Alkyl and Aryl Thiol Addition to [1.1.1]Propellane: Scope and Limitations of a Fast Conjugation Reaction

Article abstract of DOI:10.1002/chem.201704105

Herein the addition of different thiols to the strained carbon–carbon bond of [1.1.1]propellane (1) is reported. The reaction pathway was investigated, addition reactions with substituted thiols, hydrogen sulfide and protected cysteine were performed, and

Full text of DOI:10.1002/chem.201704105

A Journal of
Accepted Article
Title: Alkyl and aryl thiol addition to [1.1.1]propellane - scope and
limitations of a fast conjugation reaction
Authors: Robin M. Bär, Stefan Kirschner, Martin Nieger, and Stefan
Bräse
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To be cited as: Chem. Eur. J. 10.1002/chem.201704105
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Alkyl and aryl thiol addition to [1.1.1]propellane – scope and
limitations of a fast conjugation reaction
Robin M. Bär,[a] Stefan Kirschner,[a] Martin Nieger,[b] Stefan Bräse*,[a],[c]
Abstract: Herein we report the addition of different thiols to the
strained carbon-carbon bond of [1.1.1]propellane (1). We investigated
the reaction pathway, performed the addition with substituted thiols,
hydrogen sulfide and protected cysteine and verified further
modifications of the products. The clean reaction proceeds probably
through a radical chain process as we confirmed with different
deuterium labelling experiments. It shows great functional group
tolerance as halogen-, hydroxy-, methoxy-, carboxy-, amino- and
nitro-substituted thiols could be added to 1 with few by-products in
16–90% yield. Oxidation of the products offers a tuning of the polarity
and subsequent reactions of the products. The “click”-type reaction
proceeds even faster with selenols as we show in a proof-of-concept.
The thiol addition to 1 offers a facile tool for surface modifications,
conjugations and tuning of hydrophilicity in bio- and medicinal
chemistry compounds.
medicinal chemistry as bioisoster of para-substituted benzene[10]
and alkyne moieties.[11] With similar length and angle proportions,
the rigid group can alter the physicochemical properties such as
solubility and permeability and increase the three-dimensionality.
Driven by the exploration of novel chemical space for drug
development, Bunker et al. developed
a facile route to
bicyclo[1.1.1]pentylamine, a useful building block, in four steps
from 1.[12] The group of Baran reported a method for direct
“propellerization” of amines by strain-release amination.[13] This
click-like reaction[14] enables the late-stage modification of amines
via the turbo-amides.
Scheme 1. Synthesis of [1.1.1]propellane (1) by Szeimies et al.[6]
Introduction
The reaction of [1.1.1]propellanes like 4 with thiophenol (6a)
occurs rapidly, as Szeimies et al. were the first to mention in 1985
(Scheme 2).[6] The reaction of 1 with 6a became a method for
quantification of 1 in solution, given the high yield.[5, 15] However,
no systematic investigation of the thiol addition to 1 has been
published so far.[5-7, 15-16] For example, only thiophenyl itself was
used as thiol moiety. The addition of thiols to similar systems, e.g.
housanes, has already illustrated the importance of such
modifications.[17]
The unique structure and properties of propellanes have
fascinated chemists for the last 50 years.[1] The strained
molecules were named by Ginsburg et al. for their propeller-like
shape.[2] The smallest member of this group, [1.1.1]propellane (1),
was the first polyatomic molecule with predictions of stability,
vibrational spectrum and other properties prior to its synthesis.[3]
Wiberg et al. proved these predictions,[3b, 4] and enabled the study
of this compound’s reactivity.[5] An improved synthesis by
Szeimies et al. facilitated the access to 1, whereas the precursor
3 is readily available nowadays (Scheme 1).[6]
The compounds and subsequent polymers derived from 1
([n]staffanes) gained interest in material applications, e.g.
molecular construction sets,[7] liquid crystals[8] and rigid spacers.[9]
More recently, the bicyclo[1.1.1]pentyl-group found use in
Scheme 2. First addition of thiophenol (6a) to a [1.1.1]propellane (4).[6]
[a]
[b]
[c]
R. M. Bär, S. Kirschner, Prof. Dr. S. Bräse
Institute of Organic Chemistry
Karlsruhe Institute of Technology (KIT)
Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
E-mail: braese@kit.edu
Dr. M. Nieger
Department of Chemistry
University of Helsinki
In this study we added different thiols to 1 in order to obtain
bicyclo[1.1.1]pentylsulfides in simple reactions. These reactions
occurred at room temperature in short time without any catalysts
and showed good functional group tolerance. Further modification
of the thioethers enable a variety of applications, e.g. in surface
or peptide modifications or as novel building blocks in medicinal
chemistry.
P.O. Box 55 (A. I. Virtasen aukio 1)
00014 Unversity of Helsinki, Finland
Prof. Dr. S. Bräse
Institute of Toxicology and Genetics
Karlsruhe Institute of Technology (KIT)
Herman-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen,
Germany
Results and Discussion
The preparation of 1 was performed from cyclopropane 3 with
methyllithium in pentane/diethyl ether according to the optimized
Supporting information for this article is given via a link at the end of
the document
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procedure by Mondanaro and Dailey.[15] By vacuum distillation of
the volatiles into a cooling trap, a salt-free solution of 1 and methyl
bromide was obtained. In some reactions the methyl bromide led
to by-products. In this cases the procedure by Baran et al. was
used to synthesize a pure stock solution of 1 with phenyllithium.[13]
As mentioned previously, the reaction of 1 with thiophenol (6a)
occurs quantitatively and was used to quantify the amount of 1 in
the solution. With this procedures yields of 49–73% (based on 3)
were obtained.
insight into the reaction pathway we performed a competitive
reaction of 1 with 6ad and the para-methoxy derivative of
thiophenol 6l (Scheme 4). We obtained a mixture of four
deuterated and non-deuterated products (ESI S7). The existence
of 7ld supports the proposal of a bicyclo[1.1.1]pentyl radical 7r as
it cannot be formed by an insertion of 1 into 6l (Scheme 5). To
exclude a proton-deuterium exchange of the products 7ad and 7l
we stirred these compounds together in diethyl ether for two days.
No deuterated 7ld could be observed in this mixture (ESI S8).
The highly strained central bond of 1 is known to react with free
radicals.[5] The resulting bicyclo[1.1.1]pentyl radical is very stable
compared to the corresponding cation. This is the reason for very
few by-products in this kind of reaction.[18] It is already known that
1 inserts into disulfide bonds.[5] The very fast addition of
thiophenoxy radicals to 1 suggest a similar mechanism for the
thiol addition.[19]
Scheme 3. Addition of deuterated thiophenol (6ad) to 1. The central C–C bond
opens to form the bicyclo[1.1.1]pentane 7ad.
As a first step towards the elucidation of the mechanism of the
thiol addition to 1, we performed the reaction with deuterated
thiophenol (6ad) (Scheme 3). The 1H NMR spectrum of the
product 7ad showed a decreased signal for the bridgehead proton
by 85% (ESI S5). With regards to the 85% deuterated thiol 6ad
(ESI S4), this indicates the expected opening of the central CC
bond. The signals of the CH2 groups show a slight upfield shift for
the deuterated compound 7ad. In the 13C NMR spectrum both the
signals for the bridgehead carbon and the quaternary carbon of
the bicyclo[1.1.1]pentane disappear almost completely (ESI S6).
The strong through space orbital communication between these
two atoms have been known for a long time.[16b, 20]
Scheme 5. Proposed reaction pathway for the formation of 7ld.
To investigate the scope and the tolerated functional groups in
this reaction, different thiols were added to 1. Therefore, a stock
solution of the according thiol was added in a slight excess to the
propellane solution. After 15 min of stirring at room temperature,
the reaction was finished. Contrary to the reported addition of 6a
to 1 where the reaction mixture was irradiated with visible light,
the reaction also proceeds in the dark.[5] The remaining thiol was
removed by washing with NaOH-solution and the solvent was
removed in vacuo. If necessary, the product was purified via
column chromatography, but in most cases the product was
obtained purely. The results of the thiol addition are divided into
aromatic thiols (Table 1), aliphatic thiols (Table 2) and dithiols
(Table 3).
Monohalogenated aromatic thiols led to the desired product in
moderate to very good yields (Table 1, Entries 2–5), whereas
dihalogenated thiols only showed fair yields (Entries 6–7).
However, it is noteworthy that halides are tolerated in this reaction
and no by-products were detected at all. Alkyl-substituted
aromatic thiols reacted very well with 1, except for 6h which only
led to 57% yield (Entries 8–11). No by-products were obtained for
neither the alkyl-substituted nor the 2-hydroxy-substituted product
7m. The latter gave a yield of 61% (Entry 13).
Scheme 4. Competitive reaction of deuterated thiophenol (6ad) and
4-methoxythiophenol (6l) with 1. The reaction was performed in Et2O for 15 min
at room temperature.
In the case of activated aromatic thiols like 6l (Entry 12), a
nucleophilic substitution of methyl bromide in the stock solution of
1 took place. This led to the methylation of the thiols and therefore
decreased the yield of the desired products. To verify this
Szeimies et al. already proposed a radical chain mechanism for
this reaction.[6] This would request a bicyclo[1.1.1]pentyl radical 7r
that could be trapped by another thiol proton. To get a deeper
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observation, a solution of 1 and methyl bromide was treated with
an excess of 6a first to remove the propellane. After 15 min, 6l
was added and the solution was stirred for further 15 min. After
washing of the organic solution and removing the solvent, the two
expected products 7a and methylated 6l were obtained.
To overcome this issue in the thiol addition, two equivalents of the
thiols were used and the products could be separated in most
cases by column chromatography. To avoid the formation of the
by-product in order to simplify the purification, 1 was prepared
with phenyllithium according to Baran et al.[13] With no methyl
bromide in the stock solution, the sulfides were obtained purely
after one washing step.
Amino, nitro and carboxyl groups were also tolerated in the
reaction (Entries 14–18). However, the yields decreased
significantly with these thiols. Para- and ortho-substituted
aromatic thiols led to the lowest yields. As no large amounts of
by-products could be detected, we suppose that these products
are unstable. When stored at room temperature the amines 7n
and 7o decomposed after few days.
The carboxylic acids 6q and 6r did not dissolve in the nonpolar
solvents used in this reaction. To our surprise, the neat acids
without any solvent reacted with 1 in the usual stock solution to
achieve the desired product. The reaction time increased to 1 h
for the neat thiols. We suppose that to some extent, the acids
dissolve in diethyl ether and whenever the thiol reacts with 1
further acid can dissolve in solution. With this discovery, we
repeated the synthesis of 7f without dissolving the thiol prior to
the addition of 1. We obtained the product in similar yields.
For the products 7q and 7r we were able to grow single crystals
and determine the structure via X-ray diffraction (Figure 1). So far,
only a few crystal structures of bicyclo[1.1.1]pentylsulfides were
published and none of them contained a monosulfide with a
terminal bicyclopentane moiety.[16c, 21] Both carboxylic acids form
dimers and the bicyclo[1.1.1]pentyl-group shows a very short
distance between the two bridgehead carbons of 1.859 Å for 7q
and 1.852 Å for 7r, respectively.
Table 1. Results of the addition of aromatic thiols 6 to 1.
Entry
Thiol
R
Stock solution
of thiol
Product
Yield[a] [%]
quant.[b]
1
6a
H
1  in Et2O
7a
2
3
4
5
6b
6c
6d
6e
2-Cl
3-Cl
4-Cl
4-Br
1  in Et2O
1  in Et2O
1  in Et2O
1  in Et2O
7b
7c
7d
7e
58
72
87
65
1  in Et2O /
6
6f
2,6-Cl2
7f
65
neat
7
6g
6h
6i
3,5-Cl2
2-Me
1  in Et2O
1  in Et2O
1  in Et2O
1  in Et2O
1  in Et2O
1  in Et2O
1  in Et2O
1  in Et2O
1  in Et2O
0.5  in THF
neat
7g
7h
7i
60
57
8
9
4-Me
87
10
11
12
13
14
15
16
17
18
6j
2,4,6-Me3
4-tBu
7j
84
6k
6l
7k
7l
79
4-OMe
2-OH
90
6m
6n
6o
6p
6q
6r
7m
7n
7o
7p
7q
7r
61
3-NH2
64
4-NH2
16
Figure 1. Structures of 7q and 7r dimers determined by single crystal X-ray
4-NO2
47
diffraction.
2-COOH
3-COOH
30[c]
53[c]
Aliphatic thiols 8 also reacted with 1 without the formation of any
by-product (Table 2). Simple alkyl thiols such as 8a–d reacted
with 1 in poor to very good yields (Entries 1–4), whereas the
branched alkyl thiols yielded lower than the corresponding linear
alkyl thiols. It has to be noticed here, that these small compounds
neat
[a] Isolated yield. [b] Based on literature.[5] [c] 1 h reaction time.
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are volatile and the isolated yields varied in repeated reactions.
The addition of 2-mercaptoethanol (8e) and thioglycolic acid (8f)
to 1 worked well with 77% and 66% yield, respectively, and
demonstrated the tolerance of hydroxyl and carboxyl groups for
alkyl thiols (Entry 5–6). Benzyl mercaptane (8g) reacted with 1 in
53% yield (Entry 7). Unfortunately, a debenzylation of 9g to
bicyclo[1.1.1]pentylthiol was not successful, probably due to a
Scheme 6. Addition of hydrogen sulfide (10) (0.8  in THF) to 1. The reaction
was initiated with UV-light (254 nm).
rearrangement to
a
cyclobutane similar to the known
rearrangement of 1 with acids[4a] and subsequent hydrogenation.
One of the most interesting thiols was the protected cysteine 8h.
The addition of this compound to 1 enables peptide modifications
and leads to the new unnatural amino acid 9h (Entry 8).
The same disubstitution was observed for the dithiols 12 (Table
3). The compounds 13 were formed in satisfactory yields. Longer
reaction times or more equivalents of the thiols did not increase
the formation of the desired products.
Table 2. Results of the addition of aliphatic thiols 8 to 1.
Yield[a]
[%]
Table 3. Addition of dithiols to 1. Two equivalents of 1 were used to obtain
the disubstituted products 13.
Entry
Thiol
R
Stock
solution
of thiol
Product
Entry
Thiol
R
Stock solution of
thiol
Product
Yield[a] [%]
1  in
Et2O
1
2
3
4
5
6
7
8a
8b
8c
8d
8e
8f
nPr
iPr
9a
9b
9c
9d
9e
9f
81
35
67
39
77
66
53
1
2
3
12a
12b
12c
(CH2)2
(CH2)4
(CH2)6
1  in Et2O
1  in Et2O
1  in Et2O
13a
13b
13c
31
31
47
1  in
Et2O
1  in
Et2O
nBu
[a] Isolated yield.
1  in
Et2O
tBu
For potential applications it may be necessary to further modify
the products of the thiol addition to 1. To tune the polarity
oxidation is the simplest way. We performed the oxidation of 7a
with different amounts of mCPBA to obtain the sulfoxide 14 and
the sulfone 15 in a fast way and with a simple workup (Table 4).
The yields were determined by analytical HPLC and show a
smooth trend with the increasing amount of oxidizing agent.
The sulfoxide 14, which is the most polar compound of this series,
is obtained in the best yield with 1.5 equivalents of mCPBA
(Entry 3). Full oxidation of all the starting material to the sulfone
15 is achieved with 3.0 equivalents of mCPBA (Entry 7). These
products can be further modified, e.g. to sulfoximines, to enlarge
the fields of applications.[22]
1  in
Et2O
(CH2)2OH
CH2CO2H
Bn
1  in
Et2O
1  in
Et2O
8g
9g
0.1  in
THF
8
8h
9h
45
After the successful reactions of 1 with thiols we expanded our
investigation towards selenols (Scheme 7). Due to the stronger
nucleophilicity of selenols first attempts with a solution of 1 and
methyl bromide led to the methylated by-product. With the pure
stock solution of 1 the so far unknown selenobicyclus 17 was
obtained in quantitative yield.
[a] Isolated yield.
In the case of hydrogen sulfide (10) irradiation with UV-light
(254 nm) was necessary to initiate the radical formation (Scheme
6). In a first thiol addition, bicyclo[1.1.1]pentylthiol was formed,
which reacted with a second equivalent to form the disubstituted
product 11 with 64% yield.
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Experimental Section
For information concerning the measurements and working
techniques as well as the analytical data of all other compounds,
please use the supporting information. Crystallographic data can
be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Table 4. Oxidation of 7a to the sulfoxide 14 and the sulfone 15.
[1.1.1]Propellane (1): The compound was synthesized and distilled either
by general procedure a (with MeLi)[15] or by general procedure b (with
PhLi) (ESI S2–S3).[13] In either case, 1 was obtained in solution and stored
at –78 °C. The analytical data is in accordance with the literature.[4a]
Entry
Equiv. of mCPBA
Remaining
7a[a] [%]
Yield 14[a]
Yield 15[a]
[%]
[%]
1
2
3
4
5
6
7
1.00
1.20
1.50
1.80
2.00
2.50
3.00
52
47
15
12
–
46
50
70
66
43
4
2
3
1H NMR (300 MHz, CDCl3) ẟ = 2.00 (s, 6H, 3 x CH2) ppm; 13C NMR
(75 MHz, CDCl3) ẟ = 74.1 (–, 3 x CCH2), 1.0 (Cquart, 2 x CCH2) ppm.
15
The concentration of 1 was determined by using the approximately
quantitative reaction of 1 with 6a to prouct 7a.
22
57
1-(Phenylthio)-bicyclo[1.1.1]pentane (7a): In an argon flushed 10 mL flask
a 1  solution of thiol 6a in Et2O (0.68 mL, 680 µmol) was added to 1.0 mL
of the stock solution of 1 (prepared by general procedure a or b) with
unknown concentration. The reaction was stirred for 15 min at room
temperature. The mixture was diluted with 2 mL n-pentane and washed
with 1  NaOH solution. The organic phase was dried over Na2SO4 and
the solvent was removed under reduced pressure to obtain the product as
a pale yellow oil. The turnover of this reaction is assumed to be quantitative
to calculate the concentration of the solution of 1. The analytical data is in
accordance with the literature.[5]
–
96
–
quant.
–
[a] Determined by analytical HPLC.
In a competitive reaction of thiophenol (6a) and benzeneselenol
(16) with 1 about 80% of the selenide product 17 were obtained
and only 20% of the sulfide 7a (according to NMR, ESI S9). This
indicates an even more rapid reaction of seleno-compounds with
1.
1H NMR (400 MHz, CDCl3): ẟ = 7.46–7.43 (m, 2H, Ar-H), 7.33–7.26 (m,
3H, Ar-H), 2.73 (s, 1H, CH), 1.96 (s, 6H, 3 × CH2) ppm; 13C NMR (100 MHz,
CDCl3) ẟ = 134.2 (Cquart, CAr), 133.6 (+, 2 × CHAr), 128.9 (+, 2 × CHAr),
127.6 (+, CHAr), 54.1 (–, 3 × CH2), 45.8 (Cquart, CArSC), 28.8 (+, CH) ppm;
IR (ATR): 푣̃ = 2998 (m), 2909 (w), 2874 (w), 1583 (w), 1472 (w), 1438 (w),
1203 (m), 1128 (m), 1088 (w), 1066 (w), 1024 (w), 894 (w), 777 (vw),
741 (m), 691 (m), 548 (w), 502 (w), 423 (w), 385 (vw) cm-1; MS (EI,
70 eV): m/z (%) = 176 (18) [M]+, 135 (42) [M–C3H5]+, 109 (71) [M–C5H7]+,
99 (11) [M–C6H5]+, 78 (64) [C6H5+H]+, 77 (39) [C6H5]+, 67 (97) [C5H7]+, 41
(100) [C3H5]+; HRMS (EI, 70 eV): calcd for C11H1232S [M]+ 176.0654; found
176.0655.
Scheme 7. The addition of benzeneselenol (16) to 1 afforded the product 17 in
quantitative yield.
General procedure c for the thiol addition to 1 as an example for 7d:
Conclusions
Bicyclo[1.1.1]pent-1-yl(4-chlorophenyl)sulfane (7d): In an argon flushed
10 mL flask a 1  solution of thiol 6d in Et2O (0.390 mL, 390 µmol,
1.00 equiv.) was added to a solution of 1 (1.00 mL, 390 µmol, 1.00 equiv.)
prepared by general procedure a or b. The reaction was stirred for 15 min
at room temperature. The mixture was diluted with 2 mL n-pentane and
washed with 1  NaOH solution. The organic phase was dried over
Na2SO4 and the solvent was removed under reduced pressure to obtain
the product 7d as a pale yellow oil in 87% yield (71.0 mg, 337 µmol).
The thiol addition to [1.1.1]propellane is a versatile tool for many
potential applications. The reaction proceeds fast, clean, without
any catalyst and with no detectable amounts of by-products.
Functional groups like halogens, hydroxyl, methoxy, carboxyl,
amino and nitro groups are tolerated in this reaction and do not
need any protection. Aromatic thiols with substituents in ortho or
para position show lower yields in the addition to 1. Especially
amino and nitro groups destabilize the product. For the addition
of hydrogen sulfide irradiation with UV-light was necessary to
generate radicals. The synthesis of the novel amino acid 9h
enables peptide modifications that will be further studied.
Modification of the products is possible by oxidation to the
corresponding sulfoxide or sulfone. The expansion of the reaction
to selenols was successful and holds promise for even faster
additions of such compounds. This reaction is a useful tool for
modification, trapping and conjugation of thiols in many fields.
1H NMR (400 MHz, CDCl3): ẟ = 7.37–7.35 (m, 2H, Ar-H), 7.28–7.26 (m,
2H, Ar-H), 2.73 (s, 1H, CH), 1.94 (s, 6H, 3 × CH2) ppm; 13C NMR (100 MHz,
CDCl3) ẟ = 135.0 (+, 2 × CHAr), 133.8 (Cquart, CArS), 132.7 (Cquart, CArCl),
129.1 (+, 2 × CHAr), 54.1 (–, 3 × CH2), 45.7 (Cquart, CArSC) ppm; IR (ATR):
푣̃ = 2979 (m), 2909 (w), 2874 (w), 1572 (w), 1473 (m), 1387 (w), 1205 (m),
1127 (m), 1092 (m), 1012 (m), 888 (w), 819 (m), 776 (w), 744 (w), 555 (w),
542 (w), 504 (m), 449 (w) cm-1; MS (EI, 70 eV): m/z (%) = 212/210 (17/46)
[M]+, 169 (24) [M–C3H5]+, 144 (65) [M–C5H7+H]+, 134 (33) [M–C3H5–Cl]+,
108 (37) [M–C5H7–Cl]+, 85 (31) [M–C6H4Cl–CH3]+, 67 (100) [C5H7]+; HRMS
(EI, 70 eV): calcd for C11H1135Cl32S [M]+ 210.0270; found: 210.0269.
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(Bicyclo[1.1.1]pent-1-yl-3-d)(phenyl)sulfane (7ad): 7ad was synthesized
from a solution of 1 (general procedure a) according to the general
procedure c with 85% deuterated thiophenol (6ad) (ESI S3). The products
7ad (85%) and 7a (15%) were obtained as a pale yellow liquid in
quantitative yield (58 mg, 327 µmol). For 7ad the following analytical data
was obtained.
121.9 (Cquart, CArBr), 54.1 (–, 3 × CH2), 45.6 (Cquart, CArSC), 28.9 (+, CH)
ppm; IR (ATR): 푣̃ = 2979 (m), 2910 (w), 2875 (w), 1561 (w), 1471 (m),
1384 (w), 1205 (m), 1128 (m), 1090 (m), 1069 (m), 1009 (m), 895 (m),
815 (m), 776 (w), 729 (w), 549 (w), 511 (w), 492 (w), 445 (w) cm-1; MS (EI,
70 eV): m/z (%) = 256/254 (26/26) [M]+, 190/188 (30/29) [M–C5H7+H]+, 134
(54) [M–C3H5–Br]+, 109 (32) [M–C5H7–Br+H]+, 108 (40) [M–C5H7–Br]+, 85
(28) [M–C6H4Br–CH3]+, 67 (100) [C5H7]+; HRMS (EI, 70 eV): calcd for
C11H1179Br32S [M]+ 253.9759; found 253.9759.
1H NMR (400 MHz, CDCl3): ẟ = 7.46–7.43 (m, 2H, Ar-H), 7.33–7.26 (m,
3H, Ar-H), 1.95 (s, 6H, 3 × CH2) ppm; 13C NMR (100 MHz, CDCl3) ẟ =
134.2 (Cquart, CAr), 133.6 (+, 2 × CHAr), 128.9 (+, 2 × CHAr), 127.6 (+, CHAr),
54.0 (–, 3 × CH2), 45.8 (Cquart, CArSC) ppm; IR (ATR): 푣̃ = 2980 (w),
2910 (w), 2875 (w), 2227 (vw), 1583 (w), 1473 (w), 1438 (w), 1201 (m),
1120 (m), 1088 (w), 1066 (w), 1024 (w), 895 (w), 743 (m), 691 (m),
548 (w), 502 (w), 422 (vw) cm-1; MS (EI, 70 eV): m/z (%) = 177 (45) [M]+,
Bicyclo[1.1.1]pent-1-yl(2,6-dichlorophenyl)sulfane
(7f):
7f
was
synthesized from a solution of 1 (general procedure a) according to the
general procedure c, 6f was either added as a 1  solution in Et2O or as
a solid. The product 7f was obtained as a yellow solid in 65% yield (154 mg,
628 µmol).
2
2
2
135 (74) [M–C3H4 H]+, 110 (100) [M–C5H6 H+H]+, 109 (27) [M–C5H6 H]+,
100 (11) [M–C6H5]+, 77 (14) [C6H5]+, 68 (61) [C5H6 H]+; HRMS (EI, 70 eV):
calcd for C11H112H32S [M]+ 177.0717; found 177.0715.
2
m.p. 40–42 °C; 1H NMR (400 MHz, CDCl3) ẟ = 7.41 (d, 3J = 7.7 Hz, 2H,
Ar-H), 7.18 (dd, 3J = 7.7 Hz, 3J = 7.7 Hz, 1H, Ar-H), 2.67 (s, 1H, CH), 1.96
(s, 3 × CH2) ppm; 13C NMR (100 MHz, CDCl3) ẟ = 142.5 (Cquart, 2 × CArCl),
131.9 (Cquart, CArS), 130.2 (+, CHAr), 128.6 (+, 2 × CHAr), 54.7 (–, 3 × CH2),
46.0 (Cquart, CArSC), 28.5 (+, CH) ppm; IR (ATR): 푣̃ = 2980 (w), 2909 (w),
2875 (w), 1553 (m), 1422 (m), 1400 (m), 1202 (m), 1185 (m), 1123 (m),
1086 (w), 926 (w), 892 (m), 773 (s), 708 (m), 557 (w), 557 (w), 517 (w),
476 (w), 436 (w), 398 (w) cm-1; MS (EI, 70 eV): m/z (%) = 248/246/244
(1/5/7) [M]+, 209 (14) [M–Cl]+, 178 (29) [M–C5H7+H]+, 142 (28) [M–C5H7–
Cl]+, 107 (10) [M–C5H7–Cl2]+, 85 (22) [M–C6H3Cl2–CH2]+, 67 (100) [M–
C6H3Cl2S]+; HRMS (EI, 70 eV): calcd for C11H1035Cl232S [M]+ 243.9875;
found 243.9876.
Bicyclo[1.1.1]pent-1-yl(2-chlorophenyl)sulfane (7b): 7b was synthesized
from a solution of 1 (general procedure a) according to the general
procedure c. The product 7b was obtained as a yellow liquid in 58% yield
(91.0 mg, 432 µmol).
1H NMR (400 MHz, CDCl3): ẟ = 7.57–7.55 (m, 1H, Ar-H), 7.43–7.40 (m,
1H, Ar-H), 7.22–7.19 (m, 2H, Ar-H), 2.75 (s, 1H, CH), 2.02 (s, 6H, 3 × CH2)
ppm; 13C NMR (100 MHz, CDCl3) ẟ = 137.1 (Cquart, CArCl), 134.8 (+, CHAr),
133.9 (Cquart, CArS), 130.0 (+, CHAr), 128.6 (+, CHAr), 127.0 (+, CHAr), 54.4
(–, 3 × CH2), 45.4 (Cquart, CArSC), 29.3 (+, CH) ppm; IR (ATR):
푣̃ = 2959 (w), 2913 (m), 2874 (w), 1574 (vw), 1449 (m), 1427 (w),
1375 (w), 1249 (w), 1205 (m), 1123 (w), 1035 (m), 923 (vw), 894 (w),
748 (m), 658 (w), 551 (vw), 463 (vw), 432 (w) cm-1; MS (EI, 70 eV): m/z
(%) = 212/210 (10/27) [M]+, 169 (26) [M–C3H5]+, 144 (67) [M–C5H7+H]+,
134 (40) [M–C3H5–Cl]+, 108 (40) [M–C5H7–Cl]+, 85 (20) [M–C6H4Cl–CH3]+,
67 (100) [C5H7]+; HRMS (EI, 70 eV): calcd for C11H1135Cl32S [M]+ 210.0270;
found 210.0270.
Bicyclo[1.1.1]pent-1-yl(3,5-dichlorophenyl)sulfane
(7g):
7g
was
synthesized from a solution of 1 (general procedure a) according to the
general procedure c. The product 7g was obtained as a yellow liquid in
60% yield (39.0 mg, 159 µmol).
1H NMR (400 MHz, CDCl3) ẟ = 7.30 (d, 3J = 1.8 Hz, 2H, Ar-H), 7.25 (t,
3J = 1.8 Hz, 1H, Ar-H), 2.78 (s, 1H, CH), 2.02 (s, 6H, 3 × CH2) ppm;
13C NMR (100 MHz, CDCl3) ẟ = 138.1 (Cquart, CArS), 134.9 (Cquart
,
Bicyclo[1.1.1]pent-1-yl(3-chlorophenyl)sulfane (7c): 7c was synthesized
from a solution of 1 (general procedure b) according to the general
procedure c. The product 7c was obtained as a yellow liquid in 72% yield
(53.0 mg, 252 µmol).
2 × CArCl), 130.7 (+, 2 × CHAr), 127.5 (+, CHAr), 54.4 (–, 3 × CH2), 45.2
(Cquart, CArSC), 29.3 (+, CH) ppm; IR (ATR): 푣̃ = 2981 (m), 2908 (w),
2876 (w), 1554 (s), 1401 (m), 1379 (w), 1206 (m), 1141 (m), 1125 (m),
1100 (m), 894 (w), 854 (m), 795 (s), 670 (m), 428 (w) cm-1; MS (EI, 70 eV):
m/z (%) = 248/246/244 (2/10/15) [M]+, 178 (20) [M–C5H7+H]+, 142 (47) [M–
C5H7–Cl]+, 107 (12) [M–C5H7–Cl2]+, 99 (36) [C5H7S]+, 85 (14) [M–C6H3Cl2–
CH3]+, 67 (100) [M–C6H3Cl2S]+; HRMS (EI, 70 eV): calcd for C11H1035Cl232S
[M]+ 243.9875; found 243.9874.
1H NMR (400 MHz, CDCl3): ẟ = 7.44–7.43 (m, 1H, Ar-H), 7.32–7.30 (m,
1H, Ar-H), 7.24–7.22 (m, 2H, Ar-H), 2.75 (s, 1H, CH), 1.98 (s, 6H, 3 × CH2)
ppm; 13C NMR (100 MHz, CDCl3) ẟ = 136.4 (Cquart, CArCl), 134.4 (Cquart
,
CArS), 132.9 (+, CHAr), 131.3 (+, CHAr), 129.9 (+, CHAr), 127.6 (+, CHAr),
54.2 (–, 3 × CH2), 45.5 (Cquart, CArSC), 29.0 (+, CH) ppm; IR (ATR):
푣̃ = 3467 (vw), 2924 (w), 2853 (w), 1746 (w), 1575 (vw), 1461 (w),
1378 (w), 1358 (w), 1247 (w), 1206 (w), 1130 (w), 1089 (m), 1069 (w),
1006 (w), 939 (vw), 891 (w), 871 (w), 853 (w), 833 (m), 814 (w), 772 (m),
681 (w), 667 (w), 545 (vw), 524 (vw) cm-1; MS (EI, 70 eV): m/z (%) =
212/210 (15/38) [M]+, 169 (23) [M–C3H5]+, 144 (43) [M–C5H7+H]+, 134 (37)
[M–C3H5–Cl]+, 108 (36) [M–C5H7–Cl]+, 85 (20) [M–C6H4Cl–CH3]+, 67 (100)
[C5H7]+; HRMS (EI, 70 eV): calcd for C11H1135Cl32S [M]+ 210.0270; found
210.0271.
Bicyclo[1.1.1]pent-1-yl(o-tolyl)sulfane (7h): 7h was synthesized from a
solution of 1 (general procedure a) according to the general procedure c.
The product 7h was obtained as a pale yellow liquid in 57% yield (28.0 mg,
147 µmol).
1H NMR (400 MHz, CDCl3) ẟ = 7.48–7.46 (m, 1H, Ar-H), 7.24–7.12 (m, 3H,
Ar-H), 2.70 (s, 1H, CH), 2.43 (s, 3H, CH3), 1.94 (s, 6H, 3 × CH2) ppm;
13C NMR (100 MHz, CDCl3) ẟ = 141.0 (Cquart, CArCH3), 135.0 (+, CHAr),
133.5 (Cquart, CArS), 130.4 (+, CHAr), 127.9 (+, CHAr), 126.3 (+, CHAr), 54.2
(–, 3 × CH2), 45.8 (Cquart, CArSC), 29.0 (+, CH), 21.3 (+, CH3) ppm; IR
(ATR): 푣̃ = 2977 (m), 2909 (w), 2875 (w), 1589 (vw), 1469 (w), 1378 (w),
1203 (m), 1127 (m), 1061 (w), 1035 (w), 923 (vw), 896 (m), 779 (vw),
746 (s), 712 (m), 678 (w), 556 (vw), 460 (w), 424 (w) cm-1; MS (EI, 70 eV):
m/z (%) = 190 (10) [M]+, 149 (100) [M–C3H5]+, 124 (17) [M–C5H7+H]+, 91
(30) [M–C5H7S]+, 67 (18) [C5H7]+; HRMS (EI, 70 eV): calcd for C12H1432S
[M]+ 190.0811; found 190.0809.
Bicyclo[1.1.1]pent-1-yl(4-bromophenyl)sulfane (7e): 7e was synthesized
from a solution of 1 (general procedure a) according to the general
procedure c. The product 7e was obtained as a yellow liquid in 65% yield
(45.0 mg, 176 µmol).
1H NMR (500 MHz, CDCl3): ẟ = 7.44–7.41 (m, 2H, Ar-H), 7.31–7.28 (m,
2H, Ar-H), 2.73 (s, 1H, CH), 1.95 (s, 6H, 3 × CH2) ppm; 13C NMR (125 MHz,
CDCl3) ẟ = 135.2 (+, 2 × CHAr), 133.4 (Cquart, CArS), 132.0 (+, 2 × CHAr),
This article is protected by copyright. All rights reserved.

10.1002/chem.201704105
Chemistry - A European Journal
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Bicyclo[1.1.1]pent-1-yl(p-tolyl)sulfane (7i): 7i was synthesized from a
solution of 1 (general procedure a) according to the general procedure c.
The product 7i was obtained as a yellow liquid in 87% yield (45.0 mg,
236 µmol).
1440 (w), 1284 (m), 1242 (s), 1205 (m), 1171 (m), 1130 (m), 1096 (m),
1030 (m), 892 (m), 826 (m), 798 (m), 640 (w), 628 (w), 550 (w), 525 (w),
457 (vw) cm-1; MS (EI, 70 eV): m/z (%) = 206 (100) [M]+, 165 (23) [M–
C3H5]+, 140 (66) [M–C5H7+H]+, 139 (35) [M–C5H7]+, 125 (33) [M–C5H7–
CH3+H]+, 124 (9) [M–C5H7–CH3+H]+, 121 (45) [M–C4H7–OCH3]+, 85 (20)
[M–C6H4OCH3–CH3]+, 67 (18) [C5H7]+; HRMS (EI, 70 eV): calcd for
C12H14O32S [M]+ 206.0765; found 206.0764.
1H NMR (500 MHz, CDCl3): ẟ = 7.34–7.32 (m, 2H, Ar-H), 7.12–7.10 (m,
2H, Ar-H), 2.71 (s, 1H, CH), 2.34 (s, 3H, CH3), 1.92 (s, 6H, 3 × CH2) ppm;
13C NMR (125 MHz, CDCl3): ẟ = 137.7 (Cquart, CArCH3), 134.0 (+, 2 × CHAr),
130.4 (Cquart, CArS), 129.7 (+, 2 × CHAr), 54.0 (–, 3 × CH2), 45.9 (Cquart
,
2-(Bicyclo[1.1.1]pent-1-ylthio)phenol (7m): 7m was synthesized from a
solution of 1 (general procedure a) according to the general procedure c.
The product 7m was obtained as a pale yellow liquid in 61% yield (91.0 mg,
473 µmol).
CArSC), 28.7 (+, CH), 21.3 (+, CH3) ppm; IR (ATR): 푣̃ = 2978 (m), 2910 (w),
2874 (w), 1490 (m), 1447 (w), 1398 (vw), 1205 (m), 1129 (m), 1093 (w),
1018 (w), 890 (w), 808 (m), 775 (w), 733 (w), 706 (w), 549 (w), 507 (m),
449 (w) cm-1; MS (EI, 70 eV): m/z (%) = 191 (13) [M+1]+, 190 (87) [M]+,
175 (10) [M–CH3]+, 149 (100) [M–C3H5]+, 134 (32) [M–C3H5–CH3]+, 124
(85) [M–C5H7+H]+, 123 (30) [M–C5H7]+, 91 (87) [M–C5H7S]+, 85 (37) [M–
C6H4CH3–CH3]+, 67 (52) [C5H7]+; HRMS (EI, 70 eV): calcd for C12H1432S
[M]+ 190.0811; found 190.0812.
1H NMR (500 MHz, CDCl3): ẟ = 7.40 (dd, 3J = 7.5 Hz, 4J = 1.6 Hz, 1H,
Ar-H), 7.28 (ddd, 3J = 8.2 Hz, 3J = 6.3 Hz, 4J = 1.6 Hz, 1H, Ar-H), 7.00 (dd,
3J = 8.2 Hz, 4J = 1.3 Hz, 1H, Ar-H), 6.87 (ddd, 3J = 7.5 Hz, 3J = 6.3 Hz,
4J = 1.3 Hz, 1H, Ar-H), 6.70 (s, 1H, OH), 2.69 (s, 1H, CH), 1.87 (s, 6H,
3 × CH2) ppm; 13C NMR (125 MHz, CDCl3): ẟ = 157.1 (Cquart., CArOH),
136.7 (+, CHAr), 131.4 (+, CHAr), 120.7 (+, CHAr), 117.4 (Cquart., CArS), 114.8
(+, CHAr), 53.9 (–, 3 × CH2), 45.4 (Cquart., CArSC), 28.3 (+, CH) ppm; IR
(ATR): 푣̃ = 3403 (w), 2979 (m), 2909 (w), 2875 (w), 1573 (w), 1469 (s),
1342 (w), 1287 (w), 1240 (m), 1202 (s), 1128 (m), 1026 (m), 888 (m),
830 (w), 751 (s), 680 (w), 527 (w), 475 (m), 429 (w), 395 (w) cm-1; MS (EI,
70 eV): m/z (%) = 192 (5) [M]+, 151 (100) [M–C3H5]+, 126 (16) [M–C5H7+H]+,
125 (3) [M–C5H7]+, 67 (16) [C5H7]+; HRMS (EI, 70 eV): calcd for
C11H12O32S [M]+ 192.0603; found 192.0605.
Bicyclo[1.1.1]pent-1-yl(mesityl)sulfane (7j): 7j was synthesized from a
solution of 1 (general procedure a) according to the general procedure c.
The product 7j was obtained as a pale yellow liquid in 84% yield (50.0 mg,
229 µmol).
1H NMR (400 MHz, CDCl3): ẟ = 6.95–6.92 (m, 2H, Ar-H), 2.62 (s, 1H, CH),
2.46 (s, 6H, C2CH3 + C6CH3), 2.27 (s, 3H, C4CH3), 1.86 (s, 6H, 3 × CH2)
ppm; 13C NMR (100 MHz, CDCl3): ẟ = 143.6 (Cquart., C2 + C6), 138.1 (Cquart.
C4), 128.9 (+, 2 × CHAr), 128.6 (Cquart., C1), 54.2 (–, 3 × CH2), 46.4 (Cquart.
,
,
C1SC), 28.3 (+, CH), 22.4 (+, C2CH3 + C6CH3), 21.2 (+, C4CH3) ppm; IR
(ATR): 푣̃ = 2974 (m), 2908 (w), 2872 (w), 1601 (w), 1448 (w), 1373 (w),
1203 (m), 1128 (m), 1060 (w), 1030 (w), 894 (w), 848 (m), 718 (w),
562 (w), 412 (vw) cm-1; MS (EI, 70 eV): m/z (%) = 218 (5) [M]+, 203 (11)
[M–CH3]+, 177 (100) [M–C3H5]+, 162 (35) [M–C3H5–CH3]+, 119 (21) [M–
C5H7S]+; HRMS (EI, 70 eV): calcd for C14H1832S [M]+ 218.1124; found
218.1123.
3-(Bicyclo[1.1.1]pent-1-ylthiol)aniline (7n): 7n was synthesized from a
solution of 1 (general procedure a) according to the general procedure c.
The product 7n was obtained as a pale yellow liquid in 64% yield (47.0 mg,
246 µmol).
1H NMR (400 MHz, CDCl3): ẟ = 7.10–7.05 (m, 1H, Ar-H), 6.86–6.81 (m,
1H, Ar-H), 6.78–6.76 (m, 1H, Ar-H), 6.61–6.57 (m, 1H, Ar-H), 3.65 (b, 2H,
NH2), 2.72 (s, 1H, CH), 1.97 (s, 6H, 3 × CH2) ppm; 13C NMR (100 MHz,
CDCl3): ẟ = 146.7 (Cquart., CArNH2), 135.0 (Cquart., CArS), 129.6 (+, CHAr),
123.6 (+, CHAr), 119.8 (+, CHAr), 114.4 (+, CHAr), 54.2 (–, 3 × CH2), 45.6
(Cquart., CArSC), 28.8 (+, CH) ppm; IR (ATR): 푣̃ = 3351 (w), 2977 (m),
2907 (w), 2873 (w), 1616 (m), 1588 (s), 1478 (m), 1438 (w), 1297 (w),
1263 (w), 1204 (m), 1163 (w), 1127 (m), 1078 (w), 992 (w), 886 (w),
771 (m), 687 (m), 529 (w), 446 (w) cm-1; MS (EI, 70 eV): m/z (%) = 192 (6)
[M+H]+, 191 (49) [M]+, 150 (26) [M–C3H5]+, 125 (100) [M–C5H7+H]+, 124
(13) [M–C5H7]+, 106 (34) [M–C5H8–NH2]+; HRMS (EI, 70 eV): calcd for
C11H13N32S [M]+ 191.0763; found 191.0763.
Bicyclo[1.1.1]pent-1-yl(4-(tert-butyl)phenyl)sulfane
(7k):
7k
was
synthesized from a solution of 1 (general procedure a) according to the
general procedure c. The product 7k was obtained as a pale yellow liquid
in 79% yield (50.0 mg, 215 µmol).
1H NMR (400 MHz, CDCl3): ẟ = 7.38–7.35 (m, 2H, Ar-H), 7.33–7.30 (m,
2H, Ar-H), 2.71 (s, 1H, CH), 1.95 (s, 6H, 3 × CH2), 1.31 (s, 9H, 3 × CH3)
ppm; 13C NMR (100 MHz, CDCl3): ẟ = 150.7 (Cquart., CArCCH3), 133.4 (+,
2 × CHAr), 130.6 (Cquart., CArS), 125.9 (+, 2 × CHAr), 54.1 (–, 3 × CH2), 45.8
(Cquart., CArSC), 34.7 (Cquart., CCH3), 31.4 (+, 3 × CH3), 28.8 (+, CH) ppm;
IR (ATR): 푣̃ = 2961 (m), 2907 (w), 2873 (w), 1488 (w), 1460 (w), 1393 (w),
1362 (w), 1266 (w), 1203 (m), 1129 (w), 1116 (m), 1013 (w), 895 (w),
827 (m), 742 (w), 561 (m), 410 (vw) cm-1; MS (EI, 70 eV): m/z (%) = 232
(42) [M]+, 217 (100) [M–CH3]+, 151 (25) [M–CH3–C5H7]+, 85 (23) [M–
C6H4C(CH3)3–CH2]+, 67 (11) [C5H7]+, 57 (27) [C(CH3)3]+; HRMS (EI,
70 eV): calcd for C15H2032S [M]+ 232.1280; found 232.1279.
4-(Bicyclo[1.1.1]pent-1-ylthiol)aniline (7o): 7o was synthesized from a
solution of 1 (general procedure b) according to the general procedure c.
The product 7o was obtained as a yellow oil in 16% yield (11.0 mg,
57.5 µmol).
1H NMR (400 MHz, CDCl3): ẟ = 7.26–7.23 (m, 2H, Ar-H), 6.63–6.61 (m,
2H, Ar-H), 3.70 (b, 2H, NH2), 2.68 (s, 1H, CH), 1.86 (s, 6H, 3 × CH2) ppm;
13C NMR (100 MHz, CDCl3): ẟ = 146.5 (Cquart., CArNH2), 136.2 (+, 2 × CHAr),
Bicyclo[1.1.1]pent-1-yl(4-methoxyphenyl)sulfane (7l): 7l was synthesized
from a solution of 1 (general procedure b) according to the general
procedure c. The product 7l was obtained as a pale yellow liquid in 90%
yield (111 mg, 538 µmol).
121.5 (Cquart., CArS), 115.5 (+, 2 × CHAr), 53.7 (–, 3 × CH2), 46.4 (Cquart.
,
CArSC), 28.4 (+, CH) ppm; IR (ATR): 푣̃ = 3431 (w), 3342 (m), 3213 (w),
3021 (vw), 2971 (m), 2905 (w), 2872 (w), 1884 (vw), 1631 (m), 1593 (m),
1491 (m), 1423 (w), 1296 (m), 1201 (m), 1177 (m), 1125 (m), 1096 (m),
1063 (w), 1006 (vw), 935 (vw), 890 (m), 814 (s), 771 (w), 646 (w), 546 (w),
517 (s), 423 (w), 406 (w) cm-1; MS (EI, 70 eV): m/z (%) = 192 (14) [M+H]+,
191 (100) [M]+, 150 (22) [M–C3H5]+, 125 (65) [M–C5H7+H]+, 124 (62) [M–
C5H7]+, 106 (49) [M–C5H8–NH2]+; HRMS (EI, 70 eV): calcd for C11H13N32S
[M]+ 191.0763; found 191.0764.
1H NMR (400 MHz, CDCl3): ẟ = 7.40–7.35 (m, 2H, Ar-H), 6.86–6.82 (m,
2H, Ar-H), 3.81 (s, 3H, CH3), 2.69 (s, 1H, CH), 1.88 (s, 6H, 3 × CH2) ppm;
13C NMR (100 MHz, CDCl3) ẟ = 159.7 (Cquart, CArOCH3), 136.0 (+,
2 × CHAr), 124.5 (Cquart, CArS), 114.5 (+, 2 × CHAr), 55.4 (+, CH3), 53.8 (–,
3 × CH2), 46.3 (Cquart, CArSC), 28.5 (+, CH) ppm; IR (ATR): 푣̃ = 2977 (m),
2908 (w), 2874 (w), 2835 (w), 1590 (m), 1571 (w), 1491 (s), 1462 (m),
This article is protected by copyright. All rights reserved.

10.1002/chem.201704105
Chemistry - A European Journal
FULL PAPER
Bicyclo[1.1.1]pent-1-yl(4-nitrophenyl)sulfane (7p): 7p was synthesized
from a solution of 1 (general procedure b) according to the general
procedure c, but 6p was added as a 0.5  solution in THF. The product
7p was obtained as a yellow solid that melts around room temperature in
47% yield (62.0 mg, 280 µmol).
(35) [M–C5H7+H]+, 135 (28) [M–C3H5–CO2]+, 109 (10) [M–C5H7–CO2]+, 85
(20) [M–CO2H–C6H5–CH2]+, 67 (100) [C5H7]+; HRMS (EI, 70 eV): calcd for
C12H12O232S [M]+ 220.0558; found 220.0558.
For crystallographic data of this compound please use the supporting
information. CCDC 1575330 contains the supplementary crystallographic
data for this compound.
1H NMR (400 MHz, CDCl3): ẟ = 8.15–8.12 (m, 2H, Ar-H), 7.53–7.49 (m,
2H, Ar-H), 2.84 (s, 1H, CH), 2.13 (s, 6H, 3 × CH2) ppm; 13C NMR (100 MHz,
CDCl3): ẟ = 146.2 (Cquart., CArNO2), 145.6 (Cquart., CArS), 130.7 (+, 2 × CHAr),
123.9 (+, 2 × CHAr), 54.7 (–, 3 × CH2), 44.6 (Cquart., CArSC), 30.0 (+, CH)
ppm; IR (ATR): 푣̃ = 2983 (w), 2913 (w), 2877 (w), 1594 (w), 1575 (m),
1475 (w), 1336 (s), 1259 (w), 1208 (m), 1124 (m), 1090 (m), 1012 (w),
892 (w), 851 (m), 742 (m), 684 (w), 535 (w), 408 (vw) cm-1; MS (EI,
70 eV): m/z (%) = 222 (6) [M+1]+, 221 (38) [M]+, 180 (7) [M–C3H5]+, 134
(31) [M–C3H5–NO2]+, 85 (12) [M–C6H4NO2–CH3]+, 67 (100) [C5H7]+; HRMS
(EI, 70 eV) calcd for C11H11O2N32S [M]+ 221.0505; found 221.0506.
Di(bicyclo[1.1.1]pent-1-yl)sulfane (11): In a quartz cuvette under argon
atmosphere a 0.8  solution of H2S in THF (1.06 mL, 850 µmol,
1.00 equiv.) was added to a 0.37  solution of 1 (general procedure a)
(2.30 mL, 850 µmol, 1.00 equiv.) and irradiated for 1 h with a 4 W UV lamp
(254 nm). The reaction mixture was diluted with 2 mL n-pentane and
washed with 1  NaOH solution. The organic phase was dried over
Na2SO4 and the solvent was removed under reduced pressure at room
temperature to obtain the product 11 as a volatile, pale yellow liquid in 64%
yield (90.0 mg, 540 µmol).
2-(Bicyclo[1.1.1]pent-1-ylthio)benzoic acid (7q): 7q was synthesized from
a solution of 1 (general procedure b) according to the general procedure
c, but 6q was added as a solid. Afterwards the crude product was purified
1H NMR (400 MHz, CDCl3): ẟ = 2.71 (s, 2H, 2 × CH), 2.04 (s, 12H,
6 × CH2) ppm; 13C NMR (100 MHz, CDCl3): ẟ = 55.2 (–, 6 × CH2), 44.2
(Cquart., 2 × SC), 30.1 (+, 2 × CH) ppm; IR (ATR): 푣̃ = 2975 (m), 2909 (m),
2874 (m), 1447 (vw), 1201 (s), 1131 (m), 894 (m), 471 (w) cm-1; MS (EI,
70 eV): m/z (%) = 166 (9) [M]+, 125 (16) [M–C3H5]+, 99 (34) [M–C5H7]+, 85
(54) [M–(C3H5)2+H]+, 67 (100) [C5H7]+; HRMS (EI, 70 eV): calcd for
C10H1432S [M]+ 166.0811; found 166.0812.
by
column
chromatography
(SiO2,
cyclohexane/EtOAc/AcOH,
5/1/0.01). The product 7q was obtained as a white solid in 30% yield
(29.0 mg, 132 µmol).
Rf (SiO2, cyclohexane/EtOAc/AcOH, 5/1/0.01): 0.22; m.p. 125–127 °C;
1H NMR (400 MHz, CDCl3): ẟ = 8.17 (dd, 3J = 7.8 Hz, 4J = 1.5 Hz, 1H, Ar-
H), 7.64 (dd, 3J = 7.8 Hz, 4J = 1.1 Hz, 1H, Ar-H), 7.50 (ddd, 3J = 7.8 Hz,
3J = 7.6 Hz, 4J = 1.5 Hz, 1H, Ar-H), 7.34 (ddd, 3J = 7.8 Hz, 3J = 7.6 Hz,
3J = 1.1 Hz, 1H, Ar-H), 2.81 (s, 1H, CH), 2.08 (s, 6H, 3 × CH2) ppm;
13C NMR (100 MHz, CDCl3): ẟ = 169.7 (Cquart., CO2H), 132.9 (Cquart., CArS),
132.8 (+, 2 × CHAr), 132.7 (+, CHAr), 129.9 (Cquart., CArCO2H), 127.0 (+,
CHAr), 54.4 (–, 3 × CH2), 45.3 (Cquart., CArSC), 29.8 (+, CH) ppm; IR (ATR):
푣̃ = 2971 (m), 2915 (m), 2879 (m), 2643 (w), 1673 (s), 1587 (w), 1560 (m),
1463 (m), 1434 (w), 1406 (m), 1309 (m), 1251 (s), 1206 (m), 1135 (m),
1056 (m), 1043 (m), 917 (m), 893 (m), 806 (w), 737 (s), 692 (m), 650 (m),
557 (m), 491 (w), 464 (w), 416 (w) cm-1; MS (EI, 70 eV): m/z (%) = 221 (1)
[M+1]+, 220 (4) [M]+, 179 (10) [M–C3H5]+, 136 (100) [M–C3H5–CO2+H]+,
109 (11) [M–C5H7–CO2]+, 99 (64) [M–C6H4CO2H]+, 67 (37) [C5H7]+; HRMS
(EI, 70 eV): calcd for C12H12O232S [M]+ 220.0558; found 220.0559.
Bicyclo[1.1.1]pent-1-yl(propyl)sulfane (9a): 9a was synthesized from a
solution of 1 (general procedure a) according to the general procedure c.
The product 9a was obtained as a volatile, pale yellow liquid in 81% yield
(42.0 mg, 295 µmol).
1H NMR (400 MHz, CDCl3): ẟ = 2.72 (s, 1H, CH), 2.51 (t, 3J = 7.3 Hz, 2H,
CH2CH2CH3), 1.96 (s, 6H, 3 × CCH2CH), 1.60 (td,3J = 7.4 Hz, 3J = 7.3 Hz,
2H, CH2CH2CH3), 0.98 (t, 3J = 7.4 Hz, 3H, CH3) ppm; 13C NMR (100 MHz,
CDCl3): ẟ = 53.9 (–, 3 × CCH2CH), 44.7 (Cquart., CCH2CH), 33.3 (–,
CH2CH2CH3), 28.8 (+, CH), 23.9 (–, CH2CH2CH3), 13.7 (+, CH3) ppm; IR
(ATR): 푣̃ = 2961 (m), 2907 (w), 2872 (w), 1450 (w), 1376 (vw), 1291 (vw),
1205 (m), 1140 (m), 902 (w), 797 (vw) cm-1. Due to the nonpolar and
volatile nature of this compound no HRMS measurement was possible with
EI or FAB. In the ESI (S10) we attached a GC-MS spectrum of 9a.
For crystallographic data of this compound please use the supporting
information. CCDC 1575329 contains the supplementary crystallographic
data for this compound.
Bicyclo[1.1.1]pent-1-yl(isopropyl)sulfane (9b): 9b was synthesized from a
solution of 1 (general procedure a) according to the general procedure c.
The product 9b was obtained as a volatile, colourless liquid in 35% yield
(18.0 mg, 127 µmol).
3-(Bicyclo[1.1.1]pent-1-ylthio)benzoic acid (7r): 7r was synthesized from a
solution of 1 (general procedure a) according to the general procedure c,
but 6r was added as a solid. Afterwards the crude product was purified by
column chromatography (SiO2, cyclohexane/EtOAc/AcOH, 5/1/0.01). The
product 7r was obtained as a white solid in 53% yield (63.0 mg, 286 µmol).
1H NMR (400 MHz, CDCl3): ẟ = 2.96 (sept, 3J = 6.8 Hz, 1H, CH(CH3)2),
2.71 (s, 1H, CH(CH2)3), 2.00 (s, 6H, 3 × CH2), 1.28 (d, 3J = 6.8 Hz, 6H,
2 × CH3) ppm; 13C NMR (100 MHz, CDCl3): ẟ = 54.6 (–, 3 × CH2), 44.5
(Cquart., CHSC), 35.8 (+, CH(CH3)2), 29.2 (+, CH(CH2)3), 24.8 (+, 2 × CH3)
ppm; IR (ATR): 푣̃ = 2974 (w), 2908 (w), 2873 (w), 1447 (vw), 1381 (vw),
1364 (vw), 1243 (vw), 1206 (m), 1139 (w), 1050 (w), 903 (vw),
646 (vw) cm-1. Due to the nonpolar and volatile nature of this compound
no HRMS measurement was possible with EI or FAB. In the ESI (S11) we
attached a GC-MS spectrum of 9b.
Rf (SiO2, cyclohexane/EtOAc/AcOH, 5/1/0.01): 0.29; m.p. 108–110 °C;
1H NMR (400 MHz, CDCl3): ẟ = 8.12 (dd, 4J = 1.8 Hz, 4J = 1.8 Hz, 1H, Ar-
3
H), 7.94 (ddd, J = 7.8 Hz, 4J = 1.8 Hz, 4J = 1.3 Hz, 1H, Ar-H), 7.60 (ddd,
3J = 7.7 Hz, 4J = 1.8 Hz, 4J = 1.3 Hz, 1H, Ar-H), 7.35 (dd, 3J = 7.8 Hz,
3J = 7.7 Hz, 1H, Ar-H), 2.69 (s, 1H, CH), 1.93 (s, 6H, 3 × CH2) ppm;
13C NMR (100 MHz, CDCl3): ẟ = 170.5 (Cquart., CO2H), 138.4 (+, CHAr),
135.5 (Cquart., CArS), 134.7 (+, CHAr), 129.9 (Cquart., CArCO2H), 129.1 (+,
CHAr), 129.0 (+, CHAr), 54.3 (–, 3 × CH2), 45.5 (Cquart., CArSC), 29.1 (+, CH)
ppm; IR (ATR): 푣̃ = 2986 (w), 2906 (w), 2873 (w), 2544 (w), 1686 (s),
1591 (w), 1570 (w), 1474 (w), 1420 (m), 1290 (m), 1260 (m), 1204 (m),
1165 (w), 1125 (m), 1071 (m), 928 (m), 905 (m), 886 (m), 848 (w), 813 (w),
746 (m), 720 (m), 677 (m), 656 (m), 548 (m), 515 (w), 414 (w) cm-1; MS (EI,
70 eV): m/z (%) = 221 (5) [M+1]+, 220 (36) [M]+, 179 (15) [M–C3H5]+, 154
Bicyclo[1.1.1]pent-1-yl(butyl)sulfane (9c): 9c was synthesized from a
solution of 1 (general procedure a) according to the general procedure c.
The product 9c was obtained as a volatile, pale yellow liquid in 67% yield
(38.0 mg, 243 µmol).
1H NMR (400 MHz, CDCl3): ẟ = 2.72 (s, 1H, CH), 2.53 (t, 3J = 7.4 Hz, 2H,
CH2CH2CH2CH3), 1.96 (s, 6H, 3 × CCH2CH), 1.61–1.52 (m, 2H,
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CH2CH2CH2CH3), 1.44–1.35 (m, 2H, CH2CH2CH2CH3), 0.91 (t, 3J = 7.3 Hz,
3H, CH3) ppm; 13C NMR (100 MHz, CDCl3): ẟ = 53.9 (–, 3 × CCH2CH),
The product 9g was obtained as a pale yellow oil in 53% yield (94.0 mg,
494 µmol).
44.7 (Cquart.
,
CCH2CH), 33.3 (–, CH2CH2CH2CH3), 31.0 (–,
1H NMR (400 MHz, CDCl3): ẟ = 7.32–7.17 (m, 5H, Ar-H), 3.73 (s, 2H,
C6H5CH2S), 2.64 (s, 1H, CH), 1.68 (s, 6H, 3 × CCH2CH) ppm; 13C NMR
(100 MHz, CDCl3): ẟ = 138.9 (Cquart., CAr), 128.9 (+, 2 × CHAr), 128.5 (+,
2 × CHAr), 127.0 (+, CHAr), 53.8 (–, 3 × CCH2CH), 44.8 (Cquart., SC), 35.9
(–, CArCH2S), 29.0 (+, CH) ppm; IR (ATR): 푣̃ = 3060 (vw), 3026 (vw),
2974 (w), 2906 (w), 2872 (w), 1600 (vw), 1493 (w), 1451 (w), 1205 (m),
1137 (w), 1068 (w), 1028 (vw), 903 (vw), 862 (vw), 760 (vw), 696 (m),
563 (vw), 472 (vw), 440 (vw) cm-1; MS (EI, 70 eV): m/z (%) = 190 (1) [M]+,
99 (4) [M–C6H5CH2]+, 91 (100) [M–C5H7S]+, 67 (3) [C5H7]+; HRMS (EI,
70 eV) C12H1432S [M]+ 190.0811; found 190.0811.
CH2CH2CH2CH3), 28.8 (+, CH), 22.2 (–, CH2CH2CH2CH3), 13.9 (+, CH3)
ppm; IR (ATR): 푣̃ = 2959 (w), 2907 (w), 2872 (w), 1458 (vw), 1377 (vw),
1274 (vw), 1205 (m), 1141 (w), 903 (w), 745 (vw), 395 (vw) cm-1. Due to
the nonpolar and volatile nature of this compound no HRMS measurement
was possible with EI or FAB. In the ESI (S12) we attached a GC-MS
spectrum of 9c.
Bicyclo[1.1.1]pent-1-yl(tert-butyl)sulfane (9d): 9d was synthesized from a
solution of 1 (general procedure a) according to the general procedure c.
The product 9d was obtained as a volatile, pale yellow liquid in 39% yield
(22.0 mg, 141 µmol).
Fmoc-Bicyclo[1.1.1]pentyl-Cys-OtBu (9h): 9h was synthesized from a
solution of 1 (general procedure a) according to the general procedure c,
but 8h (ESI S3) was added as a 1  solution in THF. Afterwards the crude
1H NMR (400 MHz, CDCl3): ẟ = 2.69 (s, 1H, CH), 2.08 (s, 6H, 3 × CH2),
1.36 (s, 9H, 3 × CH3) ppm; 13C NMR (100 MHz, CDCl3): ẟ = 56.1 (–,
3 × CH2), 44.8 (Cquart., CSC(CH3)3), 44.1 (Cquart., C(CH3)3), 32.0 (+,
3 × CH3), 30.7 (+, CH) ppm; IR (ATR): 푣̃ = 2962 (w), 2910 (w), 2874 (w),
1456 (w), 1362 (w), 1260 (vw), 1208 (m), 1164 (w), 1135 (w), 903 (w),
803 (vw), 597 (vw) cm-1. Due to the nonpolar and volatile nature of this
compound no HRMS measurement was possible with EI or FAB. In the
ESI (S13) we attached a GC-MS spectrum of 9d.
product
was
purified
by
column
chromatography
(SiO2,
cyclohexane/EtOAc, 10:1). The product 9h was obtained as a colourless
oil in 45% yield (172 mg, 369 µmol).
Rf (SiO2, cyclohexane/EtOAc, 10:1): 0.27; 1H NMR (400 MHz, CDCl3):
ẟ = 7.78–7.75 (m, 2H, Ar-H), 7.62–7.60 (m, 2H, Ar-H), 7.42–7.38 (m, 2H,
Ar-H), 7.34–7.29 (m, 2H, Ar-H), 5.56 (d, 3J = 7.8 Hz, 1H, NH), 4.51 (dt,
3J = 7.8 Hz, 3J = 4.8 Hz, 1H, SCH2CH), 4.41 (d, 3J = 7.0 Hz, 2H,
CO2CH2CH), 4.23 (t, 3J = 7.0 Hz, 1H, CO2CH2CH), 3.02 (dd, 2J = 13.6 Hz,
3J = 4.8 Hz, 1H, SCH2CH), 2.94 (dd, 2J = 13.6 Hz, 3J = 4.8 Hz, 1H,
SCH2CH), 2.70 (s, 1H, SCCH2CH), 1.93 (s, 6H, 3 × SCCH2CH), 1.48 (s,
9H, 3 × CH3) ppm; 13C NMR (100 MHz, CDCl3): ẟ = 169.7 (Cquart., CCO2),
2-(Bicyclo[1.1.1]pent-1-ylthio)ethan-1-ol (9e): 9e was synthesized from a
solution of 1 (general procedure a) according to the general procedure c.
The organic phase was not washed with NaOH solution, but concentrated
and purified by column chromatography (SiO2, cyclohexane/EtOAc, 2:1)
The product 9e was obtained as a colourless oil in 77% yield (88.0 mg,
610 µmol).
155.8 (Cquart., NCO2), 144.0 (Cquart., CAr), 143.9 (Cquart., CAr), 141.5 (Cquart.
,
2 × CAr), 127.9 (+, 2 × CHAr), 127.2 (+, 2 × CHAr), 125.3 (+, CHAr), 125.2 (+,
CHAr), 120.1 (+, 2 × CHAr), 82.9 (Cquart., CCH3), 67.2 (–, CO2CH2CH), 54.4
Rf (SiO2, cyclohexane/EtOAc, 2:1): 0.44; 1H NMR (400 MHz, CDCl3): ẟ =
3.70 (td, 3J = 6.2 Hz, 3J = 6.1 Hz, 2H, CH2CH2OH), 2.75 (t, 3J = 6.1 Hz, 2H,
CH2CH2OH), 2.73 (s, 1H, CH), 2.09 (t, 3J = 6.2 Hz, 1H, OH), 1.98 (s, 6H,
3 × CCH2CH) ppm; 13C NMR (100 MHz, CDCl3): ẟ = 61.4 (–, CH2CH2OH),
54.1 (–, 3 × CCH2CH), 44.2 (Cquart., CS), 34.6 (–, CH2CH2OH), 28.8 (+, CH)
ppm; IR (ATR): 푣̃ = 3335 (w), 2974 (m), 2907 (w), 2872 (m), 1407 (w),
1287 (vw), 1206 (m), 1137 (m), 1041 (m), 1008 (m), 929 (w), 902 (w),
763 (w), 667 (w), 440 (vw) cm-1; MS (EI, 70 eV): m/z (%) = 145 (1) [M+H]+,
143 (1) [M–H]+, 100 (70) [M–C2H4OH+H]+, 99 (37) [M–C2H4OH]+, 85 (100)
[M–C2H4OH–CH2]+, 77 (10) [M–C5H7]+, 67 (64) [C5H7]+; HRMS (EI, 70 eV):
calcd for C7H12O132S1 [M]+ 144.0603; found 144.0605.
(+, SCH2CH), 53.8 (–, 3 × SCCH2CH), 47.3 (+, CO2CH2CH), 44.4 (Cquart.
,
SCCH2CH), 33.9 (–, SCH2CH), 28.6 (+, SCCH2CH), 28.2 (+, 3 × CH3)
ppm; IR (ATR): 푣̃ = 3331 (vw), 2976 (w), 2908 (vw), 2874 (w), 1712 (m),
1503 (w), 1449 (w), 1393 (vw), 1368 (w), 1342 (w), 1207 (m), 1151 (m),
1105 (w), 1047 (w), 999 (w), 901 (vw), 844 (w), 757 (w), 738 (m), 621 (vw),
536 (w), 424 (w) cm-1; MS (EI, 70 eV): m/z (%) = 466 (1) [M+H]+, 465 (2)
[M]+, 408 (15) [M–C(CH3)3]+, 365 (38) [M–CO2C(CH3)3+H]+, 364 (100) [M–
CO2C(CH3)3]+, 179 (65) [C14H10+H]+, 178 (100) [C14H10]+; HRMS (EI,
70 eV): calcd for C27H31O4N32S [M]+ 465.1968; found 465.1970.
1,2-Bis(bicyclo[1.1.1]pent-1-ylthio)ethane (13a): 13a was synthesized
from a solution of 1 (general procedure a) according to the general
procedure c. The product 13a was obtained as a white solid in 31% yield
(82.0 mg, 362 µmol).
2-(Bicyclo[1.1.1]pent-1-ylthio)acetic acid (9f): 9f was synthesized from a
solution of 1 (general procedure a) according to the general procedure c.
The organic phase was not washed with NaOH solution, but concentrated
and purified by column chromatography (SiO2, cyclohexane/EtOAc/
trifluoroacetic acid, 10:1:0.01). The product 9f was obtained as a
colourless oil in 66% yield (59.0 mg, 373 µmol).
m.p. 65–67 °C; 1H NMR (400 MHz, CDCl3): ẟ = 2.74 (s, 2H, 2 × CH), 2.72
(s, 4H, 2 × SCH2), 1.98 (s, 12H, 6 × CCH2CH) ppm; 13C NMR (100 MHz,
CDCl3): ẟ = 54.1 (–, 6 × CCH2CH), 44.5 (Cquart., 2 × SC), 32.2 (–,
2 × SCH2), 28.8 (+, 2 × CH) ppm; IR (ATR): 푣̃ = 2968 (s), 2904 (m),
2869 (m), 2345 (vw), 1734 (vw), 1448 (w), 1420 (m), 1261 (vw), 1205 (s),
1135 (s), 921 (w), 904 (m), 884 (w), 801 (w), 726 (m), 694 (m), 542 (w),
448 (w) cm-1; MS (EI, 70 eV): m/z (%) = 226 (14) [M]+, 159 (3) [M–C5H7]+,
127 (34) [M–C5H7S]+, 99 (92) [M–C5H7S–C2H4]+, 98 (90) [C5H6S]+, 85 (34)
[M–C5H7S–C2H4–CH2]+, 67 (100) [C5H7]+; HRMS (EI, 70 eV): calcd for
C12H1832S2 [M]+ 226.0844; found 226.0843.
Rf (SiO2, cyclohexane/EtOAc/trifluoroacetic acid, 10:1:0.01): 0.20;
1H NMR (400 MHz, CDCl3): ẟ = 3.31 (s, 2H, CSCH2), 2.75 (s, 1H, CH),
2.01 (s, 6H, 3 × CCH2CH) ppm; 13C NMR (100 MHz, CDCl3): ẟ = 175.3
(Cquart., CO2H), 53.6 (–, 3 × CCH2CH), 44.3 (Cquart., CSCH2), 33.2 (–,
CSCH2), 28.7 (+, CH) ppm; IR (ATR): 푣̃ = 2979 (m), 2910 (m), 2876 (m),
2670 (w), 1705 (s), 1419 (w), 1291 (m), 1206 (m), 1134 (m), 900 (m),
785 (w), 668 (w), 581 (w), 464 (w) cm-1; MS (EI, 70 eV): m/z (%) = 158 (1)
[M]+, 157 (2) [M–H]+, 99 (100) [M–CH2CO2H]+, 67 (79) [C5H7]+; HRMS (EI,
70 eV): calcd for C7H10O232S [M]+ 158.0402; found 158.0403.
1,4-Bis(bicyclo[1.1.1]pent-1-ylthio)butane (13b): 13b was synthesized
from a solution of 1 (general procedure a) according to the general
procedure c. The product 13b was obtained as a colourless liquid in 31%
yield (65.0 mg, 255 µmol).
Benzyl(bicyclo[1.1.1]pent-1-yl)sulfane (9g): 9g was synthesized from a
solution of 1 (general procedure a) according to the general procedure c.
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1H NMR (400 MHz, CDCl3): ẟ = 2.72 (s, 2H, 2 × CH), 2.53 (m, 4H,
2 × SCH2CH2), 1.96 (s, 12H, 6 × CCH2CH), 1.68 (m, 4H, 2 × SCH2CH2)
ppm; 13C NMR (100 MHz, CDCl3) ẟ = 134.2 (Cquart, CAr), 133.6 (+,
2 × CHAr), 128.9 (+, 2 × CHAr), 127.6 (+, CHAr), 54.1 (–, 3 × CH2), 45.8
(Cquart, CArSC), 28.8 (+, CH) ppm; IR (ATR): 푣̃ = 2996 (w), 2918 (w),
2884 (w), 1584 (vw), 1479 (vw), 1446 (m), 1301 (s), 1205 (m), 1177 (m),
1130 (s), 1078 (m), 1022 (w), 998 (w), 940 (w), 898 (w), 876 (m), 779 (w),
759 (m), 719 (m), 689 (m), 612 (s), 564 (m), 534 (m) cm-1; MS (EI, 70 eV):
m/z (%) = 209 (1) [M+H]+, 208 (2) [M]+, 191 (2) [M–OH]+, 143 (27) [M–
C5H6+H]+, 125 (51) [M–O–C5H7]+, 77 (24) [C6H5]+, 67 (100) [C5H7]+; HRMS
(EI, 70 eV): calcd for C11H1232S [M]+ 176.0654; found 176.0655.
ppm; 13C NMR (100 MHz, CDCl3): ẟ = 53.9 (–, 6 × CCH2CH), 44.7 (Cquart.
,
2 × SC), 30.8 (–, 2 × SCH2CH2), 29.7 (–, 2 × SCH2CH2), 28.8 (+, 2 × CH)
ppm; IR (ATR): 푣̃ = 2973 (m), 2907 (m), 2871 (m), 1729 (vw), 1447 (w),
1280 (w), 1205 (s), 1139 (m), 902 (w), 741 (vw), 442 (vw) cm-1; MS (EI,
70 eV): m/z (%) = 254 (3) [M]+, 155 (23) [M–C5H7S]+, 147 (62) [M–C5H7–
C3H5+H]+, 120 (10) [M–(C5H7)2]+, 100 (33) [C5H7S+H]+, 99 (63) [C5H7S]+,
89 (56) [M–C5H7–C5H7S+H]+, 87 (63) [C4H7S]+, 85 (95) [M–C5H7S–C4H8–
CH2]+, 67 (85) [C5H7]+, 55 (100) [C4H7]+; HRMS (EI, 70 eV): C14H2232S2 [M]+
254.1157; found 254.1158.
Bicyclo[1.1.1]pent-1-yl(phenyl)selane (17): 17 was synthesized from a
solution of 1 (general procedure b) according to the general procedure c.
Instead of a thiol benzeneselenol (16) was added as a 1 solution in
diethyl ether. The product 17 was obtained as a yellow liquid in quantitative
yield (133 mg, 596 µmol).
1,6-Bis(bicyclo[1.1.1]pent-1-ylthio)hexane (13c): 13c was synthesized
from a solution of 1 (general procedure a) according to the general
procedure c. The product 13c was obtained as a colourless liquid in 47%
yield (38.0 mg, 135 µmol).
1H NMR (400 MHz, CDCl3): ẟ = 7.57–7.54 (m, 2H, Ar-H), 7.30–7.25 (m,
3H, Ar-H), 2.96 (s, 1H, CH), 2.00 (s, 6H, 3 × CH2) ppm; 13C NMR (100 MHz,
CDCl3): ẟ = 135.4 (+, 2 × CHAr), 131.7 (Cquart., CAr), 128.9 (+, 2 × CHAr),
127.6 (+, CHAr), 55.4 (–, 3 × CH2), 38.9 (Cquart., CArSeC), 31.0 (+, CH) ppm;
IR (ATR): 푣̃ = 3056 (vw), 2962 (w), 2909 (w), 2874 (w), 1577 (w),
1475 (m), 1436 (w), 1299 (w), 1204 (m), 1117 (m), 1072 (w), 1021 (w),
999 (w), 883 (m), 735 (m), 690 (m), 671 (w), 471 (w) cm-1; MS (EI, 70 eV):
m/z (%) = 224/222/220 (18/19/5) [M]+, 158 (21) [M–C5H7+H]+, 157 (20) [M–
C5H7]+, 78 (33) [C6H5+H]+, 77 (41) [C6H5]+, 67 (100) [C5H7]+; HRMS (EI,
70 eV): calcd for C11H1280Se [M]+ 224.0104; found 224.0104.
1H NMR (400 MHz, CDCl3): ẟ = 2.71 (s, 2H, 2 × CH), 2.52 (m, 4H,
2 × SCH2CH2CH2), 1.95 (s, 12H, 6 × CCH2CH), 1.59 (m, 4H,
2 × SCH2CH2CH2), 1.38 (m, 4H, 2 × SCH2CH2CH2) ppm; 13C NMR
(100 MHz, CDCl3): ẟ = 53.8 (–, 6 × CCH2CH), 44.7 (Cquart., 2 × SC), 34.0
(–, 2 × SCH2CH2CH2), 30.4 (–, 2 × SCH2CH2CH2), 28.8 (+, 2 × CH), 28.1
(–, 2 × SCH2CH2CH2) ppm; IR (ATR): 푣̃ = 2974 (w), 2925 (w), 2872 (w),
1727 (vw), 1459 (vw), 1270 (vw), 1206 (m), 1141 (w), 903 (vw),
736 (vw) cm-1; MS (EI, 70 eV): m/z (%) = 282 (100) [M]+, 215 (28) [M–
C5H7]+, 148 (11) [M–(C5H7S)2]+, 100 (46) [C5H7S+H]+, 99 (96) [C5H7S]+, 87
(29) [C4H7S]+, 85 (100) [M–C5H7S–C6H12–CH2]+, 67 (81) [C5H7]+; HRMS
(EI, 70 eV): calcd for C16H2632S2 [M]+ 282.1470; found 282.1472.
Acknowledgements
1-(Phenylsulfoxide)-bicyclo[1.1.1]pentane (14): In a 10 mL flask 100 mg of
7a (567 µmol, 1.00 equiv.) were dissolved in 1.0 mL dichloromethane.
87 mg m-chloroperoxybenzoic acid (567 µmol, 1.00 equiv.) were added in
portions and the mixture was stirred for 5 min at room temperature. The
precipitate was filtered off and the filtrate was washed with Na2S2O3
solution and 1  NaOH-solution. The organic phase was dried over
Na2SO4 and the solvent was removed under reduced pressure. The crude
We greatly acknowledge the contribution of the precursor
1,1-dibromo-2,2-bis(chloromethyl)cyclopropane (3) by abcr
GmbH. R.M.B. acknowledges the SFB 1176 funded by the
German Research Council (DFG) in the context of project B3 for
funding.
product
was
purified
by
column
chromatography
(SiO2,
cyclohexane/EtOAc, 5:1) to obtain the product 14 as a colourless oil in
71% yield (77.0 mg, 400 µmol).
Keywords: [1.1.1]propellane • bicyclo[1.1.1]pentane • thiols •
hydrogen sulfide • amino acid
Rf (SiO2, cyclohexane/EtOAc, 5:1): 0.18; 1H NMR (400 MHz, CDCl3):
ẟ = 7.53–7.47 (m, 5H, Ar-H), 2.81 (s, 1H, CH), 1.88 (s, 6H, 3 × CH2) ppm;
13C NMR (100 MHz, CDCl3) ẟ = 141.7 (Cquart, CAr), 130.9 (+, CHAr), 129.0
(+, 2 × CHAr), 124.3 (+, 2 × CHAr), 55.4 (Cquart, CArSC), 49.9 (–, 3 × CH2),
27.8 (+, CH) ppm; IR (ATR): 푣̃ = 3462 (vw), 2970 (w), 2917 (w), 2880 (w),
1581 (vw), 1476 (w), 1443 (w), 1303 (vw), 1201 (m), 1129 (w), 1084 (m),
1067 (w), 1036 (m), 997 (m), 883 (w), 869 (w), 777 (w), 746 (m), 692 (m),
555 (m), 511 (m), 484 (m) cm-1; MS (EI, 70 eV): m/z (%) = 192 (2) [M]+,
126 (100) [M–C5H7+H]+, 125 (10) [M–C5H7]+, 78 (41) [C6H5+H]+, 77 (15)
[C6H5]+, 67 (61) [C5H7]+; HRMS (EI, 70 eV): calcd for C11H12O32S [M]+
192.0609; found 192.0610.
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A versatile tool for new building
blocks. Thiols can open
Robin M. Bär, Stefan Kirschner, Martin
Nieger, Stefan Bräse*
[1.1.1]propellane in simple, clean and
fast reactions with good functional
group tolerance. Even hydrogen
sulfide, amino acids and selenols can
be used in this radical reaction. The
products can be further modified to
tune the polarity. This reaction can
potentially be applied in material
modifications, bioconjugations or in
the synthesis of new medicinal
chemistry building blocks.
Page No. – Page No.
Alkyl and aryl thiol addition to
[1.1.1]propellane
limitations of
reaction
–
scope
and
a
fast conjugation
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