Additive and Vinylogous Pummerer Reactions of Amido Sulfoxides and Their Use in the Preparation of Nitrogen Containing Heterocycles

Article abstract of DOI:10.1021/jo972093h

The α-thiocarbocation generated from the Pummerer reaction of N-methyl-N-phenyl-2-[2-(toluene-4-sulfinyl)phenyl]acetamide undergoes Friedel-Crafts reaction at the γ-carbon with the tethered aromatic ring. Reductive removal of the phenylthio group from the resulting product using Raney nickel occurs in high yield, and the overall reaction represents a new method for the synthesis of a variety of 3-phenyl-substituted oxindoles. Treatment of the related N-benzyl-N-alkyl amido sulfoxide system with trifluoroacetic anhydride affords tetrahydroisoquinolone derivatives. The product distribution encountered coincides with the rotamer population of the starting amide. When the N-benzyl-N-methyl amide is used, only the normal Pummerer product is formed. In this case, the thionium ion is generated in the wrong conformation for π-cyclization to occur. The corresponding N-tert-butyl amido system, however, exists in a geometric orientation which places the benzylic group in the crucial conformation necessary for π-cyclization, and consequently, the reaction proceeds smoothly. Related cyclization reactions occur in good yield with the corresponding furanyl and cyclohexenyl N-tert-butyl amido sulfoxides. The additive Pummerer reaction of 3-phenylsulfinyl-N-benzyl-N-tert-butylacrylamide gave products derived from both 5- and 6-exo trig cyclizations. Intramolecular electrophilic aromatic substitution via six-membered ring closure ultimately afforded a dihydropyridone. The competitive process involving ipso attack of the aromatic ring on the thionium ion generates a spiro cyclohexadienyl cation that undergoes fragmentation of the adjacent σ-bond. The resulting acyl iminium ion is converted to N-tert-butyl-2-phenyl-3-phenylsulfinylacrylamide upon aqueous workup. Only cyclizations leading to five-membered rings occur with the corresponding indolyl and alkenyl N-tert-butyl amido sulfoxides.

Full text of DOI:10.1021/jo972093h

4256
J . Org. Chem. 1998, 63, 4256-4268
Ad d itive a n d Vin ylogou s P u m m er er Rea ction s of Am id o
Su lfoxid es a n d Th eir Use in th e P r ep a r a tion of Nitr ogen
Con ta in in g Heter ocycles
Albert Padwa* and J effrey T. Kuethe
Department of Chemistry, Emory University, Atlanta, Georgia 30322
Received November 14, 1997
The R-thiocarbocation generated from the Pummerer reaction of N-methyl-N-phenyl-2-[2-(toluene-
4-sulfinyl)phenyl]acetamide undergoes Friedel-Crafts reaction at the γ-carbon with the tethered
aromatic ring. Reductive removal of the phenylthio group from the resulting product using Raney
nickel occurs in high yield, and the overall reaction represents a new method for the synthesis of
a variety of 3-phenyl-substituted oxindoles. Treatment of the related N-benzyl-N-alkyl amido
sulfoxide system with trifluoroacetic anhydride affords tetrahydroisoquinolone derivatives. The
product distribution encountered coincides with the rotamer population of the starting amide. When
the N-benzyl-N-methyl amide is used, only the normal Pummerer product is formed. In this case,
the thionium ion is generated in the wrong conformation for π-cyclization to occur. The
corresponding N-tert-butyl amido system, however, exists in a geometric orientation which places
the benzylic group in the crucial conformation necessary for π-cyclization, and consequently, the
reaction proceeds smoothly. Related cyclization reactions occur in good yield with the corresponding
furanyl and cyclohexenyl N-tert-butyl amido sulfoxides. The additive Pummerer reaction of
3-phenylsulfinyl-N-benzyl-N-tert-butylacrylamide gave products derived from both 5- and 6-exo trig
cyclizations. Intramolecular electrophilic aromatic substitution via six-membered ring closure
ultimately afforded a dihydropyridone. The competitive process involving ipso attack of the aromatic
ring on the thionium ion generates a spiro cyclohexadienyl cation that undergoes fragmentation of
the adjacent σ-bond. The resulting acyl iminium ion is converted to N-tert-butyl-2-phenyl-3-
phenylsulfinylacrylamide upon aqueous workup. Only cyclizations leading to five-membered rings
occur with the corresponding indolyl and alkenyl N-tert-butyl amido sulfoxides.
Sch em e 1
The Pummerer rearrangement of sulfoxides with acid
anhydrides has been extensively utilized as a method for
synthesizing R-substituted sulfides.1-6 The initial step
of the reaction involves acylation of the sulfoxide oxygen
to form an acyloxysulfonium salt (2), thus converting this
oxygen to a good leaving group. Removal of a proton from
the R-carbon with elimination of the acyloxy group
generates a thionium ion (3), which is trapped by one of
the nucleophilic species present in the reaction medium
(Scheme 1). The finding that thionium ions may serve
as electrophiles in electrophilic substitution chemistry
has greatly extended the synthetic range of the Pum-
merer reaction.4 Thus, both inter-7 and intramolecular8
versions of the process have been used to prepare a wide
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Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, 1991; Vol. 6, pp 909-
947.
assortment of compounds. Currently, Pummerer-based
transformations are finding widespread application in
carbo-9 and heterocyclic syntheses10 by reaction of the
initially generated thionium ions with internally disposed
nucleophiles (Scheme 1).2
(4) Kennedy, M.; McKervey, M. A. In Comprehensive Organic
Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, 1991; Vol. 7, pp 193-
216.
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New York, 1980; Vol. 5, Chapter 2. Oae, S.; Numata, T.; Yoshimura,
T. Heterosulphonium Salts. In The Chemistry of the Sulphonium
Group; Stirling, C. J . M., Patai, S., Eds.; J ohn Wiley & Sons: New
York, 1981.
When R,â-unsaturated sulfoxides are used, the initially
formed oxysulfonium ion (6) may undergo reaction via
two different pathways (Scheme 2). In the additive
Pummerer reaction,11-17 nucleophilic attack occurs at the
(9) Ishibashi, H.; Harada, S.; Okada, M.; Ikeda, M.; Ishiyami, K.;
Yamashita, H.; Tamura, Y. Synthesis 1986, 847.
(10) Takano, S.; Iida, H.; Inomata, K.; Ogasawara, K. Heterocycles
1993, 35, 47.
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Commun. 1976, 642.
S0022-3263(97)02093-8 CCC: $15.00 © 1998 American Chemical Society
Published on Web 06/11/1998

Pummerer Reactions of Amido Sulfoxides
J . Org. Chem., Vol. 63, No. 13, 1998 4257
Sch em e 2
Sch em e 3
particularly interested in determining whether activated
vinyl sulfoxides such as 9 could be used as electrophilic
reagents to trigger tandem carbon-heteroatom bond
formation. In a preliminary communication, we de-
scribed a novel vinylogous Pummerer reaction of aryl
amido sulfoxides of type 12 (Scheme 3).23 Electrophilic
attack proceeded at the nucleophilic oxygen and was
followed by proton loss to give the highly reactive
intermediate 13 in which the γ-position was activated
by the positively charged sulfur atom. Attack at the
γ-carbon by a tethered π-bond resulted in an overall
annulation leading to various heterocyclic systems (i.e.,
14). In this paper we report in full the results of our
earlier investigations23 that show that the Pummerer
induced reaction of aryl amido sulfoxides with trifluoro-
acetic anhydride (TFAA) represents a convenient method
for the synthesis of oxindoles and related heterocycles.
electrophilic â-carbon atom of the O-activated substrate
producing a saturated â-functionalized thionium species
(7). Trapping with a second nucleophilic agent affords a
product (8) formally derived by the sequential attack of
two nucleophiles on an R,â-dication. This sequence of
reactions has been utilized in recent years for the
formation of heteroatom-carbon and carbon-carbon
bonds.18-20 The second pathway corresponds to the
related vinylogous Pummerer reaction of vinylic sulfox-
ides21 which involves an electrophilic thionium ion in-
termediate formed by γ-proton loss followed by sulfoxide
S-O bond scission. The resulting unsaturated thionium
ion 10 is then intercepted by a nucleophile at the
γ-position.
For the past several years we have been examining
tandem Pummerer processes with the intention of as-
sessing its viability as a general strategy for the synthesis
of carbo- and heterocyclic ring systems.22 We were
Resu lts a n d Discu ssion
Our studies began with an investigation of the Pum-
merer reaction of amido sulfoxide 18. Construction of
18 first involved the bis(bipyridyl)nickel(II)-catalyzed
thioarylation of 2-iodophenylacetic acid with sodium
p-thiocresolate.24 Conversion of the resulting acid 17 to
the corresponding amide was followed by sulfide oxida-
tion to furnish the desired sulfoxide 18 (Scheme 4).
When sodium periodate was used as the oxidant, elevated
temperatures were necessary and this resulted in the
formation of a significant amount of the corresponding
sulfone. After considerable experimentation with a
variety of oxidizing agents, we found that the best yields
are obtained using the titanium(III)-hydrogen peroxide
method of Oae.25 This procedure was found to be
particularly effective for the oxidation of highly hindered
sulfides and resulted in the isolation of sulfoxide 18 in
81% overall yield from carboxylic acid 17.
(12) Miyamoto, N.; Fukuoka, D.; Utimoto, K.; Nozaki, H. Bull. Chem.
Soc. J pn. 1974, 47, 1817.
(13) Marino, J . P.; Perez, A. D. J . Am. Chem. Soc. 1984, 106, 7643.
Marino, J . P.; de la Pradilla, R. F. Tetrahedron Lett. 1985, 26, 5381.
(14) Posner, G. H.; Asirvatham, E.; Ali, S. F. J . Chem. Soc., Chem.
Commun. 1985, 542.
(15) Craig, D.; Daniels, K.; Mackenzie, A. R. Tetrahedron Lett. 1990,
31, 6441; 1991, 32, 6973.
(16) King, R. R. J . Org. Chem. 1980, 45, 5347.
(17) Kosugi, H.; Uda, H.; Yamagiwa, S. J . Chem. Soc., Chem.
Commun. 1976, 71.
(18) Garcia, J .; Ortiz, C.; Greenhouse, R. J . Org. Chem. 1988, 53,
2634. Yamagiwa, S.; Sato, H.; Hoshi, N.; Kosugi, H.; Uda, H. J . Chem.
Soc., Perkin Trans. 1 1979, 570.
(19) Kita, Y.; Tamura, O.; Itoh, F.; Yasuda, H.; Miki, T.; Tamura,
Y. Chem. Pharm. Bull. 1987, 35, 562. Brichard, M. H.; J anousek, Z.;
Mere´nyi, R.; Viehe, H. G. Tetrahedron Lett. 1992, 33, 2511. Iwata,
C.; Maezaki, N.; Kurumada, T.; Fukuyama, H.; Sugiyama, K.; Iman-
ishi, T. J . Chem. Soc., Chem. Commun. 1991, 1408. Imanishi, T.;
Kurumada, T.; Maezaki, N.; Sugiyama, K.; Iwata, C. J . Chem. Soc.,
Chem. Commun. 1991, 1409.
(20) Marino, J . P.; Neisser, M. J . Am. Chem. Soc. 1981, 103, 7687.
Marino, J . P.; de la Pradilla, R. F.; Laborde, E. Synthesis 1987, 1088.
Kosugi, H.; Tagami, K.; Takahashi, A.; Kanna, H.; Uda, H. J . Chem.
Soc., Perkin Trans. 1 1989, 935.
(21) Craig, D.; Daniels, K.; Mackenzie, A. R. Tetrahedron 1992, 48,
7803; 1993, 49, 11263.
Treatment of 18 with trifluoroacetic anhydride (TFAA)
in CH2Cl2 at 25 °C gave the 3-substituted oxindole 19 in
91% yield which could easily be reduced with Raney
(22) Padwa, A.; Kuethe, J . T. Tetrahedron Lett. 1997, 38, 1505.
Padwa, A.; Kuethe, J . T. J . Org. Chem. 1997, 62, 774. Padwa, A.;
Kappe, C. O. J . Org. Chem. 1996, 61, 6166. Padwa, A.; Cochran, J .
E.; Kappe, C. O. J . Org. Chem. 1996, 61, 3706. Padwa, A.; Cochran,
J . E. J . Org. Chem. 1995, 60, 3938. Padwa, A.; Cochran, J . Tetrahedron
Lett. 1995, 36, 3495.
(23) Kuethe, J . T.; Cochran, J . E.; Padwa, A. J . Org. Chem. 1995,
60, 7082.
(24) Cristau, H. J .; Chabaud, B.; Chene, A.; Christol, H. Synthesis
1981, 892. Cristau, H. J .; Chabaud, B.; Labaudiniere, R.; Christol, H.
Organometallics 1985, 4, 657.
(25) Watanabe, Y.; Numata, T.; Oae, S. Synthesis 1981, 204.

4258 J . Org. Chem., Vol. 63, No. 13, 1998
Padwa and Kuethe
Sch em e 4
Sch em e 6
the product of internal cyclization on the aromatic ring.
Instead, only the normal Pummerer product (i.e., R-tri-
fluoroacetoxy sulfide 26; 66%) was formed which readily
hydrolyzed to the corresponding alcohol upon workup. On
the other hand, when the related tert-butyl amide 27 was
subjected to TFAA, the desired tetrahydroisoquinolone
derivative 28 was obtained in 83% yield (Scheme 6). The
product distribution encountered coincides with the rota-
mer population of the starting amide. It is well-known
that rotation around the acyl carbon-nitrogen bond is
restricted, leading to the existence of two geometric
isomers which are usually not separable due to the
relatively low barrier to rotation (ca. 20 kcal/mol).28 The
preference for unsymmetrical N,N-disubstituted amides
to exist predominantly with the larger substituent on
nitrogen syn to the carbonyl oxygen is well documented.29
Due to the N-benzyl-N-methylamido sulfoxide 25 pre-
ferred syn (benzyl) geometry, the thionium ion is gener-
ated in an unfavorable conformation for π-cyclization and
thus no cyclization occurs. Moreover, the failure to
isolate the tetrahydroisoquinolone derivative from the
Pummerer reaction of 25 implies that the amide linkage
does not rotate during the lifetime of the thionium ion.30
N-tert-Butylamides strongly favor the Z-rotamer,28 thereby
suggesting that amido sulfoxide 27 exists in the geomet-
ric orientation which places the benzylic group into the
crucial conformation necessary for π-cyclization. This
nicely accounts for the facility with which 27 is converted
into tetrahydroisoquinolone 28.
Sch em e 5
As an extension of these studies, amido sulfoxide 29
was prepared to evaluate the effect of an electron-rich
aryl group on the efficiency and selectivity of the cycliza-
tion process. The m-methoxy aryl-substituted amido
sulfoxide 29 was synthesized from acid 17 in 89% overall
yield and was subjected to the TFAA reaction conditions.
Although the presence of the activated aryl group seemed
to facilitate the Pummerer reaction (94% yield), there was
no discernible preference in the regiochemical mode of
cyclization since a 1:1 mixture of ortho- and para-cyclized
products was obtained (Scheme 7).
So that a cross-section of additional information could
be obtained in regard to the vinylogous Pummerer/π-
cyclization protocol, a series of different amido sulfoxides
was needed to represent a variety of different π-bonds.
Compounds ranging from substituted aromatics to simple
nickel to the known 3-phenyloxindole 20.26 We assume
that the mechanism for the conversion of 18 to 19
proceeds by the sequential set of reactions outlined in
Scheme 3 where the N-phenyl group effectively traps the
Pummerer-generated thionium ion in a Friedel-Crafts
fashion.27
In a like manner, sulfoxide 21 afforded the tetrahyd-
roquinolone derivative 22 in 85% isolated yield when
treated with TFAA at room temperature. In this case,
reductive removal of the p-tolylthio group with Raney
nickel in refluxing ethanol required 5 days and led to a
1:1 mixture of the 3-phenyl- and 3-cyclohexyl-substituted
oxindoles 23 and 24 (Scheme 5).
(28) Steward, W. E.; Siddall, T. H. Chem. Rev. 1970, 70, 517.
Siddall, T. H.; Garner, R. Can. J . Chem. 1966, 44, 2387. Oki, M. Top.
Stereochem. 1983, 14, 1.
(29) Lewin, A. H.; Frucht, M.; Chen, K. V. J .; Benedetti, E.; DiBlasio,
B. Tetrahedron 1975, 31, 207. Lewin, A. H.; Frucht, M. Org. Magn.
Reson. 1975, 7, 206. LaPlanche, L. A.; Rogers, M. T. J . Am. Chem.
Soc. 1963, 85, 3728.
(30) The fact that no cyclization occurred with amide 25 even though
ca. 30% of the rotamer population is in the correct conformation
indicates that the product distribution is determined by Curtin-
Hammett kinetics in a more complex fashion than indicated.
Interestingly, treatment of the homologous N-benzyl-
N-methylamido sulfoxide 25 with TFAA did not afford
(26) Aeberli, P.; Houlihan, W. J . J . Org. Chem. 1968, 33, 1640.
(27) J ung and co-workers have described a related trapping of an
R-ketosulfonium ion with an aromatic ring as a method for preparing
biaryls. See: J ung, M. E.; Kim, C.; Bussche, L. V. D. J . Org. Chem.
1994, 59, 3248. J ung, M. E.; J achiet, D.; Khan, S. I.; Kim, C.
Tetrahedron Lett. 1995, 36, 361.

Pummerer Reactions of Amido Sulfoxides
J . Org. Chem., Vol. 63, No. 13, 1998 4259
Sch em e 7
Sch em e 10
separated by fractional crystallization, and its structure
was unequivocally established by an X-ray crystal-
lographic study.31 Formation of 41 can be attributed to
preferential 5-exo trig cyclization which leads to the more
stable benzylic cation 40 rather than 6-endo trig cycliza-
tion which would give the tertiary cation 42. Interception
of 40 by trifluoroacetate leads to the observed product
41 (Scheme 10).
Sch em e 8
The Lewis acid mediated addition of allylsilanes to
electron deficient centers has proven to be a powerful
method for the preparation of many different types of
cyclic ring systems.32 A wide variety of allylsilanes has
been utilized, and the method has found significant use
in organic synthesis.33,34 There have been relatively few
instances of cyclization involving the intramolecular
addition of allylsilanes to thionium ions, despite the
ongoing activity in this area.35 The well-documented
reactivity of allylsilanes toward electrophiles32 suggested
that the reaction of sulfoxide 43 with a Pummerer
promoter should provide access to adduct 44 which
possesses an exocyclic double bond. Surprisingly, when
amido sulfoxide 43 was treated with TFAA, a 1:1 mixture
of dihydropyridones 45 (45%) and 46 (45%) was obtained
in high yield (Scheme 11). There was no evidence of the
anticipated desilylated compound 44 in the crude reaction
mixture. Evidently, the trifluoroacetoxy anion generated
from the Pummerer reaction is not sufficiently nucleo-
philic to attack the trimethylsilyl group, and conse-
quently, only products resulting from proton loss are
observed. This example represents a rare case of an
allylsilane cyclization where the trialkylsilyl group is
retained in the final product.36
Sch em e 9
It occurred to us at this stage of our studies that the
additive Pummerer reaction of vinyl amido sulfoxides of
alkenyl-tethered systems were considered. Ultimately,
substrates 32, 34, and 35 were studied as they contain a
range of synthetically interesting and easily attainable
functionality. Exposure of the furanyl tethered amido
sulfoxide 32 to TFAA in CH2Cl2 at 25 °C furnished 33 in
68% yield (Scheme 8). Similarly, reaction of tert-buty-
lamido sulfoxides 34 and 35 with TFAA gave the cyclized
dihydropyridones 37 and 38 in 67% and 54% yields
(Scheme 9), thereby demonstrating that tethered alkenes
can also be used in these Pummerer-induced cyclizations.
It is interesting to note that treatment of the related
amido sulfoxide 39 under standard Pummerer reaction
conditions led to pyrrolidone 41 as a mixture of diaster-
eomers in 65% yield. The major stereoisomer was
(31) The authors have deposited atomic coordinates for structure
41 with the Cambridge Data Centre. The coordinates can be obtained,
on request, from the Director, Cambridge Crystallographic Data
Centre, 12 Union Road, CB2 1EZ, U.K.
(32) Fleming, I.; Dunogues, J .; Smithers, R. The Electrophilic
Substitution of Allylsilanes and Vinylsilanes. In Organic Reactions;
Kende, A. S., Ed.; J ohn Wiley and Sons: New York, 1989; Vol. 37,
Chapter 2, p 57.
(33) Hiemstra, H.; Forgens, H. P.; Speckamp, W. N. Tetrahedron
Lett. 1985, 26, 3155.
(34) Heerding, D. A.; Hong, C. Y.; Kado, N.; Look, G. C.; Overman,
L. E. J . Org. Chem. 1993, 58, 6947.
(35) Trost, B. M.; Murayama, E. J . Am. Chem. Soc. 1981, 103, 6529.
(36) Larsen, S. D.; Grieco, P. A.; Fobare, W. F. J . Am. Chem. Soc.
1986, 108, 3512.

4260 J . Org. Chem., Vol. 63, No. 13, 1998
Padwa and Kuethe
Sch em e 11
Sch em e 13
Sch em e 12
Sch em e 14
type 47 might proceed in a related fashion. We antici-
pated that activation of the vinylic sulfoxide C-C double
bond by sulfoxide O-trifluoroacetylation would be fol-
lowed by intramolecular cyclization via nucleophilic
addition of the tethered π-bond. The resulting thionium
ion 48 could then undergo deprotonation to furnish
dihydropyridone 49 (Scheme 12).
In this context, we prepared amido sulfoxide 50 in 76%
overall yield from the reaction of 3-(phenylthio)acrylic
acid with tert-butylbenzylamine followed by titanium(III)-
H2O2 oxidation of the resulting sulfide. Extensive ex-
perimentation established that the best conditions to
induce the additive Pummerer reaction involved treating
50 with 1.1 equiv of triflic anhydride in the presence of
2.2 equiv of triethylamine at -78 °C. The reaction of 50
under these Pummerer conditions gave rise to a mixture
of dihydroisoquinoline 51 (32%) and the rearranged
N-tert-butyl-2-phenyl-3-phenylsulfenyl acrylamide 52
(45%) (Scheme 13). The formation of 51 is perfectly
consistent with the sequence of events proposed in
Scheme 12. The critical step in this transformation
involves a 6-exo trig cyclization of intermediate 53 to give
54 which is ultimately converted to 51 (Scheme 6). A
plausible mechanism for the formation of the rearranged
enamide 52 from amido sulfoxide 50 is outlined in
Scheme 14. The first step involves ipso attack of the
aromatic ring on the activated vinyl sulfoxide π-bond to
produce the spiro-substituted cyclohexadienyl cation 55.
Nitrogen-assisted fragmentation of the C-C π-bond
results in generation of acyl iminium ion 56 which is
eventually converted to 52 on aqueous workup (Scheme
14).
Sch em e 15
cyclized (58) and rearranged (59) amides (Scheme 15).
The fact that 59 was the major product formed (60%)
indicates that subtle electronic factors can influence the
ratio of five-membered vs six-membered ring cyclization.
With sulfinyl acrylamide 60, the meta arrangement of
substituents on the aromatic ring should preclude ipso
attack. Indeed, stirring a sample of 60 with triflic
anhydride afforded the expected dihydroisoquinolone 61
(63%) as the major product together with a small
quantity of acetylene 62 (8%). No signs of a rearranged
amide derived from five-membered ring cyclization (i.e.,
55) could be detected in the crude reaction mixture. More
than likely, the formation of 62 involves attack of a
triflate anion on the initially formed thionium ion fol-
lowed by deprotonation and subsequent elimination of
In a further investigation of the additive Pummerer
sequence, we examined the reaction of the related sul-
foxides 57 and 60 with triflic anhydride. In the case of
sulfoxide 57, the reaction afforded a 1:4 mixture of

Pummerer Reactions of Amido Sulfoxides
J . Org. Chem., Vol. 63, No. 13, 1998 4261
Sch em e 16
Sch em e 18
anhydride at -78 °C which provided γ-lactams 70 and
72 in 57% and 40% isolated yields, respectively. The
minor reaction product (14%) obtained from the reaction
of 71 corresponded to acetylene 73 (Scheme 18). The
formation of 70 and 72 nicely demonstrates that tethered
alkenes can also be utilized in the cyclization step of these
cascade reactions. Once again, all cyclization products
are derived from a 5-exo trig ring closure.
Sch em e 17
In conclusion, the results presented here demonstrate
the potential of both the additive and vinylogous Pum-
merer reactions for the synthesis of nitrogen heterocycles.
The reaction sequence involves formation of an electro-
philic thionium ion intermediate which is intercepted by
a π-nucleophile tethered on the amide nitrogen. The
overall transformations represent highly effective meth-
ods for converting relatively simple starting materials
into complex nitrogen heterocycles. Further application
of these sequences for the stereocontrolled synthesis of
several alkaloids is under active investigation.
triflic acid (i.e., 60 f 63 f 64 f 65 f 62) as shown in
Scheme 16.37-39
The synthesis of indoles bearing substituents at the
2- and 3-positions has been of interest for many years
due to the large number of biologically active natural
products having this substitution pattern.40 Conse-
quently, we decided to investigate the additive Pummerer
reaction where an indolyl methylene tether has been
placed on the amide nitrogen as a method for generating
highly functionalized indoles. Interestingly, the reaction
of indoyl sulfoxide 66 with triflic anhydride produced
spiro γ-lactam 68 in 51% yield as the only identifiable
product. The reaction proceeds via a 5-exo trig cyclization
to generate 67 as a transient cation which ultimately
captures water (or its equivalent) to produce 68 (Scheme
17). In this case, preferential five-membered ring cy-
clization is probably related to the enhanced electron
density at the â-position of the indole ring.40
Exp er im en ta l Section
Melting points are uncorrected. Mass spectra were deter-
mined at an ionizing voltage of 70 eV. Unless otherwise noted,
all reactions were performed in flame-dried glassware under
an atmosphere of dry argon. Solutions were evaporated under
reduced pressure with a rotary evaporator, and the residue
was chromatographed on a silica gel column using an ethyl
acetate-hexane mixture as the eluent unless specified other-
wise.
Gen er a l P r oced u r e for th e P r ep a r a tion of Secon d a r y
Allylic Am in es. To a stirred solution of 50 mmol of the
appropriate R,â-unsaturated aldehyde in 100 mL of CHCl3 was
added 5 g of MgSO4 followed by an excess of tert-butylamine.
The mixture was heated at reflux for 18 h, cooled to room
temperature, and concentrated under reduced pressure. The
crude imine was taken up in 100 mL of methanol and cooled
to 0 °C, and 50 mmol of sodium borohydride was added over
a period of 10 min. The mixture was stirred for an additional
2 h at room temperature, poured into 200 mL of water, and
extracted with CH2Cl2. The solvent was removed under
reduced pressure, and the crude product was purified by either
distillation or silica gel column chromatography to give the
pure amine.
The ability of simple π-bonds to participate as nucleo-
philes in additive Pummerer reactions was established
by exposure of amido sulfoxides 69 and 71 to triflic
(37) Treatment of the known sulfoxide i38 with triflic anhydride
under the same experimental conditions used with 59 afforded
acetylene ii,39 thereby providing support for the proposed mechanism.
Gen er a l P r oced u r e for th e P r ep a r a tion of Am id o
Su lfoxid es Der ived fr om 2-(p-Tolylsu lfen ylp h en yl)a cetic
Acid (17). A solution containing 5.9 g (22.7 mmol) of 2-io-
dophenylacetic acid41 and 4.6 g (31.7 mmol) of sodium p-
thiocresolate in 40 mL of ethylene glycol was treated with 36
(38) Proust, S. M.; Ridley, D. D. Aust. J . Chem. 1984, 37, 1677.
(39) Gupta, I.; Yates, P. J . Chem. Soc., Chem. Commun. 1982, 1227.
(40) Gilchrist, T. L. Heterocyclic Chemistry; Pitman: London, 1981.
(41) Sindelar, K.; Metysova, J .; Protiva, M. Collect. Czech. Chem.
Commun. 1972, 37, 1734.

4262 J . Org. Chem., Vol. 63, No. 13, 1998
Padwa and Kuethe
mg (0.068 mmol) of bis(bipyridine)-nickel(II) bromide.24 The
resulting mixture was heated at 150 °C for 3 h, acidified with
10% HCl, extracted with ether, and concentrated under
reduced pressure. The residue was taken up in aqueous
NaOH, washed with ether, and acidified with concentrated
HCl. The aqueous solution was extracted with ether, and the
organic extracts were dried over MgSO4 and concentrated
under reduced pressure. The resulting solid was recrystallized
from a benzene-hexane mixture to give 4.9 g (83%) of 2-(p-
tolylsulfenylphenyl)acetic acid (17): mp 115-116 °C; IR (CCl4)
afforded 0.82 g (91%) of 19 as a white solid: mp 110-111 °C;
IR (CCl4) 3053, 2925, 1709, 1488, 1082, and 748 cm-1; 1H NMR
(CDCl3, 300 MHz) δ 2.32 (s, 3H), 3.28 (s, 3H), 5.30 (brs, 1H),
and 6.81-7.49 (m, 12H); 13C NMR (CDCl3, 75 MHz) δ 21.0,
26.4, 49.9, 108.0, 122.5, 128.1, 128.2, 128.3, 128.4, 128.5, 129.9,
130.5, 130.6, 130.7, 130.8, 133.7, 136.3, 136.9, 144.3, and 176.0.
Anal. Calcd for C21H19NOS: C, 76.49; H, 5.54. Found: C,
76.39; H, 5.51.
The structure of 19 was established by reduction to oxindole
20. To a solution containing 100 mg (0.29 mmol) of 19 in 5
mL of ethanol was added 34 mg of W-2 Raney nickel. The
mixture was heated at reflux for 24 h, filtered through Celite,
and concentrated under reduced pressure. The residue was
subjected to silica gel chromatography to give 63 mg (97%) of
1-methyl-3-phenyl-1,3-dihydroindole-2-one (20) as a colorless
solid: mp 115-116 °C (lit.26 mp 116-117 °C); 1H NMR (CDCl3,
300 MHz) δ 3.24 (s, 3H), 4.60 (s, 1H), 6.89 (d, 1H, J ) 7.7 Hz),
and 7.05-7.40 (m, 8H).
1-(3,4-Dih yd r o-2H -q u in olin -1-yl)-2-(2-p -t olylsu lfen yl-
p h en yl)eth a n on e. Following the general procedure, treat-
ment of 1.0 g (3.8 mmol) of carboxylic acid 17 with 1.2 g (8.9
mmol) of 1,2,3,4-tetrahydroquinoline gave 1.4 g (99%) of 1-(3,4-
dihydro-2H-quinolin-1-yl)-2-(2-p-tolylsulfenylphenyl)etha-
none as a light yellow oil: IR (neat) 2938, 1644, 1484, 1372,
and 749 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.88 (m, 2H), 2.25
(s, 3H), 2.66 (t, 2H, J ) 6.7 Hz), 3.75 (m, 2H), 3.97 (s, 2H),
7.04 (s, 4H), and 7.12-7.33 (m, 8H); 13C NMR (CDCl3, 75 MHz)
δ 20.8, 23.7, 26.5, 39.8, 43.2, 124.3, 125.0, 125.8, 127.5, 128.2,
129.6, 130.1, 130.5, 132.0, 132.8, 134.6, 136.4, 137.4, 138.8,
1
3014, 2921, 1707, 1401, and 797 cm-1; H NMR (CDCl3, 300
MHz) δ 2.29 (s, 3H), 3.86 (s, 2H), 7.18 (m, 8H), and 10.95 (brs,
1H); 13C NMR (CDCl3, 75 MHz) δ 21.0, 39.3, 127.8, 128.3,
129.9, 130.6, 131.0, 132.0, 133.2, 135.0, 135.8, 136.9, and 177.6.
Anal. Calcd for C15H14O2S: C, 69.74; H, 5.46. Found: C,
69.75; H, 5.44.
To a solution of 1.3 g (5.0 mmol) of carboxylic acid 17 in 25
mL of benzene was added 1.3 g (10.1 mmol) of oxalyl chloride
followed by one drop of DMF. After being stirred for 2 h at
room temperature, the mixture was concentrated under re-
duced pressure, dissolved in 5 mL CH2Cl2, and added dropwise
to a mixture of the appropriate secondary amine (11.6 mmol)
in 50 mL of CH2Cl2. The solution was allowed to stir for 2 h
and was quenched with water, extracted with CH2Cl2, and
dried over MgSO4. The solvent was removed under reduced
pressure, and the residue was subjected to silica gel chroma-
tography to give the pure amide.
A mixture containing 1.0 mmol of the amido sulfide and 1.5
mmol of a 16% aqueous solution of titanium(III) chloride in
50 mL of acetonitrile/methanol (1:5) was stirred at room
temperature. To this mixture was added 0.45 mL (4 mmol)
of 30% hydrogen peroxide in 10 mL of methanol. After being
stirred for 10 min at room temperature, the mixture was
diluted with water, extracted with CHCl3, and dried over
MgSO4. Concentration under reduced pressure followed by
chromatography on silica gel afforded the pure sulfoxide.
N-Met h yl-N-p h en yl-2-(2-p -t olylsu lfen ylp h en yl)a cet a -
m id e. A solution containing 4.2 g (16.3 mmol) of carboxylic
acid 17 and 2.5 mL of triethylamine in 75 mL of CH2Cl2 was
treated with 5.4 g (20.3 mmol) of phenyl N-phenylphosphora-
midochloridate.42 The mixture was stirred for 45 min under
N2, and then 3.5 g (32.5 mmol) of N-methylaniline was added
dropwise via syringe. The solution was stirred an additional
1.5 h, acidified with 10% HCl, extracted with CH2Cl2, and dried
over MgSO4. Removal of the solvent under reduced pressure
followed by flash silica gel chromatography afforded 4.9 g (87%)
of N-methyl-N-phenyl-2-(2-p-tolylsulfenylphenyl)acetamide as
a colorless solid: mp 93-94 °C; IR (CCl4) 3053, 2918, 1659,
1374, and 698 cm-1; 1H NMR (CDCl3, 300 MHz) δ 2.26 (s, 3H),
3.24 (s, 3H), 3.61 (s, 2H), and 7.19 (m, 13H); 13C NMR (CDCl3,
75 MHz) δ 20.6, 37.1, 39.2, 126.9, 127.2, 127.3, 127.4, 129.3,
129.5, 129.9, 130.4, 132.1, 132.5, 134.6, 136.0, 137.1, 143.5,
and 170.0. Anal. Calcd for C22H21NOS: C, 76.05; H, 6.09.
Found: C, 76.03; H, 6.08.
N-Met h yl-N-p h en yl-2-(2-p -t olylsu lfin ylp h en yl)a cet a -
m id e (18). Following the general procedure, a 2.7 g (7.8
mmol) sample of the above sulfide was oxidized to give 2.6 g
(93%) of 18 as a colorless oil: IR (neat) 1652, 1588, 1488, 1367,
and 1026 cm-1; 1H NMR (CDCl3, 300 MHz) δ 2.34 (s, 3H), 3.28
(s, 3H), 3.59 (d, 1H, J ) 16.1 Hz), 3.66 (d, 1H, J ) 16.1 Hz),
7.19 (d, 4H, J ) 6.8 Hz), 7.37-7.46 (m, 8H), and 7.68-7.71
(m, 1H); 13C NMR (CDCl3, 75 MHz) δ 21.3, 37.6, 125.5, 125.6,
127.2, 128.1, 128.2, 129.7, 129.9, 130.7, 131.0, 134.2, 141.1,
141.2, 143.4, 144.1, and 169.5; HRMS calcd for C22H21NO2S
363.1293, found 363.1287.
and 170.0; HRMS calcd for
373.1499.
C24H23NOS 373.1500, found
1-(3,4-Dih yd r o-2H -q u in olin -1-yl)-2-(2-p -t olylsu lfin yl-
p h en yl)eth a n on e (21). Following the general procedure,
treatment of 0.57 g (1.5 mmol) of the above sulfide with 2.2
mL of a 16% aqueous solution of TiCl3 followed by 0.7 mL of
30% H2O2 afforded 0.56 g (95%) of 21 as a colorless oil: IR
(neat) 2921, 1560, 1486, 1380, and 1032 cm-1; 1H NMR (CDCl3,
300 MHz) δ 1.94 (m, 2H), 2.31 (s, 3H), 2.74 (t, 2H, J ) 6.7
Hz), 3.71 (m, 1H), 3.95 (m, 1H), 3.97 (s, 2H), 7.13-7.18 (m,
5H), 7.27-7.30 (m, 3H), 7.38-7.42 (m, 3H), and 7.78-7.81 (m,
1H); 13C NMR (CDCl3, 75 MHz) δ 21.1, 23.7, 26.6, 37.8, 43.1,
124.2, 125.2, 125.5, 125.8, 125.9, 126.1, 128.1, 128.5, 129.6,
130.9, 131.0, 134.1, 138.5, 140.8, 141.1, 143.4, and 169.1;
HRMS calcd for C24H23NO2S 389.1449, found 389.1447.
1-(2-p -T o ly ls u lfe n y lp h e n y l)-1,4,5,6-t e t r a h y d r o -
p yr r olo[3,2,1-ij]qu in olin -2-on e (22). To a solution of 0.29
g (0.76 mmol) of 21 in 25 mL of CH2Cl2 was added 0.12 mL of
triethylamine followed by 0.32 g (1.5 mmol) of trifluoroacetic
anhydride. After being stirred for 10 min, the reaction mixture
was diluted with CH2Cl2, washed with 10% HCl and a
saturated NaHCO3 solution, and dried over MgSO4. Removal
of the solvent under reduced pressure followed by silica gel
chromatography gave 0.24 g (85%) of 22 as a white solid: mp
166-167 °C; IR (CCl4) 2947, 1701, 1474, 1353, and 784 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 2.03 (m, 2H), 2.31 (s, 3H), 2.80
(t, 2H, J ) 5.9 Hz), 3.77 (m, 2H), 5.50 (brs, 1H), 6.87 (m, 3H),
and 7.01-7.35 (m, 8H); 13C NMR (CDCl3, 75 MHz) δ 21.0, 21.2,
24.5, 39.1, 50.8, 120.0, 121.9, 122.2, 126.8, 128.0, 128.2, 129.8,
130.5, 130.6, 130.7, 130.8, 132.7, 133.6, 136.3, 136.8, 140.1,
and 174.9. Anal. Calcd for C24H21NOS: C, 77.60; H, 5.70.
Found: C, 77.62; H, 5.75.
1-P h en yl-5,6-d ih yd r o-1H,4H-p yr r olo[3,2,1-ij]qu in olin -
2-on e (23). To a solution containing 0.9 g (2.4 mmol) of 22 in
50 mL of ethanol was added 0.5 g of W-2 Raney nickel. The
mixture was heated at reflux for 5 days, filtered through Celite,
and concentrated under reduced pressure. The residue was
subjected to silica gel chromatography. The first product
eluted from the column (0.14 g, 23% yield) was identified as
23: mp 126-127 °C; IR (CCl4) 2925, 1709, 1623, 1474, and
1346 cm-1; 1H NMR (CDCl3, 300 MHz) δ 2.00 (m, 2H), 2.78 (t,
2H, J ) 6.0 Hz), 3.71 (m, 2H), 4.57 (s, 1H), 6.98 (m, 3H), and
7.27 (m, 5H); 13C NMR (CDCl3, 75 MHz) δ 21.0, 24.4, 38.9,
52.7, 120.0, 121.9, 122.5, 126.9, 127.1, 127.2, 128.2, 128.6,
136.4, 140.1, and 174.6. Anal. Calcd for C17H15NO: C, 81.90;
H, 6.06; N, 5.62. Found: C, 81.76; H, 6.09; N, 5.59.
1-Meth yl-3-(2-p-tolylsu lfen ylp h en yl)-1,3-d ih yd r oin d ol-
2-on e (19). To a solution of 0.95 g (2.6 mmol) of 18 in 10 mL
of CH2Cl2 was added 0.36 mL of triethyamine followed by 1.1
g (5.2 mmol) of trifluoroacetic anhydride. After being stirred
for 10 min, the reaction mixture was diluted with CH2Cl2,
washed with 10% HCl, saturated NaHCO3, and dried over
MgSO4. Evaporation of the solvent under reduced pressure
(42) Mestres, R.; Palomo, C. Synthesis 1982, 288.

Pummerer Reactions of Amido Sulfoxides
J . Org. Chem., Vol. 63, No. 13, 1998 4263
1-Cycloh exyl-5,6-d ih yd r o-1H,4H-p yr r olo[3,2,1-ij]qu in -
olin -2-on e (24). The second product isolated (0.14 g, 23%
yield) was assigned as 24; mp 104-105 °C; IR (CCl4) 2925,
1702, 1481, 1353, and 784 cm-1; 1H NMR (CDCl3, 300 MHz) δ
1.02-1.51 (m, 6H), 1.63 (d, 2H, J ) 10.6 Hz), 1.76 (d, 2H, J )
10.6 Hz), 1.98 (m, 2H), 2.14 (m, 1H), 2.75 (t, 2H, J ) 6.0 Hz),
3.32 (d, 1H, J ) 3.3 Hz), 3.71 (m, 2H), 6.91 (t, 1H, J ) 7.5
133.3, 134.9, 136.4, 137.8, 139.4, and 172.0. Anal. Calcd for
C26H29NOS: C, 77.38; H, 7.24. Found: C, 77.35; H, 7.22.
N -Be n zyl-N -t er t -b u t yl-2-(2-p -t olylsu lfin ylp h e n yl)-
a ceta m id e (27). Following the general procedure, treatment
of 2.9 g (7.3 mmol) of the above sulfide with 10.5 mL of a 16%
aqueous solution of TiCl3 followed by 3.3 mL of 30% H2O2 gave
2.7 g (89%) of 27 as a colorless solid: mp 158-159 °C; IR (CCl4)
1
2954, 1645, 1381, 1026, and 748 cm-1; H NMR (CDCl3, 300
Hz), 7.00 (d, 1H, J ) 7.5 Hz), and 7.10 (d, 1H, J ) 7.5 Hz); 13
C
MHz) δ 1.45 (s, 9H), 2.32 (s, 3H), 3.73 (d, 1H, J ) 16.3 Hz),
3.83 (d, 1H, J ) 16.3 Hz), 4.59 (s, 2H), 7.15 (d, 2H, J ) 7.9
Hz), 7.22-7.33 (m, 5H), 7.38-7.43 (m, 5H), and 7.76 (m, 1H);
13C NMR (CDCl3, 75 MHz) δ 21.3, 28.6, 39.6, 49.0, 58.2, 125.4,
125.6, 125.8, 127.1, 128.2, 128.9, 129.7, 130.1, 131.2, 134.4,
138.8, 141.0, 141.1, 144.1, and 171.0. Anal. Calcd for
C26H29NO2S: C, 74.43; H, 6.97. Found: C, 74.42; H, 6.98.
2-ter t-Bu tyl-4-(2-p-tolylsu fen ylp h en yl)-2,4-d ih yd r o-1H-
isoqu in olin -3-on e (28). To a solution of 2.6 g (6.1 mmol) of
27 in 50 mL of CH2Cl2 was added 0.9 mL of triethylamine
followed by 2.6 g (12.3 mmol) of trifluoroacetic anhydride. After
the mixture was stirred for 10 min, the reaction was diluted
with CH2Cl2, washed with 10% HCl and a saturated NaHCO3
solution, and dried over MgSO4. Removal of the solvent under
reduced pressure left a crude oil which was chromatographed
on silica gel to give 2.04 g (83%) of 28 as a white foam: IR
(CCl4) 2970, 1647, 1489, 807, and 745 cm-1; 1H NMR (CDCl3,
300 MHz) δ 1.51 (s, 9H), 2.28 (s, 3H), 4.56 (d, 1H, J ) 15.5
Hz), 4.72 (d, 1H, J ) 15.5 Hz), 5.32 (brs, 1H), 6.74 (d, 1H, J )
7.5 Hz), 7.02 (d, 2H, J ) 8.0 Hz), and 7.10-7.33 (m, 9H); 13C
NMR (CDCl3, 75 MHz) δ 21.0, 28.4, 47.1, 52.7, 57.8, 125.0,
126.3, 126.9, 127.3, 127.5, 127.8, 129.7, 131.0, 131.3, 132.1,
133.2, 133.6, 136.2, 136.4, 136.6, 141.4, and 170.1; HRMS calcd
for C26H27NOS 401.1813, found: 401.1812.
N -t e r t -B u t y l -N -(3 -m e t h o x y b e n z y l )-2 -(2 -p -t o l y l -
su lfen ylp h en yl)a ceta m id e. Treatment of a 25 g (184 mmol)
sample of m-anisaldehyde with excess tert-butylamine followed
by reduction with sodium borohydride according to the general
method gave 33.4 g (94%) of tert-butyl(3-methoxybenzyl)amine
as a colorless liquid: bp 136 °C/15 mm; IR (neat) 3309, 1595,
1488, 1260, and 1040 cm-1; 1H NMR (CDCl3, 300 MHz) δ 0.85
(brs, 1H), 1.15 (s, 9H), 3.68 (d, 2H, J ) 5.7 Hz), 6.74 (m, 1H),
6.90 (m, 2H), and 7.19 (t, 1H, J ) 8.0 Hz); 13C NMR (CDCl3,
75 MHz) δ 28.9, 47.0, 50.3, 54.8, 111.9, 113.5, 120.2, 129.1,
143.0, and 159.5.
NMR (CDCl3, 75 MHz) δ 21.2, 24.6, 26.1, 26.2, 26.6, 28.2, 30.7,
38.6, 40.4, 52.6, 119.7, 121.4, 122.3, 126.4, 126.5, 140.5, and
176.2. Anal. Calcd for C15H21NO: C, 79.96; H, 8.29; N, 5.49.
Found: C, 79.77; H, 8.22; N, 5.44.
N-Ben zyl-N-m et h yl-2-(2-p -t olylsu lfen ylp h en yl)a cet a -
m id e. Following the general procedure, treatment of 1.7 g
(6.6 mmol) of carboxylic acid 17 with 1.8 g (15.1 mmol) of
N-benzylmethylamine afforded 1.6 g (67%) of N-benzyl-N-
methyl-2-(2-p-tolylsulfenylphenyl)acetamide as a 1.4:1 mixture
of rotamers in solution: IR (neat) 3057, 3022, 2924, 1644, 1491,
1
1106, 805, and 749 cm-1; H NMR (CDCl3, 300 MHz) major
rotamer δ 2.26 (s, 3H), 2.82 (s, 3H), 3.87 (s, 2H), 4.56 (s, 2H),
and 7.0-7.35 (m, 13H); minor rotamer δ 2.23 (s, 3H), 2.89 (s,
3H), 3.89 (s, 2H), 4.44 (s, 2H), and 7.0-7.35 (m, 13H); 13C NMR
(CDCl3, 75 MHz) δ 20.7, 33.6, 34.7, 38.2, 38.5, 50.7, 53.3, 126.3,
127.0, 127.2, 127.5, 127.6, 127.7, 127.8, 128.2, 128.5, 129.6,
129.7, 129.8, 129.9, 130.0, 131.9, 132.8, 132.9, 134.3, 134.4,
136.3, 136.4, 136.5, 136.7, 137.1, 170.4, and 170.7; HRMS calcd
for C23H23NOS 361.1500, found 361.1505.
N-Ben zyl-N-m et h yl-2-(2-p -t olylsu lfin ylp h en yl)a cet a -
m id e (25). Following the general procedure, treatment of 1.4
g (3.8 mmol) of the above sulfide with 5.6 mL of a 16% aqueous
solution of TiCl3 followed by reaction with 1.8 mL of 30% H2O2
gave 1.2 g (83%) of 25 as a 1.4:1 mixture of rotamers: IR (neat)
3050, 2917, 1644, 1071, 1029, and 721 cm-1; 1H NMR (CDCl3,
300 MHz) major rotamer δ 2.30 (s, 3H), 2.88 (s, 3H), 3.85-
4.06 (m, 2H), 4.56-4.64 (m, 2H), 7.12-7.54 (m, 12H), and
7.75-7.79 (m, 1H); minor rotamer δ 2.30 (s, 3H), 2.94 (s, 3H),
3.85-4.06 (m, 2H), 4.56-4.64 (m, 2H), 7.12-7.54 (m, 12H),
and 7.75-7.79 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ 21.3, 34.3,
35.0, 36.6, 37.1, 51.1, 53.6, 125.6, 126.2, 126.3, 126.5, 127.4,
127.7, 128.0, 128.3, 128.5, 128.9, 129.8, 130.4, 131.4, 131.5,
137.0, 141.3, 169.8, and 170.0; HRMS calcd for C23H23NO2S
377.1449, found 377.1446.
N -Be n zyl-2-h yd r oxy-N -m e t h yl-2-(2-p -t olylsu lfe n yl-
p h en yl)a ceta m id e (26). To a solution of 0.5 g (1.3 mmol) of
25 in 20 mL of CH2Cl2 was added 0.2 mL of triethylamine
followed by 0.55 g (2.6 mmol) of trifluoroacetic anhydride. After
being stirred for 10 min, the reaction was diluted with CH2Cl2,
washed with 10% HCl and saturated NaHCO3, and dried over
MgSO4. The solvent was removed under reduced pressure,
and the residue was chromatographed on silica gel to give 26
as 1.7:1 mixture of rotamers in solution: mp 103-104 °C; IR
(CCl4) 3402, 2925, 1645, 1488, 1381, and 1061 cm-1; 1H NMR
(CDCl3, 300 MHz) major rotamer δ 2.31 (s, 3H), 2.63 (s, 3H),
4.60 (d, 1H, J ) 14.6 Hz), 4.70 (d, 1H, J ) 6.1 Hz), 4.71 (d,
1H, J ) 14.6 Hz), 5.89 (d, 1H, J ) 6.1 Hz), 6.82 (m, 1H), and
6.99-7.37 (m, 12H); minor rotamer δ 2.26 (s, 3H), 2.92 (s, 3H),
4.27 (d, 1H, J ) 16.1 Hz), 4.34 (d, 1H, J ) 16.1 Hz), 4.77 (d,
1H, J ) 6.3 Hz), 5.96 (d, 1H, J ) 6.3 Hz), 6.82 (m, 1H), and
6.99-7.37 (m, 12H); 13C NMR (CDCl3, 300 MHz) δ 21.0, 33.6,
33.7, 51.9, 52.0, 68.2, 68.4, 126.7, 127.4, 127.6, 127.7, 127.8,
127.9, 128.0, 128.1, 128.6, 129.2, 130.0, 130.1, 130.9, 131.3,
131.6, 132.2, 132.6, 135.1, 135.3, 135.9, 136.2, 137.4, 137.5,
139.1, 139.8, 172.8, and 173.0. Anal. Calcd for C23H23NO2S:
C, 73.18; H, 6.14. Found: C, 73.13; H, 6.19.
N -Be n zyl-N -t er t -b u t yl-2-(2-p -t olylsu lfe n ylp h e n yl)-
a ceta m id e. Following the general procedure, treatment of
2.0 g (7.7 mmol) of carboxylic acid 17 with 2.9 g (17.8 mmol)
of N-tert-butylbenzylamine afforded 2.7 g (86%) of N-benzyl-
N-tert-butyl-2-(2-p-tolylsulfenylphenyl)acetamide as a colorless
solid: mp 101-102 ×a1C; IR (CCl4) 2908, 1630, 1488, 1196,
and 784 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.43 (s, 9H), 2.27
(s, 3H), 3.77 (s, 2H), 4.59 (s, 2H), 7.05 (s, 3H), and 7.03-7.33
(m, 10H); 13C NMR (CDCl3, 75 MHz) δ 21.0, 28.7, 41.6, 49.1,
58.0, 125.6, 126.8, 127.6, 127.8, 128.6, 129.8, 130.1, 132.5,
Following the general procedure, treatment of 1.5 g (5.8
mmol) of carboxylic acid 17 with 2.6 g (13.4 mmol) of tert-
butyl(3-methoxybenzyl)amine afforded 2.4 g (93%) of N-tert-
butyl-N-(3-methoxybenzyl)-2-(2-p-tolylsulfenylphenyl)aceta-
mide as a white solid: mp 88-89 °C; IR (CCl4) 2959, 1637,
1
1393, 1036, and 777 cm-1; H NMR (CDCl3, 300 MHz) δ 1.44
(s, 9H), 2.28 (s, 3H), 3.78 (s, 5H), 4.57 (s, 2H), 6.77-6.85 (m,
3H), 6.99-7.06 (m, 3H), and 7.13-7.33 (m, 6H); 13C NMR
(CDCl3, 75 MHz) δ 21.0, 28.7, 41.6, 49.1, 55.2, 58.0, 111.2,
112.3, 117.9, 127.6, 127.7, 129.7, 129.8, 130.1, 130.3, 132.5,
133.1, 135.1, 136.5, 137.7, 141.2, 160.0, and 172.0. Anal.
Calcd for C26H31NO2S: C, 74.79; H, 7.21. Found: C, 74.65;
H, 7.20.
N -t e r t -B u t y l -N -(3 -m e t h o x y b e n z y l )-2 -(2 -p -t o l y l -
su lfin ylp h en yl)a ceta m id e (29). Treatment of 2.1 g (4.9
mmol) of the above sulfide with 7.1 mL of a 16% aqueous
solution of TiCl3 followed by reaction with 2.2 mL of 30% H2O2
gave 2.1 g (96%) of 29 as a colorless oil: IR (neat) 2961, 1645,
1
1595, 1033, and 727 cm-1; H NMR (CDCl3, 300 MHz) δ 1.45
(s, 9H), 2.31 (s, 3H), 3.75 (d, 1H, J ) 16.3 Hz), 3.80 (s, 3H),
3.84 (d, 1H, J ) 16.3 Hz), 4.56 (s, 2H), 6.83 (m, 3H), 7.15 (d,
2H, J ) 7.8 Hz), 7.22-7.37 (m, 3H), 7.40 (m, 3H), and 7.76
(m, 1H); 13C NMR (CDCl3, 75 MHz) δ 21.2, 28.5, 39.5, 48.8,
55.0, 58.1, 111.1, 112.3, 117.6, 125.5, 125.7, 128.1, 129.6, 129.9,
130.0, 131.1, 134.4, 140.5, 141.0, 141.1, 144.1, 160.0, and 170.9;
HRMS calcd for C26H31NO3S 449.2025, found 449.2027.
2-ter t-Bu tyl-5-m eth oxy-4-(2-p-tolysu lfen ylp h en yl)-1,4-
d ih yd r o-2H-isoqu in olin -3-on e (30). To a solution contain-
ing 0.33 g (0.7 mmol) of 29 in 25 mL of CH2Cl2 was added
0.11 mL of triethylamine followed by 0.31 g (1.5 mmol) of
trifluoroacetic anhydride. After 10 min of stirring, the reaction
mixture was diluted with CH2Cl2, washed with 10% HCl and

4264 J . Org. Chem., Vol. 63, No. 13, 1998
Padwa and Kuethe
a saturated NaHCO3 solution, and dried over MgSO4. Re-
moval of the solvent under reduced pressure left a colorless
oil which was subjected to silica gel chromatography. The first
product eluted from the column (50% yield) contained a
colorless oil whose structure was assigned as 30 on the basis
of its spectral properties: IR (neat) 2966, 1637, 1463, 1260,
and 728 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.47 (s, 9H), 2.32
(s, 3H), 3.60 (s, 3H), 4.67 (d, 1H, J ) 17.0 Hz), 4.82 (d, 1H, J
) 17.0 Hz), 5.77 (s, 1H), 6.69 (d, 1H, J ) 8.2 Hz), 6.84 (m,
2H), 7.05 (m, 3H), 7.25 (m, 5H); 13C NMR (CDCl3, 75 MHz) δ
21.1, 28.1, 46.9, 47.7, 55.4, 57.7, 108.8, 117.3, 124.7, 126.6,
127.0, 127.7, 127.8, 129.6, 131.0, 131.3, 133.4, 135.0, 136.2,
137.5, 142.6, 156.3, and 169.9; HRMS calcd for C26H29NO2S
431.1919, found 431.1912.
136.1, 136.6, 140.0, 143.0, 146.8, and 168.4; HRMS calcd for
C24H25NO2S 391.1606, found 391.1602.
N -t er t -Bu t yl-N -cycloh e x-1-e n ylm e t h yl-2-(2-p -t olyl-
su lfen ylp h en yl)a ceta m id e. Following the general proce-
dure, treatment of 1.3 g (5.0 mmol) of carboxylic acid 17 with
1.9 g (11.6 mmol) of cyclohexenylamine43 gave 1.8 g (88%) of
N-tert-butyl-N-cyclohex-1-enylmethyl-2-(2-p-tolylsulfenylphe-
nyl)acetamide as a colorless oil: IR (neat) 2925, 1645, 1488,
1196, and 748 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.43 (s, 9H),
1.55-1.63 (m, 4H), 1.80 (m, 2H), 2.00 (m, 2H), 2.29 (s, 3H),
3.67 (s, 2H), 3.74 (s, 2H), 5.64 (brs, 1H), 7.08 (q, 4H, J ) 8.4
Hz), and 7.14-7.34 (m, 4H); 13C NMR (CDCl3, 75 MHz) δ 21.0,
22.5, 24.8, 26.4, 28.4, 41.2, 50.6, 57.3, 121.2, 127.4, 127.7, 129.7,
129.8, 130.2, 132.5, 133.0, 134.7, 134.8, 136.5, 138.1, and 171.9;
HRMS calcd for C26H33NOS 407.2283, found 407.2282.
N -t er t -Bu t yl-N -cycloh e x-1-e n ylm e t h yl-2-(2-p -t olyl-
su lfin ylp h en yl)a ceta m id e (34). Treatment of 0.23 g (0.56
mmol) of the above sulfide with 0.1 mL of a 16% aqueous
solution of TiCl3 followed by reaction with 0.25 mL of 30% H2O2
afforded 0.2 g (84%) of 34 as a clear oil: IR (neat) 2925, 1645,
1196, and 755 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.43 (s, 9H),
1.65 (m, 4H), 1.86 (m, 2H), 2.07 (m, 2H), 2.33 (s, 3H), 3.73 (s,
2H), 3.80 (s, 2H), 5.67 (brs, 1H), 7.21-7.29 (m, 3H), 7.37-
7.42 (m, 2H), 7.52 (d, 2H, J ) 8.2 Hz), and 7.74-7.77 (m, 1H);
13C NMR (CDCl3, 75 MHz) δ 21.1, 22.2, 22.3, 24.6, 26.2, 28.1,
39.1, 50.4, 57.4, 121.1, 125.3, 125.6, 127.9, 129.6, 129.8, 131.0,
134.4, 134.8, 140.9, 141.1, 143.9, and 170.6; HRMS calcd for
2-ter t-Bu tyl-7-m eth oxy-4-(2-p-tolylsu lfen ylp h en yl)-1,4-
d ih yd r o-2H-isoqu in olin -3-on e (31). The second product
eluted from the column (44% yield) was assigned as 31 on the
basis of its spectral properties: IR (neat) 2963, 1647, 1500,
1458, and 1194 cm-1 1H NMR (CDCl3, 300 MHz) δ 1.51 (s,
;
9H), 2.28 (s, 3H), 3.78 (s, 3H), 4.55 (d, 1H, J ) 15.5 Hz), 4.69
(d, 1H, J ) 15.5 Hz), 5.24 (s, 1H), 6.16 (m, 2H), 7.02 (d, 1H, J
) 8.1 Hz), and 7.13-7.32 (m, 8H); 13C NMR (CDCl3, 75 MHz)
δ 21.0, 28.3, 47.3, 52.0, 55.3, 57.8, 110.0, 113.4, 127.4, 127.7,
128.1, 128.4, 129.7, 130.9, 131.1, 133.0, 133.2, 133.6, 136.0,
136.5, 141.9, 158.1, and 170.3; HRMS calcd for C26H29NO2S
431.1919, found 431.1918.
N-ter t-Bu t yl-N-fu r a n -3-ylm et h yl-2-(2-p -t olylsu lfen yl-
p h en yl)a ceta m id e. Treatment of 4.2 g (43.7 mmol) of
3-furancarboxaldehyde with an excess of tert-butylamine fol-
lowed by reduction with sodium borohydride according to the
general procedure afforded 5.6 g (85%) of N-tert-butyl-N-furan-
3-ylmethylamine as a colorless liquid: bp 90-91 °C (27 mm);
C
26H33NO2S 423.2232, found 423.2230.
2-t er t -Bu t yl-4-(2-p -t olylsu lfe n ylp h e n yl)-2,4,5,6,7,8-
h exa h yd r o-1H-isoqu in olin -3-on e (37). To a solution of 0.17
g (0.4 mmol) of 34 in 20 mL of CH2Cl2 was added 0.06 mL of
triethylamine followed by 0.17 g (0.8 mmol) of trifluoroacetic
anhydride. After being stirred for 10 min, the reaction mixture
was diluted with CH2Cl2, washed with 10% HCl and a
saturated NaHCO3 solution, and dried over MgSO4. Removal
of the solvent under reduced pressure followed by silica gel
chromatography afforded 110 mg (67%) of 37 as a colorless
oil: IR (neat) 2918, 1637, 1196, and 741 cm-1; 1H NMR (CDCl3,
300 MHz) δ 1.38-1.58 (m, 4H), 1.44 (s, 9H), 1.68 (m, 2H), 1.88
(m, 2H), 2.30 (s, 3H), 3.85 (d, 1H, J ) 16.3 Hz), 3.94 (d, 1H, J
) 16.3 Hz), 4.53 (brs, 1H), and 7.05-7.25 (m, 8H); 13C NMR
(CDCl3, 75 MHz) δ 21.1, 22.3, 22.4, 26.7, 26.8, 28.0, 49.8, 53.1,
57.2, 124.2, 124.4, 127.1, 127.7, 129.2, 129.8, 131.4, 133.0,
133.5, 136.4, 136.6, 142.1, and 169.6; HRMS calcd for
1
IR (neat) 3317, 1502, 1360, and 896 cm-1; H NMR (CDCl3,
300 MHz) δ 0.78 (brs, 1H), 1.14 (s, 9H), 3.57 (s, 2H), 6.36 (s,
1H), and 7.33 (s, 2H); 13C NMR (CDCl3, 300 MHz) δ 28.6, 37.3,
50.1, 110.1, 124.7, 139.0, and 142.5.
Following the general procedure, treatment of 1.3 g (5.03
mmol) of carboxylic acid 17 with 1.6 g (10.1 mmol) of N-tert-
butyl-N-furan-3-ylmethylamine gave 1.5 g (75%) of N-tert-
butyl-N-furan-3-ylmethyl-2-(2-p-tolylsulfenylphenyl)aceta-
mide as a colorless solid: mp 104-105 °C; IR (CCl4) 2968,
1652, 1488, 1381, 1189, 1018, and 869 cm-1; 1H NMR (CDCl3,
300 MHZ) δ 1.44 (s, 9H), 2.28 (s, 3H), 3.85 (s, 2H), 4.36 (s,
2H), 6.28 (s, 1H), 7.05 (q, 4H, J ) 8.5 Hz), 7.13-7.36 (m, 6H);
13C NMR (CDCl3, 75 MHz) δ 20.9, 28.6, 41.2, 41.4, 57.7, 109.1,
124.6, 127.5, 127.8, 129.8, 129.9, 130.1, 132.4, 133.2, 134.8,
136.5, 137.7, 139.3, 143.3, and 171.4. Anal. Calcd for
C
26H31NOS 405.2126, found 405.2124.
N -t er t -B u t y l-N -(2-m e t h y lp e n t -2-e n y l)-2-(2-p -t o ly l-
su lfen ylp h en yl)a ceta m id e. Treatment of a 10.0 g (102
mmol) sample of 2-methyl-2-pentenal with excess tert-buty-
lamine followed by reduction with sodium borohydride accord-
C
24H27NO2S: C, 73.25; H, 6.92. Found: C, 73.18; H, 6.90.
N-ter t-Bu t yl-N-fu r a n -3-ylm et h yl-2-(2-p -t olylsu lfin yl-
ing to the general procedure afforded 11.1
g (70%) of
p h en yl)a ceta m id e (32). Treatment of 0.44 g (1.11 mmol) of
the above sulfide with 1.6 mL of a 16% aqueous solution of
TiCl3 followed by reaction with 0.5 mL of 30% H2O2 afforded
0.44 g (96%) of 32 as a colorless oil: IR (neat) 2968, 1645, 1374,
1033, and 727 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.45 (s, 9H),
2.34 (s, 3H), 3.84 (d, 1H, J ) 16.2 Hz), 3.93 (d, 1H, J ) 16.2
Hz), 4.34 (s, 2H), 6.32 (s, 1H), 7.18-7.47 (m, 9H), and 7.73-
7.76 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ 21.2, 28.5, 39.5,
41.3, 58.0, 108.9, 124.3, 125.5, 126.0, 128.2, 129.8, 130.0, 131.3,
134.6, 139.2, 140.9, 141.2, 143.7, 144.0, and 170.5; HRMS calcd
for C24H27NO3S 409.1712, found 409.1702.
N-tert-butyl-(2-methylpent-2-enyl)amine: IR (neat) 3320, 2958,
1448, and 1225 cm-1; 1H NMR (CDCl3, 300 MHz) δ 0.70 (brs,
1H), 0.95 (t, 3H, J ) 7.5 Hz), 1.11 (s, 9H), 1.65 (s, 3H), 2.02
(m, 2H), 3.06 (s, 2H), 5.29 (t, 1H, J ) 1 Hz); 13C NMR (CDCl3,
75 MHz) δ 13.9, 14.9, 20.9, 28.9, 49.9, 50.5, 126.9, and 133.6.
Following the general procedure, treatment of 1.3 g (5.0
mmol) of carboxylic acid 17 with 1.7 g (11.1 mmol) of N-tert-
butyl(2-methylpent-2-enyl)amine afforded 1.8 g (91%) of N-tert-
butyl-N-(2-methylpent-2-enyl)-2-(2-p-tolylsulfenylphenyl)ace-
tamide as a colorless solid: mp 61-62 °C; IR (CCl4) 2961, 1645,
1
1388, 1196, 805, and 748 cm-1; H NMR (CDCl3, 300 MHz) δ
5-ter t-Bu t yl-7-(2-p -t olylsu lfen ylp h en yl)-5,7-d ih yd r o-
4H-fu r o[3,2-c]p yr id in -6-on e (33). To a solution of 0.37 g
(0.9 mmol) of 32 in 25 mL of CH2Cl2 was added 0.14 mL of
triethylamine followed by 0.34 g (1.8 mmol) of trifluoroacetic
anhydride. After being stirred for 10 min, the reaction mixture
was diluted with CH2Cl2, washed with 10% HCl and a
saturated NaHCO3 solution, and dried over MgSO4. Removal
of the solvent under reduced pressure followed by silica gel
chromatography afforded 240 mg (68%) of 33 as a clear oil:
0.95 (t, 3H, J ) 7.5 Hz), 1.43 (s, 9H), 1.54 (s, 3H), 2.06 (m,
2H), 2.91 (s, 3H), 3.70 (s, 2H), 3.72 (s, 2H), 5.41 (t, 1H, J ) 7.0
Hz), 7.12 (m, 4H), and 7.27 (m, 4H); 13C NMR (CDCl3, 75 MHz)
δ 14.1, 14.3, 20.8, 21.0, 28.4, 41.1, 51.5, 57.4, 126.0, 127.3,
127.6, 129.6, 129.8, 130.4, 131.0, 132.4, 132.8, 135.0, 136.5,
137.9, and 171.9. Anal. Calcd for C25H33NOS: C, 75.90; H,
8.41; N, 3.54. Found: C, 75.68; H, 8.31; N, 3.44.
N -t er t -B u t y l-N -(2-m e t h y lp e n t -2-e n y l)-2-(2-p -t o ly l-
su lfin ylp h en yl)a ceta m id e (35). Treatment of a 0.89 g (2.3
mmol) sample of the above sulfide with 3.3 mL of a 16%
1
IR (neat) 2965, 1641, 1463, and 1190 cm-1; H NMR (CDCl3,
300 MHz) δ 1.51 (s, 9H), 2.29 (s, 3H), 4.46 (d, 2H, J ) 3.9 Hz),
5.33 (t, 1H, J ) 3.9 Hz), 6.25 (d, 1H, J ) 1.8 Hz), and 7.03-
7.27 (m, 9H); 13C NMR (CDCl3, 75 MHz) δ 21.0, 28.1, 42.4,
48.5, 58.5, 107.6, 112.3, 127.4, 128.2, 129.7, 131.1, 133.2, 133.5,
(43) De Kimpe, N.; Stanoeva, E.; Verhe, R.; Schamp, N. Synthesis
1988, 587.

Pummerer Reactions of Amido Sulfoxides
J . Org. Chem., Vol. 63, No. 13, 1998 4265
aqueous solution of TiCl3 followed by reaction with 1.0 mL of
30% H2O2 gave 0.8 g (86%) of 35 as a colorless oil: IR (neat)
2961, 1645, 1388, 1189, and 1033 cm-1; 1H NMR (CDCl3, 300
MHz) δ 0.99 (t, 3H, J ) 7.6 Hz), 1.43 (s, 9H), 1.56 (s, 3H), 2.12
(m, 2H), 2.34 (s, 3H), 3.75 (s, 2H), 3.78 (s, 2H), 5.41 (t, 1H, J
) 7.0 Hz), 7.25 (m, 3H), 7.39 (m, 2H), 7.52 (d, 2H, J ) 8.1 Hz),
and 7.76 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ 14.1, 14.3, 20.7,
21.2, 28.2, 28.3, 39.2, 51.3, 57.5, 125.5, 125.7, 126.0, 128.0,
129.7, 130.8, 131.1, 134.9, 141.0, 141.1, 144.0, and 170.7;
HRMS calcd for C25H33NO2S 411.2232, found 411.2230.
1-ter t-Bu tyl-4-eth yl-5-m eth yl-3-(2-p-tolylsu lfen ylph en yl)-
3,6-d ih yd r o-1H-p yr id in -2-on e (38). To a solution containing
0.72 g (1.7 mmol) of 35 in 35 mL of CH2Cl2 was added 0.3 mL
of triethylamine followed by 0.74 g (3.5 mmol) of trifluoroacetic
anhydride. After being stirred for 10 min, the reaction mixture
was diluted with CH2Cl2, washed with 10% HCl and a
saturated NaHCO3 solution, and dried over MgSO4. The
solvent was removed under reduced pressure, and the residue
was subjected to silica gel chromatography to give 0.37 g (54%)
of 38 as a colorless oil: IR (neat) 2961, 1645, 1460, 1203, and
rated from the other two isomers and exhibited the following
properties: mp 185-186 °C; IR (CCl4) 2975, 1780, 1687, 1218,
1161, and 748 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.22 (s, 3H),
1.54 (s, 9H), 2.33 (s, 3H), 3.21 (d, 1H, J ) 10.4 Hz), 4.16 (d,
1H, J ) 10.4 Hz), 4.19 (s, 1H), 5.85 (s, 1H), 7.05 (m, 2H), and
7.13-7.36 (m, 11H); 13C NMR (CDCl3, 75 MHz) δ 21.1, 27.0,
27.8, 42.9, 52.0, 54.7, 57.8, 81.5, 127.4, 127.5, 127.8, 128.3,
128.6, 128.9, 129.6, 130.2, 130.9, 131.5, 132.0, 135.7, 136.8,
137.5, 137.6, and 173.7. Anal. Calcd for C31H32F3NO3S: C,
67.01; H, 5.80; N, 2.52. Found: C, 66.84; H, 5.84; N, 2.48.
N-ter t-Bu tyl-2-(2-p-tolylsu lfen ylp h en yl)-N-(2-tr im eth -
ylsilylm eth yla llyl)a ceta m id e. To a stirred solution contain-
ing 250 mL of tert-butylamine at room temperature was added
dropwise 4.9 g (22.0 mmol) of 2-[(methylsulfonyloxy)methyl]-
3-trimethylsilylprop-1-ene.44 The resulting mixture was heated
at reflux for 1.5 h and cooled to room temperature, and the
solvent was removed under reduced pressure. The crude
mixture was purified by flash silica gel chromatography to give
4.3 g (98%) of tert-butyl(2-trimethylsilylmethylallyl)amine: IR
(neat) 2954, 1630, 1360, 1246, and 841 cm-1; 1H NMR (CDCl3,
300 MHz) δ -0.08 (s, 9H), 0.60 (brs, 1H), 1.00 (s, 9H), 1.48 (s,
2H), 2.95 (s, 2H), 4.49 (s, 1H), 4.70 (s, 1H); 13C NMR (CDCl3,
75 MHz) δ -1.20, 25.2, 29.0, 48.9, 49.9, 106.6, and 146.6.
To a solution containing 1.0 g (3.9 mmol) of carboxylic acid
17 in 40 mL of CH2Cl2 was added 0.69 g (4.3 mmol) of 1,1′-
carbonyldiimidazole. After 1 h of stirring, 0.8 g (4.0 mmol) of
the above amine was added and the mixture was heated at
reflux for 5 days. The solution was concentrated under
reduced pressure, and the residue was subjected to silica gel
chromatography to give 0.85 g (50%) of N-tert-butyl-2-(2-p-
tolylsulfenylphenyl)-N-(2-trimethylsilylmethyla llyl)a cet-
1
748 cm-1; H NMR (CDCl3, 300 MHz) δ 0.84 (t, 3H, J ) 7.6
Hz), 1.43 (s, 9H), 1.70 (s, 3H), 2.06 (m, 1H), 2.31 (s, 4H), 3.84
(d, 1H, J ) 16.8 Hz), 4.01 (d, 1H, J ) 16.8 Hz), 4.76 (s, 1H),
7.11 (m, 6H), and 7.25 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ
12.3, 15.4, 21.0, 23.0, 27.9, 50.7, 50.8, 57.1, 121.6, 126.8, 127.4,
128.8, 129.8, 131.5, 131.6, 132.5, 133.3, 136.7, 136.9, 142.1,
and 169.6; HRMS calcd for
393.2125.
C25H31NOS 393.2126, found
N-ter t-Bu t yl-N-(2-m et h yl-3-p h en yla llyl)-2-(2-p -t olyl-
su lfen ylp h en yl)a ceta m id e. Treatment of a 25.0 g (171
mmol) sample of R-methyl-trans-cinnamaldehyde with excess
tert-butylamine followed by reduction with sodium borohydride
according to the general procedure gave 27 g (78%) of tert-
butyl(2-methyl-3-phenylallyl)amine as a colorless liquid: bp
151 °C (18 mm); IR (neat) 2961, 1445, 1225, and 691 cm-1; 1H
NMR (CDCl3, 300 MHz) δ 0.78 (brs, 1H), 1.13 (s, 9H), 1.90 (s,
3H), 3.23 (s, 2H), 6.45 (s, 1H), and 7.22 (m, 5H); 13C NMR
(CDCl3, 75 MHz) δ 16.9, 29.0, 50.1, 51.2, 124.7, 125.8, 127.8,
128.7, 138.0, and 138.1.
amide as a clear oil: IR (neat) 2954, 1652, 1381, and 833 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 0.05 (s, 9H), 1.48 (s, 11H), 2.31
(s, 3H), 3.76 (s, 2H), 3.78 (s, 2H), 4.83 (s, 1H), 5.01 (s, 1H),
and 7.06-7.33 (m, 8H); 13C NMR (CDCl3, 75 MHz) δ -1.26,
20.9, 24.7, 28.4, 40.9, 51.6, 57.3, 107.9, 127.3, 127.5, 129.7,
129.8, 130.1, 132.5, 132.8, 134.9, 136.2, 137.9, 144.2, and 171.6;
HRMS calcd for C26H37NOSSi 439.2365, found 439.2366.
N-ter t-Bu tyl-2-(2-p-tolylsu lfin ylp h en yl)-N-(2-tr im eth -
ylsilylm eth yla llyl)a ceta m id e (43). Treatment of a 0.53 g
(1.2 mmol) sample of the above sulfide with 1.7 mL of a 16%
aqueous solution of TiCl3 followed by the addition of 0.55 mL
of 30% H2O2 afforded 0.55 g (100%) of 43 as a colorless oil: IR
(neat) 2961, 1652, 1388, 1246, and 833 cm-1; 1H NMR (CDCl3,
300 MHz) δ 0.06 (s, 9H), 1.43 (s, 9H), 1.52 (m, 2H), 2.30 (s,
3H), 3.78 (s, 2H), 3.87 (m, 2H), 4.87 (s, 1H), 4.98 (s, 1H), 7.20
(m, 3H), 7.34 (m, 2H), 7.55 (d, 2H, J ) 7.8 Hz), and 7.72 (m,
1H); 13C NMR (CDCl3, 75 MHz) δ -1.5, 20.9, 24.4, 28.0, 38.8,
51.2, 57.2, 107.5, 125.2, 125.6, 127.8, 129.3, 129.8, 130.8, 134.6,
140.5, 140.9, 144.1, 144.2, and 170.3; HRMS calcd for
Following the general procedure, treatment of 1.3 g (5.0
mmol) of acid 17 with 2.5 g (12.1 mmol) of tert-butyl(2-methyl-
3-phenylallyl)amine afforded 2.0 g (88%) of N-tert-butyl-N-(2-
methyl-3-phenylallyl)-2-(2-p-tolylsulfenylphenyl)acetamide as
a clear oil: IR (neat) 2966, 1644, 1484, 1386, 1190, and 742
1
cm-1; H NMR (CDCl3, 300 MHz) δ 1.49 (s, 9H), 1.80 (s, 3H),
2.26 (s, 3H), 3.81 (s, 2H), 3.90 (s, 2H), 6.54 (s, 1H), 7.00 (d,
2H, J ) 8.3 Hz), 7.07 (d, 2H, J ) 8.3 Hz), and 7.14-7.37 (m,
9H); 13C NMR (CDCl3, 75 MHz), δ 16.1, 20.9, 28.4, 41.3, 52.2,
57.5, 124.2, 126.3, 127.5, 127.8, 128.0, 128.7, 129.7, 129.8,
130.1, 132.4, 133.1, 134.8, 135.4, 136.4, 137.5, 137.8, and 172.0;
HRMS calcd for C29H33NOS 443.2283, found 443.2280.
N-ter t-Bu t yl-N-(2-m et h yl-3-p h en yla llyl)-2-(2-p -t olyl-
su lfin ylp h en yl)a ceta m id e (39). The reaction of a 1.9 g (4.4
mmol) sample of the above sulfide with 6.3 mL of a 16%
aqueous solution of TiCl3 followed by the addition of 2.0 mL
of 30% H2O2 afforded 1.6 g (79%) of 39 as a white foam: IR
(CCl4) 2980, 1644, 1190, 1029, and 749 cm-1; 1H NMR (CDCl3,
300 MHz) δ 1.49 (s, 9H), 1.84 (s, 3H), 2.31 (s, 3H), 3.82 (s,
2H), 3.92 (s, 2H), 6.49 (s, 1H), 7.16 (d, 2H, J ) 8.1 Hz), 7.22-
7.48 (m, 10H), and 7.80 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ
15.6, 20.7, 27.9, 38.8, 51.6, 57.2, 123.7, 125.1, 125.5, 126.0,
127.6, 127.7, 128.2, 129.3, 129.5, 130.8, 134.3, 134.9, 136.7,
140.6, 140.7, 143.6, and 170.4; HRMS calcd for C29H33NO2S
459.2232, found 459.2229.
C
26H37NO2SSi 455.2314, found 455.2312.
1-ter t-Bu t yl-3-(2-p -t olylsu lfen ylp h en yl)-5-t r im et h yl-
silylm eth yl-3,4-d ih yd r o-1H-p yr id in -2-on e (45). To a solu-
tion containing 0.21 g (0.5 mmol) of 43 in 30 mL of CH2Cl2
was added 0.07 mL of triethylamine followed by 0.19 g (0.9
mmol) of trifluoroacetic anhydride. After being stirred for 10
min, the reaction mixture was diluted with CH2Cl2, washed
with 10% HCl and a saturated NaCO3 solution, and dried over
MgSO4. The solvent was removed under reduced pressure,
and the crude oil was chromatographed on silica gel. The first
product eluted from the column contained a colorless oil (45%)
whose structure was assigned as 45: IR (neat) 2954, 1659,
1
1211, and 848 cm-1; H NMR (CDCl3, 300 MHz) δ -0.01 (s,
9H), 1.49 (s, 2H), 1.52 (s, 9H), 2.15 (dd, 1H, J ) 16.1 and 6.7
Hz), 2.33 (s, 3H), 2.46 (m, 1H), 4.32 (dd, 1H, J ) 12.3 and 6.7
Hz), 6.05 (s, 1H), 7.09 (d, 2H, J ) 8.2 Hz), 7.19 (m, 3H), and
7.31 (m, 3H); 13C NMR (CDCl3, 75 MHz) δ -1.5, 21.0, 24.7,
28.9, 34.1, 47.2, 57.5, 117.7, 119.9, 127.4, 127.9, 129.2, 129.8,
130.2, 133.3, 133.6, 134.8, 136.3, 142.1, and 169.8; HRMS calcd
for C26H35NOSSi 437.2209, found 437.2208.
Tr iflu or oa cetic Acid [1-ter t-Bu tyl-3-m eth yl-5-oxo-4-(2-
p-tolylsu lfen ylp h en ylp yr r olid in -3-yl]p h en yl Meth yl Es-
ter (41). To a solution containing 0.47 g (1.0 mmol) of a
sample of 39 in 30 mL of CH2Cl2 was added 0.16 mL of
triethylamine followed by 0.43 g (2.0 mmol) of trifluoroacetic
anhydride. After being stirred for 10 min, the reaction mixture
was diluted with CH2Cl2, washed with 10% HCl and a
saturated NaHCO3 solution, and dried over MgSO4. The
solvent was removed under reduced pressure, and the residue
subjected to silica gel chromatography to afford 41 (65%) as a
mixture of three diastereomers. One diastereomer was sepa-
1-ter t-Bu t yl-3-(2-p -t olylsu lfen ylp h en yl)-5-t r im et h yl-
silylm eth yl-3,6-d ih yd r o-1H-p yr id in -2-on e (46). A second
(44) Trost, B. M.; Vincent, J . E. J . Am. Chem. Soc. 1980, 102, 5680.

4266 J . Org. Chem., Vol. 63, No. 13, 1998
Padwa and Kuethe
product isolated (45% yield) was identified as 46: IR (neat)
2954, 1645, 1246, and 841 cm-1; 1H NMR (CDCl3, 300 MHz) δ
-0.6 (s, 9H), 1.44 (s, 2H), 1.46 (s, 9H), 2.30 (s, 3H), 3.88 (m,
2H), 4.76 (m, 1H), 5.18 (m, 1H), 7.08 (m, 3H), and 7.18 (m,
5H); 13C NMR (CDCl3, 75 MHz) δ -1.3, 21.0, 23.9, 28.0, 48.8,
50.2, 57.4, 119.0, 127.3, 127.5, 128.6, 129.7, 130.0, 130.9, 133.1,
133.3, 135.4, 136.4, 143.5, and 169.4; HRMS calcd for
(s, 2H), 5.95 (s, 2H), 6.05 (d, 1H, J ) 9.8 Hz), 6.73 (s, 2H),
6.79 (d, 1H, J ) 7.8 Hz), 7.03 (d, 1H, J ) 9.8 Hz), 7.31 (m,
3H), and 7.47 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ 28.7, 48.7,
57.7, 101.1, 106.2, 108.4, 115.8, 118.7, 127.6, 129.1, 130.6,
133.4, 137.9, 145.9, 146.5, 148.1, and 168.8. Anal. Calcd for
C
21H23NO3S: C, 68.27; H, 6.27; N, 3.79. Found: C, 68.00; H,
6.27; N, 3.72.
C
26H35NOSSi 437.2209, found 437.2200.
N-Ben zyl-N-ter t-bu tyl-3-ph en ylsu lfen ylacr ylam ide. Fol-
3-Ben zen esu lfin yl-N-b en zo[1,3]d ioxol-5-ylm et h yl-N-
ter t-bu tyla cr yla m id e (57). Treatment of 2.0 g (5.4 mmol)
of the above sulfide with 7.8 mL of a 16% aqueous solution of
TiCl3 followed by 2.5 mL of 30% H2O2 gave 1.9 g (89%) of 57
as a white solid: mp 122-123 °C; IR (CCl4) 2971, 1635, 1486,
lowing the general procedure, treatment of 2.5 g (13.8 mmol)
of 3-(phenylthio)acrylic acid with 5.7 g (34.7 mmol) of N-(tert-
butyl)benzylamine afforded 4.2 g (92%) of N-benzyl-N-tert-
butyl-3-phenylsulfenylacrylamide as a white solid: mp 100-
1238, and 1032 cm-1 1H NMR (CDCl3, 300 MHz) δ 1.48 (s,
;
101 °C; IR (CCl4) 2961, 1630, 1403, 1189, and 784 cm-1; H
9H), 4.57 (s, 2H), 5.92 (s, 2H), 6.43 (d, 1H, J ) 9.9 Hz), 6.54
(d, 1H, J ) 9.9 Hz), 6.68 (s, 2H), 6.78 (d, 1H, J ) 7.7 Hz), 7.48
(m, 3H), and 7.97 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ 28.0,
49.3, 58.0, 100.9, 105.7, 108.3, 118.2, 124.7, 128.7, 129.7, 130.3,
131.8, 143.8, 146.5, 148.0, 148.6, and 165.6. Anal. Calcd for
1
NMR (CDCl3, 300 MHz) δ 1.50 (s, 9H), 4.64 (s, 2H), 6.04 (d,
1H, J ) 9.8 Hz), 7.02 (d, 1H, J ) 9.8 Hz), 7.35 (m, 8H), and
7.48 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ 28.7, 49.0, 57.7,
115.9, 125.7, 127.0, 127.6, 128.7, 129.1, 130.6, 137.9, 139.5,
145.8, and 168.9. Anal. Calcd for C20H23NOS: C, 73.81; H,
7.12; N, 4.30. Found: C, 73.83; H, 7.17; N, 4.27.
C
21H23NO4S: C, 65.43; H, 6.01; N, 3.63. Found: C, 65.26; H,
6.07; N, 3.57.
3-Ben zen esu lfin yl-N-b en zyl-N-ter t-b u t yla cr yla m id e
(50). Treatment of 1.2 g (3.5 mmol) of the above sulfide with
5.1 mL of a 16% aqueous solution of TiCl3 followed by 1.6 mL
of 30% H2O2 gave 1.0 g (83%) of 50 as a colorless solid: mp
6-ter t-Bu t yl-8-p h en ylsu lfen ylm et h ylen e-5,8-d ih yd r o-
6H-[1,3]d ioxol[4,5-g]isoqu in olin -7-on e (58). To a stirred
solution of 0.5 g (1.3 mmol) of 56 in 35 mL of CH2Cl2 at -78
°C was added 0.29 g of triethylamine followed by 0.38 g of
triflic anhydride. After being stirred for 10 min, the reaction
mixture was diluted with water, extracted with CH2Cl2, and
dried over MgSO4. The solvent was removed under reduced
pressure, and the residue was subjected to silica gel chroma-
tography. The first product eluted from the column contained
67 mg (15%) of 58 as a white solid: mp 110-111 °C; IR (CCl4)
2961, 1630, 1609, 1388, and 1246 cm-1; 1H NMR (CDCl3, 300
MHz) δ 1.43 (s, 9H), 4.81 (s, 2H), 5.97 (s, 2H), 6.78 (m, 3H),
and 7.23 (m, 5H); 13C NMR (CDCl3, 75 MHz) δ 28.4, 50.7, 58.3,
94.5, 101.1, 106.7, 108.4, 119.3, 126.9, 127.2, 129.4, 130.7,
132.9, 146.7, 148.0, and 155.1. Anal. Calcd for C21H21NO3S:
C, 68.64; H, 5.76; N, 3.81. Found: C, 68.41; H, 5.79; N, 3.72.
2-B e n z o [1,3]d i o x o l-5-y l-N -t e r t -b u t y l-3-(p h e n y l-
su lfen yl)a cr yla m id e (59). The second product eluted from
the column contained 0.28 g (60%) of 59 as a white solid: mp
129-130 °C; IR (CCl4) 2982, 1637, 1403, 1196, and 1040 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 1.48 (s, 9H), 4.66 (s, 2H), 6.41
(d, 1H, J ) 9.9 Hz), 6.51 (d, 1H, J ) 9.9 Hz), 7.24 (m, 3H),
7.34 (m, 2H), 7.47 (m, 3H), and 7.98 (m, 2H); 13C NMR (CDCl3,
75 MHz) δ 28.1, 49.7, 58.1, 124.8, 125.2, 127.1, 128.7, 128.8,
129.8, 130.4, 138.0, 143.9, 148.6, and 165.7. Anal. Calcd for
C
20H23NO2S: C, 70.35; H, 6.79; N, 4.10. Found: C, 70.14; H,
6.77; N, 4.08.
2-ter t-Bu t yl-4-p h en ylsu lfen ylm et h ylen e-1,4-d ih yd r o-
2H-isoqu in olin -3-on e (51). To a solution of 0.51 g (1.5 mmol)
of 49 in 30 mL of CH2Cl2 at -78 °C was added 0.33 g (3.3
mmol) of triethylamine followed by 0.44 g of triflic anhydride.
After being stirred for 10 min, the reaction mixture was diluted
with water, extracted with CH2Cl2, and dried over MgSO4. The
solvent was removed under reduced pressure, and the residue
was purified by silica gel chromatography. The first product
eluted from the column contained 0.15 g (32%) of 2-tert-butyl-
4-phenylsulfenylmethylene-1,4-dihydro-2H-isoquinolin-3-one
(51) as a white solid: mp 105-106 °C; IR (CCl4) 2968, 1630,
142-143 °C; IR (CCl4) 3309, 1645, 1481, 1232, and 734 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 1.10 (s, 9H), 4.90 (brs, 1H), 5.49
(s, 1H), 5.98 (s, 2H), 6.81 (d, 1H, J ) 7.9 Hz), 6.95 (m, 2H),
7.31 (m, 3H), 7.39 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ 28.3,
50.9, 101.4, 108.4, 109.4, 120.5, 122.9, 129.2, 129.5, 129.9,
130.6, 134.8, 147.7, 148.4, 148.9, and 164.8. Anal. Calcd for
1388, and 1196 cm-1 1H NMR (CDCl3, 300 MHz) δ 1.43 (s,
;
9H), 4.91 (s, 2H), 7.22 (m, 4H), and 7.36 (m, 6H); 13C NMR
(CDCl3, 75 MHz) δ 28.4, 51.0, 58.2, 94.5, 126.1, 126.7, 127.1,
127.2, 128.7, 129.3, 130.7, 139.0, and 155.3. Anal. Calcd for
C
20H21NO3S: C, 67.58; H, 5.96; N, 3.94. Found: C, 67.48; H,
5.92; N, 3.93.
C
20H21NOS: C, 74.27; H, 6.54; N, 4.33. Found: C, 74.10; H,
N -t er t -B u t y l-N -(3,5-d im e t h o x y b e n zy l)-3-(p h e n y l-
su lfen yl)a cr yla m id e. Treatment of a 6.0 g (36 mmol) sample
of 3,5-dimethoxybenzaldehyde with a 10-fold excess of tert-
butylamine followed by reduction with sodium borohydride
according to the general procedure gave 7.7 g (96%) of tert-
butyl(3,5-dimethoxybenzyl)amine as a colorless oil: IR (neat)
2954, 1595, 1460, 1203, and 1154 cm-1; 1H NMR (CDCl3, 300
MHz) δ 0.90 (brs, 1H), 1.16 (s, 9H), 3.67 (s, 2H), 3.77 (s, 6H),
6.33 (s, 1H), and 6.51 (s, 2H); 13C NMR (CDCl3, 75 MHz) δ
29.1, 47.3, 50.5, 55.1, 98.7, 106.0, 144.0, and 160.7.
Following the general procedure, treatment of 1.3 g (7.2
mmol) of 3-(phenylthio)acrylic acid with 3.5 g (15.9 mmol) of
the above amine afforded 2.2 g (80%) of N-tert-butyl-N-(3,5-
dimethoxybenzyl)-3-(phenylsulfenyl)acrylamide as a colorless
oil: IR (neat) 2961, 1623, 1595, 1403, and 1196 cm-1; 1H NMR
(CDCl3, 300 MHz) δ 1.51 (s, 9H), 3.77 (s, 6H), 4.56 (s, 2H),
6.04 (d, 1H, J ) 9.8 Hz), 6.35 (s, 1H), 6.41 (s, 2H), 7.01 (d, 1H,
J ) 9.8 Hz), 7.36 (m, 3H), and 7.48 (m, 2H); 13C NMR (CDCl3,
75 MHz) δ 28.6, 49.1, 55.3, 57.7, 98.7, 103.7, 116.0, 127.5,
129.1, 130.6, 137.8, 142.3, 145.6, 161.2, and 168.9; HRMS calcd
for C22H27NO3S 385.1711, found 385.1712.
6.59; N, 4.22.
N-ter t-Bu t yl-2-p h en yl-3-(p h en ylsu lfen yl)a cr yla m id e
(52). The second product eluted from the column contained
210 mg (45%) of 52 as a white solid: mp 122-123 °C; IR (CCl4)
3302, 2968, 1637, 1538, and 1218 cm-1; 1H NMR (CDCl3, 300
MHz) δ 1.00 (s, 9H), 4.79 (brs, 1H), 5.53 (s, 1H), and 7.41 (m,
10H); 13C NMR (CDCl3, 75 MHz) δ 28.2, 50.8, 120.8, 128.6,
128.9, 129.2, 129.3, 129.5, 130.4, 135.1, 136.4, 149.1, and 164.7.
Anal. Calcd for C19H21NOS: C, 73.28; H, 6.80; N, 4.50.
Found: C, 73.47; H, 6.82; N, 4.45.
N-Ben zo[1,3]d ioxol-5-ylm eth yl-N-ter t-bu tyl-3-(p h en yl-
su lfen yl)a cr yla m id e. Treatment of a 20 g (133 mmol)
sample of piperonal with a 10-fold excess of tert-butylamine
followed by reduction with sodium borohydride according to
the general procedure gave 24.4 g (88%) of benzo[1,3]dioxol-
5-ylmethyl-tert-butylamine as a colorless liquid: bp 110 °C/
0.6 mm; IR (neat) 3317, 2961, 1488, 1246, and 1040 cm-1; H
1
NMR (CDCl3, 300 MHz) δ 0.91 (brs, 1H), 1.15 (s, 9H), 3.61 (s,
2H), 5.89 (s, 2H), 6.74 (m, 2H), and 6.84 (s, 1H); 13C NMR
(CDCl3, 75 MHz) δ 29.0, 46.9, 50.4, 100.6, 107.9, 108.8, 121.0,
135.4, 146.2, and 147.5.
Following the general procedure, treatment of 2.5 g (13.9
mmol) of 3-(phenylthio)acrylic acid with 6.6 g (31.9 mmol) of
the above amine afforded 4.4 g (85%) of N-benzo[1,3]dioxol-
5-ylmethyl-N-tert-butyl-3-(phenylsulfenyl)acrylamide as a white
solid: mp 97-98 °C; IR (CCl4) 2968, 1630, 1488, 1232, 1189,
and 1033 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.49 (s, 9H), 4.54
3-B e n ze n e s u lfin y l-N -t er t -b u t y l-N -(3,5-d im e t h o x y -
ben zyl)a cr yla m id e (60). Treatment of 2.2 g (5.7 mmol) of
the above sulfide with 8.2 mL of a 16% aqueous solution of
TiCl3 followed by 2.6 mL of 30% H2O2 gave 2.1 g (90%) of 60
as a clear oil: IR (neat) 2961, 1637, 1595, 1403, 1203, and 1154
1
cm-1; H NMR (CDCl3, 300 MHz) δ 1.49 (s, 9H), 3.77 (s, 6H),
4.60 (s, 2H), 6.36 (s, 3H), 6.42 (d, 1H, J ) 10.0 Hz), 6.54 (d,

Pummerer Reactions of Amido Sulfoxides
J . Org. Chem., Vol. 63, No. 13, 1998 4267
1H, J ) 10.0 Hz), 7.41 (m, 3H), and 7.96 (m, 2H); 13C NMR
(CDCl3, 75 MHz) δ 28.1, 49.8, 55.1, 58.2, 98.7, 103.4, 124.8,
128.8, 130.0, 130.4, 140.8, 143.9, 148.4, 161.2, and 165.8. Anal.
Calcd for C22H27NO4S: C, 65.81; H, 6.78; N, 3.49. Found: C,
65.66; H, 6.79; N, 3.44.
95.4, 106.8, 106.9, 117.9, 118.3, 119.3, 122.2, 124.6, 125.7,
127.2, 128.9, 129.1, 129.7, 129.9, 130.1, 135.1, 135.6, 149.8,
150.1, 153.4, 157.3, and 164.7. Anal. Calcd for C23H26N2O2S:
C, 70.02; H, 6.64; N, 7.10. Found: C, 69.91; H, 6.69; N, 6.99.
N -t e r t -B u t y l -N -(3 -m e t h y l b u t -2 -e n y l )-3 -p h e n y l -
su lfen yla cr yla m id e. To a stirred solution of tert-butylamine
was added dropwise 20 g (134 mmol) of 4-bromo-2-methyl-2-
butene. The mixture was heated at reflux for 30 min, diluted
with water, extracted with CH2Cl2, and dried over MgSO4. The
solvent was removed under reduced pressure and the product
distilled to give 10.6 g (56%) of tert-butyl(3-methylbut-2-
enyl)amine as a colorless liquid: bp 63 °C (23 mm); IR (neat)
3302, 2962, 1438, 1353, and 1232 cm-1; 1H NMR (CDCl3, 300
MHz) δ 0.90 (brs, 1H), 1.12 (s, 9H), 1.65 (s, 3H), 1.70 (s, 3H),
3.15 (m, 2H), and 5.27 (m, 1H); 13C NMR (CDCl3, 75 MHz) δ
17.6, 25.6, 29.0, 40.1, 50.1, 123.7, and 133.4.
Following the general procedure, treatment of 1.5 g (8.3
mmol) of 3-(phenylthio)acrylic acid with 2.9 g (21 mmol) of the
above amine gave 2.5 g (97%) of N-tert-butyl-N-(3-methylbut-
2-enyl)-3-phenylsulfenylacrylamide as a clear oil: IR (CCl4)
1H NMR (CDCl3, 300 MHz) δ 1.49 (s, 9H), 1.64 (s, 3H), 1.72
(s, 3H), 3.94 (m, 2H), 5.12 (m, 1H), 6.15 (d, 1H, J ) 9.8 Hz),
7.05 (d, 1H, J ) 9.8 Hz), 7.32 (m, 3H), and 7.49 (m, 2H); 13C
NMR (CDCl3, 75 MHz) δ 17.9, 25.4, 28.9, 43.8, 57.1, 116.2,
124.0, 127.4, 129.0, 130.5, 132.7, 138.1, 144.6, and 168.0. Anal.
Calcd for C18H25NOS: C, 71.24; H, 8.30; N, 4.62. Found: C,
70.95; H, 8.29; N, 4.68.
2-ter t-Bu tyl-5,7-dim eth oxy-4-ph en ylsu lfen ylm eth ylen e-
1,4-d ih yd r o-2H-isoqu in olin -3-on e (61). To a solution of 0.8
g (2.0 mmol) of 60 in 45 mL of CH2Cl2 at -78 °C was added
0.44 g (4.4 mmol) of triethylamine followed by 0.62 g (2.2
mmol) of triflic anhydride. After being stirred for 10 min, the
reaction was diluted with water, extracted with CH2Cl2, and
dried over MgSO4. The solvent was removed under reduced
pressure, and the residue purified by silica gel chromatogra-
phy. The major product eluted from the column contained 0.48
g (63%) of 61 as a colorless solid: mp 165-166 °C; IR (CCl4)
2968, 1623, 1388, 1324, and 1189 cm-1; 1H NMR (CDCl3, 300
MHz) δ 1.39 (s, 9H), 3.82 (s, 6H), 4.14 (d, 1H, J ) 15.0 Hz),
4.31 (d, 1H, J ) 15.0 Hz), 6.03 (s, 1H), 6.42 (d, 1H, J ) 2.3
Hz), 6.46 (d, 1H, J ) 2.3 Hz), 7.29 (m, 3H), and 7.45 (m, 2H);
13C NMR (CDCl3, 75 MHz) δ 28.9, 47.8, 55.3, 55.7, 57.5, 98.1,
104.0, 118.2, 126.1, 128.3, 129.2, 133.6, 134.5, 141.8, 143.8,
158.7, 160.9, and 166.7. Anal. Calcd for C22H25NO3S: C,
68.90; H, 6.57; N, 3.65. Found: C, 68.87; H, 6.58; N, 3.62.
3-P h en ylsu lfen ylpr opyn oic Acid ter t-Bu tyl(3,5-dim eth -
oxyben zyl)a m id e (62). The minor product eluted from the
column contained 60 mg (8%) of 62 as a colorless oil: IR (neat)
2961, 2153, 1630, 1381, and 1196 cm-1; 1H NMR (CDCl3, 300
MHz) δ 1.45 (s, 9H), 3.79 (s, 6H), 4.84 (s, 2H), 6.39 (s, 1H),
6.44 (s, 2H), 7.17 (m, 5H); 13C NMR (CDCl3, 75 MHz) δ 28.2,
50.9, 55.2, 58.2, 79.6, 94.3, 98.9, 103.8, 126.5, 127.0, 129.2,
130.4, 141.5, 155.1, and 161.0; HRMS calcd for C22H25NO3S
383.1555, found 383.1553.
1′-ter t-Bu t yl-2-h yd r oxy-1-m et h yl-4′-p h en ylsu lfen yl-
m et h ylen e-1,2-d ih yd r osp ir o[in d ole-3,3′-p yr r olod in ]-5′-
on e (68). Treatment of a 10 g (62.8 mmol) sample of
1-methylindole-3-carboxaldehyde with a 10-fold excess of tert-
butylamine followed by reduction with sodium borohydride
according to the general procedure gave 12.4 g (91%) of tert-
butyl(1-methylindol-3-yl)methylamine as a white solid: mp
53-54 °C; IR (CCl4) 3309, 2961, 1467, and 734 cm-1; 1H NMR
(CDCl3, 300 MHz) δ 1.23 (s, 10H), 3.74 (s, 3H), 3.93 (s, 2H),
7.09 (m, 2H), 7.25 (m, 2H), and 7.63 (d, 1H, J ) 7.8 Hz); 13C
NMR (CDCl3, 75 MHz) δ 29.1, 32.6, 37.7, 50.6, 109.2, 118.7,
118.8, 121.5, 127.1, and 127.4.
Following the general procedure, treatment of 0.25 g (1.4
mmol) of 3-(phenylthio)acrylic acid with the above amine gave
0.52 g (100%) of N-tert-butyl-N-(1-methyl-1H-indol-3-ylm-
ethyl)-3-phenylsulfenylacrylamide which was used in the next
step without further purification. To a solution of the above
sulfide in 60 mL of CH2Cl2 at 0 °C was added 0.26 g (1.5 mmol)
of m-chloroperbenzoic acid. After being stirred for 1 h, the
reaction was diluted with water, extracted with CHCl3, and
dried over MgSO4. Filtration of the extracts through a short
pad of silica gel and removal of the solvent under reduced
pressure afforded N-tert-butyl-N-(1-methyl-1H-indol-3-ylm-
ethyl)-3-phenylsulfinylacrylamide (66) as a white foam which
was immediately used in the next step without purification.
To a stirred solution of 0.54 g (1.4 mmol) of 66 at -78 °C
was added 0.3 g (3.0 mmol) of triethylamine followed by 0.43
g (1.5 mmol) of triflic anhydride. After 10 min of stirring, the
reaction was diluted with water, extracted with CH2Cl2, and
dried over MgSO4. Removal of the solvent under reduced
pressure followed by silica gel chromatography gave 0.28 g
(51%) of 68 as a white solid which consisted of an inseparable
2:1 mixture of diastereomers: mp 179-180 °C; IR (CCl4) 3324,
2975, 1630, 1488, 1317, and 1203 cm-1; 1H NMR (CDCl3, 300
MHz) major diastereomer δ 1.40 (s, 9H), 2.98 (s, 3H), 3.01 (d,
1H, J ) 11.1 Hz) 3.38 (d, 1H, J ) 12.8 Hz), 3.47 (d, 1H, J )
12.8 Hz), 5.14 (d, 1H, J ) 11.1 Hz), 5.43 (s, 1H), 6.54 (m, 1H),
6.81 (m, 1H), 7.26 (m, 2H), 7.39 (m, 3H), and 7.50 (m, 2H);
minor diastereomer δ 1.38 (s, 9H), 2.87 (s, 3H), 2.53 (brs, 1H),
3.58 (d, 1H, J ) 12.7 Hz), 3.97 (d, 1H, J ) 12.7 Hz), 5.27 (m,
1H), 5.43 (s, 1H), 6.54 (m, 1H), 6.81 (m, 1H), 7.26 (m, 2H),
7.39 (m, 3H), and 7.50 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ
28.3, 28.5, 30.5, 31.5, 47.1, 51.3, 53.2, 54.3, 56.5, 56.8, 92.1,
3-B e n ze n e s u lfin y l-N -t er t -b u t y l-N -(3-m e t h y lb u t -2-
en yl)a cr yla m id e (69). Treatment of 1.3 g (4.4 mmol) of the
above sulfide with 6.4 mL of a 16% aqueous solution of TiCl3
followed by 2.0 mL of 30% H2O2 afforded 0.95 g (67%) of 69 as
a white foam: IR (neat) 2968, 1630, 1403, 1182, and 1040 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 1.49 (s, 9H), 1.62 (s, 3H), 1.73
(s, 3H), 3.99 (brs, 2H), 5.10 (m, 1H), 6.41 (d, 1H, J ) 10.0 Hz),
6.62 (d, 1H, J ) 10.0 Hz), 7.48 (m, 3H), and 7.95 (m, 2H); 13
C
NMR (CDCl3, 75 MHz) δ 17.9, 25.4, 28.4, 44.8, 57.6, 122.3,
124.8, 128.9, 130.4, 130.9, 134.0, 143.9, 146.3, and 165.1;
HRMS calcd for C18H25NO2S 319.1606, found 319.1602.
5-t er t -Bu t yl-3-isop r op e n yl-2-p h e n ylsu lfin ylm e t h yl-
en ecyclop en ta n on e (70). To a solution of 0.83 g (2.6 mmol)
of 68 in 50 mL of CH2Cl2 at -78 °C was added 0.66 g (6.5
mmol) of triethylamine followed by 0.74 g (2.6 mmol) of triflic
anhydride. After being stirred for 10 min, the reaction mixture
was diluted with water, extracted with CH2Cl2, and dried over
MgSO4. The solvent was removed under reduced pressure and
the residue chromatographed on silica gel to give 0.45 g (57%)
of 70 as a clear oil: IR (neat) 3075, 2968, 1673, 1451, and 1239
1
cm-1; H NMR (CDCl3, 300 MHz) δ 1.44 (s, 9H), 1.69 (s, 3H),
3.22 (dd, 1H, J ) 10.0 and 2.6 Hz), 3.55 (m, 1H), 3.68 (m, 1H),
4.89 (s, 1H), 4.96 (s, 1H), 7.25 (m, 3H), and 7.40 (m, 3H); 13C
NMR (CDCl3, 75 MHz) δ 18.0, 27.3, 42.5, 48.2, 54.2, 113.4,
127.2, 128.9, 129.7, 130.6, 131.9, 134.4, 142.7, and 166.6;
HRMS calcd for C18H23NOS 301.1500, found 301.1498.
N -t er t -Bu t yl-N -(2-m e t h yl-3-p h e n yla llyl)-3-p h e n yl-
su lfen yla cr yla m id e. Following the general procedure, treat-
ment of 1.5 g (8.3 mmol) of 3-(phenylthio)acrylic acid with 3.9
g (19 mmol) of tert-butyl(2-methyl-3-phenylallyl)amine af-
forded 2.9 g (96%) of N-tert-butyl-N-(2-methyl-3-phenylallyl)-
3-phenylsulfenylacrylamide as a white solid, mp 117-118 °C;
IR (CCl4) 2968, 1630, 1559, 1403, and 1189 cm-1 1H NMR
;
(CDCl3, 300 MHz) δ 1.54 (s, 9H), 1.84 (s, 3H), 3.94 (s, 2H),
6.11 (d, 1H, J ) 9.9 Hz), 6.46 (s, 1H), 7.03 (d, 1H, J ) 9.9 Hz),
7.26 (m, 8H), and 7.46 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ
15.8, 28.1, 51.9, 56.9, 115.9, 124.8, 126.1, 127.2, 127.8, 128.4,
128.8, 130.2, 135.1, 137.0, 137.6, 144.8, and 168.4. Anal.
Calcd for C23H27NOS: C, 75.58; H, 7.45; N, 3.83. Found: C,
75.38; H, 7.47; N, 3.80.
3-P h en ylsu lfin yl-N-ter t-Bu t yl-N-(2-m et h yl-3-p h en yl-
a llyl)a cr yla m id e (71). Treatment of 2.3 g (6.3 mmol) of the
above sulfide with 9.1 mL of a 16% aqueous solution of TiCl3
followed by 2.8 mL of 30% H2O2 gave 1.4 g (56%) of 71 as a
colorless oil: IR (neat) 2975, 1637, 1403, 1189, and 1033 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 1.55 (s, 9H), 1.85 (s, 3H), 4.01
(s, 2H), 6.44 (s, 1H), 6.48 (d, 1H, J ) 9.8 Hz), 6.61 (d, 1H, J )
9.8 Hz), 7.23 (d, 2H, J ) 7.5 Hz), 7.31 (m, 2H), 7.48 (m, 4H),

4268 J . Org. Chem., Vol. 63, No. 13, 1998
Padwa and Kuethe
7.97 (d, 2H, J ) 6.8 Hz); 13C NMR (CDCl3, 75 MHz) δ 16.0,
28.1, 53.0, 57.9, 124.9, 125.1, 126.6, 128.2, 128.6, 129.0, 130.2,
130.6, 134.8, 136.8, 144.0, 148.5, and 165.9; HRMS calcd for
1374, and 1196 cm-1
9H), 1.84 (s, 3H), 4.29 (s, 2H), 6.47 (s, 1H), 7.19-7.40 (m, 10H);
13C NMR (CDCl3, 75 MHz) δ 15.9, 28.2, 54.0, 58.0, 94.4, 103.2,
125.4, 126.5, 127.1, 127.3, 128.2, 128.8, 129.4, 135.5, 137.4,
;
1H NMR (CDCl3, 300 MHz) δ 1.51 (s,
C
23H27NO2S 381.1762, found 381.1763.
1-ter t-Bu tyl-4-(h yd r oxyp h en ylm eth yl)-4-m eth yl-3-p h e-
and 160.9; HRMS calcd for C23H25NOS 363.1657, found
n ylsu lfen ylm eth ylen ep yr r olid in -2-on e (72). To a solution
of 0.8 g (2.1 mmol) of 71 in 50 mL of CH2Cl2 at -78 °C was
added 0.47 g (4.6 mmol) of triethylamine followed by 0.62 g
(2.2 mmol) of triflic anhydride. After being stirred for 10 min,
the reaction mixture was diluted with water, extracted with
CH2Cl2, and dried over MgSO4. The solvent was removed
under reduced pressure and the residue purified by silica gel
chromatography. The major product 72 isolated (0.32 g (40%))
as a colorless solid: mp 175-176 °C; IR (CCl4) 3366, 2975,
1623, 1537, and 1317 cm-1; 1H NMR (CDCl3, 300 MHz) δ 1.21
(s, 3H), 1.42 (s, 9H), 2.35 (d, 1H, J ) 2.8 Hz), 3.10 (d, 1H, J )
12.4 Hz), 3.89 (d, 1H, J ) 12.4 Hz), 4.94 (d, 1H, J ) 2.8 Hz),
5.09 (s, 1H), and 7.37 (m, 10 H); 13C NMR (CDCl3, 75 MHz) δ
16.4, 28.5, 45.3, 50.3, 56.4, 74.8, 119.2, 127.9, 128.0, 128.1,
128.4, 129.7, 135.6, 140.2, 158.9, and 164.6. Anal. Calcd for
364.1531 [M + H]+.
Ack n ow led gm en t. We gratefully acknowledge the
National Cancer Institute (CA-26750) for generous
support of this work. The use of high-field NMR
spectrometers used in these studies was made possible
through equipment grants from the NIH and NSF. We
also thank Scott M. Sheehan for determining the X-ray
crystal structure of compound 41.
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 an ORTEP drawing for structure 41 (29 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
C
23H27NO2S: C, 72.41; H, 7.13; N, 3.67. Found: C, 72.44; H,
7.11; N, 3.65.
3-P h en ylsu lfen ylp r op yn oic Acid ter t-Bu tyl(2-m eth yl-
3-p h en ya llyl)a m id e (73). The minor product 73 was isolated
(0.11 g (14%)) as a colorless oil: IR (neat) 2968, 2143, 1623,
J O972093H