Rhodium(II)-catalyzed aziridination of allyl-substituted sulfonamides and carbamates

Article abstract of DOI:10.1021/jo048990k

Several unsaturated sulfonamides underwent intramolecular aziridination when treated with PhI-(OAc)₂, MgO, and catalytic Rh ₂(OAc)₄ to give bicyclic aziridines in excellent yield. Treatment of the resulting azabicyclic sul

Full text of DOI:10.1021/jo048990k

Rh od iu m (II)-Ca ta lyzed Azir id in a tion of Allyl-Su bstitu ted
Su lfon a m id es a n d Ca r ba m a tes
Albert Padwa,* Andrew C. Flick, Carolyn A. Leverett, and Thomas Stengel
Department of Chemistry, Emory University, Atlanta, Georgia 30322
chemap@emory.edu
Received J une 15, 2004
Several unsaturated sulfonamides underwent intramolecular aziridination when treated with PhI-
(OAc)2, MgO, and catalytic Rh2(OAc)4 to give bicyclic aziridines in excellent yield. Treatment of
the resulting azabicyclic sulfonamides in methanol in the presence of p-TsOH resulted in exclusive
opening of the aziridine ring at the most substituted position affording six- and seven-membered
ring products in high yield. In contrast, the intramolecular aziridination of several cycloalkenyl-
substituted carbamates did not require a Rh(II) catalyst and proceeded via an iminoiodinane
intermediate. The resulting tricyclic aziridines underwent ring opening when treated with various
nucleophiles to give anti-derived products as expected for nucleophilic attack at the three-membered
ring. The iodine(III)-mediated reaction of a 3-indolyl-substituted carbamate, however, required a
Rh(II) catalyst. The expected aziridine was not observed, but rather simultaneous spirocyclization
of C3 and stereoselective syn-acylation at C2 occurred to give compound 41, whose structure was
unequivocally established by an X-ray crystallographic study. The reaction proceeds in a stepwise
manner via a metal-free zwitterionic intermediate which is attacked by a nucleophilic reagent on
the same side of the amide anion. Related reactions occurred with both a 2-indolyl- and
3-benzofuranyl-substituted carbamate but with lower stereoselectivity.
The chemistry of metal carbene complexes has pro-
vided chemists with exceptionally fertile ground for the
design and development of new stereoselective bond
formation processes for application to organic synthesis.1-7
Metallocarbenoid reactions involving X-H insertion
(X ) C, O, N),8 cyclopropanation,1 or ylide generation2
have been extensively used to prepare complex synthetic
targets. The development of chiral catalysts for asym-
metric reaction of metal carbenoids has also been widely
studied9 since the first report by Nozaki and co-workers
that decomposition of ethyl diazoacetate in the presence
of copper(II) complex with a chiral Schifff base ligand
resulted in enantioselective cyclopropanation of styrene.10
In recent years, chiral rhodium catalysts have been
investigated with considerable success for generating
enantiomerically enriched products in many important
transformations of diazo compounds, such as cyclopro-
panations and C-H insertions.1
While the transition-metal-catalyzed carbon trans-
fer11,12 to olefins is a highly developed process, signifi-
cantly fewer reagents and procedures are available for
the analogous nitrogen atom transfer.13 Addition of a
metallo nitrene to an olefin followed by aziridine ring
opening represents an attractive approach to a variety
of medicinally important compounds (Scheme 1).14 Vicinal
amino alcohols are found in a substantial number of
bioactive compounds15 and are also utilized for asym-
(1) For leading references, see: Doyle, M. P.; McKervey, M. A.; Ye,
T. Modern Catalytic Methods for Organic Synthesis with Diazo
Compounds; J ohn Wiley and Sons: New York, 1998.
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A.; Weingarten, M. D. Chem. Rev. 1996, 96, 223.
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B. J . Am. Chem. Soc. 1998, 120, 6844. Dauban, P.; Dodd, R. H.
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10.1021/jo048990k CCC: $27.50 © 2004 American Chemical Society
Published on Web 08/24/2004
J . Org. Chem. 2004, 69, 6377-6386
6377

Padwa et al.
SCHEME 1
SCHEME 2
SCHEME 3
metric synthesis16 and as ligands for transition-metal-
catalyzed processes.17 This functionality is not only of
importance in the chemistry of aminosugars, carbohy-
drates, and nucleosides18 but also has varied applications
in organic synthesis.19 Considering the enormous poten-
tial of the â-amino alcohol moiety for chemistry, it is not
surprising that numerous synthetic routes have been
reported.20 Based on our long-standing involvement with
metallocarbenoids derived from R-diazocarbonyl com-
pounds,2 we naturally became interested in the chemistry
of the corresponding acyl nitrenoid with the intention of
using this reactive species for the preparation of various
â-amino alcohols via aziridine intermediates.
copper(II)-catalyzed reaction is the exclusive formation
of the three-membered aziridine ring.25 Rhodium(II)
catalysts were also found to mediate aziridinations but
with a higher propensity to generate C-H insertion
products.26 The first metal-catalyzed inter- and intramo-
lecular insertions into C-H bonds by iminophenyliodi-
nanes in the presence of a Rh(II) catalyst was reported
by Breslow and Gellman.21 More recently, Du Bois and
co-workers demonstrated that it was possible to perform
stereospecific intramolecular C-H insertions starting
from either sulfamate (6) or carbamate esters (7) when
used in combination with a Rh(II) catalyst, PhI(OAc)2,
and MgO, thereby greatly enhancing the use of imino-
iodanes for organic synthesis (Scheme 3).27 The method
was elegantly highlighted as a unique strategy in a recent
synthesis of (-)-tetrodotoxin.28
Pioneered by the groups of Breslow21 and Mansuy22 in
the early 1980s, transition-metal-catalyzed nitrene trans-
fer reactions with (arene-sulfonylimino)phenyliodinanes
have become recognized in recent years as a potentially
powerful method for the synthesis of various nitrogen-
containing substrates.23 Aziridination using TsNdIPh-
and Cu(I)-based catalysts was subsequently developed
and optimized to become an efficient synthetic method
by the Evans group (Scheme 2).24 A crucial feature of the
(14) Evans, D. A.; Faul, M. M.; Bilodeau, M. T.; Anderson, B. A.;
Barnes, D. M. J . Am. Chem. Soc. 1993, 115, 5328. Davis, F. A.; Zhou,
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D. S. Bioorg. Med. Chem. Lett. 1992, 2, 1489. Dehmlow, H.; Mulzer,
J .; Seilz, C.; Strecker, A. R.; Kohlmann, A. Tetrahedron Lett. 1992,
33, 3607. Legters, J .; Willems, J . G. H.; Thijs, L.; Zwanenburg, B. Recl.
Trav. Chim. Pays-Bas 1992, 111, 59.
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Faulkner, D. J . Nat. Prod. Rep. 2000, 17, 7. Huff, J . R. J . Med. Chem.
1991, 34, 2305.
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835. Ghosh, A. K.; Fidanze, S.; Senanayake, C. H. Synthesis 1998, 937.
(17) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley-
Interscience: New York, 1994. Gomez, M.; Muller, G.; Rocamora, M.
Coord. Chem. Rev. 1999, 193-195, 769. Seyden-Pene, J . Chiral
Auxiliaries and Ligands in Asymmetric Synthesis; Wiley-Inter-
science: New York, 1995.
(18) Danishefsky, S. J .; Bilodeau, M. T. Angew. Chem., Int. Ed. Engl.
1996, 35, 1380. Gijsen, H. J . M.; Qiao, L.; Fitz, W.; Wong, C. H. Chem.
Rev. 1996, 96, 443. Banoub, J .; Boullanger, P.; LaFont, D. Chem. Rev.
1992, 92, 1167.
Inspired by the work of both Breslow21 and Du Bois27
as well as our ongoing interest in the chemistry of
rhodium carbenoids,2 we wondered whether this reaction
could also be applied to the catalytic intramolecular
aziridination of CdC bonds. When we started our studies
in this area, the transition-metal-catalyzed delivery of
nitrogen from a carbamoyl nitrene to an olefin had not
been described in the literature.29 Our plan was to utilize
an intramolecular primary carbamate cyclization to
provide for the directed aziridination reaction shown in
Scheme 4.
Nucleophilic ring opening would generate oxazolidi-
none 12, which we intended to use for the stereospecific
preparation of a variety of 1,2-amino alcohol derivatives
(12 f 13). In an earlier report, we described some
preliminary results in this area,30 and in this paper we
expand on our initial findings.
(19) Du Bois, J .; Tomooka, C. S.; Hong, J .; Carreira, E. M. J . Am.
Chem. Soc. 1997, 119, 3179. Herold, P. Helv. Chim. Acta 1988, 71,
354.
(20) Williams, D. R.; Osterhout, M. H.; Reddy, J . P. Tetrahedron
Lett. 1993, 34, 3271. Barrett, A. G. M.; Seefeld, M. A. J . Chem. Soc.,
Chem. Commun. 1993, 339. J urczak, J .; Golebiowski, A. Chem. Rev.
1989, 89, 149. Reetz, M. T. Angew. Chem., Int. Ed. Engl. 1991, 30,
1531. Bergmeier, S. C.; Stanchina, D. M. J . Org. Chem. 1997, 62, 4449.
Bruncko, M.; Schlingloff, G.; Sharpless, K. B. Angew. Chem., Int. Ed.
Engl. 1997, 36, 1483. Petasis, N. A.; Zavialov, I. A. J . Am. Chem. Soc.
1998, 120, 11798. Marshall, J . A.; Gill, K.; Seletsky, B. M. Angew.
Chem., Int. Ed. 2000, 39, 953.
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Sweeney, J . B. Chem. Soc. Rev. 2002, 31, 247.
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Org. Chem. 1996, 9, 341. Mu¨ller, P.; Baud, C.; Naegeli, I. J . Phys. Org.
Chem. 1998, 11, 597.
(21) Breslow, R.; Gellman, S. H. J . Am. Chem. Soc. 1983, 105, 6728.
(22) Mansuy, D.; Mahy, J . P.; Dure’ault, A.; Bedi, G.; Battioni, P. J .
Chem. Soc., Chem. Commun. 1984, 1161. Mahy, J . P.; Bedi, G.;
Battioni, P.; Mansuy, D. J . Chem. Soc., Perkin Trans. 2 1988, 1517.
(23) For a review on iminoiodanes and their use in organic synthesis,
see: Dauban, P.; Dodd, R. H. Synlett 2003, 1571.
(24) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J . Org. Chem. 1991,
56, 6, 6744. Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J . Am. Chem.
Soc. 1994, 116, 2742. Evans, D. A.; Faul, M. M.; Bilodeau, M. T.;
Anderson, B. A. J . Am. Chem. Soc. 1993, 115, 5328.
(27) Espino, C. G.; Wehn, P. M.; Chow, J .; Du Bois, J . J . Am. Chem.
Soc. 2001, 123, 6935. Espino, C. G.; Du Bois, J . Angew. Chem., Int.
Ed. 2001, 40, 598. Wehn, P. M.; Du Bois, J . J . Am. Chem. Soc. 2002,
124, 12950. Wehn, P. M.; Lee, J .; Du Bois, J . Org. Lett. 2003, 5, 4823.
(28) Hinman, A.; Du Bois, J . J . Am. Chem. Soc. 2003, 125, 11510.
(29) While this work was in progress, Rojas and co-workers have
described the amidoglycosylation of allyl carbamates using metallo acyl
nitrenoids; see: Levites-Agababa, E.; Menhaji, E.; Perlson, L. N.; Rojas,
C. M. Org. Lett. 2002, 4, 863.
(30) Padwa, A.; Stengel, T. Org. Lett. 2002, 4, 2137.
6378 J . Org. Chem., Vol. 69, No. 19, 2004

Aziridination of Allyl-Substituted Sulfonamides and Carbamates
SCHEME 4
SCHEME 6
SCHEME 5
copper-catalyzed aziridination reaction using iminoiodi-
nane intermediates.32 The present set of conditions,
however, led to product yields significantly higher than
those reported by these workers.33 Treatment of azabi-
cyclic sulfonamides 20 and 21 in methanol in the pres-
ence of p-TsOH resulted in exclusive opening of the
aziridine ring at the more substituted position affording
the six- and seven-membered ring products 24 and 25 in
60% and 86% yield, respectively. It should be noted that
the ring-opening reaction required the presence of a
protic acid or a Lewis acid such as boron trifluoride
etherate. In the absence of these additives, no ring-
opening reaction occurred.
Cyclic carbamates, readily available from cyclocar-
bamation of allylic or homoallylic amines and alcohols,
have often been used as crucial intermediates for highly
stereoselective construction of both 1,2- and 1,3-amino
alcohol structures.34 With the intention of exploring the
scope, generality, and synthetic opportunities of the above
metal-mediated nitrenoid cyclization reaction, we ex-
tended our initial studies to include several carbocyclic
systems containing an allylic carbamate subunit. Car-
bamic acid cycloalk-1-enylmethyl esters 26 and 27 were
obtained upon treatment of the corresponding alcohols
with CCl3C(O)NCO followed by K2CO3/MeOH.35 Applica-
tion of the Du Bois conditions to carbamates 26 and 27
afforded tricyclic aziridines 28 and 29 in 71% and 75%
yield, respectively, as the exclusive products (Scheme 7).
Interestingly, when the reactions were carried out using
iodosobenzene (PhIdO) rather than PhI(OAc)2 as the
oxidant36 in the presence of 5 equiv of an added alcohol,
the same two tricyclic aziridines (28 and 29) were
obtained in essentially identical yield. Although both
aziridines were stable to silica gel chromatography, they
did undergo reaction with various nucleophiles at room
Resu lts a n d Discu ssion
The intramolecular aziridination reaction of several
easily available unsaturated sulfonamides was chosen as
our initial test for establishing the necessary reaction
conditions since it had previously been demonstrated that
iminoiodanes can be readily prepared from sulfona-
mides.23 Following the standard protocol developed by Du
Bois,27 which consisted of treating the appropriate sul-
fonamide with PhI(OAc)2, MgO, and catalytic Rh2(OAc)4,
we found that it was possible to convert vinylphenylsul-
fonamide 14 into the bicycic aziridine 15 in 80% isolated
yield. A similar reaction occurred with the related allyl-
substituted system 16 affording 17 in 91% yield (Scheme
5). A variety of solvents and different Rh(II) carboxylate
catalysts were examined to determine the effect of the
reaction conditions on the yield and conversion. The
results of this study showed CH2Cl2 to be the solvent of
choice. Reactions conducted in THF, benzene, or aceto-
nitrile gave lower yields of the product. The nature of
the ligand in the rhodium metal did not appear to
influence the outcome of the reaction.31
We next examined a series of unsaturated acyclic
sulfonamides to establish the generality and scope of the
aziridination process. The readily available substrates 18
and 19 underwent smooth intramolecular aziridination
to give the bicyclic aziridines 20 and 21 in 85% and 91%
yield, respectively (Scheme 6). Interestingly, reaction of
the related 5-hexenyl-substituted sulfonamide 22 fur-
nished only the product derived from allylic insertion (i.e.,
23) in 70% isolated yield. Related work by Dauban and
Dodd had previously been reported which made use of a
(32) Dauban, P.; Dodd, R. H. Org. Lett. 2000, 2, 2327. Dauban, P.;
Saniere, L.; Tarrade, A.; Dodd, R. H. J . Am. Chem. Soc. 2001, 123,
7707.
(33) For some related work which appeared after our studies were
completed, see: Liang, J . J .; Yuan, S. X.; Chan, P. W. H.; Che, C. M.
Org. Lett. 2002,4, 4507. Liang, J . J .; Yuan, S. X.; Chan, P. W. H.; Che,
C. M. Tetrahedron Lett. 2003, 44, 5917.
(34) Wang, T.; Izawa, S.; Kobayashi, S.; Ohno, M. J . Am. Chem. Soc.
1982, 104, 6465. Georges, M.; Mackay, D.; Fraser-Reid, B. J . Am.
Chem. Soc. 1982, 104, 1101. Bartlett, P. A.; Tauzella, D. J .; Barstow,
J . F. Tetrahedron Lett. 1982, 23, 619.
(35) Kocovsky, P. Tetrahedron Lett. 1986, 27, 5521.
(36) Willgerodt, C. Chem. Ber. 1892, 25, 3494. White, R. E. Inorg.
Chem. 1987, 26, 3916.
(31) The asymmetric intramolecular aziridination of unsaturated
sulfonamides and carbamates catalyzed by chiral rhodium(II) com-
plexes has recently been reported; see: Liang, J . L.; Yuan, S. X.; Chan,
P. W. H.; Che, C. M. Tetrahedron Lett. 2003, 44, 5917.
J . Org. Chem, Vol. 69, No. 19, 2004 6379

Padwa et al.
SCHEME 7
SCHEME 8
SCHEME 9
and represents an efficient route to variously substituted
diamines.40 In all cases reported, the resulting products
possess trans-stereochemistry of the ensuing amino
groups.41 This is the consequence of backside attack of
the nucleophile on the aziridine ring.
temperature in the presence of either p-TsOH or LiClO4.
In most cases, the addition of 1-5 equiv of the nucleo-
phile was used. The stereochemical assignment of 30 was
unequivocally established by X-ray crystallography. The
smooth and efficient reaction with aliphatic and aromatic
amines is potentially very useful since 1,2-diamines
represent an important subunit in many biological
compounds.37 Notably, the ring-opened products (i.e., 30-
34) were completely anti-stereoselective; only the trans-
isomers were formed (ca. 80% yield) as expected for
nucleophilic attack at the three-membered ring.38
To further highlight the synthetic utility of the spiro-
cyclization reaction, the intramolecular aziridination of
carbamate 37 was examined. A Grubb’s catalyzed ring-
closing metathesis reaction of N-allyl-N-(2-hydroxym-
ethyl)-allyl-4-methylbenzenesulfonamide (35) afforded
the expected 2,5-dihydropyrrole39 36 (63%) which was
readily transformed into carbamate 37 in 80% yield
(Scheme 8). In the presence of PhIO and Rh2(OAc)4,
compound 37 was converted to 38. Azabicycle 38, how-
ever, decomposed on silica gel chromatography, and
consequently, the crude product produced from the aziri-
dination reaction was immediately treated with n-butyl-
amine in the presence of a catalytic amount of p-
toluenesulfonic acid. After the mixture was stirred for 1
h, standard workup afforded 3-oxa-1,7-diazaspiro[4.4]-
nonan-2-one 39 in 73% yield. Compound 39 is the result
of attack of n-butylamine at the less hindered terminal
carbon of the aziridine ring. The ring opening of activated
aziridines with various amines is a well-studied process
The next system we investigated corresponded to the
protected 3-indolyl carbamate 40 which was synthesized
in three steps [tosylation (82%), reduction (77%), and
carbamoylation (71%) starting from indole-3-carboxalde-
hyde. Application of the Du Bois/Espino conditions27 to
indole 40 provided oxazolidinone 41 as a single diaste-
reomer in 85% yield (Scheme 9). The expected aziridine
42 was not observed. Rather, simultaneous spirocycliza-
tion of C3 and stereoselective acetylation at C2 occurred
leading to compound 41. The stereochemical assignment
of 41 was unequivocally established by an X-ray crystal-
lographic study. The stereochemical outcome of the
reaction was totally unexpected and certainly incompat-
ible with an SN2 opening of a transient aziridine inter-
mediate (i.e., 42), since nucleophilic attack of an acetate
on the three-membered ring would have led to an anti-
configuration of the substituent groups38 as was encoun-
tered with tricyclic aziridines 28 and 29. The experimen-
tal observations suggest a close interaction of the acetate
moiety with the metal fragment, thereby favoring forma-
tion of the oxazolidinone with the syn-configuration of
substituents. Without the addition of the Rh(II) catalyst,
only recovered starting material was obtained. When the
above reaction was carried out using iodosobenzene
(PhIO) rather than PhI(OAc)2 as the oxidant in the
presence of 5 equiv of an added alcohol, indolines 47-49
(37) Reetz, M. T.; J aeger, R.; Drewlies, R.; Hubel, M. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 103.
(38) Padwa, A.; Woolhouse, A. D. In Comprehensive Heterocyclic
Chemistry; Lwowski, W., Ed.; Pergamon: Oxford, 1983; Vol. 7, pp 47-
93.
(40) Anand, R. V.; Pandey, G.; Singh, V. K. Tetrahedron Lett. 2002,
43, 3975. Ferraris, D.; Drury, W. J ., III; Cox, C.; Lectka, T. J . Org.
Chem. 1998, 63, 4568. Osborn, H. M. I.; Sweeney, J . B. Synlett 1994,
145. Matsubara, S.; Kodama, T.; Utimoto, K. Tetrahedron Lett. 1990,
31, 6379.
(39) Lindsay, K. B.; Tang, M.; Pyne, S. G. Synlett 2002, 731.
Ostergaard, N.; Pedersen, B. T.; Skjaerbaek, N.; Vedso, P.; Begtrup,
M. Synlett. 2002, 1889.
(41) Sekar, G.; Singh, V. K. J . Org. Chem. 1999, 64, 2537. Meguro,
M.; Asao, N.; Yamammoto, Y. Tetrahedron Lett. 1994, 35, 7395.
Meguro, M.; Yamamoto, Y. Heterocycles 1996, 43, 2473.
6380 J . Org. Chem., Vol. 69, No. 19, 2004

Aziridination of Allyl-Substituted Sulfonamides and Carbamates
SCHEME 10
SCHEME 11
SCHEME 12
were formed in 64%, 65%, and 50% isolated yield. The
stereochemical assignment of 49 was unequivocally
established by X-ray crystallography. Again, without the
addition of the Rh(II) catalyst, only recovered starting
material was obtained. A reasonable mechanism which
accounts for the experimental findings involves initial
formation of an iminoiodinane intermediate (i.e., 43)
followed by catalyst (Rh(II))-promoted loss of iodobenzene
to give the metallonitrene 44 (Scheme 10). Stepwise
addition across the indole π-bond to give 45 followed by
Rh(II) detachment generates the metal-free zwitterionic
intermediate 46. Attack of the neutral nucleophile will
then occur on the side of the amide anion because
deprotonation of the nucleophile and nucleophilic attack
on the N-sulfonyliminium ion can occur simultaneously
to deliver indolines 47-49.31 Another possible explana-
tion is that the nucleophile attacks iminium ion 46 from
the less congested R-face.42
The observed stereochemistry encountered with in-
dolyl-substituted carbamate 40 stands in marked con-
trast with the results obtained with cycloalkenyl car-
bamates 26 and 27 where the ring-opening reaction of
the tricyclic aziridine proceeded with complete anti-
selectivity. A clue to the differing behavior of these
systems was gleaned when it was noted that the reactions
of 26 and 27 proceeded smoothly in the absence of the
Rh(II) catalyst. This would suggest that the initially
formed iminoiodinane 50 readily reacts with the electron-
rich π-bond present in the cycloalkene ring (Scheme 11).
In the case of the indole system, however, addition of
iminoiodinane 43 to the π-bond is much slower, presum-
ably as a result of its heteroaromatic character. It is only
when 43 reacts with the Rh(II) catalyst that stepwise
addition to the indole π-bond occurs, eventually producing
acetate 41.
stereochemistry of the major diastereomer 52 was es-
tablished by NOE measurements and corresponds to the
syn-selective isomer. To further expand the scope of the
intramolecular aziridination reaction using other het-
eroaromatic ring systems, we also prepared 3-benzofura-
nyl carbamate 54 and examined its reaction with PhI-
(OAc)2 in the presence of Rh2(OAc)4 under the same
conditions used for the indolyl-substituted systems. In
contrast to the reaction that occurred with 40 which
proceeded with exclusive syn-selectivity, the amination
of 54 produced a 1.5:1-mixture of the diastereomers of
55.
What is the origin of the much higher degree of
stereocontrol encountered with 3-indolyl carbamate 40
relative to carbamates 51 and 54? We hypothesize that
the stepwise addition of the metallonitrenoid derived
from 40 across the indole π-bond will lead to a much more
stable zwitterionic intermediate (i.e., 56) than that
resulting from carbamate 51 (i.e., 57). The higher reac-
We have also studied the behavior of the closely related
2-indolyl carbamate 51 in order to determine the stereo-
selectivity of its reaction. Application of the standard Du
Bois/Espino conditions to 51 provided a 5:2 mixture of
diastereomers 52 (59%) and 53 (24%) (Scheme 12). The
(42) One of the reviewers has suggested an alternative mechanism
involving addition of the nucleophile from the coordination sphere of
the metal in 45 to give 41, 47, 48, and 49 directly, without the
intermediacy of the dipolar species 46. Although this pathway is
consistent with the observed syn-selectivity of addition, we believe that
it can be discounted because one would expect acetate transfer in all
cases, independent of other nucleophiles present.
tivity of iminium ion 57 is undoubtedly related to the
disruption of aromaticity of the benzenoid portion of the
molecule. The stereochemical controlling step in the
process involves nucleophilic addition of the acetate group
J . Org. Chem, Vol. 69, No. 19, 2004 6381

Padwa et al.
(CDCl3, 100 MHz) δ 37.2, 117.4, 127.1, 128.5, 132.2, 133.3,
136.9, 138.3, 140.2. Anal. Calcd for C9H11NSO2: C, 54.80; H,
5.62; N, 7.10. Found: C, 54.64; H, 5.55; N, 7.08.
onto the carbon atom of the N-sulfonyliminium ion. When
diastereomeric transition states involving different imi-
nium ion precursors are considered, the shorter lived and
less stable iminium ion 57 does not easily allow for facial
discrimination by the attacking acetic acid. In contrast,
the more stable and longer lived cation 56 does permit
the nucleophile to preferentially react on the same side
as the amide anion due to an electrostatic attraction.43
Although this hypothesis remains to be critically evalu-
ated, the model can also be used to understand the lack
of selectivity observed with the benzofuranyl analogue
54. With this system, the resulting oxonium ion 58 is
simply too reactive to exhibit any significant facial
discrimination as a consequence of electrostatic factors.44
In summary, the iodine(III)-mediated intramolecular
aziridination reaction of unsaturated sulfonamides occurs
readily in the presence of Rh2(OAc)4 and gives bicyclic
sultams. Several indolyl- and benzofuranyl-substituted
carbamates were also studied. The amination reaction
requires a Rh(II) catalyst and proceeds in a stepwise
manner via a metal-free zwitterionic intermediate. In
contrast, the intramolecular aziridination of several
cycloalkenyl carbamates does not require a Rh(II) cata-
lyst and takes place via an iminoiodinane intermediate.
Further mechanistic investigations and application of
acyl nitrenoid methodology to natural product synthesis
are underway in our laboratories and will be reported in
due course.
To a 0.24 g sample of the above sulfonamide in 8 mL of CH2-
Cl2 was added 0.5 g of PhI(OAc)2, 0.2 g of MgO, and 10 mg of
Rh2(OAc)4. The mixture was stirred at 40 °C under an argon
atmosphere for 8 h. The solution was filtered through a short
pad of Celite, and the solvent was removed under reduced
pressure. The residue was subjected to flash silica gel chro-
matography to give 17 as a clear oil in 91% yield: 1H NMR
(300 MHz, CDCl3) δ 1.95 (dd, 1H, J ) 4.0, 2.0 Hz), 2.52 (dd,
1H, J ) 5.0, 1.4 Hz), 3.25 (m, 2H), 3.60 (dd, 1H, J ) 17.0, 4.0
Hz), 7.31 (d, 1H, J ) 7.0 Hz), 7.50 (t, 1H, J ) 7.0 Hz), 7.65
(dt, 1H, J ) 7.5, 1.5 Hz), 7.85 (dd, 1H, J ) 7.5, 1.0 Hz); 13C
NMR (CDCl3, 100 MHz) δδ 26.1, 30.2, 49.4, 36.9, 126.3, 129.2,
129.5, 134.2. Anal. Calcd for C9H9NSO2: C, 55.37; H, 4.65; N,
7.17. Found: C, 55.24; H, 4.50; N, 7.03.
2-Th ia -1-a za bicyclo[3.1.0]h exa n e 2,2-Dioxid e (20). A
sample of but-3-ene-1-sulfonamide (18) was prepared in 45%
yield by heating a solution of 4-bromo-but-1-ene (2 mL) and
sodium sulfite (3.0 g) in 15 mL of water at reflux for 12 h. The
resulting solid was then treated with phosphorus oxychloride
for 6 h at 125 °C. The mixture was concentrated, and the
residue was taken up in acetonitrile and treated with an
aqueous ammonia solution. Standard workup afforded 18 as
a white solid in 65% yield: mp 44-45 °C; 1H NMR (300 MHz,
CDCl3) δ 2.62 (q, 2H, J ) 7.5 Hz), 3.29 (t, 2H, J ) 7.5 Hz),
5.1-5.25 (m, 2H), 5.45 (brs, 2H), 5.90 (m, 1H); 13C NMR
(CDCl3, 100 MHz) δ 28.0, 54.2, 117.3, 134.2. Anal. Calcd for
C4H9NSO2: C, 35.55; H, 6.72; N, 10.37. Found: C, 35.28; H,
6.57; N, 10.21.
To a 0.1 g sample of the above sulfonamide in 8 mL of CH2-
Cl2 was added 0.2 g of PhI(OAc)2, 0.08 g of Al2O3, and 8 mg of
Rh2(OAc)4. The mixture was stirred at 40 °C under an argon
atmosphere for 4 h. Filtration through a short pad of Celite
was followed by removal of the solvent under reduced pressure.
The residue was subjected to silica gel chromatography to give
azabicyclic sulfonamide 20 (85%) as a white solid: mp 75-77
°C; 1H NMR (300 MHz, CDCl3) δ 2.34 (dd, 1H, J ) 4.3, 3.0
Hz), 2.52 (dd, 1H, J ) 5.4, 3.0 Hz), 2.60-2.75 (m, 2H), 2.90
(ddd, 1H, J ) 13.0, 12.0, 8.0 Hz), 3.20 (m, 2H); 13C NMR
(CDCl3, 100 MHz), δδ 2.3, 30.1, 39.4, 40.6. Anal. Calcd for C4H7-
NSO2: C, 36.08; H, 5.30; N, 10.53. Found: C, 35.84; H, 5.17;
N, 10.46.
2-Th ia -1-a za bicyclo[4.1.0]h ep ta n e 2,2-Dioxid e (21). A
sample of pent-4-ene-1-sulfonamide (19) was prepared in 39%
yield by heating a solution of 5-bromopent-1-ene (1.0 g) and
sodium sulfite (3.0 g) in 15 mL of water at reflux for 12 h. The
resulting solid was then treated with phosphorus oxychloride
for 6 h at 125 °C. The mixture was concentrated, and the
residue was taken up in acetonitrile and treated with an
aqueous ammonia solution. Standard workup afforded 19 as
a clear oil: 1H NMR (300 MHz, CDCl3) δ 1.97 (q, 2H, J -7.5
Hz), 2.24 (q, 2H, J ) 7.5 Hz), 3.18 (t, 2H, J ) 7.5 Hz), 5.05-
5.15 (m, 2H), 5.24 (brs, 2H), 5.81 (m, 1H); 13C NMR (CDCl3,
Exp er im en ta l Section
1,1a -Dih yd r o-6-th ia -6a -a za cyclop r op [a ]in d en e 6,6-Di-
oxid e (15). To a 0.1 g sample of 2-vinylphenylsulfonamide
(14)45 in 10 mL of CH2Cl2 was added 0.25 g of PhI(OAc)2, 0.1
g of MgO, and 10 mg of Rh2(OAc)4. The mixture was stirred
at 40 °C under an argon atmosphere for 8 h. The solution was
filtered through a short pad of Celite, and the solvent was
removed under reduced pressure. The residue was subjected
to flash silica gel chromatography to give 15 (80%) as a clear
oil: IR (CHCl3) 2930, 1600, 1550, 1470, 1340, and 1050 cm-1
;
1H NMR (400 MHz, CDCl3) δ 2.35 (dd, 1H, J ) 4.0, 0.9 Hz),
2.92 (dd, 1H, J ) 5.0, 0.9 Hz), 4.15 (m, 1H), 7.55-7.80 (m,
4H); 13C NMR (CDCl3, 100 MHz) δ 43.2, 44.5, 123.8, 125.5,
130.5, 133.3, 137.2. Anal. Calcd for C8H7NSO2: C, 53.03; H,
3.89; N, 7.73. Found: C, 52.89; H, 3.71; N, 7.66.
1a ,2-Dih yd r o-1H-7-th ia -7a -a za cyclop r op a [b]n a p h th a -
len e 7,7-Dioxid e (17). To a solution of N-tert-butylbenzene-
sulfonamide (2 g) in 25 mL of hexane was added 1.6 M
n-butyllithium solution in hexane. After stirring for 3 h at -60
°C, the solution was warmed to -30 °C and 1 equiv of allyl
bromide was added in THF. After being stirred for 3 h, the
mixture was allowed to warm to 25 °C and was treated with
10% hydrochloric acid. The THF layer was removed, dried, and
concentrated under reduced pressure. The resulting residue
was subjected to silica gel chromatography to give 2-allylben-
zenesulfonamide (16) (70%) as a white solid: mp 121-123 °C;
1H NMR (300 MHz, CDCl3) δ 3.91 (d, 2H, J ) 6.0 Hz), 5.02
(brs, 2H), 5.15 (m, 2H), 6.10 (m, 1H), 7.35 (m, 2H), 7.5 (dt,
1H, J ) 7.5, 1.4 Hz), 8.05 (dd, 1H, J ) 8.0, 1.0 Hz); 13C NMR
100 MHz) δ 23.1, 32.2, 54.7, 116.3, 136.7. Anal. Calcd for C5H11
-
NSO2: C, 40.25; H, 7.43; N, 9.39. Found: C, 40.03; H, 7.19;
N, 9.46.
To a 0.1 g sample of the above sulfonamide in 8 mL of CH2-
Cl2 was added 0.25 g of PhI(OAc)2, 0.08 g of Al2O3, and 10 mg
of Rh2(OAc)4. The mixture was stirred at 40 °C under argon
atmosphere for 6 h. The solution was filtered through a short
pad of Celite, and the solvent was removed under reduced
pressure. The residue was subjected to flash silica gel chro-
matography to give azabicyclic sulfonamide 21 (91%) as a
white solid: mp 68-70 °C; 1H NMR (300 MHz, CDCl3) δ 1.85-
2.05 (m, 1H), 2.10 (q, 1H, J ) 5.0 Hz), 2.25 (m, 2H), 2.60 (d,
1H, J ) 5.0 Hz), 2.72 (dd, 1H, J ) 5.0, 0.8 Hz), 3.10 (ddd, 1H,
J ) 14, 12, 4.0 Hz), and 3.20 (m, 2H); 13C NMR (CDCl3, 100
MHz) δ 17.0, 18.9, 32.5, 42.7, 47.0. Anal. Calcd for C5H9-
NSO2: C, 40.80; H, 6.16; N, 9.52. Found: C, 40.66; H, 6.03;
N, 9.61.
(43) Another reasonable possibility suggested by one of the reviewers
is that the dipolar structures 56-58 might adopt different conforma-
tions, due to a buttressing effect of the tosyl group, and this may change
the steric requirements around the carbon atom that is attacked by
the nucleophile.
(44) For structures 57 and 58, there is the possibility that the
intermediate exists as a mixture of dipolar and aziridine structures,
the dipolar one being responsible for the syn-addition product and the
highly strained aziridine for the anti-addition product.
(45) Mu¨ller, P.; Baud, C.; J acquier, Y. Can. J . Chem. 1998, 76, 738.
6382 J . Org. Chem., Vol. 69, No. 19, 2004

Aziridination of Allyl-Substituted Sulfonamides and Carbamates
3-Vin yl[1,2]th ia zin a n e 1,1-Dioxid e (23). A sample of hex-
5-ene-1-sulfonamide (22) was prepared in 65% yield by heating
a solution of 6-bromohex-1-ene (1.0 g) and sodium sulfite (3.0
removed under reduced pressure, and the residue was sub-
jected to flash silica gel chromatography to give 0.09 g (75%)
of aziridine 29 as a white solid: mp 34-35 °C; IR (film) 1778,
g) in 15 mL of water at reflux for 12 h. The resulting solid
was treated with phosphorus oxychloride for 6 h at 125 °C.
The mixture was concentrated, and the residue was taken up
in acetonitrile and treated with an aqueous ammonia solution.
Standard workup afforded 22 in 62% yield as a white solid:
1219, 1133, 1076, 1038 cm-1 1H NMR (CDCl3, 400 MHz) δ
;
1.21-1.49 (m, 4H), 1.73-1.84 (m, 2H), 1.92-2.06 (m, 2H), 2.65
(m, 1H), 4.01 (d, 1H, J ) 9.4 Hz), 4.37 (d, 1H, J ) 9.4 Hz); 13
C
NMR (CDCl3, 100 MHz) δ 19.4, 20.6, 24.3, 24.9, 48.9, 49.2,
70.6, 168.4. Anal. Calcd for C8H11NO2: C, 62.73; H, 7.24; N,
9.14. Found: C, 62.54; H, 7.32; N, 9.22.
1
mp 50-51 °C; H NMR (300 MHz, CDCl3) δ 1.55 (q, 2H, J )
7.5 Hz), 1.85-1.90 (m, 2H), 2.15 (q, 2H, J ) 7.5 Hz), 3.15 (m,
6-Meth oxy-1-a za sp ir o[4.4]n on a n -2-on e (30). A 0.05 g
(0.38 mmol) sample of tetrahydro-2-oxa-3a-azacyclopropadi-
cyclopenten-3-one (28) was dissolved in 2 mL of anhydrous
methanol. A catalytic amount of p-TsOH was added. The
solution was stirred for 4 h at room temperature. The solvent
was removed under reduced pressure, and the residue was
subjected to flash silica gel chromatography to afford 0.05 g
(80%) of oxazolidinone 30 as a white solid: mp 114-115 °C;
2H), 5.0-5.1 (m, 4H), 5.80 (m, 1H); 13C NMR (CDCl3, 100 MHz)
δ 23.6, 27.7, 33.4, 55.4, 115.7, 137.9. Anal. Calcd for C6H13
-
NSO2: C, 44.15; H, 8.03; N, 8.58. Found: C, 44.06; H, 7.95;
N, 8.44.
To a 0.1 g sample of the above sulfonamide in 10 mL of CH2-
Cl2 was added 0.25 g of PhI(OAc)2, 0.1 g of Al2O3, and 10 mg
of Rh2(OAc)4. The mixture was stirred at 40 °C under an argon
atmosphere for 8 h. The solution was filtered through a short
pad of Celite, and the solvent was removed under reduced
pressure. The residue was subjected to flash silica gel chro-
matography to give 23 (70%) as a white solid: mp 95-97 °C;
1H NMR (300 MHz, CDCl3) δ 1.35-1.50 (m, 1H), 1.90 (qd, 1H,
J ) 14, 3.0 Hz), 2.25 (m, 2H), 2.85-3.0 (m, 1H), 3.20 (dt, 1H,
J ) 13, 3.5 Hz), 4.10 (m, 1H), 4.20 (brd, 1H, J ) 8.0 Hz), 5.20
(d, 1H, J ) 11 Hz), 5.30 (d, 1H, J ) 17 Hz), 5.80 (m, 1H); 13C
NMR (CDCl3, 100 MHz) δ 2.31, 29,0.8, 49.4, 58.2, 116.5, 136.7.
Anal. Calcd for C6H11NSO2: C, 44.70; H, 6.88; N, 8.69.
Found: C, 44.62; H, 6.87; N, 8.53.
4-Meth oxy[2,1]th ia zin a n e 1,1-Dioxid e (24). A 0.07 g (0.5
mmol) sample of azabicyclosulfonamide 20 in 5 mL of methanol
was stirred at room temperature in the presence of p-TsOH
for 24 h. Removal of the solvent followed by silica gel
chromatography of the residue afforded the titled compound
as a clear oil in 60% yield: 1H NMR (CDCl3, 300 MHz) δ 2.30-
2.45 (m, 2H), 3.09 (dt, 1H, J ) 13, 4.0 Hz), 3.2-3.40 (m, 2H),
3.42 (s, 3H), 3.50 (m, 2H), 4.61 (brs, 1H); 13C NMR (CDCl3,
IR (film) 1751, 1716, 1401, 1198, 1151, 1112, 1044, 1007 cm-1
;
1H NMR (CDCl3, 400 MHz) δ 1.62-1.71 (m, 3H), 1.80-1.91
(m, 3H), 3.31 (s, 3H), 3.51 (m, 1H), 4.04 (d, 1H, J ) 8.9 Hz),
4.64 (d, 1H, J ) 8.9 Hz), 7.16 (s, 1H); 13C NMR (CDCl3, 100
MHz) δ 19.2, 27.6, 35.4, 57.3, 57.4, 67.4, 70.6, 86.2, 160.4. Anal.
Calcd for C8H13NO3: C, 56.11; H, 7.66; N, 8.18. Found: C,
56.07; H, 7.53; N, 8.01.
6-Br om o-1-a za sp ir o[4.4]n on a n -2-on e (31). A 0.05 g (0.33
mmol) sample of tetrahydro-2-oxa-3a-azacyclopropadicyclo-
penten-3-one (28) was dissolved in 3 mL of anhydrous acetone.
A 0.12 g (1.3 mmol) sample of lithium bromide and a catalytic
amount of LiClO4 were added. The solution was stirred for 4
h at room temperature. The solvent was removed under
reduced pressure, and the residue was subjected to flash silica
gel chromatography to afford 0.06 g (78%) of oxazolidinone 31
as a white solid: mp 98-100 °C; IR (film) 1751, 1474,
1396, 1330, 1253, 1044 cm-1 1H NMR (CDCl3, 400 MHz) δ
;
1.70-1.99 (m, 3H), 2.07-2.19 (m, 2H), 2.32-2.41 (m, 1H),
4.19-4.21 (m, 1H), 4.25 (d, 1H, J ) 9.2 Hz), 4.68 (d, 1H,
J ) 9.2 Hz), 7.35 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 19.8,
100 MHz) δ 27.2, 45.3, 48.1, 56.4, 70.1. Anal. Calcd for C5H11
-
NSO3: C, 36.35; H, 6.71; N, 8.48. Found: C, 36.27; H, 6.58;
N, 8.30.
33.8, 34.5, 58.4, 68.8, 73.2, 159.8. Anal. Calcd for C7H10
-
BrNO2: C, 38.36; H, 4.60; N, 6.39. Found: C, 38.19; H, 4.55;
N, 6.26.
4-Meth oxy[1,2]th ia zep a n e 1,1-Dioxid e (25). A 0.1 g (0.7
mmol) sample of azabicyclosulfonamide 21 in 5 mL of methanol
was stirred at room temperature in the presence of p-TsOH
for 24 h. Removal of the solvent followed by silica gel
chromatography of the residue afforded the titled compound
in 86% yield as a clear oil: 1H NMR (CDCl3, 300 MHz) δ 1.90
(m, 2H), 2.10 (m, 2H), 3.30-3.50 (m, 7H), 3.60 (m, 1H), 5.15
(brs, 1H); 13C NMR (CDCl3, 100 MHz) δ 18.1, 31.9, 44.7, 56.8,
57.0, 78.4. Anal. Calcd for C6H13NSO3: C, 40.21; H, 7.31; N,
7.81. Found: C, 40.17; H, 7.05; N, 7.79.
Tet r a h yd r o-2-oxa -3a -a za cyclop r op a d icyclop en t en -3-
on e (28). In a sealed tube was placed 0.27 g (1.9 mmol) of
carbamic acid cyclopent-1-enylmethyl ester (26)46 in 16 mL of
anhydrous CH2Cl2. To this solution were added 0.76 g (3.4
mmol) of PhIO and 3 g of molecular sieves, and the mixture
was stirred for 12 h at 40 oC. The reaction mixture was filtered
through a short pad of Celite. The solvent was removed under
reduced pressure and the residue subjected to flash silica gel
chromatography to give 0.19 g (71%) of aziridine 28 as a
colorless oil: IR (film) 1769, 1386, 1240, 1156, 1132, 1086, 1037
cm-1; 1H NMR (CDCl3, 400 MHz) δ 1.39-1.53 (m, 1H), 1.65-
1.85 (m, 3H), 2.02 (dd, 1H, J ) 8.1 Hz), 2.13 (dd, 1H, J ) 8.1
Hz), 2.98 (d, 1H, J ) 2.5 Hz), 4.39 (d, 1H, J ) 9.4 Hz), 4.57 (d,
1H, J ) 9.4 Hz); 13C NMR (CDCl3, 100 MHz) δ 19.9, 27.2, 27.8,
52.96, 56.9, 66.8, 167.3. Anal. Calcd for C7H9NO2: C, 60.40;
H, 6.52; N, 10.07. Found: C, 60.25; H, 6.49; N, 9.92.
6-Meth oxy-3-oxa-1-azaspir o[4.5]decan -2-on e (32). A 0.05
g (0.29 mmol) sample of tetrahydro-2-oxa-3a-azacyclopenta-
[1,3]cyclopropa[1,2]benzen-3-one (29) was dissolved in 2 mL
of anhydrous methanol. A catalytic amount of p-TsOH was
added. The solution was stirred for 4 h at room temperature.
The solvent was removed under reduced pressure, and the
residue was subjected to flash silica gel chromatography to
give 0.05 g (83%) of oxazolidinone 32 as a colorless oil: IR (film)
1747, 1397, 1249, 1099, 1044, 983 cm-1; 1H NMR (CDCl3, 400
MHz) δ 1.29-1.84 (m, 8H), 3.14 (dd, 1H, J ) 7.3 Hz), 3.35 (s,
3H), 3.93 (d, 1H, J ) 8.6 Hz), 4.39 (d, 1H, J ) 8.6 Hz), 7.25 (s,
1H); 13C NMR (CDCl3, 100 MHz) δ 21.1, 22.1, 26.0, 34.8, 57.6,
60.9, 72.6, 81.5, 160.4. Anal. Calcd for C9H15NO3: C, 58.35;
H, 8.17; N, 7.56. Found: C, 58.24; H, 7.97; N, 7.50.
6-Bu tyla m in o-3-oxa -1-a za sp ir o[4.5]d eca n -2-on e (33). A
0.06 g (0.38 mmol) sample of tetrahydro-2-oxa-3a-azacyclopenta-
[1,3]cyclopropa[1,2]-benzen-3-one (29) was dissolved in 3 mL
of anhydrous CH2Cl2. A 0.08 g (1.1 mmol) sample of n-
butylamine and a catalytic amount of p-TsOH were added. The
solution was stirred for 4 h at room temperature. The solvent
was removed under reduced pressure, and the residue was
subjected to flash silica gel chromatography to give 0.07 g
(82%) of the oxazolidinone 33 as a white solid: mp 82-83 °C;
IR (film) 1744, 1647, 1542, 1284, 1036 cm-1; 1H NMR (CDCl3,
400 MHz) δ 0.91 (t, 3H, J ) 7.3 Hz), 1.23-1.51 (m, 8H), 1.68-
1.89 (m, 3H), 2.10-2.17 (m, 1H), 2.40 (d, 1H, J ) 3.2 Hz),
3.17-3.23 (m, 2H), 3.31 (dd, 1H, J ) 12.2, 3.7 Hz), 3.76 (dd,
1H, J ) 10.0, 3.7 Hz), 3.94 (dd, 1H, J ) 12.2, 10 Hz), 5.01 (s,
1H); 13C NMR (CDCl3, 100 MHz) dδ 14.0, 20.0, 20.2, 20.4, 24.1,
27.0, 32.2, 40.5, 40.6, 46.0, 68.4, 165.2. Anal. Calcd for
Tet r a h yd r o-2-oxa -3a -a za cyclop en t a [1,3]cyclop r op a -
[1,2]ben zen -3-on e (29). In a sealed tube was placed 0.12 g
(0.77 mmol) of carbamic acid cyclohex-1-enylmethyl ester (27)47
in 7 mL of anhydrous CH2Cl2. To this solution were added 0.3
g (1.4 mmol) of PhIO and 1.5 g of molecular sieves, and the
mixture was stirred for 12 h at 40 oC. The reaction mixture
was filtered through a short pad of Celite. The solvent was
C
12H22N2O2: C, 63.68; H, 9.80; N, 12.38. Found: C, 63.78; H,
9.87; N, 12.30.
J . Org. Chem, Vol. 69, No. 19, 2004 6383

Padwa et al.
6-(4-Meth oxyph en ylam in o)-3-oxa-1-azaspir o[4.5]decan -
2-on e (34). A 0.06 g (0.4 mmol) sample of tetrahydro-2-oxa-
3a-azacyclopenta[1,3]cyclopropa[1,2]benzen-3-one (29) was dis-
solved in 2 mL of anhydrous acetonitrile. A 0.05 g (0.4 mmol)
sample of p-anisidine and a catalytic amount of LiClO4 was
added. The solution was stirred for 4 h at room temperature.
The solvent was removed under reduced pressure and the
residue subjected to flash silica gel chromatography to afford
0.09 g (82%) of oxazolidinone 34 as a white solid: mp 193-
194 °C; IR (film) 1754, 1509, 1289, 1239, 1169, 1033 cm-1; 1H
NMR (CDCl3, 300 MHz) δ 1.38-1.81 (m, 8H), 3.29 (m, 1H),
3.72 (s, 3 H), 4.02 (d, 1H, J ) 9.0 Hz), 4.42 (d, 1H, J ) 9.0
Hz), 6.62 (m, 2H), 6.74 (m, 3H); 13C NMR (CDCl3, 50 MHz) δ
22.2, 22.4, 28.5, 35.6, 55.9, 58.5, 61.6, 72.1, 115.1, 116, 4, 141.3,
153.1, 160.2. Anal. Calcd for C15H20N2O3: C, 65.20; H, 7.30;
N, 10.14. Found: C, 65.36; H, 7.25; N, 10.18.
was dissolved in 240 mL of degassed CH2Cl2, and 0.8 g (2.85
mmol) of alcohol 35 was added. The solution was stirred at 40
°C for 24 h, and then an additional 0.07 g (0.079 mmol) of
Grubbs’ catalyst was added. The reaction mixture was stirred
for an additional 10 h at 40 °C in order to complete the
reaction. The solvent was removed under reduced pressure,
and the residue was subjected to flash silica gel chromatog-
raphy to give 0.45 g (63%) of 36 as a white solid: mp 94-95
1
°C; IR (film) 3510, 2856, 1338, 1161 cm-1; H NMR (CDCl3,
400 MHz) δ 1.96 (t, 1H, J ) 4.8 Hz), 2.40 (s, 3H), 4.08 (m,
6H), 5.51 (m, 1H), 7.30 (d, 2H, J ) 7.9 Hz), 7.68 (m, 2H); 13C
NMR (CDCl3, 100 MHz) δ 21.8, 54.8, 55.1, 59.7, 120.1, 127.6,
130.1, 134.1, 139.5, 143.9. Anal. Calcd for C12H15NO3S: C,
56.90; H, 5.97; N, 5.53. Found: C, 56.48; H, 5.84; N, 5.46.
Ca r ba m ic Acid 1-(Tolu en e-4-su lfon yl)-2,5-d ih yd r o-1H-
p yr r ol-3-ylm eth yl Ester (37). To a solution containing 0.07
g (0.26 mmol) of dihydropyrrole 36 in 2 mL of anhydrous CH2-
Cl2 was slowly added a solution containing 0.05 g (0.27 mmol)
of trichloroacetyl isocyanate in 0.5 mL of CH2Cl2 at 0 °C. The
solution was stirred for 3 h at room temperature. The solvent
was removed under reduced pressure, and the residue was
taken up in 2 mL of methanol. To this solution was added
0.004 g (0.03 mmol) of K2CO3, and the mixture was stirred at
25 °C for 2 h. The solvent was removed under reduced
pressure, and the residue was subjected to flash silica gel
chromatography to give 0.06 g (80%) of 37 as a white solid:
2-[[Allyl(tolu en e-4-su lfon yl)a m in o]m eth yl]a cr ylic Acid
Eth yl Ester . A 1.5 g (7.1 mmol) sample of N-allyl-4-methyl-
benzenesulfonamide48 was dissolved in DMF, and the solution
was stirred at 0 °C for 30 min. To this solution was added
0.37 g (9.3 mmol) of NaH (60% dispersion in mineral oil), and
the mixture was stirred for 0.5 h at 25 °C. To the resulting
solution was added 3.0 g (15.3 mmol) of 2-bromomethylacrylic
acid ethyl ester.49 After the reaction mixture was stirred for
12 h at 25 °C, water was added and the mixture was extracted
with ether. The organic phase was washed with brine and
dried over MgSO4. After the solvent was removed under
reduced pressure, the residue was subjected to flash silica gel
chromatography to give 1.95 g (85%) of the titled compound
mp 142-143 °C; IR (film) 3424, 1689, 1158 cm-1 1H NMR
;
(CDCl3, 400 MHz) δ 2.45 (s, 3H), 4.15-4.30 (m, 6H), 4.65 (s,
2H), 5.55 (m, 1H), 7.35 (d, 2H, J ) 8.0 Hz), 7.70 (m, 2H). Anal.
Calcd for C13H16N2O4S: C, 52.69; H, 5.44; N, 9.45. Found: C,
52.71; H, 5.56; N, 9.48.
as a colorless oil: IR (film) 1712, 1343, 1159, 1092 cm-1 1H
;
NMR (CDCl3, 400 MHz) δ 1.27 (t, 3H, J ) 7.2 Hz), 2.42 (s,
3H), 3.75 (d, 2H, J ) 6.5 Hz), 3.99 (m, 2H), 4.17 (q, 2H, J )
7.0 Hz), 5.06 (m, 1H), 5.11 (m, 1H), 5.48-5.62 (m, 1H), 5.89
(q, 1H, J ) 1.6, 1.2 Hz), 6.34 (d, 1H, J ) 1.2 Hz), 7.29 (d, 2H,
J ) 8.9 Hz), 7.70 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ 14.4,
21.7, 47.2, 51.3, 61.1, 119.7, 127.2, 127.4, 129.9, 132.6, 136.0,
137.2, 143.6, 166.1. Anal. Calcd for C16H21NO4S: C, 59.42; H,
6.54; N, 4.33. Found: C, 59.48; H, 6.47; N, 4.40.
9-Bu t yla m in o-7-(t olu en e-4-su lfon yl)-3-oxa -1,7-d ia za -
sp ir o[4.4]n on a n -2-on e (39). In a sealed tube was placed 0.17
g (0.6 mmol) of carbamate 37 in 7 mL of anhydrous CH2Cl2.
To this solution was added 0.23 g (1.0 mmol) of PhIO, 7 mg
(0.016 mmol) of Rh2(OAc)4, and 1 g of molecular sieves, and
the mixture was stirred for 6 h at 40 °C. The reaction mixture
was filtered through a short pad of Celite, and the solvent was
removed under reduced pressure. The residue was subjected
to flash silica gel chromatography, and the resulting bicyclic
aziridine 38 was immediately taken up in 4 mL of anhydrous
CH2Cl2, and 0.06 g (0.82 mmol) of n-butylamine together with
a catalytic amount of p-TsOH was added. The solution was
stirred for 1 h at room temperature. The solvent was removed
under reduced pressure, and the residue was subjected to flash
silica gel chromatography to give 0.06 g (73%) of 39 as a clear
N-Allyl-N-(2-h yd r oxym et h yla llyl)-4-m et h ylb en zen e-
su lfon a m id e (35). To a solution containing 0.1 g (0.7 mmol)
of neat DIBAL-H in 8 mL of ether was added a solution of 0.2
g (0.63 mmol) of the above ethyl ester at -78 °C. After the
mixture was stirred for 10 min, the cooling bath was removed
and the mixture was stirred for 10 h at 25 °C. The solution
was extracted with ether, and the organic phase was dried
over MgSO4. Removal of the solvent under reduced pressure
left a clear oil which was subjected to flash silica gel chroma-
tography to give 0.13 g (74%) of 35 as a colorless oil: IR (film)
1
oil: IR (film) 1655, 1534, 1343, 1163 cm-1; H NMR (CDCl3,
400 MHz) δ 0.91 (t, 3H, J ) 7.3 Hz), 1.27-1.47 (m, 4H), 2.41
(s, 3H), 2.88 (m, 1H), 2.97 (d, 1H, J ) 2.0 Hz), 3.10-3.22 (m,
4H), 3.63 (dd, 1H, J ) 4.8 Hz), 3.80 (d, 1H, J ) 11.1 Hz), 3.90
(d, 1H, J ) 11.1 Hz), 3.99 (dd, 1H, J ) 7.3 Hz), 5.02 (s, 1H),
7.29 (m, 2H), 7.67 (d, 2H, J ) 9.2 Hz); 13C NMR (CDCl3, 100
MHz) δ 14.0, 20.2, 21.8, 32.0, 40.6, 42.9, 48.0, 49.6, 52.7, 61.6,
1
1340, 1157, 1092 cm-1; H NMR (CDCl3, 400 MHz) δ 2.41 (s,
3H), 2.55 (t, 1H, J ) 6.6 Hz), 3.70 (m, 4H), 4.12 (d, 2H, J )
6.7 Hz), 4.98 (s, 1H), 5.07 (m, 2H), 5.16 (d, 1H, J ) 0.6 Hz),
5.48 (m, 1H), 7.29 (d, 2H, J ) 8.0 Hz), 7.69 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ 21.8, 49.2, 49.9, 63.6, 115.5, 119.9, 127.3,
130.0, 132.2, 137.1, 143.6, 143.8. Anal. Calcd for C14H19NO3S:
C, 59.76; H, 6.81; N, 4.98. Found: C, 59.79; H, 6.81; N, 4.93.
[1-(Tolu en e-4-su lfon yl)-2,5-dih ydr o-1H-pyr r ol-3-yl]m eth -
a n ol (36). A 0.11 g (0.13 mmol) sample of Grubbs’ catalyst50
127.8, 129.9, 134.2, 144.0, 161.1. Anal. Calcd for C17H25
-
N3O4S: C, 55.57; H, 6.86; N, 11.44. Found: C, 55.73; H, 6.91;
N, 11.29.
Ca r ba m ic Acid 1-Ben zen esu lfon yl-1H-in d ol-3-yl Meth -
yl Ester (40). To a solution containing 1.8 g (6.4 mmol) of
(1-benzenesulfonyl-1H-indol-3-yl)methanol51 in 10 mL of an-
hydrous CH2Cl2 was slowly added a 1.3 g (6.7 mmol) solution
(46) Carbamate 26 was synthesized starting from commercially
available cyclopent-1-enecarboxylic acid ethyl ester in two steps. (1)
Reduction to cyclopent-1-enyl-methanol with LiAlH2/AlCl3 (54% yield),
see: Hager, D. C.; Bentrude, W. G. J . Org. Chem. 2000, 65, 2786. (2)
Conversion of the alcohol to carbamate 26 was carried out using
trichloroacetyl isocyanate/K2CO3, MeOH (70% yield) according to the
procedure described in ref 35.
(47) Carbamate 27 was synthesized starting from commercially
available cyclohex-1-enecarbaldehyde in two steps. (1) Reduction to
cyclohex-1-enyl-methanol with LiAlH4 (84% yield), see: J ulia, S.; J ulia,
M.; Linares, H.; Blondel, J .-C. Bull. Soc. Chim. Fr. 1962, 1947. (2)
Conversion of the alcohol to carbamate 27 was carried out using
trichloroacetyl isocyanate/K2CO3, MeOH (65% yield) according to the
procedure described in ref 35.
o
of trichloroacetyl isocyanate35 in 3 mL of CH2Cl2 at 0 C. The
solution was stirred for 3 h at room temperature. The solvent
was removed under reduced pressure, and the residue was
dissolved in 10 mL of methanol. To this solution was added
0.1 g (0.7 mmol) of K2CO3, and the mixture was stirred for 2
h at 25 °C. The solvent was removed under reduced pressure,
and the residue was subjected to flash silica gel chromatog-
raphy to give 1.5 g (71%) of 40 as a white solid: mp 142-143
(50) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413.
(51) Gribble, G. W.; Keavy, D. J .; Davis, D. A., Saulnier, M. G.;
Pelcman, B.; Barden, T. C.; Sibi, M. P.; Olsen, E. R.; BelBruno, J . J . J .
Org. Chem. 1992, 57, 5878.
(48) Migata, O.; Ozawa, Y.; Ninomiga, I.; Naito, T. Tetrahedron
2000, 56, 6199.
(49) Villieras, J .; Rambaud, M. Synthesis 1982, 924.
6384 J . Org. Chem., Vol. 69, No. 19, 2004

Aziridination of Allyl-Substituted Sulfonamides and Carbamates
°C; IR (film) 1717, 1447, 1366, 1175, 1121, 1046 cm-1; 1H NMR
1H, J ) 15.9, 2.4 Hz), 4.58 (dd, 1H, J ) 15.9, 2.4 Hz), 5.29 (s,
1H), 5.49 (s, 1H), 7.19-7.23 (m, 2H), 7.25-7.42 (m, 3H), 7.46-
7.73 (m, 4H); 13C NMR (CDCl3, 100 MHz) δ 57.0, 67.7, 73.8,
76.1, 78.3, 93.1, 117.6, 124.1, 126.6, 126.9, 127.1, 129.9, 131.4,
(CDCl3, 400 MHz) δ 4.63 (s, 2H), 5.23 (d, 2H, J ) 1.0 Hz),
7.24-7.62 (m, 6H), 7.89 (m, 2H), 7.98 (d, 1H, J ) 8.3 Hz); 13
C
NMR (CDCl3, 100 MHz) δ 58.7, 113.9, 118.0, 120.0, 123.8,
125.4, 125.7, 127.1, 129.6, 129.7, 134.2, 135.4, 138.3, 156.7.
Anal. Calcd for C16H14N2O4S: C, 58.17; H, 4.27; N, 8.48.
Found: C, 58.12; H, 4.21; N, 8.36.
131.6, 134.4, 138.3, 139.6, 158.1. Anal. Calcd for C19H16
-
N2O5S: C, 59.37; H, 4.20; N, 7.29. Found: C, 59.13; H, 4.17;
N, 7.28.
Ca r ba m ic Acid 1-Ben zen esu lfon yl-1H-in d ol-2-yl Meth -
yl Ester (51). To a solution containing 0.56 g (2.0 mmol) of
(1-benzenesulfonyl-1H-indol-3-yl)methanol51 in 7 mL of anhy-
drous CH2Cl2 was slowly added a solution of 0.4 g (2.1 mmol)
of trichloroacetyl isocyanate in 1 mL of CH2Cl2 at 0 °C. The
solution was stirred for 2 h at room temperature, and the
solvent was removed under reduced pressure. The residue was
taken up in 5 mL of methanol, and 0.03 g (0.22 mmol) of K2-
CO3 was added. The mixture was stirred for 2 h, and the
solvent was evaporated. The residue was subjected to flash
silica gel chromatography to give 0.36 g (56%) of 51 as a white
solid; mp 147-148 °C; IR (film) 1721, 1449, 1368, 1355, 1175,
1090 cm-1; 1H NMR (CDCl3, 400 MHz) δ 4.67 (s, 2H), 5.50 (d,
2H, J ) 0.6 Hz), 6.73 (d, 1H, J ) 0.6 Hz), 7.23-7.54 (m, 6H),
7.83 (m, 2H), 8.12 (m, 1H); 13C NMR (CDCl3, 100 MHz) δ 60.2,
112.7, 114.8, 121.5, 124.0, 125.5, 126.7, 129.1, 129.4, 134.1,
135.6, 137.4, 139.1, 156.2. Anal. Calcd for C16H14N2O4S: C,
58.17; H, 4.27; N, 8.48. Found: C, 57.93; H, 4.19; N, 8.36.
N-P h en ylsu lfon yl-3-(m eth ylca r bon yloxy)sp ir o[2H-in -
d ole-3,2′oxa zolid in ]-5′-on e (52). In a sealed tube was placed
0.07 g (0.21 mmol) of the above carbamate in 5 mL of degassed
CH2Cl2. To this solution were added 0.11 g (0.33 mmol) PhI-
(OAc)2, 0.03 g (0.6 mmol) of MgO, and 5 mg (0.01 mmol) of
Rh2(OAc)4. The mixture was heated for 14 h at 80 °C, filtered
through a short pad of Celite, and concentrated under reduced
pressure. The resulting residue contained 0.06 g (83%) of a
2.5:1 mixture of indoline diastereomers. Flash silica gel
chromatography of the crude solid afforded 0.045 g (59%) of
the syn-diastereomer 52 as a white solid: mp 191-193 °C; IR
(film) 1759, 1353, 1222, 1164, 1088, 1027, 754 cm-1; 1H NMR
(CDCl3, 400 MHz) δ 2.11 (s, 3H), 4.76 (d, 1H, J ) 9.4 Hz),
5.02 (d, 1H, J ) 9.4 Hz), 5.94 (s, 1H), 7.04 (brs, 1H), 7.11 (t,
1H, J ) 7.8 Hz), 7.32 (d, 1H, J ) 7.8 Hz), 7.40 (t, 1H, J ) 7.8
Hz), 7.54 (t, 2H, J ) 7.8 Hz), 7.61 (t, 1H, J ) 7.8 Hz), 7.66 (d,
1H, J ) 7.8 Hz), 7.93 (d, 2H, J ) 7.8 Hz); 13C NMR (CDCl3,
100 MHz) δ 20.7, 29.9, 77.5, 84.5, 114.1, 123.2, 124.4, 126.7,
127.2, 129.8, 131.9, 134.0, 139.9, 141.0, 157.9, 170.6.; Anal.
Calcd for C18H16N2O6S: C, 55.66; H, 4.15; N, 7.21. Found: C,
55.30; H, 3.89; N, 6.90.
N-P h en ylsu lfon yl-2-(m eth ylca r bon yloxy)sp ir o[3H-in -
d ole-3,2′-oxa zolid in ]-5′-on e (41). In a sealed tube was placed
0.11 g (0.3 mmol) of carbamate 40 in 10 mL of CH2Cl2. To this
mixture was added 0.17 g (0.5 mmol) of PhI(OAc)2, 0.04 g (0.9
mmol) of MgO, and 0.008 g (0.017 mmol) of Rh2(OAc)4, and
the mixture was stirred for 12 h at 40 °C. The mixture was
filtered through a short pad of Celite, the solvent was removed
under reduced pressure, and the residue was subjected to flash
silica gel chromatography to give 0.11 g (85%) of indoline 41
as the exclusive product: mp 189-190 °C; IR (film) 1766, 1366,
1220, 1171, 1109, 1036 cm-1 1H NMR (CDCl3, 400 MHz) δ
;
2.00 (s, 3H), 3.91 (s, 3 H), 4.08 (d, 1H, J ) 9.2 Hz), 6.27 (s,
1H), 6.63 (s, 1H), 7.12-7.64 (m, 7H), 7.85-7.87 (m, 2H); 13C
NMR (CDCl3, 50 MHz) δ 20.6, 67.2, 74.7, 87.4, 114.9, 124.3,
125.7, 127.2, 129.1, 129.7, 131.5, 134.2, 138.8, 140.3, 159.4,
169.8. Anal. Calcd for C18H16N2O6S: C, 55.66; H, 4.15; N, 7.21.
Found: C, 55.38; H, 4.00; N, 7.27.
N-P h en ylsu lfon yl-2-m et h oxysp ir o[3H -in d ole-3,2′ox-
a zolid in ]-5′-on e (47). The reaction of 0.07 g (0.2 mmol) of
carbamate 40, 0.17 g (0.8 mmol) of PhIO, 0.07 g (2.0 mmol) of
methanol, 0.006 g (0.014 mmol) of Rh2(OAc)4, and 2 g of
molecular sieves in 6 mL of CH2Cl2 was stirred in a sealed
tube at 40 °C for 6 h. The reaction mixture was filtered through
a short pad of Celite, the solvent was removed under reduced
pressure, and the residue was subjected to flash silica gel
chromatography to afford 0.05 g (64%) of 47 as a white solid:
mp 228-229 °C; IR (film) 1772, 1356, 1206, 1172, 1036 cm-1
;
1H NMR (CDCl3, 400 MHz) δ 3.17 (d, 1H, J ) 9.2 Hz), 3.42 (d,
1H, J ) 9.2 Hz), 3.61 (s, 3H), 5.02 (s, 1H), 5.44 (s, 1H), 7.20-
7.26 (m, 2H), 7.38-7.48 (m, 3H), 7.58-7.71 (m, 4H); 13C NMR
(CDCl3, 100 MHz) δ 57.2, 67.9, 73.6, 95.7, 117.9, 124.1, 126.6,
126.9, 129.8, 131.3, 131.9, 134.3, 138.5, 139.7, 158.4. Anal.
Calcd for C17H16N2O5S: C, 56.65; H, 4.48; N, 7.78. Found: C,
56.53; H, 4.41; N, 7.69.
N-P h en ylsu lfon yl-2-(2-p r op en yloxy)sp ir o[3H -in d ole-
3,2′oxa zolid in ]-5′-on e (48). The reaction of 0.07 g (0.2 mmol)
of carbamate 40, 0.18 g (0.8 mmol) of PhIO, 0.12 g (2.0 mmol)
of 2-propen-1-ol, 0.007 g (0.015 mmol) of Rh2(OAc)4, and 2 g of
molecular sieves in 6 mL of CH2Cl2 was stirred in a sealed
tube at 40 °C for 6 h. The reaction mixture was filtered through
a short pad of Celite, the solvent was removed under reduced
pressure, and the residue was subjected to flash silica gel
chromatography to give 0.05 g (65%) of 48 as a white solid:
mp 94-95 °C; IR (film) 1766, 1447, 1360, 1171, 1090, 1038
NOE experiments performed on 52 showed that irradiation
of the singlet at δ 5.94 produced enhancements for the
methylene set of hydrogens at δ 4.76 and 5.02. The minor
indoline diastereomer 53 could not be fully separated from the
major isomer but showed characteristic peaks in the NMR at
δ 2.16 (s, 3H), 4.78 (d, 1H, J ) 9.4 Hz), 5.15 (d, 1H, J ) 9.4
Hz), 6.05 (s, 1H).
1
cm-1; H NMR (CDCl3, 400 MHz) δ 3.41 (d, 1H, J ) 9.2 Hz),
4.28-4.33 (ddt, 1H, J ) 12.5, 6.4, 1.3 Hz), 4.42-4.47 (ddt, 1H,
J ) 12.5, 5.3, 1.4 Hz), 5.17 (s, 1H), 5.23-5.36 (m, 2H), 5.52 (s,
1H), 5.82-5.92 (m, 1H), 7.17-7.27 (m, 2H), 7.38-7.48 (m, 3H),
7.57-7.62 (m, 1H), 7.65-7.70 (m, 3H); 13C NMR (CDCl3, 100
MHz) δ 67.8, 70.3, 73.7, 93.7, 117.8, 119.3, 124.0, 126.5, 126.9,
129.8, 131.3, 131.9, 133.0, 134.3, 138.4, 139.7, 158.3. Anal.
Calcd for C19H18N2O5S: C, 59.05; H, 4.70; N, 7.25. Found: C,
58.87; H, 4.68; N, 7.19.
Ca r ba m ic Acid Ben zofu r a n -3-ylm eth yl Ester (54). To
a solution of 0.5 g (3.4 mmol) of benzofuran-3-ylmethanol52 in
8 mL of anhydrous CH2Cl2 was slowly added a solution of 0.7
g (3.6 mmol) of trichloroacetyl isocyanate in 1 mL of CH2Cl2
at 0 °C. The solution was stirred for 1.5 h at room temperature.
The solvent was removed under reduced pressure, and the
residue was taken up in 6 mL of methanol. To this solution
was added 0.07 g (0.5 mmol) of K2CO3, and the mixture was
stirred at 25 °C for 2 h. The solvent was removed under
reduced pressure, and the residue was subjected to flash silica
gel chromatography to give 0.5 g (82%) of 54 as a white solid:
mp 115-116 °C; IR (film) 1679, 1598, 1451, 1338, 1190, 1104,
N-P h en ylsu lfon yl-2-et h yn yloxysp ir o[3H -in d ole-3,2′-
oxa zolid in ]-5′-on e (49). The reaction of 0.07 g (0.2 mmol) of
carbamate 40, 0.18 g (0.8 mmol) of PhIO, 0.11 g (1.96 mmol)
of 2-propyn-1-ol, 0.007 g (0.015 mmol) of Rh2(OAc)4, and 2 g
of molecular sieves in 6 mL of CH2Cl2 was stirred in a sealed
tube at 40 °C for 6 h. The reaction mixture was filtered through
a short pad of Celite, the solvent was removed under reduced
pressure, and the residue was subjected to flash silica gel
chromatography to give 0.03 g (50%) of 49 as a white solid:
mp 159-161 °C; IR (film) 1767, 1604, 1361, 1171, 1103, 1040
1
742 cm-1; H NMR (CDCl3, 400 MHz) δ 4.64 (brs, 2 H), 5.27
(s, 2H), 7.28-7.35 (m, 2H), 7.50 (d, 1H, J ) 8.4 Hz), 7.66-
(52) Henke, B. R.; Aquino, C. J .; Birkemo, L. S.; Croom, D. K.;
Dougherty, R. W., J r.; Ervin, G. N.; Grizzle, M. K.; Hirst, G. C.; J ames,
M. K.; J ohnson, M. F.; Queen, K. L.; Sherrill, R. G.; Sugg, E. E.; Suh,
E. M.; Szewczyk, J . W.; Unwalla, R. J .; Yingling, J .; Willson, T. M. J .
Med. Chem. 1997, 40, 2706.
1
cm-1; H NMR (CDCl3, 400 MHz) δ 2.54 (t, 1H, J ) 2.4 Hz),
3.21 (d, 1H, J ) 9.2 Hz), 3.46 (d, 1H, J ) 9.5 Hz), 4.48 (dd,
J . Org. Chem, Vol. 69, No. 19, 2004 6385

Padwa et al.
7.69 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ 57.6, 111.9, 116.3,
120.1, 123.2, 125.0, 126.9, 144.3, 155.7, 156.7. Anal. Calcd for
C10H9NO3: C, 62.82; H, 4.74; N, 7.33. Found: C, 62.73; H, 4.80;
N, 7.28.
The minor diastereomer could not be fully separated from
the major isomer but showed characteristic peaks in the NMR
at δ 2.16 (s, 3H), 4.55 (d, 1H, J ) 9.6 Hz), 4.89 (d, 1H, J ) 9.6
Hz), 5.62 (brs, 1H), 6.59 (s, 1H), 6.94 (d, 1H, J ) 7.6 Hz), 7.12
(t, 1H, J ) 7.6 Hz), 7.35-7.41 (m,2 H).
2-(Me t h ylca r b on yloxy)sp ir o[3H -b e n zofu r a n yl-3,2′-
oxa zolid in ]-5′-on e (55). In a sealed tube was placed 0.12 g
(0.21 mmol) of the above carbamate in 8 mL of degassed R,R,R-
trifluorotoluene. To this solution were added 0.3 g (0.95 mmol)
of PhI(OAc)2, 0.07 g (1.6 mmol) of MgO, and 14 mg (0.03 mmol)
of Rh2(OAc)4. The mixture was heated for 3 h at 90 °C, filtered
through a short pad of Celite, and concentrated under reduced
pressure. The resulting solid residue contained 0.06 g of a 1.5:1
mixture of the dihydrobenzofuran diastereomers. Fractional
crystallization of the crude solid afforded the major diastere-
omer as a white solid: mp 162-163 °C; IR (film) 1751, 1215,
1052, 990, 759 cm-1; 1H NMR (CDCl3, 400 MHz) δ 2.17 (s, 3H),
4.35 (d, 1H, J ) 9.2 Hz), 4.64 (d, 1H, J ) 9.2 Hz), 5.83 (brs,
1H), 6.55 (s, 1H), 6.93 (d, 1H, J ) 7.6 Hz), 7.12 (t, 1H, J ) 7.6
Hz), 7.33-7.40 (m, 2 H); 13C NMR (CDCl3, 100 MHz) δ 21.1,
67.5, 74.7, 99.9, 111.6, 123.7, 123.9, 124.9, 131.9, 157.6, 158.2,
169.4. Anal. Calcd for C12H11NO5: C, 57.83; H, 4.45; N, 5.62.
Found: C, 57.38; H, 4.45; N, 5.34.
Ack n ow led gm en t. This research was supported by
the National Institutes of Health. We thank our col-
league, Dr. Kenneth Hardcastle, for his assistance with
the X-ray crystallographic studies and the University
Research Committee of Emory University for funds to
acquire a microwave reactor.
Su p p or tin g In for m a tion Ava ila ble: ORTEP drawings
for structures 30, 41, and 48. The authors have deposited
atomic coordinates for these structures with the Cambridge
Crystallographic Data Centre. This material is available free
of charge via the Internet at http://pubs.acs.org.
J O048990K
6386 J . Org. Chem., Vol. 69, No. 19, 2004