Chemoselective lactam formation in the addition of benzenesulfonyl bromide to N-allyl acrylamides and N-allyl 3,3-dimethylacrylamides

Article abstract of DOI:10.1021/jo9820770

Chemoselectivity in the addition and cyclization reactions of PhSO₂Br to N-allyl acrylamides has been confirmed due to the higher reactivity of the acrylic C=C bond toward the sulfonyl radical than that of the allyl C=C bond. Formation of γ-lactams by C(β)→C(α) cyclization can be achieved with N- allyl 3,3-dimethylacrylamides.

Full text of DOI:10.1021/jo9820770

2346
J . Org. Chem. 1999, 64, 2346-2352
Ch em oselective La cta m F or m a tion in th e Ad d ition of
Ben zen esu lfon yl Br om id e to N-Allyl Acr yla m id es a n d N-Allyl
3,3-Dim eth yla cr yla m id es
Chen Wang* and Glen A. Russell†
Department of Chemistry, Iowa State University, Ames, Iowa 50011-3111
Received October 15, 1998
Chemoselectivity in the addition and cyclization reactions of PhSO2Br to N-allyl acrylamides has
been confirmed due to the higher reactivity of the acrylic CdC bond toward the sulfonyl radical
than that of the allyl CdC bond. Formation of γ-lactams by CâfCR cyclization can be achieved
with N-allyl 3,3-dimethylacrylamides.
Sch em e 1
In tr od u ction
Functionalized γ-lactams are important intermediates
in organic synthesis,1 and many natural products of
potential use in medicine and agriculture have a γ-lactam
skeleton.2 Generally, the γ-lactam skeleton is constructed
through formation of the acyl-N bond.3 Recently, forma-
tion of the CRCâ bond by Pd-catalyzed4 or radical5
cyclizations have received attention. In those radical
cyclization reports, the R-carbamoyl radical, generated
from the corresponding halide,5a,b mercury halide,5c or
other precursor under thermolysis, photolysis, or media-
tion of Cu+, Ni0, Fe0, Mn3+, etc., intramolecularly adds
to another CdC bond in a 5-exo or 5-endo mode.5d-g This
kind of cyclization is defined as a CRfCâ radical cycliza-
tion in this paper (Scheme 1, only exo cyclization is
depicted). Surprisingly, we have not found any report of
a CâfCR cyclization, which, if possible, would provide a
new approach to the γ-lactam skeleton with different
functionality.
Sch em e 2
In fact, CâfCR radical cyclization has been attempted
by M. P. Bertrand and his colleagues (Scheme 2).6 They
* Corresponding author. Phone: 515-294-7050. Fax: 515-294-0105.
E-mail: ycwang@iastate.edu.
† Deceased.
(1) (a) J asperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991,
91, 1237. (b) Sell, M. S.; Klein, W. R.; Rieke, R. D. J . Org. Chem. 1995,
60, 1077. (c) J ayaraman, M.; Puranik, V. G.; Bhawal, B. M. Tetrahedron
1996, 52, 9005. (d) Palomo, C.; Cossio, F. P.; Cuevas, C.; Odriozola, J .
M.; Ontoria, J . M. Tetrahedron Lett. 1992, 33, 4827. (e) Ede, N. J .;
Rae, I. D.; Hearn, M. T. W. Tetrahedron Lett. 1990, 31, 6071. (f) Giese,
B.; Kopping, B.; Gobel, T.; Dickhaut, J .; Thoma, G.; Kulicke, K. J .;
Trach, F. Org. React. 1996, 48, 301.
(2) (a) Moody, C. M.; Young, D. W. Tetrahedron Lett. 1994, 35, 7277.
(b) Bergmann, R.; Gericke, R. J . J . Med. Chem. 1990, 33, 492. (c)
Nilsson, B. M.; Ringdahl, B.; Hacksell, U. J . Med. Chem. 1990, 33,
580. (d) Hartwig, W.; Born, L. J . Org. Chem. 1987, 52, 4352. (e) Uno,
H.; Baldwin, J . E.; Russell, A. T. J . Am. Chem. Soc. 1994, 116, 2139.
(3) Curran, D. P. Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, U.K., 1991; Vol. 4, p 779.
(4) Giambastiani, G.; Pacini, B.; Porcelloni, M.; Poli, G. J . Org.
Chem. 1998, 63, 804.
(5) (a) Nagashima, H.; Ozaki, N.; Ishii, M.; Seki, K.; Washiyama,
M.; Itoh, K. J . Org. Chem. 1993, 58, 464. (b) Benedetti, M.; Forti, L.;
Ghelfi, F.; Pagnoni, U. M.; Ronzoni, R. Tetrahedron 1997, 53, 14031.
(c) Russell, G. A.; Li, C.; Chen, P. J . Am. Chem. Soc. 1996, 118, 9831.
(d) Goodall, K.; Parsons, A. F. Tetrahedron Lett. 1997, 38, 491. (e)
Cassayre, J .; Quiclet-Sire, B.; Saunier, J .-B.; Zard, S. Z. Tetrahedron
1998, 54, 1029. (f) Clough, J . M.; Pattenden, G.; Wight, P. G.
Tetrahedron Lett. 1989, 30, 7469. (g) Davies, D. T.; Kapur, N.; Parsons,
A. F. Tetrahedron Lett. 1998, 39, 4397.
reported that the reaction of TolSO2Br with amide 1a
yielded only sulfones 4 and 5, which originate from
radical adduct 2. Compounds 6, 7, and 8, originating from
intermediate 3, were not found. This result contrasts with
what is predicted based on polar effects, because the
electrophilic radical TolSO2•, generated by photolysis of
TolSO2Br, would be expected to add preferentially to the
nucleophilic allyl CdC bond, rather than the electrophilic
acrylic CdC bond of 1a . Bertrand explained this observa-
tion by postulating that the initial additions of TolSO2•
(6) (a) Riggi, I. D.; Gastaldi, S.; Surzur, J .-M.; Bertrand, M. P. J .
Org. Chem. 1992, 57, 6118. (b) Bertrand, M. P. Org. Prep. Proced. Int.
1994, 26, 257.
10.1021/jo9820770 CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/12/1999

Chemoselective Lactam Formation
J . Org. Chem., Vol. 64, No. 7, 1999 2347
Ta ble 2. Rea ction s of P h SO2Br a n d N-Allyl
3,3-Dim eth yla cr yla m id es u n d er Su n la m p Ir r a d ia tion in
Aceton itr ile
Sch em e 3
amide, R )
products (yield, %)
11a , CH2CHdCH2
12a (34),a 13a (13)a
14 (37, c/t ) 2 or 1/2)b
12b (50), 11f (21)
12c (62), 13c (37)
12d (37),a 13d (15)a
no reaction
11b, CMe3
11c, CH2Ph
11d , Me
11e, Ph
Ta ble 1. Rea ction s of P h SO2Br a n d N-Allyl Acr yla m id es
u n d er Su n la m p Ir r a d ia tion in Aceton itr ile
amide, R )
products (yield, %)
11f, H
15 (72)
1a , CH2CHdCH2
1b, CMe3
1c, CH2Ph
1d , Me
1e, Ph
1f, H
9a (83, c/t ) 1/6.1)
a
Lactams 12a and 13a , 12d and 13d , are inseparable by TLC;
9b (93, c/t ) 1/5.0)
their yields were calculated from the 1H NMR ratio of the two
mixtures, respectively. 14 consists of inseparable cis and trans
isomers whose ratio was determined by GC-MS without assign-
ment.
9c (46, c/t ) 1/4.6) 10c (15)
9d (50, c/t ) 1/2.5) 10d (41)
9e (25, trans only) 10e (20)
10f (46)
b
was irritiated at room temperature. The uncyclized
acrylic CdC bond adducts could not be isolated pure due
to their partially dehydrobromination on TLC plates, they
were further treated with 2 equiv of triethylamine at rt
for about 30 min, and then the dehydrobrominated
products 10c-f were isolated by another TLC separation.
to the acrylic and allyl CdC bonds are reversible, and
that the cyclization rate kRâ is significantly greater than
kâR and kââ′ (Scheme 2). Since 3 only undergoes slow
cyclization processes (kâR and kââ′), it can regenerate 1a ,
which in turn produces 2 which yields product 5 due to
the rapid kRâ cyclization process and a small amount of
uncyclized product 4.6a
Though plausible, Bertrand’s explanation has yet to
be confirmed. While reversible addition of the sulfonyl
radical to CdC bonds has been observed in many cases,7
there is no report confirming Bertrand’s postulate as to
the relative rates of kRâ and kâR. On the other hand, from
the known rates of radical cyclizations which cover 2
orders of magnitude (Scheme 3),8 we believe that kRâ is
unlikely to be greater than kââ′. Also, Bertrand’s explana-
tion could not account for the fact that acrylic CdC bond
mono adduct 4 was the only uncyclized product,6a and
allyl CdC bond mono adduct 8 was not observed. As we
see it, even if 3 fails to cyclize (kâR and kââ′) to yield 6
and/or 7, respectively, it could still be intercepted by
TolSO2Br to yield 8.
Thus, we set out to understand the chemoselectivity
depicted in Scheme 2 and to try to realize CâfCR radical
cyclization. Since the sulfonyl group is a very versatile
functional group in organic synthesis9 and PhSO2• is a
stronger electrophilic radical than TolSO2•, we used
PhSO2Br to investigate its addition and cyclization
reactions with N-allyl acrylamides, and N-allyl 3,3-
dimethyl acrylamides where the CâfCR cyclizations can
be enforced by steric effects. In this paper we report our
results and rationale.
The cis/trans configurations of the products 9a -e were
determined by 2D NOE, where there is NOE coupling
between PhSO2CH2 and BrCH2 for the cis products, but
no coupling is observed for the trans products. This
method of assigning the stereochemistry of the products
gives the same results as Bertrand’s method, where the
13C NMR chemical shift of the cis PhSO2CH2 is about 63
ppm, while that of the trans isomer is about 57 ppm.
NOE coupling between the two methine H’s can be
observed in both cis and trans products and therefore
cannot be used as a criterion for the stereo configuration
assignment. Another possible structure with the groups
PhSO2 and Br reversed in products 9 is excluded by
HMBC (Heteronuclear Multiple Bond Correlation) 2D
spectroscopy. In the HMBC spectrum, one methine H
correlates to CdO (δ ∼ 171 ppm) and PhSO2CH2 (δ ∼ 63
or 57 ppm), while the other methine H correlates to CH2-
NR (δ ∼ 50 ppm) and BrCH2 (δ ∼ 35 ppm). Overall,
CRfCâ cyclization shows trans selectivity.
2. Addition an d Cyclization Reaction s of P h SO2Br
to N-Allyl 3,3-Dim eth yla cr yla m id es. We have found
that CâfCR cyclizations can be observed in the reactions
of PhSO2Br and N-allyl 3,3-dimethylacrylamides as
shown in Table 2. Addition of 20 mol % Bu3SnSnBu3 was
necessary for the complete reaction of amides 11c and
11d . CâfCâ′ cyclized product 14 was observed from the
reaction of amide 11a . The allyl CdC bond adduct 15
was also observed in the reaction of amide 11f, and amide
11f is an unexpected product in the reaction of amide
11b. There is no reaction for amide 11e. The trans
configuration of lactam 13 were determined by the
observed NOE coupling between PhSO2CH2CH and BrC-
(CH3)2, and between CHCBrMe2 and PhSO2CH2.
Resu lts
1. Addition an d Cyclization Reaction s of P h SO2Br
to N-Allyl Acr yla m id es. Table 1 summarizes the reac-
tions of PhSO2Br and N-allyl acrylamides (eq 1) under
sunlamp irradiation in acetonitrile. Typically, 0.2 M of
an amide along with 1.1 equiv of PhSO2Br in acetonitrile
(7) (a) Kuehne, M. E.; Damon, R. E. J . Org. Chem. 1977, 42, 1825.
(b) Ueno, Y.; Miyano, T.; Okawara, M. Tetrahedron Lett. 1982, 23, 443.
(c) Stork, G.; Mook, R. J . Am. Chem. Soc. 1987, 109, 2829. (d) Smith,
T. A. K.; Whitham, G. H.; J . Chem. Soc., Chem. Commun. 1985, 897.
(8) (a) Curran, D. P.; Tamine, J . J . Org. Chem. 1991, 56, 2746-
2750. (b) Serra, A. C.; da Correa, C. M. M.; do Vale, M. L. C.
Tetrahedron 1991, 47, 9463. (c) Beckwith, A. L. J .; Hawthorne, D. G.;
Solomon, D. H. Aust. J . Chem. 1976, 29, 995. (d) Beckwith, A. L. J .
Tetrahedron 1981, 37, 3073.
(9) (a) Chatgilialoglu, C. The Chemistry of Sulphones and Sulphox-
ides; Patai, S., Rappoport, Z., Stirling, C. J . M., Eds.; J ohn Wiley &
Sons Ltd.: New York, 1988; p 1089. (b) Simpkins, N. S. Tetrahedron
1990, 46, 6951.

2348 J . Org. Chem., Vol. 64, No. 7, 1999
Wang and Russell
Ta ble 3. Mea su r em en t of r (16/17) a n d r (16/18)
reaction time (min)
The stereoselectivity of the CâfCR cyclizations cannot
be measured, because the cis products, and maybe some
trans products, dehydrobrominated readily to yield lac-
tam 12 during TLC separation.
entrya
R (M1/M2)
15
30
45
60
1
2
3
R (16/17)
R (16/17)
R (16/18)
9.5
10.6
2.3
10.0
11.0
2.2
8.3
11.3
2.0
6.8
8.3
1.7
a
Initial molar ratio for entries (by 1H NMR): (1) 16:17:PhSO2Br
) 1.00:1.12:0.90. (2) 16:17:PhSO2Br ) 1.00:1.21:1.27. (3) 16:18:
PhSO2Br ) 1.00:1.16:1.70. The concentration of amide 16 was 0.20
M initially for all entries.
Sch em e 4
Sch em e 5
3. Com p etition Exp er im en ts. The relative reactivity
of an acrylic CdC bond vs an allyl CdC bond toward
PhSO2• can be quantified by using eqs 3, 4, and 5, where
[M1]0 and [M2]0 are the initial concentrations of olefins
M1 and M2, and [M1]t, [M2]t are the concentrations of
olefins M1 and M2 at time t.10
Sch em e 6
Equation 5 holds true only if the radical addition step
is the rate-determining step and the only step consuming
M1 and M2. Though reversibility of the radical addition
step may complicate the relative reactivity measurement,
eq 5 has been shown to be reliable for the addition of
TolSO2I to CdC bonds because of the fast iodo-transfer
step following the radical addition step.10a The bromo-
transfer rate has been estimated to be about one-third
that of the iodo-transfer rate from the corresponding
benzenesulfonyl halides.11
Several reactions were set up in NMR tubes with CD3-
CN as the solvent and (Me3Si)2O as the internal stan-
dard. N,N-Diisopropylacrylamide (16), N-allyl-N-benzyl-
acetamide (17), N,N-diallylacetamide (18) were chosen
for the measurement of R (16/17), R (16/18) (Table 3).
results are consistent. Because there are two allyl CdC
bonds in 18, and every adduct radical intramolecularly
cyclizes onto the other allyl CdC bond (Scheme 4), the
consuming rate of the allyl CdC bonds of 18 is acceler-
ated roughly by 4 compared to that of 17 if the CdC bond
of 18 is as reactive as that of 17. In this case R (16/18)
should be about one-fourth of R (16/17), which is very
close to the experimental data. Our experiments also
showed that in each entry, R was nearly constant within
short reaction times, and not affected by either the ratio
of the components or the conversion of the reaction,
showing the validity of the relative reactivity measure-
ments. So, we believe that in amide 1 the acrylic CdC
bond is about 10 times as reactive as the allyl CdC bond
toward PhSO2•, and reversibility of the addition of the
sulfonyl radical here is not a concern.
From Table 3, R (16/17) is about 10, and R (16/18) only
2.3, much lower than R (16/17). We believe these two
(10) (a) Takahara, Y.; Lino, M.; Matsuda, M. Bull. Chem. Soc. J pn.
1976, 49, 2268. (b) da Silva Correa, C. M. M.; Waters, W. A. J . Chem.
Soc., Perkins Trans. 2 1972, 1575. (c) Serra, A. C.; da Silva Correa, C.
M. M.; do Vale, M. L. C. Tetrahedron 1991, 47, 9463. (d) Gozdz, A. S.;
Maslak, P. J . Org. Chem. 1991, 56, 2179.
(11) (a) DaSilva Correa, C. M. M.; Oliveira, M. A. B. C. S. J . Chem.
Soc., Perkins Trans. 2 1983, 711. (b) Chatgilialoglu, C. J . Org. Chem.
1986, 51, 1, 2871.
4. Ad d ition a n d Cycliza tion Rea ction s w ith Oth er
Electr op h ilic Ra d ica ls. Some other electrophilic radi-
cals, such as CH3C(O)S•, Cl3C•, and (NC)2CH• were also
tested in our work (Schemes 5 and 6, and eqs 6 and 7).
All of these radicals added only to the acrylic CdC bond,
except for amide 11a .

Chemoselective Lactam Formation
J . Org. Chem., Vol. 64, No. 7, 1999 2349
Sch em e 7
Sch em e 8
Discu ssion
be about the same as the kââ′ for amide 1a . Thus, we
suggest the following sequence of rates:
The results presented in Table 1 are consistent with
Bertrand’s report. Only CRfCâ cyclization processes are
observed. The electrophilicity of the sulfonyl radicals does
not promote CâfCR cyclization (Scheme 2). Also, the
trend in yields of products 9 is consistent with the report
that the cis-trans rotamer population of an amide like
1 is controlled by the substituent R (Scheme 7).6a,12 Amide
1 is about 100% cis-populated when R is t-Bu, and 100%
trans-populated when R is Ph or H. While the cis rotamer
favors the cyclization process, the trans rotamer disfavors
this process. The rotation barrier of the C(O)-N bond is
about 16-22 kcal/mol,8a but it may be lower in the adduct
radical.
k
âR (11a ) ∼ kââ′ (11a ) ∼ kââ′ (1a ) .
H-transfer to 22 ∼ H-transfer to 20 . kRâ (1a)
It is very conservative to say kââ′ (1a ) is about 100 times
greater than kRâ (1a ), because the radical cyclization rate
has been confirmed to be accelerated by heteroatom (N
atom) substitution and decelerated by the presence of a
carbonyl group (Scheme 3).8b,c Thus, the fact that uncyc-
lized acrylic CdC mono adducts of amides 1 were
observed (Table 1), but no uncyclized allyl CdC mono
adduct has been seen (Table 2) except for the formation
of adduct 15, suggests that the CâfCR and CâfCâ′
cyclization rates of 11a are faster than the CRfCâ
cyclization rate of 1a . No CâfCâ′ cyclized product was
observed from the reaction of amide 1a in eq 1 even
though kââ′ (1a ) is greater than kRâ (1a ) strongly suggests
that Bertrand’s assumption is not correct.
Rate constants kâR (1a ) and kRâ (1a ) cannot be com-
pared directly because no product from the former
cyclization process is observed, and kâR (1a ) may be
different from kâR (11a ). Beckwith reported that the
dimethyl groups at the new radical center show little
effect on the cyclization rate of 5-hexenyl radicals (Scheme
8).14 However, in amide 1a , the acryl CdC bond and Cd
O bond are conjugated in a planar conformation, and they
are not in amide 11a .15 The effect of this conformation
difference on the rate of cyclizations is difficult to be
estimated quantitatively. By guess, we postulate that the
difference between kâR (1a ) and kâR (11a ) may be within
1 order of magnitude. As pointed before, kâR (11a ) is about
2 orders of magnitude greater than kRâ (1a ). Therefore
we think kâR (1a ) may be greater than, or at least
comparable with, kRâ (1a ).
A significant yield of the cis CâfCR cyclized product
was obtained from the reaction of amide 11a (Scheme
6). However, the CRfCâ cyclization gave mainly trans
products (eq 1). This observation is also consistent with
the general assumption that a fast cyclization process has
an early transition state which gives cis-predominant
products, while a slow cyclization process has a late
transition state which gives trans-predominant products.
In amide 1, the acrylic CdC bond is about 10 times as
reactive as the allyl CdC bond toward a sulfonyl radical
as quantified by the competition experiments. This result
is unexpected and may be explained by stabilization
It is interesting to note that while the uncyclized
products 10c-f were generally produced (Table 1), no
allyl CdC bond adduct (like 8 shown in Scheme 2) was
observed. The result from the reaction of amide 1f is
especially striking: uncyclized product 10f was the only
product isolated. This observation shows that the chemose-
lectivity here is not related to any cyclization process,
and attack on the acrylic CdC bond is strongly preferred
to attack on the allyl CdC bond. This conclusion is
confirmed by the results of competition experiments.
No cyclized product was observed in the reaction
depicted in Scheme 5, which means the rate of CRfCâ
cyclization of 1a (or adduct radical 20) is much slower
(about 1 order of magnitude) than that of the H-transfer
from CH3C(O)SH to intermediate 20. The high yield of
cyclized products observed in Scheme 6 suggests that the
rates of CâfCR and CâfCâ′ cyclizations of amide 11a (or
adduct radical 22) are much faster (about 1 order of
magnitude) than that of the H-transfer from CH3C(O)-
SH to intermediate 22. An analogous observation that
the rate of H-transfer from CH3C(O)SH is slower than
that of CâfCâ′ cyclization has been reported by Padwa.13
The rate of H-transfer from CH3C(O)SH to intermediate
22 should be about the same as that to intermediate 20,
or the former one might be slightly faster because
intermediate 20 is more stable than intermediate 22.
From Table 2, the ratio of yields of kâR cyclized products
(12a and 13a ) to kââ′ cyclized product (14) is about 1.27.
In Scheme 6, this ratio is about 0.95. This shows that
the kââ′ for amide 11a , or more accurately, for the allyl
CdC adduct radical of 11a , is about the same as its kâR
.
It is reasonable to suppose the kââ′ for amide 11a would
(12) (a) Stock, G.; Mah, R. Heterocycles 1989, 28, 723. (b) Sato, T.;
Wado, Y.; Nishimoto, N.; Ishibashi, H. Ikeda, M. J . Chem. Soc., Perkin
Trans. 1 1989, 879.
(13) Padwa, A.; Nimmesgern, H.; Wong, G. S. K. J . Org. Chem. 1985,
50, 5620.
(14) Beckwith, A. L. J .; Blair, I. A.; Phillipou, G. Tetrahedron Lett.
1974, 2251.
(15) Cottee, F. H.; Timmons, C. J . J . Chem. Soc. (B) 1968, 326.

2350 J . Org. Chem., Vol. 64, No. 7, 1999
Wang and Russell
The cis isomer was isolated as a yellow solid, mp 135-137
effects due to delocalization of the R-carbamoyl radical
over the carbonyl group. Though the relative reactivity
of olefins of a homologous series toward a sulfonyl radical
is predictable,6b,10 no general statement could be found
to predict the relative reactivity of different olefins such
as acrylic and allyl CdC bonds. An acrylic CdC bond of
alkyl acrylates was reported as reactive as an allyl CdC
bond of alkyl allyl ethers toward a sulfonyl radical.10c We
also use similar competition experiments to find out that
the acrylic CdC bond of 16 is 3 times as reactive as that
of ethyl acrylate which is only 1.6 times as reactive as
the allyl CdC bond of allyl acetate. The reason for the
reactivity difference between acrylamides and acrylates
is not clear and may be partially explained as the N atom
of acrylamides is less electronegative than the O atom
of acrylates.
1
°C. IR (cm-1) 1693, 1305, 1146; H NMR (C6D6) δ 2.56 (dd, J
) 6.8, 10.0 Hz, 1H), 2.64 (m, 1H), 2.79 (dd, J ) 0.8, 10.0 Hz,
1H), 2.99 (dd, J ) 12.4, 14.0 Hz, 1H), 3.08 (ddd, J ) 1.6, 7.2,
12.4 Hz, 1H), 3.12 (dd, J ) 8.0, 10.4 Hz, 1H), 3.38 (dd, J )
3.6, 10.4 Hz, 1H), 3.53 (dd, J ) 6.4, 15.2 Hz, 1H), 3.63 (dd, J
) 6.4, 15.2 Hz, 1H), 3.80 (dd, J ) 1.6, 14.0 Hz, 1H), 4.87 (dd,
J ) 1.2, 17.6 Hz, 1H), 4.90 (dd, J ) 1.2, 10.4 Hz, 1H), 5.44
(ddt, J ) 10.4, 17.6, 6.4 Hz, 1H), 6.82-7.67 (m, 5H); 13C NMR
δ 33.48, 35.54, 40.41, 45.95, 49.63, 52.68, 119.27, 128.15,
129.78, 131.92, 134.40, 139.07, 170.70; HREIMS m/z (relative
intensity) 371.0184 (53, calcd for C15H1879BrNO3S 371.0191),
292 (24), 230 (59), 150 (34), 136 (76), 77 (58), 40 (100).
N-ter t-Bu tyl-4-(br om om eth yl)-3-[(ph en ylsu lfon yl)m eth -
yl]-2-p yr r olid on e (9b) was isolated as a 1:5 mixture of cis
and trans isomers (from 1H NMR). Only the major isomer
(assigned as trans by NOESY spectrum) can be assigned from
1
1
the H NMR spectrum of the mixture. H NMR (C6D6) δ 1.18
(s, 9H), 2.18-2.28 (m, 1H), 2.58 (dd, J ) 10.0, 14.0 Hz, 1H),
2.66 (ddd, J ) 2.0, 10.0, 14.0 Hz, 1H), 2.72 (dd, J ) 5.6, 10.0
Hz, 1H), 3.12 (dd, J ) 6.0, 10.0 Hz, 1H), 3.26 (dd, J ) 8.4,
10.0 Hz, 1H), 3.75 (dd, J ) 2.0, 14.0 Hz, 1H), 3.89 (dd, J )
3.6, 10.0 Hz, 1H), 6.85-7.75 (m, 5H); 13C NMR δ the trans
isomer 27.74, 35.76, 39.46, 42.88, 49.12, 54.98, 57.89, 128.09,
129.62, 134.20, 139.36, 171.61; the cis isomer 27.79, 33.34,
35.05, 41.69, 48.35, 52.77, 54.90, 128.03, 129.71, 134.28,
139.16, 170.60; HREIMS m/z (relative intensity) 387.0502 (42,
calcd for C16H2279BrNO3S 387.0504), 332 (29), 230 (100), 192
(33), 190 (34), 77 (10), 57 (27).
Other strong electrophilic radicals, such as Cl3C• and
(NC)2CH•, afford only CRfCâ cyclized products (eqs 6 and
7). Overall, it is unlikely that the electrophilicity of the
attacking radical itself can shift the chemoselectivity of
addition from an acrylic CdC bond to an allyl CdC bond.
Con clu sion s
Chemoselectivity in the radical addition and cyclization
reactions of PhSO2Br to N-allyl acrylamides is confirmed
due to the higher reactivity of the acrylic CdC bond
toward the sulfonyl radical than that of the allyl CdC
bond. The CâfCR cyclization can be observed with N-allyl
3,3-dimethylacrylamides, which shows a different ste-
reoselectivity from that of the CRfCâ cyclization.
N-Ben zyl-4-(br om om eth yl)-3-[(ph en ylsu lfon yl)m eth yl]-
2-p yr r olid on e (9c). The trans isomer was isolated as a light
1
yellow oil. IR (cm-1) 1691, 1307, 1151; H NMR δ 2.80-2.90
(m, 1H), 2.98 (ddd, J ) 2.8, 9.6, 10.0 Hz, 1H), 3.17 (dd, J )
7.6, 10.0 Hz, 1H), 3.18 (dd, J ) 10.0, 14.4 Hz, 1H), 3.44 (dd, J
) 8.4, 10.0 Hz, 1H), 3.70 (dd, J ) 7.2, 10.4 Hz, 1H), 3.85 (dd,
J ) 2.8, 14.4 Hz, 1H), 3.90 (dd, J ) 3.2, 10.4 Hz, 1H), 4.40 (d,
J ) 14.8 Hz, 1H), 4.48 (d, J ) 14.8 Hz, 1H), 7.20-8.10 (m,
10H); 13C NMR δ 35.70, 39.62, 41.64, 47.30, 50.00, 57.68,
128.12, 128.16, 128.33, 129.05, 129.70, 134.33, 135.63, 139.25,
171.79; HREIMS m/z (relative intensity) 421.0345 (43, calcd
for C19H2079BrNO3S 421.0347), 252 (66), 250 (64), 186 (26), 91
(100).
Exp er im en ta l Section
IR spectra were measured as thin films on NaCl plate. NMR
spectra were recorded in CDCl3 or as stated otherwise (1H at
400 MHz and 13C at 100 MHz). All mp’s were determined
without correction. Photostimulated reactions utilized a 275
W fluorescent sunlamp and 5 mm NMR tubes. Yields were
based on the starting acrylamides. PhSO2Br was prepared
according to a literature procedure.16 Amides 1a -f, 11a -f, 16,
17, 18 were prepared from the appropriate acyl chlorides and
corresponding amines according to a literature procedure.6a
Gen er a l P r oced u r e for t h e Ad d it ion of P h SO2Br t o
Am id es. A mixture of an amide (0.20 mmol) and PhSO2Br
(0.22 mmol) in 1.0 mL of CH3CN was irradiated in a 5 mm
NMR tube at room temperature until the starting amide
disappeared as indicated by TLC analysis. The products were
obtained by TLC separation on 20 × 10 cm silica gel plates
with hexanes-ethyl acetate as the eluent. Procedures for
reactions depicted in Scheme 5, eqs 6 and 7 are similar except
using thioacetic acid together with 10 mol % AIBN, bromo-
trichloromethane, or bromodicyanomethane instead of using
PhSO2Br.
The cis isomer was isolated as a white solid, mp 118-120
1
°C. IR (cm-1) 1692, 1305, 1150; H NMR (C6D6) δ 2.52 (dd, J
) 6.4, 10.0 Hz, 1H), 2.57 (m, 1H), 2.73 (dd, J ) 0.4, 10.0 Hz,
1H), 3.00 (dd, J ) 12.4, 14.4 Hz, 1H), 3.07 (dd, J ) 8.0, 10.4
Hz, 1H), 3.15 (ddd, J ) 2.0, 7.6, 12.4 Hz, 1H), 3.32 (dd, J )
3.2, 10.4 Hz, 1H), 3.85 (dd, J ) 2.0, 14.4 Hz, 1H), 4.00 (d, J )
14.4 Hz, 1H), 4.30 (d, J ) 14.4 Hz, 1H), 7.25-8.10 (m, 10H);
13C NMR δ 33.33, 35.57, 40.42, 47.41, 49.65, 52.71, 128.15,
128.16, 128.63, 129.03, 129.80, 134.42, 135.71, 139.09, 170.95;
HREIMS m/z (relative intensity) 421.0347 (17, calcd for
C
19H2079BrNO3S 421.0347), 361 (15), 359 (13), 252 (8), 186 (7),
104 (8), 91 (100).
N-Meth yl-4-(br om om eth yl)-3-[(ph en ylsu lfon yl)m eth yl]-
2-p yr r olid on e (9d ). The trans isomer was isolated as a
colorless oil. IR (cm-1) 1695, 1306, 1151; 1H NMR (C6D6) δ
2.18-2.28 (m, 1H), 2.32 (s, 3H), 2.40 (dd, J ) 7.6, 9.6 Hz, 1H),
2.55 (dd, J ) 10.0, 12.0 Hz, 1H), 2.57 (ddd, J ) 0.4, 8.0, 10.0
Hz, 1H), 2.69 (dd, J ) 8.4, 9.6 Hz, 1H), 3.17 (dd, J ) 8.8, 10.0
Hz, 1H), 3.74 (dd, J ) 0.4, 12.0 Hz, 1H), 3.86 (dd, J ) 4.0,
10.0 Hz, 1H), 6.82-7.75 (m, 5H); 13C NMR δ 30.18, 35.79,
39.63, 41.39, 52.67, 57.74, 128.15, 129.67, 134.31, 139.16,
171.72; HREIMS m/z (relative intensity) 345.0035(36, calcd
for C13H1679BrNO3S 345.0034), 266 (11), 252 (14), 204 (23), 202
(51), 124 (34), 110 (100).
The cis isomer was isolated as a white solid, mp 95-97 °C.
IR (cm-1) 1690, 1304, 1149; 1H NMR (C6D6) δ 2.33 (s, 3H), 2.44
(dd, J ) 6.4, 10.0 Hz, 1H), 2.53-2.60 (m, 1H), 2.59 (dd, J )
0.8, 10.0 Hz, 1H), 2.98 (ddd, J ) 1.2, 6.8, 13.2 Hz, 1H), 3.02
(dd, J ) 1.2, 10.4 Hz, 1H), 3.09 (dd, J ) 8.0, 10.4 Hz, 1H),
3.35 (dd, J ) 3.6, 10.4 Hz, 1H), 3.80 (dd, J ) 9.6, 10.4 Hz,
1H), 6.82-7.75 (m, 5H); 13C NMR δ 30.05, 33.68, 35.48, 40.05,
52.22, 52.75, 128.12, 129.77, 134.39, 139.06, 170.98; HREIMS
m/z (relative intensity) 345.0034 (15, calcd for C13H1679BrNO3S
N-Allyl-4-(br om om eth yl)-3-[(p h en ylsu lfon yl)m eth yl]-
2-p yr r olid on e (9a ). The trans isomer was isolated as a yellow
1
oil. IR (cm-1) 1689, 1307, 1151; H NMR δ (C6D6) 2.24-2.34
(m, 1H), 2.62 (t, J ) 9.6 Hz, 1H), 2.65 (dd, J ) 3.0, 9.6 Hz,
1H), 2.69 (ddd, J ) 2.0, 9.2, 9.6 Hz, 1H), 2.89 (dd, J ) 8.8, 9.6
Hz, 1H), 3.25 (dd, J ) 8.4, 10.0 Hz, 1H), 3.48 (dd, J ) 6.0,
15.2 Hz, 1H), 3.66 (dd, J ) 6.0, 15.2 Hz, 1H), 3.73 (dd, J )
2.0, 9.6 Hz, 1H), 3.81 (dd, J ) 3.6, 10.0 Hz, 1H), 4.88 (dd, J )
1.0, 16.8 Hz, 1H), 4.92 (dd, J ) 1.0, 10.0 Hz, 1H), 5.42 (ddt, J
) 10.0, 16.8, 6.0 Hz, 1H), 6.80-7.70 (m, 5H); 13C NMR δ 35.81,
39.67, 41.66, 45.89, 50.13, 57.72, 119.03, 128.18, 129.70,
131.65, 134.33, 139.23, 171.52; HREIMS m/z (relative inten-
sity) 371.0179 (62, calcd for C15H1879BrNO3S 371.0191), 292
(12), 230 (36), 150 (35), 136 (74), 77 (68), 40 (100).
(16) Poshkus, A. C.; Herweh, J . E.; Magnotta, F. A. J . Org. Chem.
1963, 28, 2766.

Chemoselective Lactam Formation
J . Org. Chem., Vol. 64, No. 7, 1999 2351
345.0034), 266 (18), 252 (14), 204 (31), 202 (51), 124 (30), 110
(82), 77 (45), 69 (100).
1688, 1307, 1147; 1H NMR (C6D6) δ 1.24 (s, 3H), 2.33 (s, 3H),
2.50-2.60 (m, 2H), 2.98 (dd, J ) 6.8, 10.4 Hz, 1H), 3.10-3.20
(m, 1H), 3.26 (dd, J ) 0.8, 10.4 Hz, 1H), 4.14 (d, J ) 14.4 Hz,
1H), 4.46 (d, J ) 14.4 Hz, 1H), 7.50-7.85 (m, 5H); 13C NMR δ
19.87, 23.12, 31.32, 47.70, 48.88, 59.72, 125.80, 128.08, 128.12,
128.62, 129.05, 129.73, 134.30, 136.00, 139.18, 146.80, 167.96;
tr a n s-N-P h en yl-4-(br om om eth yl)-3-[(p h en ylsu lfon yl)-
m eth yl]-2-p yr r olid on e (9e) was isolated as a yellow solid,
mp 105-107 °C. IR (cm-1) 1700, 1307, 1151; 1H NMR δ 2.90-
3.10 (m, 1H), 3.12 (ddd, J ) 2.4, 9.0, 9.6 Hz, 1H), 3.28 (dd, J
) 9.6, 14.1 Hz, 1H), 3.78 (dd, J ) 7.8, 8.4 Hz, 1H), 3.81 (dd, J
) 7.5, 10.5 Hz, 1H), 3.90 (dd, J ) 2.4, 14.1 Hz, 1H), 4.01 (dd,
J ) 8.4, 10.0 Hz, 1H), 4.06 (dd, J ) 3.6, 10.5 Hz, 1H), 7.10-
8.00 (m, 10H); 13C NMR δ 35.16, 39.43, 42.87, 51.84, 57.56,
120.31, 125.58, 128.23, 129.24, 129.75, 134.41, 138.68, 139.21,
170.96; HREIMS m/z (relative intensity) 407.0187 (51, calcd
for C18H1879BrNO3S 407.0191), 268 (98), 266 (100), 186 (37),
172 (56), 104 (26), 77 (64).
HREIMS m/z (relative intensity) 369.1407 (74, calcd for C21H23
-
NO3S 369.1399), 228 (19), 214 (72), 91 (100), 83 (30).
N-Meth yl-4-[(ph en ylsu lfon yl)m eth yl]-3-isopr opyliden e-
2-p yr r olid on e (12d ) was isolated as a 2.5:1 mixture with 13d .
1H NMR (C6D6) δ 1.25 (s, 3H), 2.31 (s, 3H), 2.52 (s, 3H), 2.52-
2.60 (m, 2H), 2.87 (dd, J ) 6.8, 10.4 Hz, 1H), 3.15-3.22 (m,
1H), 3.27 (dd, J ) 0.8, 10.8 Hz, 1H), 6.88-6.95 (m, 3H), 7.60-
7.70 (m, 2H); 13C NMR δ 19.24, 22.81, 30.13, 31.06, 50.99,
59.86, 125.99, 128.14, 129.74, 134.30, 139.35, 144.27, 168.08;
N-Ben zyl-N-(2-p r op en yl)-3-(p h en ylsu lfon yl)a cr yla m -
id e (10c) was isolated as a colorless oil. IR (cm-1) 1653, 1320,
HREIMS m/z (relative intensity) 293.1085 (49, calcd for C15H19
-
1
1148; H NMR (2 rotamers) δ 3.95 (d, J ) 4.8, 1.2H), 4.06 (d,
NO3S 293.1086), 138 (100), 84 (58).
J ) 6.0 Hz, 0.8H), 4.62 (s, 0.8H), 4.65 (s, 1.2H), 5.15-5.35 (m,
2H), 5.7-5.9 (m, 2H), 7.15-7.95 (m, 10H); 13C NMR δ (2
rotamers, * for overlapping peaks) 48.97, 49.49, 49.64, 50.73,
118.12, 118.93, 126.75*, 128.06, 128.31, 128.36, 128.41, 128.57,
128.99, 129.37, 129.72, 129.76, 131.29, 132.01, 132.26, 134.32,
134.37, 135.98, 136.55, 138.99, 139.06, 141.86, 141.68, 163.31,
163.56; HREIMS m/z (relative intensity) 341.1081 (25, calcd
for C19H19NO3S 341.1086), 300 (41), 200 (72), 146 (43), 125 (58),
106 (69), 91 (100), 77 (29).
N-Allyl-3-(1-br om o-1-m eth yleth yl)-4-[(p h en ylsu lfon yl)-
m eth yl]-2-p yr r olid on e (13a ) was isolated as a 1:2.3 mixture
1
with 12a (from 1H NMR). H NMR δ (* for overlapping peaks
with 12a ) 1.79 (s, 3H), 1.94 (s, 3H), 2.47 (d, J ) 3.6 Hz, 1H),
3.0-4.2* (m, 7H), 5.21-5.30* (m, 2H), 5.68-5.73* (m, 1H),
7.61-7.95* (m, 5H); 13C NMR δ 30.42, 31.32, 34.62, 45.77,
50.27, 60.04, 61.74, 67.77, 119.10, 128.26, 129.76*, 131.65,
134.40, 139.23, 169.75; HREIMS m/z (relative intensity)
399.0498 (1, calcd for C17H2279BrNO3S 399.0502), 319 (60), 178
(18), 164 (100), 77 (16).
N-Met h yl-N-(2-p r op en yl)-3-(p h en ylsu lfon yl)a cr yla m -
id e (10d ) was isolated as a yellow oil. IR (cm-1) 1651, 1321,
1151; 1H NMR (2 rotamers) δ 3.01 (s, 1.7H), 3.09 (s, 1.3H),
4.00-4.10 (m, 2H), 5.13-5.30 (m, 2H), 5.65-5.88 (m, 1H), 7.28
(d, J ) 14.7 Hz, 1H), 7.43 (d, J ) 14.7 Hz, 1H), 7.55-7.95 (m,
5H); 13C NMR (2 rotamers) δ 34.56, 35.27, 50.80, 52.68, 117.88,
118.61, 128.35, 128.37, 129.74, 129.76, 131.13, 131.24, 131.89,
132.08, 134.33, 134.37, 139.05, 139.10, 141.11, 141.37, 162.72,
163.38; HREIMS m/z (relative intensity) 265.0769 (36, calcd
for C13H15NO3S 265.0773), 142 (13), 124 (79), 77 (24), 70 (100).
N-P h en yl-N-(2-p r op en yl)-3-(p h en ylsu lfon yl)a cr yla m -
id e (10e) was isolated as a colorless oil. IR (cm-1) 1653, 1320,
1149; 1H NMR δ 4.36 (d, J ) 6.2 Hz, 1H), 5.08-5.17 (m, 2H),
5.85 (ddt, J ) 1.2, 10.2, 16.8 Hz, 1H), 6.78 (d, J ) 14.7 Hz,
1H), 7.30 (d, J ) 14.7 Hz, 1H), 7.13 (m, 2H), 7.40-7.80 (m,
8H); 13C NMR δ 53.06, 119.00, 127.96, 128.31, 128.97, 129.66,
130.19, 132.03, 132.08, 134.24, 139.14, 140.80, 140.95, 162.18;
tr a n s-N-Ben zyl-3-(1-br om o-1-m eth yleth yl)-4-[(p h en yl-
su lfon yl)m eth yl]-2-p yr r olid on e (13c) was isolated as a
1
yellow oil. IR (cm-1) 1682, 1292, 1146; H NMR (C6D6) δ 1.65
(s, 3H), 1.85 (s, 3H), 2.05 (d, J ) 5.2 Hz, 1H), 2.48 (dd, J )
11.2, 14.0 Hz, 1H), 2.80-2.90 (m, 1H), 2.99 (dd, J ) 2.4, 14.0
Hz, 1H), 3.12 (dd, J ) 4.0, 10.4 Hz, 1H), 3.44 (dd, J ) 8.8,
10.4 Hz, 1H), 3.98 (d, J ) 14.4 Hz, 1H), 4.44 (d, J ) 14.4 Hz,
1H), 6.80-7.85 (m, 10H); 13C NMR δ 30.47, 31.31, 34.66, 47.23,
50.15, 59.98, 61.72, 67.78, 128.11, 128.24, 128.57, 129.03,
129.72, 134.37, 135.86, 139.10, 169.97; HREIMS m/z (relative
intensity) 369.1408 [59, calcd for C21H23NO3S (M - HBr)
369.1399], 228 (19), 214 (69), 91 (100); CIMS m/z 469/467 (M
+ NH4+).
tr a n s-N-Meth yl-3-(1-br om o-1-m eth yleth yl)-4-[(p h en yl-
su lfon yl)m eth yl]-2-p yr r olid on e (13d ) was isolated as a
1:2.5 mixture with 12d . 1H NMR (C6D6) δ 1.62 (s, 3H), 1.86
(s, 3H), 2.40 (s, 3H), 1.98 (d, J ) 5.6 Hz, 1H), 2.52 (dd, J )
12.0, 14.0 Hz, 1H), 2.78-2.85 (m, 1H), 2.98 (dd, J ) 4.4, 10.4
Hz, 1H), 3.05 (dd, J ) 2.8, 14.0 Hz, 1H), 3.33 (dd, J ) 8.8,
10.4 Hz, 1H), 6.88-6.95 (m, 3H), 7.60-7.70 (m, 2H); 13C NMR
δ 30.05, 31.31, 31.34, 34.89, 52.69, 59.80, 61.66, 67.89, 128.22,
129.74, 134.38, 139.12, 170.04; HREIMS m/z (relative inten-
sity) 293.1085 [49, calcd for C15H19NO3S (M - HBr) 293.1086],
138 (100), 84 (58); CIMS m/z 376/374 (M + H+).
HREIMS m/z (relative intensity) 327.0926 (4, calcd for C18H17
-
NO3S 327.0929), 186 (100), 132 (30), 125 (25), 77 (34).
N-(2-P r op en yl)-3-(p h en ylsu lfon yl)a cr yla m id e (10f) was
isolated as a white solid, mp 119-121 °C. IR (cm-1) 1653, 1308,
1
1148; H NMR δ 3.96 (m, 2H), 5.17-5.25 (m, 2H), 5.78-5.60
(m, 1H), 5.95-6.05 (br, 1H), 6.94 (d, J ) 14.7 Hz, 1H), 7.33 (d,
J ) 14.7 Hz, 1H), 7.55-7.92 (m, 5H); 13C NMR δ 42.71, 117.82,
128.38, 128.37, 129.80, 133.43, 134.47, 138.97, 140.77, 161.82.
HREIMS m/z (relative intensity) 251.0619 (35, calcd for C12H13
-
N-(3,3-Dim eth yla cr yloyl)-3-(br om om eth yl)-2-[(p h en yl-
su lfon yl)m eth yl]p yr r olid in e (14) was isolated as a 1:2 or
2:1 (from GC-MS) mixture of cis and trans isomers without
NO3S 251.0616), 142 (22), 125 (73), 110 (65), 77 (41), 56 (100),
41 (38).
1
N-Allyl-4-[(p h en ylsu lfon yl)m eth yl]-3-isop r op ylid en e-
2-p yr r olid on e (12a ) was isolated as a 2.3:1 mixture with 13a
assignment. H NMR δ 1.88 (s, 3H), 2.10 (s, 3H), 2.5-4.0 (m,
10H), 5.76 (s, 1H), 7.61-7.95 (m, 5H); 13C NMR δ major isomer
20.41, 27.36, 30.36, 36.33, 42.39, 48.80, 50.25, 54.14, 116.94,
128.18, 129.82, 134.43, 139.20, 151.45, 166.75; minor isomer
20.43, 27.38, 30.36, 35.06, 43.58, 48.80, 50.82, 54.67, 116.91,
128.18, 129.82, 134.43. 139.14, 151.31, 166.70; HREIMS m/z
(relative intensity) 399.0502 (40, calcd for C17H2279BrNO3S
399.0504), 320 (19), 318 (37), 246 (57), 176 (28), 83 (100), 55
(16).
1
(from H NMR). 1H NMR δ (* for overlapping peaks with 13a )
1.63 (s, 3H), 2.21 (s, 3H), 3.0-4.2* (m, 7H), 5.21-5.30* (m,
2H), 5.68-5.73* (m, 1H), 7.61-7.95* (m, 5H); 13C NMR δ
19.39, 22.86, 31.17, 45.63, 48.45, 59.95, 118.69, 126.19, 128.19,
129.76*, 132.32, 134.31, 139.37, 144.91, 167.59; HREIMS m/z
(relative intensity) 319.1242 (57, calcd for C17H21NO3S 319.1242),
178 (17), 164 (100), 82 (25).
N-ter t-Bu t yl-4-[(p h en ylsu lfon yl)m et h yl]-3-isop r op yl-
id en e-2-p yr r olid on e (12b) was isolated as a white solid, mp
N-[(2-Br om o-3-p h en ylsu lfon yl)p r op yl]-3,3-d im et h yl-
a cr yla m id e (15) was isolated as a light yellow solid, mp 130-
132 °C. IR (cm-1) 1650, 1308, 1146; H NMR δ 1.86 (s, 3H),
1
1
118-120 °C. IR (cm-1) 1681, 1306, 1153; H NMR δ 1.39 (s,
9H), 1.58 (s, 3H), 2.17 (s, 3H), 3.00 (dd, J ) 1.2, 14.0 Hz, 1H),
3.17 (dd, J ) 7.2, 14.0 Hz, 1H), 3.25-3.35 (m, 1H), 3.45 (dd, J
) 6.8, 10.8 Hz, 1H), 3.59 (dd, J ) 0.8, 10.8 Hz, 1H), 7.61-7.95
(m, 5H); 13C NMR δ 19.22, 22.86, 27.80, 31.05, 46.79, 54.38,
59.63, 127.84, 128.18, 129.75, 134.29, 139.49, 143.39, 168.60;
2.16 (s, 3H), 3.60-3.80 (m, 4H), 4.43 (pentet, J ) 6.0 Hz, 1H),
5.59 (s, 1H), 5.88-5.93 (b, 1H), 7.50-8.10 (m, 5H); 13C NMR
δ 20.18, 27.47, 43.48, 45.27, 61.78, 117.88, 128.52, 129.70,
134.48, 139.18, 152.21, 167.08; HREIMS m/z (relative inten-
sity) 279.0924 [22, calcd for C14H17NO3S (M - HBr) 279.0929],
138 (97), 83 (100), 55 (20); CIMS m/z 379/377 (M + NH4+).
N-Acetyl-3-(br om om eth yl)-2-[(p h en ylsu lfon yl)m eth yl]-
p yr r olid in e (19) was isolated as a 1:2 or 2:1 (from GC-MS)
mixture of cis and trans isomers without assignment. 1H NMR
HREIMS m/z (relative intensity) 335.1554 (57, calcd for C18H25
-
NO3S 335.1555), 320 (100), 180 (20), 124 (37).
N-Ben zyl-4-[(ph en ylsu lfon yl)m eth yl]-3-isopr opyliden e-
2-p yr r olid on e (12c) was isolated as a yellow oil. IR (cm-1
)

2352 J . Org. Chem., Vol. 64, No. 7, 1999
Wang and Russell
δ 2.07 (s, 3H), 2.50-4.00 (m, 10H), 7.50-8.10 (m, 5H); 13C
NMR δ major isomer 22.47, 29.91, 36.27, 42.62, 49.05, 50.71,
53.92, 128.17, 129.86, 134.50, 139.22, 169.87; HREIMS m/z
(relative intensity) 359.0188 (16, calcd for C14H1879BrNO3
359.0191), 318 (19), 316 (17), 224 (19), 204 (100), 176 (48), 137
(18), 96 (58), 77 (47), 43 (99).
1H), 2.57 (dd, J ) 7.2, 9.6 Hz, 1H), 2.73 (t, J ) 10.0 Hz, 1H),
2.86 (dd, J ) 8.0, 9.6 Hz, 1H), 3.24 (dd, J ) 3.6, 10.0 Hz, 1H),
3.42 (dd, J ) 3.2, 11.2 Hz, 1H), 3.55-3.67 (m, 2H), 4.88-4.95
(m, 2H), 5.47 (ddt, J ) 10.8, 16.8, 6.0 Hz, 1H); 13C δ NMR
35.79, 40.03, 45.68, 45.89, 50.19, 56.08, 98.70, 119.02, 131.86,
172.70; HREIMS m/z (relative intensity) 346.9243 (12, calcd
for C10H1379Br35Cl3NO 346.9246), 314 (8), 217 (16), 122 (80),
68 (100).
N,N-Dia llyl-3-(a cetylth io)p r op ion a m id e (21) was iso-
1
lated as a colorless oil. IR (cm-1) 1694, 1651; H NMR δ 2.30
(s, 3H), 2.62 (t, J ) 6.6 Hz, 2H), 3.15 (t, J ) 6.6 Hz, 2H), 3.83
(d, J ) 4.8 Hz, 2H), 3.97 (d, J ) 6.0 Hz, 2H), 5.10-5.20 (m,
4H), 5.75-5.85 (m, 2H); 13C NMR δ 24.99, 30.68, 33.31, 48.23,
49.09, 116.87, 117.65, 132.66, 133.26, 171.00, 196.54; HREIMS
m/z (relative intensity) 227.0984 (16, calcd for C11H17BNO2S
227.0980), 184 (47), 152 (49), 124 (45), 96 (25), 70 (21), 56 (87),
43 (99), 41 (100).
P r ep a r a tion of N-Acetyl-N-a llyla cr yla m id e (26). To the
solution of NaH (240 mg) in anhydrous ethyl ether (10 mL)
cooled to 0 °C was added dropwise N-allylacrylamide (220 mg,
2 mmol). After the gaseous bubbling subsided, the solution was
stirred for another 10 min, acryloyl chloride (0.32 mL, 4 mmol)
was added dropwise, and stirring was continued another 30
min. Then the solution was hydrolyzed by cautious addition
of water, extracted with ether, and dried over MgSO4. Puri-
fication by column chromatography on silica gel gave a light
N-Allyl-3-(1-m eth yleth yl)-4-[(a cetylth io)m eth yl]-2-p yr -
r olid on e (23). The trans isomer was isolated as a colorless
1
oil. IR (cm-1) 1694; H NMR δ 0.90 (d, J ) 6.8 Hz, 3H), 1.03
1
yellow liquid of 26 (200 mg, 65%). IR (cm-1) 1703, 1694; H
(d, J ) 6.8 Hz, 3H), 2.18 (dd, J ) 4.4, 4.8 Hz, 1H), 2.22-2.27
(m, 1H), 2.30-2.40 (m, 1H), 2.35 (s, 3H), 2.91 (t, J ) 13.2 Hz,
1H), 2.93 (dd, J ) 4.8, 10.4 Hz, 1H), 3.06 (dd, J ) 5.6, 13.2
Hz, 1H), 3.44 (dd, J ) 8.4, 10.4 Hz, 1H), 3.79 (dd, J ) 6.0,
15.2 Hz, 1H), 3.95 (dd, J ) 6.0, 15.2 Hz, 1H), 5.10-5.20 (m,
2H), 5.69 (ddt, J ) 9.6, 17.6, 6.0 Hz, 1H); 13C NMR δ 18.46,
20.27, 29.23, 30.87, 32.97, 34.66, 45.36, 50.87, 54.05, 118.31,
132.53, 174.87, 195.46; HREIMS m/z (relative intensity)
255.1294 (27, calcd for C13H21NO2S 255.1293), 212 (37), 180
(16), 166 (7), 136 (12), 124 (100), 83 (28), 55 (10), 43 (32).
The cis isomer was isolated as a colorless oil. IR (cm-1) 1699;
1H NMR δ 1.11 (d, J ) 6.8 Hz, 3H), 1.15 (d, J ) 6.8 Hz, 3H),
2.00 (octet, J ) 6.8 Hz, 1H), 2.31 (dd, J ) 6.8, 8 Hz, 1H), 2.35
(s, 3H), 2.50-2.60 (m, 1H), 2.82 (dd, J ) 13.6 Hz, 14.0, 1H),
3.02 (dd, J ) 5.6, 10.0 Hz, 1H), 3.13 (dd, J ) 4.8, 13.6 Hz,
1H), 3.30 (dd, J ) 7.2, 10.0 Hz, 1H), 3.83 (dd, J ) 6.4, 15.2
Hz, 1H), 3.92 (dd, J ) 6.4, 15.2 Hz, 1H), 5.15-5.25 (m, 2H),
5.70 (ddt, J ) 10.0, 17.2, 6.4 Hz, 1H); 13C NMR δ 20.01, 22.46,
26.78, 28.40, 30.83, 36.75, 45.40, 50.13, 51.27, 118.47, 132.76,
174.51, 195.48; HREIMS m/z (relative intensity) 255.1296 (26,
calcd for C13H21NO2S 255.1293), 213 (28), 180 (8), 166 (26),
136 (15), 124 (100), 83 (14), 43 (32).
NMR δ 2.46 (s, 3H), 4.36 (d, J ) 4.8 Hz, 2H), 5.14 (dd, J )
0.8, 16.4 Hz, 1H), 5.21 (dd, J ) 0.8, 10.4 Hz, 1H), 5.80 (dd, J
) 1.6, 10.4 Hz, 1H), 5.88 (ddt, J ) 10.4, 16.4, 4.8 Hz, 1H),
6.43 (dd, J ) 1.6, 16.8 Hz, 1H), 6.73 (dd, J ) 10.4, 16.8 Hz,
1H); 13C NMR δ 26.30, 46.70, 116.72, 130.53, 130.57, 133.00,
168.94, 173.39; HREIMS m/z (relative intensity) 153.0790 (11,
calcd for C8H11NO 153.0790), 111 (32), 98 (28), 55 (100), 43
(61).
N-Acetyl-4-(br om om eth yl)-3-(2,2-d icya n oeth yl)-2-p yr -
r olid on e (27) was isolated as a light yellow oil. IR (cm-1) 2260,
1
1729, 1704; H NMR δ 2.31 (ddd, J ) 4.8, 10.8, 14 Hz, 1H),
2.40-2.46 (m, 1H), 2.47 (ddd, J ) 10.8, 11.2, 14.0 Hz, 1H),
2.50 (s, 3H), 2.87 (dt, J ) 3.6, 10.8 Hz, 1H), 3.47 (dd, J ) 9.2,
12.0 Hz, 1H), 3.52 (dd, J ) 6.0, 10.8 Hz, 1H), 3.61 (dd, J )
4.4, 10.8 Hz, 1H), 4.12 (dd, J ) 8.4, 12.0 Hz, 1H), 4.86 (dd, J
) 4.8, 11.2 Hz, 1H); 13C NMR δ 20.27, 25.27, 31.11, 32.11,
38.26, 44.34, 47.69, 112.18, 112.50, 170.50, 174.39; HREIMS
m/z (relative intensity) 297.0113 (5, calcd for C11H1279BrN3O2
297.0113), 271 (2), 258 (2), 221 (2), 175 (2), 139 (2), 126 (3), 84
(2), 42 (100).
Ack n ow led gm en t. This work was supported by
grants from the National Science Foundation and the
Petroleum Research Fund.
N-(3,3-Dim eth ylacr yloyl)-4-m eth yl-3-[(acetylth io)m eth -
yl]p yr r olid in e (24) was isolated as a 2: 1 or 1:2 (from GC-
MS) mixture of cis and trans isomers without assignment. 1H
NMR δ 0.96 (d, J ) 6.8 Hz, 3H, minor isomer), 1.06 (d, J )
6.4 Hz, 3H, major isomer), 1.82 (s, 3H), 2.03 (s, 3H), 2.31 (s,
3H), 2.70-4.00 (m, 8H), 5.71 (s, J ) 10.0 Hz, 1H); HREIMS
m/z (relative intensity) 255.1296 (27, calcd for C13H21NO2S
255.1293), 212 (5), 166 (33), 130 (10), 83 (100), 55 (18), 43 (10).
N-Allyl-4-(br om om eth yl)-3-(2,2,2-tr ich lor oeth yl)-2-p yr -
r olid on e (25). A 1:4 mixture of cis and trans isomers were
found by GC-MS. Only the trans isomer was isolated pure as
Su p p or tin g In for m a tion Ava ila ble: 1H, 13C NMR, and
1
2D H-1H NOESY spectra for compounds 9a -e, the mixture
of 12a and 13a , the mixture of 12d and 13d , 13c, 23, 25 and
27; 1H and 13C NMR spectra for compounds 10c-f, 12b-c,
1
14, 15, 19 and 21; H NMR spectrum for compound 24. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
a yellow oil. IR (cm-1) 1695; H NMR (C6D6) δ 1.90-1.99 (m,
1H), 2.17 (dd, J ) 7.6, 11.2 Hz, 1H), 2.31 (dt, J ) 3.2, 7.6 Hz,
J O9820770