Inter- and intramolecular addition/cyclizations of sulfonamide anions with alkynyliodonium triflates. Synthesis of dihydropyrrole, pyrrole, indole, and tosylenamide heterocycles

Article abstract of DOI:10.1021/jo9605814

The synthesis of dihydropyrroles, pyrroles, and indoles through [3-atom + 2-atom] combination of ethyl or aryl tosylamide anions with phenyl(propynyl)iodonium triflate, and the base-mediated intramolecular bicyclization of alkynyliodonium-bearing tosylamide or tosylimide substrates to furnish bicyclic and tricyclic tosylenamide (-enimide) products, is described. A detailed discussion of the scope, limitations, byproduct formation, and the basis for observed diastereoselectivity is presented.

Full text of DOI:10.1021/jo9605814

5440
J . Org. Chem. 1996, 61, 5440-5452
In ter - a n d In tr a m olecu la r Ad d ition /Cycliza tion s of Su lfon a m id e
An ion s w ith Alk yn yliod on iu m Tr ifla tes. Syn th esis of
Dih yd r op yr r ole, P yr r ole, In d ole, a n d Tosylen a m id e Heter ocycles
Ken S. Feldman,* Michelle M. Bruendl, Klaas Schildknegt, and Adolph C. Bohnstedt
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802
Received March 28, 1996X
The synthesis of dihydropyrroles, pyrroles, and indoles through [3-atom + 2-atom] combination of
ethyl or aryl tosylamide anions with phenyl(propynyl)iodonium triflate, and the base-mediated
intramolecular bicyclization of alkynyliodonium-bearing tosylamide or tosylimide substrates to
furnish bicyclic and tricyclic tosylenamide (-enimide) products, is described. A detailed discussion
of the scope, limitations, byproduct formation, and the basis for observed diastereoselectivity is
presented.
The unique reactivity of alkynyliodonium salts 2 sug-
philicity of the alkynyliodonium species 6 has been well
documented with a host of soft nucleophiles (malonates
and related â-dicarbonyls,1c,i,j,p sulfinate,1e,k thiolate,1r and
thiocyanate,1b carboxylate/phosphate/sulfonate,1d,q and
azide,1l,o inter alia); however, clear limitations prevent
extension to more nucleophilic species.1n Amine-derived
substrates represent a notable omission.1f Upon nucleo-
philic addition to the â-carbon of the alkynyliodonium
salt, an intermediate alkylidene carbene 8 of orthogonal
reactivity is generated, Scheme 1. This reactive and
mildly electrophilic singlet carbene has four conceivable
fates:3 (1) rearrangement (1,2 shift, path a), (2) C-H
insertion (path b), (3) cycloaddition (path c), and (4)
dimerization (not shown). The relative rates of these
options depend upon the nature of R and Nu, and
scattered reactivity data allow deduction of qualitative
rankings for these paths. 1,2-Shifts of hydrogen (t1/2 <1
ps for the parent ethylidene),3k aryl, and TMS groups
apparently proceed more rapidly than any other options,
and alkyne formation (path a) will predominate in these
cases. Both 1,5 C-H insertion (path b) and alkene
cycloaddition (path c) can compete with 1,2-alkyl shifts,
and it is this key observation that opens a window of
opportunity for synthesis. 1,5 C-H insertion appears to
prevail over either inter- or intramolecular alkene cy-
cloaddition, which is, in turn, faster than 1,2-alkyl shifts.
Of course it is possible that exceptions to these gener-
alizations will emerge as more data becomes available.
The results shown in Table 1 demonstrate that the
yield of the dihydropyrrole product 16 from combination
of anion 14 with the prototype iodonium salt 151s is
extremely sensitive to the nature of the protecting group
P, eq 3. No conditions were found which permitted either
the lithium amide 14a (or the parent amine) or the
weakly acidic benzamide 14b to participate in N-C bond
formation. The much more acidic triflamide 14c and
trifluoroacetamide 14d did furnish modest amounts of
gests that they may serve as versatile reagents in
heterocycle synthesis.1 In particular, combination of
nitrogen-bearing substrates with alkynyliodonium spe-
cies (eqs 1 and 2) might provide products congruent with
substructures contained within several alkaloid families.
The reduction of the strategy described in eqs 1 and 2 to
practice could permit access to five-membered ring
products with either endocyclically (e.g., 3) or exocycli-
cally disposed nitrogen atoms (e.g., 5).2
These two-step transformations initiate with nucleo-
philic capture by the iodonium salt. The potent electro-
X Abstract published in Advance ACS Abstracts, August 1, 1996.
(1) (a) Stang, P. J . Angew. Chem., Int. Ed. Engl. 1992, 31, 285 and
references cited therein. (b) Fischer, D. R.; Williamson, B. L.; Stang,
P. J . Synlett 1992, 535. (c) Bachi, M. D.; Bar-Ner, N.; Crittell, C. M.;
Stang, P. J .; Williamson, B. L. J . Org. Chem. 1991, 56, 3912. (d) Stang,
P. J . Russ. Chem. Bull. 1993, 42, 12. (e) Williamson, B. L.; Tykwinski,
R. R.; Stang, P. J . J . Am. Chem. Soc. 1994, 116, 93. (f) March, P.;
Williamson, B. L.; Stang, P. J . Synthesis 1994, 1255. (g) Tykwinski,
R. R.; Whiteford, J . A.; Stang, P. J . J . Chem. Soc., Chem. Commun.
1993, 1800. (h) Ochiai, M., In Reviews on Heteroatom Chemistry,
Volume 2; Oae, S., Ed.; MYU: Tokyo, 1989; p 92. (i) Ochiai, M.;
Kunishima, M., Nagao, Y.; Fuji, K.; Shiro, M.; Fujita, E. J . Am. Chem.
Soc. 1986, 108, 8281. (j) Ochiai, M.; Ito, T.; Takaoka, Y.; Kunishima,
M.; Tani, S.; Nagao, Y. J . Chem. Soc. Chem. Commun. 1990, 118. (k)
Ochiai, M.; Kunishima, M.; Tani, S.; Nagao, Y. J . Am. Chem. Soc. 1991,
113, 3135. (l) Ochiai, M.; Kunishima, M.; Fuji, K.; Nagao, Y. J . Org.
Chem. 1988, 53, 6144. (m) Ochiai, M.; Takaoka, Y.; Nagao, Y. J . Am.
Chem. Soc. 1988, 110, 6565. (n) Margida, A.; Koser, G. F. J . Org. Chem.
1984, 49, 4703. (o) Kitamura, T.; Stang, P. J . Tetrahedron Lett. 1988,
29, 1887. (p) Tykwinski, R. R.; Stang, P. J .; Peisky, N. E. Tetrahedron
Lett. 1994, 35, 23. (q) Stang, P. J . Acc. Chem. Res. 1991, 24, 304. (r)
Stang, P. J .; Zhdankin, V. V. J . Am. Chem. Soc. 1991, 113, 4571. (s)
Zhdankin, V. V.; Scheuller, M. C.; Stang, P. J . Tetrahedron Lett. 1993,
34, 6853.
(3) (a) Stang, P. J . Acc. Chem. Res. 1982, 15, 348, and references
cited therein. (b) Stang, P. J . Chem. Rev. 1978, 383. (c) Stang, P. J .
Isr. J . Chem. 1981, 21, 119. (d) Stang, P. J . Acc. Chem. Res. 1978, 11,
107. (e) Taber, D. F.; Meagley, R. P. Tetrahedron Lett. 1994, 35, 7909.
(f) Gilbert, J . C.; Giamalva, D. H.; Weerasooriya, U. J . Org. Chem.
1983, 48, 5251. (g) Gilbert, J . C.; Giamalva, D. H.; Baze, M. E. J . Org.
Chem. 1985, 50, 2557. (h) Baird, M. S.; Baxter, A. G. W.; Hoorfar, A.;
J efferies, I. J . Chem. Soc., Perkin Trans. 1, 1991, 2575. (i) Karpf, M.;
Huguet, J .; Dreiding, A. S. Helv. Chim. Acta 1982, 65, 13. (j) Kim, S.;
Cho, C. M. Tetrahedron Lett. 1994, 35, 8405. (k) Gallo, M. M.;
Hamilton, T. P.; Schaeffer, H. F., III. J . Am. Chem. Soc. 1990, 112,
8714, and references cited therein. (l) Fisher, R. H.; Baumann, M.;
Ko¨brich, G. Tetrahedron Lett. 1974, 1207.
(2) (a) Schildknegt, K.; Bohnstedt, A. C.; Feldman, K. S.; Samban-
dam, A. J . Am. Chem. Soc., 1995, 117, 7544. (b) Feldman, K. S.;
Bruendl, M. M.; Schildknegt, K. J . Org. Chem. 1995, 60, 7722.
S0022-3263(96)00581-6 CCC: $12.00 © 1996 American Chemical Society

Addition/Cyclizations of Sulfonamide Anions
J . Org. Chem., Vol. 61, No. 16, 1996 5441
Sch em e 1
workup conditions. This methyl-substituted product 18
hydrolyzed more readily than the phenyl analog 16e to
furnish the ketoamide 19, eq 4. The relatively indis-
criminate nature of the highly energetic alkylidene
carbene intermediate is emphasized by the equally facile
insertion into the secondary C-H bond of 17 (BDE ∼ 95
kcal/mol) as compared to the slightly activated benzylic
position (BDE ∼ 85 kcal/mol) of 14e.
The â-methoxylated substrate 20 participated in the
[3 + 2] addition with phenyl(propynyl)iodonium triflate
(15) as well, although two unexpected products were
isolated after workup, eq 5. The major adduct, pyrrole
23, logically follows through ready elimination of metha-
nol from the putative (but never observed) dihydropyrrole
intermediate 22. The second, minor product exhibits
spectral data consistent with the heterocycle 25. The
formation of this product could involve initial carbene
trapping by the nucleophilic ether oxygen to furnish an
intermediate ylide 24. Formal demethylation of this
species by some extant nucleophile such as triflate,
tosylamide anion, or methoxide followed by protonation
of the resultant vinyl anion, perhaps by dihydropyrrole
22, yields 25. A similar DME adduct has been observed
by Stang upon treatment of tert-butyl(phenyl)iodonium
tosylate with sodium azide in that solvent.1o
Ta ble 1. Yield of Dih yd r op yr r ole 16 a s a F u n ction of
P r otectin g Gr ou p P
entry
P in 14
est pKa of PHN
yield of 16 (%)
a
b
c
d
e
f
H
PhCO
CF3SO2
CF3CO
tolSO2
TMS(CH2)2SO2
415a
235b
105c
175d
165e
175f
-
-
16
28
67
9
the [3 + 2] dihydropyrrole adducts 16c and 16d , respec-
tively. However, the highest yields consistently attended
the tosylamide substrate 14e. Optimization studies
probing the effects of solvent (THF, Et2O, DME, PhH,
CH2Cl2), metal counterion (Li, Na, K, Ce), reagent ratios,
temperature (-78 °C to 60 °C), sequence (and rate) of
addition, and concentration (0.001 to 0.1 M in 14e)
converged on the reaction parameters shown with eq 3
for best yield. It is notable that these conditions require
no more than 1 equiv of each component for optimum
yields. Some of the product tosylenamides 16 proved to
be quite hydrolytically labile,4 and minimizing exposure
to acid upon workup and chromatographic isolation (Et3N
in the eluent) was essential to suppress hydrolysis (vide
infra). It is apparent from the data in Table 1 that pKa
(DMSO) is not the sole determinant of successful reaction
in this series.
The lithiated cyclohexyltosylamide substrate 26 differs
from the previous entries in that it features both a
substituted R-position and diastereotopic hydrogens avail-
able for C-H insertion by the intermediate carbene.
Treatment of anion 26 with phenyl(propynyl)iodonium
triflate (15) affords moderate amounts of dihydropyrrole
product 28 as a single cis-fused diastereomer, Scheme 2.
In this case, addition of the iodonium salt 15 to a
refluxing solution of amide anion was critical in elevating
the yield; reaction at 25 °C under otherwise identical
conditions afforded only 22% of 28. In addition to
formation of the expected dihydropyrrole product, an
equal amount (45%) of the curious THF adduct 32 was
isolated. Apparently, a formal oxidation of THF has
occurred, perhaps with concomitant reduction of the
alkynyliodonium salt to the parent alkyne 30 (undetec-
ted). A plausible mechanistic interpretation of this
transformation is suggested in Scheme 2. Formation of
Several readily available substrates 17, 20, 26, 33, and
36a /b were examined for their capacity to participate in
this reaction. The first two species, 17 and 20, test the
question of functional group compatibility at the C-H
insertion site, while the latter four substrates, which bear
substituents at both the R and â positions, examine the
diastereoselectivity of alkylidene carbene C-H insertion.
n-Propyltosylamide 17 furnished dihydropyrrole prod-
uct 18 in good yield if careful attention was paid to
(4) (a) Hegedus, L. S.; Holden, M. S. J . Org. Chem. 1986, 51, 1171.
(b) Hegedus, L. S.; McKearin, J . M. J . Am. Chem. Soc. 1982, 104, 2444.

5442 J . Org. Chem., Vol. 61, No. 16, 1996
Feldman et al.
Ta ble 2. Tosylin d ole Syn th esis fr om Tosyla n ilid es 43
a n d Alk yn yliod on iu m Sa lt 15
Sch em e 2
entry
R in 43
yield of 45/46(%)
45:46 ratio
a
b
c
d
e
H
CH3
OCH3
CO2CH3
CO2t-Bu
66
59
61
51
46
-
1:1
1.4:1
1.2:1
1.3:1
insertion into the benzylic C-H position is possible.
Unfortunately, only minor amounts of dihydropyrrole
product 37a was observed in the former case. These
substrates reveal a significant limitation of this approach
to dihydropyrrole synthesis: substituents at the R posi-
tion are barely tolerated, and in any event 1,2-relative
asymmetric induction is modest at best.
The use of more electrophilic alkynyliodonium salts to
overcome the sluggish reactivity of R-substituted ethyl-
tosylamides was briefly examined with the propiolate and
propynylphenone species 39 and 41,7 respectively. In
both cases (eqs 6 and 7), moderate amounts of the
alkynylated species 40 and 42 were obtained to the
exclusion of 1,5 C-H insertion products. It is unclear
at present whether these transformations followed the
alkylidene carbene/1,2-shift mechanism (Scheme 1) or a
more orthodox conjugate addition/iodonium salt elimina-
tion sequence initiated by amide anion addition to the
iodonium-bearing carbon of the alkyne electrophile.
Sch em e 3
the key THF-derived electrophile 31 might result from
initial (reversible) nucleophilic capture of salt 15 by THF,
followed by elimination of the elements of propyne and
PhI. The base 26 may play a role in siphoning off the
THF adduct 29 by deprotonation of Ha. Isolation of this
particular byproduct is unique to the cyclohexyltosyla-
mide substrate and may simply be a reflection of both
the higher temperature (60 °C) employed compared to
the other cases (∼ 25 °C) and the inherent sluggishness
of the R-substituted tosylamide in direct nucleophlic addi-
tion to 15 (vide infra).6 Further studies are in progress
to test this mechanistic proposal and to probe the genera-
lity of this THF oxidation/nucleophile-trapping sequence.
Further attempts to discern diastereoselective C-H
insertion with the R and â substituted ethyltosylamide
substrates 33 and 36a /b did not furnish encouraging
results, Scheme 3. In each case, optimization studies
could not improve the yields past the values shown, and
recovered starting tosylamide accounted for the majority
of the material isolated. Three dihydropyrroles resulted
from reaction of the silyl ether 33 with iodonium salt 15.
Thus, only modest regioselectivity favoring alkylidene
carbene insertion into a secondary C-H bond (34) over
a primary C-H bond (35), and minimal diastereoselec-
tivity in the secondary C-H insertion species 34, was
observed. The R-phenylated substrates 36a and 36b
remove the regiochemical ambiguity noted above as only
Extension of this [3-atom + 2-atom] nitrogen hetero-
cycle synthesis to indole targets would require tosylanil-
ides as the three-atom component. In this instance,
alkylidene carbene insertion into a much more refractory
aryl C-H bond (BDE ∼ 103 kcal/mol) would be necessary
to secure the indole product, a transformation which
enjoys scant precedent.1g However, the ready availability
of the precursor tosylanilides and the lack of a prereq-
uisite for further aryl ring activation suggested that
successful realization of this strategy might provide a
novel and useful complement to current art.8 In fact,
treatment of the lithium salt of tosylanilide itself with
phenyl(propynyl)iodonium triflate (15) furnished the
desired 2-methylindole nucleus 45a in 66% yield, eq 8
and Table 2, entry a.
(5) All pKa data were taken from Bordwell, F. G. Acc. Chem. Res.
1988, 21, 456. The following model compounds (in DMSO) were used
for comparison: (a) NH3 41; (b) PhCONH2 23.4; (c) F3CSO2NH2 9.7;
(d) F3CCONH2 17.2; (e) PHSO2NH2 16.1; (f) CH3SO2NH2 17.5.
(6) Control experiments demonstrated that alkynyliodonium salt 15
remains unchanged for 72 h at rt in THF-d8 and only suffers ∼20%
decomposition (to unidentified materials) after 7 h at 60 °C in THF-
d8.
(7) Williamson, B. L.; Stang, P. J .; Arif, A. M. J . Am. Chem. Soc.
1993, 115, 2590.
(8) Gribble, G. W. Contemp. Org. Synth. 1994, 1, 145.

Addition/Cyclizations of Sulfonamide Anions
J . Org. Chem., Vol. 61, No. 16, 1996 5443
Sch em e 4
example is the only instance throughout the entire study
in which intermolecular insertion into solvent was seen.
The basis for this unusual reactivity in the triflamide
case remains obscure.
The intramolecular variant of this tosylamide/iodonium
salt combination is particularly well suited to the con-
struction of (at least) bicyclic nitrogen-containing skeleta
which are related to several cyclopentylamine-containing
naturally occurring alkaloids. At the outset, this chem-
istry was not without its risks: (1) preparation of the
sensitive alkynyliodonium unit from its alkynylstannane
precursor requires a very reactive electrophilic iodinating
reagent which might be incompatible with the tosylamide
moiety, and (2) activation of the cyclization precursor (e.g.
54) with base raises the specter of untoward reaction with
the alkynyliodonium unit (addition, propargyl deproto-
nation?) in competition with tosylamide deprotonation.
Nevertheless, this cyclization sequence proceeds smoothly
and normally in higher yields than the intermolecular
cases to afford annelated cyclopentenyltosylamide prod-
ucts in which the size of the nitrogen bearing ring
depends upon the tether length connecting nucleophile
with electrophile. The initial studies focused on three
key issues (eq 10): (1) What tether length n is acceptable?
(2) What functionality (X, R, R1) are tolerated/bene-
ficial? (3) What level of diastereoselectivity can be
achieved?
Meta substituents on the tosylanilide ring introduce
an issue of regioselectivity upon carbene C-H insertion.
The meta-functionalized substrates 43b-43e were ex-
amined in this indole synthesis to test the premise that
the facility of C-H insertion might be modulated by the
through space orbital interaction shown in 44. In
practice, only modest and unidirectional selectivity for
insertion into the least sterically encumbered C-Hb bond,
irrespective of the electronic character of the cognate
R-Ar bond, was detected (Table 2, entries b-e). Indole
formation from iodonium salt 15 and o-methyltosylanilide
(47) did not proceed in any detectable amount, plausibly
due to the repulsive peri-type steric interactions indicated
in 47a which would be unavoidable as the carbene
approaches the C-H bond, eq 9.
In each instance, and especially with 47, indole forma-
tion was accompanied by substantial quantities (10-30%)
of a highly colored, purple, unstable product which
1
displayed characteristic signals in the H and 13C NMR
spectra of the crude reaction mixtures. Although these
byproducts defied all attempts at purification/isolation,
the spectral evidence in hand, coupled with literature
precedent and subsequent results in the intramolecular
series (vide infra) suggests an “azulene”-type structural
assignment 51, Scheme 4.9 These products 51 might
arise through a mechanistic pathway that features
alkylidene carbene addition to an alkene in the toluene
ring of the tosyl unit, followed by electrocyclic opening
of the exceedingly strained norcaradiene intermediate 50.
Thus, the penalty for relying on a relatively slow aryl-H
insertion appears to be the emergence of a normally
uncompetitive CdC addition.
Attempts to suppress this unwanted addition process
focused on either removing, or at least hindering, the
offending tolyl unit. Toward this end, substrates 52a -
52c were combined with phenyl(propynyl)iodonium tri-
flate (15) under standard conditions, but no useful results
were forthcoming. The steric hindrance strategy (mesityl
52a or trisyl 52b) did not afford any characterizable
products, while complete replacement of the tolyl ring
with CF3 (52c) furnished only modest amounts of indole
(∼30%) along with the THF-alkylidene carbene inter-
molecular insertion product 53 in similar yield. This
The substrates designed to probe these questions,
59a -f, 62, 63, and 66, were assembled via standard
propargyl anion chemistry where appropriate, Scheme
5. The tosylamide functionality was introduced by the
method of Weinreb.10 The eight-membered ring cycliza-
tion precursor tosylamide 66 was prepared by a slightly
different route, starting with ester 64, which relied on
alkyne introduction through a Corey-Fuchs procedure11
as the requisite parent alkynol was not readily available.
These cyclization substrates were stored as their alky-
nylstannanes, which themselves were rather labile and
only survived chromatography if the silica gel was first
deactivated with 10-20% H2O and ∼0.1% Et3N was
included in the eluant. The alkynyliodonium salts were
generated in situ as required and used immediately in
cyclization experiments.
The tosylurea substrate 62 was prepared from cyclo-
hexanecarboxaldehyde (60) as shown in Scheme 5. It is
notable that stannylation of the dianion derived from
double deprotonation of the tosylurea alkyne precursor
to 62 only occurred on carbon. Tosylimide 63 was readily
(10) Henry, J . R.; Marcin, L. R.; McIntosh, M. C.; Scola, P. M.;
Harris, G. D., J r.; Weinreb, S. M. Tetrahedron Lett. 1989, 30, 5709.
(11) Corey, E. J .; Fuchs, P. L. Tetrahedron Lett. 1972, 3769.
(9) Gilbert, J . C.; Blackburn, B. K. Tetrahedron Lett. 1990, 31, 4727.

5444 J . Org. Chem., Vol. 61, No. 16, 1996
Feldman et al.
Ta ble 3. Ba se-Med ia ted Bicycliza tion of
Sch em e 5
Alk yn yliod on iu m Tosyla m id es a n d Tosylim id es
Sch em e 6
able and the requisite stannane 70 was obtained without
event.
The prototype case 59a , Table 3, entry a, established
that the transformation proceeds as desired to furnish
bicyclic tosylenamide products 71a /b. Optimization stud-
ies with 59a converged on a set of “best” parameters
(THF solvent, 0.08 M, 1 equiv of t-BuOK, -40 °C f rt)
similar to those derived for the intermolecular case. The
intermediate alkynyliodonium salt did not share the
stability of its lower molecular weight analogs (e.g., 15),
and decomposition often foiled attempts at isolation and
purification. Accordingly, an experimental protocol was
devised which limited the exposure of these fragile
intermediates to adventitious moisture or warm temper-
atures (see Experimental Section).
available from the precursor 58a already in hand. Again,
stannylation proceeded exclusively on carbon. The prepa-
ration of the final cyclization substrate, 70, was slightly
more involved and is detailed in Scheme 6. Nevertheless,
both propargyl anion alkylation and Mitsunobu-based
introduction of the tosylamide functionality proved reli-
Examination of the bicyclization results summarized
in Table 3 indicates that five- and six-membered rings
are readily accessible through intramolecular addition of

Addition/Cyclizations of Sulfonamide Anions
J . Org. Chem., Vol. 61, No. 16, 1996 5445
Sch em e 7
tosylamide or tosylimide anions to alkynyliodonium salts.
At least in the one constrained case examined, a seven-
membered ring can be formed (entry j). All efforts
directed toward eight-membered ring synthesis with
substrate 66 failed.
Tosylamide, tosylimide, and tosylurea moieties are
equally efficient nucleophilic cyclization initiators based
on this limited data set. At the C-H insertion end, the
results of this study mirror prior efforts to delineate the
reactivity patterns of alkylidene carbenes. Primary
(entry b), secondary (entries c, d, and g) benzylic (entries
a and h), and tertiary (entries f and j) C-H bonds all
react with similar facility. In addition, ether functional-
ity at the insertion site (entries d, f, and j) is compatible
with the reactive carbenic intermediate (compare 21b),
with the proviso that product lability may thwart isola-
tion of the first formed adduct. Thus, the silyl ether
74a /b readily hydrolyzes upon chromatography to furnish
the ring-opened product 82, eq 11. Similarly, while the
ketal products derived from 59f and 70 can be detected
1
in the H NMR spectrum of the crude reaction product,
exposure to (deactivated) silica gel led to nitrogen-
assisted solvolysis and delivered either hydrolysis (e.g.,
77) or elimination products (e.g., 80). The tosylimide
(urea) products 78a /b and 79a /b appear more resistant
in general to silica gel-mediated hydrolysis of the enimide
functionality.
the molecular periphery will engender differential steric
interactions which will influence the energies of these
diastereomeric transition states. Application of this
model only to the intramolecular bicyclizations is war-
ranted at present as the intermolecular dihydropyrrole
series did not afford meaningful results with R,â-disub-
stituted ethyltosylamide substrates.
Attempts to effect alkylidene carbene/Ar-H insertion
with substrate 59e afforded only trace amounts of the
desired indenyltosylamide 75. Rather, formal addition
of the carbene to the tolyl ring led, via a putative
norcaradiene intermediate (cf. 50), to an azulene-type
product 76 related to those observed in the indole series.
Why the alkylidene carbene intermediate derived from
59e scarcely participates in aryl C-H insertion while the
related carbene 49 does so with facility remains a matter
of speculation.
The levels of 1,2 and 1,3 diastereoselectivity attainable
in this bicyclization sequence are highly variable and it
is difficult to draw generalizations from these limited
examples. The prototype case 59a (entry a) shows only
a barely discernable preference for the 1,3 syn product
with R ) Ph, similar to that seen with both the related
imide substrate 63 (entry h) and 59d (R ) OTBDMS,
entry d). Matters improve for those substrates designed
to test 1,2 relative asymmetric induction (entries b, c,
and g). In these instances, selectivity ranges from
3-3.5:1 favoring the 1,2 syn isomers (entries b and c) to
as much as 16:1 with the similar (to 59c) tosylurea
substrate 62 (entry g).
A framework for discussing these stereochemical re-
sults can be developed from the seminal model for
alkylidene carbene C-H 1,5 insertion proposed by Gilbert.3g
The question of diastereoselectivity in these transforma-
tions has been subject to only scattered experimental
inquiry3e and no theoretical examination. A priori, two
diastereotopic transition states featuring flattened chair-
like (84a ) and boatlike (84b) conformations can be posited
for insertion of the archetype alkylidene carbene 83, eq
12. Within this context, attachment of substituents along
This simple two-state model can be expanded to
rationalize the striking difference in diastereoselectivity
between the similar examples 73a /b and 78a /b. In both
cases, nitrogen nucleophile cyclization into the tethered
alkynyliodonium salt presumably affords similar alky-
lidene carbene intermediates 85C and 85N, respectively,
Scheme 7. In principle, all four 1,5-disposed hydrogens
Ha-Hd in 85 are available for insertion through the
transition states approximated by 86C/N-89C/N. Two
of these species (88 and 89) have boatlike dispositions
and none of the observed products 73a /b or 78a /b could
have derived from them. Rather, the observed stereo-
chemical outcome of these cyclizations is only consistent
with reaction through the chairlike alternatives 86C/N
and 87C/N. The structural rigidity in 85 permits iden-
tification of salient transannular steric interactions in
the bicyclization series that are not so apparent in the
more flexible intermolecular cases. In the two chairlike
constructs 87C and 87N, a syn pentane-like collision

5446 J . Org. Chem., Vol. 61, No. 16, 1996
Feldman et al.
2,3-Dih yd r o-5-m et h yl-3-p h en yl-1-[(t r iflu or om et h yl)-
su lfon yl]p yr r ole (16c). A solution of n-BuLi (2.5 M in
hexane, 0.41 mL, 1.0 mmol, 2 equiv) was added dropwise to a
deoxygenated 0 °C solution of N-(2-phenylethyl)trifluoro-
methanesulfonamide (0.26 g, 1.0 mmol, 2 equiv) in 50 mL of
THF. After 15 min the solution was charged with phenyl-
(propynyl)iodonium triflate (15) (0.20 g, 0.51 mmol) and stirred
at rt for 20 h. The reaction solution was then concentrated in
vacuo, and the crude product residue was purified by flash
column chromatography, eluting with hexane-Et2O (9:1, with
0.1% triethylamine), to give 41 mg (28%) of pure 16c as a light
yellow oil: IR (thin film) 1223 cm-1; 1H NMR (300 MHz, C6D6)
δ 7.10-6.80 (m, 5 H), 4.48 (q, J ) 1.3 Hz, 1 H), 3.91 (m, 1 H),
3.57 (ddd, J ) 10.9, 6.9, 1.0 Hz, 1 H), 3.39 (m, 1 H), 1.81 (dd,
J ) 2.1, 1.5 Hz, 3 H); 13C NMR (50 MHz, CDCl3) δ 142.0, 138.8,
128.9, 127.4, 127.1, 120.1 (q, J ) 324.8 Hz), 115.1, 59.2, 45.2,
14.1; EIMS m/z (relative intensity) 291 (M+, 100), 158 (52),
105 (40); HRMS calcd for C12H12F3NO2S 291.0541, found
291.0562.
between a hydrogen (C series) or tosyl group (N series)
and the indicated cyclohexyl methylene is evident. In
the alternative chairlike conformer 86C only, a transan-
nular interaction between the R-oriented hydrogen on
C(1) (Y ) H,H) and the indicated cyclohexyl methylene
appears prominant. This interaction is absent in the
tosylurea series 86N (Y ) O). The observed results with
59c suggest that, to the extent that this model is
applicable, the interaction shown in 87C is more penal-
izing than that in 86C, and so 73a is favored. This
difference is amplified in the tosylimide series 62, as the
former interaction now involves the much larger tosyl
group (in 87N), while the latter interaction (in 86N) is
removed along with the offending R-hydrogen. Hence,
the observed diastereoselectivity with 62 is enhanced
compared with 59c. While this model provides a post
facto rationale for the observed selectivity, only further
testing will determine if it has any predictive value.
In summary, the tandem nucleophile addition/carbene
insertion sequence characteristic of alkynyliodonium
salts has been extended to include sulfonamide and
sulfonimide nucleophiles. Intermolecular combination
leads to a [3-atom + 2-atom] strategy for dihydropyrrole,
pyrrole, and indole synthesis. An intramolecular version
demonstrates for the first time that the reactive alky-
nyliodonium electrophile can be generated in the pres-
ence of the (pre)nucleophile. The cyclopentenyltosyl-
amide and -imide products of these bicyclizations are
formed with varying (and only sketchily understood)
levels of diastereoselectivity.
Rea ction of N-[(4-Meth ylp h en yl)su lfon yl]cycloh exy-
la m in e. Following general procedure A, n-BuLi (2.5 M in
hexane, 0.30 mL, 0.75 mmol, 1 equiv) was added to cyclohex-
anesulfonamide (0.19 g, 0.75 mmol) in 75 mL of THF at -78
°C. The reaction was heated to reflux, followed by addition of
phenyl(propynyl)iodonium triflate (15) (0.31 g, 0.78 mmol, 1.04
equiv) in 8 mL of THF. After 3 h at reflux, the reaction was
cooled to rt. Purification of the crude product by flash
chromatography with 4% Et2O/petroleum ether (with 0.1%
Et3N) as eluent afforded 0.10 g of 28 as a colorless oil (45%)
and 0.11 g of 32 as a colorless oil (45%).
cis-3a ,4,5,6,7,7a -Hexa h yd r o-2-m eth yl-1-[(4-m eth ylp h e-
n yl)su lfon yl]in d ole (28). Spectral data obtained matches
that reported in the literature.4b IR (CCl4) 1357, 1168 cm-1
;
1H NMR (300 MHz, C6D6) δ 7.77 (d, J ) 8.3 Hz, 2 H), 6.82 (d,
J ) 8.0 Hz, 2 H), 4.46 (s, 1 H), 4.12 (dt, J ) 6.3, 2.5 Hz, 1 H),
2.25 (m, 1 H), 2.11 (dd, J ) 2.7, 1.4 Hz, 3 H), 2.02 (m, 1 H),
1.91 (s, 3 H), 1.68 (m, 1 H), 1.40 (m, 1 H), 1.31-0.86 (m, 5H);
13C NMR (75 MHz, C6D6) δ 142.8, 139.6, 138.2, 129.6, 127.4,
117.9, 63.0, 39.8, 28.9, 26.0, 21.4, 21.1, 21.0, 16.3; EIMS m/z
(relative intensity) 291 (M+, 16.2), 136 (100); HRMS calcd for
C16H21NO2S: 291.1293, Found 291.1299.
Exp er im en ta l Section
Tetrahydrofuran (THF), dimethoxyethane (DME), and di-
ethyl ether (Et2O) were dried by distillation from sodium/
benzophenone under argon (Ar). Benzene and methylene
chloride (CH2Cl2) were dried by distillation from CaH2 under
Ar. Liquid (flash)12 chromatography was carried out using 32-
63 µm silica gel and the indicated solvent system. Hexane,
Et2O, petroleum ether, and pentane used in flash chromatog-
raphy were distilled from CaH2 prior to use. All moisture and
air sensitive reactions were carried out in predried glassware
under an inert atmosphere of Ar. All melting points are
uncorrected. Low and high resolution mass spectra (EIMS,
HRMS) were obtained at 50-70 eV by electron impact.
Chemical impact mass spectra (CIMS) were obtained with
isobutane as the reagent gas. Combustion analyses were
performed by Midwest Microlabs, Indianapolis, IN. 13C NMR
spectra are provided in the supporting information to establish
purity for those compounds which were not subject to combus-
tion analyses.
Gen er a l P r oced u r e A (In ter m olecu la r Tosyla m id e/
Alk yn yliod on iu m Ad d ition s). n-BuLi (1 equiv) in hexane
was added dropwise over several minutes to a deoxygenated,
stirring solution of the appropriate sulfonamide in THF (∼0.01
M) at -78 °C. The reaction was warmed either to rt or reflux
(as indicated) and phenyl(propynyl)iodonium triflate (15)
(∼1.04 equiv) was added dropwise via syringe over 15 min as
a ∼0.10 M solution in deoxygenated THF. Stirring was
maintained for the indicated time, at which point the solution
was diluted with an equal volume of Et2O and poured into an
equal volume of ice/brine. The aqueous layer was extracted
with Et2O (3×), and the combined organic phases were washed
with H2O and brine, dried over anhydrous MgSO4, filtered,
and concentrated in vacuo. The resulting residue was purified
via flash chromatography on silica gel with the indicated
solvent system.
4-Meth yl-N-cycloh exyl-N-(2-tetr a h yd r ofu r yl)ben zen e-
su lfon a m id e (32): IR (CDCl3) 1329, 1159 cm-1; 1H NMR (300
MHz, C6D6) δ 8.07 (d, J ) 8.3 Hz, 2 H), 6.83 (d, J ) 7.9 Hz, 2
H), 5.48 (t, J ) 6.7 Hz, 1 H), 3.86 (m, 1 H), 3.46 (dt, J ) 5.0,
7.8 Hz, 1 H), 3.35 (m, 1 H), 1.88 (s, 3 H), 2.27-0.85 (m, 14H);
13C NMR (75 MHz, C6D6) δ 142.2, 141.4, 129.3, 127.8, 89.0,
67.8, 57.7, 34.1, 31.7, 31.4, 26.8, 25.5, 25.4, 21.1; CIMS m/z
(relative intensity) 324 (MH+, 100); HRMS calcd for C17H25
NO3S: 323.1555, found 323.1546.
-
Tosylyn a m id e 40. Sulfonamide 38 (218 mg, 0.654 mmol)
dissolved in 3 mL of THF was cooled to -78 °C and treated
with 2.5 M BuLi in hexanes (262 µL, 0.654 mmol, 1 equiv).
After 5 min, (tert-butyloxy)[phenyl[[(trifluoromethyl)sulfonyl]-
oxy]iodo]acetylene (39) (313 mg, 0.654 mmol, 1 equiv) was
added in one portion, and the reaction was stirred for 1 h
without external cooling. The solution was diluted with 25
mL of Et2O and poured into a saturated NH4Cl solution. The
organic phase was washed once with brine, dried over Na2-
SO4, filtered, and concentrated in vacuo. Flash chromatogra-
phy (20% Et2O in hexanes, silica gel pretreated with 1% Et3N
(w/v) in hexanes) of the resulting residue gave 121 mg of
ynamide 40 as a colorless oil (40%). IR (CCl4) 2214, 1749, 1702
1
cm-1; H NMR (200 MHz, CDCl3) δ 7.47 (d, J ) 8.3 Hz, 2H),
(12) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
(13) Stang, P. J .; Williamson, B. L.; Zhdankin, V. V. J . Am. Chem.
Soc. 1991, 113, 5780.
7.35-7.10 (m, 7H), 4.78 (dd, J ) 11.0, 4.4 Hz, 1H), 3.69 (s,
3H), 3.34 (dd, J ) 14.5, 4.4 Hz, 1H), 3.08 (dd, J ) 14.4, 11.0

Addition/Cyclizations of Sulfonamide Anions
J . Org. Chem., Vol. 61, No. 16, 1996 5447
aldehyde as a clear oil: IR (thin film) 3284, 1723 cm-1 1H
NMR (200 MHz, CDCl3) δ 9.75 (t, J ) 1.6 Hz, 1 H), 7.75 (d, J
) 8.3 Hz, 2 H), 7.31 (d, J ) 8.0 Hz, 2 H), 4.90 (m, 1 H), 2.97
(q, J ) 6.5 Hz, 2 H), 2.82 (m, 1 H), 2.55 (td, J ) 6.7, 1.6 Hz, 2
H), 2.43 (s, 3 H), 2.09 (d, J ) 2.4 Hz, 1 H), 1.80-1.30 (m, 4 H);
13C NMR (50 MHz, CDCl3) δ 200.3, 143.4, 136.8, 129.7, 127.0,
84.9, 70.8, 48.2, 42.6, 31.2, 27.0, 25.1, 21.4; CIMS m/z (relative
intensity) 294 (MH+, 100), 276 (23), 184 (63).
Hz, 1H), 2.41 (s, 3H), 1.51 (s, 9H); 13C NMR (50 MHz, CDCl3)
δ 168.8, 153.0, 145.1, 135.4, 133.6, 129.6, 129.0, 128.6, 127.9,
127.0, 82.9, 77.5, 71.9, 62.9, 52.8, 35.9, 28.2, 21.6; EIMS m/z
(relative intensity) 457 (M+, 6), 401 (36); HRMS calcd for
C24H27NO6S 457.1559, found 457.1571.
;
Tosylyn a m in e 42. Sulfonamide 36a (119 mg, 0.411 mmol)
and benzoyl[phenyl[[(trifluoromethyl)sulfonyl]oxy]iodo]acetylene
41 (198 mg, 0.411 mmol) gave 109 mg of the title compound
as a colorless oil via the same procedure as employed for the
This aldehyde (0.64 g, 2.2 mmol) and triethyl orthoformate
(0.36 g, 2.4 mmol, 1.1 equiv) were heated at 50 °C in 0.30 mL
of ethanol. After 3 h the reaction was poured over ice/brine
(1:1), extracted with Et2O, dried over anhydrous Na2SO4, and
concentrated in vacuo. Purification of the crude product
residue by flash column chromatography, eluting with hex-
ane-Et2O (1:1), gave 0.42 g (52%) of pure tosylamide diethyl
synthesis of tosylynamide 42 (64%). IR (CCl4) 2194, 1638 cm-1
;
1H NMR (200 MHz, CDCl3) δ 8.15 (dt, J ) 6.0, 1.2 Hz, 2H),
7.70-7.40 (m, 5H), 7.30-7.20 (m, 5H), 7.13 (d, J ) 8.2 Hz,
2H), 4.87 (dd, J ) 8.7, 6.8 Hz, 1H), 2.35 (s, 3H), 2.30-1.95 (m,
2H), 0.91 (t, J ) 7.3 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ
176.8, 145.2, 138.3, 137.0, 134.6, 133.5, 129.6, 129.0, 128.6,
128.5, 128.3, 127.7, 126.9, 89.2, 79.4, 66.1, 27.7, 21.6, 11.0;
EIMS m/z (relative intensity) 417 (M+, 4), 299 (3); HRMS, calcd
for C25H23NO3S 417.1399, found 417.1397.
1
acetal as a clear oil: IR (thin film) 3283 cm-1; H NMR (200
MHz, CDCl3) δ 7.75 (d, J ) 8.3 Hz, 2 H), 7.30 (d, J ) 8.6 Hz,
2 H), 4.80 (bs, 1 H), 4.70 (m, 1 H), 3.76-3.43 (m, 4 H), 2.95 (q,
J ) 6.6 Hz, 2 H), 2.43 (m, 1 H), 2.42 (s, 3 H), 2.04 (d, J ) 2.4
Hz, 1 H), 1.77-1.34 (m, 6 H), 1.20 (t, J ) 7.0 Hz, 3 H); 13C
NMR (75 MHz, CDCl3, DEPT) δ C, 143.3, 136.9, 86.2; CH,
129.6 (2), 127.0 (2), 101.3, 70.2, 27.2; CH2, 62.1, 61.2, 42.9,
38.9, 31.7, 27.1; CH3, 21.4, 15.3, 15.2; EIMS m/z (relative
intensity) 367 (M+, 0.5), 322 (9), 103 (100); HRMS calcd for
Gen er a l P r oced u r e B. Alk yla tion s of Tr ilith ia ted
4-P en tyn -1-ol a n d 5-Hexyn -1-ol. 4-Pentyn-1-ol or 5-hexyn-
1-ol (1 equiv) was added to a -78 °C solution of n-BuLi (2.5 M
in hexanes, ∼3.7 equiv) in deoxygenated THF (∼0.6 M based
on alkynol). This solution was stirred without external cooling
for the indicated time and then cooled (0 °C or -78 °C, see
below), and the alkyl halide (1-1.6 equiv) was added. The
reaction was once again stirred without external cooling for
the indicated time and then cautiously poured into saturated
NH4Cl, extracted with Et2O, washed with brine, dried over
anhydrous Na2SO4, and concentrated in vacuo. R-Alkylated
acetylenes were isolated by flash column chromatography of
the crude product residue on silica gel. In some cases
distillation of starting material from the crude product residue
preceded chromatography.
Gen er a l P r oced u r e C. Mitsu n obu Rea ction of N-(t-
Bu toxyca r bon yl)-p-tolu en esu lfon a m id e w ith Alcoh ols.
Adapted from the method of Weinreb.10 Diethyl azodicarboxy-
late (2.6 equiv) was added dropwise to a deoxgenated rt
solution of alkynol substrate (1 equiv), N-BOC p-toluene-
sulfonamide (1.5 equiv), and triphenylphosphine (3 equiv) in
THF (∼0.1 M based on alkynol). After the indicated time, the
reaction was concentrated in vacuo and the crude product
residue was purified by flash column chromatography on silica
gel.
Gen er a l P r oced u r e D. Dep r otection of BOC-Tosyla -
m id es. A ∼0.1 M deoxygenated rt solution of substituted
N-BOC p-toluenesulfonamide in CH2Cl2 was acidified with
trifluoroacetic acid (5-10 equiv, see below). After the indi-
cated time the reaction solution was poured into saturated
NaHCO3, extracted with CH2Cl2, washed with water, dried
over anhydrous Na2SO4, and concentrated in vacuo. Second-
ary p-toluenesulfonamides were isolated by flash column
chromatography of the crude product residue on silica gel.
Gen er al P r ocedu r e E: Stan n ylation of Lith iated Acety-
len es w ith Tr ibu tyltin Ch lor id e. A deoxygenated -78 °C,
∼0.06 M solution of terminal alkyne substrate in THF was
treated with a 2.5 M hexane solution of n-BuLi (2 equiv based
on alkyne). The reaction was kept at -78 °C or warmed to
0 °C for the indicated time, and then n-Bu3SnCl was added
(1 equiv based on alkyne). The reaction solution was then
stirred without external cooling and, after the indicated time,
poured over saturated NH4Cl solution, extracted with Et2O,
washed with brine, dried over anhydrous Na2SO4, and con-
centrated in vacuo. Stannylated alkynes were isolated by flash
column chromatography of the crude product residue on silica
gel.
C
19H29NO4S 367.1817, found 367.1836.
Following general procedure E, a -78 °C solution of this
tosylamide (0.42 g, 1.1 mmol, 1.0 equiv) in 20 mL of THF was
treated with 2.5 M n-BuLi (1.00 mL, 2.50 mmol, 2.2 equiv).
This solution was warmed at 0 °C for 20 min, and then n-Bu3-
SnCl (0.37 g, 1.1 mmol, 1 equiv) was added. The resulting
solution was allowed to react at rt for 1 h. Following the
indicated workup, purification of the crude product residue by
flash column chromatography, eluting with hexane-Et2O (2.3:
1), gave 0.48 g (64%) of pure 59f as a clear oil: IR (thin film)
1
3279 cm-1; H NMR (200 MHz, CDCl3) δ 7.75 (d, J ) 8.3 Hz,
2 H), 7.30 (d, J ) 7.9 Hz, 2 H), 4.74 (m, 1 H), 4.63 (t, J ) 6.1
Hz, 1 H), 3.78-3.42 (m, 4 H), 2.95 (q, J ) 6.6 Hz, 2 H), 2.45
(m, 1 H), 2.42 (s, 3 H), 1.80-1.44 (m, 9 H), 1.44-1.14 (m, 15
H), 1.00-0.83 (m, 15 H); 13C NMR (75 MHz, CDCl3, DEPT) δ
C, 143.2, 136.9, 113.2, 83.5; CH, 129.6 (2), 127.0 (2), 101.8,
28.7; CH2, 62.6, 61.1, 43.0, 39.5, 32.2, 28.8 (3), 27.1, 26.8 (3),
10.9 (3); CH3, 21.4, 15.3, 15.2, 13.6 (3); CIMS m/z (relative
intensity) 658 (MH+, 38), 612 (80), 554 (49). Anal. Calcd for
C31H55NO4SSn: C, 56.71; H, 8.44; N, 2.13; S, 4.88. Found:
C, 56.46; H, 8.13; N, 2.24; S, 4.79.
Tosyla m id e 61. A solution of 2.5 M n-BuLi in hexanes
(14.20 mL, 35.50 mmol, 1 equiv) was added over 5 min to a 0
°C solution of (trimethylsilyl)acetylene (3.47 g, 35.4 mmol) in
100 mL of deoxygenated THF. After 15 min the solution was
charged with cyclohexanecarboxaldehyde (60) (3.19 g, 28.5
mmol, 0.8 equiv) and stirred at rt for 2 h. The reaction solution
was then poured over ice/saturated NH4Cl (1:1), extracted with
Et2O, washed with brine, dried over anhydrous Na2SO4, and
concentrated in vacuo. The resulting residue was diluted with
200 mL of methanol and treated with solid K2CO3 (∼2 g). After
2 h the reaction was poured over ice/saturated NH4Cl solu-
tion/1 M HCl (1:1:1), extracted with Et2O, washed with brine,
dried over anhydrous Na2SO4, and concentrated in vacuo to
give 3.44 g (88%) of the pure acetylenated alcohol as a clear
oil: IR (thin film) 3379, 3300 cm-1; 1H NMR (300 MHz, CDCl3)
δ 4.16 (m, 1 H), 2.47 (d, J ) 2.2 Hz, 1 H), 2.01 (d, J ) 5.5 Hz,
1 H), 1.88-1.76 (m, 4 H), 1.70 (m, 1 H), 1.59 (m, 1 H), 1.39-
0.98 (m, 5 H); 13C NMR (75 MHz, CDCl3, DEPT) δ C, 83.9;
CH, 73.6, 67.0, 43.8; CH2, 28.3, 27.9, 26.3, 25.8, 25.76; CIMS
m/z (relative intensity) 139 (MH+, 4), 121 (100), 93 (63).
Following general procedure C, diethyl azodicarboxylate
(1.66 g, 9.52 mmol, 2.6 equiv) was added dropwise to a
deoxygenated rt solution of this alcohol (0.50 g, 3.6 mmol),
N-BOC p-toluenesulfonamide (1.50 g, 5.53 mmol, 1.5 equiv),
and triphenylphosphine (2.85 g, 10.9 mmol, 3 equiv) in 100
mL of THF. After 20 h the reaction was concentrated in vacuo,
and the crude product residue was purified by flash column
chromatography, eluting with hexane-Et2O (4:1), to give 1.05
g (74%) of pure BOC-protected tosylimide as a clear oil that
crystallized upon standing: mp 130-132°; IR (CCl4) 3312,
Tosyla m id e 59f. A solution of sulfur trioxide-pyridine
complex (1.16 g, 7.29 mmol, 3 equiv) in 5 mL of DMSO was
combined with a solution of the hydroxytosylamide derived
from 58d (0.72 g, 2.4 mmol) and triethylamine (3.63 g, 35.9
mmol, 15 equiv) in 5 mL of DMSO. After 1.5 h the reaction
solution was poured over ice/1 M HCl (1:1) and extracted with
CH2Cl2. The organic layer was washed with water, dried over
anhydrous Na2SO4, and concentrated in vacuo. Purification
of the crude product residue by flash column chromatography,
eluting with hexane-Et2O (1:1), gave 0.41 g (57%) of pure

5448 J . Org. Chem., Vol. 61, No. 16, 1996
Feldman et al.
1737 cm-1; 1H NMR (300 MHz, C6D6) δ 8.04 (d, J ) 8.3 Hz, 2
H), 6.77 (d, J ) 8.4 Hz, 2 H), 5.31 (dd, J ) 10.4, 2.5 Hz, 1 H),
2.53 (m, 1 H), 2.23 (m, 2 H), 2.05 (d, J ) 2.5 Hz, 1 H), 1.85 (s,
3 H), 1.65 (m, 2 H), 1.47 (m, 1 H), 1.19 (s, 9 H), 1.31-0.86 (m,
5 H); 13C NMR (75 MHz, C6D6, DEPT) δ C, 150.5, 143.7, 138.6,
83.9, 81.8; CH, 129.2 (2), 128.4 (2), 72.7, 55.7, 41.2; CH2, 31.5,
29.9, 26.3, 26.1, 25.9; CH3, 27.8 (3), 21.1; CIMS m/z (relative
intensity) 391 (M+, 5), 336 (100), 182 (78). Anal. Calcd for
C21H29NO4S: C, 64.42; H, 7.47; N, 3.58; S, 8.19. Found: C,
64.53; H, 7.61; N, 3.56; S, 8.18.
5H), 2.95-2.43 (m, 5H), 2.17 (d, J ) 2.4 Hz, 1H), 1.87-1.73
(m, H); 13C NMR (50 MHz, CDCl3) δ 177.7, 141.2, 128.4, 126.0,
85.1, 70.7, 39.7, 36.0, 33.2, 27.4; EIMS m/z (relative intensity)
202 (M+, 10), 157 (15); HRMS calcd for C13H14O2 202.0994,
found 202.1009.
This acid (0.85 g, 4.2 mmol) in 5 mL of THF was treated
with TsNCO (0.70 mL, 4.6 mmol, 1.1 equiv) and then Et3N
(0.59 mL, 4.2 mmol, 1 equiv), which caused the immediate
evolution of CO2. After 0.5 h at rt, 1 mL of H2O and 50 mL of
Et2O were added, and the solution was washed once with 50
mL of 1 N HCl and once with brine. Drying (Na2SO4) of the
organic phase, filtration, solvent evaporation, and flash chro-
matography of the residue (50% Et2O in hexane) gave 1.40 g
of the derived tosylimide as a viscous oil (94%). IR (CCl4) 2116,
1727 cm-1; 1H NMR (200 MHz, CDCl3) δ 9.12 (s, 1H), 7.94 (d,
J ) 8.4 Hz, 2H), 7.35-7.05 (m, 7H), 2.90-2.53 (m, 3H), 2.53-
2.40 (m, 2H), 2.39 (s, 3H), 2.16 (d, J ) 2.4 Hz, 1H), 1.78-1.60
(m, 2H); 13C NMR (50 MHz, CDCl3) δ 168.7, 145.1, 140.9, 135.3,
129.5, 128.3, 125.9, 84.9, 71.6, 41.5, 35.7, 33.0, 27.2, 21.6; EIMS
m/z (relative intensity) 355 (M+, 4), 264 (2); HRMS calcd for
C20H21NO3S 355.1242, found 355.1243.
Following general procedure D, a rt solution of this BOC-
protected tosylamide (1.84 g, 4.71 mmol) in 100 mL of CH2Cl2
was acidified with trifluoroacetic acid (5.32 g, 46.7 mmol, 10
equiv) and allowed to react for 20 h. Following the indicated
workup, the crude product residue was purified by flash
column chromatography, eluting with hexane-Et2O (4:1), to
give 1.22 g (89%) of pure 61 as a white solid: mp 132-134 °C;
1
IR (CCl4) 3311, 3289 cm-1; H NMR (300 MHz, C6D6) δ 7.82
(d, J ) 8.3 Hz, 2 H), 6.79 (d, J ) 8.5 Hz, 2 H), 4.42 (d, J ) 9.4
Hz, 1 H), 3.97 (ddd, J ) 9.4, 6.1, 2.4 Hz, 1 H), 1.89 (s, 3 H),
1.70-1.40 (m, 5 H), 1.58 (d, J ) 2.2 Hz, 1 H), 1.30 (m, 1 H),
1.06-0.84 (m, 5 H); 13C NMR (75 MHz, CDCl3, DEPT) δ C,
143.4, 137.3, 80.8; CH, 129.5 (2), 127.4 (2), 73.1, 50.7, 42.9;
CH2, 28.9, 28.0, 26.0, 25.7, 25.6; CH3, 21.5; CIMS m/z (relative
intensity) 292 (MH+, 5), 200 (100), 184 (10).
To this sulfonimide (1.40 g, 3.94 mmol) in 15 mL of THF at
-78 °C was added KHMDS (2.36 gm, 11.8 mmol, 3 equiv)
followed by n-Bu3SnCl (1.28 mL, 4.72 mmol, 1.2 equiv). The
reaction solution was treated 0.5 h later with saturated
aqueous NH4Cl and then diluted with 100 mL of Et2O. The
organic phase was washed once with 100 mL of H2O and once
with brine, dried over Na2SO4, filtered, and concentrated in
vacuo at rt. Flash chromatography (30% Et2O/hexane) of the
residue using wet silica (20% w/w H2O) yielded 1.61 g of
alkynylstannane 63 as a clear colorless oil (63%). IR (thin film)
Tosyla ted Ur ea 62. A deoxygenated 0 °C solution of
secondary tosylamide 61 (1.00 g, 3.44 mmol) in 60 mL of THF
was treated sequentially with a solution of 2.5 M n-BuLi (1.40
mL, 3.50 mmol, 1 equiv) followed after 20 min by p-toluene-
sulfonyl isocyanate (0.68 g, 3.4 mmol, 1 equiv). The reaction
solution was stirred at rt for 1 h and then poured into ice-cold
brine and extracted with EtOAc. The organic phase was dried
over anhydrous Na2SO4 and concentrated in vacuo. Purifica-
tion of the crude product residue by flash column chromatog-
raphy, eluting with hexane-EtOAc (1:1) followed by EtOAc,
gave 1.10 g (65%) of the pure urea derivative as a white solid:
mp 150-152o; IR (KBr), 3278, 1605 cm-1; 1H NMR (200 MHz,
(D3C)2CO) δ 7.91 (d, J ) 8.4 Hz, 2 H), 7.52 (d, J ) 8.2 Hz, 2
H), 7.16 (d, J ) 8.1 Hz, 2 H), 7.07 (d, J ) 8.0 Hz, 2 H), 5.18 (d,
J ) 10.4 Hz, 1 H), 2.73 (d, J ) 2.5 Hz, 1 H), 2.39 (m, 1 H),
2.31 (s, 6 H), 2.14 (m, 1 H), 1.91-1.48 (m, 4 H), 1.34-1.00 (m,
3 H), 1.00-0.70 (m, 2 H); 13C NMR (50 MHz, D3COD) δ 157.8,
144.4, 142.5, 142.3, 140.1, 129.7, 129.5, 129.4, 127.5, 83.5, 73.6,
56.1, 42.3, 32.5, 30.6, 27.4, 26.9, 26.8, 21.5, 21.4; CIMS m/z
(relative intensity) 489 (MH+, 4), 335 (6), 292 (100).
1
3241, 2143 cm-1; H NMR (200 MHz, CDCl3) δ 9.37 (bs, 1H),
7.93 (d, J ) 8.3 Hz, 2H), 7.35-7.10 (m, 7H), 2.87-2.60 (m,
3H), 2.41 (m, 2H), 2.40 (s, 3H), 1.75-1.20 (m, 14H), 1.09 (t, J
) 7.9 Hz, 6H), 0.93 (t, J ) 7.2 Hz, 9H); 13C NMR (50 MHz,
CDCl3) δ 168.6, 144.8, 141.0, 135.8, 129.4, 128.4, 128.3, 126.0,
112.1, 88.6, 42.3, 36.2, 33.1, 28.9, 28.7, 27.0, 21.6, 13.6, 11.1;
EIMS m/z (relative intensity) 645 (M+, 2), 588 (100); HRMS
calcd for C32H47NO3SSn (M+ - Bu) 588.1593, found 588.1644.
1,1-Dibr om oa lk en yl Alcoh ol 65. To a deoxygenated -78
°C solution of LDA (38.1 mmol, 1.1 equiv) in 125 mL of THF
was added 60 mL of DMPU followed after 10 min by ethyl
4-methylpentanoate (5.00 g, 34.7 mmol). This solution was
held at -78 °C for 1 h, and then 1-bromo-5-(tert-butyldimeth-
ylsilyloxy)pentane (12.7 g, 45.2 mmol, 1.3 equiv) was added.
The resulting solution was allowed to react at rt for 2 h and
then poured over ice-cold 1 M HCl/brine (1:1), extracted with
Et2O, washed with brine, dried over anhydrous Na2SO4,
filtered, and concentrated in vacuo. The resulting crude
product residue was added to a deoxygenated 0 °C suspension
of LiAlH4 (1.63 g, 43.0 mmol, 1.2 equiv) in 100 mL of Et2O.
This mixture was heated at reflux for 1 h and then recooled
to 0 °C, quenched with ice, and filtered, and the precipitate
was rinsed with Et2O. The filtrate was washed with water
and then with brine, dried over anhydrous Na2SO4, filtered,
and concentrated in vacuo. Purification of the crude product
residue by flash column chromatography, eluting with hex-
ane-Et2O (4:1), gave 4.26 g (41%) of pure alkylated alcohol
A 0 °C deoxygenated solution of this urea derivative (0.343
g, 0.704 mmol) in 30 mL of THF was treated with a 1 M THF
solution of lithium bis(trimethylsilyl)amide (1.60 mL, 1.60
mmol, 2.3 equiv). After 20 min, n-Bu3SnCl (0.240 g, 7.37
mmol, 1.04 equiv) was added, and the resulting solution was
allowed to stir at rt for 40 min. The reaction solution was
then poured into ice-cold brine and extracted with Et2O. The
organic phase was washed with brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. Purification of the crude
product residue by flash column chromatography, eluting with
hexane-EtOAc (1:2), gave 0.28 g (51%) of pure 62 as a light
yellow oil: IR (CCl4) 3534, 1598 cm-1 1H NMR (200 MHz,
;
(D3C)2CO) δ 8.01 (d, J ) 8.2 Hz, 2 H), 7.55 (d, J ) 8.0 Hz, 2
H), 7.18 (d, J ) 8.1 Hz, 2 H), 7.11 (d, J ) 8.1 Hz, 2 H), 5.28
(bs, 1 H), 2.39-2.15 (m, 3 H), 2.34 (s, 6 H), 1.92-1.50 (m, 10
H), 1.48-1.25 (m, 8 H), 1.20-0.98 (m, 9 H), 0.88 (t, J ) 7.2
Hz, 9 H); 13C NMR (75 MHz, (D3C)2CO) δ 158.1, 143.4, 142.4,
141.8, 139.8, 129.5, 129.3, 129.2, 126.8, 109.7, 86.9, 56.5, 42.5,
32.2, 29.9, 29.6, 27.6, 26.9, 26.6, 26.3, 21.5, 21.3, 13.9, 11.5;
FABMS m/z (relative intensity) 778 (MH+, 18), 721 (68), 524
(100).
1
as a clear oil. IR (thin film) 3334 cm-1; H NMR (300 MHz,
CDCl3) δ 3.60 (t, J ) 6.5 Hz, 2 H), 3.51 (m, 2 H), 1.75-1.60
(m, 2 H), 1.60-1.45 (m, 3 H), 1.32 (m, 5 H), 1.25-1.04 (m, 3
H), 0.89 (s, 9 H), 0.88 (m, 6 H), 0.05 (s, 6 H); 13C NMR (75
MHz, CDCl3) δ 65.7, 63.2, 40.6, 38.0, 32.8, 31.2, 26.5, 26.2,
25.9, 25.3, 22.9, 18.3, -5.3; EIMS m/z (relative intensity) 302
(M+, 1), 245 (7), 97 (100).
A solution of sulfur trioxide-pyridine complex (4.78 g, 30.0
mmol, 2 equiv) in 20 mL of DMSO was combined with a
solution of the above alcohol (4.11 g, 13.6 mmol) and triethy-
lamine (6.53 g, 64.6 mmol, 4.7 equiv) in 10 mL of DMSO. After
1.5 h the reaction solution was poured over ice/1 M HCl (1:1)
and extracted with CH2Cl2. The organic layer was washed
with water, dried over anhydrous Na2SO4, filtered, and
concentrated in vacuo. The crude aldehyde product was added
as a solution in 5 mL of CH2Cl2 to a deoxygenated 0 °C solution
of triphenylphosphine (7.45 g, 28.4 mmol, 2.1 equiv) and
carbon tetrabromide (4.71 g, 14.2 mmol, 1 equiv) in 40 mL of
Tosylim id e 63. Alcohol 58a (1.23 g, 6.53 mmol) in 20 mL
of acetone was cooled to 0 °C and treated with J ones reagent
in 1 mL portions until TLC indicated the absence of starting
material. The mixture was diluted with 70 mL of EtOAc and
washed with H2O until the aqueous and organic phases were
nearly colorless. The organic phase was dried over Na2SO4,
filtered, and concentrated in vacuo. Flash chromatography
(383:16:1 CH2Cl2:MeOH:HOAc) of the resulting residue gives
0.85 g of the derived acid as a pale yellow oil (64%). IR (thin
1
film) 2115, 1713 cm-1; H NMR (200 MHz, CDCl3) δ 7.35 (m,

Addition/Cyclizations of Sulfonamide Anions
J . Org. Chem., Vol. 61, No. 16, 1996 5449
CH2Cl2. The solution was stirred at 0 °C for 1 h and then
diluted with pentane, and the resulting mixture was filtered,
rinsing the precipitate with pentane. Concentration of the
filtrate in vacuo and purification of the resulting residue by
flash column chromatography, eluting with hexane, gave 2.77
g of a clear oil that was immediately treated with a 1 M THF
solution of n-Bu4NF (12 mL, 12 mmol) and stirred at rt for 1
h. The reaction solution was then poured over ice-cold 1 M
HCl/brine (1:1), extracted with Et2O, washed with brine, dried
over anhydrous Na2SO4, filtered, and concentrated in vacuo.
Purification of the crude product residue by flash column
chromatography, eluting with hexane-Et2O (4:1) and then
with hexane-Et2O (1:1), gave 1.74 g (37%) of pure 65 as a
clear oil. IR (thin film) 3334 cm-1; 1H NMR (300 MHz, CDCl3)
δ 6.09 (d, J ) 9.8 Hz, 1 H), 3.64 (t, J ) 6.6 Hz, 2 H), 2.46 (m,
1 H), 1.66-1.50 (m, 4 H), 1.50-1.14 (m, 8 H), 0.89 (dd, J )
6.6, 4.0 Hz, 6 H); 13C NMR (75 MHz, CDCl3) δ 143.8, 87.5,
62.8, 44.0, 41.7, 34.8, 32.6, 26.8, 25.8, 25.7, 23.4, 22.3.
tion of the residue by flash chromatography (3% Et2O/hexane)
afforded 9.01 g of the silyl ether (97%) as a colorless oil. 1H
NMR (200 MHz, CDCl3) δ 7.50 (d, J ) 7.9 Hz, 1 H), 7.27-7.19
(m, 2 H), 7.16-6.92 (m, 1 H), 3.82 (t, J ) 7.0 Hz, 2 H), 2.97 (t,
J ) 6.9 Hz, 2 H), 0.86 (s, 9 H), -0.03 (s, 6 H); 13C NMR (50
MHz, CDCl3) δ 138.4, 132.6, 131.7, 127.9, 127.1, 124.6, 62.5,
39.6, 25.9, 18.3, -5.4; CIMS m/z (relative intensity) 315 (MH+,
34), 299 (10), 257 (97), 185 (90). Anal. Calcd for C14H23
BrOSi: C, 53.33; H, 7.35. Found: C, 53.28; H, 7.58.
-
A flask containing Mg turnings (2.05 g, 84.2 mmol) was
flame dried under an argon stream, cooled, and charged with
25 mL of Et2O followed by 250 µL of 1,2-dibromoethane. After
the initiation reaction subsided, the silyl ether (13.3 g, 42.1
mmol) was added dropwise so as to maintain a gentle reflux.
After addition of this compound was complete, the reaction
was refluxed for 1 h and cooled to 0 °C, and methoxyallene (6
mL, 70 mmol, 1.7 equiv) in 15 mL of Et2O and CuI (135 mg,
0.71 mmol, 0.02 equiv) were added over 5 min. Over the next
10 min, an exothermic reaction took place which was controlled
by maintaining the ice bath. The resulting light brown slurry
was allowed to slowly warm to rt and stirred there for 10 h.
The reaction was then cooled to 0 °C and slowly treated with
30 mL of aqueous KCN (0.4g)/NH4Cl (4.0 g). Et2O was added
(100 mL), and the organic phase was washed twice with 100
mL portions of 1 N HCl and once with 100 mL of brine. Drying
of the organic layer over Na2SO4, solvent evaporation, and
flash chromatography of the residue (1% Et2O/hexane) gave
8.95 g (77%) of silyl ether 68 as a colorless oil. IR (thin film)
3311, 2120 cm-1; 1H NMR (200 MHz, CDCl3) δ 7.50-7.40 (m,
1 H), 7.27-7.18 (m, 3 H), 3.83 (t, J ) 7.0 Hz, 2 H), 3.64 (d, J
) 2.7 Hz, 2 H), 2.89 (t, J ) 7.0 Hz, 2 H), 2.18 (t, J ) 2.7 Hz,
1 H), 0.87 (s, 9 H), -0.02 (s, 6 H); 13C NMR (50 MHz, CDCl3)
δ 136.9, 134.6, 130.1, 128.6, 126.9, 126.7, 82.1, 70.6, 63.9, 36.1,
25.9, 22.6, 18.3, -5.5; CIMS m/z (relative intensity) 275 (MH+,
8), 217 (36).
Tosyla m id e 66. A -78 °C solution of the 1,1-dibromovinyl
alcohol 65 (1.66 g, 4.85 mmol) in 25 mL of THF was treated
with 2.5 M n-BuLi (6.2 mL, 15 mmol, 3.2 equiv). This solution
was stirred at -78 °C for 1 h and then warmed to rt and held
there for 1 h. The reaction was then poured over ice-cold 1 M
HCl/brine (1:1), extracted with Et2O, washed with water and
then with brine, dried over anhydrous Na2SO4, filtered, and
concentrated in vacuo. The resulting residue was dissolved
in a solution of N-BOC p-toluenesulfonamide (1.97 g, 7.26
mmol, 1.5 equiv) and triphenylphosphine (3.80 g, 14.5 mmol,
3 equiv) in 50 mL of THF and treated with dropwise addition
of diethyl azodicarboxylate (3.43 g, 19.7 mmol, 2.6 equiv). After
20 h the reaction was concentrated in vacuo, and the crude
product residue was purified by flash column chromatography,
eluting with hexane-Et2O (5:1), to give 1.82 g (86%) of pure
BOC-protected tosylimide as a clear thick oil. IR (thin film)
1
3306, 1728 cm-1; H NMR (200 MHz, CDCl3) δ 7.78 (d, J )
8.4 Hz, 2 H), 7.30 (d, J ) 8.3 Hz, 2 H), 3.81 (m, 2 H), 2.44 (s,
3 H), 2.40 (m, 1 H), 2.03 (d, J ) 2.4 Hz, 1 H), 1.95-1.65 (m, 3
H), 1.55-1.10 (m, 8 H), 1.33 (s, 9 H), 0.90 (m, 6 H); 13C NMR
(50 MHz, CDCl3) δ 151.0, 143.9, 137.6, 129.2, 127.8, 87.9, 83.9,
69.0, 47.1, 44.2, 35.2, 30.1, 29.4, 27.9, 26.8, 26.6, 25.8, 23.3,
21.6, 21.5.
Tosyla m id e Aceta l 69. Alkyne 68 (1.86 g, 6.78 mmol)
dissolved in 12 mL of THF was cooled to -78 °C and treated
with n-BuLi (6.0 mL of 2.5 M in hexanes, 14.9 mmol, 2.2
equiv). After stirring for 15 min at -78 °C and 30 min at rt,
the resulting dilithiated intermediate was cooled to -78 °C,
and 2 mL of HMPT was added followed by 2-iodoacetaldehyde
dimethyl acetal (1.6 mL, 14 mmol, 2.0 equiv). The reaction
was allowed to slowly warm to rt over 4 h and stirred an
additional 4 h. Residual carbanions were quenched at 0 °C
by the addition of 10 mL of saturated NH4Cl and the solution
was diluted with 100 mL of Et2O. The organic phase was
washed twice with 100 mL portions of 1 N HCl and once with
100 mL of brine. Drying (Na2SO4) of the organic phase, solvent
evaporation, and flash chromatography of the residue (5%
Et2O/hexane as eluent) gave 2.00 g of the alkylated alkyne
Following general procedure D, a rt solution of the BOC-
protected tosylimide (1.77 g, 4.07 mmol) in 100 mL of CH2Cl2
was acidified with trifluoroacetic acid (4.59 g, 40.2 mmol, 10
equiv) and allowed to react for 20 h. The indicated workup
afforded 1.31 g (96%) of the pure tosylamide as a yellow oil.
1
IR (thin film) 3286 cm-1; H NMR (200 MHz, CDCl3) δ 7.76
(d, J ) 8.3 Hz, 2 H), 7.30 (d, J ) 8.5 Hz, 2 H), 4.86 (bt, J ) 6.0
Hz, 1 H), 2.92 (q, J ) 6.7 Hz, 2 H), 2.42 (s, 3 H3), 2.35 (m, 1
H), 2.00 (d, J ) 2.4 Hz, 1 H), 1.82 (m, 1 H), 1.58-1.02 (m, 10
H), 0.89 (m, 6 H); 13C NMR (75 MHz, CDCl3) δ 143.2, 136.9,
129.6, 127.0, 87.6, 69.1, 44.1, 43.1, 35.0, 29.35, 29.3, 26.6, 26.3,
25.7, 23.2, 21.6, 21.4.
(81%) as a colorless oil. IR (thin film) 3309, 2115 cm-1 1H
;
NMR (200 MHz, CDCl3) δ 7.53-7.45 (m, 1 H), 7.25-7.10 (m,
3 H), 4.58 (dd, J ) 6.9, 4.7 Hz, 1 H), 4.17-4.08 (m, 1 H), 3.80
(t, J ) 7.3 Hz, 2 H), 3.39 (s, 3 H), 3.31 (s, 3 H), 3.10-2.75 (m,
2 H), 2.20 (d, J ) 2.5 Hz, 1 H), 2.10-2.02 (m, 2 H), 0.88 (s, 9
H), 0.01 (s, 6 H); 13C NMR (75 MHz, CDCl3) δ 139.4, 135.9,
130.6, 127.5, 126.9, 126.8, 102.7, 85.9, 70.5, 64.1, 53.8, 52.5,
40.4, 36.0, 29.3, 25.9, 18.3, -5.4, -5.5; CIMS m/z (relative
intensity) 361.1 ((M - H)+, 8), 331.1 (42), 299.1 (21), 273.1
(38). Anal. Calcd for C21H34O3Si: C, 69.56; H, 9.45. Found:
C, 69.37; H, 9.56.
Following general procedure E, a -78 °C solution of this
tosylamide (1.24 g, 3.70 mmol) in 75 mL of THF was treated
with 2.5 M n-BuLi (3.10 mL, 7.75 mmol, 2.1 equiv). This
solution was warmed to 0 °C and held there for 1 h, and then
n-Bu3SnCl (1.20 g, 3.69 mmol, 1 equiv) was added. The
resulting solution was allowed to react at rt for 1 h. The
indicated workup afforded 2.20 g (93%) of pure 66 as a light
yellow oil. IR (thin film) 3280 cm-1 1H NMR (200 MHz,
;
CDCl3) δ 7.76 (d, J ) 8.3 Hz, 2 H), 7.30 (d, J ) 8.1 Hz, 2 H),
4.73 (bs, 1 H), 2.92 (m, 2 H), 2.42 (s, 3 H), 2.36 (m, 1 H), 1.70-
1.15 (m, 23 H), 1.00-0.75 (m, 21 H); 13C NMR (50 MHz, CDCl3)
δ 143.1, 137.1, 129.6, 127.0, 115.1, 81.9, 44.8, 43.2, 35.6, 30.9,
29.5, 28.9, 27.8, 26.8, 26.5, 25.9, 23.3, 21.6, 21.4, 13.6, 11.0;
EIMS m/z (relative intensity) 623 (M+, 0.6), 569 (73), 91 (100).
This silyl ether (2.26 g, 6.23 mmol) in 10 mL of THF was
cooled to 0 °C and treated with 9.4 mL of a 1.0 M n-Bu4NF in
THF solution (9.4 mmol, 1.5 equiv). After 2 h at 0 °C, 50 mL
of Et2O was added, and the mixture was washed twice with
50 mL portions of water. Drying (Na2SO4) of the organic
phase, solvent evaporation, and flash chromatography of the
residue (50% EtOAc/hexane) gave 1.39 g of the desilylated
Silyl Eth er 68. Alcohol 67 (5.92 g, 29.4 mmol) was
dissolved in 30 mL of DMF and treated with imidazole (4.01
g, 58.9 mmol, 2.0 equiv) and TBDMSCl (4.88 g, 32.4 mmol,
1.1 equiv) at 0 °C. The reaction solution was warmed to rt
and stirred for 24 h and then diluted with 100 mL of Et2O.
This mixture was washed twice with 100 mL portions of 1 N
HCl and once with 100 mL of brine. The organic phase was
dried (Na2SO4), filtered, and concentrated in vacuo. Purifica-
alcohol (90%) as a viscous oil. IR (CCl4) 3632, 3311, 2290 cm-1
;
1H NMR (200 MHz, CDCl3) δ 7.55-7.50 (m, 1 H), 7.29-7.19
(m, 3 H), 4.55 (dd, J ) 7.0, 4.7 Hz, 1 H), 4.08-3.99 (m, 1 H),
3.88 (t, J ) 6.7 Hz, 2 H), 3.39 (s, 3 H), 3.31 (s, 3 H), 3.10-2.80
(m, 2 H), 2.22 (d, J ) 2.7 Hz, 1 H), 2.15-1.90 (m, 2 H); 13C
NMR (75 MHz, CDCl3) δ 139.5, 135.4, 130.2, 127.8, 127.2,
127.1, 102.7, 85.8, 70.5, 63.3, 53.9, 52.5, 40.3, 35.6, 29.2; CIMS

5450 J . Org. Chem., Vol. 61, No. 16, 1996
Feldman et al.
m/z (relative intensity) 248.2 (M+, 3), 231.2 (8), 217.2 (13).
Anal. Calcd for C15H20O3: C, 72.55; H, 8.12. Found: C, 72.44;
H, 8.12.
alkynyl(phenyl)iodonium triflate salt may be assayed by 1H
NMR. In practice, however, this intermediate was recooled
to -40 °C, dissolved in precooled THF (∼0.08 M), and charged
with potassium tert-butoxide (∼1 equiv based on iodonium
salt). The resulting solution was allowed to warm to rt and,
after the indicated time, was poured over ice/brine (1:1),
extracted with Et2O, dried over anhydrous Na2SO4, and
concentrated in vacuo. Product heterocycles were isolated by
flash column chromatography of the crude product residue on
silica gel.
Following general procedure C, this alcohol (3.16 g, 12.7
mmol), BOC-p-toluenesulfonamide (3.79 g, 14.0 mmol, 1.1
equiv), and triphenylphosphine (6.66 g, 25.4 mmol, 2.0 equiv)
were dissolved in 50 mL of THF. Diethyl azodicarboxylate
(3.40 mL, 21.6 mmol, 1.7 equiv) was added and the reaction
solution was stirred at rt for 10 h. The volatiles were
evaporated in vacuo and flash chromatography of the residue
(25% Et2O/hexane) furnished 5.69 g (89%) of the BOC-
protected tosylimide as a viscous oil. IR (CCl4) 3312, 2116,
Con ver sion of 59a in to 71a /71b. Following general
procedure F, cyano(phenyl)iodonium triflate (0.298 g, 0.787
mmol, 1 equiv) was added to a deoxygenated -40 °C solution
of alkynylstannane 59a (0.496 g, 0.787 mmol) in 10 mL of CH2-
Cl2. After 45 min the solution was diluted with 30 mL of
hexane, the solvent layer was quickly decanted off, and the
remaining residue was rinsed with 10 mL of hexane and dried
in vacuo to yield 0.491 g (0.680 mmol, 86% yieldscorrected
(1H NMR) for 4% residual hexane) of alkynyl(phenyl)iodonium
triflate as a white foam. 1H NMR (200 MHz, CDCl3) δ 8.04
(d, J ) 7.8 Hz, 2 H), 7.71 (d, J ) 8.2 Hz, 2 H), 7.59 (m, 1 H),
7.46 (m, 2 H), 7.33-7.12 (m, 5 H), 7.04 (d, J ) 7.7 Hz, 2 H),
5.85 (bs, 1 H), 3.00 (m, 2 H), 2.86 (m, 1 H), 2.59 (m, 2 H), 2.36
(s, 3 H), 1.71 (m, 4 H). This salt was cooled to -40 °C,
dissolved in 10 mL of THF, charged with potassium tert-
buoxide (79 mg, 0.71 mmol, 1.04 equiv based on iodonium
intermediate), and allowed to react at rt for 1 h. Following
the indicated workup, purification of the crude product residue
by flash column chromatography, eluting with hexane-Et2O
(4:1, with 0.1% triethylamine), gave 0.167 g (73% yield) of the
fused phenyl-substituted enamides 71a /71b as a 1.4:1 mixture
1
1724 cm-1; H NMR (200 MHz, CDCl3) δ 7.80 (d, J ) 8.4 Hz,
2 H), 7.55 (d, J ) 7.7 Hz, 1 H), 7.31-7.20 (m, 5 H), 4.53 (dd,
J ) 6.7, 4.8 Hz, 1 H), 4.22-4.11 (m, 1 H), 4.02-3.89 (m, 2 H),
3.38 (s, 3 H), 3.32 (s, 3 H), 3.68-2.95 (m, 2 H), 2.43 (s, 3 H),
2.22 (d, J ) 2.6 Hz, 1 H), 2.20-1.92 (m, 2 H), 1.38 (s, 9 H); 13
C
NMR (75 MHz, CDCl3) δ 150.7, 144.0, 139.5, 137.3, 135.1,
130.5, 129.2, 127.9, 127.7, 127.4, 127.2, 102.6, 86.0, 84.2, 70.4,
53.9, 52.3, 47.9, 40.6, 33.4, 29.1, 27.8, 21.5; CIMS m/z (relative
intensity) 501.1 (M+, 8), 470.2 (10), 414.2 (22). Anal. calcd
for C27H35NO6S: C, 64.65; H, 7.03; N, 2.79. Found: C, 64.47;
H, 7.20; N, 2.90.
This tosylimide (5.69 g, 11.4 mmol) was dissolved in 50 mL
of dry MeOH and 35 mL of trimethyl orthoformate. Acetyl
chloride (14 mL) was added slowly, and the mixture was
brought to reflux and held there for 5 h. The reaction solution
was cooled to 0 °C, and 20 g of NaHCO3 was carefully added.
The resulting mixture was diluted with 150 mL of water and
extracted twice with 150 mL portions of CH2Cl2. Drying (Na2-
SO4) of the organic layer, solvent evaporation, and flash
chromatography of the residue (50% Et2O/hexane) afforded
1
of diastereoisomers by H NMR integration. EIMS m/z (rela-
tive intensity) 339 (M+, 12), 262 (5), 184 (63); HRMS calcd for
3.89 g of 69 (85%) as a viscous oil. IR (CCl4) 3302, 2116 cm-1
;
C
20H21NO2S 339.1293, found 339.1271. Each isomer was
1H NMR (200 MHz, CDCl3) δ 7.71 (d, J ) 8.3 Hz, 2 H), 7.46
(dd, J ) 7.6, 1.7 Hz, 1 H), 7.35-7.00 (m, 5 H), 4.56 (t, J ) 6.2
Hz, 1 H), 4.47 (dd, J ) 7.0, 4.6 Hz, 1 H), 3.90-3.81 (m, 1 H),
3.36 (s, 3 H), 3.27 (s, 3 H), 3.30-3.12 (m, 2 H), 3.02-2.70 (m,
2 H), 2.41 (s, 3 H), 2.17 (d, J ) 2.5 Hz, 1 H), 2.13-1.83 (m, 2
H); 13C NMR (75 MHz, CDCl3) δ 143.1, 139.0, 136.8, 134.8,
129.9, 129.5, 127.7, 127.2, 127.1, 126.9, 102.4, 85.5, 70.6, 53.7,
52.4, 43.7, 40.0, 32.4, 29.0, 21.3; CIMS m/z (relative inten-
sity) 401.6 (M+, 1), 370.6 (100), 338.6 (96). Anal. Calcd for
partially purified from this mixture by additional flash column
chromatography, eluting with hexane-EtOAc (19:1, with 0.1%
triethylamine).
71a . 1H NMR (200 MHz, C6D6) δ 7.81 (d, J ) 8.3 Hz, 2 H),
7.26-7.05 (m, 5 H), 6.80 (d, J ) 8.5 Hz, 2 H), 5.48 (t, J ) 1.9
Hz, 1 H), 4.04 (m, 1 H), 3.80 (dd, J ) 10.3, 8.1 Hz, 1 H), 3.35
(m, 1 H), 2.46 (m, 1 H), 2.01 (m, 1 H), 1.88 (s, 3 H), 1.26-1.02
(m, 2 H), 0.82 (m, 1 H); 13C NMR (75 MHz, C6D6) δ 148.4, 146.2,
143.3, 129.8, 128.8, 128.7, 127.4, 127.0, 126.6, 104.6, 55.9, 49.4,
47.7, 42.0, 29.5, 21.2.
C
22H27NO4S: C, 65.81; H, 6.78; N, 3.49. Found: C, 65.60; H,
6.83; N, 3.50.
71b. 1H NMR (300 MHz, C6D6) δ 7.82 (d, J ) 8.3 Hz, 2 H),
7.38-7.12 (m, 7 H), 5.35 (t, J ) 2.9 Hz, 1 H), 4.19 (bd, J ) 8.2
Hz, 1 H), 4.05 (dd, J ) 10.0, 8.0 Hz, 1 H), 3.70 (ddd, J ) 11.5,
10.2, 5.5 Hz, 1 H), 3.02 (m, 1 H), 2.47 (s, 3 H), 2.04-1.86 (m,
3 H), 1.40 (dq, J ) 11.7, 8.0 Hz, 1 H); 13C NMR (75 MHz, C6D6)
δ 149.0, 145.5, 143.5, 136.1, 129.5, 128.6, 127.9, 127.5, 126.4,
103.8, 55.9, 55.5, 47.9, 39.1, 29.4, 21.1.
Tosyla m id e 70. To tosylamide 69 (147 mg, 0.366 mmol)
in 3 mL of THF at 0 °C was added 1.1 mL of a 1 M LiHMDS
solution in THF (1.1 mmol, 3 equiv) followed by 119 µL of Bu3-
SnCl (0.439 mmol, 1.2 equiv). The reaction solution was
treated 0.5 h later with saturated aqueous NH4Cl and then
diluted with 20 mL of Et2O. The organic phase was washed
once with 20 mL of H2O, dried over Na2SO4, and concentrated
in vacuo. Flash chromatography (35% Et2O/hexane) of the
residue using wet silica (12% w/w H2O) yielded 166 mg of 70
(66%) as a clear, colorless oil. IR (thin film) 3279, 2145 cm-1
;
1H NMR (200 MHz, CDCl3) δ 7.71 (d, J ) 8.3 Hz, 2 H), 7.54
(dd, J ) 7.7, 1.5 Hz, 1 H), 7.27 (d, J ) 7.3 Hz, 2 H) 7.22-6.99
(m, 3 H), 4.61-4.53 (m, 2 H), 3.86 (dd, J ) 9.6, 5.5 Hz, 1 H),
3.38 (s, 3 H), 3.26 (s, 3 H), 3.31-3.12 (m, 2 H), 2.98-2.70 (m,
2 H), 2.41 (s, 3 H), 2.08-1.83 (m, 2 H); 1.70-1.50 (m, 6 H),
1.45-1.25 (m, 6 H), 1.05-0.90 (m, 6 H), 0.90 (t, 9 H); 13C NMR
(75 MHz, CDCl3) δ 143.2, 140.3, 137.2, 134.6, 129.7, 128.2,
127.3, 127.1, 127.0, 112.0 103.1, 85.0, 54.4, 52.3, 43.7, 41.3,
32.3, 30.9, 28.9, 26.9, 21.5, 13.7, 11.1; CIMS m/z (relative
intensity) 692.5 (MH+, 3), 690.1 (3), 634.4 (4). Anal. Calcd
for C34H53NO4SSn: C, 59.14; H, 7.74; N, 2.03. Found: C,
58.69; H, 7.77; N, 2.20.
Con ver sion of 59b in to 72a /72b. Following general
procedure F, cyano(phenyl)iodonium triflate (0.316 g, 0.834
mmol, 1 equiv) was added to a -40 °C deoxygenated solution
of alkynylstannane 59b (0.473 g, 0.834 mmol) in 10 mL of CH2-
Cl2. After 45 min, the solution was diluted with 30 mL of
hexane, the solvent layer was quickly decanted off, and the
remaining residue was rinsed with 10 mL of hexane and dried
in vacuo to yield 0.477 g (0.726 mmol, 87% yieldscorrected
Gen er a l P r oced u r e F . In tr a m olecu la r Ta n d em Con -
ju ga te Ad d ition -Ca r ben e In ser tion Rea ction s. Cyano-
(phenyl)iodonium triflate13 (1 equiv) was added to a -40 °C
deoxygenated ∼0.08 M solution of alkynylstannane (1 equiv)
in CH2Cl2. After 45 min the reaction solution was diluted with
three times its volume of hexane, the solvent layer was quickly
decanted, and the remaining alkynyl(phenyl)iodonium triflate
residue was washed with an additional 1 volume of hexane
and dried in vacuo in an ice bath. The purity of the resulting
(
1H NMR) for 4% residual hexane) of alkynyl(phenyl)iodonium
triflate as a white foam. 1H NMR (200 MHz, CDCl3) δ 8.05
(d, J ) 7.5 Hz, 2 H), 7.73 (d, J ) 8.3 Hz, 2 H), 7.62 (m, 1 H),
7.48 (m, 2 H), 7.27 (d, J ) 8.1 Hz, 2 H), 5.85 (bs, 1 H), 3.00
(bs, 2 H), 2.77 (m, 1 H), 2.39 (s, 3 H), 1.68 (m, 3 H), 0.85 (m,

Addition/Cyclizations of Sulfonamide Anions
J . Org. Chem., Vol. 61, No. 16, 1996 5451
6 H). This salt was cooled to -40 °C, dissolved in 10 mL of
THF, charged with potassium tert-butoxide (85 mg, 0.76 mmol,
1.05 equiv based on iodonium intermediate), and allowed to
react at rt for 1 h. Following the indicated workup, purifica-
tion of the crude product residue by flash column chromatog-
raphy, eluting with hexane-Et2O (4:1, with 0.1% triethy-
lamine), gave 0.133 g (66%) of the methyl-substituted bicyclic
56.6, 55.6, 53.6; CH2, 55.5, 31.7, 28.8, 27.8, 26.7, 26.5; CH3,
21.1.
1
enamides 72a /72b as a 3:1 mixture of diastereoisomers by H
NMR integration: EIMS m/z (relative intensity) 277 (M+, 34),
262 (64), 183 (39); HRMS calcd for C15H19NO2S 277.1136, found
277.1134. A purified sample of the major isomer 72a was
separated from this mixture by additional flash column
chromatography, eluting with hexane-EtOAc (19:1, with 0.1%
triethylamine).
72a . 1H NMR (300 MHz, C6D6) δ 7.82 (d, J ) 8.3 Hz, 2 H),
6.79 (d, J ) 8.0 Hz, 2 H), 5.34 (s, 1 H), 3.78 (dd, J ) 10.0, 8.0
Hz, 1 H), 3.33 (ddd, J ) 11.6, 10.1, 5.6 Hz, 1 H), 2.46 (ddd, J
) 14.5, 7.3, 2.8 Hz, 1 H), 2.21 (dddd, J ) 14.5, 9.5, 3.0, 1.6 Hz,
1 H), 2.10 (m, 1 H), 1.87 (s, 3 H), 1.64 (m, 1 H), 1.20 (pentet,
J ) 6.0 Hz, 1 H), 0.82 (qd, J ) 11.6, 8.1 Hz, 1 H), 0.75 (d, J )
6.7 Hz, 3 H); 13C NMR (50 MHz, C6D6) δ 146.9, 143.4, 136.2,
129.5, 100.2, 56.3, 55.6, 44.7, 41.6, 28.4, 21.1, 18.0.
73b. 1H NMR (300 MHz, C6D6) δ 7.82 (d, J ) 8.3 Hz, 2 H),
6.83 (d, J ) 8.5 Hz, 2 H), 5.18 (m, 1 H), 3.81 (dd, J ) 10.0, 8.2
Hz, 1 H), 3.32 (ddd, J ) 11.7, 10.1, 5.7 Hz, 1 H), 3.02 (m, 1 H),
2.51 (m, 1 H), 1.90 (s, 3 H), 1.85 (m, 1 H), 1.58 (m, 2 H), 1.45
(m, 1 H), 1.26 (m, 1 H), 1.20-0.98 (m, 5 H), 0.89 (qd, J ) 11.6,
8.2 Hz, 1 H); 13C NMR (75 MHz, C6D6) δ 146.5, 143.5, 135.9,
129.6, 126.8, 103.8, 67.3, 57.7, 55.3, 53.4, 40.6, 29.0, 28.7, 28.3,
24.6, 21.2.
Con ver sion of 59d in to 74a /74b. Following general
procedure F, cyano(phenyl)iodonium triflate (0.114 g, 0.302
mmol, 1 equiv) was added to a -40 °C deoxygenated solution
of alkynylstannane 59d (0.210 g, 0.302 mmol) in 4 mL of CH2-
Cl2. After 45 min, the solution was diluted with 12 mL of
hexane, the solvent layer was quickly decanted off, and the
remaining residue was rinsed with 4 mL of hexane and dried
in vacuo to yield 0.143 g (0.177 mmol, 59% yieldscorrected
(1H NMR) for 6% residual hexane) of alkynyl(phenyl)iodonium
triflate as a white foam. 1H NMR (200 MHz, CDCl3) δ 8.11
(d, J ) 8.4 Hz, 2 H), 7.79 (d, J ) 8.3 Hz, 2 H), 7.70 (m, 1 H),
7.56 (m, 2 H), 7.33 (d, J ) 8.0 Hz, 2 H), 5.56 (bt, J ) 6.1 Hz,
1 H), 3.63 (m, 2 H), 2.95 (m, 3 H), 2.46 (s, 3 H), 1.88-1.50 (m,
6 H), 0.87 (s, 9 H), 0.01 (s, 6 H). This salt was cooled to -40
°C, dissolved in 4 mL of THF, charged with potassium tert-
butoxide (21 mg, 0.19 mmol, 1.06 equiv based on iodonium
intermediate), and allowed to react at rt for 1 h. Following
the indicated workup, purification of the crude product residue
by flash column chromatography, eluting with hexane-Et2O
(9:1, with 0.1% triethylamine), gave 47 mg (64%) of the fused
bicyclic eneamides 74a /74b as a 1.8:1 mixture of unassigned
diastereoisomers by 1H NMR integration. The product mix-
ture proved to be unstable and underwent facile hydrolysis
upon standing to yield 20 mg (60%) of the cyclopentenone
derivative 82 as a light yellow oil: IR (thin film) 3274, 1692
72b. 1H NMR (200 MHz, C6D6) δ 7.80 (d, J ) 8.4 Hz, 2 H),
6.86 (d, J ) 8.0 Hz, 2 H), 5.31 (s, 1 H), 3.81 (m, 1 H), 3.36
(ddd, J ) 11.6, 10.1, 5.6 Hz, 1 H), 2.78 (m, 1 H), 2.56 (m, 1 H),
1.96 (m, 1 H), 1.92 (s, 3 H), 1.65 (m, 1 H), 1.27 (pentet, J ) 6.0
Hz, 1 H), 1.06 (m, 1 H), 0.51 (d, J ) 7.1 Hz, 3 H); 13C NMR (50
MHz, C6D6) δ 145.5, 135.9, 129.6, 98.2, 55.9, 52.4, 44.4, 32.3,
23.0, 15.9.
Con ver sion of 59c in to 73a /73b. Following general
procedure F, cyano(phenyl)iodonium triflate (0.308 g, 0.812
mmol, 1 equiv) was added to a -40 °C deoxygenated solution
of alkynylstannane 59c (0.494 g, 0.812 mmol, 1 equiv) in 10
mL of CH2Cl2. After 45 min, the solution was diluted with 30
mL of hexane, the solvent layer was quickly decanted off, and
the remaining residue was rinsed with 10 mL of hexane and
dried in vacuo to yield 0.488 g (0.684 mmol, 84% yieldscorrected
(1H NMR) for 6% residual hexane) of alkynyl(phenyl)iodonium
triflate as a white foam. 1H NMR (200 MHz, CDCl3) δ 8.05
(d, J ) 8.6 Hz, 2 H), 7.73 (d, J ) 8.2 Hz, 2 H), 7.62 (m, 1 H),
7.49 (m, 2 H), 7.27 (d, J ) 8.2 Hz, 2 H), 5.81 (bs, 1 H), 3.00 (m,
2 H), 2.74 (m, 1 H), 2.39 (s, 3 H), 1.80-1.45 (m, 7 H), 1.23-
0.95 (m, 6 H). This salt was cooled to -40 °C, dissolved in 10
mL of THF, charged with potassium tert-butoxide (81 mg, 0.73
mmol, 1.06 equiv based on iodonium intermediate), and
allowed to react at rt for 1 h. Following the indicated workup,
purification of the crude product residue by flash column
chromatography, eluting with hexane-Et2O (4:1, with 0.1%
triethylamine), gave 0.150 g (69%) of the fused tricyclic
eneamides 73a /73b as a 3.5:1 mixture of diastereoisomers by
1H NMR integration: EIMS m/z (relative intensity) 317 (M+,
24), 253 (100), 91 (63); HRMS Calcd for C18H23NO2S 317.1449,
found 317.1466. A purified sample of the major isomer 73a
was separated from this mixture by additional flash column
chromatography, eluting with hexane-EtOAc (19:1, with 0.1%
triethylamine).
1
cm-1; H NMR (200 MHz, CDCl3) δ 7.74 (d, J ) 8.3 Hz, 2 H),
7.66 (m, 1 H), 7.30 (d, J ) 8.4 Hz, 2 H), 6.15 (dt, J ) 5.7, 2.1
Hz, 1 H), 4.80 (bs, 1 H), 2.94 (m, 2 H), 2.80 (m, 1 H), 2.43 (s,
3 H), 2.35-2.20 (m, 2 H), 1.85-1.30 (m, 4 H); 13C NMR (90
MHz, CDCl3) δ 212.0, 163.6, 143.4, 136.9, 133.7, 129.7, 127.1,
44.0, 43.0, 35.6, 28.1, 27.1, 21.5; CIMS m/ z (relative intensity)
294 (MH+, 100), 138 (35), 123 (47).
Con ver sion of 59f in to 77. Following general procedure
F, cyano(phenyl)iodonium triflate (0.156 g, 0.410 mmol, 1
equiv) was added to a -40 °C deoxygenated solution of
alkynylstannane 59f (0.269 g, 0.410 mmol) in 5 mL of CH2-
Cl2. After 45 min, the solution was diluted with 15 mL of
hexane, the solvent layer was quickly decanted off, and the
remaining residue was rinsed with 5 mL of hexane and dried
in vacuo to yield 0.236 g (0.318 mmol, 77% yieldscorrected
(1H NMR) for 3% residual hexane) of alkynyl(phenyl)iodonium
triflate as a white foam. 1H NMR (200 MHz, CDCl3) δ 8.05
(d, J ) 7.8 Hz, 2 H), 7.73 (d, J ) 8.1 Hz, 2 H), 7.65 (m, 1 H),
73a . 1H NMR (300 MHz, C6D6) δ 7.82 (d, J ) 8.3 Hz, 2 H),
6.83 (d, J ) 8.5 Hz, 2 H), 5.43 (d, J ) 0.6 Hz, 1 H), 3.81 (dd,
J ) 10.0, 8.2 Hz, 1 H), 3.32 (ddd, J ) 11.7, 10.1, 5.7 Hz, 1 H),
2.30 (m, 1 H), 2.11 (m, 1 H), 1.90 (s, 3 H), 1.85 (m, 1 H), 1.58
(m, 2 H), 1.45 (m, 1 H), 1.26 (m, 1 H), 1.20-0.98 (m, 5 H),
0.89 (qd, J ) 11.6, 8.2 Hz, 1 H); 13C NMR (75 MHz, C6D6,
DEPT) δ C, 147.8, 143.4, 136.2; CH, 129.5 (2), 127.6 (2), 105.5,

5452 J . Org. Chem., Vol. 61, No. 16, 1996
Feldman et al.
7.52 (m, 2 H), 7.28 (d, J ) 8.9 Hz, 2 H), 5.28 (m, 1 H), 3.57 (m,
3 H), 2.87 (m, 4 H), 2.41 (s, 3 H), 2.35 (m, 1 H), 1.80-1.42 (m,
6 H), 0.82 (m, 6 H). This salt was cooled to -40 °C, dissolved
in 5 mL of THF, charged with potassium tert-butoxide (37 mg,
0.33 mmol, 1.03 equiv based on iodonium intermediate), and
allowed to react at rt for 1 h. The reaction solution was then
diluted with 1 mL of water, acidified with oxalic acid (0.100 g,
1.11 mmol, 3.4 equiv), and allowed to react at rt for 20 h.
Following the described workup, purification of the crude
product residue by flash column chromatography, eluting with
hexane-EtOAc (1:1, with 0.1% triethylamine), gave 48 mg
(50%) of pure enone 77 as a white solid: mp 142-144 °C; IR
h at rt and then diluted with 50 mL of Et2O. The organic
phase was washed once with aqueous KF and once with brine,
dried over Na2SO4, filtered, and concentrated in vacuo. Flash
chromatography of the residue (25% Et2O in hexanes, silica
gel pretreated with 1% Et3N (w/v) in hexanes) provided 42 mg
(54%) of the bicyclic enimides 79a /b as a 2.3:1 mixture of
diastereomers. The relative stereochemistries of 79a /b were
assigned by comparison of the alkene-H region of the 1H NMR
spectrum of the mixture with the nearly identical signals in
the analogous and stereochemically well-characterized system
71a /b. IR (CCl4) 1766 cm-1; 1H NMR (200 MHz, CDCl3) δ 7.98
(d, J ) 8.4 Hz, 2H, minor diastereomer), 7.97 (d, J ) 8.3 Hz,
2H, major diastereomer), 7.40-7.10 (m, 7H), 5.75 (t, J ) 3.0
Hz, 1H, minor diastereomer), 5.67 (t, J ) 2.1 Hz, 1H, major
diastereomer), 4.25-4.05 (m, 1H), 3.30-3.05 (m, 1H), 2.75-
2.40 (m, 1H), 2.46 (s, 3H), 2.40-2.00 (m, 2H), 1.50-1.30 (m,
1H); 13C NMR (50 MHz, CDCl3) δ 174.7, 174.5, 145.6, 144.2,
143.3, 142.7, 142.5, 135.0, 134.9, 129.74, 129.72, 128.54,
128.48, 128.1, 127.1, 127.0, 126.7, 126.5, 108.9, 107.4, 52.2,
51.7, 42.2, 42.0, 40.5, 39.7, 39.0, 21.7; EIMS m/z (relative
intensity) 353 (M+, 26); HRMS calcd for C20H19NO3S 353.1086,
found 353.1104.
1
(CCl4) 1711 cm-1; H NMR (200 MHz, CDCl3) δ 7.76 (d, J )
8.3 Hz, 2 H), 7.35 (d, J ) 8.3 Hz, 2 H), 6.02 (m, 1 H), 3.90-
3.65 (m, 2 H), 2.86 (m, 1 H), 2.53 (dd, J ) 18.0, 6.7 Hz, 1 H),
2.45 (s, 3 H), 2.23-1.82 (m, 4 H), 1.25 (m, 1 H); 13C NMR (50
MHz, CDCl3) δ 204.4, 170.9, 145.2, 134.2, 130.0, 127.4, 112.2,
45.6, 40.2, 38.1, 26.1, 22.4, 21.6; CIMS m/z (relative intensity)
292 (MH+, 81), 157 (61), 138 (100); HRMS calcd for C15H17
NO3S 291.0929, found 291.0917.
-
Con ver sion of 62 to 78a /b. Following general procedure
F, cyano(phenyl)iodonium triflate (0.302 g, 0.796 mmol, 1
equiv) was added to a -40 °C deoxygenated solution of
alkynylstannane 62 (0.619 g, 0.796 mmol) in 10 mL of CH2-
Cl2. After 45 min, the solution was diluted with 30 mL of
hexane, the solvent layer was quickly decanted off, and the
remaining residue was rinsed with 10 mL of hexane and dried
in vacuo to yield 0.528 g (0.591 mmol, 74% yieldscorrected
(1H NMR) for 6% residual hexane) of alkynyl(phenyl)iodonium
triflate as a white foam. 1H NMR (200 MHz, CDCl3) δ 8.17
(d, J ) 7.4 Hz, 2 H), 8.05 (d, J ) 8.3 Hz, 2 H), 7.83 (d, J ) 8.1
Hz, 2 H), 7.71 (d, J ) 7.5 Hz, 2 H), 7.57 (m, 1 H), 7.50 (d, J )
7.9 Hz, 2 H), 7.40 (d, J ) 7.4 Hz, 2 H), 5.81 (s, 1 H), 5.31 (s, 1
H), 4.76 (m, 1 H), 2.50 (s, 6 H), 1.76-1.44 (m, 8 H), 1.40-1.06
(m, 2 H). This salt was cooled to -40 °C, dissolved in 10 mL
of THF, charged with potassium tert-butoxide (70 mg, 0.63
mmol, 1.06 equiv based on iodonium intermediate), and
allowed to react at rt for 1 h. Purification of the crude product
residue by flash column chromatography, eluting with hex-
ane-EtOAc (4:1, with 0.1% triethylamine), gave 0.126 g (44%)
of two compounds in a 16:1 ratio. The major compound proved
Con ver sion of 70 in to Dien e 80. To alkynylstannane 70
(77 mg, 0.11 mmol) in 2 mL of CH2Cl2 at -50 °C was added
cyano(phenyl)iodonium triflate (42 mg, 0.11 mmol, 1.0 equiv)
in one portion, and the reaction was stirred at -40 °C for 0.5
h to furnish a clear solution. Hexanes (10 mL) was added,
leading to a white precipitate. The supernatant was quickly
decanted, and the solid was washed once with 3 mL of hexane
and dried in vacuo. The crude iodonium salt was cooled to
-78 °C, and 5 mL of THF was added followed by 110 µL of a
1.0 M LiHMDS in THF solution (0.11 mmol, 1.0 equiv). The
reaction solution was warmed to rt and stirred there for
another 12 h. The solution was diluted with 25 mL of Et2O
and then treated with 10 mL of brine. The organic phase was
washed once with water, dried over Na2SO4, and the residue
was purified by flash chromatography (30% Et2O/hexane
containing 0.5% triethylamine) to provide 23 mg (56%) of diene
80 as a white solid. mp 161-163° dec; IR (CCl4) 2360 cm-1
;
1H NMR (300 MHz, C6D6) δ 7.72 (d, J ) 8.3 Hz, 2 H), 6.90-
6.87 (m, 2 H), 6.80-6.75 (m, 1 H), 6.67 (d, J ) 7.6 Hz, 1 H),
6.62 (d, J ) 8.2 Hz, 2 H), 6.42 (s, 1 H), 3.86-3.82 (m, 2 H),
3.30 (s, 3 H), 3.23 (s, 2 H), 2.56-2.53 (m, 2 H), 1.71 (s, 3 H);
13C NMR (75 MHz, C6D6, DEPT) δ C, 165.8, 143.2, 139.1, 137.7,
134.6, 114.0, 65.9; CH, 129.6, 129.3, 127.5, 126.6, 126.3, 124.5,
102.5; CH2, 49.7, 40.6, 36.5; CH3, 56.8, 21.0; CIMS m/z (rela-
tive intensity) 368.4 (MH+, 41), 367.4 (32). Anal. Calcd for
C21H21NO3S: C, 68.64; H, 5.76; N, 3.81. Found: C, 68.47; H,
5.79 ; N, 3.74.
1
to be cyclic urea 78a . mp 158-160°; IR (CCl4) 1774 cm-1, H
NMR (300 MHz, CDCl3) δ 7.89 (d, J ) 8.4 Hz, 2 H), 7.88 (d, J
) 8.4 Hz, 2 H), 7.34 (d, J ) 8.2 Hz, 2 H), 7.33 (d, J ) 8.2 Hz,
2 H), 5.45 (m, 1 H), 4.60 (m, 1 H), 3.06 (bs, 1 H), 2.70 (m, 1 H),
2.46 (s, 3 H), 2.44 (s, 3 H), 1.94 (m, 1 H), 1.70-1.45 (m, 3 H),
1.18-1.00 (m, 3 H), 0.88 (m, 1 H); 13C NMR (75 MHz, CDCl3,
DEPT) δ C, 150.8, 146.2, 145.8, 133.7, 133.5, 132.9; CH, 129.9
(2), 128.5, 128.0, 110.0, 67.0, 45.9, 43.0; CH2, 27.4, 23.3, 21.9,
21.2; CH3, 21.7, 21.68; EIMS m/z (relative intensity) 486 (M+,
23), 331 (21), 91 (100); HRMS Calcd for C24H26N2O5S2 486.1283,
found 486.1278.
Ack n ow led gm en t. We thank the NIH (GM37681)
for financial support of this work.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization data for 16d , 16e, 18, 19, 23,
25, 34, 35, 37a , 45a -e, 46b-e, 53, 58a -e, and 59a -e, and
copies of 13C NMR spectra for 16c, 32, 40, 42, 61, 62, 63, 65,
66, 68, 71b, 72a /b, 73a /b, 77, 78a , 79a /b, and 82 (33 pages).
This material is contained in libraries on microfiche, im-
mediately 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.
Con ver sion of 63 in to 79a /b. To alkynylstannane 63 (141
mg, 0.219 mmol) in 3.5 mL of CH2Cl2 at -40 °C was added
cyano[[(trifluoromethyl)sulfonyl]oxy]iodobenzene (83 mg, 0.22
mmol, 1 equiv) in one portion, and the reaction was stirred at
-40 °C for 0.5 h to furnish a clear solution. Triethylamine
(62 µL, 0.44 mmol, 2 equiv) was added, and external cooling
bath was removed. The reaction solution was stirred for 0.5
J O9605814