Phosphorothioic acids and related compounds as surrogates for H 2S-synthesis of chiral tetrahydrothiophenes

Article abstract of DOI:10.1021/ja210758n

The convenient preparation of chiral tetrahydrothiophenes (THTs) in high enantiopurity via phosphorothioic acids and related compounds is reported. We consider these to be safer alternatives to the use of H₂S which is a highly toxic gas. Each o

Full text of DOI:10.1021/ja210758n

Article
pubs.acs.org/JACS
Phosphorothioic Acids and Related Compounds as Surrogates for
H2SSynthesis of Chiral Tetrahydrothiophenes
Forest J. Robertson and Jimmy Wu*
Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, United States
S
* Supporting Information
ABSTRACT: The convenient preparation of chiral tetrahydrothiophenes
(THTs) in high enantiopurity via phosphorothioic acids and related compounds
is reported. We consider these to be safer alternatives to the use of H2S which is
a highly toxic gas. Each of the THTs is derived from a common intermediate,
thereby greatly enhancing the flexibility of the synthesis. The key transformation
is a base-promoted, intramolecular, carbon−sulfur bond-forming event. These reactions are highly stereospecific as they operate
through a double SN2 displacement mechanism. The methodology is amenable to a broad array of functional groups and
heterocycles. The tetrahydrothiophene motif is important because it is present in a number of bioactive natural products. They
have also been utilized to promote various asymmetric transformations including hydrogenation, epoxidation, cyclopropanation,
and aziridination reactions.
react with carbon-based electrophiles to form two different
carbon−sulfur bonds. However, a major concern with the use
of H2S is that it is a highly toxic gas. Inhalation at
concentrations >500 ppm causes pulmonary edema resulting
in immediate collapse followed by death.1 Related compounds
such as NaSH or Na2S (hydrate) are less dangerous since they
are solids but their exposure to mild acid will nonetheless
generate H2S. Therefore, while these reagents are quite useful,
they are impractical to use on larger scales and in industrial
processes.
1. INTRODUCTION
For a number of years now, our laboratories have been
developing new methods of incorporating sulfur into
compounds through the construction of carbon−sulfur bonds.
In particular, we are interested in discovering novel processes
for the synthesis of thioethers and saturated sulfur heterocycles.
Classical means for the preparation of these compounds nearly
always employ nucleophilic or electrophilic sulfur reagents in
which one of the carbon−sulfur bonds is already present
(Figure 1). For example, the respective reactions of thiols or
Our group has been exploring the use of dialkyl
phosphorothioic acids 1−2 as safer alternatives to H2S (Scheme
1). These are odorless compounds that are resistant to
hydrolysis under both acidic and basic conditions. They can
be stored at room temperature in air for extended periods of
time without any appreciable decomposition. Furthermore,
phosphorothioic acids are easily prepared on multigram scale in
one pot from the corresponding dialkyl phosphite.
Figure 1. Synthesis of thioethers with sulfur reagents containing pre-
existing C−S bonds.
sulfenyl chlorides with electrophiles or nucleophiles are limited
by the presence of pre-existing carbon−sulfur bonds (Figure 1).
The breadth of the synthesis of thioethers and sulfur
heterocycles would be greatly expanded if there were a reagent
available in which both carbon substituents on either side of
sulfur could be independently defined (Scheme 1). One such
Scheme 1. Phosphorothioic Acids as Surrogates for H2S
We have previously reported the use of 2 as a surrogate for
H2S in the synthesis of thioethers (eq 1).2 This is a two-step
method in which the first step is either the UV-promoted3 or
reagent is hydrogen sulfide (i.e., H2S), which is doubly
nucleophilic at sulfur. H2S is quite versatile and can sequentially
Received: November 15, 2011
Published: January 12, 2012
© 2012 American Chemical Society
2775
dx.doi.org/10.1021/ja210758n | J. Am. Chem.Soc. 2012, 134, 2775−2780

Journal of the American Chemical Society
Article
Ga(OTf)-catalyzed4−6 preparation of the corresponding
phosphorothioate esters7,8 from phosphorothioic acids and
either alcohols or ethers. Treatment of the phosphorothioate
esters with an exogenous alkoxide completes the synthesis of
the thioethers. This methodology is substantially more efficient
than other means for obtaining the title compounds. The
transformation is stereospecific because it proceeds via a double
SN2 pathway. We reasoned that phosphorothioic acids could
also be utilized as H2S surrogates in intramolecular variants.
This would provide facile access to chiral tetrahydrothiophenes
via enantioenriched chiral alcohol 3 (eq 2). The key step is a
base-promoted cyclization event to forge the second carbon−
sulfur bond, a reaction that is analogous to what we reported
for the intermolecular, one-pot, synthesis of thioethers.2
The tetrahydrothiophene9 moiety is quite important and is
found in a number of bioactive natural products. Among these
are α-glucosidase inhibitors (i.e., salacinol, kotalanol, salaprinol,
and ponkoranol),10,11 oral hypocholesterolemic agents (i.e.,
breynin A−B and epibreynin B),12,13 brain-type cholecystokinin
(CCK) receptor antagonists (i.e., tetronothiodin),14 agonists/
antagonists for the human A3 adenosine receptor,15 and biotin
which is required for gluconeogenesis, fatty acid production/
metabolism, and amino acid metabolism.16 They are also useful
as easily displaceable ligands in gold complexes.17
Tetrahydrothiophenes have also been utilized as chiral
ligands for various enantioselective transformations. Hauptman
and co-workers demonstrated that rhodium complexes with
chiral bis(phosphinite) ligands 518 are effective in asymmetric
hydrogenation reactions. Metzner and co-workers19 showed
that sulfur ylides derived from 6−7 can promote enantiose-
lective epoxidation reactions while Huang20 demonstrated the
utility of 8 in aziridinations. Aggarwal’s group used sulfur ylides
derived from 9 as stereoselective epoxidation,21 cyclopropana-
tion,22 and aziridination reagents.23
2. RESULTS AND DISCUSSION
We envisioned accessing the obligatory enantioenriched alcohol
3, and eventually the chiral tetrahydrothiophenes, via
asymmetric reduction of the corresponding ketone (Scheme
Scheme 2. Proposed Synthesis of Requisite Chiral Alcohol
2). This stereoselective transformation could be accomplished
through a number of different methods; but in particular, we
elected to focus our attention on the Corey−Bakshi−Shibata
(CBS) reduction which makes use of chiral oxazaborolidine
(OAB) catalysts.30 The CBS protocol is effective for ketones
flanked by an aromatic group on one side and a linear alkyl
chain on the other. There have also been a few instances in
which the generation of chiral alcohols in this manner was
shown to work well in the presence of sulfides.31 However, we
were uncertain if the phosphorothioate functional group would
be compatible with the catalyst or lead to diminished
selectivities. As an alternative, if this route should prove
unfeasible, we could also explore the use of Noyori’s
asymmetric transfer hydrogenation protocol, which can also
be compatible with sulfur functional groups.32
In order to answer these critical questions at the earliest stage
possible, we decided to begin our studies with the commercially
available chloroketone 12a (Table 1). Initial alkylation attempts
Table 1. Optimization of 1st C−S Bond Formation
With respect to the synthesis of enantioenriched tetrahy-
drothiophenes, there have been few precedents. We outline
here the more notable reports. Metzner19 and Huang’s20
preparation of 6−8 relied on the double displacement reaction
of the corresponding mesylated diol with Na2S. Wang,24
Hogberg,25 and Besada26 have also reported syntheses of chiral
̈
tetrahydrothiophenes. These methods were based on conjugate
additions, sulfur ylides, or singlet oxygen-mediated rearrange-
ments.
Njardarson and co-workers27 have developed copper-
catalyzed ring expansions of vinyl thiiranes to yield
dihydrothiophenes while Maguire and co-workers28 published
an enantioselective C−H insertion approach toward chiral
sulfolanes. Block and co-workers reported the [3,3] sigmatropic
rearrangement of bispropenyl sulfides to yield thiophenes and
dihydrothiophenes.29 Although the chemistries described in
these reports do not provide direct access to tetrahydrothio-
phenes, they are superb examples of the synthesis of 5-
membered sulfur heterocycles.
were carried out between 12a and diethylphosphorothioic acid
(1) in the presence of various bases or AgNO3 (entries 1−4).
These experiments led to uniformly unacceptably low yields.
We also examined the use of sodium diethylphosphorothioate
13 which furnished the desired product in 63% yield (entry 6).
The use of independently prepared iodide 12b led to a 98%
isolated yield of 14a (entry 7). Interestingly, substantially lower
yields were obtained for the alkylation of iodide 12b that was
prepared in situ with NaI/NEt3 (entry 5).
Herein, we describe an efficient stereospecific synthesis of
enantioenriched tetrahydrothiophenes which utilizes phosphor-
othioic acids and related compounds as H2S surrogates.
With ketophosphorothioate ester 14a in hand, we proceeded
to examine the key enantioselective reduction step (Scheme 3).
CBS reduction of ketone 14a furnished alcohol 16a in 94%
2776
dx.doi.org/10.1021/ja210758n | J. Am. Chem.Soc. 2012, 134, 2775−2780

Journal of the American Chemical Society
Article
highly efficient method for its preparation (Scheme 5). The
Scheme 3. CBS Reduction and Chiral THT Formation
commercially available chloroester 20 (∼0.5 US$/gram) was
Scheme 5. Synthesis of Common Intermediate 19
yield. Unfortunately, attempts to determine the enantiopurity
of 16a at this time was unsuccessful. At issue were difficulties in
resolving the enantiomers of the corresponding racemic alcohol
using chiral HPLC analysis. Instead, we elected to complete the
synthesis of the desired chiral tetrahydrothiophene 17a by
constructing the second carbon−sulfur bond.
After surveying several different reaction parameters, we
settled on the use of NaH in DMF as optimized conditions for
the cyclization event (Scheme 3).33 Tetrahydrothiophene 17a
was isolated in 82% yield. Gratifyingly, the determination of the
enantiomeric excess of 17a was possible at this point and was
measured to be 97% ee. As a control, we also carried out the
asymmetric reduction of chloroketone 12a to the alcohol 18
(96% ee, eq 3). The fact that similar levels of enantioinduction
was observed for both chloride 18 and tetrahydrothiophene
17a supports the notions that (1) the initial asymmetric
reduction of 12a occurred at very high levels and that (2) there
was little to no loss of enantiopurity in the cyclization event.
Having established that phosphorothioate esters are compatible
with CBS asymmetric reductions, we proceeded by developing
a more streamlined synthesis of the requisite ketones.
treated with NaI in acetone to generate the corresponding
iodide, in situ. The addition of sodium diethylphosphorothioate
13 to the reaction mixture provided 21 in 85% isolated yield.
Weinreb amide formation following the Merck protocol gave
the desired product 19 in 96% yield.34
Having developed an effective synthesis of the common
intermediate 19, we then set out to determine if its reaction
with organomagnesium reagents would be compatible with the
presence of the phosphorothioate ester moiety at the terminus
of the molecule. Previously, our group has demonstrated that
allylic phosphorothioate esters will undergo transition metal-
free3 or Cu(I)-catalyzed cross-coupling reactions with various
Grignard reagents.7 Our own experiences with this functional
group led us to believe that alkyl phosphorothioate esters are
significantly less reactive than the related allylic systems and
would likely not interfere with ketone formation.
Gratifyingly, treatment of 19 with various organomagnesium
reagents furnished ketones 14a−o in very good to excellent
yields. The Grignard reagents were prepared from the
corresponding aryl halide and magnesium turnings or by
halogen-magnesium exchange as described by Knochel and co-
workers.35 As is evident in Table 2, we can access a wide
Table 2. Scope of Ketone Formation
Although chloroketone 12a and several other substrates were
commercially available, we realized that the generality of the
described chiral tetrahydrothiophene synthesis would be greatly
expanded if all of the ketone precursors could be prepared from
a single common intermediate (Scheme 4). In this manner, we
Scheme 4. Streamlined Retrosynthesis of THTs
would also gain access to tetrahydrothiophenes whose
syntheses would require the use of noncommercially available
chloroketones.
We imagined that Weinreb amide 19 could potentially serve
as the putative common intermediate (Scheme 4). The reaction
between 19 and various functionalized organomagnesium
reagents would lead to an array of phosphorothioate ketones
that could then be carried forth to the desired chiral
tetrahydrothiophenes.
a
b
c
Reaction required 3 h. Warmed to rt. Required an additional 3.0
d
equiv of Ar-MgBr. Required 12 equiv of LiCI.
assortment of ketones. These include products that contain
electron-withdrawing and -donating groups as well as a broad
range of functionalities (i.e., halides, esters, nitriles, ketals, and
amides) and heterocycles (i.e., indolyl, furanyl, and thienyl).
After exploring several unsuccessful routes toward Weinreb
amide 19, we settled on the following two pot procedure as a
2777
dx.doi.org/10.1021/ja210758n | J. Am. Chem.Soc. 2012, 134, 2775−2780

Journal of the American Chemical Society
Article
Interestingly, the use of organolithium reagents resulted in
significantly lower yields.
Next, we converted ketones 14a−o to the desired chiral
alcohols using the CBS procedure described in Scheme 3
(Table 3). In each case, high yields were achieved for the CBS
single crystal X-ray analysis (Figure 2). The stereochemical
configurations of the remaining tetrahydrothiophenes were
assigned based on analogy.
Table 3. Asymmetric Ketone Reduction
Figure 2. Confirmation of Absolute Stereochemistry via Single Crystal
X-ray Analysis of Sulfone (S)-22.
Curiously, two substrates (i.e., 17h, 17j) in Table 4 were
isolated in nearly racemic form. We considered the possibility
that under the basic reaction conditions (excess NaH), the
products were undergoing racemization (Scheme 6). The
Scheme 6. Proposed Mechanism of Racemization for 17h
a
Used 1.2 equiv BH3 THF.
reduction, but as was the case before, we elected to postpone
determination of stereoselectivity levels until after the second
carbon−sulfur bond-forming event.
Treatment of the chiral alcohols with NaH in DMF at 55 °C
led to efficient ring closure (Table 4). With the exception of a
conjugated nitrile and ester in the para positions of 17h and
17j, respectively, could potentially serve as stabilizing groups
for the putative anions resulting from deprotonation with NaH.
To support this conjecture, we prepared ketone 17p which
has a nitrile in the meta position. We reasoned that by moving
the nitrile out of conjugation with the benzylic site we would
reduce the acidity of the relevant proton, thereby retarding the
rate of deprotonation/racemization. Indeed CBS reduction of
17p followed by tetrahydrothiophene formation generated the
expected product in 74% ee (Table 5, entry 1). This is a
Table 4. Scope of Chiral Tetrahydrothiophene Formation
Table 5. Improvement of ee for Substrates Possessing
EWG’s
substantial improvement to the enantiopurity observed for the
4-CN-substituted tetrahydrothiophene 17h (cf. Table 4,
compound 17h, 0% ee). We could further improve the ee of
tetrahydrothiophene 17p to 82% ee by reducing the amount of
NaH (1.2 equiv) used in the cyclization. A similar reduction in
the amount of NaH also improved the enantiopurity of 4-CN-
and 4-t-BuO2C-substituted tetrahydrothiophenes (entries 3−
4). We also observed a concomitant increase in isolated yield.
a
The ee was determined on this corresponding sulfone after oxidation
with mCPBA.
handful of compounds (vide infra), high enantioselectivities
were obtained for each of the tetrahydrothiophenes. Again,
broad substrate scope and functional group compatibility was
demonstrated. We confirmed the absolute stereochemistry of
17e by oxidation to the corresponding sulfone 22 followed by
2778
dx.doi.org/10.1021/ja210758n | J. Am. Chem.Soc. 2012, 134, 2775−2780

Journal of the American Chemical Society
Article
Subjecting enantioenriched 17h to the typical reaction
conditions (NaH/DMF) resulted in nearly complete race-
mization of the product (eq 4). Taken together, the data
described in Table 5 and eq 4, support the notion that the
reason tetrahydrothiophenes 17h and 17j were isolated in
racemic fashion in Table 4 was due to racemization resulting
from deprotonation during the course of the reaction.
substantially safer to handle. That these important products are
all derived from a common intermediate 19 permits the
streamlined preparation of various analogs. Each step of the
synthesis is tolerant to a broad range of functional groups and
the presence of numerous types of heterocycles. Future work in
our laboratories will include the exploration of these chiral
tetrahydrothiophenes as organocatalysts and as chiral ligands in
select asymmetric transformations. The availability of chiral 2-
aryl tetrahydrothiophenes also permits further examination of
stereochemical issues associated with the alkylation or
protonation of the carbanion of the corresponding sulfoxides.38
4. EXPERIMENTAL SECTION
With respect to the mechanism of tetrahydrothiophene
formation, we believe that the chiral alcohol is first
deprotonated by NaH to generate a transient alkoxide 25
(Scheme 7). The next step, which is transfer of the phosphate
General Procedure for Ketone Preparation. To a solution of
19 (0.134 mmol, 40.0 mg) in THF (0.18 mL) at −78 °C was added 1
M PhMgBr (0.401 mmol, 0.401 mL). The reaction mixture was
warmed to 0 °C and stirred for 0.5 h. The reaction was quenched with
a saturated aqueous NH4Cl (50 mL), extracted with Et2O (50 mL),
washed with brine (50 mL), dried with MgSO4, and concentrated in
vacuo. The residue was purified by silica gel chromatography (50%
EtOAc/hexanes) to afford 14a as a pale yellow oil.
Scheme 7. Proposed Mechanism
General Procedure for CBS Reduction. To a flame-dried round-
bottom flask was added 15 (1.0 M in toluene, 0.029 mmol, 0.029 mL).
The toluene was removed in vacuo, BH3·THF (1.0 M in THF, 0.176
mmol, 0.176 mL) was added, and the solution was cooled to 0 °C. A
solution of 14a (0.293 mmol, 10.0 mg) in THF (0.084 mL) was added
to the solution of 15 and borane. After 5 min, the reaction was deemed
complete as judged by TLC analysis. The reaction was quenched at 0
°C with MeOH (10 mL) and then the reaction mixture was
concentrated in vacuo. The residue was purified by silica gel
chromatography (50% EtOAc/hexanes) to afford 16a as a pale yellow
oil.
General Procedure for Tetrahydrothiophene Formation. To
a solution of 16a (0.300 mmol, 95.0 mg) in DMF (6.0 mL) was added
NaH (0.600 mmol, 24.0 mg). This solution was placed in a preheated
oil bath that was set to 55 °C, and the reaction was stirred overnight.
The reaction was diluted with Et2O (50 mL), washed with a 1:1
H2O:brine solution (2 × 50 mL), dried with MgSO4, concentrated in
vacuo, and the residue was purified by silica gel chromatography (5%
EtOAc/hexanes) to afford 17a as a clear and colorless oil.
group onto oxygen, is driven by the relatively strong
phosphorus−oxygen bond that is formed.8 The resultant
thiolate is highly nucleophilic and displaces phosphate to
furnish the desired 5-membered ring. The high enantiopurity
that we observe in the isolated tetrahydrothiophenes supports
the notion that the carbon−sulfur bond-forming event occurs
via an SN2-type pathway at the stereodefining step.
To extend this methodology to other ring sizes, we have
applied this chemistry to a representative synthesis of chiral
thietanes 30. Thus, conversion of chloroketone 27 to 28 was
accomplished in one-pot transformation. CBS reduction of
ketone 28 furnished enantioenriched alcohol 29 which cyclized
to the desired thietane 30 (74% yield, 87% ee) upon treatment
with NaH. Thietanes are important compounds utilized by
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures and spectral data (1H NMR, 13C
NMR, IR, HRMS, HPLC) for all new compounds and the CIF
file for compound (S)-22. This material is available free of
charge via the Internet at http://pubs.acs.org.
certain animals as a means for chemical communication.36
A
limited number of achiral syntheses of thietanes have been
reported.37 Unfortunately, numerous attempts to apply this
methodology to the synthesis of chiral thianes, failed.
AUTHOR INFORMATION
■
Scheme 8. Synthesis of Chiral Thietane 30
Corresponding Author
jimmy.wu@dartmouth.edu
ACKNOWLEDGMENTS
■
Financial support for this research was provided by an NSF
CAREER Award (CHE-1052824), Dartmouth College, and the
Walter and Constance Burke Foundation. F.J.R. acknowledges
the United States Department of Education for a GAANN
fellowship.
REFERENCES
(1) Reiffenstein, R. J. Annu. Rev. Pharmacol. Toxicol. 1992, 109.
(2) Robertson, F.; Wu, J. Org. Lett. 2010, 12, 2668.
(3) Han, X.; Zhang, Y.; Wu, J. J. Am. Chem. Soc. 2010, 132, 4104.
(4) Han, X.; Wu, J. Org. Lett. 2010, 12, 5780.
■
3. CONCLUSIONS
We have demonstrated a facile synthesis of chiral tetrahy-
drothiophenes using phosphorothioic acids and related
compounds. These are synthetic equivalents to H2S that are
2779
dx.doi.org/10.1021/ja210758n | J. Am. Chem.Soc. 2012, 134, 2775−2780

Journal of the American Chemical Society
Article
(5) Forthe synthesis ofcarbon−sulfur bonds directly from alcohols
“on-water”,see: Cozzi, P. G.; Zoli, L. Angew. Chem., Int. Ed. 2008, 47,
4162.
(6) Forsynthesis of carbon−sulfurbonds directly from alcohols
catalyzed by stoichiometric In(III),see: Snyder, S. A.; Breazzano, S.
P.; Ross, A. G.; Lin, Y.; Zografos, A. L. J. Am. Chem. Soc. 2009, 131,
1753.
(7) We have also reportedthe use of phosphorothioate esters in
Cu(I)-catalyzed C−C bond-formingreactions with organomagnesium
reagents, see: Lauer, A. M.; Mahmud, F.; Wu, J. J. Am. Chem. Soc.
2011, 133, 9119.
(27) Rogers, E.; Araki, H.; Batory, L. A.; McInnis, C. E.; Njardarson,
J. T. J. Am. Chem. Soc. 2007, 129, 2768.
(28) Flynn, C. J.; Elcoate, C. J.; Lawrence, S. E.; Maguire, A. R. J. Am.
Chem. Soc. 2010, 132, 1184.
(29) Block, E.; Zhao, S. H. Tetrahedron Lett. 1990, 31, 4999.
(30) Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. 1998, 37, 1986.
(31) (a) Cho, B. T.; Choi, O. K.; Kim, D. J. Tetrahedron: Asymm.
2002, 13, 697. (b) Cho, B. T.; Shin, S. H. Tetrahedron 2005, 61, 6959.
(32) (a) Kitamura, M.; Ohkuma, O.; Inoue, S.; Sayo, N.;
Kumobayashi, H.; Akutagawa, S.; Ohta, T.; Takaya, H.; Noyori, R. J.
Am. Chem. Soc. 1988, 110, 629. (b) Tranchier, J.-P.; Ratovelomanana-
Vidal, V.; Genet
Ratovelomanana-Vidal, V.; Savignac, P.; Genet
1996, 37, 7721.
̂
, J.-P. Tetrahedron Lett. 1997, 38, 2951. (c) Gautier, I.;
(8) For the conversion of α-ketophosphorothioate esters into
̂
, J.-P. Tetrahedron Lett.
alkenes, see. (a) Maciagiewicz, I.; Dybowski, P.; Skowronska, A.
̨
Tetrahedron 2003, 59, 6057. (b) Maciagiewicz, I.; Dybowski, P.;
Skowronska, A. Tetrahedron Lett. 1999, 40, 3791. (c) Krawczyk, E.
Synthesis 2006, 716. (d) Tanaka, K.; Uneme, H.; Ono, N.; Kaji, A.
Chem. Lett. 1979, 1039. (e) Tanaka, K.; Uneme, H.; Ono, N.; Kaji, A.
Synthesis 1979, 890.
(33) For a leading referencefor the related conversion of epoxides to
thiiranes, see: Kaboudin, B.; Norouzi, H. Tetrahedron Lett. 2004, 45,
1283.
(34) Williams, J. M.; Jobson, R. B.; Yasuda, N.; Marchesini, G.;
Dolling, U.; Grabowski, E. J. J. Tetrahedron. Lett. 1995, 36, 5461.
(35) (a) Knochel, P.; Dohle, W.; Gommermann, N.; Kneisel, F. F.;
Kopp, F.; Korn, T.; Sapountzis, I.; Vu, V. A. Angew. Chem., Int. Ed.
2003, 42, 4302. (b) Jensen, A. E.; Dohle, W.; Sapountzis, I.; Lindsay,
D. M.; Vu, V. A.; Knochel, P. Synthesis 2002, 565.
(36) (a) Brinck, C.; Erlinge, S.; Sandell, M. J. Chem. Ecol. 1983, 9,
727. (b) Crump, D. R. J. Chem. Ecol. 1980, 6, 837. (c) Crump, D. R. J.
Chem. Ecol. 1980, 6, 341. (d) Zhang, J.; Sun, L.; Zhang, Z.; Wang, Z.;
Chen, Y.; Wang, R. J. Chem. Ecol. 2002, 28, 1287.
(37) (a) Ueno, Y.; Yadav, L. D. S.; Okawara, M. Synthesis 1981, 547.
(b) Yadav, L. D. S.; Kapoor, R. Synthesis 2002, 1502.
(38) (a) Durst, T.; McClory, M. R. J. Am. Chem. Soc. 1971, 93, 3077.
(b) Bory, S.; Lett, R.; Moreau, B.; Marquet, A. Tetrahedron Lett. 1972,
13, 4921. (c) Bory, S.; Marquet, A. Tetrahedron Lett. 1973, 14, 4158.
(d) Nishihata, K.; Nishio, M. Chem. Commun. 1971, 958. (e) Brown,
T. J.; Chapman, R. F.; Cook, D. C.; Hart, T. W.; McLay, I, M.; Jordan,
R.; Mason, J. S.; Palfreyman, M. N.; Walsh, R. J. A.; Withnall, M. T.;
Aloup, J.-C.; Cavero, I.; Farge, D.; James, C.; Mondot, S. J. Med. Chem.
1992, 35, 3613.
(9) Rajappa, S.; Deshmukh, A. R. Thiophenes and their Benzo
Derivatives: Reactivity. In Comprehensive Heterocyclic Chemistry III;
Katritzky, A. R.; Ramsden, C. A.; Scriven, E. F. V.; Taylor, R. J. K.,
Eds.; Elsevier: Amsterdam, 2008; Vol. 3, pp 793−797.
(10) (a) Yoshikawa, M.; Murakami, T.; Shimada, H.; Matsuda, H.;
Yamahara, J.; Tanabe, G.; Muraoka, O. Tetrahedron Lett. 1997, 38,
8367. (b) Yoshikawa, M.; Murakami, T.; Yashiro, K.; Matsuda, H.
Chem. Pharm. Bull. 1998, 46, 1339. (c) Yoshikawa, M.; Morikawa, T.;
Matsuda, H.; Tanabe, G.; Muraoka, O. Bioorg. Med. Chem. 2002, 10,
1547.
(11) (a) Yoshikawa, M.; Xu, F.; Nakamura, S.; Wang, T.; Matsuda,
H.; Tanabe, G.; Muraoka, O. Heterocycles 2008, 75, 1397. (b) Tanabe,
G.; Sakano, M.; Minematsu, T.; Matsuda, H.; Yoshikawa, M.;
Muraoka, O. Tetrahedron 2008, 64, 10080.
(12) Meng, D.; Chen, W.; Zhao, W. J. Nat. Prod. 2007, 70, 824.
(13) Trost, W. IRCS Med. Sci. 1986, 14, 905.
(14) Page, P. C. B.; Vahedi, H.; Batchelor, K. J.; Hindley, S. J.; Edgar,
M.; Beswick, P. Synlett 2003, 7, 1022.
(15) Jeong, L. S.; Jin, D. Z.; Kim, H. O.; Shin, D. H.; Moon, H. R.;
Gunaga, P.; Chun, M. W.; Kim, Y.-C.; Melman, N.; Gao, Z.-G.;
Jacobsen, K. A. J. Med. Chem. 2003, 46, 3775.
(16) De Clercq, P. J. Chem. Rev. 1997, 97, 1755.
(17) Uson, R.; Laguna, A.; Laguna, M.; Briggs, D. A.; Murray, H. H.;
Fackler, J. P. (Tetrahydrothiophene)Gold(I) or Gold(III) Complexes.
In Inorganic Syntheses; Kaesz, H. D., Ed.; John Wiley & Sons: New
York, 1989; Vol. 26, pp 85−91.
(18) Hauptman, E.; Shapiro, R.; Marshall, W. Organometallics 1998,
17, 4976.
̀
(19) (a) Zanardi, J.; Lamazure, D.; Miniere, S.; Reboul, V.; Metzner,
P. J. Org. Chem. 2002, 67, 9083. (b) Zanardi, J.; Leriverend, C.; Aubert,
D.; Julienne, K.; Metzner, P. J. Org. Chem. 2001, 66, 5620. (c) Julienne,
K.; Metzner, P. J. Org. Chem. 1998, 63, 4532. (d) Julienne, K.;
Metzner, P.; Henryon, V. J. Chem. Soc., Perkin Trans. 1 1999, 731.
(20) Gui, Y.; Shen, S.; Wang, H.-Y.; Li, Z. Y.; Huang, Z.-Z. Chem.
Lett. 2007, 36, 1436.
(21) (a) Aggarwal, V. K.; Alonso, E.; Bae, I.; Hynd, G.; Lydon, K. M.;
Palmer, M. J.; Patel, M.; Porcelloni, M.; Richardson, J.; Stenson, R. A.;
Studley, J. R.; Vasse, J. L.; Winn, C. L. J. Am. Chem. Soc. 2003, 125,
10926. (b) Aggarwal, V. K.; Bae, I.; Lee, H.-Y.; Richardson, J.;
Williams, D. T. Angew. Chem., Int. Ed. 2003, 42, 3274.
(22) Riches, S. L.; Saha, C.; Filgueira, N. G.; Grange, E.; McGarrigle,
E. M.; Aggarwal, V. K. J. Am. Chem. Soc. 2010, 132, 7626.
(23) (a) Illa, O.; Arshad, M.; Ros, A.; McGarrigle, E. M.; Aggarwal, V.
K. J. Am. Chem. Soc. 2010, 132, 1828. (b) Aggarwal, V. K.; Alonso, E.;
Fang, G.; Ferrara, M.; Hynd, G.; Porcelloni, M. Angew. Chem., Int. Ed.
2001, 40, 1433.
(24) Luo, G.; Zhang, S.; Duan, W.; Wang, W. Tetrahedron Lett. 2009,
50, 2946.
(25) Karlsson, S.; Hogberg, H. Org. Lett. 1999, 1, 1667−1669.
̈
(26) Besada, P.; Per
́ ́
ez, M.; Gomez, G.; Fall, Y. Tetrahedron Lett.
2009, 50, 6941.
2780
dx.doi.org/10.1021/ja210758n | J. Am. Chem.Soc. 2012, 134, 2775−2780