Exploration of braverman reaction chemistry. Synthesis of tricyclic dihydrothiophene dioxide derivatives from bispropargyl sulfones

Article abstract of DOI:10.3987/COM-09-11840

The base-mediated bicyclization of unsymmetrical bispropargyl sulfones furnishes varying yields of dihydroisobenzothiophene dioxides through a presumed diradical intermediate. Attempts to trap a putative thiophene dioxide intermediate via Diels-Alder reac

Full text of DOI:10.3987/COM-09-11840

HETEROCYCLES, Vol. 81, No. 1, 2010
117
HETEROCYCLES, Vol. 81, No. 1, 2010, pp. 117 - 143. © The Japan Institute of Heterocyclic Chemistry
Received, 24th September, 2009, Accepted, 26th October, 2009, Published online, 28th October, 2009
DOI: 10.3987/COM-09-11840
EXPLORATION OF BRAVERMAN REACTION CHEMISTRY.
SYNTHESIS OF TRICYCLIC DIHYDROTHIOPHENE DIOXIDE
DERIVATIVES FROM BISPROPARGYL SULFONES
Ken S. Feldman* and Brandon R. Selfridge
Chemistry Department, The Pennsylvania State University, University Park,
Pennsylvania 16802 USA
ksf@chem.psu.edu
Abstract – The base-mediated bicyclization of unsymmetrical bispropargyl
sulfones furnishes varying yields of dihydroisobenzothiophene dioxides through a
presumed diradical intermediate. Attempts to trap a putative thiophene dioxide
intermediate via Diels-Alder reaction with a pendant alkyne were not successful.
INTRODUCTION
The spontaneous thermal cyclization of bisallenyl sulfones to furnish thiophene dioxide derivatives was
first reported by Braverman in 1974.1 Subsequent studies revealed that this transformation likely
proceeds through a diyl intermediateꢀfollowed by several tautomerizations, 4 ꢀ 5 ꢀ 6 ꢀ 7 ꢀ 8 (Scheme
1), rather than an intramolecular Diels-Alder reaction of either a bis(3-aryl)allenyl sulfone (i.e., 4 ꢀ 6
directly) or a related allenyl, propargyl sulfone.2-4 The key to successful development of this
transformation involved identifying mild methods to access the reactive bisallenyl sulfone, and in
2000/2001 Braverman described a facile procedure based upon simple treatment of the propargyl alcohol
1 with SCl2; a series of [2,3]-sigmatropic shifts then delivers the bisallenyl sulfone 4.2,3 In addition, a
base-mediated alternative process that begins with bispropargylic sulfone 9 was introduced in this work, 9
ꢀ 8. The reported yield for this latter process approached quantitative, although there was no report of
a yield or description of an experimental procedure for the 1 ꢀ 8 reaction.3 The formation of a
thiophene dioxide such as 7, whether transiently or as an isolable intermediate,1,4 raised the possibility of
linking the Braverman chemistry with the rich Diels-Alder chemistry of thiophene dioxides5-8 in a
multi-step transformation that could forge several new rings from simple precursors. Thus, tethering a
dienophile trap to a nascent thiophene dioxide emerging from the Braverman chemistry might test the
hypothesis that intramolecular Diels-Alder cycloaddition might compete with proton transfer within an
intermediate like 7 and ultimately deliver a pentacyclic product. Probing this hypothesis first would

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HETEROCYCLES, Vol. 81, No. 1, 2010
require the development of Braverman chemistry with an unsymmetrical bisallenyl sulfone, a type of
substrate heretofore unexamined, in order to introduce both the dienophile and the thiophene dioxide into
the same molecule. Our preliminary attempts to access such substrates and execute an unsymmetrical
Braverman reaction, as well as a test of the premise that the intermediate thiophene dioxide can be
trapped by a pendant dienophile, are described below.
Ph
Ph
Ph
H
[2,3]
Ph
•
•
[2,3]
SCl2
O
H
H
O
–O S
H
S
+
O
S
OH
•
X
Ph
3
X
pyridine
1
2
4
a X = Cl or
b X = O–C(Ph)CꢀCH
1
pyridine
•
O2S
O2S
O2S
O2S
•
H
5
Ph
7
8
Ph
no yield reported
6
Ph
Ph
Ph
DBU
O
[4]
8
~ 100% Braverman3
44% this work
S
O
Ph
9
Scheme 1. Braverman's early contributions.2,3
RESULTS AND DISCUSSION
Our initial attempts to reproduce the Braverman chemistry with propargyl alcohol 1 led to mixed results.
The base-mediated cyclization of the bispropargylic sulfone 9 to furnish tricycle 8 proceeded in moderate
yield (44%) in our hands (Scheme 1). However, the more intriguing process starting from two
equivalents of the propargyl alcohol 1 and SCl2 could not be brought to a satisfying endpoint. After
much exploration of temperatures, solvents, reagent concentrations, etc., we were able to achieve no
better than a 9% yield of the same tricycle 8 that was formed from the DBU-mediated isomerization of 9.
Under alternative conditions where the SCl2 is metered into the reaction slowly so as to ensure that its
concentration is never high, the reaction takes a different course and delivers the symmetrical ether 10 as
the only identifiable product. Presumably this ether results from simple SN2-like substitution of X (X =
SCl or SOR) within an intermediate ꢀCꢁC–CH(X)Ph. This disappointing turn of events served to focus
our attention on the bispropargyl sulfone route.

HETEROCYCLES, Vol. 81, No. 1, 2010
119
Ph
O
conc. SCl2
H
H
Ph
dil. SCl2
H
O2S
Et2O, -78 oC
pyridine
9%
Et2O, -78 oC
pyridine
23%
OH
Ph
10
1
Ph
8
Scheme 2. Attempts to reproduce Braverman chemistry.
SYNTHESIS OF BISPROPARGYL SULFONE SUBSTRATES
The unsymmetrically substituted bispropargyl sulfone substrates 15a-15e were prepared by convergent
coupling of the 1,8-nonadiynylmercaptans 13a and 13b with the propargyl bromides 14a-14d to furnish a
thioether product, which was immediately oxidized to the requisite sulfone, Scheme 3. The inaugural
substrate chosen for study was the bispropargylic sulfone 15a. An alternative convergent coupling plan
utilizing the mercaptan equivalent of 14a and the bromide analogue of 13a did not provide any sulfide
product. The mercaptan of 13a was introduced via tosylation of the alcohol 12a followed by SN2
displacement of the derived tosylate with thioacetic acid and then reductive removal of the acetate
fragment (sequence A). In subsequent substrate syntheses, a route employing Mitsunobu chemistry for
direct displacement of the alcohol in 12b with thioacetic acid gave superior yields (sequence B).
The propargyl bromides 14b-14d were assembled from the corresponding aryl bromides or iodides 16a,
16b, and 16d, respectively. The conversion of the aryl propargyl alcohol derived by Sonogashira coupling
of 16a into the corresponding bromide 14b was particularly challenging and accounts for the low yield
for this sequence; it appeared that the lability of the bromide 14b during workup/purification is the likely
culprit. The bismethoxymethyl ether bromide 16c combined with propargyl alcohol under standard
Sonogashira conditions to provide the arylated propargyl alcohol in poor yield, and so recourse was made
to the corresponding iodide 16d, prepared by metalation of 16c followed by I2 quench of the intermediate
lithiate.
The cyclization substrates 15a-15e all were obtained as spectroscopically pure light yellow oils that
displayed no tendency to decompose upon storage at room temperature. No partial isomerization of a
propargyl moiety into an allene unit was observed. Characteristic 1H NMR signals at ꢀ 4.2–4.6 indicate
the presence of propargylic sulfone substructures, and the geminal coupling of the diastereotopic
methylene protons (J ~ 17 Hz) confirms this assignment.

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HETEROCYCLES, Vol. 81, No. 1, 2010
SH
OH
A) i) TsCl, Et3N
ii) MeC(O)SH, CsF
iii) LiAlH4
R
OHC
R
A) HCꢀCMgBr
or
+
or
B) TBSCꢀCLi
H
H
H
B) i) MeC(O)SH,
Ph3P, DIAD
ii) K2CO3, MeOH
12a R = H
12b R = TBS
58%
60%
13a R = H
13b R = TBS
33%
60%
A
B
11
H
R1
A) K2CO3
or
R2
B) LiNTMS2
or
R
R3
mCPBA
SO2
Br
C) NaH
R3
15a R = R1 = R2 = H , R3 = OMe
A 37%
14a R1 = R2 = H , R3 = OMe
14b R1 = H, R2 = R3 = OMe
14c R2 = H, R1 = R3 = OMe
14d R2 = H, R1 = R3 = OMOM
15b R =TBS, R1 = R2 = H , R3 = OMe
15c R = TBS, R1 = H, R2 = R3 = OMe
15d R = TBS, R2 = H, R1 = R3 = OMe
15e R = TBS, R2 = H, R1 = R3 = OMOM
B 44%
C 68%
C 47%
B 41%
R1
R2
R1
1) HCꢀCCH2OH
cat. Pd(PPh3)4
pyrrolidine
R2
R1
R2
Br
2) A) PPh3, Br2
or
B) MsCl; Bu4NF
R3
X
R3
16a R1 = H, R2 = R3 = OMe, X = I
16b R2 = H, R1 = R3 = OMe, X = Br
16c R2 = H, R1 = R3 = OMOM, X = Br
16d R2 = H, R1 = R3 = OMOM, X = I
A 23% 14b R1 = H, R2 = R3 = OMe
A 42%
B 45%
14c R2 = H, R1 = R3 = OMe
14d R2 = H, R1 = R3 = OMOM
n-BuLi
I2 97%
Scheme 3. Synthesis of bispropargyl sulfone substrates.
BASE-MEDIATED BICYCLIZATION OF THE BISPROPARGYL SULFONE SUBSTRATES
The base promoted bicyclizations (Braverman reaction) of the bispropargyl sulfones prepared as
illustrated in Scheme 3 were explored next. The simple methoxyphenyl-bearing substrate 15a was
chosen to probe the influence of different bases and solvents on the efficiency of the reaction. The
pendant alkyne was introduced to assess the possibility that the putative intermediate thiophene dioxide
(cf. 7, Scheme 1) could be intercepted in an IMDA reaction prior to its isomerization into the naphthalene
product (cf. 7 ꢀ 8, Scheme 1).
Scheme 4. Cyclization of bispropargyl sulfone 15a.

HETEROCYCLES, Vol. 81, No. 1, 2010
121
Table 1. Optimizing the yield of 17 formation from bicyclization of 15a.
entry
base
solvent temperature yield
(oC)
17 (%)
1
2
3
4
5
6
7
8
9
10
t-BuOK THF
t-BuOK THF
rt
---a
110
---a
---a
---a
t-BuOK t-BuOH rt
t-BuOK toluene 105
DBU
DBU
CHCl3
THF
0
88
0
13
7
DMAP THF
rt
rt
Et3N
Et3N
none
CHCl3
~100
~100
50
toluene 110
DMF
110
aIn all cases, complex mixtures resulted from which no characterizable compounds could be isolated.
No evidence for allene-containing material was detected in the crude product mixtures.
Exposure of bispropargyl sulfone 15a to a range of bases in a variety of solvents helped delineate the
optimum conditions for product formation (Table 1). It is evident that several distinct sets of reaction
conditions successfully produced the tricyclic product 17, whose structure was suggested by key spectral
data (H @ ꢀ8.19; triplet for methine proton next to sulfur) and later confirmed by single crystal X-ray
analysis.10 Essentially quantitative yield of 17 could be achieved when the relatively mild base
triethylamine was used in either CHCl3 or toluene. The temperature of the reaction medium did not
seem to be a critical parameter, at least within the range 25 oC to 110 oC; both temperature extremes led to
the same high yield of tricyclic product. However, no set of reaction conditions could be identified
where the presumptive thiophene dioxide intermediate could be trapped in a Diels-Alder cycloaddition
with the tethered alkyne. In all cases, even when exogenous base was omitted (Table 1, entry 10),
Diels-Alder cycloaddition was not competitive with the tautomerizations from a presumed thiophene
dioxide/dihydronaphthalene intermediate to the observed naphthalene/dihydrothiophene dioxide product
17.
One approach that might circumvent the tautomerization leading to the naphthalene-containing product is
to force an otherwise labile methylene proton into the plane of the ꢁ-system in order to suppress
deprotonation. Scheme 5 describes the Braverman cyclization chemistry of one such substrate, 15b.
Subjection of this silylated bispropargyl sulfone to the optimized conditions from Table 1 led to a good
yield of tricyclic material. Thus, at the very least, the terminal silyl group did not complicate the

122
HETEROCYCLES, Vol. 81, No. 1, 2010
Braverman cascade sequence. Furthermore, the formation of a partially unisomerized product 19 was in
line with the expectations of the tautomerization suppression hypothesis; reaction through an unobserved
intermediate thiophene dioxide 18 will engender A1,3-type interactions between the alkyl tether and the
pseudoequatorial substituent at the benzylic position. This interaction should be less sterically
penalizing when the equatorial substituent is a proton, but in that arrangement, poor overlap between the
C–H bond and the ꢀ-system is likely to suppress deprotonation. However, once again, the putative
thiophene dioxide intermediate was not long-lived enough to participate in an IMDA reaction with the
attached alkyne; isomerization of the other alkene apparently was just too fast.
H
H
TBS
MeO
TBS
Et3N
O2S
SO2
SO2
toluene
reflux
H
Sit-BuMe2
H
64%
A1,3
OMe
OMe
15b
18
19
Scheme 5. Base-mediated cyclization of a bispropargyl sulfone bearing an o-methoxyphenyl ring and a
TBS group; formation of a dihydronaphthalene product.
One workaround to this olefin positioning issue might involve raising the oxidation level of a tricyclic
species like 19 to generate, at least in situ, an orthonaphthoquinonedimethane-thiophene dioxide species
(cf. 24, Scheme 8). Two distinct approaches to accomplish the introduction of another oxidized
substituent into the bispropargyl sulfone cyclization precursor were explored. One manifestation of this
plan is illustrated in Scheme 6, where an additional ortho-OMe group serves as this sacrificial oxidation
level marker. The idea behind this substrate choice derived from the expectation that an intermediate
such as 20 might eliminate the elements of either MeOH or MeOTBS to furnish the extended
orthonaphthoquinonedimethane system, a potentially very reactive Diels-Alder partner for the alkyne.
However, in one of the more surprising twists of this research, attempted Braverman cyclization of the
o,o’-blocked substrate 15c furnished a low yield of the familiar tricycle 19! Clearly, a formal reduction
has occurred, but the source of the reducing agent and the mechanism by which putative intermediate 20
is processed further into 19 remains mysterious.
H
TBS
TBS
MeO
TBS
Et3N
?
OMe
SO2
SO2
SO2
toluene reflux
H
H
OMe
OMe
OMe
?
28%
20
19
15c
Scheme 6. Base-mediated cyclization of a bispropargyl sulfone bearing an o,o'-dimethoxyphenyl ring and
a TBS group; formation of the dihydronaphthalene product 19 again.

HETEROCYCLES, Vol. 81, No. 1, 2010
123
A second attempt to implement the same strategy for oxidation level elevation followed with the
protected hydroquinone-containing substrates 15d and 15e, Scheme 7. In these instances, the
introduction of a higher oxidation level (= orthonaphthoquinonedimethane-thiophene dioxide) was
planned for post-cyclization chemistry, given the surprising course of the Braverman reaction with 15c.
These species participated in triethylamine-mediated cyclization without event and furnished the expected
dihydro tricycles 21 and 22, respectively, by analogy with the cyclization of 15b into 19.
H
RO
TBS
RO TBS
Et3N
SO2
SO2
H
OR
toluene reflux
benzene reflux
15d R = Me
15e R = MOM
46%
45%
21 R = Me
22 R = MOM
OR
Scheme 7. Base-mediated cyclization of a bispropargyl sulfone bearing either an o,m-dimethoxyphenyl
ring or an o,m-dimethoxymethyeneoxyphenyl ring and a TBS group.
ATTEMPTS TO FORCE THIOPHENE DIOXIDE FORMATION/INTRAMOLECULAR
DIELS-ALDER CYCLOADDITION
There are some precedents for the formation of orthoquinonedimethane intermediates from either
photochemically
or
thermolytically
induced
chelatotropic
extrusion
of
SO2
from
dihydroisobenzothiophene dioxides,11,12 and so heating the sulfone 17 over the temperature range 180 –
o
340 C, as well as irradiation (254 - 300 nm, room temperature), were explored in an attempt to force
Diels-Alder cycloaddition of the terminal alkyne (Scheme 8). However, in no instance was anything
other than returned starting material or uncharacterizable decomposition products observed. For the
o
naphthalene system 17, decomposition began at ~ 240 C, and irradiated returned only starting material.
Oxidation of naphthalene 17 gave the paraquinone 23, a species that, in principle, offered two different
approaches to generating a reactive intermediate (orthonaphthoquinonedimethane or thiophene dioxide)
for Diels-Alder cycloaddition. Unfortunately, neither thermolysis nor photolysis of 23 led to anything
o
characterizable. Decomposition set in at ~ 270 C, whereas irradiation at 350 nm also destroyed the
compound. Furthermore, treatment of 23 with a variety of bases (i.e., pyridine, Et3N, i-Pr2NEt, pyridine,
DBU, KOt-Bu, and i-Pr2NLi) with the intent of effecting an internal redox reaction via proton
tautomerization (= formal oxidation of the dihydrothiophene ring to a thiophene dioxide with concomitant
reduction of the paraquinone to the hydroquinone or hydroquinone dianion) did not provide any reason to
be optimistic. Thus, in the final analysis, the innate thermodynamic preference13 that favors a
naphthalene/dihydrothiophene dioxide structure rather than the dihydronaphthalene/thiophene dioxide

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HETEROCYCLES, Vol. 81, No. 1, 2010
tautomer dominated the chemistry of this system, and no Diels-Alder-capable intermediates with
sufficient lifetime to engage in cycloaddition could be accessed.
O
OH
OH
base
??
Jones
reagent
60%
SO2
SO2
SO2
H
H
H
OMe
O
23
17
24
180 - 340 oC
180 - 340 oC
no reaction or
decomposition
or hv (254, 300 nm)
or hv (350 nm)
Scheme 8. Attempts to access orthonaphthoquinonedimethane-type intermediates from tricyclic
naphthalene 17.
The acquisition of the non-naphthalenic tricycle 19 from Braverman cyclization of the TBS-substituted
bispropargyl sulfone 15b offered the possibility of further manipulation into a thiophene dioxide
intermediate without the burden of overcoming the naphthalene moiety's aromatic resonance energy.
This strategy for generating the thiophene dioxide moiety from 19 involved oxidation to the
aforementioned orthonaphthoquinonedimethane-thiophene dioxide construct, cf. 24. Efforts towards
that end included treating 19 with epoxidizing reagents (H2O2/base, mCPBA, CF3CO3H), but only
unconsumed starting material resulted. Direct, benzylic-type oxidation (CrO3, KMnO4, SeO2, DDQ) was
no more promising, affording either unreacted 19 or decomposition products. Deprotonation of an
acidic proton ꢀ- to the sulfonyl moiety did afford a tractable anion, and trapping of that anion with Ph2S2
produced the ꢀ-sulfide 25a in moderate yield. The corresponding sulfoxide 25b and sulfone 25c also
were available from the sulfide. Treatment of the ꢀ-sulfonyl anion with other electrophiles (Br2, CN-Br,
BrCCl3, TsCl) did not afford any of the oxidized product. Exposure of the sulfide 25a to a fluoride
source did not promote the intended elimination of TBS-SPh, and only the naphthalene-containing
product 26 resulted. A similar attempt with the sulfone 25c led only to decomposition of the starting
material without formation of any isolable product. Attempts to effect [2,3]-sigmatropic rearrangement
of the allylic sulfoxide within 25b might have generated a transient thiophene dioxide product, but only
the formal direct displacement product, alcohol 27, was formed. The mechanism of this transformation
remains a matter of speculation. Once again, our attempts to access a thiophene dioxide intermediate
were thwarted.

HETEROCYCLES, Vol. 81, No. 1, 2010
125
TBS
TBS
n-BuLi;
1 equiv.
mCPBA
48%
2 equiv.
mCPBA
59%
25a X = 0
25b X = 1
25c X = 2
Ph2S2
SO2
SO2
H
H
65%
SOXPh
OMe
OMe
19
TBS
Bu4NF
0 oC
Et2NH
25a
25b
SO2
SPh
SO2
OH
H
toluene
110 oC
28%
H
OMe
OMe
86%
26
27
Scheme 9. Attempts to isomerize or oxidize 19 to furnish a thiophene dioxide intermediate.
The final attempts at accessing an IMDA-capable thiophene dioxide intermediate from the Braverman
cyclization tricycles focused on the hydroquinone derivatives 21 and 22, Scheme 10. The objective in
this instance was to convert the hydroquinone ethers to the paraquinone as per 17 ꢀ 23 and in so doing
provide a substrate whose tautomerization to a thiophene dioxide product might not be so unfavorable.
Unlike the fully aromatic system of 23, we hoped that the cross-conjugated diene of such an oxidation
product (cf. 28) might be more prone to isomerization and afford access to the desired
orthonaphthoquinonedimethane-thiophene dioxide 24. Unfortunately, the first substrate examined,
dimethyl ether 21, was not a competent oxidation substrate as it decomposed readily under a variety of
oxidation conditions. Apparently, the diene of 21 confers an unwanted sensitivity to the system that is
not shared by the fully aromatic naphthalene analogue 17.
The bis MOM ether analogue 22 did not suffer from this disadvantage. In this instance, removal of the
MOM protecting groups provided a labile hydroquinone that decomposed upon standing but which could
be oxidized immediately after acquisition to generate the requisite paraquinone containing tricycle 28.
Base-
and/or
fluoride-mediated
isomerization
of
28
into
the
corresponding
orthonaphthoquinonedimethane-thiophene dioxide 24 was attempted next, under the premise that the
normal thermodynamic unfavorability13 (vide supra) might be mitigated somewhat by the gain in aromatic
resonance energy upon concurrent paraquinone ꢀ hydroquinone reduction. However, treating this
substrate with base and/or fluoride led only to uncharacterizable mixtures with no evidence for thiophene
dioxide formation. Thus, in the final analysis, no evidence was forthcoming that supported the notion
that introduction of a strategically placed oxygen function into the aromatic ring of the bispropargyl
sulfone substrates promoted further oxidation of the remaining rings to generate a thiophene
dioxide-containing species.

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HETEROCYCLES, Vol. 81, No. 1, 2010
base
and/or
fluoride
MOMO
TBS
O
O
TBS
HO
TBS
R
R
1) AcCl
MeOH
SO2
SO2
SO2
H
2) PhI(OAc)2
not
observed
OMOM
39%
OH
R = (CH2)4CꢀCH
24
22
28
Scheme 10. Oxidation of the tricyclic Braverman product; attempts to formulate a
orthonaphthoquinonedimethane-thiophene dioxide intermediate.
CONCLUSIONS
In summary, we have successfully prepared a range of unsymmetrical bispropargyl sulfones featuring a
variety of OR (R = Me or MOM) placements on the aryl ring that caps one propargyl unit and either a
proton or a TBS group at the terminus of the other propargyl unit. These species all participated in a
Braverman cyclization cascade to furnish tricyclic products with varying efficiency. Depending upon
the alkyne substituent (H or TBS), the tricyclic product either isomerized to a naphthalene-containing
species (H substituent) or remained as a dihydronaphthalene isomer (TBS substituent). Unfortunately,
all efforts to generate and then utilize a thiophene dioxide tautomer in intramolecular Diels-Alder
cycloaddition with a pendant alkyne were frustrated by competitive isomerizations that consistently
delivered the naphthalene product, presumably a thermodynamic sink. Thus, linking the Braverman
sequence with thiophene dioxide Diels-Alder chemistry was not achieved.
EXPERIMENTAL
GENERAL EXPERIMENTAL
Moisture- and oxygen-sensitive reactions were carried out in flame-dried glassware under an inert
nitrogen atmosphere. Dry ether (Et2O), toluene, acetonitrile (MeCN), dichloromethane (CH2Cl2),
methanol (MeOH), tetrahydrofuran (THF) and dimethylformamide (DMF) were purified by passing these
solvents through activated alumina columns. Reagents were purchased at the highest commercial quality
and used without further purification unless otherwise stated. Reactions were monitored by thin layer
chromatography carried out on 0.25 mm E. Merck silica gel plates (60F-254) with UV visualization and
PMA staining. Purification of products via flash chromatographywas performed with 40-63 m silica gel
and the solvent system indicated. Melting points are uncorrected.
4-Phenyl-1,3-dihydro-naphtho[2,3-c]thiophene 2,2-Dioxide (8). A stirring solution of alkyne 1 (50
mg, 0.39 mmol) in 5 mL of Et2O was treated with pyridine (35 ꢀL, 0.44 mmol). After 1 h, the reaction
mixture was cooled to -78 °C and freshly distilled SCl2 (13 ꢀL, 0.94 mmol) was added dropwise. After
1 h at -78 °C, saturated aqueous NaHCO3 (10 mL) was added. The resulting solution was partitioned

HETEROCYCLES, Vol. 81, No. 1, 2010
127
between Et2O and H2O and the aqueous layer was extracted with Et2O (3 x 10 mL). The combined
organic fractions were dried over Na2SO4, filtered, and concentrated in vacuo to give a light yellow oil.
Purification of this oil by SiO2 flash column chromatography (gradient, 25% Et2O/hexanes ꢀ 50%
Et2O/hexanes as eluent) gave tetracycle 8 (4.9 mg, 9%) as a light yellow oil. Spectral data matched those
reported by Braverman.3
1,1’-(Oxydi-2-propyn-1-ylidene)bis-benzene (10). A stirring solution of alkyne 1 (0.100 g, 0.774
mmol) in 10 mL of Et2O was treated with pyridine (70 ꢀL, 0.87 mmol). After 1 h, the reaction mixture
was cooled to -78 °C and a solution of freshly distilled SCl2 (26 ꢀL, 0.39 mmol) in 330 ꢀL of CH2Cl2 was
added to the reaction solution. After 1 h at -78 °C, saturated aqueous NaHCO3 (10 mL) was added.
The resulting solution was partitioned between Et2O and H2O and the aqueous layer was extracted with
Et2O (3 x 5 mL). The combined organic fractions were dried over Na2SO4, filtered, and concentrated in
vacuo to give a light yellow oil. Purification of this oil by SiO2 flash column chromatography (gradient,
10% Et2O/hexanes ꢀ Et2O as eluent) gave bis-propargylic ether 10 (21.7 mg, 23%) as a colorless oil.
Spectral data matched those reported by Bustelo.14
Nona-1,8-diyne-3-ol (12a). To a stirring solution of hept-6-ynal15 (11) (1.01 g, 9.14 mmol) in 75 mL of
THF at 0 °C was added a solution of ethynylmagnesium bromide in THF (0.5M, 21.9 mL, 11.0 mmol).
The reaction mixture was stirred at 0 °C for 2 h and then saturated NH4Cl (100 mL) was added. The
resulting solution was partitioned between Et2O and H2O and the aqueous layer was extracted with Et2O
(3 x 100 mL). The combined organic fractions were washed with brine (300 mL), dried over Na2SO4,
filtered, and concentrated in vacuo to afford nona-1,8-diyn-3-ol (12a) (0.717 g, 58%) as a colorless oil.
1
A yield of 90% was obtained on a 32 mg scale. IR (thin film) 3950, 3500, 2115 cm-1; H NMR (300
MHz, CDCl3) ꢁ 4.32 (qd, J = 6.1, 2.0 Hz, 1H), 2.49 (br s, 1H), 2.43 (d, J = 2.1 Hz, 1H), 2.19-2.13 (m,
2H), 1.91 (t, J = 2.6, 1H), 1.71-1.64 (m, 2H), 1.57-1.46 (m, 4H); 13C NMR (75 MHz, CDCl3) ꢁ 84.8, 84.2,
72.9, 68.4, 65.8, 61.9, 36.9, 27.9, 24.1, 18.2; GC-MS (EI) m/z (relative intensity) 136.2 (5%, M+).
1-(tert-Butyldimethylsilanyl)nona-1,8-diyne-3-ol (12b). To a stirring solution of TBS acetylene (6.32
g, 44.9 mmol) in 80 mL of THF at 0 °C was added n-BuLi (2.5 M in hexanes, 18 mL, 45 mmol) dropwise.
The reaction mixture was stirred for 10 min at 0 °C and then a solution of hept-6-ynal (4.95 g, 44.9
mmol) in 20 mL of THF was added. The reaction mixture was stirred at room temperature for 2 d, and
then saturated NH4Cl (100 mL) was added. The resulting solution was partitioned between Et2O and
H2O and the aqueous layer was extracted with Et2O (3 x 100 mL). The combined organic fractions were
washed with brine (300 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give a colorless oil.
Purification of this oil by SiO2 flash column chromatography (gradient, 5% Et2O/hexanes ꢀ 10%
Et2O/hexanes as eluent) afforded 1-(tert-butyldimethylsilanyl)nona-1,8-diyn-3-ol (12b) (4.78 g, 43%) as a
1
colorless oil. A yield of 60% was obtained on a 1.41 g scale. IR (thin film) 3400, 3307, 2175 cm-1; H

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HETEROCYCLES, Vol. 81, No. 1, 2010
NMR (360 MHz, CDCl3) ꢀ 4.36 (t, J = 5.1 Hz, 1H), 2.21-2.16 (m, 2H), 1.97 (brs, 1H), 1.93 (t, J = 2.1 Hz,
13
1H), 1.71-1.70 (m, 2H), 1.60-1.54 (m, 4H), 0.92 (s, 9H), 0.09 (s, 6H); C NMR (90 MHz, CDCl3) ꢀ
107.3, 87.7, 84.2, 68.4, 62.6, 37.3, 28.1, 26.0, 24.3, 18.3, 16.4, -4.7; LRMS (ESI) m/z (relative intensity)
251.3 (70%, M + H+).
Nona-1,8-diyne-3-thiol (13a). To a stirring solution of nona-1,8-diyn-3-ol (12a) (0.668 g, 4.88 mmol)
in 1.55 mL at 0 °C was added p-toluenesulfonyl chloride (0.998 g, 5.23 mmol). The reaction mixture
was stirred for 3 h and then H2O (25 mL) was added. The resulting solution was partitioned between Et2O
and H2O and the aqueous layer was extracted with Et2O (3 x 30 mL). The combined organic fractions
were washed with 1M HCl (100 mL) and brine (100 mL), dried over Na2SO4, filtered, and concentrated in
vacuo to give a yellow oil. Purification of the oil by SiO2 flash column chromatography (5 %
EtOAc/hexanes as eluent) gave toluene-4-sulfonic acid 1-ethynyl-hept-6-ynyl ester (0.988 g, 70%) as a
yellow oil. IR (thin film) 3292, 2123 cm-1; 1H NMR (300 MHz, CDCl3) ꢀ 7.76 (dt, J = 8.4, 1.8 Hz, 2H),
7.29 (d, J = 8.3 Hz, 2H), 5.00 (td, J = 6.5, 2.1 Hz, 1H), 2.39 (s, 3H), 2.38 (s, 1H), 2.11 (td, J = 6.6, 2.6
13
Hz, 2H), 1.90 (t, J = 2.6 Hz, 1H), 1.83-1.73 (m, 2H), 1.56-1.40 (m, 4H); C NMR (75 MHz, CDCl3) ꢀ
144.8, 133.5, 129.6, 127.9, 83.7, 79.4, 76.2, 70.7, 68.6, 34.9, 27.4, 23.5, 21.5, 18.0; LRMS (ESI) m/z
(relative intensity) 308.1 (100%, M + NH4+); HRMS (ESI) m/z calcd for [C16H22NO3S]+, 308.1320, found
308.1316.
To a stirring solution of CsF (0.44 g, 2.9 mmol) in 10 mL of DMF was added thioacetic acid (274 ꢁL,
3.89 mmol). The reaction mixture was stirred for 20 min, and then a solution of toluene-4-sulfonic acid
1-ethynyl-hept-6-ynyl ester (0.832 g, 2.87 mmol) in 5 mL of DMF was added. The reaction mixture
was stirred for 20 h at 50 °C and then H2O (10 mL) were added. The resulting solution was partitioned
between Et2O and H2O and the aqueous layer was extracted with Et2O (3 x 30 mL). The combined
organic fractions were sequentially washed with saturated aqueous NaHCO3 (100 mL) and brine (100
mL), dried over Na2SO4, filtered, and concentrated in vacuo to give a crude yellow oil. Purification of the
oil by SiO2 flash column chromatography (10% Et2O/hexanes as eluent) afforded thioacetic acid
1
S-(1-ethynyl-hept-6-ynyl) ester (0.433 g, 78%) as a yellow oil. IR (thin film) 3294, 1695 cm-1; H NMR
(300 MHz, CDCl3) ꢀ 4.22 (td, J = 6.8, 2.5 Hz, 1H), 2.31 (s, 3H), 2.26 (d, J = 2.6 Hz, 1H), 2.20-2.13 (m,
2H), 1.92 (t, J = 2.6 Hz, 1H), 1.77-1.70 (m, 2H), 1.62-1.50 (m, 4H); 13C NMR (75 MHz, CDCl3) ꢀ 193.9,
84.0, 82.2, 71.6, 68.5, 34.9, 33.3, 30.2, 27.7, 26.0, 18.2; GC-MS (EI) m/z (relative intensity) 194.0 (5%,
M+).
To a stirring solution of LiAlH4 (49.1 mg, 1.29 mmol) in 10 mL of Et2O at 0 °C was added a solution of
thioacetic acid S-(1-ethynyl-hept-6-ynyl) ester (346 mg, 1.78 mmol) in 5 mL of Et2O. The reaction
mixture was warmed to room temperature, stirred for 14 h, and poured into ice-cold H2O. The resulting
solution was partitioned between Et2O and H2O and the aqueous layer was extracted with Et2O (3 x 20

HETEROCYCLES, Vol. 81, No. 1, 2010
129
mL). The combined organic fractions were sequentially washed with 1M H3PO4 (60 mL) and then brine
(60 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give a crude yellow oil. Purification of
this oil by passing through a thin pad of SiO2 (33% Et2O/hexanes as eluent) gave thiol 13a (125 mg, 46%)
1
as a yellow oil. A yield of 60% was obtained on a 2.12 g scale. IR (thin film) 3293 cm-1; H NMR
(400 MHz, CDCl3) ꢀ 3.53-3.51 (m, 1H), 3.26 (s, 1H), 2.17-2.14 (m, 3H), 1.93 (d, J = 2.4 Hz, 1H),
13
1.76-1.73 (m, 2H), 1.59-1.49 (m, 4H); C NMR (75 MHz, CDCl3) ꢀ 85.0, 84.0, 71.4, 68.5, 38.5, 28.3,
27.6, 26.1, 18.2; GC-MS (EI) m/z (relative intensity) 152.0 (100%, M+).
1-(tert-Butyldimethylsilanyl)nona-1,8-diyne-3-thiol (13b). To a stirring solution of PPh3 (4.28 g, 19.5
mmol) and 1-(tert-butyldimethylsilanyl)nona-1,8-diyn-3-ol (12b) (4.44 g, 17.7 mmol) in 60 mL of THF
at 0 °C was added DIAD (3.04 mL, 19.5 mmol) dropwise. The reaction mixture was stirred for 10 min
at 0 °C and then treated with thiolacetic acid (1.06 mL, 19.5 mmol). After 2 h at 0 °C, the reaction
mixture was concentrated in vacuo to give a yellow oil. Purification of this oil by SiO2 flash column
chromatography
(10%
Et2O/hexanes
as
eluent)
afforded
thioacetic
acid
S-{1-[(tert-butyldimethylsilanyl)ethynyl]hept-6-ynyl} ester (3.84 g, 70%) as a yellow oil. IR (thin film)
3295, 2150, 1690 cm-1; 1H NMR (300 MHz, CDCl3) ꢀ 4.29 (t, J = 6.8 Hz, 1H), 2.32 (s, 3H), 2.19 (td, J =
6.7, 2.6 Hz, 2H), 1.93 (t, J = 2.7 Hz, 1H), 1.77-1.74 (m, 2H), 1.62-1.56 (m, 4H), 0.91 (s, 9H), 0.09 (s,
13
6H); C NMR (75 MHz, CDCl3) ꢀ 194.1, 104.2, 86.7, 84.1, 68.4, 35.5, 34.4, 30.2, 27.8, 26.0 (2), 18.2,
16.5, -4.7; LRMS (ESI) m/z (relative intensity) 309.2 (100%, M + H+).
To a stirring suspension of K2CO3 (1.89 g, 12.4 mmol) in 130 mL of MeOH was added thioacetic acid
S-{1-[(tert-butyldimethylsilanyl)ethynyl]hept-6-ynyl} ester (3.84 g, 12.4 mmol) in 20 mL of MeOH.
The reaction mixture was stirred for 3 h at room temperature at which time 1M H3PO4 (200 mL) was
added. The resulting solution was partitioned between Et2O and H2O and the aqueous layer was
extracted with Et2O (3 x 200 mL). The combined organic fractions were washed with brine (500 mL),
dried over Na2SO4, filtered, and concentrated in vacuo to give thiol 13b (2.84 g, 86%) as a yellow oil. A
1
yield of 98% was obtained on a 4.91 g scale. IR (thin film) 3295, 2150 cm-1; H NMR (360 MHz,
CDCl3) ꢀ 3.60 (app q, J = 6.5 Hz, 1H), 2.20 (td, J = 6.8, 2.5 Hz, 2H), 2.13 (d, J = 6.5 Hz, 1H), 1.94 (t, J
13
= 2.5 Hz, 1H), 1.79-1.77 (m, 2H), 1.64-1.56 (m, 4H), 0.93 (s, 9H), 0.09 (s, 6H); C NMR (90 MHz,
CDCl3) ꢀ 107.4, 86.0, 84.1, 68.5, 38.9, 29.4, 27.9, 26.1, 26.05, 18.3, 16.6, -4.7; LRMS (ESI) m/z (relative
intensity) 267.2 (30%, M + H+).
1-(3-Bromo-prop-1-ynyl)-2-methoxybenzene (14a). To a stirring solution of 2-iodoanisole (13.9 mL,
107 mmol) in 350 mL of THF was sequentially added propargyl alcohol (21.6 mL, 371 mmol),
Pd(PPh3)2Cl2 (1.09 g, 1.40 mmol), Et3N (40.5 mL, 291 mmol), and CuI (1.08 g, 5.67 mmol). After 14 h,
the reaction mixture was poured into H2O (400 mL). The resulting solution was partitioned between
EtOAc and H2O and the aqueous layer was extracted with EtOAc (3 x 250 mL). The combined organic

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HETEROCYCLES, Vol. 81, No. 1, 2010
fractions were dried over Na2SO4, filtered, and concentrated in vacuo to give a light yellow oil.
Purification of this oil by SiO2 flash column chromatography (50% EtOAc/hexanes as eluent) gave
3-(2-methoxy-phenyl)-prop-2-yn-1-ol (17.3 g, 100%) as a light yellow solid. Spectral data matched those
reported by Franks.16
A stirring solution of PPh3 (28.1 g, 107 mmol) in 350 mL of CH2Cl2 was cooled to 0 ºC and Br2 (5.47 mL,
107 mmol) was added dropwise to the reaction mixture.
A
solution of
3-(2-methoxyphenyl)-prop-2-yn-1-ol (17.3 g, 107 mmol) in 100 mL of CH2Cl2 was added dropwise to the
reaction mixture and solution was stirred for an additional 4 h at 0 ºC. The reaction mixture was
warmed to room temperature and concentrated in vacuo to give a light yellow oil. Purification of the oil
by SiO2 flash column chromatography (10% benzene/hexanes) gave bromide 14a (18.9 g, 79%) as a
colorless oil whose spectral data matched those reported by Dai.9
2-(3-Bromo-prop-1-ynyl)-1,3-dimethoxybenzene
(14b).
To
a
stirring
solution
of
1-iodo-2,6-dimethoxybenzene (15.0 g, 56.8 mmol) in 120 mL of pyrrolidine was added propargyl alcohol
(3.31 mL, 114 mmol) and Pd(PPh3)4 (3.33 g, 2.84 mmol). The reaction mixture was heated at 45 °C for
3 d and then saturated aqueous NH4Cl (120 mL) was added.
The resulting solution was partitioned
between EtOAc and H2O and the aqueous layer was extracted with EtOAc (3 x 10 mL). The combined
organic fractions were dried over Na2SO4, filtered, and concentrated in vacuo to give a yellow oil.
Purification of this oil by SiO2 flash column chromatography (gradient, 12:7:1 Et2O/hexanes/CH2Cl2 ꢀ
8:1:1 Et2O/hexanes/CH2Cl2) afforded 3-(2,6-dimethoxy-phenyl)-prop-2-yn-1-ol (9.39 g, 86%) as a white
1
solid. mp 92-94 °C; IR (thin film) 3378, 2214 cm-1; H NMR (300 MHz, CDCl3) ꢀ 7.20 (t, J = 8.4 Hz,
1H), 6.50 (d, J = 8.4 Hz, 2H), 4.56 (d, J = 5.1 Hz, 2H), 3.84 (s, 6H), 2.26 (t, J = 5.4 Hz, 1H) ; 13C NMR
(90 MHz, CDCl3) ꢀ 161.4, 129.8, 103.3, 100.6, 96.0, 77.6, 55.9, 51.8; LRMS (ESI) m/z (relative
intensity) 193.2 (100%, M + H+); HRMS (ESI) m/z calcd for [C11H13O3]+, 193.0865, found 193.0867.
To a stirring solution of PPh3 (12.8 g, 48.9 mmol) in 125 mL of CH2Cl2 at 0 °C was added Br2 (2.51 mL,
48.9 mmol).
The reaction mixture was held at this temperature for 30 min and then a solution of
3-(2,6-dimethoxy-phenyl)-prop-2-yn-1-ol (9.39 g, 48.9 mmol) in 75 mL CH2Cl2 was added to the reaction
solution. After an additional 2 h at 0 °C the reaction mixture was concentrated in vacuo to give an
off-white solid. Purification of this solid by SiO2 flash column chromatography (gradient, 17:2:1
hexanes/ Et2O/CH2Cl2 ꢀ 3:6:1 hexanes/ Et2O/CH2Cl2) afforded bromide 14b (2.77 g, 23%) as an
off-white solid. A yield of 31% was obtained on a 75 mg scale. mp 90-92 °C; IR (thin film) 2205 cm-1;
1H NMR (300 MHz, CDCl3) ꢀ 7.17 (app t, J = 8.4 Hz, 1H), 6.95 (d, J = 8.4 Hz, 2H), 4.26 (s, 2H), 3.78 (s,
13
6H); C NMR (90 MHz, CDCl3) ꢀ 161.5, 130.2, 103.1, 99.9, 92.1, 79.4, 55.7, 16.2; LRMS (ESI) m/z
(relative intensity) 255.1 (100%, M + H+).

HETEROCYCLES, Vol. 81, No. 1, 2010
131
2-(3-Bromo-prop-1-ynyl)-1,4-dimethoxybenzene
(14c).
To
a
stirring
solution
of
1-bromo-2,5-dimethoxybenzene (17.0 g, 78.1 mmol) in 250 mL of pyrrolidine was added propargyl
alcohol (9.17 mL, 156 mmol) and Pd(PPh3)4 (4.76 g, 3.91 mmol). The reaction mixture was heated at
reflux for 14 h, cooled to room temperature, and then saturated aqueous NH4Cl (120 mL) was added.
The resulting solution was partitioned between EtOAc and H2O and the aqueous layer was extracted with
EtOAc (3 x 10 mL). The combined organic fractions were dried over Na2SO4, filtered, and concentrated
in vacuo to give a yellow oil. Purification of this oil by SiO2 flash column chromatography (gradient,
20% EtOAc/hexanes ꢀ 30% EtOAc/hexanes) afforded 3-(2,5-dimethoxyphenyl)-prop-2-yn-1-ol (6.70 g,
45%) as an orange solid. Spectral data matched those reported by Franks.16
To a stirring solution of PPh3 (8.29 g, 31.6 mmol) in 80 mL of CH2Cl2 at 0 °C was added Br2 (1.63 mL,
31.7 mmol). After 30 min, a solution of 3-(2,5-dimethoxyphenyl)-prop-2-yn-1-ol (6.06 g, 31.5 mmol) in
40 mL CH2Cl2 was added to the reaction mixture. After an additional 5 h, the reaction solution was
concentrated in vacuo to give an off-white solid. Purification of this solid by SiO2 flash column
chromatography (10% EtOAc/hexanes as eluent) afforded bromide 14c (7.47 g, 93%) as an off-white
1
solid. mp 47-48 °C; IR (thin film) 2205 cm-1; H NMR (360 MHz, CDCl3) ꢀ 6.91 (d, J = 2.9 Hz, 1H),
13
6.84-6.73 (m, 2H), 4.18 (s, 2H), 3.78 (s, 3H), 3.72 (s, 3H); C NMR (90 MHz, CDCl3) ꢀ 154.6, 152.9,
118.2, 116.2, 111.8, 111.5, 88.0, 83.0, 56.2, 55.6, 15.6; LRMS (ESI) m/z (relative intensity) 255.1 (80%,
M + H+).
2-(3-Bromoprop-1-ynyl)-1,4-bis-methoxymethoxybenzene (14d). To a stirring suspension of 60%
NaH (2.8 g, 53 mmol) in 100 mL of DMF at 0 °C was added a solution of bromohydroquinone (5.00 g,
26.5 mmol) in 50 mL DMF. After 10 min, chloromethyl methyl ether (4.4 mL, 53 mmol) was added
and the mixture was warmed to room temperature and stirred for an additional 14 h. To the reaction
mixture was added H2O (300 mL). The resulting solution was partitioned between EtOAc and H2O and
the aqueous layer was extracted with EtOAc (3 x 300 mL). The combined organic fractions were
washed with H2O (3 x 300 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give
2-bromo-1,4-bis-methoxymethoxy-benzene (16d) (7.34 g, 100%) as a colorless oil. IR (thin film) 1484
cm-1; 1H NMR (300 MHz, CDCl3) ꢀ 7.30 (d, J = 2.9 Hz, 1H), 7.09 (dd, J = 9.0, 0.8 Hz, 1H), 6.95 (ddd, J
= 9.0, 2.9, 0.8 Hz, 1H), 5.18 (d, J = 1.0 Hz, 2H), 5.11 (d, J = 1.0 Hz, 2H), 3.53 (d, J = 1.0 Hz, 3H), 3.48
13
(d, J = 1.1 Hz, 3H); C NMR (75 MHz, CDCl3) ꢀ 152.4, 148.8, 121.3, 117.4, 116.3, 113.2, 95.7, 94.9,
56.2, 55.8.
To a stirring suspension of NaH (0.174 g, 7.25 mmol) in 150 mL of THF was added a solution of
2-bromo-1,4-bis-methoxymethoxybenzene (16d) (7.07 g, 25.5 mmol) in 20 mL of THF. After 30 min,
the reaction mixture was cooled to -84 °C and n-BuLi (2.5 M in hexanes, 12.3 mL, 30.6 mmol) was added
dropwise via syringe. The reaction solution was held at this temperature for 10 min after which a

132
HETEROCYCLES, Vol. 81, No. 1, 2010
solution of I2 (13.0 g, 51.0 mmol) in 45 mL was added. The reaction mixture was allowed to warm to
room temperature and aqueous Na2S2O3 was added. The resulting solution was partitioned between
CH2Cl2 and H2O and the aqueous layer was extracted with CH2Cl2 (3 x 60 mL). The combined organic
fractions were dried over Na2SO4, filtered, and concentrated in vacuo to give
2-iodo-1,4-bis-methoxymethoxybenzene (8.01 g, 97%) as a light brown oil. IR (thin film) 1478 cm-1; 1H
NMR (400 MHz, CDCl3) ꢀ 7.46 (s, 1H), 7.08-6.92 (m, 2H), 5.14 (s, 2H), 5.07 (s, 2H), 3.49 (s, 3H), 3.44
13
(s, 3H); C NMR (90 MHz, CDCl3) ꢀ 152.6, 151.3, 127.2, 117.3, 115.8, 95.6, 95.0, 87.3, 56.3, 55.9.
LRMS (ESI) m/z (relative intensity) 294.1 (10%, M + NH4+).
To a stirring solution of 2-iodo-1,4-bis-methoxymethoxybenzene (3.27 g, 10.1 mmol) in 100 mL of
pyrrolidine was added propargyl alcohol (1.20 mL, 19.7 mmol) and Pd(PPh3)4 (0.563 g, 0.505 mmol).
The reaction mixture was heated at reflux for 16 h, and then allowed to cool to room temperature.
Saturated aqueous NH4Cl (100 mL) was added.
The resulting solution was partitioned between EtOAc
and H2O, and the aqueous layer was extracted with EtOAc (3 x 100 mL). The combined organic
fractions were dried over Na2SO4, filtered, and concentrated in vacuo to give a yellow oil. Purification
of this oil by SiO2 flash column chromatography (60% Et2O/hexanes as eluent) afforded
3-(2,5-bis-methoxymethoxy-phenyl)-prop-2-yn-1-ol (1.22 g, 48%) as a light brown oil. A yield of 66%
1
was obtained on a 23 mg scale. IR (thin film) 3425 cm-1; H NMR (360 MHz, CDCl3) ꢀ 7.05-7.04 (m,
1H), 6.98 (dd, J = 9.0, 2.2 Hz, 1H), 6.91-6.88 (m, 1H), 5.12 (s, 2H), 5.04 (s, 2H), 4.45 (d, J = 1.8 Hz, 2H),
13
3.45 (s, 3H), 3.40 (s, 3H), 1.16 (t, J = 1.8 Hz, 1H); C NMR (90 MHz, CDCl3) ꢀ 152.8, 151.6, 121.0,
118.2, 116.8, 114.0, 95.6, 94.9, 91.7, 81.3, 56.1, 55.8, 51.4; LRMS (ESI) m/z (relative intensity) 253.2
(100%, M + H+).
To a stirring solution of 3-(2,5-bis-methoxymethoxyphenyl)prop-2-yn-1-ol (1.22 g, 4.83 mmol) and
Et3N (2.0 mL, 14 mmol) in 20 mL of Et2O at 0 °C was added MsCl (416 ꢁL, 5.40 mmol). After 1 h,
saturated aqueous NaHCO3 (30 mL) was added. The resulting solution was partitioned between Et2O
and H2O and the aqueous layer was extracted with Et2O (25 mL) followed by EtOAc (25 mL). The
combined organic fractions were dried over Na2SO4, filtered, and concentrated in vacuo to give the
mesylate. To the crude mesylate was added 20 mL of CHCl3 and NBu4Br (2.46 g, 7.63 mmol). The
resulting solution was refluxed 30 min and concentrated in vacuo. EtOAc (20 mL) was added to the
crude mixture, washed with H2O (20 mL) followed by brine (20 mL). The organic fraction was dried
with Na2SO4 and concentrated in vacuo to give bromide 14d (1.48 g, 97%) as a tacky orange solid. This
1
material was used without further purification. IR (thin film) 2226 cm-1; H NMR (360 MHz, CDCl3) ꢀ
7.06 (d, J = 2.9 Hz, 1H), 6.98 (d, J = 9.0 Hz, 1H), 6.92 (dd, J = 9.0, 2.9 Hz, 1H), 5.13 (s, 2H), 5.05 (s,
13
2H), 4.15 (s, 2H), 3.47 (s, 3H), 3.41 (s, 3H); C NMR (90 MHz, CDCl3) ꢀ 153.0, 151.6, 120.9, 118.7,

HETEROCYCLES, Vol. 81, No. 1, 2010
133
116.9, 113.5, 95.6, 94.8, 87.9, 82.8, 56.1, 55.7, 15.3; LRMS (ESI) m/z (relative intensity) 315.0 (90%, M
+ H+).
1-Methoxy-2-[3-(nona-1,8-diyne-3-sulfonyl)prop-1-ynyl]benzene (15a). To a stirring suspension of
K2CO3 (0.254 g, 1.84 mmol) in 7 ml of MeCN was added a solution of thiol 13a (0.432 g, 2.83 mmol) in
3 mL of MeCN. The reaction mixture was stirred for 10 min and then bromide 14a (404 ꢀL, 2.83
mmol) was added. The reaction mixture was heated at 60 °C for 14 h, cooled to room temperature, and
then 1M phosphoric acid (10 mL) was added. The resulting solution was partitioned between Et2O and
H2O and the aqueous layer was extracted with Et2O (3 x 10 mL). The combined organic fractions were
washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give the sulfide as a
1
yellow oil, which was carried on without further purification. IR (thin film) 3284, 2214 cm-1; H NMR
(300 MHz, CDCl3) ꢁ 7.36 (dd, J = 7.5, 1.7 Hz, 1H), 7.26 (td, J = 7.9, 1.7 Hz, 1H), 6.87 (td, J = 7.5, 1.0
Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 3.92-3.86 (m, 1H), 3.85 (s, 3H), 3.81 (d, J = 16.8 Hz, 1H), 3.62 (d, J =
16.8 Hz, 1H), 2.39 (d, J = 2.4 Hz, 1H), 2.19 (td, J = 6.9, 2.6 Hz, 2H), 1.92 (t, J = 2.6 Hz, 1H), 1.82 (t, J
= 7.0 Hz, 2H), 1.69-1.51 (m, 4H); 13C NMR (75 MHz, CDCl3) ꢁ 159.9, 133.3, 129.6, 120.2, 111.9, 110.4,
89.3, 83.9, 82.8, 79.5, 72.1, 68.4, 55.5, 34.0, 33.7, 27.7, 26.2, 20.1, 18.1; LRMS (ESI) m/z (relative
intensity) 297.1 (60%, M + H+).
A stirring suspension of crude sulfide from above and Na2CO3 (1.07 g, 10.1 mmol) in 65 ml of CH2Cl2
was treated with 70% mCPBA (0.917 g, 5.04 mmol). The reaction mixture was heated at reflux for 12 h,
cooled to room temperature, and then saturated aqueous NaHCO3 (70 mL) was added. The resulting
solution was partitioned between CH2Cl2 and H2O and the aqueous layer was extracted with CH2Cl2 (3 x
100 mL). The combined organic fractions were sequentiallywashed with 1M H3PO4 (200 mL) and brine
(200 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give a crude yellow oil. Purification
of this oil by SiO2 flash column chromatography (5% Et2O/hexanes, then CH2Cl2 as eluent) gave sulfone
15a (0.343 g, 37% over 2 steps) as a light yellow oil. IR (thin film) 3272, 2359 cm-1; 1H NMR (300 MHz,
CDCl3) ꢁ 7.38 (d, J = 7.5 Hz, 1H), 7.31 (tdd, J = 8.0, 1.7, 1.0 Hz, 1H), 6.88 (tt, J = 7.5, 1.0 Hz, 1H), 6.85
(d, J = 8.4 Hz, 1H), 4.55 (dd, J = 17.0, 1.0 Hz, 1H), 4.44-4.39 (m, 1H), 4.13 (d, J = 17.0 Hz, 1H), 3.84 (s,
3H), 2.60 (d, J = 2.5 Hz, 1H), 2.20 (td, J = 6.1, 2.0 Hz, 2H), 2.13-2.07 (m, 1H), 2.01-1.92 (m, 1H), 1.93
13
(t, J = 2.6 Hz, 1H), 1.85-1.79 (m, 1H), 1.60-1.53 (m, 3H); C NMR (75 MHz, CDCl3) ꢁ 160.6, 133.5,
130.6 (2), 120.4, 110.6, 84.5, 83.7, 79.9, 75.8, 68.7 (2), 55.7, 44.3, 44.2, 27.7, 25.8, 25.7, 18.1; LRMS
(ESI) m/z (relative intensity) 346.2 (50%, M + NH4+). HRMS (ESI) m/z calcd for [C19H24NO3S]+,
346.1477, found 346.1474.
tert-Butyl-{3-[3-(2-methoxyphenyl)-prop-2-yne-1-sulfonyl]nona-1,8-diynyl}dimethylsilane
(15b).
To a stirring solution of solid LHMDS (3.39 g, 20.3 mmol) in 120 mL of THF at 0 °C was added a
solution of thiol 13b (5.14 g, 19.3 mmol) in 120 mL of THF. The reaction mixture was stirred for 5 min

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HETEROCYCLES, Vol. 81, No. 1, 2010
at 0 °C and treated with bromide 14a (2.9 mL, 19 mmol). After 14 h, the reaction mixture was warmed to
room temperature and H2O (120 mL) was added. The resulting mixture was partitioned between Et2O and
H2O and the aqueous layer was extracted with Et2O (3 x 200 mL). The combined organic fractions were
washed with brine (500 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give
tert-butyl-{3-[3-(2-methoxyphenyl)prop-2-ynylsulfanyl]nona-1,8-diynyl}dimethylsilane as a yellow oil
that was used without further purification. IR (thin film) 3295, 2150 cm-1; 1H NMR (360 MHz, CDCl3)
ꢀ 7.38 (dd, J = 7.2, 1.6 Hz, 1H), 7.26 (td, J = 7.9, 1.8 Hz, 1H), 6.90-6.83 (m, 2H), 3.91 (t, J = 7.2 Hz,
1H), 3.82 (s, 3H), 3.80 (d, J = 16.9 Hz, 1H), 3.65 (d, J = 16.6 Hz, 1H), 2.19 (td, J = 6.5, 2.5 Hz, 2H),
1.93 (t, J = 2.5 Hz, 1H), 1.83 (q, J = 7.0 Hz, 2H), 1.75-1.66 (m, 2H), 1.58 (q, J = 7.2 Hz, 2H), 0.95 (s,
13
9H), 0.12 (s, 6H); C NMR (90 MHz, CDCl3) ꢀ 160.0, 133.5, 129.4, 120.2, 112.1, 110.4, 105.1, 89.1,
86.9, 84.0, 79.4, 68.3, 56.0, 35.1, 34.0, 27.8, 26.1, 26.0, 20.2, 18.2, 16.4, -4.6; LRMS (ESI) m/z (relative
intensity) 433.0 (100%, M + Na+). HRMS (ESI) m/z calcd for M + NH4+, [C25H38NOSSi]+, 428.2443,
found 428.2427.
To
a
stirring solution of tert-butyl-{3-[3-(2-methoxyphenyl)-prop-2-ynylsulfanyl]nona-1,8-
diynyl}dimethylsilane (7.15 g, 17.3 mmol) in 500 mL of CH2Cl2 was added 70-75% mCPBA (8.57 g,
34.6 mmol). The reaction mixture was stirred for 1.5 h and then treated with Et3N (5.2 mL, 37 mmol)
followed by H2O (500 mL). The resulting solution was partitioned between CH2Cl2 and H2O and the
aqueous layer was extracted with CH2Cl2 (3 x 400 mL). The organic fractions were washed with brine
(800 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give a yellow oil. Purification of
this oil by SiO2 flash column chromatography (8:1:1 hexanes/Et2O/CH2Cl2 as eluent) afforded linear
1
sulfone 15b (3.74 g, 44% over 2 steps) as a yellow oil. IR (thin film) 3284, 2355, 1326, 1126 cm-1; H
NMR (300 MHz, CDCl3) ꢀ 7.40 (dd, J = 7.6, 1.6 Hz, 1H), 7.33 (td, J = 3.9, 1.7 Hz, 1H), 6.93-6.85 (m,
2H), 4.55 (d, J = 16.9 Hz, 1H), 4.42 (dd, J = 10.5, 4.3 Hz, 1H), 4.13 (d, J = 16.9 Hz, 1H), 3.85 (s, 3H),
2.22 (td, J = 6.7, 2.6 Hz, 2H), 2.17-2.00 (m, 1H), 1.93 (t, J = 2.5 Hz, 1H), 1.88-1.75 (m, 1H), 1.74-1.58
(m, 4H), 0.94 (s, 9H), 0.13 (s, 6H); 13C NMR (75 MHz, CDCl3) ꢀ 160.6, 133.5, 130.5, 120.3, 110.8, 110.6,
97.4, 93.0, 84.3, 83.7, 79.9, 68.6, 55.7, 54.7, 44.1, 27.7, 26.0, 25.9, 25.8, 18.1, 16.6, -5.0; LRMS (ESI)
m/z (relative intensity) 460.3 (90%, M + NH4+). HRMS (ESI) m/z calcd for M + NH4+, [C25H38NO3SSi]+,
460.2342, found 460.2342.
tert-Butyl-{3-[3-(2,6-dimethoxyphenyl)prop-2-yne-1-sulfonyl]nona-1,8-diynyl}dimethylsilane (15c).
To a stirring solution of NaH (75 mg, 1.9 mmol) in 14 mL of THF at 0 °C was added a solution of thiol
13b (0.50 g, 1.9 mmol) in 3 mL of THF. The reaction mixture was held at this temperature for 15 min and
then bromide 14b (0.479 g, 1.88 mmol) in 3 mL of CH2Cl2 was added to the reaction solution. After an
additional 30 min at 0 °C, H2O (10 mL) was added. The resulting solution was partitioned between
EtOAc and H2O and the aqueous layer was extracted with EtOAc (3 x 10 mL). The combined organic

HETEROCYCLES, Vol. 81, No. 1, 2010
135
fractions were dried over Na2SO4, filtered, and concentrated in vacuo to give a yellow oil. Purification
of this oil by SiO2 flash column chromatography (5% Et2O/hexanes) afforded
tert-butyl-{3-[3-(2,6-dimethoxyphenyl)prop-2-ynylsulfanyl]nona-1,8-diynyl}dimethylsilane (0.657 g,
80%) as a yellow oil. IR (thin film) 3295, 2155 cm-1; 1H NMR (300 MHz, CDCl3) ꢀ 7.17 (app t, J = 8.4
Hz, 1H), 6.48 (d, J = 8.4 Hz, 2H), 4.01 (t, J = 6.9 Hz, 1H), 3.85-3.79 (m, 1H), 3.83 (s, 6H), 3.66 (d, J =
16.8 Hz, 1H), 2.16 (td, J = 6.9, 2.6 Hz, 2H), 1.89 (t, J = 2.6 Hz, 1H), 1.82-1.77 (m, 2H), 1.73-1.52 (m,
13
4H), 0.91 (s, 9H), 0.08 (s, 6H); C NMR (75 MHz, CDCl3) ꢀ 161.5, 129.4, 105.4, 103.3, 101.3, 93.5,
86.6, 84.1, 75.7, 68.3, 55.9, 34.9, 33.9, 27.9, 26.4, 26.0, 20.6, 18.2, 16.5, -4.6; LRMS (ESI) m/z (relative
intensity) 441.1 (100%, M + H+).
To
a
stirring solution of tert-butyl-{3-[3-(2,6-dimethoxyphenyl)prop-2-ynylsulfanyl]nona-1,8-
diynyl}dimethylsilane (0.108 g, 0.243 mmol) in 10 mL of CH2Cl2 at room temperature was added
70-75% mCPBA (0.123 g, 0.498 mmol). The reaction mixture was stirred for 3 h and then saturated
aqueous NaHCO3 (10 mL) was added.
The resulting solution was partitioned between EtOAc and H2O
and the aqueous layer was extracted with EtOAc (3 x 10 mL). The combined organic fractions were
dried over Na2SO4, filtered, and concentrated in vacuo to give a yellow oil. Purification of this oil by
SiO2 flash column chromatography (gradient, 18:1:1 hexanes/Et2O/CH2Cl2 ꢀ 4:5:1 hexanes/Et2O/
1
CH2Cl2) afforded sulfone 15c (98 mg, 85%) as a yellow oil. IR (thin film) 3284, 1326, 1114 cm-1; H
NMR (300 MHz, CDCl3) ꢀ 7.29 (app t, J = 8.4 Hz, 1H), 6.56 (d, J = 8.5 Hz, 2H), 4.61 (dd, J = 10.5, 4.1
Hz, 1H), 4.57 (d, J = 17.0 Hz, 1H), 4.15 (d, J = 16.9 Hz, 1H), 3.86 (s, 6H), 2.24 (td, J = 6.7, 2.6 Hz, 2H),
2.08-2.05 (m, 1H), 1.98 (t, J = 2.6 Hz, 1H), 1.95-1.82 (m, 1H), 1.75-1.60 (m, 4H), 0.97 (s, 9H), 0.16 (s,
6H); 13C NMR (75 MHz, CDCl3) ꢀ 162.6, 131.3, 104.0, 98.3, 97.6, 93.2, 84.9, 84.4, 81.4, 69.0, 56.6, 54.8,
45.1, 28.4. 26.6, 26.5, 26.3, 18.6, 17.1, -4.6; LRMS (ESI) m/z (relative intensity) 490.2 (100%, M +
NH4+); HRMS (ESI) m/z calcd for M + NH4+, [C26H40NO4SiS]+, 490.2447, found 490.2453.
tert-Butyl-{3-[3-(2,5-dimethoxyphenyl)-prop-2-yne-1-sulfonyl]nona-1,8-diynyl}dimethylsilane (15d).
To a stirring solution of NaH (0.118 g, 2.96 mmol) in 30 mL of THF at 0 °C was added a solution of thiol
13b (0.789 g, 2.96 mmol) in 10 mL of THF. After 15 min, a solution of bromide 14c (0.755 g, 2.96
mmol) in 5 mL of CH2Cl2 was added to the reaction solution. After an additional 30 min at 0 °C, H2O
(50 mL) was added. The resulting solution was partitioned between EtOAc and H2O and the aqueous
layer was extracted with EtOAc (3 x 50 mL). The combined organic fractions were dried over Na2SO4,
filtered, and concentrated in vacuo to give tert-butyl-{3-[3-(2,5-dimethoxyphenyl)-prop-2-
ynylsulfanyl]nona-1,8-diynyl}dimethylsilane as a yellow oil. This material was used without further
purification. IR (thin film) 3284 cm-1; 1H NMR (300 MHz, CDCl3) ꢀ 6.90 (d, J = 2.8 Hz, 1H), 6.79 (d, J
= 2.8 Hz, 1H), 6.77 (s, 1H), 3.87 (t, J = 8.3 Hz, 1H), 3.80 (s, 3H), 3.78 (d, J = 19.3 Hz, 1H), 3.72 (s, 3H),
3.62 (d, J = 16.7 Hz, 1H), 2.17 (td, J = 6.9, 2.6 Hz, 2H), 1.90 (t, J = 2.6 Hz, 1H), 1.81-1.77 (m, 2H),

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HETEROCYCLES, Vol. 81, No. 1, 2010
13
1.70-1.66 (m, 2H), 1.64-1.53 (m, 2H), 0.92 (s, 9H), 0.09 (s, 6H); C NMR (75 MHz, CDCl3) ꢀ 154.6,
153.1, 118.3, 115.4, 112.7, 111.9, 105.0, 89.3, 87.1, 84.1, 79.4, 68.4, 56.3, 55.7, 35.3, 34.1, 27.9, 26.4,
26.1, 20.2, 18.2, 16.5, -4.6; LRMS (ESI) m/z (relative intensity) 441.3 (100%, M + H+).
To a stirring solution of the crude tert-butyl-{3-[3-(2,5-dimethoxyphenyl)-prop-2-ynylsulfanyl]nona-1,8-
diynyl}dimethylsilane in 45 mL of CH2Cl2 at room temperature was added 70-75% mCPBA (1.61 g, 5.92
mmol). The reaction mixture was stirred for 1 h and then Et3N (883 ꢁL, 6.34 mmol) followed by
saturated aqueous NaHCO3 (50 mL) were added. The resulting solution was partitioned between CH2Cl2
and H2O and the aqueous layer was extracted with CH2Cl2 (3 x 50 mL). The combined organic fractions
were dried over Na2SO4, filtered, and concentrated in vacuo to give an orange oil. Purification of this oil
by SiO2 flash column chromatography (10% EtOAc/hexanes as eluent) afforded linear sulfone 15d (0.657
g, 47% over 2 steps) as an orange oil. IR (thin film) 3284, 1326, 1126 cm-1; 1H NMR (360 MHz, CDCl3)
ꢀ 6.90 (d, J = 2.9 Hz, 1H), 6.85 (d, J = 3.2 Hz, 1H), 6.76 (d, J = 9.0 Hz, 1H), 4.51 (d, J = 16.6 Hz, 1H),
4.39 (dd, J = 10.4, 4.3 Hz, 1H), 4.10 (d, J = 16.9 Hz, 1H), 3.78 (s, 3H), 3.71 (s, 3H), 2.19 (td, J = 6.7, 2.7
Hz, 2H), 2.13-2.03 (m, 1H), 1.90 (t, J = 2.5 Hz, 1H), 1.86-1.72 (m, 1H), 1.64-1.50 (m, 4H), 0.92 s, 9H),
0.11 (s, 6H); 13C NMR (90 MHz, CDCl3) ꢀ 155.1, 153.0, 118.1, 116.4, 111.9, 111.2, 97.4, 92.9, 84.1, 83.6,
79.9, 68.6, 56.2, 55.7, 54.8, 44.0, 27.6, 25.9 (2), 25.8, 18.0, 16.5, -5.1; LRMS (ESI) m/z (relative
intensity) 490.2 (100%, M + NH4+); HRMS (ESI) m/z calcd for M + NH4+, [C26H40NO4SiS]+, 490.2447,
found 490.2438.
{3-[3-(2,5-Bis-methoxymethoxyphenyl)-prop-2-yne-1-sulfonyl]nona-1,8-diynyl}tert-butyldimethylsil
ane (15e). To a stirring solution of LHMDS (0.742 g, 4.19 mmol) in 30 mL of THF at 0 °C was added a
solution of thiol 13b (1.12 g, 4.19 mmol) in 15 mL of THF. After 15 min, a solution of bromide 14d
(1.32 g, 4.19 mmol) in 10 mL of THF was added to the reaction solution and after an additional 14 h at
0 °C, H2O (60 mL) was added. The resulting solution was partitioned between CH2Cl2 and H2O and the
aqueous layer was extracted with CH2Cl2 (3 x 60 mL). The combined organic fractions were dried over
Na2SO4, filtered, and concentrated in vacuo to give a yellow oil. Purification of this oil by SiO2 flash
column chromatography (95:4:1 hexanes/Et2O/CH2Cl2 as eluent) afforded {3-[3-(2,5-bis-
methoxymethoxyphenyl)-prop-2-ynylsulfanyl]nona-1,8-diynyl}tert-butyldimethylsilane (1.33 g, 63%) as
a yellow oil. A yield of 68% was obtained on a 0.389 g scale. IR (thin film) 3295, 2155 cm-1; 1H NMR
(360 MHz, CDCl3) ꢀ 7.05 (d, J = 2.9 Hz, 1H), 6.99 (d, J = 9.0, 1H), 6.91 (dd, J = 9.0, 2.9 Hz, 1H), 5.14
(s, 2H), 5.07 (s, 2H), 3.87 (t, J = 7.0 Hz, 1H), 3.76 (d, J = 16.9 Hz, 1H), 3.60 (d, J = 16.6 Hz, 1H), 3.49
(s, 3H), 3.44 (s, 3H), 2.18 (td, J = 6.8, 2.5 Hz, 2H), 1.91 (t, J = 2.7 Hz, 1H), 1.82-1.76 (m, 2H), 1.70-1.60
(m, 2H), 1.60-1.53 (m, 2H), 0.92 (s, 9H), 0.09 (s, 6H); 13C NMR (90 MHz, CDCl3) ꢀ 153.0, 151.8, 121.0,
117.9, 117.1, 114.7, 105.0, 95.7, 95.0, 89.2, 87.1, 84.1, 79.2, 68.4, 56.2, 55.9, 35.2, 34.0, 27.9, 26.4, 26.1,
20.2, 18.2, 16.5, -4.6; LRMS (ESI) m/z (relative intensity) 518.3 (100%, M + NH4+).

HETEROCYCLES, Vol. 81, No. 1, 2010
137
To
a
stirring solution of {3-[3-(2,5-bismethoxymethoxyphenyl)-prop-2-ynylsulfanyl]nona-1,8-
diynyl}tert-butyldimethylsilane (0.830 g, 1.66 mmol) in 50 mL of CH2Cl2 was added mCPBA (0.857 g,
3.49 mmol). After 90 min, additional mCPBA (82 mg, 0.33 mmol) was added to the reaction mixture.
After 30 min, saturated aqueous NaHCO3 (50 mL) was added. The resulting solution was partitioned
between CH2Cl2 and H2O, and the aqueous layer was extracted with CH2Cl2 (50 mL). The combined
organic fractions were washed with 1M phosphoric acid (50 mL). The aqueous fraction was
back-extracted with CH2Cl2 (50 mL). The combined organic fractions were dried over Na2SO4, filtered,
and concentrated in vacuo to give a yellow oil. Purification of this oil by SiO2 flash column
chromatography (gradient, 5% Et2O/hexanes ꢀ 15% Et2O/hexanes as eluent) afforded linear sulfone 15d
(0.528 g, 60%). IR (thin film) 3284, 1331, 1149 cm-1; 1H NMR (360 MHz, CDCl3) ꢀ 7.03 (d, J = 2.5 Hz,
1H), 6.98-6.90 (m, 2H), 5.10 (s, 2H), 5.02 (s, 2H), 4.48 (d, J = 16.9 Hz, 1H), 4.35 (dd, J = 10.4, 4.1 Hz,
1H), 4.10 (d, J = 16.9 Hz, 1H), 3.42 (s, 3H), 3.37 (s, 3H), 2.16-2.13 (m, 2H), 2.09-1.92 (m, 2H), 1.90 (t, J
13
= 2.5 Hz, 1H), 1.82-1.69 (m, 1H), 1.62-1.47 (m, 3H), 0.86 (s, 9H), 0.07 (s, 6H); C NMR (90 MHz,
CDCl3) ꢀ 153.2, 151.4, 120.6, 118.7, 116.5, 112.8, 97.3, 95.2, 94.6, 92.8, 83.7, 83.5, 79.9, 68.7, 55.9, 55.6,
54.7, 43.7, 27.5, 25.7 x 2, 25.6, 17.8, 16.3, -5.2; LRMS (ESI) m/z (relative intensity) 550.0 (100%, M +
NH4+).
1-Hex-5-ynyl-5-methoxy-1,3-dihydro-naphtho[2,3-c]thiophene 2,2-Dioxide (17). A stirring solution
of sulfone 15a (209 mg, 0.635 mmol) in 20 mL of CHCl3 was treated with Et3N (136 ꢁL, 0.953 mmol).
The reaction mixture was stirred for 3 d and concentrated in vacuo to give tricycle 17 (209 mg, 100%) as
1
a yellow solid. mp 141-143 ºC; IR (thin film) 3284, 1308, 1126 cm-1; H NMR (400 MHz, CDCl3) ꢀ
8.19 (s, 1H), 7.68 (s, 1H), 7.44-7.39 (m, 2H), 6.84 (d, J = 6.8 Hz, 1H), 4.43 (s, 2H), 4.29 (t, J = 7.1 Hz,
1H), 3.99 (s, 3H), 2.27 (td, J = 7.0, 2.1 Hz, 2H), 2.25-2.04 (m, 2H), 1.98 (t, J = 2.2 Hz, 1H), 1.88-1.76 (m,
2H), 1.75-1.60 (m, 2H); 13C NMR (75 MHz, CDCl3) ꢀ 155.1, 134.3, 134.0, 127.05, 127.02, 125.1, 124.1,
120.0, 119.8, 104.6, 83.9, 68.7, 64.9, 55.6, 55.2, 29.0, 28.2, 25.6, 18.1; LRMS (ESI) m/z (relative
intensity) 346.1 (100%, M + NH4+).
tert-Butyl-(3-hex-5-ynyl-8-methoxy-2,2-dioxo-2,4-dihydro-1H-2ꢀ6-naphtho[2,3-c]thiophen-4-yl)dim
ethylsilane (19). To a refluxing solution of linear sulfone 15b (0.125 g, 0.282 mmol) in 10 mL of
toluene was added Et3N (59 ꢁL, 0.42 mmol). The reaction mixture was held at reflux for 14 h and then
cooled to room temperature and concentrated in vacuo to give a yellow oil. Purification of this oil by
SiO2 flash column chromatography (gradient 10% Et2O/hexanes ꢀ 20% Et2O/hexanes as eluent) afforded
1
tricycle 19 (80 mg, 64%) as a yellow oil. IR (thin film) 3300, 1290, 1120 cm-1; H NMR (360 MHz,
CDCl3) ꢀ 7.10 (app t, J = 7.9 Hz, 1H), 7.00 (s, 1H), 6.71 (d, J = 7.6 Hz, 1H), 6.64 (d, J = 8.3 Hz, 1H),
4.01-3.82 (m, 3H), 3.82 (s, 3H), 2.58-2.50 (m, 1H), 2.45-2.36 (m, 1H), 2.21 (td, J = 7.0, 2.7 Hz, 2H), 1.93
13
(t, J = 2.7 Hz, 1H), 1.86-1.79 (m, 2H), 1.62-1.58 (m, 2H), 0.91 (s, 9H), 0.00 (s, 3H), -0.35 (s, 3H); C

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HETEROCYCLES, Vol. 81, No. 1, 2010
NMR (90 MHz, CDCl3) ꢀ 155.4, 146.6, 137.9, 131.8, 128.5, 125.8, 120.2, 120.1, 119.6, 107.8, 84.0, 68.6,
55.5, 53.3, 34.6, 28.1, 27.3, 26.8, 23.5, 18.4, 18.0, -4.5, -6.2; LRMS (ESI) m/z (relative intensity) 443.3
(100%, M + H+). HRMS (ESI) m/z calcd for [C25H38NO3SSi]+, 460.2342, found 460.2350.
Conversion of Dimethoxy Sulfone 15c to Tricycle 19. To a refluxing solution of linear sulfone 15c
(66 mg, 0.14 mmol) in 5 mL of toluene was added Et3N (29 ꢁL, 0.21 mmol). The reaction mixture was
heated at reflux for 14 h, cooled to room temperature and concentrated in vacuo to give a yellow oil.
Purification of this oil by SiO2 flash column chromatography (gradient, 5% Et2O/hexanes ꢀ 30%
Et2O/hexanes as eluent) afforded tricycle 19 (17 mg, 28%) as a yellow oil.
tert-Butyl-(3-hex-5-ynyl-5,8-dimethoxy-2,2-dioxo-2,4-dihydro-1H-2ꢀ6-naphtho[2,3-c]thiophen-4-yl)
dimethylsilane (21). To a solution of sulfone 15d (0.206 g, 0.434 mmol) in 10 mL of toluene at 110 °C
was added Et3N (90 ꢁL, 0.65 mmol). The reaction mixture was held at reflux for 14 h, cooled to room
temperature and concentrated in vacuo to give a yellow oil. Purification of this oil by SiO2 flash column
chromatography (10% Et2O/hexanes as eluent) afforded tert-butyl-(3-hex-5-ynyl-5,8-dimethoxy-2,2-
dioxo-2,4-dihydro-1H-2ꢀ6-naphtho[2,3-c]thiophen-4-yl)dimethylsilane (21) (95 mg, 46%) as a tacky
yellow solid. IR (thin film) 3284, 1284, 1114 cm-1; 1H NMR (360 MHz, CDCl3) ꢀ 6.93 (s, 1H), 6.64 (d,
J = 9.0 Hz, 1H), 6.57 (d, J = 9.0 Hz, 1H), 4.25 (s, 1H), 3.95 (d, J = 15.1 Hz, 1H), 3.86 (d, J = 15.5 Hz,
1H), 3.74 (s, 6H), 2.53-2.44 (m, 2H), 2.16 (td, J = 5.6, 2.2 Hz, 2H), 1.91-1.87 (m, 1H), 1.86-1.73 (m, 2H),
1.59-1.53 (m, 2H), 0.84 (s, 9H), -0.04 (s, 3H), -0.38 (s, 3H); 13C NMR (90 MHz, CDCl3) ꢀ 149.7, 148.5,
147.1, 132.1, 126.6, 125.7, 120.9, 120.0, 109.9, 107.5, 83.9, 68.5, 55.8, 54.8, 53.3, 28.0, 27.8, 27.0, 26.7,
23.7, 18.3, 17.9, -4.3, -5.7; LRMS (ESI) m/z (relative intensity) 473.2 (100%, M + H+).
tert-Butyl-(3-hex-5-ynyl-5,8-bis-methoxymethoxy-2,2-dioxo-2,4-dihydro-1H-2ꢀ6-naphtho[2,3-c]thio
phen-4-yl)dimethylsilane (22). A solution of sulfone 15e (0.528 g, 0.991 mmol) in 10 mL of benzene
was heated to reflux and then treated with Et3N (242 ꢁL, 1.49 mmol). The reaction mixture was held at
this temperature for 3 d, cooled to room temperature, and concentrated in vacuo to give a yellow oil.
Purification of this oil by SiO2 flash column chromatography (gradient, 10% Et2O/hexanes ꢀ 40%
Et2O/hexanes as eluent) afforded tricycle 22 (0.237 g, 45 %) as yellow oil. IR (thin film) 3284, 1284,
1114 cm-1; 1H NMR (360 MHz, CDCl3) ꢀ 6.92 (s, 1H), 6.89 (d, J = 9.4 Hz, 1H), 6.76 (d, J = 9.0 Hz, 1H),
5.16-5.02 (m, 4H), 4.23 (s, 1H), 3.95 (d, J = 15.1 Hz, 1H), 3.86 (d, J = 15.1 Hz, 1H), 3.42 (s, 3H), 3.39 (s,
3H), 2.53-2.40 (m, 2H), 2.12 (td, J = 5.6, 2.2 Hz, 2H), 1.87 (s, 1H), 1.80-1.74 (m, 2H), 1.56-1.50 (m, 2H),
0.83 (s, 9H), -0.05 (s, 3H), -0.34 (s, 3H); 13C NMR (90 MHz, CDCl3) ꢀ 148.0, 147.3, 146.6, 132.3, 126.3,
121.7, 119.9, 119.8, 114.6, 111.9, 95.1, 95.0, 83.7, 68.4, 56.1, 55.8, 53.2, 27.8, 26.89, 26.87, 26.6, 23.5,
18.1, 17.7, -4.5, -5.7; LRMS (ESI) m/z (relative intensity) 533.3 (100%, M + H+).
1-Hex-5-ynyl-2,2-dioxo-2,3-dihydro-1H-2ꢀ6-naphtho[2,3-c]thiophene-5,8-dione (23). A stirring
solution of sulfone 17 (0.209 g, 0.635 mmol) in 15 ml of acetone was treated with Jones reagent (695 ꢁL,

HETEROCYCLES, Vol. 81, No. 1, 2010
139
2.54 mmol) at 0 °C. The reaction mixture was warmed to room temperature and stirred for 14 h after
which time additional Jones reagent (695 ꢀL, 2.54 mmol) was added. The reaction mixture was stirred
for 1 h at room temperature and then isopropanol (15 mL) and H2O (15 mL) were added. The resulting
solution was partitioned between Et2O and H2O and the aqueous layer was extracted with Et2O (3 x 30
mL). The combined organic fractions were washed with brine (100 mL), dried over Na2SO4, filtered,
and concentrated in vacuo to give a yellow oil. Purification of this yellow oil by SiO2 flash column
chromatography (15:4:1 hexanes/Et2O/CH2Cl2, then 13:5:2 hexanes/Et2O/CH2Cl2 as eluent) gave quinone
1
23 (126 mg, 60%) as a yellow oil. IR (thin film) 3272, 1666, 1314, 1132 cm-1; H NMR (300 MHz,
CDCl3) ꢁ 8.02 (app d, J = 5.1 Hz, 2H), 7.01 (s, 2H), 7.68 (s, 1H), 4.41 (app s, 2H), 4.29 (dd, J = 8.4, 6.0
Hz, 1H), 2.25 (td, J = 6.8, 2.6 Hz, 2H), 2.19-2.11 (m, 2H), 1.97 (t, J = 2.6 Hz, 1H), 1.84-1.76 (m, 2H),
13
1.67 (q, J = 4.4 Hz, 2H); C NMR (90 MHz, CDCl3) ꢁ 183.9, 183.8, 142.4, 138.7 (2), 136.6, 132.0,
131.8, 124.2, 123.5, 83.6, 69.0, 65.3, 55.3, 28.7, 28.0, 25.6, 18.1; LRMS (ESI) m/z (relative intensity)
351.2 (100%, M + Na+).
tert-Butyl-(3-hex-5-ynyl-8-methoxy-2,2-dioxo-1-phenylsulfanyl-2,4-dihydro-1H-2ꢀ6-naphtho[2,3-c]ꢀ
thiophen-4-yl)dimethylsilane (25a). To a stirring solution of tricycle 19 (0.24 g, 0.55 mmol) in 7 mL
of THF at -78 °C was added n-BuLi (2.5M in hexanes, 220 ꢀL, 0.55 mmol) dropwise. The reaction
mixture was held at this temperature for 15 min and then diphenyl disulfide (1.2 g, 5.5 mmol) was added
and the solution was warmed to 0 °C over 30 min. The mixture was held at this temperature for 4 h and
then H2O (10 mL) was added. The resulting solution was partitioned between Et2O and H2O and the
aqueous layer was extracted with Et2O (3 x 10 mL). The combined organic fractions were washed with
brine (30 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give a yellow oil. Purification of
this oil by SiO2 flash column chromatography (95:5:2 hexanes/Et2O/CH2Cl2 as eluent) afforded thiophenyl
adduct 25a (0.197 g, 65%) as a yellow oil.
IR (thin film) 3284, 1297, 1108 cm-1; 1H NMR (360 MHz,
CDCl3) ꢁ 7.65 (dd, J = 9.4, 1.8 Hz, 2H), 7.37-7.29 (m, 3H), 7.22 (s, 1H), 7.12 (dd, J = 7.9, 7.9 Hz, 1H),
6.73 (d, J = 7.9 Hz, 1H), 6.65 (d, J = 8.3 Hz, 1H), 5.06 (d, J = 1.1 Hz, 1H), 3.92 (s, 1H), 3.83 (s, 3H),
2.58-2.50 (m, 1H), 2.43-2.37 (m, 1H), 2.21 (td, J = 7.0, 2.7 Hz, 2H), 1.92 (t, J = 2.7 Hz, 1H), 1.87-1.81
(m, 2H), 1.64-1.54 (m, 2H), 0.94 (s, 9H), 0.08 (s, 3H), -0.34 (s, 3H);13C NMR (90 MHz, CDCl3) ꢁ 158.8,
145.3, 138.3, 133.0, 131.9, 130.4, 129.3, 129.2, 128.2, 127.5, 123.9, 120.3, 119.8, 107.9, 84.0, 68.7, 67.7,
56.3, 34.8, 28.2, 27.7, 26.8, 24.1, 18.5, 18.0, -4.0, -6.2; LRMS (ESI) m/z (relative intensity) 568.3 (100%,
M + NH4+). HRMS (ESI) m/z calcd for M + NH4+, [C31H42NO3S2Si]+, 568.2375, found 568.2397.
(1-Benzenesulfinyl-3-hex-5-ynyl-8-methoxy-2,2-dioxo-2,4-dihydro-1H-2ꢀ6-naphtho[2,3-c]thiophen-
4-yl)-tert-butyldimethylsilane (25b). To a stirring solution of phenyl sulfide 25a (0.173 g, 0.314
mmol) in 25 mL of CH2Cl2 was added 70-75% mCPBA (75 mg, 0.31 mmol). The reaction mixture was
stirred for 2 h at room temperature and then saturated aqueous NaHCO3 (25 mL) was added. The resulting

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HETEROCYCLES, Vol. 81, No. 1, 2010
solution was partitioned between CH2Cl2 and H2O and the aqueous layer was extracted with CH2Cl2 (3 x
25 mL). The combined organic fractions were washed with brine (100 mL), dried over Na2SO4, filtered,
and concentrated in vacuo to give a yellow oil. Purification of this oil by SiO2 flash column
chromatography (17:3:1 hexanes/EtOAc/CH2Cl2 as eluent) afforded sulfoxide 25b (79 mg, 44%) as a
yellow oil. A yield of 48% was obtained on a 427 mg scale. IR (thin film) 3295, 1291, 1149 cm-1; 1H
NMR (360 MHz, CDCl3) ꢀ 7.94 (d, J = 4.0 Hz, 2H), 7.64-7.56 (m, 3H), 7.16 (app t, J = 7.9, 1H), 6.95 (s,
1H), 6.79 (d, J = 7.6 Hz, 1H), 6.67 (d, J = 8.3 Hz, 1H), 4.60 (s, 1H), 3.97 (s, 1H), 3.81 (s, 3H), 2.56-2.52
(m, 1H), 2.48-2.39 (m, 1H), 2.27-2.19 (m, 2H), 2.00-1.95 (m, 1H), 1.91-1.73 (m, 2H), 1.67-1.55 (m, 2H),
1.01 (s, 9H), 0.22 (s, 3H), -0.14 (s, 3H); 13C NMR (90 MHz, CDCl3) ꢀ 156.1, 146.9, 142.9, 138.3, 131.9,
130.3, 129.39, 129.38, 126.4, 125.4, 121.3, 120.1, 119.7, 107.5, 83.8, 80.7, 68.7, 56.2, 34.8, 28.0, 27.7,
26.6, 23.6, 18.4, 17.9, -6.7; LRMS (ESI) m/z (relative intensity) 567.3 (100%, M + H+).
(1-Benzenesulfonyl-3-hex-5-ynyl-8-methoxy-2,2-dioxo-2,4-dihydro-1H-2ꢀ6-naphtho[2,3-c]thiophen-
4-yl)-tert-butyldimethylsilane (25c). To a stirring solution of thiophene 25a (72 mg, 0.13 mmol) in 5
mL of CH2Cl2 at room temperature was added 70-75% mCPBA (86 mg, 0.34 mmol). The reaction
mixture was stirred for 30 min at room temperature and saturated aqueous NaHCO3 (10 mL) was added.
The resulting solution was partitioned between CH2Cl2 and H2O and the aqueous layer was extracted with
CH2Cl2 (3 x 10 mL). The combined organic fractions were washed with brine (30 mL), dried over
Na2SO4, filtered, and concentrated in vacuo to give a yellow oil. Purification of this oil by SiO2 flash
column chromatography (gradient, 5% Et2O/hexanes ꢀ 20% Et2O/hexanes as eluent) afforded sulfone
25c (45 mg, 59%) as a yellow oil. IR (thin film) 3284, 1303, 1108 cm-1; 1H NMR (360 MHz, CDCl3) ꢀ
8.09 (d, J = 7.2 Hz, 2H), 7.70-7.66 (m, 1H), 7.60-7.55 (m, 2H), 7.45 (s, 1H), 7.14 (app t, J = 7.9 Hz, 1H),
6.78 (d, J = 7.6 Hz, 1H), 6.67 (d, J = 7.9 Hz, 1H), 5.07 (s, 1H), 3.96 (s, 1H), 3.83 (s, 3H), 2.47-2.43 (m,
1H), 2.36-2.34 (m, 1H), 2.17 (td, J = 7.0, 2.5 Hz, 2H), 1.92 (t, J = 2.5 Hz, 1H), 1.82-1.64 (m, 2H),
13
1.63-1.53 (m, 2H), 0.93 (s, 9H), 0.07 (s, 3H), -0.18 (s, 3H); C NMR (90 MHz, CDCl3) ꢀ 156.2, 147.0,
138.3, 138.2, 134.6, 130.4, 130.0, 129.7, 129.0, 127.4, 120.1, 120.0, 119.9, 108.1, 83.8, 78.3, 68.7, 55.5,
35.5, 28.0, 27.8, 27.4, 26.6, 23.8, 18.6, 17.9, -5.5, -7.0; LRMS (ESI) m/z (relative intensity) 600.2 (100%,
M + NH4+). HRMS (ESI) m/z calcd for [C31H42NO5S2Si]+, 600.2274, found 600.2277.
1-Hex-5-ynyl-5-methoxy-3-phenylsulfanyl-1,3-dihydro-naphtho[2,3-c]thiophene 2,2-Dioxide (26).
To a stirring solution of 25a (17 mg, 0.031 mmol) in 1 mL of THF at 0 °C was added Bu4NF (1.0 M in
THF, 33 ꢁL, 0.032 mmol). The reaction mixture was stirred for 20 min at 0 °C and then H2O (5 mL)
were added. The resulting solution was partitioned between Et2O and H2O and the aqueous layer was
extracted with Et2O (3 x 10 mL). The combined organic fractions were washed with brine (30 mL), dried
with Na2SO4, filtered, and concentrated in vacuo to give a 1:1 mixture of diastereomers of thiophenyl
1
adduct 26 (12 mg, 86%) as a yellow oil. IR (thin film) 3284, 1314, 1102 cm-1; H NMR (300 MHz,

HETEROCYCLES, Vol. 81, No. 1, 2010
141
CDCl3, mixture of diastereomers) ꢀ 8.52 (s, 1H), 8.46 (s, 1H), 7.76-7.59 (m, 6H), 7.44-7.30 (m, 10H),
6.85 (d, J = 7.3 Hz, 2H), 5.56 (s, 1H), 5.50 (s, 1H), 4.29 (t, J = 7.2 Hz, 1H), 4.17 (t, J = 7.1 Hz, 1H), 4.02
(s, 6H), 2.29-2.20 (m, 6H), 2.20-2.01 (m, 2H), 1.97-1.94 (m, 2H), 1.91-1.81 (m, 4H), 1.73-1.62 (m, 4H);
13C NMR (90 MHz, CDCl3, mixture of diastereomers) ꢀ 155.4 (2), 134.52, 134.48, 133.9, 133.1, 132.9 (2),
132.5, 131.2, 129.3 (2), 129.2 (2), 128.95, 128.93, 128.65, 128.62, 127.7 (2), 125.30, 125.26, 124.01,
123.8, 121.7, 121.5, 119.86, 119.84, 83.96, 83.93, 71.7, 70.6, 68.7 (2), 63.9, 62.2, 55.6 (2), 29.7, 28.16,
28.13, 26.1, 25.8, 25.6, 18.1 (2); LRMS (ESI) m/z (relative intensity) 454.2 (100%, M + NH4+). HRMS
(ESI) m/z calcd for M + NH4+, [C25H28NO3S2]+, 454.155, found 454.1510.
4-(tert-Butyl-dimethyl-silanyl)-3-hex-5-ynyl-8-methoxy-2,2-dioxo-2,4-dihydro-1H-2ꢀ6-naphtho[2,3-
c]thiophen-1-ol (27). To a stirring solution of sulfoxide 25b (0.213 g, 0.376 mmol) in 5 mL of toluene
was added Et2NH (389 ꢁL, 3.76 mmol). The reaction mixture was then heated at 65 °C for 36 h and
then warmed to 110 °C for an additional 12 h. The reaction solution was cooled to room temperature
and H2O (5 mL) was added. The resulting solution was partitioned between EtOAc and H2O and the
aqueous layer was extracted with EtOAc (3 x 10 mL). The combined organic fractions were dried over
Na2SO4, filtered, and concentrated in vacuo to give a yellow oil. Purification of this oil by SiO2 flash
column chromatography (gradient, 5-15% Et2O/hexanes, then 30% EtOAc/hexanes as eluent) afforded a
3:1 mixture of diastereomers of alcohol 27 (49 mg, 28%) as a yellow oil. IR (thin film) 3389, 3295,
1269, 1120 cm-1; 1H NMR (400 MHz, CDCl3, major isomer) ꢀ 7.24-7.07 (m, 2H), 6.65-6.60 (m, 2H), 5.35
(s, 1H), 3.93-3.78 (m, 1H), 3.78 (s, 3H), 2.60-2.44 (m, 1H), 2.44-2.30 (m, 1H), 2.26-2.10 (m, 2H), 1.89 (s,
1H), 1.86-1.69 (m, 2H), 1.69-1.48 (m, 2H), 0.86 (s, 9H), -0.05 (s, 3H), -0.37 (s, 3H), OH not observed;
13C NMR (90 MHz, CDCl3, major isomer) ꢀ 155.9, 146.1, 138.5, 129.8, 129.1, 127.8, 121.0, 119.9, 119.6,
107.9, 84.4, 83.9, 68.6, 55.9, 34.8, 28.0, 27.2, 26.7, 23.7, 18.3, 17.9, -4.6, -6.2; LRMS (ESI) m/z
(relative intensity) 476.3 (90%, M + NH4+).
4-(tert-Butyldimethylsilanyl)-3-hex-5-ynyl-2,2-dioxo-2,4-dihydro-1H-2ꢀ6-naphtho[2,3-c]thiophene-
5,8-dione (28). A stirring solution of MOM-protected hydroquinone 22 (47 mg, 0.088 mmol) in 1 mL
of MeOH was treated with acetyl chloride (25.2 ꢁL, 0.352 mmol). After 3 h, H2O (10 mL) was added to
the reaction solution. The resulting solution was partitioned between EtOAc and H2O and the aqueous
layer was extracted with EtOAc (3 x 10 mL). The combined organic fractions were dried over Na2SO4,
filtered, and concentrated in vacuo to give 4-(tert-butyldimethylsilanyl)-3-hex-5-ynyl-2,2-dioxo-2,4-
dihydro-1H-2ꢀ6-naphtho[2,3-c]thiophene-5,8-diol as a colorless oil. This material was used without
further purification.
To a stirring solution of this crude dihydroquinone in 1.5 mL of CH2Cl2 was added iodobenzene diacetate
(31 mg, 0.097 mmol). After 15 min, the reaction mixture was concentrated in vacuo to give a pink oil.
Purification of this oil by flash column chromatography (Florasil, 20% EtOAc/hexanes as eluent) afforded

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HETEROCYCLES, Vol. 81, No. 1, 2010
4-(tert-butyldimethylsilanyl)-3-hex-5-ynyl-2,2-dioxo-2,4-dihydro-1H-2ꢀ6-naphtho[2,3-c]thiophene-5,8-
dione (28) (33 mg, 39% over 2 steps) as a pink oil. IR (thin film) 3284, 1643 cm-1; 1H NMR (300 MHz,
CDCl3) ꢀ 6.78 (d, J = 10.1 Hz, 1H), 6.89 (d, J = 10.0 Hz, 1H), 6.71 (s, 1H), 4.22 (s, 1H), 3.97-3.96 (m,
2H), 2.55-2.44 (m, 2H), 2.22 (td, J = 6.9, 2.6 Hz, 2H), 1.98 (t, J = 2.6 Hz, 1H), 1.90-1.79 (m, 2H),
13
1.63-1.56 (m, 2H), 0.92 (s, 9H), 0.05 (s, 3H), -0.08 (s, 3H); C NMR (75 MHz, CDCl3) ꢀ 184.8, 183.4,
143.9, 140.7, 136.7, 136.4, 135.6, 134.8, 132.1, 117.1, 83.7, 69.0, 52.9, 29.3, 28.0, 27.1, 26.5, 24.2, 18.0,
1.0, -4.0, -5.0; LRMS (ESI) m/z (relative intensity) 443.2 (100%, M + H+).
ACKNOWLEDGEMENTS
Financial support from the National Institutes of Health, General Medical Sciences Division under the
auspices of GM-37681 is gratefully acknowledged. The X-ray crystallography facility of the Huck
Institutes for the Life Sciences is supported through CHE-0131112 from the National Science
Foundation.
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13. Density functional calculations on the model systems i-iii with the B3LYP 631G* functional on
Spartan '04:
Me
Me
Me
SO2
SO2
SO2
Rel. total
energy
(kcal/mol)
i
ii
iii
0.0
18
30
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