035 g (13%) of thiol 24: IR (neat) 2927, 2858, 1678, 1407,
and 1367 cm-1; 1H NMR (CDCl3, 400 MHz) δ 1.52 (t, 1H, J )
7.3 Hz), 2.56-2.60 (m, 2H), 2.74-2.78 (m, 2H), 2.96-3.00 (m,
to -40 °C and was treated with 0.1 g (0.5 mmol) of DMTSF.
After the solution was stirred for 10 min at -40 °C, 0.3 mL
(2.5 mmol) of triethylamine was added dropwise. After the
solution was warmed to 0 °C, the solution was diluted with
ether and 10 mL of a saturated sodium bicarbonate was added.
The layers were separated, and the aqueous layer was
extracted with ether. The combined organic layer was dried
over MgSO4, concentrated under reduced pressure, and puri-
fied by flash silica gel chromatography to give 0.12 g (92%) of
disulfide 27 as a colorless oil: IR (neat) 1701, 1445, 1345, and
2H), 3.25 (d, 2H, J ) 7.3 Hz), and 3.67 (t, 2H, J ) 8.9 Hz); 13
C
NMR (CDCl3, 75 MHz) δ 17.8, 21.4, 34.7, 34.8, 40.2, 109.7,
141.7, and 170.7. HRMS Calcd for C8H11NOS: 169.0561.
Found: 169.0560.
953 cm-1 1H NMR (CDCl3, 300 MHz) δ 1.64-1.99 (m, 6H),
;
2.01-2.40 (m, 2H), 2.31 (s, 3H), 3.08 (t, 1H, J ) 7.7 Hz), 3.19
(dd, 2H, J ) 5.4 and 2.4 Hz), 3.27-3.49 (m, 2H), and 4.77 (t,
1H, J ) 2.4 Hz); 13C NMR (CDCl3, 75 MHz) δ 21.6, 23.6, 32.9,
37.0, 39.1, 39.8, 42.5, 52.0, 59.6, 94.7, 151.0, and 173.9. HRMS
Calcd for C12H17NOS2: 255.0752. Found: 255.0746.
1-(2-Cyclop e n t -1-e n yl-e t h yl)-5-t h ioxo-p yr r olid in -2-
on e (25). A 3.9 g (20 mmol) sample of 1-(2-cyclopent-1-enyl-
ethyl)-pyrrolidine-2,5-dione60 and 4.1 g (10 mmol) of Lawes-
son’s reagent were suspended in 100 mL of toluene, and the
mixture was heated at reflux for 30 min. The solvent was
removed under reduced pressure, and the residue was purified
by flash silica gel chromatography to give 3.3 g (78%) of
thiosuccinimide 25 as a pale-yellow oil: IR (neat) 1748, 1440,
1396, and 1178 cm-1; 1H NMR (CDCl3, 400 MHz) δ 1.77-1.87
(m, 2H), 2.24-2.31 (m, 4H), 2.38 (t, 2H, J ) 7.4 Hz), 2.66-
2.71 (m, 2H), 3.08-3.13 (m, 2H), 3.96-4.02 (m, 2H), and 5.36
(s, 1H); 13C NMR (CDCl3, 100 MHz) δ 23.6, 28.0, 28.9, 32.7,
35.2, 38.9, 40.9, 126.2, 140.7, 178.7, and 210.7. Anal. Calcd
for C11H15NOS: C, 63.12; H, 7.22; N, 6.69. Found: C, 63.27;
H, 7.20; N, 6.65.
Further reduction of 27 with Raney-Ni in ethanol afforded
lactam 28 in 95% yield.
2-(2-Cyclopen t-1-en yl-eth yl)-3-th ioxo-2,3-dih ydr o-isoin -
d ol-1-on e (30). A sample containing 0.85 g of 2-(2-cyclopent-
1-enyl-ethyl)-isoindole-1,3-dione61 was dissolved in 40 mL of
toluene and was treated with 0.7 g of Lawesson’s reagent. After
the solution was heated for 30 min at reflux, the solvent was
removed under reduced pressure and the residue was purified
by flash silica gel chromatography to give 0.46 g (51%) of
thiophthalimide 30 as a pale-yellow oil: IR (neat) 2838, 1752,
1
1598, and 1460 cm-1; H NMR (CDCl3, 400 MHz) δ 1.86 (m,
2H), 2.25 (m, 2H), 2.33 (m, 2H), 2.49 (m, 2H), 4.17 (t, 2H, J )
7.3 Hz), 5.38 (s, 1H), 7.69 (m, 2H), 7.76 (dd, 1H, J ) 5.5 and
3.2 Hz), and 7.95 (dd, 1H, J ) 5.5 and 3.2 Hz); 13C NMR
(CDCl3, 100 MHz) δ 23.5, 29.4, 32.6, 35.1, 39.5, 122.6, 123.8,
126.0, 127.3, 133.1, 134.0, 137.1, 140.7, 169.5, and 196.7.
HRMS Calcd for C15H15NOS: 257.0874. Found: 257.0865
10b-Mer ca p to-1,2,3,5,10b,10c-h exa h yd r o-5a -a za -cyclo-
p en ta [c]flu or en -6-on e (32). A sample of 0.3 g of thiophthal-
imide 30 was dissolved in 25 mL of CH2Cl2, and the mixture
was deoxygenated by bubbling argon through the solution for
15 min. The solution was irradiated with a 450-W Hanovia
high-pressure Hg lamp for 1 h in a Pyrex test tube. The solvent
was removed under reduced pressure, and the residue was
purified by silica gel chromatography to give 0.19 g (64%) of
photoproduct 32 as a white solid: mp 104-105 °C; IR (neat)
2-Th ia -10-a za -tetr a cyclo[8.3.01,7.03,7]tr id eca -11-on e (26).
A 1.3 g (6.2 mmol) sample of thiosuccinimide 25 was dissolved
in 100 mL of benzene, and the mixture was deoxygenated by
bubbling argon through the solution for 15 min. The solution
was irradiated for 1 h through a Pyrex filter with a 450-W
Hanovia high-pressure Hg lamp. The solvent was removed
under reduced pressure, and the residue was purified by flash
silica gel chromatography to give 0.97 g (74%) of thietane 26
as a white solid: mp 95-97 °C; IR (neat) 1701, 1398, 1327,
1
and 1156 cm-1; H NMR (CDCl3, 400 MHz) δ 1.39 (dt, 1H, J
) 13.6 and 6.0 Hz), 1.59-1.69 (m, 1H), 1.73-1.93 (m, 5H),
2.20-2.37 (m, 4H), 2.58-2.70 (m, 1H), 3.45-3.56 (m, 2H), and
4.02 (dd, 1H, J ) 9.8 and 7.7 Hz); 13C NMR (CDCl3, 100 MHz)
δ 25.0, 31.6, 32.8, 33.5, 34.6, 37.1, 40.4, 42.6, 67.6, 78.7, and
172.8. Anal. Calcd. for C11H15NOS: C, 63.12; H, 7.22; N, 6.69.
Found: C, 62.94; H, 7.24; N, 6.64.
1
2954, 1689, 1466 and 1390 cm-1; H NMR (CDCl3, 300 MHz)
δ 1.56-1.68 (m, 1H), 1.86-2.16 (m, 4H), 2.41-2.43 (m, 3H),
3.80-3.88 (m, 1H), 4.61-4.70 (m, 1H), 5.64 (d, 1H, J ) 2.4
Hz), 7.47-7.51 (m, 1H), 7.53-7.63 (m, 2H), and 7.86 (d, 1H, J
) 7.7 Hz); 13C NMR (CDCl3, 75 MHz) δ 24.2, 29.23, 30.6, 37.8,
51.0, 70.6, 113.8, 122.4, 123.9, 129.1, 130.9, 132.1, 140.8, 149.5,
and 165.1. HRMS Calcd for C15H15NOS: 257.0874. Found:
257.0872.
2-(2-Cycloh ex-1-en yl-eth yl)-3-th ioxo-2,3-d ih yd r o-isoin -
d ol-1-on e (31). A 5.1 g (20 mmol) sample of 2-(2-cyclohex-1-
enyl-ethyl)-isoindole-1,3-dione61 and 8.1 g (20 mmol) of Lawes-
son’s reagent were suspended in 45 mL of toluene, and the
mixture was heated at reflux for 20 min. The solvent was
removed under reduced pressure, and the residue was purified
by flash silica gel chromatography to give 5.0 g of thiophthal-
imide 31 as an orange solid: mp 48-49 °C; IR (neat) 2858,
1731, 1603, 1470, and 1347 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 1.51 (m, 2H), 1.62 (m, 2H), 1.87 (m, 2H), 2.04 (m, 2H), 2.32
(t, 2H, J ) 7.3 Hz), 4.11 (t, 2H, J ) 7.3 Hz), 5.54 (s, 1H), 7.67
(m, 2H), 7.75 (ddd, 1H, J ) 8.1, 4.8, and 3.6 Hz), 7.95 (ddd,
1H, J ) 6.3, 3.6, and 0.7 Hz); 13C NMR (CDCl3, 75 MHz) δ
22.1, 22.7, 25.2, 28.1, 35.9, 39.6, 122.5, 123.6, 123.7, 127.2,
132.9, 133.8, 134.1, 137.0, 169.5, and 196.7. Anal. Calcd for
7,7-Sp ir o-cyclop en tyl-h exa h yd r o-p yr r olizin -3-on e (28).
A 0.18 g (0.9 mmol) sample of thietane 26 was added in one
portion to a slurry of 2.0 g of Raney-Ni in 15 mL of ethanol at
room temperature, and the mixture was heated for 6 h at 80
°C. The mixture was allowed to cool to room temperature,
filtered through a pad of Celite, and washed with ethanol, and
the solvent was removed under reduced pressure. The residue
was purified by flash silica gel column chromatography to give
0.086 g (55%) of lactam 28 as an oil: IR (neat) 2951, 2869,
1693, 1411, and 1278 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.16-
1.22 (m, 1H), 1.48-1.80 (m, 8H), 1.88-2.07 (m, 3H), 2.41 (ddd,
1H, J ) 16.7, 9.9 and 2.9 Hz), 2.68 (dt, 1H, J ) 16.8 and 9.5
Hz), 3.11-3.17 (m, 1H), 3.35-3.42 (m, 1H), and 3.79 (t, 1H, J
) 7.3 Hz); 13C NMR (CDCl3, 100 MHz) δ 20.9, 24.8, 25.0, 30.8,
34.5, 34.7, 35.1, 40.4, 40.8, 50.3, 68.9, and 174.7. Anal. Calcd.
for C11H17NO: C, 73.69; H, 9.56; N, 7.82. Found: C, 73.42; H,
9.51; N, 7.78.
7a -Eth oxy-7,7-sp ir o-cyclop en tyl-h exa h yd r op yr r olizin -
3-on e (29). The minor component isolated from the above
silica gel column contained 0.011 g (7%) of aminal 29, which
1
was obtained as a very labile oil; H NMR (CDCl3, 300 MHz)
δ 1.13-1.28 (m, 1H), 1.16 (t, 3H, J ) 7.2 Hz), 1.28-1.48 (m,
1H), 1.50-1.82 (m, 5H), 1.83-2.17 (m, 4H), 2.29-2.48 (m, 2H),
2.69-2.83 (m, 1H), 3.04-3.11 (m, 1H), and 3.34-3.47 (m, 3H).
2,5,6,7-Tetr a h yd r o-p yr r olizin -3-on e (27). A 0.11 g (0.5
mmol) sample of thietane 26 in 3 mL of acetonitrile was cooled
C
16H17NOS: C, 70.81; H, 6.31; N, 5.16. Found: C, 70.74; H,
6.31; N, 5.17.
12b-Mer ca p to-2,3,4,6,12b,12c-h exa h yd r o-1H-isoin d olo-
[1,2-a ]isoqu in -olin -8-on e (33). A 0.3 g sample of thiophthal-
imide 31 was dissolved in 25 mL of CH2Cl2 in a Pyrex test
(60) Machida, M.; Oda, K.; Kanaoka, Y. Chem. Pharm. Bull. 1984,
32, 950.
(61) Machida, M.; Oda, K.; Kanaoka, Y. Tetrahedron, 1985, 41, 4995.
J . Org. Chem, Vol. 69, No. 1, 2004 41

Padwa et al.
tube, and the mixture was deoxygenated by bubbling argon
through the solution for 15 min. The solution was irradiated
with a 450-W Hanovia high-pressure Hg lamp for 1.5 h. The
solvent was removed under reduced pressure, and the residue
was purified by flash silica gel to give 0.22 g (73%) of
photoproduct 33 as a white solid: mp 174-175 °C; IR (neat)
of toluene was treated with 3.2 g (44 mmol) of the known
buten-3-enylamine.64 The mixture was heated at reflux for 3
h in a Dean-Stark apparatus and then allowed to cool to room
temperature. The solvent was removed under reduced pres-
sure, and the resulting oily residue was purified by flash silica
gel chromatography to give 4.7 g (94%) of the titled compound
as a colorless oil: IR (neat) 3078, 2941, 1770, 1717, and 1405
1
2459, 1690, 1614, 1404 and 1260 cm-1; H NMR (CDCl3, 400
1
MHz) δ 1.27-1.35 (m, 2H), 1.74-1.83 (m, 2H) 1.90-2.00 (m,
3H), 2.29-2.43 (m, 2H), 2.46 (d, 1H, J ) 2.9 Hz), 3.86 (dd,
1H, J ) 18.1 and 1.6 Hz), 4.59 (ddd, 1H, J ) 18.1, 6.7 and 3.8
Hz), 5.55 (t, 1H, J ) 2.1 Hz), 7.49 (t, 1H, J ) 7.5 Hz), 7.58 (t,
1H, J ) 7.5 Hz), 7.73 (d, 1H, J ) 7.5 Hz), and 7.85 (d, 1H, J
) 7.5 Hz); 13C NMR (CDCl3, 100 MHz) δ 25.3, 25.7, 29.0, 34.1,
36.5, 46.9, 70.8, 116.9, 123.0, 124.0, 129.1, 130.4, 131.9, 135.6,
150.0, and 164.2. Anal. Calcd for C16H17NOS: C, 70.82; H, 6.32;
N, 5.17. Found: C, 70.76; H, 6.29; N, 5.05.
cm-1; H NMR (CDCl3, 400 MHz) δ 1.93 (d, 6H, J ) 5.1 Hz),
2.29-2.35 (m, 2H), 3.52-3.56 (m, 2H), 4.98-5.29 (m, 2H), and
5.66-5.77 (m, 1H); 13C NMR (CDCl3, 100 MHz) δ 8.8, 33.1,
37.3, 117.4, 134.8, 137.2, and 172.3.
1-Bu t-3-en yl-3,4-d im eth yl-5-th ioxo-1,5-d ih yd r o-p yr r ol-
2-on e (42). A solution containing 2.8 g (16 mmol) of the above
dione in 100 mL of toluene was treated with 2.8 g (7.0 mmol)
of Lawesson’s reagent. The mixture was heated at reflux for
2 h and then cooled to room temperature. The solvent was
removed under reduced pressure, and the resulting oily residue
was subjected to flash silica gel chromatography to give 2.2 g
(73%) of monothiomaleimide 42 as a red oil: IR (neat) 3078,
2938, 1725, and 1396 cm-1; 1H NMR (CDCl3, 400 MHz) δ 1.91
(dd, 3H, J ) 2.9 and 1.3 Hz), 2.07 (dd, 3H, J ) 2.9 and 1.3
Hz), 2.33-2.39 (m, 2H), 3.88 (t, 2H, J ) 1.3 Hz), 4.97-5.05
(m, 2H), and 5.70-5.77 (m, 1H); 13C NMR (CDCl3, 100 MHz)
δ 9.1, 10.9, 32.5, 40.4, 117.3, 130.2, 134.7, 141.0, 174.3, and
202.5. HRMS Calcd for C10H13NOS: 195.0718. Found: 195.0716.
8a -Mer ca p to-1,2-d im eth yl-8,8a -d ih yd r o-5H-in d olizin -
3-on e (43). A solution containing 0.5 g (2.6 mmol) of 42 in
100 mL of CH2Cl2 was deoxygenated by bubbling Ar through
the solution for 15 min. The solution was irradiated with a
450-W Hanovia medium-pressure Hg lamp for 2.5 h. The
solvent was removed under reduced pressure, and the residue
was purified by flash silica gel chromatography to give 0.3 g
(62%) of indolizidone 43 as a colorless oil: IR (neat) 3050, 2919,
2515, 1678, 1417, and 1133 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 1.79 (d, 3H, J ) 1.1 Hz), 2.04 (d, 3H, J ) 1.1 Hz), 2.12-2.21
(m, 2H), 2.44-2.50 (m, 1H), 3.69-3.77 (m, 1H), 4.06-4.44 (m,
1H), 5.70-5.74 (m, 1H), and 5.84-5.88 (m, 1H); 13C NMR
(CDCl3, 100 MHz) δ 8.6, 10.5, 36.1, 37.4, 67.9, 121.0, 124.8,
127.5, 153.6, and 168.1. Anal. Calcd for C10H13NOS: C, 61.52;
H, 6.72; N, 7.18. Found: C, 61.47; H, 6.50; N, 6.88.
2,3,4,6-Tet r a h yd r o-1H -isoin d olo[1,2-a ]isoq u in olin -8-
on e (34). A 0.047 g sample of lactam 33 was dissolved in 4
mL of methanol, and 0.03 g of p-toluenesulfonic acid was
added. The reaction mixture was allowed to stir for 24 h at
room temperature. The solvent was removed under reduced
pressure, and the residue was purified by flash silica gel
chromatography to give (64%) of compound 34 as a white
solid: mp 95-96 °C; IR (neat) 2931, 2862, 1690, 1404, and
1
1112; H NMR (CDCl3, 400 MHz) δ 1.86-1.92 (m, 2H) 2.25-
2.31 (m, 2H), 2.56-59 (m, 2H), 2.89-2.91 (m, 2H), 3.83-3.86
(m, 2H), 5.85 (t, 1H, J ) 4.5 Hz), 7.43 (dt, 1H, J ) 7.63 and
1.0 Hz), 7.53 (dt; 1H, J ) 7.9 and 1.0 Hz), 7.82 (d, 1H, J ) 7.6
Hz), and 7.88 (d, 1H, J ) 1.0 Hz); 13C NMR (CDCl3, 100 MHz)
δ 22.7, 25.4, 25.5, 29.2, 38.1, 119.4, 123.3, 123.6, 128.1, 128.2,
128.4, 130.7, 130.8, 131.4, 135.2, and 165.3. Anal. Calcd for
C16H15NO: C, 80.97; H, 6.38; N, 5.91. Found: C, 80.73; H, 6.24;
N, 5.85.
2-(3-Meth yl-bu t-3-en yl)-3-th ioxo-2,3-d ih yd r o-isoin d ol-
1-on e (35). A 1.0 g (4.5 mmol) sample of 2-(3-methyl-but-3-
enyl)-isoindole-1,3-dione62 and 1.2 g (2.9 mmol) of Lawesson’s
reagent were suspended in 80 mL of toluene, and the mixture
was heated at reflux for 20 min. The solvent was removed
under reduced pressure, and the resulting residue was purified
by flash silica gel chromatography to give 0.69 g (69%) of
thioimide 35 as an orange oil: IR (neat) 2971, 1737, 1644, and
1465 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.83 (s, 3H), 2.43 (t,
2H, J ) 7.3 Hz), 4.17 (t, 2H, J ) 7.3 Hz), 4.69 (s, 1H), 4.75 (s,
1H), 7.68 (m, 2H), 7.76 (dd, 1H, J ) 5.6 and 3.1 Hz); 13C NMR
(CDCl3, 100 MHz) δ 22.4, 35.7, 39.4, 112.7, 122.7, 123.7, 127.2,
133.1, 134.0, 137.1, 142.1, 169.6, and 196.7. Anal. Calcd for
3,4-Dim e t h yl-1-(3-m e t h yl-b u t -3-e n yl)p yr r ole -2,5-d i-
on e. A solution of 3.0 g (24 mmol) of 2,3-dimethyl-maleic
anhydride in 120 mL of toluene was treated with 3.2 g (38
mmol) of the known 3-methyl-but-3-enylamine.65 The mixture
was heated at reflux for 3 h in a Dean-Stark apparatus and
then allowed to cool to room temperature. The solvent was
removed under reduced pressure, and the resulting oily residue
was purified by flash silica gel chromatography to give 4.4 g
(96%) of the title compound as a colorless oil: IR (neat) 3075,
2941, 1770, 1716, and 1407 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 1.74 (s, 3H), 1.92 (d, 6H, J ) 1.0 Hz), 2.26 (t, 2H, J ) 7.3
C
13H13NOS: C, 67.50; H, 5.66; N, 6.06. Found: C, 67.34; H,
5.75; N, 5.94.
10b-Mer ca p to-2-m eth yl-1,10b-d ih yd r o-4H-p yr id o[2,1-
a ]isoin d ol-6-on e (36). A sample of 0.15 g of thiophthalimide
35 was dissolved in 25 mL of CH2Cl2, and the mixture was
deoxygenated by bubbling argon through the solution for 15
min. The solution was irradiated with a 450-W Hanovia high-
pressure Hg lamp for 1 h in a Pyrex test tube. The solvent
was removed under reduced pressure, and the residue was
purified by silica gel chromatography to give 0.11 g (73%) of
photoproduct 36 as a white solid: mp 102-104 °C (lit63 mp
101-102.5 °C); IR (neat) 2839, 1700, 1466 and 1396 cm-1; 1H
NMR (CDCl3, 300 MHz) δ 1.80 (s, 3H), 2.39-2.45 (m, 1H), 2.55
(s, 1H), 2.70-2.78 (m, 1H), 3.81-3.91 (m, 1H), 4.58-4.65 (m,
1H), 5.62(d, 1H, J ) 0.4 Hz), 7.47-7.59 (m, 1H), 7.62-7.69
(m, 2H), and 7.84 (dd, 1H, J ) 1.0 and 6.7 Hz); 13C NMR
(CDCl3, 75 MHz) δ 23.3, 37.1, 43.6, 66.3, 117.8, 122.1, 123.9,
129.2, 129.7, 130.5, 132.3, 149.9, and 164.8. Anal. Calcd for
Hz), 3.59 (t, 2H, J ) 7.3 Hz), 4.63 (s, 1H), and 4.71 (s, 1H); 13
C
NMR (CDCl3, 100 MHz) δ 8.8, 22.2, 36.4, 36.7, 112.6, 137.1,
142.4, and 172.3.
3,4-Dim eth yl-1-(3-m eth yl-bu t-3-en yl)-5-th ioxo-1,5-d ih y-
d r op yr r ol-2-on e (44). A solution of 2.9 g (15 mmol) of the
above dione in 100 mL of toluene was treated with 2.7 g (6.6
mmol) of Lawesson’s reagent. The mixture was heated at
reflux for 2 h and then cooled to room temperature. The solvent
was removed under reduced pressure, and the resulting oily
residue was subjected to flash silica gel chromatography to
give 2.1 g (69%) of monothiomaleimide 44 as a red oil: IR
(neat) 3073, 2939, 1731, and 1350 cm-1; 1H NMR (CDCl3, 400
MHz) δ 1.77 (s, 3H), 1.92 (d, 3H, J ) 1.3 Hz), 2.07 (d, 3H, J )
1.3 Hz), 2.30 (t, 2H, J ) 7.0 Hz), 3.91-3.95 (m, 2H), 4.65 (d,
1H, J ) 1.0 Hz), and 4.72 (d, 1H, J ) 1.0 Hz); 13C NMR (CDCl3,
100 MHz) δ 9.1, 10.9, 22.5, 39.6, 112.5, 130.2, 141.1, 142.5,
174.3, and 202.5; HRMS Calcd for C11H15NOS: 209.0874.
Found: 209.0871.
C
13H13NOS: C, 67.50; H, 5.66; N, 6.06. Found: C, 67.58; H,
5.49; N, 5.89.
1-Bu t-3-en yl-3,4-d im eth yl-p yr r ole-2,5-d ion e. A solution
of 3.5 g (28 mmol) of 2,3-dimethylmaleic anhydride in 120 mL
(62) Stille, J . K.; Becker, Y. J . Org. Chem. 1980, 45, 2139.
(63) Oda, K.; Machida, M.; Kanaoka, Y. Chem. Pharm. Bull. 1992,
40, 585.
(64) J acobson, M. A.; Williard, P. G. J . Org. Chem. 2002, 67, 3915.
(65) Cox, E. F.; Caserio, M. C.; Silver, M. S.; Roberts, J . D. J . Am.
Chem. Soc. 1961, 83, 2719.
42 J . Org. Chem., Vol. 69, No. 1, 2004

Photochemical and Radical Cyclizations
8a-Mer capto-1,2,7-tr im eth yl-8,8a-dih ydr o-5H-in dolizin -
3-on e (45). A solution containing 0.5 g (2.6 mmol) of 44 in
100 mL of CH2Cl2 was deoxygenated by bubbling Ar through
the solution for 15 min. The solution was irradiated with a
450-W Hanovia medium-pressure Hg lamp for 2.5 h. The
solvent was removed under reduced pressure, and the residue
was purified by flash silica gel chromatography to give 0.32 g
(64%) of indolizidone 45 as a colorless oil: IR (neat) 2968, 2917,
2513, 1704, 1412, and 1126 cm-1; 1H NMR (CDCl3, 400 MHz)
δ 1.73 (s, 3H), 1.80 (d, 3H, J ) 1.3 Hz), 1.81 (s, 1H), 2.06 (d,
3H, J ) 1.3 Hz), 2.11-2.17 (m, 1H), 2.29 (d, 1H, J ) 16.8 Hz),
3.67-3.74 (m, 1H), 4.35-4.41 (m, 1H), 5.56 (d, 1H, J ) 1.3
Hz); 13C NMR (CDCl3, 100 MHz) δ 8.7, 10.6, 23.3, 37.2, 40.8,
68.5, 118.4, 127.6, 128.9, 153.3, and 168.2. Anal. Calcd for
13C NMR (CDCl3, 100 MHz) δ 8.7, 12.3, 25.6, 26.0, 30.3, 34.6,
36.2, 45.0, 73.0, 117.2, 127.2, 135.6, 155.0, and 167.3. Anal.
Calcd for C14H19NOS: C, 67.44; H, 7.69; N, 5.62. Found: C,
67.30; H, 7.55; N, 5.38.
1-Bu t-3-en yl-p yr r olid in e-2,5-d ith ion e (53). To a solution
containing 2.1 g (14 mmol) of the known 1-(but-3-enyl)-
pyrrolidine-2,5-dione59 in 50 mL of toluene was added 8.2 g
(20 mmol) of Lawesson’s reagent, and the mixture was heated
at reflux for 30 min. The solvent was removed under reduced
pressure, and the residue was purified by flash silica gel
chromatography to give 0.98 g (40%) of dithiosuccinimide 53
as a pale-yellow oil: IR (neat) 1639, 1419, and 1363 cm-1; 1H
NMR (CDCl3, 300 MHz) δ 2.41 (m, 2H), 3.16 (s, 4H), 4.36 (t,
2H, J ) 7.6 Hz), 5.12 (m, 2H), and 5.80 (m, 1H); 13C NMR
(CDCl3, 75 MHz) δ 29.8, 41.1, 44.6, 117.3, 133.9, and 211.9.
HRMS Calcd for C8H11NS2: 185.0333. Found: 185.0331.
C
11H15NOS: C, 63.13; H, 7.23; N, 6.70. Found: C, 63.02; H,
6.95; N, 6.49.
1-(2-Cycloh ex-1-en yl-et h yl)-3,4-d im et h yl-p yr r ole-2,5-
d ion e. A solution containing 2.5 g (20 mmol) of 2,3-dimethyl-
maleic anhydride in 120 mL of toluene was treated with 2.5 g
(20 mmol) of the commercially available 2-cyclohex-1-enyl-
ethylamine. The mixture was heated at reflux for 3 h in a
Dean-Stark apparatus and then allowed to cool to room
temperature. The solvent was removed under reduced pres-
sure, and the resulting oily residue was purified by flash silica
gel chromatography to give 4.2 g (91%) of the titled compound
2-Th ia-7-aza-tr icyclo[5.3.0.01,4]deca-8-th ion e (54). A 0.19
g (1.0 mmol) sample of dithiosuccinimide 53 was dissolved in
50 mL of benzene, and the mixture was deoxygenated by
bubbling argon through the solution for 15 min. The solution
was irradiated through a Pyrex filter with a 450-W Hanovia
high-pressure Hg lamp for 25 min. The solvent was removed
under reduced pressure, and the residue was purified by flash
silica gel chromatography to give 0.083 g (43%) of thietane
54: IR (neat) 2942, 1476, 1323, 1122, and 1026 cm-1; 1H NMR
(CDCl3, 300 MHz) δ 2.01-2.19 (m, 2H), 2.23-2.34 (m, 1H),
2.64-2.72 (m, 2H), 2.96-3.18 (m, 2H), 3.28 (t, 1H, J ) 9.5
Hz), 3.65-3.72 (m, 1H), 3.79-3.90 (m, 1H), and 4.39-4.46 (m,
1H); 13C NMR (CDCl3, 75 MHz) δ 23.2, 33.2, 38.0, 43.5, 46.5,
50.6, 84.1, and 198.4. Anal. Calcd for C8H11NS2: C, 51.88; H,
5.99; N, 7.57. Found: C, 51.80; H, 6.12; N, 7.44.
as a colorless oil: IR (neat) 2931, 1770, 1716, and 1406 cm-1
;
1H NMR (CDCl3, 400 MHz) δ 1.47-1.68 (m, 4H), 1.88-1.95
(m, 4H), 1.93 (d, 6H, J ) 0.6 Hz), 2.13-2.17 (m, 2H), 3.54 (t,
2H, J ) 7.3 Hz), and 5.34 (brs, 1H); 13C NMR (CDCl3, 100
MHz) δ 8.8, 22.4, 23.0, 25.5, 28.0, 36.6, 37.0, 123.8, 134.5,
137.1, and 172.3.
1-(2-Cycloh ex-1-en yl-eth yl)-3,4-d im eth yl-5-th ioxo-1,5-
d ih yd r op yr r ol-2-on e (46). A solution containing 3.5 g (15
mmol) of the above dione in 100 mL of toluene was treated
with 3.0 g (7.5 mmol) of Lawesson’s reagent. The mixture was
heated at reflux for 2 h and then cooled to room temperature.
The solvent was removed under reduced pressure, and the
resulting oily residue was subjected to flash silica gel chro-
matography to give 2.7 g (68%) of monothiomaleimide 46 as a
1,2,5,6-Tetr a h yd r o-p yr r olizin e-3-th ion e (55). The second
fraction isolated from the column contained 0.036 g (19%) of
thione 55: IR (neat) 2925, 1495, 1344 and 1127 cm-1; 1H NMR
(CDCl3, 300 MHz) δ 2.61-2.69 (m, 2H), 2.96-3.03 (m, 2H),
3.32 (t, 2H, J ) 7.6 Hz), 3.79 (t, 2H, J ) 7.9 Hz), and 5.00 (t,
1H J ) 2.2 Hz); 13C NMR (CDCl3, 100 MHz) δ 20.1, 33.8, 43.9,
47.3, 103.6, 150.1, and 192.7. HRMS Calcd for C7H9NS:
139.0456. Found: 139.0454.
1
red oil; IR (neat) 3025, 2932, 1728, and 1396 cm-1; H NMR
7-Me r ca p t om e t h yl-1,2,5,6-t e t r a h yd r o-p yr r olizin -3-
on e (56). Recrystallization of a sample of 54 from ethyl acetate
gave the ring-opened product 56 as a yellow solid: mp 107-
108 °C; IR (neat) 2946, 1486, and 1168 cm-1; 1H NMR (CDCl3,
400 MHz) δ 1.58 (t, 3H, J ) 7.6 Hz), 2.58-2.62 (m, 2H), 3.00-
3.02 (m, 2H), 3.21-3.28 (m, 4H), 3.75-3.79 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ 19.3, 2.52, 34.7, 43.8, 46.8, 116.1, 145.3,
and 192.4. Anal. Calcd for C8H11NS2: C, 51.85; H, 5.98; 7.56.
Found: C, 51.89; H, 5.99; N, 7.54.
(CDCl3, 400 MHz) δ 1.46-1.61 (m, 4H), 1.92-2.02 (m, 4H),
1.92 (d, 3H, J ) 1.0 Hz), 2.07 (d, 3H, J ) 1.0 Hz), 2.19 (t, 2H,
J ) 7.3 Hz), 3.88 (t, 2H, J ) 7.3 Hz), and 5.35 (brs, 1H); 13C
NMR (CDCl3, 100 MHz) δ 9.1, 22.4, 23.0, 25.5, 28.3, 36.3, 39.9,
123.8, 130.2, 134.5, 141.0, 174.3, and 202.5. HRMS Calcd for
C
14H19NOS: 249.1187. Found: 249.1184.
10b-Mer capto-1,2-dim eth yl-7,8,9,10,10a,10b-h exah ydr o-
5H-p yr r olo[2,1-a ]-isoqu in olin -3-on e (47). A solution of 0.5
g (2.0 mmol) of 46 in 100 mL of CH2Cl2 was deoxygenated by
bubbling Ar through the solution for 15 min. The solution was
irradiated with a 450-W Hanovia medium-pressure Hg lamp
for 2.5 h, and the solvent was removed under reduced pressure.
The residue was purified by flash silica gel chromatography
to give 0.36 g (72%) of indolizidone 47 as a 1:3 mixture of
diastereomers. The minor diastereomer 47a was isolated as a
white solid: mp 104-105 °C; IR (neat) 2929, 2851, 1693, 1410,
1-(3-Meth yl-bu t-3-en yl)-p yr r olid in e-2,5-d ith ion e (57).
A 1.4 g (8.3 mmol) sample of the known 1-(3-methylbut-3-enyl)-
pyrrolidine-2,5-dione58 and 3.8 g (9.5 mmol) of Lawesson’s
reagent were suspended in 75 mL of toluene, and the mixture
was heated at reflux for 30 min. The solvent was removed
under reduced pressure, and the residue was purified by flash
silica gel chromatography to give 0.8 g (49%) of dithioimide
57:16b IR (neat) 3073, 2971, 2689, 1644, 1419, and 1168 cm-1
;
1
and 1125 cm-1; H NMR (CDCl3, 400 MHz) δ 0.82 (dq, 1H, J
1H NMR (CDCl3, 300 MHz) δ 1.81 (s, 3H), 2.33 (t, J ) 8.3 Hz,
2H), 3.16 (s, 4H), 4.39 (t, 2H, J ) 8.3 Hz), 4.75 (s, 1H), and
4.81 (s, 1H); 13C NMR (CDCl3, 75 MHz) δ 22.7, 33.1, 41.2, 44.3,
112.4, 142.0, and 211.8. Anal. Calcd for C9H13NS2: C, 54.26;
H, 6.58; N, 7.03. Found: C, 54.42; H, 6.55; N, 6.98.
) 12.4 and 3.8 Hz), 1.16-1.25 (m, 1H), 1.35-1.48 (m, 2H),
1.71-1.75 (m, 1H), 1.80 (d, 3H, J ) 1.3 Hz), 1.82-1.84 (m,
1H), 1.93-2.00 (m, 1H), 2.05 (d, 3H, J ) 1.3 Hz), 2.13-2.17
(m, 1H), 2.31-2.36 (m, 2H), 3.69 (dd, 1H, J ) 17.8 and 2.2
Hz), 4.39 (dd, 1H, J ) 17.8 and 4.4 Hz), 5.47 (brs, 1H); 13C
NMR (CDCl3, 100 MHz) δ 8.7, 11.7, 26.5, 29.9, 30.8, 36.6, 36.8,
48.8, 71.7, 114.1, 129.2, 139.4, 151.2, and 168.3. Anal. Calcd
for C14H19NOS: C, 67.44; H, 7.69; N, 5.62. Found: C, 67.25;
H, 7.40; N, 5.33.
4-Met h yl-2-t h ia -7-a za -t r icyclo[5.3.0.01,4]d eca -8-t h ion e
(58). A 0.1 g sample of dithiosuccinimide 57 was dissolved in
25 mL of benzene, and the mixture was deoxygenated by
bubbling argon through the solution for 15 min. The solution
was irradiated with a 450-W Hanovia high-pressure Hg lamp
for 15 min in a Pyrex test tube. At the end of this time, the
solvent was removed under reduced pressure and the resulting
orange residue was purified by flash silica gel column chro-
matography to give 0.073 g (72%) of thietane 58,16b a light-
yellow oil that crystallized on standing: mp 81-82 °C; 1H
The major diastereomer 47b was obtained as a white solid;
dec 155 °C; IR (neat) 2923, 2855, 2493, 1677, and 1420 cm-1
;
1H NMR (CDCl3, 400 MHz) δ 1.20-1.46 (m, 3H), 1.48 (s, 1H),
1.69-2.00 (m, 3H), 1.80 (d, 3H, J ) 1.0 Hz), 2.03-2.22 (m,
2H), 2.14 (d, 3H, J ) 1.0 Hz), 3.68 (dd, 1H, J ) 117.8 and 1.3
Hz), 4.31-4.38 (m, 1H), and 5.50 (dd, 1H, J ) 4.4 and 2.2 Hz);
J . Org. Chem, Vol. 69, No. 1, 2004 43

Padwa et al.
NMR (CDCl3, 300 MHz) δ 1.30 (s, 3H), 1.72 (m, 1H), 2.09 (m,
1H), 2.33 (m, 2H), 2.83 (m, 1H), 2.92 (m, 1H), 2.99 (m, 1H),
3.08 (m, 1H), 3.80 (m, 1H), and 4.32 (m, 1H); 13C NMR (CDCl3,
75 MHz) δ 23.0, 30.9, 33.5, 40.9, 43.6, 45.8, 55.6, 86.6, and
197.7. Anal. Calcd for C9H13NS2: C, 54.26; H, 6.58; N, 7.03.
Found: C, 54.07; H, 6.42; N, 6.87.
4.30 (m, 1H); 13C NMR (CDCl3, 100 MHz) δ 17.8, 18.5, 28.0,
28.8, 34.4, 40.3, 41.5, 43.2, 45.9, 57.7, 85.8, and 197.4. HRMS
Calcd for C12H17NS2: 239.0802. Found: 239.0802.
6-Cycloh e x-1-e n yl-5-m e r ca p t o-1-a za -b icyclo[3.2.0]-
h ep ta n e-2-th ion e (64). The second compound isolated from
silica gel column chromatography contained 0.056 g (30%) of
64 as a colorless oil, which consisted of a mixture of a 1:1
mixture of diasteromers: 1H NMR (CDCl3, 300 MHz) δ 1.66
(m, 5H), 1.95 (m, 1H), 2.14 (m, 1H), 2.42 (dd, 1H, J ) 13.4
and 8.7 Hz), 2.60 (dd, 1H, J ) 13.4 and 7.3 Hz), 2.94 (dd, 1H,
J ) 17.8 and 8.5 Hz), 3.30 (ddd, 1H, J ) 17.1, 8.1 Hz, and 4.4
Hz), 3.32 (t, 1H, J ) 7.8 Hz), 4.08 (dd, 1H, J ) 10.3 and 7.8
Hz), 4.36 (dd, 1H, J ) 10.3 and 7.8 Hz), and 5.66 (dd, 1H, J )
3.4 and 1.9 Hz); 13C NMR (CDCl3, 75 MHz) δ 22.2, 22.4, 25.3,
28.6, 43.4, 45.5, 53.4, 56.9, 87.5, 126.3, 133.4, and 207.3. HRMS
Calcd for C12H17NS2: 239.0802. Found: 239.0800.
1-(4-Met h a n esu lfon yl-b u t -3-en yl)-p yr r olid in e-2,5-d i-
on e. A solution containing 1.9 g (8.2 mmol) of methanesulfo-
nylmethyl-phosphonic acid diethyl ester66 in 40 mL of THF at
-78 °C was treated with 3.4 mL (8.2 mmol) of 2.4 M
n-butyllithium in hexane, and the mixture was allowed to stir
for 30 min. A solution of 1.28 g (8.2 mmol) of the known 3-(2,5-
dioxo-pyrrolidin-1-yl)-propionaldehyde67 in 10 mL of THF was
added dropwise to the reaction mixture. The solution was
allowed to warm gradually to room temperature and was
stirred continuously overnight. The mixture was quenched by
the addition of 15 mL of an aqueous NH4Cl solution and
extracted with ethyl acetate. The combined organic layers were
dried over MgSO4, and the solvent was removed under reduced
pressure. The crude mixture was purified by flash silica gel
column chromatography to give 1.9 g (45%) of the titled
compound as a white solid: mp 127-128 °C; IR (neat) 1772,
1697, 1403, 1306, and 1132 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 2.57 (dq, 2H, J ) 7.0 and 1.2 Hz), 2.72 (s, 4H), 2.91 (s, 3H),
3.80 (t, 2H, J ) 7.0 Hz), 6.45 (d, 1H, J ) 15.1 Hz), and 6.83
(dt, 1H, J ) 15.1 and 6.7 Hz); 13C NMR (CDCl3, 75 MHz) δ
28.3, 29.7, 36.7, 42.8, 132.0, 143.7, and 177.1. Anal. Calcd for
C9H13NO4S: C, 46.74; H, 5.67; N, 6.06. Found: C, 46.73; H,
5.69; N, 6.03.
7-Meth yl-1,2,5,6-tetr a h yd r o-p yr r olizin e-3-th ion e (59).
The minor component (10%) isolated from column chromatog-
raphy was identified as thioamide 59: IR (neat) 2930, 1487,
1325, and 1109 cm-1 1H NMR (CDCl3, 300 MHz) δ 1.69 (t,
;
3H, J ) 1.4 Hz), 2.54-2.60 (m, 2H), 2.86-2.91 (m, 2H), 3.28-
3.33 (m, 2H), and 3.76-3.82 (m, 2H); 13C NMR (CDCl3, 75
MHz) δ 12.5, 19.1, 38.1, 43.9, 47.1, 114.1, 143.9, and 190.6.
HRMS Calcd for C8H11NS: 153.0612. Found: 153.0610.
1-(2-Cyclop en t-1-en yl-eth yl)-p yr r olid in e-2,5-d ith ion e
(60). To a solution of 0.78 g (4.0 mmol) of the known 1-(2-
cyclopent-1-enyl-ethyl)-pyrrolidine-2,5-dione60 in 50 mL of
toluene was added 2.0 g (4.8 mmol) of Lawesson’s reagent, and
the mixture was heated at reflux for 30 min. The solvent was
removed under reduced pressure, and the residue was purified
by flash silica gel chromatography to give 0.5 g (58%) of
dithiosuccinimide 60 as a yellow oil: IR (neat) 2843, 1419, and
1
1362 cm-1; H NMR (CDCl3, 400 MHz) δ 1.85 (m, 2H), 2.29
(m, 4H), 2.40 (t, 2H, J ) 7.1 Hz), 3.16 (s, 4H), 4.41 (t, 2H, J )
7.1 Hz), and 5.42 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 23.4,
27.0, 32.7, 35.4, 41.3, 44.3, 125.9, 140.5, and 211.9. Anal. Calcd
for C11H15NS2: C, 58.62; H, 6.71; N, 6.21. Found: C, 58.69; H,
6.74; N, 6.21.
2-Th ia -10-a za -tetr a cyclo[8.3.01,7.03,7]tr id eca -11-th ion e
(61). A 0.24 g (1.8 mmol) sample of dithiosuccinimide 60 was
dissolved in 50 mL of benzene, and the mixture was deoxy-
genated by bubbling argon through the solution for 15 min.
The solution was irradiated with a 450-W Hanovia high-
pressure Hg lamp for 20 min. The solvent was removed under
reduced pressure, and the residue was purified by flash silica
gel to give 0.12 g (48%) of thietane 61 as a light-yellow solid:
mp 94-96 °C; IR (neat) 2949, 1478, 1455, 1324, and 929 cm-1
;
1H NMR (CDCl3, 400 MHz) δ 1.40 (dt, 1H, J ) 13.7 and 5.8
Hz), 1.76-2.01 (m, 6H), 2.20-2.43 (m, 3H), 2.92-3.15 (m, 2H),
3.53 (dd, 1H, J ) 4.8 and 1.2 Hz), 3.74-3.85 (m, 1H), and 4.41
(dd, 1H, J ) 12.6 and 7.8 Hz); 13C NMR (CDCl3, 100 MHz) δ
25.0, 33.5, 34.0, 34.6, 36.3, 42.7, 43.9, 45.6, 66.7, 83.1, and
197.9. Anal. Calcd for C11H15NS2: C, 58.62; H, 6.71; N, 6.21.
Found: C, 58.59; H, 6.84; N, 6.22.
1-(4-Meth a n esu lfon yl-bu t-3-en yl)-5-th ioxo-p yr r olid in -
2-on e (72). A 0.65 g (1.6 mmol) sample of Lawesson’s reagent
was added to 0.75 g (3.2 mmol) of the above succinimide in 50
mL of toluene, and the mixture was heated at reflux. After
cooling to room temperature, the solvent was evaporated under
reduced pressure and the oily residue was purified by flash
silica gel column chromatography to afford 0.32 g (40%) of
thiosuccinimide 72 as a yellow oil which solidified on stand-
ing: mp 64-66 °C; IR (neat) 1751, 1638, 1344, 1299, and 1132
1-(2-Cycloh ex-1-en yl-et h yl)-p yr r olid in e-2,5-d it h ion e
(62). A 6.7 g (32 mmol) sample of the known 1-(2-cyclohex-1-
enyl-ethyl)-pyrrolidine-2,5-dione60 and 13 g (32 mmol) of
Lawesson’s reagent were suspended in 60 mL of toluene, and
the mixture was heated at reflux for 30 min. The solvent was
removed under reduced pressure, and the residue was purified
by flash chromatography to give 4.4 g (57%) of dithiosuccin-
imide 62 as a yellow oil that crystallized on standing: mp 44-
1
cm-1; H NMR (CDCl3, 300 MHz) δ 2.62 (m, 2H, J ) 7.2 and
1.4 Hz), 2.71-2.76 (m, 2H), 2.91 (s, 3H), 3.11-3.16 (m, 2H),
4.04 (t, 2H, J ) 7.2 Hz), 6.42 (d, 1H, J ) 15.1 Hz), and 6.85
(dt, J ) 15.4 and 7.0 Hz); 13C NMR (CDCl3, 75 MHz) δ 28.6,
28.8, 38.9, 40.1, 42.7, 132.0, 143.7, 178.7, and 210.7; Anal.
Calcd for C9H13NO3S2: C, 43.70; H, 5.30; N, 5.66. Found: C,
43.74; H, 5.35; N, 5.65.
45 °C; IR (neat) 2853, 1419, 1358, and 1086 cm-1 1H NMR
;
(CDCl3, 400 MHz) δ 1.53 (m, 2H), 1.60 (m, 2H), 1.95 (m, 2H),
2.03 (m, 2H), 2.23 (t, 2H, J ) 7.8 Hz), 3.15 (s, 4H), and 4.35 (t,
2H, J ) 7.8 Hz), and 5.44 (s, 1H); 13C NMR (CDCl3, 100 MHz)
δ 22.4, 23.0, 25.5, 28.6, 33.6, 41.4, 44.8, 124.0, 134.3, and 212.1.
Anal. Calcd for C12H17NS2: C, 60.20; H, 7.16; N, 5.85. Found:
C, 60.26; H, 7.18; N, 5.74.
5-(2-Oxo-5-t h ioxo-p yr r olid in -1-yl)-p en t -2-en oic Acid
Meth yl Ester (73). A 3.2 g (7.9 mmol) sample of Lawesson’s
reagent was added to 3.7 g of methyl 5-(2,5-dioxo-1-pyrroli-
dino)-2-pentenoate67 in dry toluene, and the mixture was
heated at reflux for 1 h. The solvent was removed under
reduced pressure, and the oily residue was subjected to flash
silica gel column chromatography to give 2.1 g (53%) of the
monothiosuccinimide 73 as a yellow oil: IR (neat) 2842, 1761,
2-T h ia -11-a za -t e t r a c y c lo [9.3.01,8.03,8]t e t r a d e c a -12-
th ion e (63). A 0.2 g sample of dithiosuccinimide 62 was
dissolved in 25 mL of benzene, and the mixture was deoxy-
genated by bubbling argon through the solution for 15 min.
The solution was irradiated with a 450-W Hanovia high-
pressure Hg lamp for 30 min at room temperature in a Pyrex
test tube. The solvent was removed under reduced pressure,
and the residue was purified by flash chromatography to give
0.056 g (30%) of thietane 63 as a light-yellow solid: mp 78-
1
1725, 829, and 717 cm-1; H NMR (CDCl3, 300 MHz) δ 2.54
(dq, 2H, J ) 7.2 and 1.2 Hz), 2.70-2.75 (m, 2H), 3.11-3.16
(m, 2H), 3.72 (s, 3H), 4.02 (t, 2H, J ) 7.2 Hz), 5.86 (dd, 1H, J
) 15.6 and 1.44 Hz), and 6.89 (dt, 1H, J ) 15.6 and 8.4 Hz);
13C NMR (CDCl3, 75 MHz) δ 28.6, 29.2, 38.7, 40.4, 51.6, 123.2,
79 °C; IR (neat) 2933, 2863, 1478, 1319, 1158, and 1026 cm-1
;
1H NMR (CDCl3, 400 MHz) δ 1.41 (m, 2H), 1.60 (m, 1H), 1.77
(m, 4H), 1.98 (m, 2H), 2.18 (m, 1H), 2.45 (m, 2H), 2.95 (m,
1H), 3.09 (m, 1H), 3.41 (t, 1H, J ) 5.1 Hz), 3.80 (m, 1H), and
(66) Shahak, I.; Almog, J . Synthesis, 1969, 170.
(67) Taber, D. F.; Hoerrner, R. S.; Hagen, M. D. J . Org. Chem. 1991,
56, 1287.
44 J . Org. Chem., Vol. 69, No. 1, 2004

Photochemical and Radical Cyclizations
144.2, 166.4, 178.6, and 210.6. HRMS Calcd for C10H13NO3S:
227.0616. Found: 227.0623.
to cool to room temperature. The solvent was evaporated under
reduced pressure, and the resulting residue was purified by
flash column chromatography to give 0.11 g (68%) of pyrrolizi-
done 78 as a colorless oil.
(5-Oxo-2,5,6,7-tetr ah ydr o-3H-pyr r olizin -1-yl)-acetic Acid
Meth yl Ester (79). A 0.17 g (0.75 mmol) sample of monothio-
imide 75 was dissolved in 50 mL of toluene and was treated
with 0.25 g (0.87 mmol) tributyltin hydride and 0.025 g (0.15
mmol) of AIBN. The resulting solution was heated at reflux
for 2 h. The reaction mixture was allowed to cool to room
temperature and was evaporated under reduced pressure. The
oily residue was subjected to flash silica gel chromatography
to afford 0.099 g (67%) of pyrrolizidinone 79 as a white solid:
7-Ben zyl-1,2,5,6-tetr a h yd r o-p yr r olizin -3-on e (77). To a
solution of 0.16 g (0.64 mmol) of 1-(4-phenyl-but-3-enyl)-5-
thioxo-pyrrolidin-2-one (71)55c in 50 mL of toluene was added
0.18 g (0.73 mmol) of tris-trimethylsilylsilane68 and 0.02 g (0.13
mmol) of AIBN. The mixture was heated at reflux, and
additional quantities of AIBN were added at 30 min intervals.
The mixture was heated for an additional 30 min after the
last addition of AIBN. The solution was cooled to room
temperature and concentrated under reduced pressure, and
the crude residue was purified by flash silica gel column
chromatography to give 0.03 g (28%) of the known pyrrolizidine
7755c as a colorless oil: IR (neat) 1685, 1431, 1408, 1364, 1264,
and 702 cm-1; 1H NMR (CDCl3, 300 MHz) δ 2.35-2.40 (m, 2H),
2.68-2.73 (m, 2H), 2.77-2.83 (m, 2H), 3.33 (s, 2H), 3.61 (t,
2H, J ) 8.9 Hz), and 7.15-7.33 (m, 5H); 13C NMR (CDCl3, 75
MHz) δ 17.9, 33.5, 34.8, 36.3, 40.0, 110.5, 126.5, 128.7, 128.8,
129.3, 140.5, and 170.5.
mp 64-65 °C; IR (neat) 1721, 1670, 1434, 1260, and 994 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 2.49-2.54 (m, 2H), 2.69-2.75
(m, 2H), 2.88-2.94 (m, 2H), 3.01 (s, 2H), 3.59-3.66 (m, 2H),
and 3.66 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 17.8, 32.3, 34.6,
36.4, 40.1, 52.0, 103.5, 143.0, 170.6, and 171.4. HRMS Calcd
for C10H13NO3: 195.0895. Found: 195.09012.
An alternative method that was also used involved dissolv-
ing a 0.18 g (0.8 mmol) sample of monothioimide 75 in 50 mL
of toluene. The solution was treated with 0.24 g (0.95 mmol)
of tris(trimethylsilyl)silane and 0.026 g (0.16 mmol) of AIBN,
and the mixture was heated at reflux. At 30 min intervals, a
total of four additional 0.026 g samples of AIBN were added
to the refluxing mixture. After the last addition was complete,
the mixture was allowed to stir for 30 min and was then
allowed to cool to room temperature. The solvent was evapo-
rated under reduced pressure, and the resulting oily residue
was purified by flash column chromatography to give 0.12 g
(75%) of pyrrolizidone 79.
Meth a n esu lfon ylm eth yl-1,2,5,6-tetr a h yd r o-p yr r olizin -
3-on e (78). A 0.2 g (0.8 mmol) sample of the monothioimide
72 was dissolved in 50 mL of toluene and was treated with
0.28 g (0.95 mmol) of tributyltin hydride and 0.027 g (0.16
mmol) of AIBN. The resulting mixture was heated at reflux
for 2 h and cooled to room temperature, and the solvent was
evaporated under reduced pressure. The oily residue was
subjected to flash silica gel chromatography to afford 0.085 g
(48%) pyrrolizidone 78 as a colorless oil: IR (neat) 1721, 1670,
1434, 1260, and 994 cm-1; 1H NMR (CDCl3, 300 MHz) δ 2.63-
2.66 (m, 2H), 2.74-2.79 (m, 2H), 2.89 (s, 3H), 3.01-3.11 (m,
2H), 3.65-3.72 (m, 2H), and 3.72 (s, 2H); 13C NMR (CDCl3, 75
MHz) δ 18.1, 34.4, 36.3, 40.3, 40.5, 53.8, 97.3, 148.9, and 170.9.
FAB HRMS [(C9H13NO3S) + Li]+ Calcd: 222.0776. Found:
222.0786.
Pyrrolizidone 78 was also prepared in the following manner.
A 0.19 g (0.8 mmol) sample of monothioimide 72 was dissolved
in 50 mL of toluene and was treated with 0.23 g (0.92 mmol)
of tris(trimethylsilyl)silane and 0.025 g (0.15 mmol) of AIBN,
and the mixture was heated at reflux. At 30 min intervals, a
total of four additional 0.023 g samples of AIBN were added
to the refluxing mixture. After the last addition, the mixture
was allowed to stir for an additional 30 min and was allowed
Ack n ow led gm en t. We gratefully acknowledge the
National Science Foundation (CHE-0132651) for gener-
ous support of this work. We also thank Dr. Kenneth
Hardcastle for his assistance with the X-ray crystal
structures of compounds 17 and 47b as well as Ben-
jamin R. Cohen for some experimental assistance.
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra for new compounds lacking analyses together
with ORTEP drawings for compounds 17 and 47b in PDF
format. This material is available free of charge via the
Internet at http://pubs.acs.org.
(68) Chatgilialoglu, C.; Griller, D.; Lesage, M. J . Org. Chem. 1988,
53, 3, 3642.
J O035127W
J . Org. Chem, Vol. 69, No. 1, 2004 45