Alkynyliodonium salts in organic synthesis. Preparation of annelated dihydropyrroles by cascade addition/bicyclization of dienyltosylamide anions with phenyl(propynyl)iodonium triflate

Article abstract of DOI:10.1021/jo9907538

The addition of simple pentadienyltosylamide derivatives to the two- carbon electrophile phenyl(propynyl)iodonium triflate initiates a sequence of transformations that furnishes complex, highly functionalized cyclopentenannelated dihydropyrrole products in moderate yields with complete stereoselection. This sequence demonstrates that diyls resulting from homolytic scission of alkylidene carbene-alkene adducts can be readily accessed under mild experimental conditions and that, in the presence of appropriate pendant functionality, these diyls can productively cyclize. The isomeric isoprene-derived tosylamides follow an abbreviated reaction course and deliver azabicyclo[3.1.0]hexanes via an isomerization that competes with diyl formation.

Full text of DOI:10.1021/jo9907538

5650
J . Org. Chem. 1999, 64, 5650-5660
Alk yn yliod on iu m Sa lts in Or ga n ic Syn th esis. P r ep a r a tion of
An n ela ted Dih yd r op yr r oles by Ca sca d e Ad d ition /Bicycliza tion of
Dien yltosyla m id e An ion s w ith P h en yl(p r op yn yl)iod on iu m Tr ifla te
Ken S. Feldman* and David. A. Mareska
Chemistry Department, The Pennsylvania State University, University Park, Pennsylvania 16802
Received May 5, 1999
The addition of simple pentadienyltosylamide derivatives to the two-carbon electrophile phenyl-
(propynyl)iodonium triflate initiates a sequence of transformations that furnishes complex, highly
functionalized cyclopentenannelated dihydropyrrole products in moderate yields with complete
stereoselection. This sequence demonstrates that diyls resulting from homolytic scission of alkylidene
carbene-alkene adducts can be readily accessed under mild experimental conditions and that, in
the presence of appropriate pendant functionality, these diyls can productively cyclize. The isomeric
isoprene-derived tosylamides follow an abbreviated reaction course and deliver azabicyclo[3.1.0]-
hexanes via an isomerization that competes with diyl formation.
Sch em e 1
Serial cyclization of polyolefinic substrates via propa-
gating reactive intermediates remains among the most
efficient of the canonical strategies for converting simple
acyclic precursors into polycyclic products. Whereas the
bulk of the efforts in this area have utilized either
anionic, cationic, or radical intermediates, one recent
unconventional example of this process was proposed to
proceed in succession through an alkylidene carbene and
then a trimethylenemethane diyl en route to the cyclo-
pentannelated pyrroles 3 from the pentadienyl substrates
1 and the alkynyliodonium salt 2.1 Intramolecular cap-
ture of these reactive species limits both regiochemical
and stereochemical options, and consequently these
transformations proceed with high levels of selectivity
for the products 3 and 5 (Scheme 1). A detailed account
of this work is presented, including descriptions of
substrate synthesis, presentation of addition/cyclization
results, and analysis of mechanistic/selectivity issues.
The ready accessibility and high reactivity of alkyli-
dene carbenes has encouraged their use in several C-C
bond forming processes.2 Estimates of the ∆Hf of the
parent species, vinylidene H2CdC: 6a , converge on a
value (101 ( 6 kcal/mol) even greater than one of the
most reactive organic intermediates known, singlet me-
thylene.3 High level computational analysis of 6a de-
scribes a geometry (CdC ) 1.33 Å, C-H ) 1.09 Å) not
remarkably different than ethylene.4 Electronic structure
calculations support assignment of a singlet ground state
separated by a 48 kcal/mol barrier from the nearly
inaccessible triplet isomer.3b The dominant reactivity
profile exhibited by a free alkylidene carbene 6 is mild
electrophilicity, as indicated by a F ) -0.64 for cycload-
dition with substituted styrenes (compare F+ ) -0.62 for
Cl2C: addition to styrenes).5
Sch em e 2
Low-temperature methods for the preparation of these
transient intermediates utilize a wide variety of unre-
lated precursors, Scheme 2. Ketonic 7 or alkenic 9
precursors have documented utility in delivering a range
of substituted alkylidene carbenes under mild conditions,
whereas the more exotic N-nitrosooxazolindones 10 or
hydrazone derivatives 11 have seen less service in this
regard.2a A more recent entry point into alkylidene
carbene chemistry, the alkynyliodonium salts 12,7 have
(1) (a) Feldman, K. S.; Mareska, D. A.; J . Am. Chem. Soc. 1998,
120, 4027. (b) Feldman, K. S.; Mareska, D. A. Tetrahedron Lett. 1998,
39, 4781.
(2) Kirmse, W. Angew. Chem., Int. Ed. Engl. 1997, 36, 1164. (b)
Stang, P. J . Chem. Rev. 1978, 78, 333.
(3) (a) Ervin, K. M.; Ho, J .; Lineberger, W. C. J . Phys. Chem. 1989,
91, 5974. (b) Bodor, N.; Dewar, M. J . S.; Wasson, J . S. J . Am. Chem.
Soc. 1972, 94, 9095.
(4) Gallo, M. M.; Hamilton, J . P.; Schaeffer, H. F. III J . Am. Chem.
Soc. 1990, 112, 8714.
(5) Gilbert, J . C.; Giamalva, D. H. J . Org. Chem. 1992, 57, 4185.
(6) Seyferth, D.; Mui, J . Y. P.; Damrauer, R. J . Am. Chem. Soc. 1968,
90, 6182.
10.1021/jo9907538 CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/24/1999

Alkynyliodonium Salts in Organic Synthesis
J . Org. Chem., Vol. 64, No. 15, 1999 5651
Sch em e 3
Sch em e 4
received increasing attention plausibly due to their
versatility. Unique among the alkylidene carbene precur-
sors, these salts offer the opportunity to bring together
two distinct R- and R1-containing components during
preparation of the free carbene. This advantage becomes
particularly significant when alkylidene carbenes bearing
heteroatoms (R1 ) N, O, S species) are required.
trimethylenemethane-type diyls. This latter point is not
without merit, as the cleavage temperature of 16 is
strikingly lower than that for the comparable bond
rupture in an unstrained methylenecyclopropane system
(g200 °C).11
These monosubstituted carbon species participate in
the types of reactions usually reserved for highly reactive
and electrophilic disubstituted carbenes, including formal
dimerization, intermolecular X-H, or intramolecular 1,5
C-H insertion, 1,2 substituent shift, and alkene cyclo-
addition.2b When either R or R1 (cf. 6) is H, Ar, or SiR′3,
the 1,2 substituent shift precedes all other options and
an alkyne product is formed.2b,7 Alkyl or heteroatom
substituents on an alkylidene carbene raise the barrier
for this shift and permit the slower X-H or C-H
insertions to prevail. The selectivity among C-H bonds
(tertiary > secondary > primary)8 is in accord with the
expectations of reaction through an electron deficient
transition state.5 Only when both 1,2 shift and 1,5 C-H
insertion have been suppressed can alkene cycloaddition
emerge as the major reaction pathway. Numerous studies
have shown that alkene geometry is faithfully translated
into product stereochemistry as befitting a concerted
cycloaddition between two singlet species.2b,5
An intramolecular variant of the alkylidene carbene/
alkene cycloaddition was explored by Ko¨brich et al.
(Scheme 3), who discovered that this high energy inter-
mediate was capable of delivering materially strained
alkenes 14 and 16.9 Whereas the bicyclo[4.1.0]heptene
species 14 was isolable, the existence of the lower
homologue 16 could only be inferred from formation of
the dimerization product 18. Later studies by Berson and
Salinero provided unequivocal evidence for the inter-
mediacy of a trimethylenemethane diyl 17.10 This trans-
formation, while of little preparative value, did reveal
that (1) intramolecular cycloaddition of an alkylidene
carbene with a pendant alkene is capable of generating
highly strained bicycloalkene products, and (2) the
imbedded methylenecyclopropane constructs so formed
are prone to facile homolytic C-C bond scission to furnish
This situation might be improved, however, by pre-
senting the intermediate diyl with a suitable internal
trap. Much effort has been directed toward developing
tethered alkene/trimethylenemethane diyl cycloadditions
as an effective polyquinane synthesis strategy by Little
and co-workers.12 A trap in the form of an adjacent alkene
offers a more direct pathway for conversion of a reactive
diyl intermediate into an stable product. This chemistry
has been explored in seminal thermolysis studies on both
vinylmethylenecyclopropane isomers 19 and 21, Scheme
4.13 Much mechanistic inquiry ultimately provided a
coherent picture of these thermolyses that featured a
common intermediate, the orthogonal vinyltrimethylen-
emethane species 20,14 as the precursor to methylenecy-
clopentene product formation. Recently, Cohen et al. have
developed this rearrangement into a useful and stereo-
selective cyclopentene annelation sequence, 23a /b f 24a /
b.15 The relatively high temperatures required for reor-
ganization in these comparatively unstrained systems are
in sharp contrast to the Ko¨brich work where the vinyl-
methylenecyclopropane cleaves at < -40 °C.
Thus, the basic stratagem underlying the synthesis of
dihydropyrroles 3 involves choosing the appropriate
unsaturated substrate 1 that will deliver, upon combina-
tion with 2, an alkylidene carbene whose primary reac-
tivity option is limited to internal alkene addition. Once
this addition occurs, the strained bicyclo[3.1.0]hexene
product can cleave to furnish a reactive trimethylen-
emethane diyl through chemistry analogous to the
Ko¨brich/Berson work (e.g., 16 f 17). However, unlike the
(11) Chesick, J . P. J . Am. Chem. Soc. 1963, 85, 220.
(12) (a) Little, R. D. Chem. Rev. 1996, 96, 93. (b) Little, R. D. Chem.
Rev. 1986, 86, 875.
(13) (a) Billups, W. E.; Leavell, K. H.; Lewis, E. S.; Vanderpool, S.
J . Am. Chem. Soc. 1973, 95, 8096. (b) Kende, A. S.; Riecki, E. E. J .
Am. Chem. Soc. 1972, 94, 1397. (c) Roth, W. R.; Schmidt, T. Tetrahe-
dron Lett. 1971, 3639. (d) Pikulin, S.; Berson, J . A. J . Am. Chem. Soc.
1985, 107, 8274. (e) Shields, T. C.; Billups, W. E.; Lepley, A. R. J . Am.
Chem. Soc. 1968, 90, 4749. (f) Gilbert, J . C.; Higley, D. P. Tetrahedron
Lett. 1973, 2075.
(7) (a) Stang, P. J .; Zhdankin, V. V. Tetrahedron 1998, 54, 10927.
(b) Stang, P. J . In Modern Acetylene Chemistry; Stang, P. J ., Diederich,
F., Eds.; Wiley-VCH: Weinheim, Germany, 1995.
(8) Gilbert, J . C.; Giamalva, D. H.; Weerasooriya, U. J . Org. Chem.
1983, 48, 5251.
(9) (a) Ko¨brich, G.; Heinemann, H. J . Chem. Soc., Chem. Commun.
1969, 493. (b) Ko¨brich, G.; Baumann, M. Angew. Chem., Int. Ed. Engl.
1972, 11, 52.
(10) (a) Salinero, R. F.; Berson, J . A. Tetrahedron Lett. 1982, 23,
1447. (b) Salinero, R. F.; Berson, J . A. J . Am. Chem. Soc. 1979, 101,
7094.
(14) Direct (IR) detection of triplet-4-methylene-2-pentene-1,5-
diyl: Maier, G.; Senger, S. J . Am. Chem. Soc. 1997, 119, 5852.
(15) (a) Davidson, E. R.; Gajewski, J . J .; Shook, C. A.; Cohen, T. J .
Am. Chem. Soc. 1995, 33, 8495. (b) Shook, C. A.; Romberger, M. L.;
J ung, S.-H.; Xiao, M.; Sherbine, J . P.; Zhang, B.; Lin, F.-T.; Cohen, T.
J . Am. Chem. Soc. 1993, 115, 10754.

5652 J . Org. Chem., Vol. 64, No. 15, 1999
Ta ble 1. Syn th esis of th e Dien yltosyla m id es 28 fr om th e Cor r esp on d in g Alcoh ols 25
Feldman
entry
dienol
R
R1
R2
tosylamide
yield (%)
a
b
c
d
e
25a
25b
25c
25d
25e
H
H
H
H
H
(E)-H3CCHdCH
(H3C)2CdCH
(E)-TMSCHdCH
(E)-PhCHdCH
(E)-p-(O2N)C6H4
CHdCH
H
H
H
H
H
28a
28b
28c
28d
28e
59
17
46
26
37
f
g
h
25f
25g
25h
H
H
(Z)-PhCHdCH-
H
H
H
28f
28g
28h
42
26
53
(E)-PhCHdCH
H
CHdCH2
Sch em e 5
earlier studies, incorporation of the second (adjacent)
alkene into the substrate provides a low-energy pathway
for intramolecular quenching of the diyl that leads to
methylenecyclopentene formation. The reduction of this
hypothesis to practice is described below.
Resu lts a n d Discu ssion
The lack of relevant precedents for all of the projected
reaction steps after alkylidene carbene generation from
dienyltosylamide 1 and alkynyliodonium salt 2 suggested
that a thorough examination of both substrate substit-
uents and reaction parameters would be necessary to
develop fully the desired bicyclization sequence. The
earlier work of Ko¨brich and Berson demonstrated that
cyclopropyl substituents profoundly influenced the facil-
ity of C-C bond scission within an annelated methyl-
enecyclopropane substructure.9,10 Thus, the electronic
properties of the distal substituent R in 1 may play a
decisive role in the completion of the planned reaction
cascade. Similarly, the connectivity pattern in isomer 4
may introduce different reaction options to a putative
bicyclo[3.1.0]hexene intermediate, as will become appar-
ent as the cyclization studies unfold. Finally, the level of
stereochemical control inherent in this transform will be
probed with alkene isomers of the prototype (E,E)-diene.
A comparison between the diastereoselectivity observed
upon formation of 3 from these isomeric substrates and
the related Cohen work will illuminate some of the subtle
control elements that contribute to stereoselectivity upon
cyclization of an orthogonal bis allylic radical related to
20. For simplicity of analysis, the readily available and
stable alkynyliodonium salt 2 will be used in all cases.
Functional group incompatibilities that emerged for
certain substituents R during substrate synthesis neces-
sitated the development of two distinct approaches to the
panel of desired tosylamides. The majority of the desired
dienyltosylamides, 28a-h , were prepared from the readily
available alcohol precursors 25, eq 1 in Table 1. Initial
efforts at direct displacement of the alcohol-derived
tosylates or mesylates with the anion of toluenesulfon-
amide were uniformly disappointing. Classical Mitsunobu
approaches likewise were frustrated by low yields and
the predominance of SN2′-like products. Eventual re-
course to the highly activated Mitsunobu reagent cya-
nomethylenetributylphosphorane (CMBP, 27) developed
by Tsunoda16 provided the dienyltosylamide derivatives
in an acceptable compromise between yield and ease of
product isolation, Table 1. Diallylation of tosylamide 26
was occasionally a problem, and the transformation failed
entirely for substrates 25 with R1 ) p-(H3CO)C6H4CHd
CH and PhHCdCH-CHdCH (R ) R2 ) H). In the
former case, SN2′-type products predominantly were
formed.
The two substrates 28i and 28j were prepared by
phosphonate-mediated olefination of the requisite alde-
hydes 32 and 33, respectively, using the allylic phospho-
nate reagent 31, Scheme 5. The N-BOC analogue of
tosylamide 31 has been reported to condense smoothly
with aldehyde 32.17 In both cases examined, the desired
polyalkenylated product was formed with complete (E)
selectivity, albeit in modest yields. The methyl sorbate
derivative 28k was prepared via the Mitsunobu-gener-
ated N-BOC intermediate 35 in overall modest yield.
The initial attempts at addition/bicyclization utilized
the sorbyltosylamide 28a and iodonium salt 2 under
conditions previously identified as conducive to alky-
lidene carbene generation.18 A complex product mixture
ensued, from which a single bicyclic material was iso-
lated, eq 2. Subsequent careful examination of the crude
reaction mixture (1H NMR, extensive chromatography)
did not provide any evidence for alternative cyclization
products such as the putative methylenecyclopropane
intermediate 43 (R ) CH3, R1 ) H) or the regioisomeric
diyl closure product 47 (R, R1 ) CH3, H) (cf. Scheme 7,
vide infra). The overall framework connectivity, as well
as the stereochemical details, was deduced from applica-
tion of HMQC, HMBC, and DNOE NMR techniques, cf.
(17) Connell, R. D.; Helquist, P.; Akermark, B. J . Org. Chem. 1989,
54, 3359.
(16) Tsunoda, T.; Yamamoto, H.; Goda, K.; Ito, S. Tetrahedron Lett.
1996, 37, 2457.
(18) Feldman, K. S.; Bruendl, M. M.; Schildknegt, K.; Bohnstedt,
A. C. J . Org. Chem. 1996, 61, 5440.

Alkynyliodonium Salts in Organic Synthesis
J . Org. Chem., Vol. 64, No. 15, 1999 5653
Ta ble 3. Ad d ition /Bicycliza tion of Dien yltosyla m id es 28
w ith P h en ylp r op yn yliod on iu m Tr ifla te (2) To F u r n ish
An n ela ted Dih yd r op yr r ole P r od u cts 3
3a . The cis stereochemical assignment implied by the
DNOE results was corroborated by the near zero coupling
observed between Ha and Hb. The formation of this
bicyclic product was consistent with the gross expecta-
tions outlined earlier, although both stereochemical and
regiochemical control elements remain unidentified at
this juncture.
diethyl-
tosyl-
bicyclic
yield recovered
entry amide
R
R1 product 3 (%)
28 (%)
a
b
c
d
e
f
28a
28b
28c
28d
28e
28f
28g
28h
CH3
CH3
TMS
Ph
p-(O2N)C6H4
p-(H3CO)C6H4
(E)-PhCHdCH
CO2CH3
H
CH
H
H
H
H
H
H
3a
-
24
-
17
16
20
14
29
10
21
50
3c
3d
3e
3i
3j
-
27
58
12
51
35
-
g
h
The inherent low yield and difficulty in chromato-
graphic isolation of the bicyclic product 3a hindered
optimization studies with 28a . Subsequent cyclization
experiments with the phenyl analogue 28d revealed that
not only were the preliminary yields of bicyclic product
better, but the chromatography was cleaner as well.
Thus, this substrate was chosen for extensive yield
optimization studies, eq 3. Variables examined in these
experiments included concentration, reagent ratio (28d :
2), rate and order of addition, base, solvent, temperature,
and time. The results of these trials indicated that the
yield of bicycle 3d did not vary significantly as concentra-
tion (0.01 to 0.1 M), addition rate (0.3 to 4 h), or base
(LiNTMS2, KNTMS2, NaNTMS2, or n-BuLi) were changed.
However, the order of addition did matter, and the yield
of 3d was highest when a solution of 2 was added to 28d /
base and not the reverse. Three experimental parameters
did modestly influence product yield: reagent ratio,
solvent, and temperature. A survey of these variables,
all examined at 0.01-0.05 M concentration with n-BuLi
as base and an addition time of 4-5 h, is presented in
Table 2. The upshot of these yield optimization studies
with the phenyl-bearing substrate 28d follows: 1.5 equiv
of phenyl(propynyl)iodonium triflate (2) in THF added
to the preformed tosylamide anion (1 equiv of n-BuLi) in
refluxing THF (total concentration ) 0.05 M) over 4-5
h maximizes the yield of the annelated dihydropyrrole
product 3d .
difference in the yield of 3d (or amount of recovered
diene) compared to the unperturbed reaction.
The optimized conditions described in Table 2,
entry e, were exported to addition/bicyclization reactions
for the remainder of the dienyltosylamide substrates
28a -c,e,i-k , eq 4 and Table 3. While it is difficult to
draw sweeping generalizations from this limited data set,
it does appear that those dienyltosylamide substrates
(28a and 28c) whose substituent R cannot engage in
conjugative radical stabilization (Table 3, entry a, R )
CH3, and entry c, R ) TMS) did not perform as well as
the R ) aryl or R ) vinyl analogues. For example, the
p-methoxyphenyl-substituted dienyltosylamide 28i and
iodonium salt 2 combined with nearly equal efficiency
as did the carefully optimized phenyl case 28d . Dienyl-
tosylamide substrates bearing electron-withdrawing func-
tionality (Table 3, entry e, R ) p-nitrophenyl, and entry
h, ) CO2CH3) participated poorly, if at all, in this
transformation. It is possible that either intramolecular
or intermolecular competitive conjugate addition reac-
tions between the tosylamide anion and the Michael
acceptor portion of these species diverted substrate from
the desired reaction channel. The terminally disubsti-
tuted dienyltosylamide 28b failed to provide characteriz-
able product(s) upon combination with 2, an observation
that draws attention to the role of steric hindrance at a
site of eventual bond formation (vide infra). The viny-
logue of 28d , trienyltosylamide 28j, was only moderately
successful in delivering the desired bicyclic product 3j, a
result that may in part reflect the sensitive nature of the
triene unit. An overall requirement for radical-stabilizing
groups that are at the same time immune to nucleophilic
addition seems to characterize the higher yielding ex-
amples of this addition/bicyclization cascade.
Ta ble 2. Op tim iza tion of 3d F or m a tion fr om 28d a n d 2
yield 3d
recovered
The isomeric (E, Z)- and (Z, E)-dienyltosylamide sub-
strates 28f and 28g, respectively, were designed to probe
the relationship between starting alkene geometry and
product stereochemistry. Extrapolation from the Cohen
work (Scheme 4) would lead to the expectation that at
least 28f might afford a bicyclic product featuring a trans
disposition between CH3 and Ph. From this perspective,
it was surprising to discover that both diene geometrical
isomers furnished the same cis-substituted bicyclic prod-
uct 3d already in hand from the (E,E) isomer 28d . No
evidence for alternative products was forthcoming upon
careful examination of the crude reaction mixture, al-
though the conspicuously low yields still leave open the
possibility that minor isomers escaped detection. Appar-
entry
solvent
equiv 2
temp (°C)
(%)
28d (%)
a
b
c
d
e
f
DME
PhH
1.0
1.0
1.0
1.0
1.5
2.0
1.0
1.0
85
80
110
65
65
65
36
41
38
52
58
49
27
24
34
15
26
14
14
17
20
7
PhCH3
THF
THF
THF
THF
THF
g
h
-78 f 25
25
Finally, nucleophilic additives designed to temper the
reactivity of the putative intermediate alkylidene carbene
were included in a few scouting experiments. The pres-
ence of either 1 equiv of Ph3P or Ph2S in the reaction of
28d with 2, however, did not lead to any meaningful

5654 J . Org. Chem., Vol. 64, No. 15, 1999
Feldman
Sch em e 6
the CH2 unit of 28h might serve as the source of this
hydrogen, but no labeling studies to test these hypotheses
were conducted.
The accumulated experimental evidence from the stud-
ies described herein and from prior work in bis allylic
radical chemistry13,15 permit formulation of an inclusive
mechanistic picture that rationalizes both the regiochem-
istry and the stereochemistry of cyclopentenannelated
dihydropyrrole synthesis from the penta-2,4-dienyltosyl-
amide derivative 28, Scheme 7. Initial conjugate addition
of the amide anion derived from 28 to the iodonium salt
2 proceeds through the putative alkylidene carbene 42
to furnish the highly strained azabicyclo[3.1.0]hexene
derivative 43, which formally contains a trans alkene in
a six-membered ring. Note that the trans arrangement
of Ha and Hb on the cyclopropyl core precludes direct [3,3]
sigmatropic reorganization leading to 48. Scission of the
labile cyclopropane C-C bond in 43 then affords an
intermediate orthogonal bis allylic radical 44a . This
pivotal species can continue down one of two competing
pathways: (1) diyl cyclization, along either rotational
direction a or b to furnish the cyclopentene products 47
or 48, respectively, or (2) allyl radical bond rotation to
access the isomeric diradical 44b. Diradical 44b could
then proceed along similar channels to provide the
stereoisomeric product 50 (or its regioisomer similar to
47, not pictured).
The regiochemical outcome of this diyl cyclization is
determined by the direction of rotation (a or b) taken by
44a (or 44b, if applicable). Two independent types of
steric interactions that can impact on the direction of
rotation chosen can be identified. Rotation along pathway
a introduces a burgeoning Hx/H3C A1,3 steric interaction
as the forming bond closes (cf. 45). In contrast, rotation
in the alternate b direction engenders only a presumably
less penalizing Hx/H A1,3 steric interaction upon diradical
closure. The second identifiable type of steric interaction
stems from incipient crowding along the forming bonds
in both 45 and 46. These interactions plausibly favor
cyclization at the secondary site in 45 over closure at a
tertiary carbon in 46. It would seem that these two
distinct types of steric interactions are in opposition, but
which effect dominates? The exclusive formation of 48
(path b) supports a hypothesis that identifies the A1,3
steric elements as major determinants of product regio-
chemistry while at the same time relegating the steric
interactions at the site of bond formation itself to only a
minor role. An electronic component to this regiochemical
preference for 48 over 47 may arise as well. 6-31G*//6-
31G**MP2-level calculations on the simple allylic radical
model system 51 revealed that the tertiary carbon bears
higher electron density in the SOMO than does the
secondary carbon. This observation is consistent with a
model for diyl collapse in which reaction at the tertiary
radical site is intrinsically favored.
ently, there must be some mechanistic divergence be-
tween the Cohen examples and the reactions described
in eq 5.
A very different type of product was observed upon use
of a 2-substituted dienyltosylamide substrate in place of
the 1-substituted analogues. The isoprenyltosylamide
substrate 28h was allowed to react with iodonium salt 2
under the optimized conditions with the anticipation that
an annelated dihydropyrrole product 36 would emerge
following sequential passage through an alkylidene car-
bene, a strained azabicyclo[3.1.0]hexene, and an orthogo-
nal bis allylic radical, Scheme 6. However, the reality was
very different. A single bicyclic product, the azabicyclo-
[3.1.0]hexane species 5, was isolated in moderate yield.
This unexpected reaction course was not anomalous, as
formation of the similar products 39 and 40 from the
simple allylic tosylamides 37 and 38, respectively, was
observed as well. Evidently, the lack of a vinyl substitu-
ent at the alkene terminus of the allylic tosylamide is
sufficient to divert this complex cascade down an alter-
native pathway when compared to the 1-dienyl-contain-
ing substrates.
An attempt to determine the origin of the unexpected
ring juncture hydrogen Ha in 5 was pursued with the
trideuterated version of 2, the iodonium salt 41, eq 6.
Combining 28h with 41 under standard conditions af-
forded only the dideuterioazabicyclo[3.1.0]hexane product
d2-5, eq 6. This result disqualifies the methyl group of 2
as the source of Ha. A few subsequent experiments
extended the search for the origin of Ha. Combination of
28h with 2 in d8-THF did not afford any deuterated 5,
while treatment of 5 with LiNTMS2 and then D2O
returned only unchanged 5. Use of n-BuLi instead of
LiNTMS2 as base led to identical results, suggesting that
the presence of H-NTMS2 in the reaction medium was
not crucial for the deprotonation/reprotonation sequence.
Finally, reaction of the phenylsulfonyl analogue of 28h
with 2 delivered the PhSO2 analogue of 5 in 31% yield.
Since this product is formed in the absence of the tolyl’s
methyl group, this latter experiment rules out H3C-
PhSO2N as the Ha donor in the 28h /2 reaction. It is
conceivable that either the arylsulfonyl ortho protons or
The stereochemical outcome of diyl cyclization depends
on the relative rates of allylic radical isomerization (44a
f 44b) and cyclization (44a f 48). Retention of stereo-

Alkynyliodonium Salts in Organic Synthesis
J . Org. Chem., Vol. 64, No. 15, 1999 5655
Sch em e 7
Sch em e 8
chemical information when the strained vinylmethyl-
enecyclopropane 43 is converted to bicyclic product 48
requires that the cyclization rate exceeds the isomeriza-
tion rate. Since preservation of starting alkene geometry
upon addition/bicyclization was not observed (cf. 28d and
28f f 3d ), it is apparent that equilibration of the allylic
radicals 44a and 44b must be faster than closure. Thus,
the curious case of 28f cyclization to give the cis stere-
ochemical arrangement of CH3 and Ph in product 3d can
be rationalized. In this instance, the first-formed diyl 44a
(R ) H, R1 ) Ph) places a bulky phenyl substituent
directly under the five-membered ring. As the radical
termini approach each other, the growing repulsive
interactions between R1 ) Ph and the ring in 46 must
retard the rate of bond formation. The alternative
isomerization pathway to 44b is evidently favored, and
this diyl (R1 ) Ph, R ) H), which positions only a
hydrogen under the five-membered ring, then rapidly
closes to furnish the “wrong” stereoisomer 50 (R1 ) Ph,
R ) H). The Cohen chemistry provides an interesting
counterpoint to this behavior. In that series, stereochem-
ical integrity is largely maintained upon diyl formation
and cyclization, indicating that closure of either of the
bis allylic radicals 52a or 52b is faster than equilibration.
Apparently, placing a SPh substituent under the cyclo-
heptenyl ring in 52b is not as energetically penalizing
as forcing a phenyl ring under the cyclopentenyl ring of
44a (R1 ) Ph).
Two mechanistic hypotheses can be offered to explain
the formation of the azabicyclo[3.1.0]hexane 5 from
isoprenyltosylamide 28h and iodonium salt 2, Scheme
8. The point of departure from the pentadienyltosylamide
chemistry might come as early as the alkylidene carbene
stage, wherein sluggish addition of the carbene in 53 to
the adjacent 1,1-disubstituted alkene may permit emer-
gence of a normally slower 1,3-[H] shift (53 f 56, via
54).19 Ring opening of the derived cyclopropene in 54
provides access to vinylcarbene 56,20 which can cyclize
by intramolecular cyclopropanation to generate 5. Alter-

5656 J . Org. Chem., Vol. 64, No. 15, 1999
Feldman
equiv) was added via syringe over 5 min to [4-(toluenesulfona-
mide)-(2E)-butenyl)]phosphonic acid diethyl ester 31 (1.0
equiv) in THF at -78 °C, and the solution was stirred for 15
min. The appropriate aldehyde (0.90 equiv) was added over
15 min, and the reaction solution was warmed to room
temperature over 2 h and then stirred for an additional 1 h.
After dilution with EtOAc, the organic layer was poured into
an ice-cold mixture of 1:1 saturated NaHCO3 solution and
brine. The aqueous phase was extracted twice with EtOAc,
and the combined organic phases were dried with MgSO4,
filtered, and concentrated in vacuo. Purification of the crude
product via flash chromatography with the indicated solvent
system followed by recrystallization from the mobile phase
yielded the desired penta-2,4-dienyltoluenesulfonamides.
N-(2E,4E)-Hexa -2,4-d ien ylt olu en esu lfon a m id e (28a ).
Following general procedure A, sorbyl alcohol (25a ) (1.17 g,
11.9 mmol) was dissolved in 50 mL of C6H6 followed by the
addition of p-toluenesulfonamide (2.74 g, 16.0 mmol) and
CMBP (3.87 g, 16.0 mmol). The crude product was chromato-
graphed with 3:7 Et2O/hexane followed by recrystallization
from the mobile phase to yield 1.80 g of pure 28a (59%) as a
white solid. mp 88-89 °C; IR (CDCl3) 3383, 1662, 1332, 1169
natively, the carbene 53 may, in fact, follow the expected
course and generate the strained azabicyclo[3.1.0]hexene
55. Carbon-carbon bond homolysis may be energetically
prohibitive in this case since the cyclopropyl methylene
carbon entirely lacks a radical-stabilizing group (compare
to 43, which has a vinyl appendage at this position). In
this scenario, an alternative pathway for strain relief
involving a formal 1,3-[H] shift becomes manifest. This
1,3-[H] shift could, in principle, occur through either an
intramolecular pathway (55 f 5′) or through a stepwise
intermolecular proton-transfer sequence (55 f 5). In
support of this latter proposition, many instances of base-
mediated isomerization of methylenecyclopropanes into
vinylcyclopropanes have been recorded.21 The complete
absence of deuterium incorporation at the ring juncture
position R in 5 upon combination of 28h and 41 (Scheme
6) permits exclusion of both the vinylcarbene pathway
and the intramolecular 1,3-[H] shift. By default, the
bimolecular proton transfer sequence, presumably medi-
ated by the anion derived from 28h , appears to be the
most likely route by which 5 is formed.
1
cm-1; H NMR (300 MHz, CDCl3) δ 7.73 (d, J ) 8.3 Hz, 2 H),
7.29 (d, J ) 8.1 Hz, 2 H), 5.97 (m, 2 H), 5.62 (m, 1 H), 5.35 (dt,
J ) 6.5, 14.8 Hz, 1 H), 4.59 (t, J ) 5.9 Hz, 1 H), 3.57 (t, J )
6.3 Hz, 2 H), 2.42 (s, 3 H), 1.71 (d, J ) 6.8 Hz, 3 H); 13C NMR
(50 MHz, CDCl3) δ 143.4, 137.0, 133.6, 130.6, 130.2, 129.7,
127.1, 124.4, 45.2, 21.5, 18.0; CIMS m/z (relative intensity)
Exp er im en ta l Section
Moisture and oxygen sensitive reactions were carried out
in flame-dried glassware under an argon atmosphere. Tet-
rahydrofuran (THF), dimethoxyethane (DME), and dioxane
were distilled from sodium benzophenone ketyl under an argon
atmosphere immediately before use. Toluene, benzene (C6H6),
and dichloromethane (CH2Cl2) were distilled from calcium
hydride (CaH2) under an argon atmosphere immediately before
use. n-Butyllithium (2.5 M hexanes), lithium hexamethylsi-
lylamide (1.0 M THF), sodium hexamethylsilylamide (1.0 M
THF), potassium hexamethylsilylamide (0.5 M toluene), so-
dium hydride (NaH, 60% in oil), and methyllithium (1.6 M
Et2O) were used as purchased. Purification of products via
flash chromatography22 was performed with 32-63 mm silica
gel and the solvent systems indicated. Hexane and diethyl
ether (Et2O) used in flash chromatography were distilled from
CaH2 prior to use, whereas ethyl acetate (EtOAc) was used as
purchased. Melting points are uncorrected. Chemical impact
mass spectra (CIMS) were obtained with isobutane as the
252 (MH+, 44), 184 (95), 81 (100). Anal. Calcd for C13H17
-
NO2S: C, 62.12; H, 6.82; N, 5.57; S, 12.76; found: C, 62.30;
H, 6.80; N, 5.66; S, 12.76.
N -(2E ,4E )-5-Me t h ylh e xa -2,4-d ie n ylt olu e n e su lfon a -
m id e (28b). Following general procedure A, (E)-5-methylhexa-
2,4-dienol (25b)23 (0.54 g, 4.8 mmol) was dissolved in 24 mL
of C6H6 followed by the addition of p-toluenesulfonamide (0.82
g, 4.8 mmol) and CMBP (1.74 g, 7.2 mmol). The crude product
was purified on silica gel with 3:7 Et2O/hexane followed by
recrystallization from the mobile phase to yield 0.21 g of pure
28b (17%) as a white solid. mp 92-94 °C; IR (CDCl3) 3378,
1
1331, 1161 cm-1; H NMR (300 MHz, CDCl3) δ 7.75 (d, J )
8.3 Hz, 2 H), 7.31 (d, J ) 8.0 Hz, 2 H), 6.28 (dd, J ) 10.9, 15.0
Hz, 1 H), 5.71 (d, J ) 11.0, 1 H), 5.37 (dt, J ) 6.5, 15.0 Hz, 1
H), 4.27 (t, J ) 5.8 Hz, 1H), 3.62 (t, J ) 6.3 Hz, 2 H), 2.43 (s,
3 H), 1.75 (s, 3 H), 1.69 (s, 3 H); 13C NMR (50 MHz, CDCl3) δ
143.4, 137.0, 136.9, 130.1, 129.7, 127.2, 124.1, 123.7, 45.5, 25.9,
21.5, 18.3; CIMS m/z (relative intensity) 266 (MH+, 7), 184
(98), 95 (100). Anal. Calcd for C14H19NO2S: C, 63.37; H, 7.22;
N, 5.28; S, 12.08. Found: C, 63.31; H, 7.20; N, 5.34; S, 12.18.
N-(2E,4E)-(5-Tr im eth ylsilyl)-p en ta -2,4-d ien yltolu en e-
su lfon a m id e (28c). Following general procedure A, dienol
25c24 (0.24 g, 1.56 mmol) was dissolved in 8 mL of C6H6
followed by the addition of p-toluenesulfonamide (0.27 g, 1.6
mmol) and CMBP (0.56 g, 2.3 mmol). The crude product was
chromatographed with 3:7 Et2O/hexane and recrystallized
from the mobile phase to yield 0.22 g of pure 28c (46%) as a
1
reagent gas. Copies of H and 13C NMR spectra are provided
in the Supporting Information to establish purity for those
compounds that were not subjected to combustion analyses.
Gen er a l P r oced u r e A: Syn th esis of Der iva tives of
P en t a -2,4-d ien ylt olu en esu lfon a m id es 28a -h via Mit -
su n obu Rea ction s. p-Toluenesulfonamide (1.0 equiv) was
added to a solution of dienol (1.0 equiv) in C6H6 or CH2Cl2,
and the mixture was purged with inert gas. CMBP (1.5 equiv)
dissolved in like solvent was added over several minutes via
syringe, and the resulting solution was stirred overnight at
room temperature. Concentration of the crude reaction mixture
in vacuo followed by purification via flash chromatography on
silica gel with the indicated solvent system and recrystalliza-
tion yielded the desired penta-2,4-dienyltoluenesulfonamides.
Gen er a l P r oced u r e B for Syn th esis of Der iva tives of
P en ta -2,4-d ien yltolu en esu lfon a m id es via Hor n er -Em -
m on s Wittig Rea ction s. Sodium hexamethylsilylamide (2.0
white solid. mp 74-75 °C; IR (CDCl3) 3389, 1331, 1155 cm-1
;
1H NMR (300 MHz, CDCl3) δ 7.74 (d, J ) 8.3 Hz, 2 H), 7.31
(d, J ) 8.4 Hz, 2 H), 6.38 (dd, J ) 10.0, 18.3 Hz, 1 H), 6.08
(dd, J ) 10.0, 15.2 Hz, 1 H), 5.80 (d, J ) 18.3 Hz, 1 H), 5.53
(dt, J ) 6.3, 15.2 Hz, 1 H), 4.55 (t, J ) 6.1 Hz, 1 H), 3.61 (t, J
) 6.2 Hz, 2 H), 2.43 (s, 3 H), 0.05 (s, 3 H); 13C NMR (50 MHz,
CDCl3) δ 143.5, 142.5, 137.0, 136.0, 135.7, 129.7, 127.8, 127.2,
45.0, 21.5, -1.4; CIMS m/z (relative intensity) 310 (MH+, 23),
172 (100). Anal. Calcd for C15H23NO2SSi: C, 58.21; H, 7.49;
N, 4.53; S, 10.36; found: C, 58.09; H, 7.52; N, 4.61; S, 10.31.
N-(2E,4E)-5-P h e n ylp e n t a -2,4-d ie n ylt olu e n e su lfon a -
m id e (28d ). Following general procedure A, (2E,4E)-5-phe-
nylpenta-2,4-dienol (25d )25 (0.59 g, 3.7 mmol) was dissolved
in 18 mL of C6H6 followed by the addition of p-toluenesulfona-
(19) Wolinski, J .; Clark, G. W.; Thorstenson, P. C. J . Org. Chem.
1976, 41, 745.
(20) Davies, H. M. L.; Houser, J . H.; Thornley, C. J . Org. Chem.
1995, 60, 7529.
(21) (a) Weber, W.; de Meijere, A. Chem. Ber. 1985, 118, 2450. (b)
Arora, S.; Binger, P.; Ko¨ster, R. Synthesis 1973, 146. (c) Vincens, M.;
Dumont, C.; Vidal, M. Can. J . Chem. 1979, 57, 2314. (d) Akhachin-
skaya, T. V.; Shapiro, I. O.; Donskaya, N. A.; Shabarov, Y. S.;
Shatenshtein, A. I. J . Org. Chem. USSR 1985, 21, 421. (e) Akhachin-
skaya, T. V.; Donskaya, N. A.; Grishin, Y. K.; Shabarov, Y. S. J . Org.
Chem. USSR 1987, 23, 295. (f) Petasis, N. A.; Bzowej, E. I. Tetrahedron
Lett. 1993, 43, 943. (g) Ullman, E. F.; Fanshawe, W. J . J . Am. Chem.
Soc. 1961, 83, 2379.
(23) Boyd, J .; Epstein, W.; Fra´ter, G. J . Chem. Soc., Chem. Commun.
1976, 380.
(24) Chou, W.-N.; White, J . B. Tetrahedron Lett. 1991, 32, 7637.
(25) Ishii, Y.; Gao, C.; Xu, W.-X.; Iwasaki, M.; Hidai, M. J . Org.
Chem. 1993, 58, 6818.
(22) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.

Alkynyliodonium Salts in Organic Synthesis
J . Org. Chem., Vol. 64, No. 15, 1999 5657
mide (0.63 g, 3.7 mmol) and CMBP (1.35 g, 5.6 mmol). The
crude product was chromatographed with 1:1 Et2O/hexane
followed by recrystallization from the mobile phase to yield
0.31 g of pure 28d (26%) as a white solid. mp 124-126 °C; IR
(CDCl3) 3386, 1335, 1161 cm-1; 1H NMR (200 MHz, CDCl3) δ
7.76 (d, J ) 8.3 Hz, 2 H), 7.39-7.22 (m, 7 H), 6.66 (dd, J )
10.0, 15.6 Hz, 1 H), 6.47 (d, J ) 15.6 Hz, 1 H), 6.26 (dd, J )
10.0, 15.1 Hz, 1 H), 5.63 (dt, J ) 6.4, 15.1 Hz, 1 H), 4.44 (bs,
1 H), 3.69 (t, J ) 6.3 Hz, 2 H), 2.43 (s, 3 H); 13C NMR (50
MHz, CDCl3) δ 143.5, 137.0, 136.8, 133.4, 133.2, 129.7, 128.6,
127.8, 127.7, 127.5, 127.1, 126.4, 45.1, 21.5; CIMS m/z (relative
δ 7.73 (d, J ) 8.3 Hz, 2 H), 7.35-7.20 (m, 7 H), 6.58 (dd, J )
11.2, 15.1 Hz, 1 H), 6.40 (d, J ) 11.5 Hz, 1 H), 6.10 (dd, J )
11.4 Hz, 1 H), 5.66 (dt, J ) 6.5, 15.1 Hz, 1 H), 4.90 (t, J ) 6.2
Hz, 1 H), 3.63 (t, J ) 6.3 Hz, 2 H), 2.38 (s, 3 H); 13C NMR (75
MHz, CDCl3) δ 143.4, 137.0, 136.8, 130.7, 130.1, 129.6, 129.1,
128.8, 128.7, 128.2, 127.1 (2 C), 45.1, 21.4; EIMS m/z (relative
intensity) 313 (M+, 3); HRMS calcd for C18H19NO2S 313.1034,
found 313.0980.
N-(2Z,4E)-5-P h en ylp en t a -2,4-d ien ylt olu en esu lfon -
a m id e (28 g). DIBAL in toluene (10.9 mL of a 1 M solution,
10.9 mmol) was added to a solution of methyl (2Z,4E)-5-
phenylpenta-2,4-dienoate28 (1.0 g, 5.3 mmol) in 18 mL of
benzene at room temperature. After 10 h at room temperature,
the solution was cooled to 0 °C and excess DIBAL was
quenched with CH3OH. This solution was poured into 10%
aqueous HCl, and the mixture was extracted twice with
EtOAc. The combined organic phases were washed with brine,
dried with MgSO4, filtered, and concentrated in vacuo. Chro-
matography of the residue on silica gel with 1:1 Et2O/hexane
as eluent afforded 747 mg of the dienol 25g (88%). 1H NMR
(200 MHz, CDCl3) δ 7.3 (m, 5 H), 7.11 (dd, J ) 15, 10 Hz, 1
H), 6.73 (d, J ) 15 Hz, 1 H), 6.31 (t, J ) 10 Hz, 1 H), 5.73 (dt,
J ) 10, 5 Hz, 1 H), 4.45 (d, J ) 5 Hz, 2 H), 1.77 (bs, 1 H).
intensity) 314 (MH+, 13), 184 (100). Anal. Calcd for C18H19
-
NO2S: C, 68.98; H, 6.11; N, 4.47; S, 10.23; found: C, 68.71;
H, 6.01; N, 4.53; S, 10.38.
N-(2E,4E)-5-(4-Nit r op h en yl)p en t a -2,4-d ien ylt olu en e-
su lfon a m id e (28e). DIBAL in toluene (24.5 mL of a 1 M
solution, 24.5 mmol) was added to a solution of ethyl (2E,4E)-
5-(4-nitrophenyl)penta-2,4-dienoate26 (3.0 g, 12.1 mmol) in 30
mL of benzene at room temperature. After 18 h at room
temperature, the solution was cooled to 0 °C and excess DIBAL
was quenched with CH3OH. This solution was poured into 10%
aqueous HCl, and the mixture was extracted three times with
EtOAc. The combined organic phases were washed with brine,
dried with MgSO4, filtered, and concentrated in vacuo. Chro-
matography of the residue on silica gel with 1:1 EtOAc/hexane
as eluent furnished 1.62 g of the dienol 25e (65%). IR (CDCl3)
Following general procedure A, dienol 25g (0.75 g, 4.7 mmol)
was dissolved in 24 mL of C6H6 followed by the addition of
p-toluenesulfonamide (0.80 g, 4.7 mmol) and CMBP (1.71 g,
7.1 mmol). The crude product was chromatographed with 1:1
Et2O/hexane followed by recrystallization from the mobile
phase to yield 0.39 g of pure 28g (26%) as a white solid. mp
3695, 3613, 1513, 1378 cm-1 1H NMR (300 MHz, CDCl3) δ
;
8.15 (d, J ) 8.9 Hz, 2H), 7.49 (d, J ) 8.8 Hz, 2H), 6.92 (dd, J
) 15.6, 11 Hz, 1H), 6.56 (d, J ) 15.7 Hz, 1H), 6.45 (dd, J )
15.2, 10.4 Hz, 1H), 6.09 (dt, J ) 15.3, 5.5 Hz, 1H), 4.29 (d, J
) 5.5 Hz, 2H), 1.73 (bs, 1H); 13C NMR (75 MHz, CDCl3) δ
146.7, 143.7, 136.0, 132.7, 130.2, 130.0, 126.7, 124.0, 63.0.
Following general procedure A, (2E,4E)-5-(4-nitrophenyl)-
penta-2,4-dienol (25e) (1.33 g, 6.5 mmol) was dissolved in 32
mL of CH2Cl2 followed by the addition of p-toluenesulfonamide
(1.11 g, 6.5 mmol) and CMBP (2.36 g, 9.8 mmol). The crude
product was chromatographed with 1:1 EtOAc/hexane followed
by recrystallization from the mobile phase to yield 0.71 g of
pure 28e (30%) as a yellow microcrystalline solid. mp 174-
179 °C; IR (CDCl3) 3389, 1519, 1343, 1161 cm-1; 1H NMR (200
MHz, CDCl3) δ 8.16 (d, J ) 8.9 Hz, 2 H), 7.77 (d, J ) 8.3 Hz,
2 H), 7.47 (d, J ) 8.8 Hz, 2 H), 7.33 (d, J ) 8.0 Hz, 2 H), 6.81
(dd, J ) 10.3, 15.6 Hz, 1 H), 6.52 (d, J ) 15.7 Hz, 1 H), 6.32
(dd, J ) 10.4, 15.2 Hz, 1 H), 5.81 (dt, J ) 6.2, 15.2 Hz, 1 H),
4.46 (t, J ) 5.8 Hz, 1 H), 3.72 (t, J ) 6.1 Hz, 2 H), 2.44 (s, 3
H); 13C NMR (90 MHz, CDCl3) δ 146.9, 143.7, 143.3, 137.0,
132.4, 131.9, 131.4, 130.8, 129.8, 127.2, 126.8, 124.1, 45.0, 21.5;
CIMS m/z (relative intensity) 359 (MH+, 26), 184 (87) 172
(100). Anal. Calcd for C18H18N2O4S: C, 60.32; H, 5.06; N, 7.82;
S, 8.94; found: C, 60.25; H, 5.01; N, 7.70; S, 8.67.
1
88-90 °C; IR (CDCl3) 3378, 1336, 1161 cm-1; H NMR (360
MHz, CDCl3) δ 7.78 (d, J ) 8.2 Hz, 2 H), 7.35-7.22 (m, 7 H),
6.79 (dd, J ) 11.2, 15.4 Hz, 1 H), 6.53 (d, J ) 15.4 Hz, 1 H),
6.19 (dd, J ) 11.0 Hz, 1 H), 5.35 (dt, J ) 3.3, 10.6 Hz, 1 H),
4.69 (t, 1 H), 3.82 (t, J ) 7.1 Hz, 2 H), 2.41 (s, 3 H); 13C NMR
(75 MHz, CDCl3) δ 143.5, 136.8, 136.7, 135.1, 132.4, 129.7,
128.6, 128.0, 127.2, 126.6, 125.0, 122.5, 40.4, 21.5; CIMS m/z
(relative intensity) 314 (MH+, 9), 184 (74), 67 (100). Anal. Calcd
for C18H19NO2S: C, 68.98; H, 6.11; N, 4.47; S, 10.23; found:
C, 69.33; H, 6.29; N, 4.48; S, 10.22.
N-2-Meth ylen ebu t-3-en yltolu en esu lfon am ide (28h ). Fol-
lowing general procedure A, 2-methylene-3-butenol29 (0.34 g,
4.0 mmol) was dissolved in 50 mL of C6H6 followed by the
addition of p-toluenesulfonamide (0.94 g, 5.5 mmol) and CMBP
(1.33 g, 5.5 mmol). The crude product was chromatographed
with 3:7 Et2O/hexane to yield 0.50 g of pure 28h (53%) as a
white solid. mp 45-47 °C; IR (CDCl3) 3365, 1337 cm-1 1H
;
NMR (300 MHz, CDCl3) δ 7.77 (dd, J ) 1.8, 6.5 Hz, 2 H), 7.31
(d, J ) 8.0 Hz, 2 H), 6.29 (dd, J ) 11.0, 17.7 Hz, 1 H), 5.13 (m,
4 H), 3.73 (d, J ) 6.2 Hz, 2 H), 2.43 (s, 3 H); 13C NMR (75
MHz, CDCl3) δ 143.5, 140.7, 136.7, 136.0, 129.7, 127.1, 118.1,
114.8, 44.1, 21.5; CIMS m/z (relative intensity) 238 (MH+, 100);
HRMS calcd for C12H15NO2S 237.0823, found 237.0816.
N -(2E ,4Z)-5-P h e n ylp e n t a -2,4-d ie n ylt olu e n e su lfon a -
m id e (28f). DIBAL in toluene (7.0 mL of a 1 M solution, 7.0
mmol) was added to a solution of methyl (2E,4Z)-5-phenyl-
penta-2,4-dienoate27 (0.64 g, 3.4 mmol) in 17 mL of benzene
at room temperature. After 2 h at room temperature, the
solution was cooled to 0 °C and excess DIBAL was quenched
with CH3OH. This solution was poured into 10% aqueous HCl,
and the mixture was extracted twice with EtOAc. The com-
bined organic phases were washed with brine, dried with
MgSO4, filtered, and concentrated in vacuo. Chromatography
of the residue on silica gel with 1:1 EtOAc/hexane as eluent
furnished 378 mg of the dienol 25f (69%). 1H NMR (200 MHz,
CDCl3) δ 7.3 (m, 5 H), 6.82 (ddd, J ) 16, 12, 1 Hz, 1 H), 6.49
(d, J ) 12 Hz, 1 H), 6.37 (t, J ) 12 Hz, 1 H), 6.01 (dt, J ) 15,
5 Hz, 1 H), 4.22 (dd, J ) 6, 1 Hz, 2 H), 1.48 (bs, 1 H).
N -(2E ,4E )-5-(4-Me t h oxyp h e n yl)p e n t a -2,4-d ie n ylt ol-
u en esu lfon a m id e (28i). Following general procedure B,
sodium hexamethylsilylamide (1.3 mL, 1.3 mmol) was added
to phosphonate sulfonamide 31 (0.23 g, 0.64 mmol) followed
by p-methoxybenzaldehyde (32) (0.078 g, 0.58 mmol). The
crude product was chromatographed with 1:1 Et2O/hexane and
recrystallized from the mobile phase to yield 0.096 g of pure
28i (43%) as a white solid. mp 137-140 °C; IR (CDCl3) 3389,
1
1333, 1169 cm-1; H NMR (300 MHz, CDCl3) δ 7.76 (d, J )
8.1 Hz, 2 H), 7.32-7.26 (m, 4 H), 6.84 (d, J ) 8.6 Hz, 2 H),
6.52 (dd, J ) 9.9, 15.6 Hz, 1 H), 6.42 (d, J ) 15.6 Hz, 1 H),
6.22 (dd, J ) 9.9, 15.1 Hz, 1 H), 5.57 (dt, J ) 6.6, 15.0 Hz, 1
H), 4.43 (t, J ) 6.0 Hz, 1 H), 3.69 (t, J ) 6.3 Hz, 2 H), 3.81 (s,
3 H), 2.43 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ 159.4, 143.5,
137.0, 133.9, 133.0, 129.7, 129.6, 127.7, 127.2, 126.4, 125.4,
114.1, 55.3, 45.3, 21.5; CIMS m/z (relative intensity) 344 (MH+,
68), 172 (100). Anal. Calcd for C19H21NO3S: C, 66.45; H, 6.16;
N, 4.08; S, 9.33; found: C, 66.16; H, 6.32; N, 4.05; S, 9.27.
Following general procedure A, dienol 25f (0.27 g, 1.7 mmol)
was dissolved in 8 mL of C6H6 followed by the addition of
p-toluenesulfonamide (0.29 g, 1.7 mmol) and CMBP (0.60 g,
2.5 mmol). The crude product was chromatographed with 2:3
Et2O/hexane to yield 0.22 g of pure 28f (42%) as a thick oil.
IR (CDCl3) 3378, 1332, 1162 cm-1; 1H NMR (300 MHz, CDCl3)
(26) Huang, Y.; Shen, Y.; Zheng, J .; Zhang, S. Synthesis 1985, 57.
(27) Myrboh, B.; Asokan, C. V.; Ila, H.; J unjappa, H. Synthesis 1984,
50.
(28) Lu, X.; Huang, X.; Ma, S. Tetrahedron Lett. 1992, 33, 2535.
(29) Riley, R. G.; Silverstein, R. M.; Katzenellenbogen, J . A.; Lenox,
R. S. J . Org. Chem. 1974, 39, 1957.

5658 J . Org. Chem., Vol. 64, No. 15, 1999
Feldman
N-(2E,4E,6E)-7-P h en ylh epta-2,4,6-tr ien yltolu en esu lfon -
a m id e (28j). Following general procedure B, sodium hexam-
ethylsilylamide (1.4 mL, 1.4 mmol) was added to the phos-
phonate sulfonamide (0.25 g, 0.7 mmol) followed by cinnam-
aldehyde (0.085 g, 0.64 mmol). The crude product was
chromatographed with 1:1 Et2O/hexane and recrystallized
from the mobile phase to yield 0.051 g of pure 28i (23%) as
light yellow flakes. mp 138-143 °C; IR (CDCl3) 3378, 1335,
flash chromatography with 3:7 Et2O/hexane and recrystallized
from the mobile phase to yield 0.82 g of pure 30 (57%) as a
white solid. mp 82-83 °C; IR (CDCl3) 1727, 1367, 1155 cm-1
;
1H NMR (300 MHz, CDCl3) δ 7.80 (d, J ) 8.4 Hz, 2 H), 7.30
(d, J ) 8.2 Hz, 2 H), 5.91 (m, 2 H), 4.45 (d, J ) 4.4 Hz, 2 H),
4.08 (d, J ) 4.3 Hz, 2 H), 2.44 (s, 3 H), 1.36 (s, 9 H); 13C NMR
(50 MHz, CDCl3) δ 150.6, 144.3, 137.0, 129.7, 129.2 (2 C),
128.2, 84.5, 47.3, 44.1, 27.9, 21.6; CIMS m/z (relative intensity)
303 (MH+ - t-Bu, 100), 268 (MH+ - t-Bu and Cl, 63). Anal.
Calcd for C16H22NO4SCl: C, 53.40; H, 6.16; Cl, 9.85; N, 3.89;
S, 8.91; found: C, 53.02; H, 6.16; Cl, 9.72; N, 3.87; S, 9.22.
1
1162 cm-1; H NMR (360 MHz, CDCl3) δ 7.76 (d, J ) 8.3 Hz,
2 H), 7.39-7.20 (m, 7 H), 6.77 (dd, J ) 10.0, 15.5 Hz, 1 H,),
6.55 (d, J ) 15.6 Hz, 1 H), 6.35-6.14 (m, J ) 10.0, 15.1 Hz, 1
H), 5.56 (dt, J ) 6.5, 14.3 Hz, 1 H), 4.46 (t, J ) 5.9 Hz, 1 H),
3.66 (t, J ) 6.3 Hz, 2 H), 2.43 (s, 3 H); 13C NMR (90 MHz,
CDCl3) δ 143.5, 137.1, 137.0, 134.0, 133.4, 133.4, 131.5, 129.7,
128.6, 128.5, 127.7, 127.5, 127.2, 126.4, 45.3, 21.5; CIMS m/z
(relative intensity) 340 (MH+, 44), 169 (100); HRMS calcd for
Dieth yl [4-(Tolu en esu lfon a m id e)-(E)-2-bu ten yl)]p h os-
p h on a te (31). Chlorosulfonamide 30 (1.47 g, 4.1 mmol),
sodium iodide (0.12 g, 0.82 mmol), and triethyl phosphite (1.5
g, 9.0 mmol) were added to a thick-walled Schlenk tube
equipped with a Teflon stopcock. This mixture was sealed
under vacuum and heated to 110 °C for 22 h, at which time it
was cooled to room temperature and diluted with EtOAc. This
solution was washed three times with a saturated solution of
sodium thiosulfite and once with brine. All aqueous phases
were extracted twice with EtOAc, and the combined organic
layers were dried with Na2SO4, filtered, and concentrated. The
crude product was purified via flash chromatography with
EtOAc to yield two products: 1.24 g of pure N-Boc derivative
of 31 (66%) and 0.24 g of 31 (16%), both as colorless oils.
C
20H21NO2S 339.1293, found 339.1282.
Meth yl (E,E)-6-Tolu en esu lfon ylam in oh exa-2,4-dien oate
(28k ). Triphenylphosphine (5.42 g, 20.7 mmol), N-tert-butoxy-
carbonyl-p-toluenesulfonamide (2.51 g, 9.3 mmol), and ester
alcohol 3430 (1.47 g, 10.3 mmol) were dissolved in 60 mL of
THF at room temperature. Diisopropyl azodicarboxylate (5.1
mL, 25.7 mmol) was added dropwise, and the reaction solution
was stirred overnight. After concentration in vacuo, the crude
product was purified via flash chromatography with 1:4 EtOAc/
hexane to yield pure 35 (30%) as a white solid. mp 99-101
Trifluoroacetic acid (0.67 g, 5.9 mmol) was added to a
solution of the BOC-protected derivative of 31 (0.54 g, 1.2
mmol) in 5 mL of CH2Cl2. After being refluxed for 20 h, the
solution was diluted with EtOAc and poured into an ice cold
saturated solution of NaHCO3. The aqueous layer was ex-
tracted twice with EtOAc, and the combined organic phases
were dried with Na2SO4, filtered, and concentrated. The crude
product was purified via flash chromatography to yield 0.37 g
°C; IR (CDCl3) 1720, 1372, 1154 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 7.76 (d, J ) 8.4 Hz, 2 H), 7.31 (d, J ) 8.0 Hz, 2 H),
7.27 (m, 1 H), 6.37 (dd, J ) 11.1, 15.2 Hz, 1 H), 6.14 (dt, J )
6.1, 15.3 Hz, 1 H), 5.90 (d, J ) 15.4 Hz, 1 H), 4.53 (d, J ) 6.0
Hz, 2 H), 3.76 (s, 3 H), 2.43 (s, 3 H), 1.35 (s, 9 H); 13C NMR
(75 MHz, CDCl3) δ 167.2, 150.6, 144.4, 143.5, 137.0, 136.7,
130.9, 129.3, 128.1, 121.8, 84.7, 51.6, 47.8, 27.9, 21.6; CIMS
m/z (relative intensity) 339 (MH+, - t-Bu). Anal. Calcd For
of pure 31 (86%) as a colorless oil. IR (CDCl3) 1708, 1166 cm-1
;
1H NMR (200 MHz, CDCl3) δ 7.74 (d, J ) 8.3 Hz, 2 H), 7.30
(d, J ) 8.8 Hz, 2 H), 5.57 (m, 2 H), 5.04 (t, J ) 6.1 Hz, 1 H),
4.04 (m, 4 H), 3.54 (m, 2 H), 2.51 (dd, J ) 5.6, 21.8, 2 H), 2.43
(s, 3 H), 1.30 (t, J ) 7.0 Hz, 6 H); 13C NMR (50 MHz, CDCl3)
δ 143.3, 137.0, 130.2 (d, J ) 14.5 Hz), 129.6, 127.1, 122.9 (d,
J ) 10.9 Hz); 61.9 (d, J ) 6.6 Hz), 44.9 (d, J ) 2.1 Hz), 30.0
(d, J ) 139.5 Hz), 21.5, 16.4 (d, J ) 5.9 Hz); CIMS m/z (relative
intensity) 362 (MH+, 100); HRMS calcd for C15H24NO5PS
362.1191, found 362.1190.
C
19H25NO6S: C, 57.71; H, 6.37; N, 3.54; S, 8.11. Found: C,
57.67; H, 6.38; N, 3.52; S, 8.07.
The BOC-sulfonamide 35 (1.21 g, 3.1 mmol) was dissolved
in CH2Cl2 and purged with Ar. Trifluoroacetic acid (1.74 g,
15.3 mmol) was added, and the reaction solution was stirred
at room temperature for 21 h. The crude product was diluted
with EtOAc and poured into ice cold saturated aqueous sodium
bicarbonate. The aqueous phase was extracted twice with
EtOAc, and the combined organic phases were washed with
saturated sodium chloride, dried with anhydrous Na2SO4,
filtered, and concentrated. The crude product was then purified
via flash chromatography with 2:3 EtOAc/hexane to yield pure
28k as a white solid (35%). mp 132-135 °C; IR (CDCl3) 3392,
Gen er a l P r oced u r e C for th e Ad d ition /Cycliza tion of
Dien yltosyla m id es 28 w ith P h en yl(p r op yn yl)iod on iu m
Tr ifla te (2). n-BuLi (1 equiv, 2.5 M in hexane) was added over
several minutes to a deoxygenated, stirring solution of the
appropriate sulfonamide in the indicated solvent (∼0.01 M)
at -78 °C. The reaction was warmed to 0 °C for 0.5 h and
then heated to reflux and held there. Phenyl(propynyl)-
iodonium triflate 231 (indicated equiv) was added dropwise via
syringe over 4 h as a ∼0.4 M solution in the indicated solvent.
Stirring was maintained for an additional 1 h, at which time
the solution was cooled to room temperature, diluted with
Et2O, and washed with brine. The aqueous layer was extracted
twice with Et2O, and the combined organic phases were dried
over anhydrous MgSO4, filtered, and concentrated in vacuo.
The resulting residue was purified via flash chromatography
with the indicated solvent system.
1
1332, 1162 cm-1; H NMR (300 MHz, CDCl3) δ 7.75 (d, J )
8.3 Hz, 2 H), 7.31 (d, J ) 8.0 Hz, 2 H), 7.14 (dd, J ) 11.0. 18.6
Hz, 1 H), 6.24 (dd, J ) 11.0, 15.1 Hz, 1 H), 5.90 (dt, J ) 5.9,
15.3 Hz, 1 H), 5.81 (d, J ) 15.4 Hz, 1 H), 3.74 (s, 3 H), 3.71 (t,
J ) 5.9 Hz, 2 H), 2.43 (s, 3 H); 13C NMR (75 MHz, CDCl3) δ
167.1, 143.8, 143.1, 136.9, 136.4, 130.1, 129.8, 127.1, 121.8,
51.6, 44.7, 21.5; CIMS m/z (relative intensity) 296 (MH+, 100).
Anal. Calcd for C14H17NO4S: C, 56.97; H, 5.80; N, 4.74; S,
10.85. Found: C, 56.81; H, 5.96; N, 4.81; S, 10.91.
N,N-(ter t-Bu t oxyca r b on yl)-(4-ch lor o-(E)-2-b u t en yl)-
tolu en esu lfon a m id e (30). N,N-Dimethylformamide (DMF,
9 mL) was added at 0 °C to NaH (0.19 g, 4.8 mmol) and tert-
butoxycarbonyl-p-toluenesulfonamide (1.09 g, 4.0 mmol), and
the solution was stirred for 15 min. (E)-1,4-Dichloro-2-butene
(1.5 g, 12.0 mmol) in 3 mL of DMF was added via syringe all
at once. The orange solution was stirred for 10 min and then
heated at 65 °C for 3 h. After cooling the reaction solution to
room temperature, 5 mL of H2O was added to quench any
remaining NaH. Ethyl acetate was used to partition the
phases, and the organic layers were washed sequentially with
saturated solutions of sodium thiosulfite and 1:1 NaHCO3/
brine. All aqueous layers were extracted twice with EtOAc,
and the combined organic phases were dried with Na2SO4,
filtered, and concentrated. The crude product was purified via
N-(Tolu en esu lfon am ide)-6,6a-dim eth yl-1,2,6,6a-tetr ah y-
d r ocyclop en ta [b]p yr r ole (3a ). Following general procedure
C, n-BuLi (0.20 mmol) was added to sulfonamide 28a (50 mg,
0.20 mmol) in 20 mL of THF. Phenyl(propynyl)iodonium
triflate (2) (120 mg, 0.30 mmol) was dissolved in ∼0.5 mL of
THF and added via syringe over 4 h. The crude mixture was
chromatographed with 2:23 Et2O/hexane and 3:7 Et2O/hexane
to yield 14 mg of pure 3a (24%) as a foam and recovered 28a
(8.5 mg, 17%). IR (CDCl3) 3045, 1599, 1335, 1159 cm-1 1H
;
NMR (300 MHz, CDCl3) δ 7.76 (d, J ) 8.3 Hz, 2 H), 7.28 (d, J
) 8.4 Hz, 2 H), 6.05 (dd, J ) 2.7, 5.9 Hz, 1 H), 5.92 (d, J ) 6.0
Hz, 1 H), 5.25 (bs, 1 H), 4.32 (dd, J ) 13.9, 1.0 Hz, 1 H), 4.27
(30) Closa, M.; de March, P.; Figueredo, M.; Font, J .; Soria, A.
Tetrahedron 1997, 53, 16803.
(31) Zhdankin, V. V.; Scheuller, M. C.; Stang, P. J . Tetrahedron Lett.
1993, 34, 6853-6856.

Alkynyliodonium Salts in Organic Synthesis
J . Org. Chem., Vol. 64, No. 15, 1999 5659
(ddd, J ) 13.9, 3.3, 1.1 Hz, 1 H), 3.02 (bq, J ) 7.3 Hz, 1 H),
2.42 (s, 3 H), 1.29 (d, J ) 7.3 Hz, 3 H), 1.15 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 157.1, 147.1, 143.0, 138.0, 129.5, 127.4,
123.2, 107.9, 80.2, 58.7, 46.9, 21.5, 18.3, 13.2; CIMS m/z
19.8; CIMS m/z (relative intensity) 382 (MH+, 100); HRMS
calcd for C22H23NO3S 381.1399, found 381.1388.
N-(Tolu en esu lfon a m id e)-6a -m et h yl-6-st yr yl-1,2,6,6a -
tetr a h yd r ocyclop en ta [b]p yr r ole (3j). Following general
procedure C, n-BuLi (0.15 mmol) was added to sulfonamide
28j (50 mg, 0.15 mmol) in 15 mL of THF. Phenyl(propynyl)-
iodonium triflate (2) (86 mg, 0.22 mmol) was dissolved in ∼0.5
mL of THF and added via syringe over 4 h. The crude mixture
was chromatographed with 2:23 Et2O/hexane and 3:7 Et2O/
hexane to yield 20 mg of pure 5d (35%) as a colorless foam
and recovered 1d (11 mg, 21%). IR (CDCl3) 3025, 1599, 1338,
1157 cm-1; 1H NMR (300 MHz, C6D6) δ 7.80 (d, J ) 8.3 Hz, 2
H), 7.47 (d, J ) 7.2 Hz, 2 H), 7.20-7.04 (m, 4 H), 6.71 (d, J )
8.5 Hz, 2 H), 6.53 (d, J ) 16.3 Hz, 1 H), 5.91 (d, J ) 6.0 Hz, 1
H), 5.83 (dd, J ) 6.0, 2.6 Hz, 1 H), 4.82 (s, 1 H), 4.22 (ddd, J
) 14.0, 3.3, 1.2 Hz, 1 H), 4.13 (dd, J ) 14.0, 0.9 Hz, 1 H), 4.00
(m, 1 H), 1.85 (s, 3 H), 1.17 (s, 3 H); 13C NMR (75 MHz, CDCl3)
δ 156.2, 143.2, 143.1, 137.7, 137.6, 131.5, 129.5, 128.5, 127.9,
127.6, 127.2, 126.3, 124.8, 108.8, 80.3, 58.6, 54.8, 21.4, 19.8;
CIMS m/z (relative intensity) 378 (MH+, 6), 91 (100); HRMS
calcd for C23H23NO2S 377.1449, found 377.1443.
3-Tolu en esu lfon yl-4-m et h ylen e-1-vin yl-3-a za b icyclo-
[3.1.0]h exa n e (5). Dienyltosylamide 28h (50 mg, 0.21 mmol)
was dissolved in 4.5 mL of THF and cooled to 0 °C. Lithium
hexamethylsilylamide (0.21 mL of a 1 M solution in THF, 0.21
mmol) was added slowly, and the reaction solution was stirred
for 30 min at 0 °C before being brought to reflux. Phenyl-
(propynyl)iodonium triflate (2) (82 mg, 0.21 mmol) was dis-
solved in THF to a total volume of 0.5 mL and added via
syringe over ∼15 min. After refluxing an additional 30 min,
the mixture was diluted with Et2O and washed with brine.
The organic phases were dried with MgSO4, filtered, concen-
trated, and chromatographed with 2:25 Et2O/hexane to yield
27 mg of pure 5 (46%) as a colorless oil. IR (CDCl3) 3090, 1643,
1349, 1167 cm-1; 1H NMR (300 MHz, C6D6) δ 7.71 (d, J ) 8.4
Hz, 2 H), 6.70 (d, J ) 8.0 Hz, 2 H), 5.47 (s, 1 H), 5.12 (dd, J )
10.7, 17.3 Hz, 1 H), 4.73 (dd, J ) 0.9, 10.7 Hz, 1 H), 4.64 (dd,
J ) 0.9, 17.3 Hz, 1 H), 4.44 (s, 2 H), 3.76 (s, 1 H), 1.82 (s, 3 H),
1.43 (dd, J ) 4.0, 8.2 Hz, 1 H), 0.46 (m, 1 H), -0.49 (m, 1 H);
13C NMR (75 MHz, C6D6) δ 145.4, 143.5, 136.8, 136.4, 129.5,
127.5, 113.5, 90.8, 54.8, 31.8, 27.4, 21.1, 17.5; EIMS m/z
(relative intensity) 275 (M+, 6), 120 (62), 91 (100); HRMS calcd
for C15H17NO2S 275.0980, found 275.0979.
(relative intensity) 291 (MH+, 100); HRMS calcd for C16H19
NO2: 290.1215, found 290.1210.
-
N-(Tolu en esu lfon a m id e)-6a -m eth yl-6-(tr im eth ylsilyl)-
1,2,6,6a -tetr a h yd r ocyclop en ta [b]p yr r ole (3c). Following
general procedure C, n-BuLi (0.16 mmol) was added to
sulfonamide 28c (50 mg, 0.16 mmol) in 16 mL of THF. Phenyl-
(propynyl)iodonium triflate (2) (95 mg, 0.24 mmol) was dis-
solved in ∼0.5 mL of THF and added via syringe over 4 h.
The crude mixture was chromatographed with 2:23 Et2O/
hexane and 3:7 Et2O/hexane to yield 15 mg of pure 3c (27%)
as an oil and recovered 28c (10.0 mg, 20%). IR (CDCl3) 1336,
1157 cm-1; 1H NMR (300 MHz, C6D6) δ 7.83 (d, J ) 8.3 Hz, 2
H), 6.78 (d, J ) 8.4 Hz, 2 H), 5.88 (m, 1 H), 5.80 (dd, J ) 2.9,
5.4 Hz, 1 H), 4.88 (bs, 1 H), 4.17 (m, 2 H), 2.76 (bs, 1 H), 1.89
(s, 3 H), 1.31 (s, 3 H), 0.26 (s, 9 H); 13C NMR (90 MHz, CDCl3)
δ 159.8, 144.2, 142.9, 138.1, 129.4, 127.3, 121.8, 108.2, 79.9,
51.8, 44.4, 22.4, 21.5, 0.1; EIMS m/z (relative intensity) 347
(MH+, 5), 73 (100); HRMS calcd for C18H25NO2SSi 347.1375,
found 347.1369.
N-(Tolu en esu lfon a m id e)-6a -m eth yl-6-p h en yl-1,2,6,6a -
tetr a h yd r ocyclop en ta [b]p yr r ole (3d ). Following general
procedure C, n-BuLi (0.16 mmol) was added to sulfonamide
28d (50 mg, 0.16 mmol) in 16 mL of THF. Phenyl(propynyl)-
iodonium triflate (2) (94 mg, 0.24 mmol) was dissolved in ∼0.5
mL of THF and added via syringe over 4 h. The crude mixture
was chromatographed with 2:23 Et2O/hexane and 3:7 Et2O/
hexane to yield 33 mg of pure 3d (58%) as a colorless foam
and recovered 28d (7 mg, 14%). IR (CDCl3) 3032, 1599, 1337,
1
1158 cm-1; H NMR (300 MHz, CDCl3) δ 7.60 (d, J ) 8.4 Hz,
2 H), 7.43 (m, 2 H), 7.31 (m, 3 H), 7.19 (d, J ) 8.4 Hz, 2 H),
6.29 (dd, J ) 5.9, 2.7 Hz, 1 H), 6.11 (dd, J ) 5.6, 1.8 Hz, 1 H),
5.38 (t, J ) 1.3, 0.9 Hz, 1 H), 4.32 (m, 3 H), 2.37 (s, 3 H), 0.93
(s, 3 H); 13C NMR (50 MHz, CDCl3) δ 156.4, 145.6, 143.1, 138.6,
137.3, 131.0, 129.3, 127.7, 127.4, 126.9, 124.6, 108.7, 81.5, 59.0,
58.8, 21.4, 19.6; CIMS m/z (relative intensity) 353 (MH+, 100);
HRMS calcd for C21H21NO2S 352.1371, found 352.1370.
N-(Tolu en esu lfon a m id e)-6-(4-n itr op h en yl)-6a -m eth yl-
1,2,6,6a -tetr a h yd r ocyclop en ta [b]p yr r ole (3e). Following
general procedure C, n-BuLi (0.14 mmol) was added to
sulfonamide 28e (50 mg, 0.14 mmol) in 14 mL of THF. Phenyl-
(propynyl)iodonium triflate (2) (82 mg, 0.21 mmol) was dis-
solved in ∼0.5 mL of THF and added via syringe over 4 h.
The crude mixture was chromatographed with 2:23 EtOAc/
hexane and 3:7 EtOAc/hexane to yield 7 mg of pure 3e (12%)
as an oil and recovered 28e (29%). IR (CDCl3) 3049, 1599, 1348,
3-Tolu e n e su lfon yl-2-m e t h yle n e -3-a za b icyclo[3.1.0]-
h exa n e (39). Tosylamide 3732 (100 mg, 0.47 mmol) was
dissolved in 10 mL of THF and cooled to 0 °C. Lithium
hexamethylsilylamide (0.50 mL of a 1 M solution in THF, 0.50
mmol) was added slowly and the reaction stirred 30 min at 0
°C before being brought to reflux. Phenyl(propynyl)iodonium
triflate (2) (196 mg, 0.50 mmol) was dissolved in THF to a total
volume of 0.5 mL and added via syringe over ∼15 min. After
refluxing an additional 30 min, the mixture was diluted with
Et2O and washed with brine. The organic phases were dried
with MgSO4, filtered, concentrated, and chromatographed with
2:25 Et2O/hexane to yield 47 mg of pure 39 (39%) as a colorless
1
1159 cm-1; H NMR (360 MHz, CDCl3) δ 8.19 (d, J ) 8.8 Hz,
2 H), 7.60 (d, J ) 8.9 Hz, 2 H), 7.59 (d, J ) 8.3 Hz, 2 H), 7.23
(d, J ) 8.4 Hz, 2 H), 6.37 (dd, J ) 6.0, 2.8 Hz, 1 H), 6.07 (d, J
) 6.0 Hz, 1 H), 5.44 (s, 1 H), 4.47 (s, 1 H), 4.35 (dd, J ) 14.5,
2.9 Hz, 1 H), 4.28 (d, J ) 13.4 Hz, 1 H), 2.39 (s, 3 H), 0.97 (s,
3 H); 13C NMR (90 MHz, CDCl3) δ 155.3, 147.1, 146.5, 143.6,
143.5, 136.9, 131.9, 129.5, 127.7, 125.8, 122.6, 109.9, 81.5, 58.9
(2C), 21.5, 19.6; CIMS m/z (relative intensity) 397 (MH+, 100);
HRMS calcd for C21H20N2O4S 396.1148, found 396.1144.
N-(Tolu en esu lfon am ide)-6-(4-m eth oxyph en yl)-6a-m eth -
yl-1,2,6,6a -tetr a h yd r ocyclop en ta [b]p yr r ole (3i). Following
general procedure C, n-BuLi (0.12 mmol) was added to
sulfonamide 28i (41 mg, 0.12 mmol) in 12 mL of THF. Phenyl-
(propynyl)iodonium triflate (2) (70 mg, 0.18 mmol) was dis-
solved in ∼0.5 mL of THF and added via syringe over 4 h.
The crude mixture was chromatographed with 1:10 Et2O/
hexane and 1:1 Et2O/hexane to yield 23 mg of pure 3i (51%)
as a foam and recovered 28i (10 mg, 25%). IR (CDCl3) 3049,
1602, 1337, 1249, 1155 cm-1; 1H NMR (300 MHz, C6D6) δ 7.67
(d, J ) 8.3 Hz, 2 H), 7.49 (d, J ) 8.8 Hz, 2 H), 6.88 (d, J ) 8.8
Hz, 2 H), 6.65 (d, J ) 8.4 Hz, 2 H), 5.87 (dd, J ) 5.9, 2.7 Hz,
1 H), 5.80 (d, J ) 5.9 Hz, 1 H), 4.89 (d, J ) 2.3 Hz, 1 H), 4.51
(s, 1 H), 4.33 (dd, J ) 14.0, 3.5 Hz, 1 H), 4.11 (d, J ) 14.0 Hz,
1 H), 3.35 (s, 3 H), 1.82 (s, 3 H), 0.97 (s, 3 H); 13C NMR (75
MHz, C6D6) δ 159.3, 156.8, 146.2, 142.5, 138.6, 132.5, 130.9,
129.4, 128.1, 124.5, 113.3, 109.0, 81.4, 59.2, 58.4, 54.7, 21.0,
oil. IR (CDCl3) 3048, 1637, 1343, 1161 cm-1 1H NMR (300
;
MHz, CDCl3) δ 7.70 (d, J ) 8.3 Hz, 2 H), 7.29 (d, J ) 8.0 Hz,
2 H), 5.02 (s, 1 H), 4.44 (s, 1 H), 3.81 (dd, J ) 4.6, 10.3 Hz, 1
H), 3.76 (d, J ) 10.3 Hz, 1 H), 2.42 (s, 3 H), 1.90 (m, 1 H), 1.57
(m, 1 H), 0.69 (m, 1 H), -0.25 (m, 1 H); 13C NMR (90 MHz,
CDCl3) δ 145.4, 143.9, 135.2, 129.5, 127.1, 90.2, 53.2, 22.7, 21.5,
13.2, 11.0; EIMS m/z (relative intensity) 249 (M+, 6), 184 (100);
HRMS calcd for C13H15NO2S 249.0823, found 249.0830.
3-Tolu en esu lfon yl-6-m eth yl-2-m eth ylen e-3-a za bicyclo-
[3.1.0]h exa n e (40). Tosylamide 3816 (100 mg, 0.44 mmol) was
dissolved in 9 mL of THF and cooled to 0 °C. Lithium
hexamethylsilylamide (0.47 mL of a 1 M solution in THF, 0.47
mmol) was added slowly, and the reaction solution was stirred
for 30 min at 0 °C before being brought to reflux. Phenyl-
(propynyl)iodonium triflate (2) (184 mg, 0.47 mmol) was
dissolved in THF to a total volume of 0.5 mL and added via
(32) Sanghavi, N. M.; Parab, V. L.; Patravale, B. S. Patel, M. N.
Synth. Commun. 1989, 19, 1499.

5660 J . Org. Chem., Vol. 64, No. 15, 1999
Feldman
syringe over ∼15 min. After refluxing an additional 30 min,
the mixture was diluted with Et2O and washed with brine.
The organic layers were dried with MgSO4, filtered, concen-
trated, and chromatographed with 2:25 Et2O/hexane to yield
47 mg of pure 40 (33%) as a colorless oil. IR (CDCl3) 3049,
1643, 1349, 1167 cm-1; 1H NMR (300 MHz, C6D6) δ 7.74 (d, J
) 8.3 Hz, 2 H), 6.71 (d, J ) 8.0 Hz, 2 H), 5.46 (s, 1 H), 4.44 (s,
1 H), 3.65 (d, J ) 10.3 Hz, 1 H), 3.51 (dd, J ) 5.0, 10.3 Hz, 1
H), 1.81 (s, 3 H), 1.22 (m, 1 H), 0.59 (m, 1 H), 0.46 (d, J ) 6.1
Hz, 3 H), 0.02 (m, 1 H); 13C NMR (90 MHz, CDCl3) δ 145.4,
143.8, 135.3, 129.5, 127.2, 89.2, 76.3, 53.4, 31.0, 21.1, 19.1, 15.9;
EIMS m/z (relative intensity) 263 (M+, 6), 198 (100); HRMS
calcd for C14H17NO2S 263.0980, found 263.0984.
ature and concentrated in vacuo. Purification of the residue
by chromatography on SiO2 with 1:19 Et2O/hexane furnished
690 mg of (tributylstannyl)propyne-d3 (66%) as a colorless oil.
The material was used immediately in the next step.
A 50 mL Schlenk flask was charged with cyano(phenyl)-
iodonium triflate (0.72 g, 1.9 mmol) and dichloromethane. The
mixture was purged with Ar and cooled to -45 °C. (Tributyl-
stannyl)propyne-d3 (0.69 g, 2.1 mmol) was dissolved in 3 mL
of CH2Cl2 and added over 15 min to the cold reaction mixture.
The reaction solution was then stirred for 1.25 h at -45 °C f
-25 °C, after which time 50 mL of freshly distilled hexane
was added via cannula, which caused the iodonium salt to
precipitate. The microcrystalline solid was collected without
exposure to air, rinsed with hexane, and then recrystallized
with the precipitation method mentioned above (CH2Cl2/
hexane) to yield 0.48 g of 41 (58%) as a white solid. mp ) 112
d 3-P r op yn yl(p h en yl)iod on iu m Tr ifla te (41). n-BuLi (2.8
mL of a 2.5 M solution in hexane, 6.9 mmol) was added to a
stirring solution of (trimethylsilyl)acetylene (0.68 g, 6.9 mmol)
in 7 mL of THF and 7 mL of DMPU at 0 °C. D3CI (1.07 g, 7.4
mmol) was added slowly (exothermic), and the reaction solu-
1
°C; IR (CDCl3) 2179 cm-1; H NMR (300 MHz, CDCl3) δ 8.06
(m, 2 H), 7.65 (m, 1 H), 7.54 (m, 2 H); 13C NMR (75 MHz,
CDCl3) δ 134.0, 132.5, 132.3, 121.9, 116.1, 106.8, 20.8; LR
MALDI m/z (cation) 245.9811; HRMS calcd for C10H5D3I
245.9859, found 245.9871.
o
tion was stirred at 0 C for 14 h. The mixture was poured into
ice-cold H2O and extracted twice with pentane. The organic
layers were dried over MgSO4, filtered, and the pentane/THF
was removed by short-path distillation at 1 atm. The residue
(∼0.45 g, ∼3.9 mmol) of crude (trimethylsilyl)propyne-d3 was
used directly in the next step.
This crude sample of (trimethylsilyl)propyne-d3 and bis
tributyltin oxide (0.94 g, 1.57 mmol) in 10 mL of THF was
treated with n-Bu4NF (0.079 mL of a 1 M solution in THF,
0.079 mmol), and the reaction solution was brought to reflux.
After 2.5 h at reflux, the mixture was cooled to room temper-
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and 13C
NMR spectra for compounds 3a ,c-e,i-j, 5, 28f,h ,j, 31, 39, and
40. This material is available free of charge via the Internet
at http://pubs.acs.org.
J O9907538