Thiete Dioxides as Templates Towards Twisted Scaffolds and Macrocyclic Structures

Article abstract of DOI:10.1002/chem.201905751

Thiete dioxide units have been employed as a template for further functionalization through C?H activation strategies. Using simple thiete dioxide building blocks, a new library of axially chiral molecules has been synthesized that owe their stability to electrostatic interactions in the solid state. Similar starting materials were further engaged in the formation of cyclic trimeric structures, opening the pathway to unprecedented macrocyclic ring systems.

Full text of DOI:10.1002/chem.201905751

A Journal of
Accepted Article
Title: Thiete Dioxides as Templates towards Novel Twisted Scaffolds
and Macrocyclic Structures
Authors: Andreas N Baumann, Felix Reiners, Peter Mayer, Alexander
F Siegle, Oliver Trapp, and Dorian Didier
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Thiete Dioxides as Templates towards Novel Twisted Scaffolds
and Macrocyclic Structures
Andreas N. Baumann,[a]† Felix Reiners,[a]† Alexander F. Siegle,[a] Peter Mayer, Oliver Trapp[a] and
Dorian Didier*[a]
Abstract: Thiete dioxide units have been employed as a template for
further functionalization through C-H activation strategies. Using
simple thiete dioxide building blocks, a new library of axially chiral
molecules has been synthesized, owing their stability to electrostatic
interactions in the solid state. Similar starting materials were further
engaged in the formation of novel cyclic trimeric structures, opening
on the design of unprecedented macrocyclic ring systems.
novel catalysts[7] and atropisomers[8] but plays an important role in
drug design.[9] Beside that, thiete dioxide-based macrocycles can
be interesting analogs to the known compound class, namely
spherands, which were first reported by Cram in 1979.[10] They
can be classified as macrocyclic ligands with limited
conformational flexibility. With a preorganization and an electron-
pair-lined cavity, they are strong complexation receptors for ions,
such as lithium, sodium or potassium.[11] Indeed, the binding
constant for lithium ions is one of the strongest reported to
date.[12,13] With this in mind, the preparation of thiete dioxide based
macrocyclic structures was envisioned. Therefore, 3-substituted
thiete dioxide units bearing a bromide at the meta position of the
aryl substituent were utilized (Scheme 1).
Introduction
Thiete dioxides possess unique electronic and structural
properties.[1] Although natural products containing thiete cores
were not to be found in the literature, they constitute an interesting
entry point to their saturated analogs, thietanes, which have found
applications in drug discovery or demonstrated their interesting
properties in life-science as pesticide or sweetener.[2]
In the course of our program dedicated to the development of
efficient routes towards unsaturated four-membered rings, we
recently put together simple strategies for the synthesis and
functionalization of cyclobutenes,[3] azetines[4] and 2H-thiete
dioxides,[5] as well as their involvement in accessing sophisticated
fused ring systems.[6] Concerning 2H-thiete dioxides, two
sequences were developed. While the first one relies on an -
lithiation/transmetalation/Negishi cross-coupling sequence, the
second is based on C-H activation strategy and allows for a broad
and tolerant functionalization of the unsaturated S-containing
four-membered ring scaffold.
Scheme 1. Thiete dioxide units as a common template for accessing axially
chiral disubstituted structures and macrocyclic analogues to the known
spherand, first reported by Cram.
Given that such structures constitute a unique entry in the
repertoire of strained heterocycles, we set out to take the next
step in their architectural diversification. We describe herein the
study of palladium-catalyzed C-H functionalization of
3-substituted thiete dioxides towards the formation of chiral
disubstituted thiete dioxides and thiete dioxide-based
macrocycles (Scheme 1). Axial chirality is of great importance in
many areas of chemistry and is not limited to the synthesis of
Results and Discussion
The project was initiated by synthesizing a range of 3-substituted
thiete dioxide building blocks. Starting from commercially
available 3-thietanone, the addition of an organomagnesium or an
organolithium furnished the corresponding tertiary alcohols after
hydrolysis (Scheme 2). The crude product was subsequently
oxidized with mCPBA to give thietane 1. Desired building blocks
2a-t were obtained upon addition of mesyl chloride and
trimethylamine, triggering a -elimination to generate the double
bond. For simple aromatic systems (phenyl, naphthyl, anthryl), we
have witnessed a general decrease in efficiency with increasing
sterical hindrance (from 78% for 2a to 25% for 2c). However, the
[a]
MSc. A. N. Baumann, MSc. F. Reiners, Dr. Alexander F. Siegle, Dr.
Peter Mayer, Prof. Dr. Oliver Trapp, Dr. D. Didier
Department of Chemistry
Ludwig-Maximilians University
Butenandtstraße 5-13, 81377 Munich
E-mail: dorian.didier@cup.uni-muenchen.de
These authors contributed equally to the manuscript
†
Supporting information for this article is given via a link at the end of
the document.
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procedure proved to be quite versatile, allowing for the
introduction of a variety of substituents, including electron
deficient groups (p-fluorophenyl, m-trifluomethylphenyl or 8-
quinolinyl) and electron rich substituents (p-, m- or o-
methoxyphenyl). A broad range of functionalized compounds (2a-
u) was isolated in moderate to good yields over three synthetic
steps (22 to 78%).
Scheme 2. Synthetic scope of monofunctionalized thiete dioxides.
In the course of our study on the functionalization of thiete
dioxides through C-H activation, we synthesized a range of bis-
arylated structures such as 3a (70%), employing catalytic
amounts of Pd(OAc)2 in the presence of pivalic acid, tricyclohexyl
phosphine and potassium carbonate (Scheme 3). In our previous
report, we showed that such catalytic system preferentially follows
a BIES (base-assisted intramolecular electrophilic substitution)
mechanism. Having two naphthyl groups at positions 3 and 4, four
different conformers of 3a (out;out, out;in, in;out and in;in) can be
anticipated. Although steric factors could have ruled out
conformers II, III and IV, a crystal structure of compound 3a
(Scheme 3) showed that conformer III (in;in) is exclusively
observed in the solid state.[14]
In 3a(III), two -bonds are twisted, providing the molecule with a
helical shape. In addition to steric factors, it has been
demonstrated that electronic effects can play a determinant role
in the geometrical arrangement of electron-poor strained ring
systems, as in the present case.[15] The observation of such thiete
dioxide-based double axial chirality in the solid state might provide
the opportunity towards the development of novel chiral scaffolds.
However, despite having evidence for chirality in the crystal
structure of 3a(III), we questioned the configurational stability of
the structures in solution, as no evidence for enantiomer
We first investigated the influence of different aromatic groups on
the axial chirality. 3b and 3c were synthesized from 2b and 2c
respectively and 1-bromoisoquinoline in 43-70% yield.
9-Bromoanthracene was also used as a cross-coupling partner,
giving 3d in 62%, that also showed axial chirality in the solid state.
However, the rigidity of the two aryl groups results in interplanar
angles () of 63.1° and 80.4° in the structures of 3a and 3d,
respectively, which does not allow them for adapting to one
[16]
another
- separation of enantiomers in solution remained
unsuccessful. As Wittig already observed when synthesizing
phenanthrene derivatives,[17] electrostatic interactions play a
determinant role in the stabilization of axial chirality. We
envisioned to modulate the nature of the aryl substituents to
increase their affinity for one another. We therefore designed new
structures to evaluate the impact of electron-donor and electron-
acceptor moieties, as well as their bulkiness, on the stabilization
of the stereointegrity.
In order to increase potential interactions, some flexibility was
added to the cross-coupling partner in such way that the molecule
could gain stability by decreasing the interplanar angle between
the aromatic moieties at positions 2 and 3. Moreover, given the
initial polarization of the thiete dioxide moiety,[6c] electron deficient
coupling partners were chosen to be introduced at position 2. With
3-naphthylthiete dioxide 2b as starting material, molecules 4a and
separation
could
be
demonstrated
under
various
chromatographic conditions, probably due to a low rotation barrier. 4b were synthesized from 4-(2-bromophenyl)pyridine and (2-
We became interested in studying the influence of substituents
and electronic effects on both aryl parts of the structure.
bromophenyl)(phenyl)methanone, respectively (Scheme 3).
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Scheme 3. Diversification of the axially chiral thiete dioxides library.
As evidenced by X-ray measurements, these chains seem to fold
on top of the naphthyl group. The implementation of flexibility
through a keto group or a -bond between the phenyl and the aryl
moiety at position 2 allowed for reaching interplanar angles of
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15.4° (4a) and 14.1° (4b) between the naphthyl at position 3 and
the phenyl group. The bulkiness of the aryl at position 3 was
further increased by implementation of a mesityl group (from 2e).
Similarly, folding of the side phenylpyridyl chain (electron poor)
onto the mesityl moiety was observed in the solid state (4d),
showing however a wider interplanar angle of 36.8°. Same
observations were made when mesityl was replaced by electron-
richer aromatics such as 3,4,5-trimethoxyphenyl or 4-
methoxyphenyl in structures 4f and 4g, synthesized from thiete
dioxides 2j and 2f, respectively. It is worth noting that methoxy-
substituted aryls at position 3 are in the same plane as the thiete
core (0° dihedral angle), inducing a wider interplanar angle (4f =
54°). Next, 3-([1,1'-biphenyl]-2-yl)-thiete dioxide 2d was used as
starting material in order to introduce flexibility at position 3.
C-H functionalization was performed with neutral, electron-rich
and electron-poor aryl and heteroaryl coupling partners, giving
products 5a-f in moderate to good yields, up to 93%. Surprisingly,
the “out” conformation of the biphenyl was favored in all cases, as
attested by the crystal structures of 5a and 5h. The absence of
folding was also witnessed when electron-enriched biaryl (p-
MeO) was introduced at position 3 (5g, 60%), in the presence of
an electron-poor phenyl (p-NO2). The presence of a larger pyrenyl
moiety at position 4 did not positively influence intramolecular
interactions (5h). However, the introduction of an electron-
donating group on the naphthyl moiety (2-methoxynaphthalen-1-
yl) tremendously decreased the interplanar angle when having
flexible electron-deficient biaryl moieties at position 2, probably
due to stronger non-covalent interactions. Compounds 6a and 6b
were synthesized employing 4-(2-bromophenyl)pyridine and 2-
bromo-3',5'-dinitro-1,1'-biphenyl, respectively, and displayed
torsion angles of 5.8° and 8.0°. Interestingly, splitting in 13C NMR
signals of 6a were observed,[13] pointing out the higher structural
constraint of the molecule. Although examples 5a-h did not show
any folding in the solid state, the presence of an additional flexible
chain at position 2 allowed for both biaryl to fold onto one another.
Starting from 3-substituted thiete dioxides 2d and 2i, tetraarylated
scaffolds 6c and 6d were generated in 57 to 88% yield using 4-
(2-bromophenyl)pyridine. X-ray measurements revealed that the
flexibility given to both chains at positions 3 and 2 was profitable
to the system, allowing for a better adaptation of the different
groups with their respective counterpart. For instance, the
electron-rich phenyl moiety C in compound 6c was found to be
placed in opposition to the phenyl group B with a torsion angle of
11.1°, and the electron-poor pyridyl group A opposes the phenyl
group D with a torsion angle of 16.7°. Similar observations were
made for compound 6d, although a wider angle of 23.1° was
measured between aromatic rings B and C. Unfortunately,
despite having optimized the electrostatic interactions, none of
the abovementioned examples showed any stable chirality in
solution. Tuning the electronic properties of the substituents as
well as their bulkiness did not allow for two enantiomers to be
observed, even at low temperature, pointing out the low rotation
barrier of these systems.
coupling partner, as a template in the C-H functionalization step.
For this purpose, mono-arylated thiete dioxides possessing a
bromide at the meta position of the aryl moiety (2l, 2n, 2p-u) were
engaged in the presence of the above-mentioned catalytic system.
Scheme 4. Thiete dioxide units as a base for macrocyclic structure formation.
Although different products of successive couplings can be
expected (linear oligomers or macrocycles), trimeric macrocycles
were observed as the major components of the reaction (Scheme
4). Given the specific geometry of the starting material, it was
postulated that the entropic factor plays a determinant role in the
The variations of both substituents and coupling partners allowed
for the synthesis of a wide range of sophisticated structures with
specific geometries. To push the diversification further, we
envisioned to employ thiete dioxide units that could act as the
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formation of the trimers, disfavoring larger sizes of cyclic
structures (although they were observed as side products in mass
spectroscopy in certain cases). Even though full conversion of
starting materials 2 was observed after 16h, 7a-h were obtained
in low to moderate yields (15 to 45%), which we attributed to the
very low solubility of the products in common solvents. Best yields
(42 to 45%) were obtained for m-methoxy and m-fluoro-phenyl
derivatives (7e and 7d) and the reaction proved to tolerate bulkier
substituents like t-butyl and phenyl groups at the meta position
with reduced isolated yields (7c and 7f-g, 15 to 19%). Considering
procedures for the synthesis of related macrocyclic spherands,
the yields between 20 and 45% are quite good. Moreover, a gram
scale procedure of macrocycle 7e was successful conducted in
similar yield of 41%. Interestingly, we were able to synthesize
larger trimeric cyclic “naphthyl-thiete dioxide-based macrocycle”
7h, for which the solubility problems in classical solvents did not
allow for its isolation in more than 20% yield. Crystal structures of
7a and 7e confirm the cyclic structures, consisting of three thiete
dioxide units. Moreover, due to non-aromaticity of the cyclic
system and sterical repulsion a non-planar ring system can be
observed in the X-ray structures.
Scheme 5. Attempts to synthesize alternative cyclic structures.
As a next step, we attempted to form a macrocycle showing more
structural similarity to the spherand reported by Cram, which
bears methoxy-groups inside the cavity (Scheme 1).[8] For this
purpose, 2o was chosen as the building unit. The reaction
resulted in the trimeric structure 7i, giving a modest yield of 15%
(Scheme 5). Although the compound was identified in mass
spectrometry, 1H and 13C NMR remained inconclusive and no
crystal structure could be obtained. After further investigation of
the reaction, we observed that in certain cases a tetrameric
structure was formed. When employing 2r as the thiete dioxide-
unit, we were able to not only isolate structure 7g, but also isolate
the tetrameric structure 8a in a very modest yield of 6%. Despite
Conclusions
In this work, we at first expanded our scope of 3-substituted thiete
dioxide-based building blocks, forming new compounds
containing bulkier aromatic substituents, as well as new functional
groups. We were then able to functionalize these, following a
simple C-H-activation strategy. Thereby, we created a new library
of 2,3-disubstituted thiete dioxides, showing axial chirality in the
solid state. We then showed that the thiete dioxide-unit can also
act as the coupling partner itself, allowing for the synthesis of
novel macrocyclic compounds. In conclusion, our results show
that the thiete dioxide moiety can be used as a very versatile
platform for molecular design, which makes it an attractive
structure for further investigation.
1
the bad solubility of the compound, we were able to record a H
spectrum, showing widely broadened signals compared to the
spectrum of the corresponding trimer 7g. This phenomenon can
be attributed to the constricted flexibility of such system, and
conducting NMR measurements at higher temperature allowed us
to acquire sharper signals. Furthermore, we employed the p-
bromo-phenyl thiete dioxide 2u in the attempt to form the tetramer
8b. Unfortunately, no reaction was observed.
Experimental Section
General procedure A for the synthesis of thiete dioxides 2a-u: A flask was
charged with thietan-3-one (10.0 mmol, 1.0 equiv.) and THF (0.5 M) was
added. The reaction mixture was cooled to -78 °C and a solution of
organolithium reagent (1.30 equiv.) was added dropwise. Alternatively, the
reaction mixture was cooled to -30 °C and a solution of organomagnesium
reagent (1.30 equiv.) was added dropwise. After stirring for 60 min the
mixture was brought to ambient temperature and quenched with a solution
of saturated aqueous NH4Cl. The aqueous phase was extracted with
dichloromethane (3 × 50 mL) and washed with a solution of saturated
aqueous NaCl (1 × 50 mL). The combined organic phases were dried over
magnesium sulfate and concentrated in vacuo. The residue, containing the
thietanol, was dissolved in dichloromethane (50 mL), cooled to 0 °C and
mCPBA (20.0 mmol, 2.0 equiv., 77%) was added portion wise. After TLC
showed full conversion of the thietanol (approx. 10 min) water was added.
The aqueous phase was extracted with dichloromethane (3 × 50 mL) and
washed with a solution of saturated aqueous NaCl (1 × 50 mL). The
combined organic layers were dried over magnesium sulfate, filtered and
concentrated in vacuo. The residue, containing the thietanol dioxide 1, was
dissolved in dichloromethane (50 mL) and triethylamine (30 mmol, 3.0
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equiv.) was added. Mesyl chloride (30 mmol, 3.0 equiv.) was subsequently
added dropwise and the mixture was stirred until TLC indicated full
conversion of the starting thietanol dioxide 1 (approx. 30 min) water was
added. The aqueous phase was extracted with dichloromethane (3 × 50
mL) and washed with a solution of saturated aqueous NaCl (1 × 50 mL).
The combined organic phases were dried over magnesium sulfate, filtered
and concentrated in vacuo. The crude thiete dioxides 2a-u were purified
by flash column chromatography with appropriate solvent mixtures.
concentrated in vacuo and purified by flash-column chromatography on
silica gel with the appropriate solvent mixture to obtain pure 7a-i.
Representative example
-
synthesis 7d: Using 3-(3-bromo-5-
methoxyphenyl)-2H-thiete 1,1-dioxide (2q) according to general
procedure C, provided 7d (2.14 g, 3.43 mmol, 42%) as yellowish solid. Rf
= 0.2 (hexane/EtOAc 5:5, UV, KMnO4). 1H NMR (400 MHz, CDCl3) δ 7.27
(s, 3H), 7.22-7.20 (m, 3H), 6.89-6.87 (m, 3H), 4.83 (s, 6H), 3.89 ppm (s,
9H). 13C NMR (101 MHz, CDCl3) δ 160.8, 150.6, 139.7, 132.1, 128.8,
119.0, 116.7, 114.7, 72.1, 56.0 ppm. HRMS (ESI-Quadrupole): m/z: [M+-
H] Calcd for C30H23O932S3+: 623.0504; found: 623.0507. IR (Diamond-ATR,
Representative example - synthesis 2g: Using (2-methoxynaphthalen-1-
yl)magnesium bromide according to general procedure A, provided 2g
(1.59 g, 6.1 mmol, 61%) as a white solid. Rf = 0.2 (hexane/EtOAc 7:3, UV,
KMnO4, PAA). 1H NMR (400 MHz, CDCl3) δ 8.07-8.02 (m, 1H), 7.96 (d, J
= 9.2 Hz, 1H), 7.86-7.81 (m, 1H), 7.59-7.52 (m, 1H), 7.46 – 7.39 (m, 1H),
7.29 (d, J = 9.1 Hz, 1H), 7.00 (s, 1H), 5.08 (s, 2H), 4.00 ppm (s, 3H). 13C
NMR (101 MHz, CDCl3) δ 156.2, 145.1, 143.9, 133.4, 131.5, 129.0, 129.0,
128.5, 124.5, 123.3, 112.4, 112.2, 74.5, 56.4 ppm. HRMS (EI-Orbitrap):
m/z: [M]+ Calcd for C14H12O332S+: 260.0507; found: 260.0501. IR
neat) 휈̃푚푎푥: 1585 (m), 1362 (m), 1291 (s), 1261 (s), 1226 (s), 1182 (s),
1156 (m), 1129 (vs), 1064 (s), 1050 (s), 1017 (m), 1000 (s), 985 (s), 861
(m), 822 (m), 806 (m), 800 (m), 736 cm-1 (m). Melting point: 265 (±2) °C
decomposition.
Acknowledgements
(Diamond-ATR, neat) 휈̃푚푎푥: 1286 (vs), 1277 (s), 1255 (m), 1193 (vs), 1167
(s), 1156 (m), 1134 (s), 1116 (s), 1094 (s), 1065 (s), 1056 (s), 1027 (m),
820 (s), 790 (s), 750 (s), 668 cm-1 (s). Melting point: 135 (±2) °C.
We would like to thank the Chemical Industry Fund (FCI), the
Deutsche Forschungsgemeinschaft (DFG grant DI 2227/2-1,
Sonderforschungsbereich SFB749), and the Ludwig-Maximilians-
Universität München (LMU) for financial support.
General procedure B for the synthesis of 2,3-disubstituted thiete dioxides
3-6: A pressure tube was charged with 2H-thiete 1,1- dioxide derivatives
2a-k (0.2 mmol, 1 equiv.) and 2 mL toluene was added. Subsequently were
added K2CO3 (55 mg, 0.4 mmol, 2.0 equiv.), Pd(OAc)2 (1.8 mg, 8 μmol, 4
mol%), tricyclohexylphosphane (PCy3) (4.5 mg, 16 μmol, 8 mol%), the
corresponding halogenide (0.3 mmol, 1.5 equiv.) and a few drops of pivalic
acid (~7 μL, 30 mol%). The mixture was stirred at 110 °C in the sealed
pressure tube until TLC showed consumption of the starting 2H-thiete 1,1-
dioxides (approx. 16 hours). After cooling to ambient temperature, the tube
was opened and a 1:1 mixture of H2O:Et2O (4 mL) was added. The
aqueous phase was extracted with Et2O (3 x 20 mL). The combined
organic phases were dried over magnesium sulfate, filtrated, concentrated
in vacuo and purified by flash-column chromatography on silica gel with
the appropriate solvent mixture to obtain pure 3-6.
Keywords: Thiete dioxides • Axial Chirality • Macrocycles • C-H
Functionalization • Four-membered Rings
[1]
[2]
S. Leśniak, W. J. Kinart, J. Lewkowski, in Thietanes and Thietes:
Monocyclic. In: Comprehensive Heterocyclic Chemistry III: Elsevier,
2008, pp. 389-428.
a) E. E. Klen, I. L. Nikitina; N. N. Makarova, A. F. Miftakhova, O. A.
Ivanova, F. A. Khaliullin, E. K. Alekhin, Pharm. Chem. J. 2017, 50, 642-
648; (b) L. Mercklè, J. Dubois, E. Place, S. Thoret, F. Guéritte, D.
Guénard, C. Poupat, A. Ahond and P. Potier, J. Org. Chem. 2001, 66,
5058-5065. (c) P. Renold; W. Zambach; P. Maienfisch; M. Muehlebach,
PCT Int. Appl. WO2009080250; (d) T. M. Brennan; M. E. Hendrick, U.S.
4411925.
Representative
example
-
synthesis
4b:
Using
(2-
bromophenyl)(phenyl)methanone according to general procedure B,
provided 4b (70 mg, 0.17 mmol, 85%) as a white solid. Rf = 0.2
(hexane/EtOAc 8:2, UV, KMnO4, PAA). 1H NMR (400 MHz, CDCl3) δ 7.92
(dd, J = 7.7, 1.1 Hz, 1H), 7.67 (dd, J = 8.3, 1.2 Hz, 1H), 7.63-7.53 (m, 3H),
7.46-7.34 (m, 3H), 7.29 (ddd, J = 8.3, 6.8, 1.4 Hz, 1H), 7.25-7.17 (m, 3H),
7.10 (t, J = 7.8 Hz, 2H), 7.04 (dd, J = 8.3, 1.5 Hz, 2H), 4.87 (s, 2H). 13C
NMR (101 MHz, CDCl3) δ 194.4, 151.0, 141.3, 139.0, 135.0, 133.6, 132.9,
131.3, 131.2, 129.9, 129.8, 129.6, 129.3, 129.3, 128.9, 127.9, 127.5, 127.2,
127.1, 126.5, 126.5, 125.0, 124.8, 72.5 ppm. LRMS (DEP/EI-Orbitrap):
m/z (%): 346.1 (30), 331.1 (15), 239.1 (60). HRMS (EI-Orbitrap): m/z: [M-
SO2]+ Calcd for C26H18O+: 346.1358; found: 346.1359. IR (Diamond-ATR,
[3]
[4]
[5]
[6]
M. Eisold, A. N. Baumann, G. M. Kiefl, S. T. Emmerling, D. Didier, Chem.
Eur. J. 2017, 23, 1634-1644.
A. N. Baumann, M. Eisold, A. Music, G. Haas, Y. M. Kiw, D. Didier, Org.
Lett. 2017, 19, 5681-5684.
M. Eisold, A. Müller-Deku, F. Reiners, D. Didier, Org. Lett. 2018, 20,
4654-4658.
(a) A. N. Baumann, M. Eisold, D. Didier, Org. Lett. 2017, 19, 2114-2117.
(b) A. N. Baumann, A. Music, M. Eisold, D. Didier, J. Org. Chem. 2018,
83, 783-792. (c) A. N. Baumann, F. Reiners, T. Juli, D. Didier, Org. Lett.
2018, 20, 6736-6740.
[7]
(a) R. Noyori, H. Takaya, Acc. Chem. Res. 1990, 23, 345-350. (b) G.
Bringmann, A. J. Price Mortimer, P. A. Keller, M. J. Gresser, J. Garner
M. Breuning, Angew. Chem. Int. Ed. 2005, 44, 5384-5427 (c) G. Storch,
O. Trapp, Angew. Chem. Int. Ed. 2015, 54, 3580-3586. (d) G. Storch, O.
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Rominger, O. Trapp, Synthesis 2017, 49, 3485-3494. (f) J. F. Scholtes,
O. Trapp, Angew. Chem. Int. Ed. 2019, 58, 6306-6310.
neat) 휈̃푚푎푥: 1656 (s), 1299 (s), 1286 (m), 1266 (m), 1256 (m), 1184 (m),
1135 (s), 1114 (m), 927 (m), 799 (m), 777 (s), 761 (m), 704 cm-1 (vs).
Melting point: 181 (±2) °C.
General procedure C for the synthesis of macrocyclic structures 7a-i: A
pressure tube was charged with 2H-thiete 1,1- dioxides derivative 2l-u
(0.2 mmol, 1 equiv.) and 2 mL toluene was added. Subsequently were
added K2CO3 (55 mg, 0.4 mmol, 2.0 equiv.), Pd(OAc)2 (1.8 mg, 8 μmol, 4
mol%), tricyclohexylphosphane (PCy3) (4.5 mg, 16 μmol, 8 mol%) and a
few drops of pivalic acid (~7 μL, 30 mol%). The mixture was stirred at
110 °C in the sealed pressure tube until TLC showed consumption of the
starting 2H-thiete 1,1- dioxides (approx. 16 hours). After cooling to ambient
temperature, the tube was opened and a 1:1 mixture of H2O:CH2Cl2 (4 mL)
was added. The aqueous phase was extracted with CH2Cl2 (3 x 20 mL).
The combined organic phases were dried over magnesium sulfate, filtrated,
[8]
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Entry for the Table of Contents (Please choose one layout)
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Andreas N. Baumann, Felix Reiners,
Alexander F. Siegle, P. Mayer, O. Trapp,
Dorian Didier*
Page No. – Page No.
Thiete Dioxides as Templates
towards Novel Twisted Scaffolds and
Macrocyclic Structures
Text for Table of Contents
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