Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes

Article abstract of DOI:10.3762/bjoc.12.71

Reactions of dihetaryl and aryl/hetaryl thioketones with 2-diazopropane, diazoethane, and (trimethylsilyl)diazomethane were studied at variable temperature. The experiments showed that reactions with 2-diazopropane carried out at -75°C occur mainly via th

Full text of DOI:10.3762/bjoc.12.71

Diradical reaction mechanisms in [3 + 2]-cycloadditions of
hetaryl thioketones with alkyl- or trimethylsilyl-substituted
diazomethanes
Grzegorz Mlostoń*1, Paulina Pipiak1 and Heinz Heimgartner2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2016, 12, 716–724.
1Department of Organic and Applied Chemistry, University of Łódź,
Tamka 12, PL 91-403 Łódź, Poland and 2Department of Chemistry,
University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich,
Switzerland
doi:10.3762/bjoc.12.71
Received: 15 January 2016
Accepted: 23 March 2016
Published: 14 April 2016
Email:
Grzegorz Mlostoń* - gmloston@uni.lodz.pl
Associate Editor: C. Stephenson
* Corresponding author
© 2016 Mlostoń et al; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
[3 + 2]-cycloadditions; diazoalkanes; diradicals; 1,3-dithiolanes;
reaction mechanisms; thioketones
Abstract
Reactions of dihetaryl and aryl/hetaryl thioketones with 2-diazopropane, diazoethane, and (trimethylsilyl)diazomethane were
studied at variable temperature. The experiments showed that reactions with 2-diazopropane carried out at –75 °C occur mainly via
the initially formed, relatively stable 1,3,4-thiadiazolines as products of the [3 + 2]-cycloaddition of the diazo dipole onto the C=S
bond. The latter decompose only at higher temperature (ca. −40 °C) to generate thiocarbonyl S-isopropanide. In the absence of the
starting thioketone, the corresponding thiiranes and/or ethene derivatives, formed from them via spontaneous desulfurization, are
the main products. In contrast, reactions with diazoethane occurred predominantly via initially formed diradicals, which in cascade
processes gave sterically crowded 4,4,5,5-tetrahetaryl-1,3-dithiolanes as major products. Finally, the reaction of dihetaryl thioke-
tones with (trimethylsilyl)diazomethane occur smoothly at −75 °C leading to the corresponding 4,4,5,5-tetrahetaryl-1,3-dithiolanes
as the exclusive [3 + 2]-cycloadducts formed via a cascade of postulated diradicals. The presence of S or Se atoms in the hetaryl
rings is of importance for stabilizing diradical intermediates. Remarkably, in no single case, the ‘head-to-head dimerization’ of aryl/
hetaryl and dihetaryl substituted thiocarbonyl ylides was observed.
Introduction
Cycloaddition reactions belong to the most important classes of In addition to their practical importance, discussions on the
organic reactions, and [3 + 2]- cycloadditions, also known as mechanism contribute significantly to the development of
1,3-dipolar cycloadditions or Huisgen reactions, offer a fundamental concepts in organic chemistry [3-7]. The first
universal tool for the preparation of five-membered hetero- general concept of concerted [3 + 2]-cycloadditions was formu-
cycles with a variable number of heteroatoms in the ring [1,2]. lated by Huisgen [4]. However, some time later, Huisgen and
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Beilstein J. Org. Chem. 2016, 12, 716–724.
co-workers reported stepwise [3 + 2]-cycloadditions via zwitter- phenone S-methanide (a thiocarbonyl ylide) 3a at ca. −45 °C,
ionic intermediates [8,9]. Large differences of energies of the when the evolution of N2 takes place [16-20]. An analogous
frontier orbitals of dipole and dipolarophile, as well as steri- course of the reaction with diazomethane was observed in the
cally demanding groups at the terminus of the dipole, were case of thiofluorenone (1b, Scheme 1).
pointed out as requirements for the initiation of the ‘zwitter-
ionic pathway’. In addition to the experimental findings, new When the decomposition of 2a or 2b was performed in the pres-
reports dealing with computational studies aimed at the demon- ence of a suitable dipolarophile, the corresponding [3 +
stration of new zwitterionic [3 + 2]-cycloadditions were 2]-cycloadducts were formed, whereas in the absence of a dipo-
published [10-12]. Finally, a third concept for the interpretation larophile, the ‘head-to-head dimerization’ leading to 2,2,3,3-
of the mechanism of [3 + 2]-cycloadditions, formulated by Fire- tetraaryl-1,4-dithianes 4a,b is the exclusive reaction.
stone, is based on the assumption that they occur via diradical
intermediates [13-15].
Heteroatoms such as S and Se are known to stabilize radical
centers [21]. In our ongoing studies on thioketones and their ap-
Reactions of aromatic thioketones with diazomethane are well plications in the cycloaddition chemistry, we described in a
established. For example, in the case of thiobenzophenone (1a), recent publication the unexpected course of the reaction of
the reaction performed at –65 ºC occurs without evolution of N2 diazomethane with aryl/selenophen-2-yl thioketones of type 1c,
and the in situ formed 2,2-diphenyl-1,3,4-thiadiazoline 2a can leading to unusual dimers 5 of intermediate thiocarbonyl ylides
be subsequently used as a precursor of the reactive thiobenzo- of type 3c [22] (Scheme 2). In a competitive reaction, the latter
Scheme 1: ‘Head-to-head dimerization’ of diarylthioketone S-methanides 3a,b leading to 2,2,3,3-tetrasubstituted 1,4-dithianes 4a,b.
Scheme 2: Diradical nature of the reactive intermediate 3c in the reaction of phenyl selenophen-2-yl thioketone 1c with diazomethane.
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Beilstein J. Org. Chem. 2016, 12, 716–724.
react with the starting thioketone 1c to give 1,3-dithiolanes of Results and Discussion
type 6 which are, apparently, also formed via a diradical path- The first experiment performed with thiobenzophenone (1a)
way, leading to the sterically crowded 4,4,5,5-tetrasubstituted and 2-diazopropane (7a) at ca. −75 °C in THF led to a change
isomers exclusively.
of the blue color of the solution without evolution of N2. The
addition of the solution of 7a was continued until the color of
In other studies, performed with cycloaliphatic thioketones, e.g. the mixture changed to pale red. The mixture was warmed up,
with adamantane-2-thione or 2,2,4,4-tetramethyl-3-thioxocyclo- and around 0 °C the evolution of N2 was observed. The
butanone, the growing stability of the corresponding 1,3,4-thia- 1H NMR analysis of the crude product revealed the presence of
diazolines obtained in reactions with diazomethane, diazo- only one singlet for two Me groups located at 1.62 ppm. After
ethane, and 2-diazopropane was reported based on kinetic data chromatographic work-up, the only product isolated as color-
[9,17-19]. The same tendency was observed in a series of reac- less crystals was identified as 2,2-dimethyl-3,3-diphenylthi-
tions with aromatic thioketones: for example, the reaction of irane (8a; Scheme 3, Table 1). The same result was obtained
thiobenzophenone (1a) with diazoethane performed at −70 °C when the reaction was carried out at ca. −60 or −15 °C.
led to the formation of a relatively stable 2-methyl-1,3,4-thia-
diazoline, which could be identified in the low temperature Similar experiments were performed with thiofluorenone (1b)
1H NMR spectrum [20]. To the best of our knowledge, there are and 7a. Whereas at −75 °C and −60 °C the corresponding
no reports on the course of reactions of either diaryl, aryl/ thiirane 8b and ethene 9b, formed via spontaneous desulfuriza-
hetaryl or dihetaryl thioketones with 2-diazopropane.
tion of 8b, were obtained as the sole products, in the experi-
ment carried out at –15 ºC, the sterically crowded 1,3-dithio-
Prompted by these observations, we decided to examine reac- lane 10b was also detected as a minor product (14% yield,
tions of aryl/hetaryl and dihetaryl thioketones 1 with some Table 1). In the latter case, thiirane 8b and ethene 9b were
diazomethane derivatives, such as 2-diazopropane (7a), diazo- found in 24 and 37% yield, respectively. According to the liter-
ethane (7b), and (trimethylsilyl)diazomethane (7c), and to ature, reaction of thiobenzophenone (1a) with diazoethane (7b)
compare their outcome with earlier reported reactions with performed at –75 °C led to 5-methyl-2,2-diphenyl-1,3,4-thia-
diazomethane [22]. An important question was if in these reac- diazoline as the exclusive product [20]. After warming the reac-
tions the corresponding 2-substituted 1,3,4-thiadiazolines of tion mixture to room temperature, the only products observed in
type 2 can be obtained at low temperature and subsequently the mixture were 2,2-diphenyl-3-methylthiirane (8i) and 1,1-
used as precursors of new thiocarbonyl ylides. The latter may diphenylpropene (9i) as the product of its desulfurization. On
be potentially useful for the [3 + 2]-cycloaddition reactions with the other hand, the experiment with 1a and 7b performed at
diverse dipolarophiles leading to five-membered S-heterocycles, room temperature led to the 1,3-dithiolane 10i as the major
such as di- and tetrahydrothiophenes, 1,3-oxathiolanes, 1,3- product (87%) accompanied by small amounts of thiirane 8i and
dithiolanes, etc.
ethene 9i [23].
Scheme 3: Formation of thiiranes 8 and/or 1,3-dithiolanes 10 in the reaction of aryl/aryl, aryl/hetaryl and dihetaryl thioketones 1 with 2-diazopropane
(7a), diazoethane (7b), and (trimethylsilyl)diazomethane (7c) (Table 1).
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A different result was observed in the reaction of 7a with dithiolane 10d was also observed (7%). The amount of the latter
di(thiophen-2-yl) thioketone (1d). In that case, the reaction at product increased to 36% when the reaction was performed at
−75 °C afforded also the expected thiirane 8d as the major −60 °C and to 58% at −15 °C. The corresponding experiments
product, accompanied by small amounts of the corresponding with 1c and 7b led to increased amounts of 1,3-dithiolane 10k,
alkene 9d. However, in that case 4,4,5,5-tetrasubstituted 1,3- established as 43% at −75 °C, 81% at −60 °C, and 85% at
Table 1: Reactions of aryl/aryl, aryl/hetaryl, and hetaryl/hetaryl thioketones 1 with 2-diazopropane (7a), diazoethane (7b), and (trimethylsilyl)diazo-
methane (7c).
Entry
Thioketone 1
Diazoalkane 7
T [°C] Product 8/9
Yields 8/9 [%]a
Product 10 Yield 10 (or 4)
(and/or 4)
[%]a
−15
−60
−75
86
80 (76b)
75
–
–
–
7a
1
8a/9a
8b/9b
8c/9c
R1 = R2 = Me
1a
1b
−15
−60
−75
61 (41b)
85
76
14 (12d)
2
3
7a
7a
10b
10c
–
–
−15
−60
−75
42
74 (57b)
63
61
13 (11d,e)
18
1c
1d
1e
−15
−60
−75
56
87 (75b + 2c)
97
58
36 (32d)
7
4
5
7a
7a
8d/9d
8e/9e
10d
10e
−15
−60
−75
50
84 (61c)
68
49
20 (17d)
27
−15
−60
−75
40 (17b + 7c)
67 (63d,e)
6
7
7a
7a
8f/9f
85
96
10f
38
–
1f
−15
−60
−75
38
51 (40c)
69
70
31 (28d,e)
36
8g/9g
10g
1g
−15
−60
−75
36
88 (65c)
72
68
21 (17d,e)
21
8
9
7a
8h/9h
8i/9i
10h
10i
1h
1a
traces (see, ref. [23])
93b + 3c
87
7b
rt
−75
(see, ref. [23])
–
R1 = Me, R2 = H
(see, ref. [20])
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Beilstein J. Org. Chem. 2016, 12, 716–724.
Table 1: Reactions of aryl/aryl, aryl/hetaryl, and hetaryl/hetaryl thioketones 1 with 2-diazopropane (7a), diazoethane (7b), and (trimethylsilyl)diazo-
methane (7c). (continued)
−15
−60
−75
3
82
73 (61d)
57
10
7b
8j/9j
9 (6c)
14
10j
1b
1d
1e
−15
−60
−75
39
32 (25c)
69
85
81 (72d)
43
11
12
7b
7b
8k/9k
8l/9l
10k
10l
−15
−60
−75
11
5 (3c)
12
76
86 (79d)
87
−15
−60
−75
6
59 (48c)
62
79
35 (27d,e)
28
13
14
15
7b
7b
8m/9m
8n/9n
10m
10n
1f
1c
1a
−15
−60
−75
20
83 (71c)
65
75
36 (28d,e)
30
7c
10o
and 4c
36 (33d)
39 (22f)
−75
−75
–
–
R1 = Me3Si, R2 = H
53f
see ref. [26]
16
7c
4d
1b
1d
1e
17
18
7c
7c
−75
−75
–
–
10r
95 (87d)
85 (76d)
10s
aYields determined by 1H NMR with a weighed amount of 1,1,2,2-tetrachloroethane as a standard. bYield of isolated product 8. cYield of isolated prod-
uct 9. dYield of isolated product 10. eIsolated as mixtures of isomeric products. fYield of isolated product 4.
−15 °C (Table 1). The same tendency, i.e., an increasing some cases tri- and tetrasubstituted thiiranes partially under-
amount of 1,3-dithiolanes 10 in the case of the less-substituted went spontaneous extrusion of sulfur to form the corresponding
diazoethane (7b) and at higher temperature, was observed for tri- or tetrasubstituted ethene derivatives 9. In these cases, com-
the reactions with thiofluorenone (1b), di(selenophen-2-yl)-, plete desulfurization was achieved by treatment of the reaction
(phenyl)(thiophen-2-yl)-, (phenyl)(selenophen-2-yl)-, and other mixture with tris(diethylamino)phosphine, and the respective
aryl hetaryl thioketones 1 (Table 1). As mentioned before, in ethenes 9 were isolated as the final products.
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Beilstein J. Org. Chem. 2016, 12, 716–724.
It is worth mentioning that in the case of the non-symmetrical introduction of Me or Me3Si groups. Upon this assumption, all
aryl/hetaryl thioketones 1c, 1f–h and 2-diazopropane (7a), the reactions performed at −75 °C should lead to the corresponding
formed 1,3-dithiolanes 10 were isolated as mixtures of cis- and cycloadducts 2 with complete conversion of the starting thioke-
trans-isomers. In the 1H NMR spectra, they could be identified tones 1. Only after warming up above −45/40 °C compounds 2
based on the presence of two and one signal, respectively, for are expected to decompose yielding the reactive thiocarbonyl
the Me2C(2) group. The mixtures of 1,3-dithiolanes 10 ob- ylide 3. Under these conditions, the latter intermediates can
tained from the reactions of diazoethane (7b) with thioketones undergo either 1,3-dipolar electrocyclization to give thiiranes 8
1c,f consisted of only two instead of the expected three dia- or dimerization leading to 1,4-dithianes 4 [20,26]. This reaction
stereoisomers. In all cases they belong to the same group of course resulting in the exclusive formation of thiiranes 8 was
regioisomers. The regioselective formation of products 10 was observed in the case of thiobenzophenone (1a) and thiofluo-
proved by 13C NMR spectroscopy: the signals attributed to C(2) renone (1b) with 2-diazopropane (7a). However, the reaction of
were found in narrow regions at 54.9–59.4 ppm for 10c, 10f–h 1b with 7a carried out at −15 °C yielded also a small amount of
and 43.1–45.6 ppm for 10m,n, respectively. In addition, the 1,3-dithiolane 10b. This result can be interpreted by the partial
structure of the sterically crowded 4,4,5,5-tetrasubstituted aryl/ decomposition of 2b in the presence of the non-converted
hetaryl 1,3-dithiolanes 10 could be confirmed by the presence thioketone 1b. The replacement of aromatic thioketones 1a,b by
of only two signals for the three C(sp3)-atoms of the hetero- di(thiophen-2-yl) thioketone (1d) in the reaction with 7a
cycle, whereas in the isomeric 2,2,4,4-tetraaryl/hetaryl 1,3- resulted in the formation of comparable amounts of thiirane 8d
dithiolanes, three signals for these atoms are expected (cf. [19]). and 1,3-dithiolane 10d, whereas at −75 °C 8d is again the major
product. It is worth mentioning that the analogous experiment
Trimethylsilyldiazomethane (7c) is widely applied as a prac- carried out at –60 ºC, i.e., below the expected decomposition
tical and useful synthetic equivalent of the hazardous diazo- temperature of 1,3,4-thiadiazoline 2d, led to substantial increase
methane [24,25]. In our earlier publications, its reactions with of the amount of 10d. A similar tendency was observed in other
thiofluorenone (1b) and S-methyl (phosphonyl)dithioformate, studied cases with hetaryl thioketones and 7a. The replacement
leading to the expected 1,3,4-thiadiazoline derivatives, which of the latter by diazoethane (7b), leading to the less stable 1,3,4-
are stable at −60 °C, were reported [26,27]. At higher tempera- thiadiazolines 2, resulted in a general increase of the corre-
ture, in both reactions, dimers of the intermediate thiocarbonyl sponding 1,3-dithiolanes 10, which were formed in substantial
S-(trimethylsilyl)methanides were formed in the absence of a amounts, even in experiments performed at −75 °C. However,
dipolarophile after evolution of N2. An analogous test experi- the most striking results were observed in reactions performed
ment with 7c and thiobenzophenone (1a) was carried out in the with dihetaryl thioketones 1d and 1e with trimethylsilyldiazo-
course of the present study at −75 °C, and in this case slow methane (7c). In both experiments, the only products formed
decolorization of the reaction solution was observed. In contrast were the corresponding, sterically crowded 4,4,5,5,-tetrahetaryl-
to the experiment with 1b, complete decolorization of the blue substituted 1,3-dithiolanes 10r and 10s. These results clearly
reaction solution was observed before the addition of the total, demonstrate that 7c, similarly to diazomethane [22], reacts
equimolar amount of 7c. After warming up and typical work-up smoothly with dihetaryl thioketones 1 with no formation of the
procedure, the corresponding 1,3-dithiolane 10o and 1,4- expected 1,3,4-thiadiazolines 2 and after release of N2 even at
dithiane 4c in a ratio of 2:1 were found as products identified in low temperature, the intermediate diradicals of type 3 attack the
the 1H NMR spectrum of the crude reaction mixture. Thus, in parent thioketones 1 yielding 1,3-dithiolanes 10 via stabilized
this reaction dimerization of the intermediate thiocarbonyl ylide 1,5-diradicals 12. In both cases no tendency for the formation of
and its reaction with another molecule of 1a were competitive dimers of the intermediate ‘thiocarbonyl ylide’ was observed
pathways. Finally, the reactions of 7c with symmetrically (Scheme 4).
substituted dihetaryl thioketones 1d and 1e were performed at
−75 °C, and in both cases, the sterically crowded 4,4,5,5-tetra- Based on these results, the reaction mechanism can be pro-
hetaryl-1,3-dithiolanes 10r and 10s, respectively, were ob- posed as formulated in Scheme 4. It seems likely that the first
tained as sole products.
step comprising the reaction of a hetaryl thioketone 1 with 7a,
7b, and 7c is not a concerted process, but the diradical or
The obtained results can be explained by the assumption that in zwitterionic intermediate of type 11 is formed and, depending
the case of hetaryl thioketones 1 stepwise mechanisms via on the number and type of stabilizing substituents and the reac-
diradical intermediates govern the formation of the isolated 1,3- tion temperature, they undergo two competitive reactions: elim-
dithiolanes 10 (Scheme 3). Based on earlier studies, the stability ination of N2 leading to thiocarbonyl ylide 3 or 1,5-ring closure
of 1,3,4-thiadiazolines 2, which are considered as potential pre- to give 1,3,4-thiadiazoline 2. When the rapid elimination of N2
cursors of thiocarbonyl ylides 3, should be increased by the occurs in the presence of the non-converted thioketone 1, the
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Beilstein J. Org. Chem. 2016, 12, 716–724.
hetaryl thioketones 1 with the in situ generated thiocarbonyl
S-methanides [28]. The missing formation of dimers from thio-
carbonyl ylides 3 derived from hetaryl thioketones can be ex-
plained by steric hindrance resulting from the presence of the
Me or Me3Si groups in the S-methanide moiety. However, elec-
tronic effects resulting from the diradical nature of the interme-
diate thiocarbonyl ylides, can also play certain role. The same
effect was observed in the case of diaryldiazomethanes used in
reactions with aryl/hetaryl thioketones [29,30].
Experimental
General information: Melting points were determined in capil-
laries using a MEL-TEMP II apparatus (Aldrich) and are uncor-
rected. IR spectra were recorded with a FTIR NEXUS spec-
trophotometer as KBr pellets or as film; absorptions (ν) in cm−1.
1H and 13C NMR spectra were measured on a Bruker Avance
III (1H at 600 and 13C at 150 MHz) instrument in CDCl3; chem-
ical shifts (δ) are given in ppm, solvent signals as reference,
coupling constants (J) in Hz. The multiplicity of the 13C signals
was deduced from DEPT, supported by 1H,13C HMQC spectra.
1H NMR data are presented as follows: chemical shift, multi-
plicity (br = broad, s = singlet, d = doublet, t = triplet,
q = quartet, m = multiplet), coupling constant, integration. The
mass spectra were recorded on a Finnigan MAT-95 (ESI).
Elemental analyses were performed in the Microanalytical Lab-
oratory of the Chemistry Faculty of the University of Łódź.
Applied reagents such as 2-diazopropane (7a) and diazoethane
(7b) were prepared by known methods according to the litera-
ture protocols [31,32]. Thiobenzophenone (1a), fluorene-9-
thione (thiofluorenone, 1b), symmetrical dihetaryl thioketones
1d,e, and nonsymmetrical aryl/hetaryl thioketones 1c, 1f–h
Scheme 4: Proposed competitive mechanisms in the reactions of aryl/
hetaryl and dihetaryl thioketones 1 with 2-diazopropane (7a), diazo-
ethane (7b), and (trimethysilyl)diazomethane (7c).
stabilized 1,5-diradical 12 is formed as precursor of the steri- were obtained from the corresponding ketones using the known
cally crowded 1,3-dithiolane 10. The alternatively formed 1,3,4- procedures [33]. Other reagents used in the present study were
thiadiazolines 2a and 2b are expected to be stable at –75 ºC and commercially available.
eliminate N2 only at enhanced temperature generating thiocar-
bonyl ylide 3. As in that case the starting diaryl (or dihetaryl) Reaction of thioketones 1a–h with 2-diazopropane (7a) and
thioketone 1 is completely consumed, the 1,3-dithiolane 10 diazoethane (7b) – General procedure: Corresponding thioke-
cannot be formed. The results obtained with 7c demonstrate that tones 1a–h (1 mmol) were dissolved in freshly distilled THF
its reaction with dihetaryl thioketones 1 occurs without forma- (2.5 mL) and the solution was cooled to the corresponding tem-
tion of 1,3,4-thiadiazolines as intermediate [3 + 2]-cyclo- perature (−15, −60, −75 °C; acetone/dry ice). Then, the mixture
adducts. Elimination of N2 from the initially formed diradical of was treated with small portions of ethereal 2-diazopropane (7a)
type 11 leads immediately to the new diradical species 3, which or diazoethane (7b) solution, until the intense color of the
adds regioselectively to the C=S group of the non-converted thioketone vanished. Then, the mixture was allowed to warm
thioketone 1.
slowly to rt (ca. 2–4 h). After removal of the solvent under
vacuum, the residue was subjected to 1H NMR analysis in
This interpretation is consistent with the course of the reactions CDCl3 solution with a weighed amount of 1,1,2,2-tetra-
of aryl/hetaryl thioketones 1 with diazomethane, in which the chloroethane as a standard. Crude products were purified by CC
formation of sterically crowded 1,3-dithiolanes side-by-side (CHCl3/hexane 2:8).
with 12-membered dimers of the thiocarbonyl ylide was ob-
served [22]. In addition, it corresponds to the diradical mecha- In crude mixtures obtained from 2-diazopropane (7a) and
nism postulated for the formal [3 + 2]-cycloaddition of aryl/ thioketones 1c,e,g,h and from diazoethane (7b) and thioketones
722

Beilstein J. Org. Chem. 2016, 12, 716–724.
1b–f, the presence of thiirane and the corresponding ethylene 13C NMR (150 MHz, CDCl3) δ 151.2, 149.8, 144.0, 142.9 (for
was evidenced based on the 1H NMR spectra. In these cases, no 8 Carom), 131.3, 131.1, 130.5, 127.5, 127.1, 127.0, 126.6, 126.1,
isolation of the thiirane was performed; after addition of 125.4, 125.2, 125.0 (for 32 CHarom), 78.8, 78.4 (C-4 + C-5, for
tris(dimethylamino)phosphine desulfurization leading to the cis and trans), 55.4, 55.3 (C-2, cis and trans) 33.1 (CH3-cis),
ethane derivative was carried out.
32.9 (for 2 CH3-trans), 32.5 (CH3-cis) ppm; anal. calcd for
C25H22S4 (450.70): C, 66.62; H, 4.92; S, 28.46; found: C,
Reaction of thioketones 1d–e with (trimethylsilyl)diazo- 66.46; H, 4.91; S, 28.33.
methane (7c) – General procedure: The corresponding
thioketones 1d–e (1 mmol) were dissolved in freshly distilled 1,1-Di(thiophen-2-yl)-propene (9k): Yield: 52 mg (25%) –
THF (2.5 mL) and the solution was cooled to −75 °C (acetone/ After desulfurization of tiirane 8k. Yellow oil; IR (film) ν: 3104
dry ice). Then, the mixture was treated with small portions of an (w), 3071 (w), 2930 (w), 2908 (w), 2850 (w), 1438 (m), 1362
ethereal solution of 7c (1 mmol). The mixture was kept in a (w), 1249 (m), 1223 (m), 1036 (w), 850 (s), 836 (s), 818 (s),
cold bath, and the intense color of the thioketone vanished after 695 (s) cm−1; 1H NMR (600 MHz, CDCl3) δ 7.23–7.22 (m, 1H,
15 min. Subsequently, the mixture was allowed to slowly warm Harom), 7.01–7.00 (m, 1H, Harom), 6.96–6.94 (m, 1H, Harom),
to rt (ca. 2–4 h). After removal of the solvent under vacuum, the 6.90–6.89 (m, 1H, Harom), 6.80–6.79 (m, 1H, Harom), 6.71–6.70
residue was subjected to the 1H NMR analysis in CDCl3 solu- (m, 1H, Harom), 6.18 (q, J = 7.2 Hz, 1H, =CH), 1.74 (d, J = 7.2
tion with a weighed amount of 1,1,2,2-tetrachloroethane Hz, 3H, CH3) ppm; 13C NMR (150 MHz, CDCl3) δ 129.4,
as an internal standard. Crude products were purified by CC 139.8, 146.8 (2 Carom, Carom, C=), 127.6, 127.0, 126.6, 126.3,
(CHCl3/hexane 2:8).
125.5, 124.8, 123.4 (6 CHarom, =CH), 15.6 (CH3) ppm; anal.
calcd for C11H10S2 (206.33): C, 64.04; H, 4.89; S, 31.08;
2,2-Dimethyl-3,3-diphenylthiirane (8a): Yield: 182 mg found: C, 63.83; H, 4.98; S, 31.14.
(76%). White crystals; mp 66–67 °C (chromatographic purifica-
tion); IR (KBr) ν: 2987 (w), 2921 (w), 1596 (w), 1490 (m), 2-Trimethylsilyl-4,4,5,5-tetra(thiophen-2-yl)-1,3-dithiolane
1443 (m), 773 (m), 747 (m), 705 (s), 691 (m) cm−1; 1H NMR (10r): Yield: 220 mg (87%). Yellow crystals: mp 152–154 °C
(600 MHz, CDCl3) δ 7.60–7.58 (m, 4H, Harom), 7.31–7.29 (m, (hexane/CH2Cl2); IR (KBr) ν: 2951 (w), 1618 (w), 1424 (m),
4H, Harom), 7.23–7.21 (m, 2H, Harom), 1.62 (s, 6H, CH3) ppm; 1250 (s), 1232 (m), 1122 (m), 1077 (m), 1050 (m), 842 (s),
13C NMR (150 MHz, CDCl3) δ 142.4 (for 2 Carom), 129.4, 752 (s), 699 (s), 632 (m) cm−1; 1H NMR (600 MHz, CDCl3) δ
127.9, 126.8 (for 10 CHarom), 67.8, 52.9 (C-2, C-3), 27.9 7.23–7.22 (m, 2H, Harom), 7.20–7.19 (m, 2H, Harom), 6.96–6.95
(2 CH3) ppm; ESIMS m/z (%): 241 (100, [M + H]+); anal. calcd (m, 2H, Harom), 6.89–6.87 (m, 2H, Harom), 6.83–6.81 (m, 4H,
for C16H16S (240.36): C, 79.95; H, 6.71; S, 13.34; found: C, Harom), 3.89 (s, 1H, ((CH3)3Si)HC), 0.34 (s, 9H, (CH3)3Si)
79.69; H, 6.50; S, 13.40.
ppm; 13C NMR (150 MHz, CDCl3) δ 148.1, 146.1 (for 4
Carom), 130.2, 129.4, 127.0, 125.6, 125.5, 125.4 (for 12
1,1-Di(thiophen-2-yl)-2-methylpropene (9d): Yield: 4 mg CHarom), 74.9 (C-4, C-5), 36.5 (C-2), −1.53 ((CH3)3Si) ppm;
(2%). Yellow oil; IR (film) ν: 2927 (w), 2908 (w), 2850 (w), anal. cald for C22H22S6Si (506.89): C, 52.13; H, 4.37; S, 37.96;
1436 (m), 1369 (m), 1227 (m), 1016 (w), 827 (m), 693 (s) found: C, 52.44; H, 4.55; S,37.71.
cm−1; 1H NMR (600 MHz, CDCl3) δ 7.29 (d, J = 5.4 Hz, 2H,
Harom), 7.04–7.02 (m, 2H, Harom), 6.91 (d, J = 3.6 Hz, 2H,
Supporting Information
Harom), 2.03 (s, 6H, CH3) ppm; 13C NMR (150 MHz, CDCl3)
δ 144.9, 137.1 (Carom, Carom-C=), 126.6, 126.4, 124.9 (for 6
Supporting Information File 1
CHarom), 122.9 (C=C(CH3)2), 23.3 (2 CH3) ppm; anal. calcd for
C12H12S2 (220.35): C, 65.41; H, 5.49; S, 29.10; found: C,
65.31; H, 5.76; S, 28.81.
Experimental data for selected compounds 8–10, and the
original 1H and 13C NMR spectra for all products.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-12-71-S1.pdf]
2,2-Dimethyl-4,5-diphenyl-4,5-di(thiophen-2-yl)-1,3-dithio-
lane (10f): Isolated as a mixture of cis-, trans-isomers
(crude product ratio 65:35). Yield: 142 mg (63%).
White crystals; mp 153–154 °C (MeOH/CHCl3);
IR (KBr) ν: 3062 (w), 2919 (w), 1595 (w), 1490 (m), 1443 (m),
1231 (m), 1156 (m), 854 (w), 697 (s) cm−1; 1H NMR
(600 MHz, CDCl3) δ 7.59–6.68 (m, 32H, Harom), 1.86 (s, 3H,
CH3-cis), 1.70 (s, 6H, CH3-trans), 1.39 (s, 3H, CH3-cis) ppm;
Acknowledgements
The authors thank the National Science Center (Cracow,
Poland) for generous financial support (Grant Maestro-3 (Dec-
2012/06/A/ST5/00219). Skilful performance of microanalyses
by Ms Hanna Jatczak and Ms Agnieszka Cieślińska (University
of Łódź) is gratefully acknowledged.
723

Beilstein J. Org. Chem. 2016, 12, 716–724.
25.Fuchs, L. P., Ed. Handbook of Reagents for Organic Synthesis,
Reagents for Silicon-Mediated Organic Synthesis; John Wiley & Sons:
Hoboken, NJ, U.S.A., 2011; p 590.
References
1. Padwa, A., Ed. 1,3-Dipolar Cycloaddition Chemistry; John Wiley &
Sons: Hoboken, NJ, U.S.A., 1984; Vol. 1, 2.
26.Mlostoń, G.; Urbaniak, K.; Linden, A.; Heimgartner, H. Pol. J. Chem.
2007, 81, 1849–1860.
2. Padwa, A.; Pearson, W. H., Eds. Synthetic Applications of 1,3-Dipolar
Cycloaddition Chemistry Toward Heterocycles and Natural Products;
John Wiley & Sons: Hoboken, NJ, U.S.A., 2002.
3. Sustmann, R. Pure Appl. Chem. 1974, 40, 569–593.
doi:10.1351/pac197440040569
27.Mloston, G.; Urbaniak, K.; Linden, A.; Heimgartner, B. Heterocycles
2007, 73, 419–432. doi:10.3987/COM-07-S(U)12
28.Mlostoń, G.; Pipiak, P.; Linden, A.; Heimgartner, H. Helv. Chim. Acta
2015, 98, 462–473. doi:10.1002/hlca.201500057
4. Huisgen, R. Angew. Chem., Int. Ed. 1963, 2, 565–598.
doi:10.1002/anie.196305651
29.Mlostoń, G.; Urbaniak, K.; Pawlak, A.; Heimgartner, H. Heterocycles
2016, in press. doi:10.3987/COM-15-S(T)8
5. Huisgen, R. J. Org. Chem. 1976, 41, 403–419.
doi:10.1021/jo00865a001
30.Mlostoń, G.; Hamera, R.; Heimgartner, H.
Phosphorus, Sulfur Silicon Relat. Elem. 2015, 190, 2125–2133.
doi:10.1080/10426507.2015.1071817
6. Woodward, R. B.; Hoffmann, R. Angew. Chem., Int. Ed. Engl. 1969, 8,
781–853. doi:10.1002/anie.196907811
31.Schweizer, E. E.; Kim, C. S. J. Org. Chem. 1971, 36, 4033–4041.
doi:10.1021/jo00825a006
7. Fukui, K.; Yonezawa, T.; Shingu, H. J. Chem. Phys. 1952, 20,
722–725. doi:10.1063/1.1700523
32.Hudlicky, T.; Short, R. P. J. Org. Chem. 1982, 47, 1522–1527.
doi:10.1021/jo00347a031
8. Huisgen, R.; Mloston, G.; Giera, H.; Langhals, E. Tetrahedron 2002,
58, 507–519. doi:10.1016/S0040-4020(01)01147-4
9. Huisgen, R.; Mloston, G.; Langhals, E. Helv. Chim. Acta 2001, 84,
1805–1820.
33.Mlostoń, G.; Urbaniak, K.; Gębicki, K.; Grzelak, P.; Heimgartner, H.
Heteroat. Chem. 2014, 25, 548–555. doi:10.1002/hc.21191
doi:10.1002/1522-2675(20010613)84:6<1805::AID-HLCA1805>3.0.CO
;2-T
10.Khlebnikov, A. F.; Konev, A. S.; Virtsev, A. A.; Yufit, D. S.; Mloston, G.;
Heimgartner, H. Helv. Chim. Acta 2014, 97, 453–470.
doi:10.1002/hlca.201300405
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
11.Jasiński, R. J. Fluorine Chem. 2015, 176, 35–39.
doi:10.1016/j.jfluchem.2015.04.020
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
12.Siadati, S. A. Tetrahedron Lett. 2015, 56, 4857–4863.
doi:10.1016/j.tetlet.2015.06.048
13.Firestone, R. A. J. Org. Chem. 1968, 33, 2285–2290.
doi:10.1021/jo01270a023
14.Firestone, R. A. Tetrahedron 1977, 33, 3009–3039.
doi:10.1016/0040-4020(77)80448-1
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
15.Firestone, R. A. Int. J. Chem. Kinet. 2013, 45, 415–428.
doi:10.1002/kin.20776
(http://www.beilstein-journals.org/bjoc)
16.Kalwinsch, I.; Li, X.; Gottstein, J.; Huisgen, R. J. Am. Chem. Soc. 1981,
103, 7032–7033. doi:10.1021/ja00413a073
The definitive version of this article is the electronic one
which can be found at:
17.Huisgen, R.; Mloston, G.; Giera, H.; Langhals, E.; Polborn, K.;
Sustmann, R. Eur. J. Org. Chem. 2005, 1519–1531.
doi:10.1002/ejoc.200400765
doi:10.3762/bjoc.12.71
18.Huisgen, R.; Li, X.; Mloston, G.; Knorr, R.; Stephenson, D. S.
Tetrahedron 1999, 55, 12783–12796.
doi:10.1016/S0040-4020(99)00790-5
19.Huisgen, R.; Li, X.; Mlostoń, G.; Fluka, C. Eur. J. Org. Chem. 2000,
1695–1702.
doi:10.1002/(SICI)1099-0690(200005)2000:9<1695::AID-EJOC1695>3
.0.CO;2-4
20.Huisgen, R.; Kalwinsch, I.; Li, X.; Mloston, G. Eur. J. Org. Chem. 2000,
1685–1694.
doi:10.1002/(SICI)1099-0690(200005)2000:9<1685::AID-EJOC1685>3
.0.CO;2-6
21.Oae, S. Organic Sulfur Chemistry: Structure and Mechanism; CRC
Press, Inc.: Boca Raton, FL, U.S.A., 1992.
22.Mlostoń, G.; Urbaniak, K.; Linden, A.; Heimgartner, H. Helv. Chim. Acta
2015, 98, 453–461. doi:10.1002/hlca.201500050
23.Schönberg, A.; Cernik, D.; Urban, W. Ber. Dtsch. Chem. Ges. 1931,
64, 2577–2581. doi:10.1002/cber.19310640941
24.Shioiri, T.; Aoyama, T.; Snowden, T. e-EROS Encyclopedia of
Reagents for Organic Synthesis, 2006.
doi:10.1002/047084289X.rt298.pub2
724