Alkynyliodonium salts in organic synthesis, dihydrofuran formation via a formal stevens shift of a carbon substituent within a disubstituted-carbon oxonium ylide

Article abstract of DOI:10.1021/jo0011080

The addition of p-toluenesulfinate to the silyl, 1-furanyl, and 1-pyranyl ethers of 1-hydroxybut-3-ynyl(phenyl)iodonium triflate triggers a sequence of reactions that ultimately delivers 2-substituted 3-p-toluenesulfonyldihydrofuran products in variable yields. A putative 1,2-group shift within an unsaturated oxonium ylide (Stevens rearrangement) accounts for the oxygen-to-carbon transfer of the ether substituent. Deuterium labeling studies clarify the mechanistic course of this shift by providing evidence consistent with intramolecular substituent transfer and by identifying the primary source of the proton that intercepts the ylide in the major yield-limiting process.

Full text of DOI:10.1021/jo0011080

J . Org. Chem. 2000, 65, 8659-8668
8659
Alk yn yliod on iu m Sa lts in Or ga n ic Syn th esis. Dih yd r ofu r a n
F or m a tion via a F or m a l Steven s Sh ift of a Ca r bon Su bstitu en t
w ith in a Disu bstitu ted -Ca r bon Oxon iu m Ylid e
Ken S. Feldman* and Michelle Laci Wrobleski
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802
ksf@chem.psu.edu
Received J uly 21, 2000
The addition of p-toluenesulfinate to the silyl, 1-furanyl, and 1-pyranyl ethers of 1-hydroxybut-3-
ynyl(phenyl)iodonium triflate triggers a sequence of reactions that ultimately delivers 2-substituted
3-p-toluenesulfonyldihydrofuran products in variable yields. A putative 1,2-group shift within an
unsaturated oxonium ylide (Stevens rearrangement) accounts for the oxygen-to-carbon transfer of
the ether substituent. Deuterium labeling studies clarify the mechanistic course of this shift by
providing evidence consistent with intramolecular substituent transfer and by identifying the
primary source of the proton that intercepts the ylide in the major yield-limiting process.
Sch em e 1
The continuing development of alkynyliodonium salt-
derived chemistry for use in heterocycle synthesis has
led to efficient sequences for the preparation of indoles,
dihydropyrroles, and variously cyclopentannelated dihy-
dropyrroles.1 The extension of this methodology to dihy-
drofuran synthesis, 1 f 2 (eq 1), is described herein.
≈ 100 kcal/mol for H2CdC:)4 can be accessed under mild
conditions that tolerate the presence of a range of
electron-rich reaction partners. Much earlier work has
delineated the reactivity profile of these unsaturated
carbenes, which includes [1,2]-shift to reformulate an
alkyne, 1,5- (and occasionally 1,3-) C-H insertion to
provide cyclopentene (or cyclopropene)-type products, and
alkene cycloaddition to afford methylenecyclopropanes.5
More recently, alkylidene carbene “insertion” into the
lone pair of an appropriately positioned oxygen atom has
been proposed, a process that furnishes an intermediate
oxonium ylide 6.6 The fate of the largely unknown
disubstituted-carbon-containing oxonium ylide 6 is not
readily predicable, but argument by analogy with related
trisubstituted-carbon-containing oxonium ylides 8 (Scheme
2, X ) O, R2 ) lone pair) suggested that perhaps a 1,2-
migration of R1 from oxygen to carbon within 6 (formal
Stevens rearrangement) might occur to deliver the ox-
acyclic product 7.
Work on this transformation was initiated after a chance
observation revealed that alkylidene carbenes, derived
from alkynyliodonium salts by nucleophile addition (vide
infra), had an unexpected propensity for combination
with heteroatom lone pairs over the expected 1,5 C-H
bond insertion.2 This dihydrofuran synthesis effectively
merges two otherwise unrelated transforms, nucleophilic
addition to alkynyliodonium salts and the Stevens rear-
rangement, in a multistep reaction cascade that affords
new C-S, C-O, and C-C bonds at the expense of a C-O
ether linkage.
Alkynyl(phenyl)iodonium triflates 3 are potent yet
selective electrophiles that combine with many polariz-
able nucleophiles to furnish singlet alkylidene carbenes
5 following loss of PhI from the intermediate ylide 4
(Scheme 1).3 As a consequence of the unique reactivity
of the iodonium salts 3, the high energy carbene 5 (∆Hf
The Stevens rearrangement (8 f 10, Scheme 2) has
been examined for X ) N, O, and S, but the bulk of the
definitive mechanistic work has been directed toward the
ammonium ion series (8, X ) N, R1, R2 ) alkyl or aryl).7
The consensus view, buttressed by a wealth of experi-
mental evidence, cites a bond homolysis/radical recom-
(1) (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, (c)
Feldman, K. S.; Bruendl, M. M.; Schildknegt, K.; Bohnstedt, A. C. J .
Org. Chem. 1996, 61, 5440, (d) Feldman, K. S.; Mareska, D. A. J . Am.
Chem. Soc. 1998, 120, 4027, (e) Feldman, K. S.; Mareska, D. A.;
Tetrahedron Lett. 1998, 39, 4781, (f) Feldman, K. S.; Mareska, D. A.
J . Org. Chem. 1999, 64, 5650.
(2) (a) Feldman, K. S.; Mingo, P. A.; Hawkins. P. C. D., Heterocycles
1999, 51, 1283. (b) See also: Sueda, T.; Nagaoka, T.; Goto, S.; Ochiai,
M. J . Am. Chem. Soc. 1996, 118, 10141.
(3) (a) Zhdankin, V. V.; Stang, P. J . Tetrahedron 1998, 54, 10927.
(b) Varvoglis, A. Tetrahedron 1997, 53, 1179.
(4) (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.
(5) Kirmse, W. Angew. Chem., Int. Ed. Engl. 1997, 36, 1164.
(6) Feldman, K. S.; Wrobleski, M. L. Org. Lett. 2000, 2, 2603.
10.1021/jo0011080 CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/18/2000

8660 J . Org. Chem., Vol. 65, No. 25, 2000
Feldman and Wrobleski
Sch em e 2
tion Stevens sequence. On the other hand, the Kim
example does not speak to the heterolysis mechanism
proposed for the Stevens-like conversion of ylide 11 into
the [1,2]-shift product 13. Bearing these examples in
mind, we undertook exploratory studies of the conversion
of butynyliodonium salt ethers 1 into the cyclized Stevens
rearrangement products 2. In particular, a survey of
migrating groups R (cf. 1) in which radical stabilizing
ability (as required for 9) or cation stabilizing ability (as
required for 12) was highlighted, helped delineate the
scope of the process.6 In follow-up studies to these
preliminary experiments, select deuterium-labeled sub-
strates were prepared as mechanistic probes to augment
the structure/reactivity information. Taken together,
these mechanistic investigations help illuminate some of
the subtleties that accompany the [1,2]-shift of R from
oxygen in 1 to carbon in 2.
bination pathway (e.g., 9) to rationalize the formation of
10. In the oxonium ylide series, (8, X ) O, R2 ) lone pair),
the detection of radical recombination products (e.g., R1-
R1) and a migrating aptitude for R1 that scales with
radical stability have been taken as evidence in support
of the homolysis/recombination pathway as well.8 How-
ever, the [1,2]-shift for one special case of trisubstituted-
carbon oxonium ylide, the ketal-derived species 11, may
deviate from this radical-mediated process. Speculation
that an oxygen-assisted heterolysis of the scissile C-O
bond in 11 could furnish the nucleophile-electrophile
partners in 12 en route to the formal Stevens rearrange-
ment product 13, or the competitively formed â-H trans-
fer product 14, has been advanced.9
Resu lts a n d Discu ssion
The substrates 1a -h examined in this study were all
derived from 4-butynol (18), eq 3. Ethers 19a -e have
It is difficult to discern which, if any, of these mecha-
nistic options might be applicable to the [1,2]-shift within
6, given the differences in hybridization and geometry
between the anionic carbon in 6 and those in 8 or 11. A
single relevant precedent from Kim’s laboratory, which
relies on an Eschenmoser-type fragmentation of an epoxy
hydrazone to generate the alkylidene carbene 15 (eq 2),
been described,11 as have the alkynylstannanes 20a and
20c.12 The remaining ethers 19f-h were prepared by
TsOH-catalyzed exchange between 18 and cis/trans 1-hy-
droxy-2-methyltetrahydropyran or 2-methoxy-1,3-diox-
ane, respectively. The derived stannanes 20b,d -h were
prepared in good yield (see Experimental Section) by
stannylation of the alkyne anions. The alkyne-tin bond
of these species was rather labile to hydrolysis, and so
purification was best accomplished by flash chromatog-
raphy on silica gel deactivated by pretreatment with 5%
Et3N in hexane. The alkynyliodonium salts 1a -h were
prepared according to the procedure of Stang13 and used
immediately in the next step. Whereas many simple
alkynylphenyliodonium salts are stable microcrystalline
solids at room temperature, the particular functionalized
alkynyliodonium salts used in this investigation typically
decomposed when exposed to temperatures much above
0 °C. Therefore, their preparation and manipulation were
conducted at low temperatures (-30 to - 42 °C), with
final solvent removal performed at <0 °C in vacuo. In
describes only silicon transfer in a system that failed to
furnish [1,2]-shift products with carbon migrating groups
(allyl, benzyl) normally proficient in the Stevens rear-
rangement of trisubstituted-carbon oxonium ylides.10
Whether the silicon shift proceeds through the ylide 16
or by direct carbene insertion into the O-Si bond remains
an open question.
This discouraging precedent suggests that ylides 6
derived from alkynyliodonium salts 3 might not be
suitable platforms for the homolysis/radical recombina-
(7) (a) Ollis, W. D.; Rey, M.; Sutherland, I. O.; Closs, G. L. J . Chem.
Soc., Chem. Commun. 1975, 543. (b) Dolling, U. H.; Closs, G. L.; Cohen.
A. H. J . Chem. Soc., Chem. Commun. 1975, 545. (c) Maeda, Y.; Sato,
Y. J . Chem. Soc., Perkin Trans. 1 1997, 1491. (d) Heard, G. L.; Yates,
B. F. Aust. J . Chem. 1995, 48, 1413.
(8) (a) Eberlein, T. H.; West, F. G.; Tester, R. W. J . Org. Chem. 1992,
57, 3479. (b) West, F. G.; Eberlein, T. H.; Tester, R. W. J . Chem. Soc.,
Perkin Trans. 1 1993, 2857. (c) West, F. G.; Glaeske K. W.; Naidu, B.
N. Synthesis 1993, 977. (d) Kirmse, W.; Schnitzler, D. Tetrahedron Lett.
1994, 35, 1699.
(11) (a) Morimoto, Y.; Yokoe, C.; Kurihara, H.; Kinoshita, T.
Tetrahedron 1998, 54, 12197. (b) Daniel, D.; Middleton, R.; Henry, H.
L.; Okamura, W. H. J . Org. Chem. 1996, 61, 5617. (c) Burns, C. J .;
Gill, M.; Saubern, S. Aust. J . Chem. 1997, 50, 1067. (d) Griffiths, J .;
Murphy, J . A. Tetrahedron 1992, 48, 5543. (e) Berque, I.; Le Menez,
P.; Razon, P.; Mahuteau, J .; Fe´re´zou, J .-P.; Pancrazi, A.; Ardisson, J .;
Brion, J .-D. J . Org. Chem. 1999, 64, 373.
(12) (a) Kashman, Y.; Groweiss, A.; Lidor, R.; Blasberger, D.;
Carmely, S. Tetrahedron 1985, 41, 1905. (b) Leteux, C.; Veyrie`res, A.
J . Chem. Soc., Perkin Trans I 1994, 2647.
(9) (a) Doyle, M. P.; Ene, D. G.; Forbes, D. C.; Tedrow, J . S.
Tetrahedron Lett. 1997, 38, 4367. (b) Oku, A.; Murai, N.; Baird, J . J .
Org. Chem. 1997, 62, 2123.
(13) Stang, P. J .; Williamson, B. L.; Zhdankin, V. V. J . Am. Chem.
Soc., 1991, 113, 5870.
(10) Kim, S.; Cho, C. M. Tetrahedron Lett. 1995, 36, 4845.

Alkynyliodonium Salts in Organic Synthesis
J . Org. Chem., Vol. 65, No. 25, 2000 8661
this manner, the white solid or pale yellow oily iodonium
salts exhibited no signs of decomposition (darkening,
liquefaction). The diastereomeric alkynes 19f and 19g
were cleanly separated by silica gel chromatography, and
the pure isomers were carried forward independently in
the next step. Since the alkynyliodonium salts were not
isolated, the reported product yields in the cyclization/
rearrangement sequence are based on the alkynylstan-
nanes 20a -h .
compounds was formed. The major product isolated in
the allyl case was the protonated dihydrofuran 22 (36%),
a result suggesting that the desired ylide 23 was formed
but did not participate in either [2,3]- or [1,2]-allyl shifts,
eq 5. The benzyl ether substrate also afforded the
The silyl ether substrate 1a was examined first in light
of the precedent shown in eq 2. p-Toluenesulfinate was
chosen as the test case nucleophile as a consequence of
its documented success in generating alkylidene carbenes
from alkynyliodonium salts14 and the expectation that
the enol ether product would be more stable to hydrolysis
if also substituted with a sulfone moiety rather than a
N or O group derived, inter alia, from amide or phenoxide
nucleophiles. Toward this end, the white solid alkynyli-
odonium salt 1a at -42 °C was dissolved in prechilled
(-42 °C) CH2Cl2 and treated with 1 equiv of sodium
p-toluenesulfinate. After warming to room temperature,
aqueous workup, and chromatographic purification, a
single new compound featuring TBDMS and p-TolSO2
groups in a 1:1 ratio (1H NMR) was isolated. Further
spectroscopic analysis confirmed that the product was
indeed the cyclized/rearranged dihyrofuran species 21 as
desired (eq 4). Treatment of this silylalkene with n-Bu4-
dihydrofuran 22 (e10%), along with several alkyne-
containing products in small amounts, and significantly,
∼ 5% of p-TolSO2CH2Ph. Again, it appears the ylide 24
was formed, at least to a small extent, but it decomposed
by alternative pathways unrelated to the desired [1,2]-
shift (e.g., p-TolSO2 attack on R(R′)O(+)-CH2Ph with
expulsion of the good oxonium leaving group to ultimately
provide 22). These results are consistent with the obser-
vations of Kim (vide supra), and suggest that C-O bond
homolysis within ylides of the type 23/24 does not
compete with dealkylation and anion protonation. Thus,
the goal of observing classic Stevens-type radical chem-
istry with the disubstituted-carbon ylide series is not
likely to be met.
The search for a Stevens-type rearrangement with
particularly stable carbocationic migrating groups began
with the 1-THP derivative 1e. The initial experiment run
under the best-case conditions with 1a (CH2Cl2, -42 °C
f rt) furnished two dihydrofuran-containing products 26
and 22 in similar amounts, eq 6. The formation of the
NF in THF cleanly effects desilylation to furnish the
dihydrofuran product 22 displaying a characteristic vinyl
1
proton15 (δ 7.19, t, J ) 1.8 Hz) in the H NMR spectrum.
The good yield and lack of detectable byproducts upon
conversion of 1a into 21 suggested that further optimiza-
tion might be possible. However, substitution of THF as
solvent and exploring a range of temperatures (cf. eq 4)
did not improve on the initial run.
Both allyl and benzyl units have high migratory
aptitudes in the Stevens rearrangement, although their
mechanisms ([2,3]-sigmatropic shift vs homolysis/radical
recombination, respectively) may be dissimilar.8,16 Thus,
the substrates 1b and 1c were examined as probes for
these classical Stevens rearrangement processes. In both
cases, treatment of the alkynyliodonium salts in either
CH2Cl2 or THF with p-toluenesulfinate over a range of
temperatures (-15 °C (CH2Cl2) to 65 °C (THF)) did not
afford any detectable 2-substituted dihydrofuran prod-
ucts. Both TLC and 1H NMR analysis of the crude
reaction mixture indicated that a multitude of new
formal [1,2]-shift product 26 was gratifying, but any
mechanistic speculation vis a` vis homolysis vs heterolysis
of the C-O bond in putative ylide intermediate 25 would
be premature at this point. Optimization studies pro-
ceeded with 1e and a survey of solvents and temperatures
revealed that, for this substrate, THF at reflux afforded
the highest yield of desired product 26. Variation among
other experimental parameters (concentration (0.15 f
0.30 M in 1e), order of addition, rate of addition) had little
effect on yield. Thus, an optimized procedure wherein a
-42 °C solution of the alkynyliodonium salt in THF was
added rapidly via cannula into a refluxing suspension of
1.3-1.5 equiv of sodium p-toluenesulfinate in THF was
standardized for subsequent substrates. The structural
assignment of 26 was suggested by the spectral data upon
comparison to the data for 21 and 22 and secured by
HMBC NMR analysis that clearly indicated the carbon
connectivity. The 2-bond and 3-bond coupling between
the unique methine hydrogen and the alkene carbons,
(14) (a) Tykwinski, R. R.; Williamson, B. L.; Fischer, D. R.; Stang,
P. J .; Arif, A. M. J . Org. Chem. 1993, 58, 5235. (b) Ochiai, M.;
Kunishima, M.; Tani, S.; Nagao, Y. J . Am. Chem. Soc. 1991, 113, 3135.
(15) The phenylsulfonyl analogue of 22 is known. The key vinyl
resonance in the 1H NMR spectrum of this compound occurs at δ 7.25
(t, J ) 1.8 Hz). Carretero, J . C.; de Diego, J . E.; Hamdouchi, C.
Tetrahedron 1999, 55, 15159.
(16) (a) Roskamp, E. J .; J ohnson, C. R. J . Am. Chem. Soc. 1986,
108, 6062. (b) Pirrung, M. C.; Werner, J . A. J . Am. Chem. Soc. 1986,
108, 6060. (c) Clark, J . S. Tetrahedron Lett. 1992, 33, 6193. (d) Brogan,
J . B.; Bauer, C. B.; Rogers, R. D.; Zercher, C. K. Tetrahedron Lett. 1996,
37, 5053.

8662 J . Org. Chem., Vol. 65, No. 25, 2000
Feldman and Wrobleski
which unambiguously defined the attachment point of
the THP and dihydrofuran rings, was particularly diag-
nostic.
The tetrahydrofuran analogue 1d performed similarly
under the optimized conditions to furnish a modest yield
of the cyclization/rearrangement product 27 along with
substantial quantities of the proton trapping product 22,
eq 7. The structural identity of 27 rests on a comparison
of spectral data with those of 26.
istry. It is noteworthy that the yield of the proton
trapping byproduct 22 remained constant with these
substrates, but it is less than that observed with the nor-
methyl species 1e.
The final substrate examined, ortho ester 1h , was
selected to explore further the influence of cation stabi-
lization on [1,2]-shift efficiency, eq 8. On the basis of the
results to this point, the more stable carbocation flanked
by two oxygen atoms in intermediate ylide 30 might be
expected to facilitate the [1,2]-shift and lead to enhanced
yields of the 2-substituted dihydrofuran product 31. The
observed result is in accord with this hypothesis. Treat-
ment of alkynyliodonium salt 1h with p-toluenesulfinate
under standard conditions afforded a superior yield of
the desired [1,2]-shift product 31. In addition, not even
trace amounts of the proton trapping product 22 could
be detected. This latter observation may point to a role
for the C(3) hydrogen in the THF or THP rings of 1d -g
in forming 22. On the other hand, it may only reflect an
enhanced rate of [1,2]-shift with the dioxygen-substituted
ring compared to the process that forms 22. This issue
was addressed by using the C(3) deuterium-labeled THP
substrate 33 discussed below.
The issue of 1,2-diastereoselectivity was probed with
the trans- and cis-2-methyl-substituted tetrahydropyran
ethers 1f and 1g, respectively, Scheme 3. At the outset,
Sch em e 3
The results obtained with the range of substrates 1a-h ,
in the aggregate, beg several mechanistic questions:
(1) Do successful [1,2]-shifts occur through C-O ho-
molysis/radical recombination, through C-O heterolysis/
dipolar recombination, or via a concerted process?
(2) Is substituent O-to-C migration an inter- or an
intramolecular process?
(3) What is the source of the vinylic proton in byproduct
22?
Insight into these issues might be gleaned from the
results of a series of reactions featuring the selectively
deuterated substrates 32-35. The THP substituent was
chosen as representative of all of the R-oxygenated ether
substrates 1d -h , and ultimately caution should be exer-
cised in extrapolating conclusions from the THP series
to the THF or 1,3-dioxane species.
the mechanistic uncertainties surrounding the [1,2] THP
shift in 1e made it difficult to develop an a priori model
for diastereoselection with 1f/g, and so these trials were
viewed as simple scouting expeditions. Exposure of the
isomerically pure trans isomer 1f to p-toluenesulfinate
in refluxing THF provided the expected mixture of
dihydrofuran-containing products 29a /b and 22 in yields
similar to the nor-methyl system 1e. Interestingly, the
formal [1,2]-shift product 29 was produced as a diaster-
eomeric mixture that strongly favored one isomer. The
gross structures of 29a /b could be deduced by comparison
of spectral data with those of the nor-methyl analogue
26, and stereochemical assignments were made on the
chromatographically purified products 29a and 29b on
the basis of the observed J 1,2 values (29a , J 1,2 ) 10.0 Hz
w trans; 29b, J 1,2 ) 3.6 Hz w cis). An identical experi-
ment with the cis methyl substrate 1g led to similar
results. In this instance, the mixture of [1,2]-shift prod-
ucts favored the cis-configured product 29b. Thus, the
[1,2]-shift of THP within ylide 28a /b appears to proceed
largely but not exclusively with retention of stereochem-
The trideuterated species 32 was designed to address
the question of inter- vs intramolecular [1,2]-shift via a
crossover experiment. The remaining three dideuterated
alkynyliodonium salts 33-35 were chosen as probes for
the source of the vinyl proton in 22. The C(3) dideuterio-
pyran entry 33 seemed like the most plausible candidate

Alkynyliodonium Salts in Organic Synthesis
J . Org. Chem., Vol. 65, No. 25, 2000 8663
for providing the 2-deutero version of 22 on the basis of
the results obtained with 1h and earlier precedent (12
f 14) from Oku’s laboratory. However, unexpected
difficulties in the synthesis of 33 opened a window of
opportunity to explore other more readily prepared
alternatives, hence the dideuterated substrates 34 and
35. The C(6) dideuteriopyran species 34 was prepared
to test for the possibility that proton transfer within an
intermediate oxonium ylide might be driven by formation
of a carbonyl ylide product, a process recently reported
by Padwa.17 Finally, the propargylic dideuterated iodo-
nium salt 35 was synthesized to examine the prospects
for intermolecular propargylic deprotonation by ylide 25,
a process that might be facilitated by the strongly
electron withdrawing nature of the phenyliodonium
group.
shown provided the C(2)-d2 valarolactone 41 in good yield
and with g95% deuterium incorporation. However, the
lactol derived from 41 by DIBAL reduction tended to lose
deuterium upon workup, presumably by enolization of
the aldehyde tautomer. This H-for-D exchange was
minimized by workup with CH3OD and, subsequently,
by combination of the lactol with butynol-d2 catalyzed
by TsOD. By these procedures, a sample of stannane 43
containing g90% deuterium at C(3) of the pyran ring,
as judged by MS and 13C NMR measurements, was
obtained.
The use of trideuterioalkynyliodonium salt 32 in a
crossover experiment to probe for inter- vs intramolecu-
larity in the THP shift is shown in eq 9. Treating a 1.0:
The alkynylstannane precursors to the iodonium salts
32-35 were prepared by straightforward syntheses from
either known deuterated starting materials (36,18a 37,18b
4818c) or by highly reliable deuterium incorporation
methodology (40 f 41, 44 f 45), Scheme 4. The level of
Sch em e 4
1.0 mixture of 39 and 20e with PhI(CN)OTf and then
sodium p-toluenesulfinate as per the standard procedure
furnished the 2-THP-containing dihydrofuran product 50
in 40% yield along with undeuterated byproduct 22. Mass
spectral analysis of the purified [1,2]-shift product re-
vealed strong MH+ signals at m/e ) 312 and 309 amu
corresponding to the trideuterio- and triprotio- versions
of 50 (50a and 50b, respectively). Small signals (ca. 10%
of the intensity of the m/e 309 and 212 signals) at m/e
310 and 311 amu, which might correspond to crossover
products 50c and 50d , can be discounted by comparison
to the mass spectrum of 26 () 50b) prepared from 1e.
In that spectrum, similar peaks (∼10% of MH+) appeared
as well. So, with at least 90% fidelity, the transfer of THP
from oxygen to carbon within ylide 25 proceeds in an
intramolecular fashion.
The origin of the vinylic hydrogen in byproduct 22 was
first investigated through a series of control experiments
designed to eliminate adventitious sources of H. Toward
this end, the conversion of alkynylstannane 20e into the
dihydrofuran products 26 and 22 was examined, in
independent experiments, with CD2Cl2 as solvent for
iodonium salt formation, with THF-d8 for the cyclization
sequence, with C6D5SO2Na or with TolSO2Na recrystal-
lized from D2O as nucleophiles, and with a D2O quench
upon termination of the reaction. In no instance was any
deuterium incorporation detected in the byproduct 22.
Turning to the specifically deuterated substrates, both
the C(6)-d2 species 34 and the propargylic-d2 analogue
35 were treated, in independent trials, with sodium
p-toluenesulfinate under standard conditions. Once again,
only protium-containing byproduct 22 was formed. The
final deuterium-containing substrate synthesized, the
C(3)-labeled system 33, was subjected to sulfinate addi-
tion and furnished 42% of the expected C(3)-dideuterated
dihydrofuran 26-d2. The product of interest, dihydrofuran
22 (25%), was examined by FABMS(+) and 1H NMR
spectroscopy to reveal that, indeed, the vinylic position
residual protium in the stannanes 39, 47, and 49 was
essentially unmeasurable by 1H NMR and MS tech-
niques. The synthesis and preservation of deuterium
content of the C(3)-d2 species 43 proved to be significantly
more challenging. After several false starts, the route
(17) Padwa, A.; Heidelbaugh, T. M.; Kuethe, J . T. J . Org. Chem.
1999, 64, 2038.
(18) (a) Dua, S.; Bowie, J . H. J . Chem. Soc., Perkin Trans. 2 1994,
2097. (b) Oakes, F. T.; Sebastian, J . F. J . Org. Chem. 1980, 45, 4959.
(c) Steiner, R.; Schumann, D.; Hoffmann, H. Org. Mass Spectrom. 1983,
18, 345.
1
had been partially deuterated. The H NMR data indi-

8664 J . Org. Chem., Vol. 65, No. 25, 2000
Feldman and Wrobleski
cated approximately 56% deuterium incorporation, where-
as the MS data was more consistent with ∼40% deute-
rium at C(1) of 22. These results suggest that to a
significant extent the vinylic proton in 22 is derived from
C(3) of the THP ring. The other source(s) for this proton
remains a mystery.
entations within the solvent cage, which presumably lie
at the heart of this anomaly, have yet to be sorted out.
In summary, a new application of alkynyliodonium
salts to the synthesis of 2-substituted-3-p-toluenesulfo-
nyldihydrofurans has been developed. This transforma-
tion features the formation of an intermediate disubsti-
tuted-carbon oxonium ylide that suffers [1,2]-shift (formal
Stevens rearrangement) en route to dihydrofuran prod-
uct. Successful reactions appear to require a relatively
stable cationic migrating group. Preliminary indications
are that moderate levels of 1,2- diastereoselectivity are
attainable. Deuterium labeling studies have helped
expose some of the mechanistic details of the multistep
sequence. The extension of this reaction to more complex
substrates is planned.
The mechanistic issues raised earlier can now be
answered with varying degrees of certainty on the basis
of these and prior results. The structure/reactivity profile
of the migrating groups R in 1 provides evidence consis-
tent with heterolytic and not homolytic scission of the
C-O bond within ylide 6. An alternative, concerted
O-to-C shift with retention of stereochemistry has been
considered by J ohnson and Roskamp in their seminal
studies on trisubstituted-carbon oxonium ylides.16a In the
case of the disubstituted-carbon oxonium ylide 6, such a
concerted shift would arguably engender a severe ener-
getic penalty as a consequence of unfavorable orbital
interactions (a 4-electron/2-orbital interaction for an in-
plane shift, poor orbital overlap/strained geometry for an
out-of-plane shift). Thus, the weight of evidence supports
the heteropolar dissociation/recombination sequence
25 f 51 f 26/22 illustrated in Scheme 5 for the proto-
typical THP case.
Exp er im en ta l Section
Gen er a l. All moisture- and air-sensitive reactions were
performed in flame-dried glassware under a positive pressure
of argon with magnetic stirring. Tetrahydrofuan (THF) and
diethyl ether (Et2O) were dried by distillation from sodium/
benzophenone under argon. Methylene chloride (CH2Cl2),
benzene, and triethylamine were distilled from calcium hy-
dride under argon. Anhydrous sodium p-toluenesulfinate was
purchased from Fluka, ground into a fine powder, and dried
under vacuum at ca. 0.2 mmHg at 120 °C for 24 h. Liquid flash
chromatography19 was carried out using 32-63 µm silica gel
and the indicated solvent. Deactivated silica gel was prepared
by treatment of the silica with 5% triethylamine in hexanes
solution prior to use. Hexanes, Et2O, and EtOAc used in flash
chromatography were distilled from calcium hydride prior to
use. All melting points are uncorrected. NMR chemical shifts
are reported in δ units using tetramethylsilane as an internal
standard. Copies of 13C NMR spectra are provided in the
Supporting Information to establish purity for those com-
pounds that were not subjected to combustion analysis.
Gen er a l P r oced u r e A. St a n n yla t ion of Ter m in a l
Alk yn es. A 2.5 M solution of n-BuLi in hexane (1 equiv) was
added to the alkynyl ether in THF at -78 °C over 5 min. The
reaction mixture was allowed to stir at -78 °C for 45 min
before the addition of tributyltin chloride (1 equiv). The
solution was warmed to ambient temperature and stirred for
2 h. The mixture was treated with saturated NH4Cl solution
and diluted with an equal volume of Et2O. The organic layer
was washed with two portions of H2O and then brine, dried
over anhydrous Na2SO4, filtered, and concentrated in vacuo
to afford the crude alkynylstannane. Purification of the crude
product by flash chromatography on deactivated silica gel
eluting with the indicated solvent afforded the alkynylstan-
nane as a colorless oil
Gen er a l P r oced u r e B. Iod on iu m Sa lt F or m a tion a n d
p-Tolu en esu lfin a te Ad d ition . Cyano(phenyl)iodonium tri-
flate13 (1 equiv) was added to a -42 °C deoxygenated solution
of the alkynylstannane in CH2Cl2. After 2 h, the solvent was
removed in vacuo at <0 °C, and the crude iodonium salt was
warmed to ∼0 °C and washed with two portions of prechilled
(-42 °C) hexanes. The solvent reside was removed in vacuo
with T < 0 °C to furnish the iodonium salt as a white solid or
light yellow oil. This species was used immediately assuming
quantitative yield.
The alkynyl(phenyl)iodonium triflate in THF at -42 °C was
cannulated rapidly into a refluxing suspension of anhydrous
sodium p-toluenesulfinate (1.3-1.5 equiv) in THF. The yellow
suspension was allowed to reflux for 30 min and then stirred
at room temperature for 10 min. The reaction mixture was
treated with saturated sodium bicarbonate solution and
diluted with an equal volume of Et2O. The organic layer was
washed sequentially with H2O and brine, dried over anhydrous
Na2SO4, filtered, and concentrated in vacuo to afford the crude
Sch em e 5
The lack of crossover products with 32 and 1e and the
high levels of diastereoselectivity seen with 1f and 1g
are consistent with a solvent cage recombination mech-
anism in which the fragments 51a /51b do not have time
to change their relative orientations significantly prior
to collapse. Finally, the anion/cation pair 51a /51b ap-
parently partitions between two energetically similar
pathways, nucleophile/electrophile capture (path a) and
proton transfer (path b), to furnish the observed products
26 and 22, respectively. In support of this hypothesis,
examination of the crude reaction mixture formed by
combining 1e with p-toluenesulfinate in THF-d8 revealed
detectable quantities of dihydropyran. This first-genera-
tion mechanistic picture rationalizes the gross features
of the conversion of 1e into 26/22, but one subtle point
remains clouded: dissociation of the cis configured ylide
28b should provide an electrophile/nucleophile pair 52/
51a , which is perfectly disposed for recombination but
is not at all aligned for C(3) proton abstraction. In this
scenario, less byproduct 22 than with the trans isomer
1d might have been expected. However, the results indi-
cate otherwise. Thus, the details of the molecular reori-
(19) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.

Alkynyliodonium Salts in Organic Synthesis
J . Org. Chem., Vol. 65, No. 25, 2000 8665
dihydrofuran product(s). Purification of this crude material
was accomplished by flash chromatography on deactivated
silica gel eluting with the indicated solvent.
Da ta for 19g: IR (film) 3310, 2122 cm-1; 1H NMR (300 MHz,
CDCl3) 4.57 (d, J ) 3.0 Hz, 1 H), 3.84-3.71 (m, 2 H), 3.53 (dt,
J ) 9.8, 7.2 Hz, 2 H), 2.48 (dt, J ) 6.8, 2.6 Hz, 2 H), 1.96 (t, J
) 2.6 Hz, 1 H), 1.81-1.46 (m, 5 H), 0.89 (d, J ) 6.8 Hz, 3 H);
13C NMR (100 MHz, CDCl3) 100.7, 81.8, 69.2, 65.6, 59.8, 35.0,
26.2, 25.7, 20.0, 16.8; MS m/e (+CI) 169 (MH+, 60). Anal. Calcd
for C10H16O2: C, 71.39; H, 9.59. Found: C, 71.19; H, 9.77.
Da ta for 19f: IR (film) 3297, 2122 cm-1; 1H NMR (300 MHz,
CDCl3) 4.09 (d, J ) 6.8 Hz, 1 H), 3.99-3.87 (m, 2 H), 3.60 (dt,
J ) 9.8, 7.2 Hz, 1 H), 3.49-3.41 (m, 1 H), 2.50 (dt, J ) 7.2, 2.6
Hz, 2 H), 1.97 (t, J ) 2.6 Hz, 1 H), 1.90-1.81 (m, 1 H), 1.64-
1.47 (m, 3 H), 1.27-1.15 (m, 1 H), 0.96 (d, J ) 6.8 Hz, 3 H);
13C NMR (75 MHz, CDCl3) 105.9, 81.4, 69.2, 66.5, 64.9, 34.9,
29.5, 24.3, 20.0, 16.7; MS m/e (+CI) 169 (MH+, 24). Anal. Calcd
for C10H16O2: C, 71.39; H, 9.59. Found: C, 71.43; H, 9.88.
Tr ibu tyl[4-(tr a n s-3-m eth yltetr a h yd r op yr a n -2-yloxy)-
bu t-1-yn yl]sta n n a n e (20f). Using General Procedure A,
2-but-3-ynyloxy-trans-3-methyltetrahydropyran (19f) (88 mg,
0.52 mmol) was converted to 0.20 g of alkynylstannane 20f
(86%) following purification of the crude product with 4% Et2O/
hexanes: IR (film) 2153 cm-1; 1H NMR (300 MHz, CDCl3) 4.10
(d, J ) 6.4 Hz, 1 H), 3.99-3.84 (m, 2 H), 3.59 (dt, J ) 9.8, 7.5
Hz, 1 H), 3.49-3.41 (m, 1 H), 2.55 (t, J ) 7.2 Hz, 2 H), 1.90-
1.81 (m, 1 H), 1.60-1.49 (m, 8 H), 1.39-1.27 (m, 8 H), 0.98-
0.88 (m, 18 H); 13C NMR (75 MHz, CDCl3) 107.9, 105.8, 83.0,
67.2, 64.9, 34.9, 29.5, 28.9 (J C-Sn119 ) 11.6 Hz), 27.0 (J C-Sn119
) 30.5 Hz), 24.4, 21.7, 16.7, 13.7, 10.9 (J C-Sn119 ) 191.8 Hz,
J C-Sn117 ) 183.8 Hz; MS m/e (+APCI) 459 (Sn120) (MH+, 5);
HRMS (+ESI) calcd for C22H43O2Sn120 (MH+) 459.2285, found
459.2263.
Tr ibu tyl[4-(cis-3-m eth yltetr a h yd r op yr a n -2-yloxy)bu t-
1-yn yl]sta n n a n e (20 g). Using General Procedure A, 2-but-
3-ynyloxy-cis-3-methyltetrahydropyran (19g) (0.15 g, 0.89
mmol) was converted to 0.35 g of alkynylstannane 20g (87%)
following purification of the crude product with 4% Et2O/
hexanes: IR (film) 2153 cm-1; 1H NMR (300 MHz, CDCl3) 4.57
(d, J ) 3.0 Hz, 1 H), 3.82-3.72 (m, 2 H), 3.54-3.46 (m, 2 H),
2.54 (dt, J ) 6.9, 1.9 Hz, 2 H), 1.80-1.43 (m, 11 H), 1.39-1.27
(m, 6 H), 1.07-0.87 (m, 18 H); 13C NMR (75 MHz, CDCl3)
108.4, 100.6, 83.0, 66.3, 59.7, 35.1, 29.1 (J C-Sn119 ) 11.6 Hz),
27.2 (J C-Sn119 ) 29.8 Hz), 26.3, 25.8, 21.7, 17.0, 13.9, 11.1
(J C-Sn119 ) 191.8 Hz, J C-Sn117 ) 183.1 Hz; MS m/e (+ESI) 481
(Sn119) (MNa+, 100); HRMS (+ESI) calcd for C22H42O2NaSn120
481.2104, found 481.2075.
(4-Allyloxy-bu t-1-yn yl)tr ibu tylsta n n a n e (20b). Using
General Procedure A, 4-allyloxybut-1-yne (19b)11b (0.29 g, 2.6
mmol) was converted to 0.65 g of alkynylstannane 20b (63%)
following purification of the crude product with 1% Et2O/
hexanes: IR (film) 2153 cm-1 1H NMR (300 MHz, CDCl3)
;
5.97-5.84 (m, 1 H), 5.29 (dd, J ) 17.0, 1.5 Hz, 1 H), 5.18 (dd,
J ) 10.6, 1.5 Hz, 1 H), 4.01 (dt, J ) 5.7, 1.5 Hz, 2 H), 3.57 (t,
J ) 7.4 Hz, 2 H), 2.54 (t, J ) 7.4 Hz, 2 H), 1.60-1.50 (m, 6 H),
1.39-1.27 (m, 6 H), 0.99-0.88 (m, 15 H); 13C NMR (75 MHz,
CDCl3) 134.7, 117.0, 107.7, 83.2, 71.9, 69.0, 28.9 (J C-Sn119
11.6 Hz), 27.0 (J C-Sn119 ) 29.8 Hz), 21.6, 13.7, 11.0 (J C-Sn119
)
)
191.8 Hz, J C-Sn117 ) 183.1 Hz); MS m/e (+CI) 343 (Sn120) (M -
Bu+, 100); HRMS (+CI) calcd for C19H35OSn120 (M - H+)
399.1710, found 399.1701.
Tr ibu tyl[4-(tetr a h yd r ofu r a n -2-yloxy)-bu t-1-yn yl]sta n -
n a n e (20d ). Using General Procedure A, 2-but-3-ynyloxytet-
rahydrofuran (19d )11d (1.1 g, 7.8 mmol) was converted to 2.0
g of alkynylstannane 20d (60%) following purification of the
crude product with 5% Et2O/hexanes: IR (film) 2145 cm-1; 1H
NMR (400 MHz, CDCl3) 5.16 (t, J ) 3.0 Hz, 1 H), 3.91-3.83
(m, 2 H), 3.75 (dt, J ) 9.5, 7.5 Hz, 1 H), 3.53 (dt, J ) 9.5, 7.5
Hz, 1 H), 2.51 (t, J ) 7.5 Hz, 2 H), 2.02-1.78 (m, 4 H), 1.67-
1.44 (m, 6 H), 1.38-1.29 (m, 6 H), 0.98-0.88 (m, 15 H); 13C
NMR (100 MHz, CDCl3) 108.0, 104.0, 83.0, 67.0, 66.1, 32.5,
29.0 (J C-Sn119 ) 11.7 Hz), 27.1 (J C-Sn119 ) 30.1 Hz), 23.5, 21.8,
13.8, 11.1 (J C-Sn119 ) 191.5 Hz, J C-Sn117 ) 182.7 Hz); MS m/e
(+FAB/3NBA) 373 (Sn120) (M - Bu+, 22); HRMS (+FAB) calcd
for C20H38O2NaSn120 453.1791, found 453.1780.
Tr ibu tyl[4-(tetr a h yd r op yr a n -2-yloxy)bu t-1-yn yl]sta n -
n a n e (20e). Using General Procedure A, 2-but-3-ynyloxytet-
rahydropyran (19e)11e (0.65 g, 4.2 mmol) was converted to 1.7
g of alkynylstannane 20e (90%) following purification of the
crude product with 5% Et2O/hexanes: IR (film) 2149 cm-1; 1H
NMR (360 MHz, CDCl3) 4.66 (t, J ) 3.2 Hz, 1 H), 3.93-3.79
(m, 2 H), 3.59-3.48 (m, 2 H), 2.56 (t, J ) 7.3 Hz, 2 H), 1.88-
1.49 (m, 12 H), 1.38-1.28 (m, 6 H), 0.98-0.86 (m, 15 H); 13C
NMR (90 MHz, CDCl3) 108.3, 99.1, 83.4, 66.6, 62.5, 31.0, 29.3
(J C-Sn119 ) 11.7 Hz), 27.4 (J C-Sn119 ) 29.6 Hz), 25.9, 22.1, 19.8,
14.1, 11.4 (J C-Sn119 ) 191.2 Hz, J C-Sn117 ) 183.1 Hz; MS m/e
(+CI) 387 (Sn120) (M - Bu+, 22); HRMS (+MALDI) calcd for
C
21H40O2NaSn120 467.1948, found 467.1953.
2-Bu t-3-yn yloxy-[1,3]-d ioxa n e (19h ). But-3-ynol (0.80
mL, 0.11 mmol) followed by p-toluenesulfonic acid monohy-
drate (10 mg, 0.055 mmol) was added to 2-methoxy-1,3-dioxane
(2.6 g, 22 mmol). The neat mixture was heated to 110-120
°C, and the methanol formed was removed with a short path
distillation apparatus. After 15 h, the reaction mixture was
cooled to room temperature. Purification of the crude product
by flash chromatography on silica gel eluting with 10% Et2O/
hexanes afforded 0.36 g (21%) of 19h as a colorless oil: IR
2-Bu t -3-yn yloxy-3-m et h ylt et r a h yd r op yr a n s (19f a n d
19g). A 1.0 M solution of DIBAL-H in hexane (42 mL, 42
mmol) was added to a -42 °C solution of 3-methyl-valerolac-
tone20 (4.3 g, 38 mmol) in 18 mL of THF over 1.5 h. The
reaction mixture was warmed to -20 °C after the addition was
complete. After 1 h, the reaction mixture was carefully treated
with 35 mL of methanol. The white slurry was filtered, and
the salts were washed with three 100 mL portions of methanol.
The solvent was removed under water aspirator pressure at
room temperature, and the residue was distilled to afford 2.5
g (59%) of impure cis- and trans-3-methylpyran-2-ol.
p-Toluenesulfonic acid monohydrate (21 mg, 0.11 mmol)
followed by but-3-ynol (0.80 mL, 0.11 mmol) was added to the
mixture of cis- and trans-3-methylpyran-2-ol (2.7 g, 23 mmol)
in 9 mL of benzene. The solution was refluxed for 3 h with
Dean-Stark collection of water. Saturated sodium bicarbonate
solution (10 mL) was added followed by 50 mL of Et2O. The
phases were separated, and the organic layer was washed
sequentially with 20 mL of saturated bicarbonate solution and
brine, dried over anhydrous Na2SO4, filtered, and concentrated
in vacuo to provide a yellow oil. Purification of the crude
product by flash chromatography on silica gel eluting with 5%
Et2O/hexanes afforded 1.5 g (89%) of a colorless oil as a mixture
of cis and trans ethers 19f/19g. The isomers were separated
by flash chromatography on silica gel eluting with 95%
benzene/hexanes.
1
(film) 3285, 2120 cm-1; H NMR (400 MHz, C6D6) 5.30 (s, 1
H), 3.90-3.85 (m, 2 H), 3.56 (t, J ) 7.0 Hz, 2 H), 3.35-3.29
(m, 2 H), 2.28 (dt, J ) 7.0, 2.5 Hz, 2 H), 1.72 (t, J ) 2.5 Hz, 1
H), 1.37-1.27 (m, 1 H), 1.06-0.98 (m, 1 H); 13C NMR (100
MHz, C6D6) 109.4, 81.4, 69.8, 63.0, 61.0, 25.1, 20.2; MS m/e
(+CI) 157 (MH+, 100). Anal. Calcd for C8H12O3: C, 61.25; H,
7.74. Found: C, 61.46; H, 7.88.
Tr ib u t yl[4-([1,3]-d ioxa n -2-yloxy)b u t -1-yn yl]st a n n a n e
(20h ). Using General Procedure A, the ortho ester 19h (0.12
g, 0.77 mmol) was converted to 0.26 g of alkynylstannane 20h
(75%) following purification of the crude product with 3% Et2O/
hexanes: IR (film) 2153 cm-1; 1H NMR (300 MHz, C6D6) 5.36
(s, 1 H), 3.97-3.89 (m, 2 H), 3.71 (t, J ) 7.2 Hz, 2 H), 3.38-
3.29 (m, 2 H), 2.56 (t, J ) 7.2 Hz, 2 H), 1.76-1.56 (m, 6 H),
1.43-1.31 (m, 7 H), 1.09-0.90 (m, 16 H); 13C NMR (75 MHz,
C6D6) 109.4, 108.4, 83.1, 63.9, 60.8, 29.4 (J C-Sn119 ) 11.6 Hz),
27.4 (J C-Sn119 ) 29.8 Hz), 25.2, 22.2, 13.9, 11.2 (J C-Sn119 ) 191.8
Hz, J C-Sn117 ) 183.8 Hz; MS m/e (+CI) 447 (Sn120) (MH+, 14);
HRMS (+CI) calcd for C20H39O3Sn120 (M + H+) 447.1921, found
447.1929.
(20) Prepared according to a procedure reported by Takacs, J . M.;
Newsome, P. W.; Kuehn, C.; Takusagawa, F. Tetrahedron 1990, 46,
5507. For characterization data see: Bachi, M. D., Bosch, E. J . Org.
Chem. 1992, 57, 4696.
ter t-Bu tyld im eth yl[3-(tolu en e-4-su lfon yl)-4,5-d ih yd r o-
fu r a n -2-yl]sila n e (21). By using a modified version of General

8666 J . Org. Chem., Vol. 65, No. 25, 2000
Feldman and Wrobleski
Procedure B (CH2Cl2 as solvent, -42 °C f room temperature),
alkynylstannane 20a (0.11 g, 0.23 mmol) was converted into
52 mg (65%) of 21 as a white solid, mp 86-87 °C: IR (KBr)
Anal. Calcd for C17H22O4S: C, 63.33; H, 6.88. Found: C, 63.00;
H, 6.94. In addition, 8 mg (16%) of 22 was isolated as a white
solid.
1
1558, 1312 cm-1; H NMR (200 MHz, CDCl3) 7.76 (d, J ) 8.2
cis-3-Meth yl-2-[3-(tolu en e-4-su lfon yl)-4,5-dih ydr ofu r an -
2-yl]tetr a h yd r op yr a n (29b). Using General Procedure B, the
alkynylstannane 20g (0.11 g, 0.24 mmol) was converted into
32 mg of dihydrofurans 29a /b (41%, 8.5:1 mixture of 29b to
29a ) as a white solid following chromatographic purification
with the solvent gradient 20% EtOAc/hexanes, 25% EtOAc/
hexanes, and 30% EtOAc/hexanes. The ratio of isomers was
calculated by averaging the integration ratios of the methyl
doublets and the C(H)O protons in the 1H NMR spectrum of
the crude product mixture. Partial purification of the indi-
vidual isomers was achieved through the aforementioned
chromatography.
Hz, 2 H), 7.32 (d, J ) 7.9 Hz, 2 H), 4.40 (t, J ) 10.0 Hz, 2 H),
2.78 (t, J ) 10.0 Hz, 2 H), 2.43 (s, 3 H), 0.99 (s, 9 H), 0.36 (s,
6 H); 13C NMR (75 MHz, CDCl3) 173.7, 143.5, 138.5, 129.6,
127.3, 125.5, 72.1, 31.3, 26.8, 21.5, 17.5, -5.0; MS m/e (+CI)
339 (MH+, 7). Anal. Calcd for C17H26O3SSi: C, 60.31; H, 7.74.
Found: C, 60.14; H, 7.69.
4-(Tolu en e-4-su lfon yl)-2,3-d ih yd r ofu r a n (22). A 1 M
solution of n-Bu4NF in THF (62 µL, 0.062 mmol) was added
to the silylalkene 21 (21 mg, 0.062 mmol) in 5 mL of THF.
After stirring for 30 min at room temperature, 1 M NH4Cl
solution was added, and the aqueous phase was extracted with
Et2O. The combined organic layers were washed with H2O and
then brine, dried over Na2SO4, filtered, and concentrated to
obtain 19 mg of a white solid, mp 106-107 °C: IR (film) 1607
Da ta for 29b: IR (film) 1622 cm-1 1H NMR (360 MHz,
;
C6D6) 7.89 (d, J ) 8.2 Hz, 2 H), 6.79 (d, J ) 8.7 Hz, 2 H), 5.65
(d, J ) 3.6 Hz, 1 H), 3.87 (dt, J ) 11.5, 3.6 Hz, 1 H), 3.69-
3.42 (m, 3 H), 2.64-2.54 (m, 1 H), 2.32-2.22 (m, 2 H), 1.88 (s,
3 H), 1.71-1.45 (m, 3 H), 1.10-1.05 (m, 1 H) with overlapping
1.08 (d, J ) 7.3 Hz, 3 H); 13C NMR (90 MHz, C6D6) 167.8, 143.6,
140.5, 130.1, 127.8, 111.2, 73.9, 70.3, 68.0, 33.3, 30.8, 30.2, 22.7,
21.5, 15.0; MS m/e (+CI) 323 (MH+, 100). Anal. Calcd for
1
cm-1; H NMR (200 MHz, CDCl3) 7.77 (d, J ) 8.2 Hz, 2 H),
7.32 (d, J ) 8.0 Hz, 2 H), 7.19 (t, J ) 1.8 Hz, 1 H), 4.59 (t, J
) 9.6 Hz, 2 H), 2.78 (dt, J ) 9.6, 1.7 Hz, 2 H), 2.43 (s, 3 H);
13C NMR (100 MHz, CDCl3)156.3, 144.0, 137.8,129.7, 127.3,
117.6, 74.0, 28.1, 21.6; MS m/e (+FAB/3NBA) 225 (MH+, 70).
Anal. Calcd for C11H12O3S: C, 58.91; H, 5.39. Found: C, 58.80;
H, 5.54.
C
17H22O4S: C, 63.33; H, 6.88. Found: C, 62.86; H, 6.93. In
addition,8 mg (16%) of 22 was isolated as a white solid.
2-[3-(Tolu en e-4-su lfon yl)-4,5-d ih yd r ofu r a n -2-yl]-[1,3]-
d ioxa n e (31). Using General Procedure B, the alkynylstan-
nane 20h (0.12 g, 0.27 mmol) was converted into 56 mg of
dihydrofuran 31 (68%) as a white solid following chromato-
graphic purification with the solvent gradient 15% Et2O/
hexanes, 20% Et2O/hexanes, 25% Et2O/hexanes, 30% Et2O/
hexanes and 50% EtOAc/hexanes, mp 184-185 °C: IR (film)
3′-(Tolu en e-4-su lfon yl)-2,3,4,5,4′,5′-h exa h yd r o[2,2′]b i-
fu r a n yl (27). Using General Procedure B, the alkynylstan-
nane 20d (0.11 g, 0.26 mmol) was converted into 26 mg of
dihydrofuran 27 (35%) as a white solid following chromato-
graphic purification with the gradient 20% Et2O/hexanes, 25%
Et2O/hexanes, and 30% Et2O/hexanes, mp 111-112 °C: IR
1
(film) 1628 cm-1; H NMR (400 MHz, CDCl3) 7.77 (d, J ) 8.0
1
Hz, 2 H), 7.32 (d, J ) 8.0 Hz, 2 H), 5.54 (t, J ) 6.0 Hz, 1 H),
4.43 (t, J ) 11.0 Hz, 2 H), 3.97-3.87 (m, 2 H), 3.01-2.93 (m,
1 H), 2.78-2.70 (m, 1H), 2.43 (s, 3 H), 2.31-2.25 (m, 1 H),
2.08-1.93 (m, 3 H); 13C NMR (100 MHz, CDCl3) 167.9, 144.0,
138.5, 129.9, 127.2, 110.7, 71.5, 70.5, 69.8, 30.8, 30.5, 26.5, 21.7;
MS m/e (+CI) 295 (MH+, 54). Anal. Calcd for C15H18O4S: C,
61.21; H, 6.16. Found: C, 61.20; H, 6.32. In addition, 15 mg
(25%)of 22 was isolated as a white solid.
1647 cm-1; H NMR (300 MHz, C6D6) 7.93 (d, J ) 8.7 Hz, 2
H), 6.81 (d, J ) 7.9 Hz, 2 H), 6.59 (s, 1 H), 3.83 (dd, J ) 10.6,
4.9 Hz, 2 H), 3.61-3.51 (m, 4 H), 2.31 (t, J ) 10.2 Hz, 2 H),
1.90-1.77 (m, 1 H) with overlapping 1.88 (s, 3 H), 0.57-0.53
(m, 1 H); 13C NMR (75 MHz, C6D6) 161.6, 143.4, 139.7, 129.8,
128.1, 113.0, 94.2, 70.3, 67.2, 30.5, 25.8, 21.1; MS m/e (+CI)
311 (MH+, 100). Anal. Calcd for C15H18O5S: C, 58.05; H, 5.84.
Found: C, 58.19; H, 6.03.
2-[3-(Tolu en e-4-su lfon yl)-4,5-dih ydr ofu r an -2-yl]tetr ah y-
d r op yr a n (26). Using General Procedure B, the alkynylstan-
nane 20e (0.15 g, 0.34 mmol) was converted into 42 mg of
dihydrofuran 26 (41%) as a white solid following chromato-
graphic purification with 25% EtOAc/hexanes, mp 98 °C
(decomp): IR (film) 1629 cm-1; 1H NMR (400 MHz, CDCl3) 7.76
(d, J ) 8.5 Hz, 2 H), 7.33 (d, J ) 8.0 Hz, 2 H), 5.09-5.06 (m,
1 H), 4.51-4.40 (m, 2 H), 4.08 (dd, J ) 11.0, 4.0 Hz, 1 H), 3.60
(dd, J ) 11.5, 2.5 Hz, 1 H), 2.99-2.91 (m, 1 H), 2.78-2.70 (m,
1 H), 2.44 (s, 3 H), 1.93-1.89 (m, 1 H), 1.77-1.54 (m, 5 H);
13C NMR (75 MHz, CDCl3) 166.2, 143.9, 138.4, 129.7, 127.1,
109.7, 71.5, 70.6, 68.9, 30.3, 29.4, 25.4, 23.0, 21.6; MS m/e (+CI)
309 (MH+, 100). Anal. Calcd for C16H20O4S: C, 62.31; H, 6.54.
Found: C, 62.46; H, 6.62. In addition,21 mg (27%) of 22 was
isolated as a white solid.
2-2H-2-([1,1-2H2]-Bu t-3-yn yloxy)tetr a h yd r op yr a n (38).
A 1-2 M hexanes solution of 6-deuteriodihydropyran18b (10
mL) and p-toluenesulfonic acid monohydrate (68 mg, 0.36
mmol) was added to [1,1-2H2]-but-3-ynol18a (0.26 g, 3.6 mmol)
in 5 mL of CH2Cl2. After 2 h, the reaction mixture was treated
with 5 mL of saturated sodium bicarbonate solution and
diluted with 50 mL of Et2O. The phases were separated, and
the organic layer was washed with 10 mL of H2O and brine,
dried over anhydrous Na2SO4, filtered, and concentrated in
vacuo to provide a yellow oil. Purification of the crude product
by flash chromatography on silica gel eluting with 5% Et2O/
hexanes afforded 329 mg (58%) of 38 as a colorless oil: IR (film)
1
3295, 2107 cm-1; H NMR (300 MHz, C6D6) 3.79-3.71 (m, 1
H), 3.38-3.32 (m, 1 H), 2.30 (s, 2 H), 1.75 (t, J ) 2.6 Hz, 1 H)
overlapping 1.75-1.70 (m, 1 H), 1.55-1.49 (m, 2 H), 1.33-
1.19 (m, 3 H); 13C NMR (75 MHz, C6D6) 98.0 (t), 81.7, 69.6,
64.8 (q), 61.4, 30.6, 25.8, 20.1, 19.3; MS m/e (+CI) 158 (MH+,
6); HRMS (+CI) calcd for C9H12D3O2 (MH+)158.1260, found
158.1263.
tr a n s-3-Meth yl-2-[3-(tolu en e-4-su lfon yl)-4,5-d ih yd r ofu -
r a n -2-yl]tetr a h yd r op yr a n (29a ). Using General Procedure
B, the alkynylstannane 20f (0.10 g, 0.22 mmol) was converted
into 30 mg of dihydrofurans 29a /b (43%, 10:1 mixture of 29a
to 29b) as a white solid following chromatographic purification
with the solvent gradient 20% EtOAc/hexanes, 25% EtOAc/
hexanes, and 30% EtOAc/hexanes. The ratio of isomers was
calculated by averaging the integration ratios of the methyl
doublets and the C(H)O protons in the 1H NMR spectrum of
the crude product mixture. Partial purification of the indi-
vidual isomers was achieved through the aforementioned
chromatography.
Tr ibu tyl[[4,4-2H2]-4-([2-2H]-tetr a h yd r op yr a n -2-yloxy)-
bu t-1-yn yl]sta n n a n e (39). Using General Procedure A, the
trideuterated but-3-ynyl ether 38 (0.16 g, 1.0 mmol) was
converted to 320 mg of alkynylstannane 39 (72%) following
purification of the crude product with 3% Et2O/hexanes: IR
1
(film) 2154 cm-1; H NMR (300 MHz, C6D6) 3.83-3.75 (m, 1
H), 3.36 (ddt, J ) 15.7, 4.1, 1.5 Hz, 1 H), 2.56 (s, 2 H), 1.79-
1.18 (m, 16 H), 1.01 (t, J ) 7.9 Hz, 6 H), 0.93 (t, J ) 7.2 Hz,
9 H); 13C NMR (75 MHz, C6D6) 108.8 (J C-Sn119 ) 36.3 Hz), 97.8
(t), 82.7, 65.6 (pentet), 61.3, 30.7, 29.3 (J C-Sn119 ) 11.6 Hz),
27.4 (J C-Sn119 ) 29.8 Hz), 25.9, 22.0, 19.3, 13.9, 11.2 (J C-Sn119
Da ta for 29a : IR (film) 1622 cm-1 1H NMR (360 MHz,
;
C6D6) 7.95 (d, J ) 8.2 Hz, 2 H), 6.81 (d, J ) 8.7 Hz, 2 H), 5.11
(d, J ) 10.0 Hz, 1 H), 3.93-3.89 (m, 1 H), 3.68-3.53 (m, 2 H),
3.42-3.35 (m, 1 H), 2.65-2.56 (m, 1 H), 2.34-2.22 (m, 1 H),
2.01-1.87 (m, 1 H), 1.88 (s, 3 H), 1.59-1.49 (m, 2 H), 1.16-
1.03 (m, 2 H) 0.92 (d, J ) 6.4 Hz, 3 H); 13C NMR (90 MHz,
C6D6) 165.1, 143.2, 140.1, 129.7, 128.5, 113.6, 76.6, 69.8, 68.6,
32.7, 32.1, 30.8, 26.6, 21.1, 17.8; MS m/e (+CI) 323 (MH+, 100).
) 191.8 Hz, J C-Sn117 ) 183.1 Hz; MS m/e (+CI) 448 (Sn120
)
(MH+, 5); HRMS (+CI) calcd for C21H38D3O2Sn120 (MH+)
448.2317, found 448.2305.
[2,2-2H2]-δ-Va ler ola cton e (41). Sodium methoxide (0.28 g,
5.2 mmol) was added to 5-benzyloxypentanoic acid methyl

Alkynyliodonium Salts in Organic Synthesis
J . Org. Chem., Vol. 65, No. 25, 2000 8667
ester21 (2.1 g, 9.4 mmol) in 20 mL of MeOD. After 17 h at
reflux, the solution was cooled to room temperature and
concentrated in vacuo. The residue was taken up in 100 mL
of Et2O and 50 mL of H2O. The aqueous layer was extracted
with three 20 mL portions of Et2O, and the combined organic
phases were rinsed with 20 mL of brine, dried over anhydrous
Na2SO4, filtered, and concentrated in vacuo to afford 1.8 g
(85%) of crude methyl 5-benzyloxy-[2,2-2H2]-pentanoate as a
colorless oil with 96% deuterium incorporation: IR (film) 1736
cm-1; 1H NMR (360 MHz, C6D6) 7.29-7.09 (m, 5 H), 4.27 (s, 2
H), 3.32 (s, 3 H), 3.20 (t, J ) 6.4 Hz, 2 H), 1.65, J ) 7.3 Hz, 2
H), 1.52-1.44 (m, 2 H); 13C NMR (75 MHz, C6D6) 173.3, 139.4,
128.5, 127.7, 127.6, 72.9, 69.9, 50.9, 33.2 (pentet), 29.4, 22.0;
MS m/e (+CI) 225 (MH+, 100); HRMS (+CI) calcd for
C13H17D2O3 225.1460, found 225.1453.
(t), 65.7, 61.5, 30.4 (pentet), 25.8, 19.3, 19.2; MS m/e (+CI) 157
(MH+, 1); HRMS (+CI) calcd for C9H11D3O2 157.1179, found
157.1182.
Tr ib u t yl[4-([3,3-2H 2]-t et r a h yd r op yr a n -2-yloxy)b u t -1-
yn yl]sta n n a n e (43). Using General Procedure A, the trideu-
terated but-3-ynyl ether 42 (78 mg, 0.50 mmol) was converted
to 170 mg of alkynylstannane 43 (76%) following purification
of the crude product with 4% Et2O/hexanes: IR (film) 2153
cm-1; 1H NMR (300 MHz, C6D6) 4.58 (s, 1 H), 3.93(dt, J ) 9.4,
7.2 Hz, 1 H), 3.88-3.75 (m, 1 H), 3.55 (dt, J ) 9.4, 7.2 Hz, 1
H), 3.40-3.34 (m, 1 H), 2.57 (t, J ) 7.2 Hz, 2 H), 1.72-1.61
(m, 7 H), 1.44-1.31 (m, 7 H), 1.1 (t, J ) 8.3 Hz, 6 H), 0.92 (t,
J ) 7.2 Hz, 11 H); 13C NMR (75 MHz, C6D6) 108.9, 98.3, 82.8,
66.4, 61.4, 30.5 (t), 29.4 (J C-Sn119 ) 10.9 Hz), 27.4 (J C-Sn119
)
29.8 Hz), 25.9, 22.2, 19.2, 13.9, 11.2 (J C-Sn119 ) 191.8 Hz,
J C-Sn117 ) 183.8 Hz; MS m/e (+CI) 447 (Sn120) (MH+, 100);
HRMS (+CI) calcd for C21H37D2O2Sn120 (M - H+) 445.2097,
found 445.2106.
10% Pd/C (43 mg, 0.40 mmol) was added to methyl 5-ben-
zyloxy-[2,2-2H2]pentanoate (1.8 g, 8.0 mmol) in 40 mL of THF.
The system was purged with Ar and then with hydrogen. The
reaction mixture was stirred under 1 atm of hydrogen for 18
h. The suspension was filtered through a plug of Celite, and
the solid was washed with 50 mL of Et2O. The solution was
concentrated in vacuo to afford 1.1 g (100%) of methyl
5-hydroxy-[2,2-2H2]pentanoate as a colorless oil: IR (film)
3408,1737 cm-1; 1H NMR (300 MHz, C6D6) 3.38 (br d, J ) 6.0
Hz, 2 H), 3.34 (s, 3 H), 1.59 (t, J ) 6.8 Hz, 2 H), 1.40-1.34 (m,
2 H); 13C NMR (75 MHz, C6D6) 173.8, 62.0, 51.0, 33.2 (pentet),
32.3, 21.4; MS m/e (+CI) 135 (MH+, 100); HRMS (+CI) calcd
for C6H11D2O3 135.0990, found 135.0996.
[6,6-2H2]-2-m eth oxytetr a h yd r op yr a n (45). A 5 mL solu-
tion of methyl 5-formylpentanoate dimethyl acetal22 (0.48 g,
2.8 mmol) in Et2O was cannulated over 10 min into a
suspension of LiAlD4 (0.11 g, 2.7 mmol) in 16 mL of Et2O at 0
°C. After 2 h at 0 °C, the reaction mixture was treated
sequentially with 0.11 mL of H2O, 0.11 mL of 15% NaOH
solution, and 0.33 mL of H2O. After 5 min, the suspension was
allowed to warm to room temperature and stirred for 1 h. The
salts were filtered and washed with five 30 mL portions of
Et2O. The combined organic washings were dried over Na2-
SO4 and concentrated to afford 0.39 g (96%) of [1,1-2H2]-5-
formylpentanol dimethyl acetal as a colorless oil: IR (film)
p-Toluenesulfonic acid monohydrate (14 mg, 0.075 mmol)
was added to methyl 5-hydroxy-[2,2-2H2]-pentanoate(1.0 g, 7.5
mmol) in 75 mL of benzene. After refluxing the solution for
48 h with Dean-Stark removal of water, the reaction mixture
was cooled to room temperature. The organic layer was washed
once with 10 mL of H2O and with two 20 mL portions of brine,
dried over anhydrous Na2SO4, filtered, and concentrated in
vacuo at 0 °C to provide 0.78 g (100%) of 90-95% pure lactone
1
3418 cm-1; H NMR (300 MHz, C6D6) 4.27 (t, J ) 5.7 Hz, 1
H), 3.14 (s, 6 H), 1.62-1.55 (m, 2 H), 1.41-1.32 (m, 4 H); 13C
NMR (75 MHz, C6D6) 104.7, 61.8 (pentet), 52.3, 32.7, 32.6, 21.3;
MS m/e (+APCI/NH4OAc in MeOH) 168 (M + NH4+, 2); HRMS
(+APCI/NH4OAc in MeOH) calcd for C6H9D2O2 (M - H+)
117.0885, found 117.0891.
p-Toluenesulfonic acid monohydrate (5 mg, 0.025 mmol) was
added to [1,1-2H2]-5-formylpentanol dimethyl acetal (0.38 g,
2.5 mmol) in 3 mL of CH2Cl2 at 0 °C. After 17 h, the solution
was concentrated in vacuo to afford 0.24 g (80%) of [6,6-2H2]-
41 as a pale yellow oil: IR (film) 1732 cm-1
;
1H NMR (400
MHz, C6D6) 3.56 (t, J ) 5.8 Hz, 2 H), 0.98-0.88 (dm, 4 H); 13
C
NMR (100 MHz, C6D6)169.7, 68.3, 29.2 (t), 22.1, 18.7. GCMS
102 (M+, 73); HRMS (+APCI) calcd for C5H7D2O2 (MH+)
103.0726, found 103.0721.
1
2-methoxytetrahydropyran (45) as a colorless oil. H NMR
(300 MHz, CDCl3) 4.44 (t, J ) 3.0 Hz, 1 H), 3.27 (s, 3 H), 1.80-
1.52 (m, 6 H); 13C NMR (75 MHz, CDCl3) 99.7, 55.0, 30.5
superimposed on 30.4 (t), 25.2, 19.3; MS m/e (+CI) 117 (M-
H+, 18); HRMS (+APCI/NH4OAc in MeOH) calcd for C6H9D2O2
(M - H+) 117.0885, found 117.0891.
[3,3-2H2]-2-([4-2H]-Bu t-3-yn yloxy)tetr a h yd r op yr a n (42).
A 1.0 M solution of DIBAL-H in hexane (6.7 mL, 6.7 mmol)
was added dropwise over 1 h to [2,2-2H2]-δ-valerolactone (41)
(0.71 g, 7.0 mmol) in 5 mL of THF at -42 °C. The reaction
mixture was warmed to -20 °C and was stirred there for 1 h.
MeOD (0.54 mL, 13.4 mmol) was added, and the cloudy
solution was warmed to room temperature. The suspension
was cooled to 0 °C and filtered, and the salts were washed
with five 20 mL portions of Et2O. The combined organic washes
were concentrated in vacuo at 0 °C to afford 0.16 g (22%) of
crude [3,3-2H2]-2-hydroxy-tetrahydropyran as a colorless oil:
CIMS m/e 103 (M - H+, 26).
2-Bu t-3-yn yloxy-[6,6-2H2]-tetr a h yd r op yr a n (46). But-3-
ynol (0.29 mL, 3.8 mmol) and p-toluenesulfonic acid monohy-
drate (3.6 mg, 0.019 mmol) were added to [6,6-2H2]-2-
methoxytetrahydropyran (45) (0.22 g, 1.9 mmol) in 6 mL of
CH2Cl2. After 19 h, the reaction mixture was treated with 5
mL of saturated sodium bicarbonate solution and diluted with
50 mL of Et2O. The phases were separated, and the organic
layer was washed with 10 mL of H2O and brine, dried over
anhydrous Na2SO4, filtered, and concentrated in vacuo at 0
°C to provide a yellow oil. Purification of the crude product by
flash chromatography on silica gel eluting with 5% Et2O/
hexanes afforded 0.10 g (34%) of 46 as a colorless oil: IR (film)
MeOD (12 mL) was added to [3,3-2H2]-2-hydroxy-tetrahy-
dropyran (0.15 g, 1.4 mmol). After 2 h, the solvent was distilled
off at atmospheric pressure, and the remaining oil was diluted
with 4 mL of benzene. [4-2H]-But-3-yn-[1-2H]-ol (0.85 mL, 1.1
mmol) and p-toluenesulfonic 2H-acid‚D2O (2 mg, 0.010 mmol)
were added. After 2 h at reflux, the solution was cooled to room
temperature. The reaction mixture was treated with 5 mL of
saturated sodium bicarbonate solution and diluted with 50 mL
of Et2O. The phases were separated, and the organic layer was
washed with 10 mL of brine, dried over anhydrous Na2SO4,
filtered, and concentrated in vacuo at 0 °C to afford a pale
yellow oil. Purification of the crude product by flash chroma-
tography on silica gel eluting with 5% Et2O/hexanes afforded
1
3294, 2122 cm-1; H NMR (300 MHz, C6D6) 4.51 (t, J ) 3.4
Hz, 1 H), 3.78 (dt, J ) 9.4, 7.2 Hz, 1 H), 3.39 (dt, J ) 9.4, 6.8
Hz, 1 H), 2.30 (td, J ) 7.2, 2.6 Hz, 2 H), 1.74 (t, J ) 2.6 Hz, 1
H) superimposed on 1.78-1.64 (m, 1 H), 1.59-1.45 (m, 2 H),
1.37-1.16 (m, 3 H); 13C NMR (75 MHz, C6D6) 98.4, 81.7, 69.6,
65.6, 60.7 (t), 30.8, 25.6, 20.3, 19.3.
Tr ib u t yl[4-([6,6-2H 2]-t et r a h yd r op yr a n -2-yloxy)b u t -1-
yn yl]sta n n a n e (47). Using General Procedure A, the dideu-
terated but-3-ynyl ether 46 (90 mg, 0.58 mmol) was converted
to 180 mg of alkynylstannane 47 (69%) following purification
of the crude product with 5% Et2O/hexanes: IR (film) 2153
cm-1; 1H NMR (360 MHz, C6D6) 4.59 (t, J ) 3.2 Hz, 1 H), 3.39
(dt, J ) 9.1, 7.3 Hz, 1 H), 3.56 (dt, J ) 9.6, 6.8 Hz, 1 H), 2.58
(t, J ) 6.8 Hz, 2 H), 1.77-1.52 (m, 9 H), 1.43-1.21 (m, 9 H),
1
0.11 g (64%) of 42 as a colorless oil: IR (film) 2590 cm-1; H
NMR (360 MHz, C6D6) 4.50 (s, 1 H), 3.82-3.71 (m, 2 H), 3.43-
3.30 (m, 2 H), 2.30 (t, J ) 6.8 Hz, 2 H), 1.75-1.68 (m, 1 H),
1.40-1.17 (dm, 3 H); 13C NMR (90 MHz, C6D6) 98.4, 81.3, 69.3
(21) Bo¨rjesson, L.; Cso¨regh, I.; Welch, C. J . J . Org. Chem. 1995, 60,
2989.
(22) Hazen, J . R. J . Org. Chem. 1970, 35, 973.

8668 J . Org. Chem., Vol. 65, No. 25, 2000
Feldman and Wrobleski
1.02 (t, J ) 8.2 Hz, 6 H), 0.92 (t, J ) 7.3 Hz, 9 H); 13C NMR
(90 MHz, C6D6) 108.9, 98.4, 82.8, 66.4, 60.7 (pentet), 30.9, 29.4
(J C-Sn119 ) 11.7 Hz), 27.4 (J C-Sn119 ) 29.6 Hz), 25.7, 22.2, 19.3,
13.9, 11.2 (J C-Sn119 ) 192.1 Hz, J C-Sn117 ) 183.1 Hz).
hexanes and 45% Et2O/hexanes. Chemical ionization mass
spectroscopy indicated no crossover as discussed in the text.
Cycliza tion of Tr ibu tyl[4-([6,6-2H2]-tetr a h yd r op yr a n -
2-yloxy)bu t-1-yn yl]sta n n a n e (47). Using General Procedure
B, the dideuterated alkynylstannane 47 (91 mg, 0.20 mmol)
was converted into 44 mg of [6,6-2H2]-2-[3-(toluene-4-sulfonyl)-
4,5-dihydrofuran-2-yl]-tetrahydropyran 26-d 2 (42%) as a white
solid following chromatographic purification with a solvent
gradient of 20% EtOAc/hexanes, 25% EtOAc/hexanes, and 30%
EtOAc/hexanes: IR (film) 1634 cm-1; 1H NMR (300 MHz, C6D6)
7.97 (d, J ) 8.1 Hz, 2 H), 6.80 (d, J ) 8.1 Hz, 2 H), 5.54 (dd,
J ) 11.1, 2.3 Hz, 1 H), 3.64-3.51 (m, 2 H), 2.56 (dt, J ) 11.1,
2.5 Hz, 1 H), 2.27 (dt, J ) 11.4, 3.3 Hz, 1 H), 1.88 (s, 3 H)
superimposed on 1.88-1.78 (m, 1 H), 1.68-1.64 (m, 1 H),
1.58-1.33 (m, 1 H), 1.39-1.33 (m, 3 H); 13C NMR (75 MHz,
C6D6)166.7, 143.2, 140.2, 129.9, 111.0, 71.3, 69.9, 68.0 (t), 30.6,
29.0, 25.6, 23.2, 21.1. One aromatic carbon at 127.1 is buried
under the benzene signals; MS m/e (+CI) 311 (MH+, 100);
HRMS (+CI) calcd for C16H19D2O4S (MH+) 311.1286, found
311.1288. In addition, 9 mg (20%) of the byproduct 22 with no
deuterium incorporation into the 2-position was isolated.
Cycliza tion of Tr ibu tyl[[3,3-2H2]-4-(tetr a h yd r op yr a n -
2-yloxy)-bu t-1-yn yl]sta n n a n e (49). Using General Proce-
dure B, the dideuterated alkynylstannane 49 (0.10 g, 0.22
mmol) was converted into 26 mg of dihydrofuran 26-d 2 (40%)
as a white solid following chromatographic purification with
a solvent gradient of 25% EtOAc/hexanes, 30% EtOAc/hexanes,
Tr ibu t yl[[3,3-2H 2]-4-(t et r a h yd r op yr a n -2-yloxy)-b u t -1-
yn yl]sta n n a n e (49). Pyridine (3.7 mL, 45.5 mmol) and
p-toluenesulfonyl chloride (3.2 g, 16.9 mmol) were added to
the monotetrahydropyranyl ether of [1,1-2H2]-ethylene glycol18c
(2.0 g, 13.0 mmol) in 13 mL of CH2Cl2. After 12 h, the reaction
mixture was treated with 10 mL of saturated sodium bicar-
bonate solution and diluted with 50 mL of Et2O. The phases
were separated, and the organic layer was washed with 10
mL of H2O and brine, dried over anhydrous Na2SO4, filtered,
and concentrated in vacuo at 0 °C to provide a yellow oil.
Purification of the crude product by flash chromatography on
silica gel eluting with a gradient of 10% Et2O/hexanes to 25%
Et2O/hexanes afforded 3.2 g (82%) of 2-(tetrahydropyran-2-
yloxy)-[1,1-2H2]-ethyl tosylate as a colorless oil: IR (film) 1598
cm-1; 1H NMR (360 MHz, C6D6) 7.75 (d, J ) 8.2 Hz, 2 H), 6.69
(d, J ) 8.7 Hz, 2 H), 4.36 (t, J ) 3.2 Hz, 1 H), 3.65-3.57 (m,
1 H) superimposed by 3.59 (d, J ) 11.8 Hz, 1 H), 3.29-3.24
(m, 1 H) superimposed by 3.26 (d, J ) 12.3 Hz, 1 H), 1.88 (s,
3 H), 1.63-1.55 (m, 1 H), 1.44-1.40 (m, 2 H), 1.32-1.12 (dm,
3 H); 13C NMR (90 MHz, C6D6)144.1, 134.5, 129.8, 129.7, 98.6,
68.8 (pentet), 64.7, 61.5, 30.5, 25.7, 21.1, 19.2; MS m/e (+CI)
303 (MH+, 100); HRMS (+CI) calcd for C14H19D2O5S (MH+)
303.1235, found 303.1239.
1
and 40% EtOAc/hexanes: IR (film)1631 cm-1; H NMR (360
A 2.5 M solution of n-BuLi in hexane (1.7 mL, 4.2 mmol)
was added to trimethylsilylacetylene (0.60 mL, 4.3 mmol) in
3 mL of THF at -78 °C. After 1 h, the reaction mixture was
warmed to 0 °C, and a 4 mL THF solution of 2-(tetrahydro-
pyran-2-yloxy)-[1,1-2H2]-ethyl tosylate (1.0 g, 3.3 mmol) and 3
mL of anhydrous DMSO were added. The orange solution was
allowed to warm to room temperature and stirred for 12 h.
The reaction mixture was treated with 5 mL of H2O and
diluted with 50 mL of Et2O. The phases were separated and
the aqueous layer was extracted with two 20 mL portions of
Et2O. The combined organic layers were washed with 20 mL
of H2O and brine, dried over anhydrous Na2SO4, filtered, and
concentrated in vacuo to provide 0.46 g of a light yellow oil.
Purification of the crude product by flash chromatography on
silica gel eluting with 8% Et2O/hexanes afforded 0.30 g (39%)
of [4-([3,3-2H2]-tetrahydropyran-2-yloxy)but-1-ynyl]trimethyl-
MHz, C6D6) 7.94 (d, J ) 8.7 Hz, 2 H), 6.81 (d, J ) 7.8 Hz, 2
H), 5.54 (dd, J ) 11.4, 2.3 Hz, 1 H), 3.90 (dt, J ) 11.4, 2.3 Hz,
1 H), 3.61 (d, J ) 9.1 Hz, 1 H), 3.54 (d, J ) 9.1 Hz, 1 H), 3.42
(dt, J ) 11.4, 2.3 Hz, 1 H), 1.89 (s, 3 H), 1.88-1.78 (m, 1 H),
1.72-1.52 (m, 2 H), 1.48-1.23 (m, 2 H), 1.09-1.06 (m, 1 H);
13C NMR (90 MHz, C6D6)166.7, 143.0, 140.2, 129.8, 110.9, 71.4,
69.8, 68.8, 30.0 (pentet), 29.0, 25.9, 23.3, 21.1. One aromatic
carbon at 127.1 is buried under the benzene signals; MS m/e
(+CI) 311 (MH+, 100); HRMS (+CI) calcd for C16H19D2O4S
(MH+) 311.1286, found 311.1285. In addition, 10 mg (20%) the
byproduct 22 with no deuterium incorporation into the 2-posi-
tion was isolated.
Cycliza tion of Tr ibu tyl[4-([3,3-2H2]-tetr a h yd r op yr a n -
2-yloxy)bu t-1-yn yl]sta n n a n e (43). Using General Procedure
B, the dideuterated alkynylstannane 43 (0.12 g, 0.27 mmol)
was converted into 35 mg of dihydrofuran 26-d 2 (42%) as a
white solid following chromatographic purification with a
solvent gradient of 25% EtOAc/hexanes, 30% EtOAc/hexanes,
silane as a colorless oil: IR (film) 2176 cm-1 1H NMR (360
:
MHz, C6D6) 4.54 (t, J ) 3.2 Hz, 1 H), 3.82(d, J ) 10.0 Hz, 1
H), 3.78-3.75 (m, 1 H), 3.45 (d, J ) 9.6 Hz, 1 H), 3.35 (ddt, J
) 10.9, 4.1, 1.4 Hz, 1 H), 1.79-1.69 (m, 1 H), 1.59-1.46 (m, 2
H), 1.40-1.19 (m, 3 H), 0.19 (s, 9 H); 13C NMR (90 MHz, C6D6)
104.7, 98.2, 85.4, 65.3, 61.2, 30.6, 25.6, 21.0 (t), 19.1, -0.22;
MS m/e (+CI) 229 (MH+, 100); HRMS (+CI) calcd for
1
and 40% EtOAc/hexanes: IR (film) 1633 cm-1; H NMR (300
MHz, C6D6) 7.94 (d, J ) 8.3 Hz, 2 H), 6.83 (d, J ) 7.9 Hz, 2
H), 5.42 (s, 1 H), 3.90 (d, J ) 11.3 Hz, 1 H), 3.69-3.52 (m, 2
H), 3.42 (t, J ) 9.0 Hz, 1 H), 2.64-2.53 (m, 1 H), 2.34-2.23
(m, 1 H), 1.90 (s, 3 H) superimposed on 1.90-1.81 (m, 1 H),
1.64-1.35 (m, 2 H), 1.08 (br d, J ) 11.7 Hz, 1 H); 13C NMR
(75 MHz, C6D6) 166.6, 143.3, 140.2, 129.8, 111.0, 71.2, 69.9,
68.7, 30.6, 28.5 (pentet), 25.8, 23.0, 21.1. One aromatic carbon
at 127.1 is buried under the benzene signals; MS m/e (+CI)
311 (MH+, 100); HRMS (+CI) calcd for C16H19D2O4S (MH+)
311.1286, found 311.1279.
C
12H21D2O2Si (MH+) 229.1593, found 229.1589.
Bis(tributyltin)oxide (0.50 mL, 0.97 mmol) and a 1.0 M
solution of tetrabutylammonium fluoride in THF (14 µL, 0.014
mmol) were added to [4-([3,3-2H2]-tetrahydropyran-2-yloxy)-
but-1-ynyl]trimethylsilane (0.21 g, 0.92 mmol) in 11 mL of
THF. The reaction mixture was refluxed for 3 h and then
cooled to room temperature. The solution was concentrated
to afford a light yellow oil. Purification of the crude product
by flash chromatography on deactivated silica gel eluting with
5% Et2O/hexanes afforded 0.22 g (54%) of the stannane 49 as
a colorless oil: IR (film) 2153 cm-1; 1H NMR (360 MHz, C6D6)
4.58 (t, J ) 3.6 Hz, 1 H), 3.92(d, J ) 9.6 Hz, 1 H), 3.83-3.76
(m, 1 H), 3.55 (d, J ) 9.6 Hz, 1 H), 3.39-3.33 (m, 1 H), 1.71-
1.52 (m, 7 H), 1.43-1.24 (m, 10 H), 1.03-0.94 (m, 16 H); 13C
NMR (100 MHz, C6D6)108.8, 98.4, 82.8, 66.3, 61.4, 30.8, 29.3
(J C-Sn119 ) 10.7 Hz), 27.4 (J C-Sn119 ) 29.1 Hz), 25.9, 21.6
(pentet), 19.4, 13.9, 11.2 (J C-Sn119 ) 192.5 Hz, J C-Sn117 ) 184.0
Hz); MS m/e (+CI) 447 (Sn120) (MH+, 100); HRMS (+CI) calcd
for C21H37D2O2Sn120 (M - H+) 445.2098, found 445.2101.
Cr ossover Exp er im en t, 32 + 1e. Using General Procedure
B, a mixture of the undeuterated alkynylstannane 20e (78 mg,
0.18 mmol) and the trideuterioalkynylstannane 39 (79 mg, 0.18
mmol) were converted into 44 mg of dihydrofurans 50a and
26 (40%) as a white solid following chromatographic purifica-
tion with the solvent gradient 25% Et2O/hexanes, 35% Et2O/
In addition, 15 mg (25%) of the byproduct 22 with some
deuterium incorporation into the 2-position was isolated: IR
(film)1608 cm-1 1H NMR (360 MHz, C6D6) 7.79 (d, J ) 8.2
;
Hz, 2 H), 6.97 (s, 0.44 H), 6.79 (d, J ) 8.2 Hz, 2 H), 3.62 (t, J
) 10.0 Hz, 2 H), 2.23 (t, J ) 9.1 Hz, 2 H), 1.89 (s, 3 H); 13C
NMR (90 MHz, C6D6)156.2, 143.3, 139.5, 129.8, 118.7 (d), 73.5,
28.2, 21.1. One aromatic carbon at 127.3 is buried under the
benzene signals; MS m/e (+CI) 226 (MH+, 67); HRMS (+CI)
calcd for C11H12DO3S (MH+) 226.0648, found 226.0649.
Ack n ow led gm en t. We thank the National Insti-
tutes of Health (GM37681) for support of this work.
Su p p or tin g In for m a tion Ava ila ble: Copies of 13C NMR
spectra for 19f-h , 20b, 20d -h , 38, 39, 41-43, 45-47, 49,
and the cyclization products from 43, 47, and 49. This material
is available free of charge via the Internet at http://pubs.acs.org.
J O0011080