Reactions of chlorosulfanyl derivatives of cyclobutanones with different nucleophiles

Article abstract of DOI:10.1002/hlca.200690082

The reactions of 3-chloro-3-(chlorosulfanyl)-2,2,4,4-tetramethylcyclobutan- l-one (2) with N, O, S, and P nucleophiles occur by substitution of Cl at the S-atom. Whereas, in the cases of secondary amines, alkanols, phenols, thiols, thiophenols, and di- an

Full text of DOI:10.1002/hlca.200690082

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Helvetica Chimica Acta – Vol. 89 (2006)
Reactions of Chlorosulfanyl Derivatives of Cyclobutanones with Different
Nucleophiles
by Agnieszka Majchrzaka)1), Grzegorz Mloston´*b), Anthony Lindena), and Heinz Heimgartner*a)
a) Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich
(phone: +41446354282; fax: +41446356836; e-mail: heimgart@oci.unizh.ch)
b
´
´
) Section of Heteroorganic Compounds, University of Łódz, Narutowicza 68, PL-90-136 Łódz
The reactions of 3-chloro-3-(chlorosulfanyl)-2,2,4,4-tetramethylcyclobutan-1-one (2) with N, O, S,
and P nucleophiles occur by substitution of Cl at the S-atom. Whereas, in the cases of secondary amines,
alkanols, phenols, thiols, thiophenols, and di- and trialkyl phosphates, the initially formed substitution
products were obtained, the corresponding products with allyl and propargyl alcohols undergo a [2,3]-sig-
matropic rearrangement to give allyl and allenyl sulfoxides, respectively. Analogous substitution reac-
tions were observed when 3-chloro-3-(chlorodisulfanyl)-2,2,4,4-tetramethylcyclobutan-1-one (3) was
treated with N, O, and S nucleophiles. The reaction of 3 with Et3P led to an unexpected product via cleav-
G
age of the SÀS bond (cf. Scheme 13). In the reactions of 2 with primary amines and H2O, the substitution
products react further via elimination of HCl to yield the corresponding thiocarbonyl S-imides and the
thiocarbonyl S-oxide, respectively. Whereas the latter could be isolated, the former were not stable
but could be intercepted by MeOH( Scheme 4) or adamantanethione (Scheme 5). The structures of
some of the substitution products were established by X-ray crystallography.
1. Introduction. – Some years ago, it has been reported that the reaction of 2,2,4,4-
tetramethyl-3-thioxocyclobutanone (1) with PCl5 and SCl2 provides the chlorosulfanyl
derivative 2 and chlorodisulfanyl derivative 3, respectively, in good yield [1] (Scheme
1). Due to the polar character of the SÀCl bond in 2 and 3, a nucleophilic substitution
Scheme 1
1
)
Part of the planned Ph.D. thesis of A. M., Universität Zürich.
ꢀ 2006 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 89 (2006)
1043
of Cl is possible. It is already known that the reactions of 2 and 3 with thioacetic S-acid
give the corresponding stable thio-esters 4 and 5 [2]. As 2 and 3 represent stable and
easily accessible sulfanyl chlorides, their derivatization with various nucleophiles
could be examined.
2. Results andDiscussion. – 2.1. Reactions of Chlorosulfanyl and Chlorodisulfanyl
Derivatives 2 and 3, respectively, with NNucleophiles . In a first set of experiments,
chloro
N
G
reacted with 2 equiv. of secondary amines (R2
AHCTREUNG
reactions were carried out in analogy to procedures described for transformations of
simple sulfanyl chlorides [3][4]. The nucleophilic substitution at the S-atom was accom-
plished under mild conditions, and hardly any by-products were formed. The required
reaction times are relatively short, and the 3-chloro-3-(aminosulfanyl)cyclobutanones 6
and their disulfanyl variants 7 were formed in good yields. The products 6 and 7
(Scheme 2) were separated by filtration from the precipitated amine hydrochlorides
that were formed as second products. The crude products showed a purity of ca.
90%, and, if possible, they were further purified by crystallization2). In the cases of
compounds 6a and 7a, suitable crystals for an X-ray crystal-structure determination
were obtained (Fig. 1).
Scheme 2
In an analogous series, 2 and 3 were reacted with primary amines. In this case, sub-
sequent HCl elimination of the adducts 8 to give sulfinimides 9 (thiocarbonyl S-imides)
should be possible (Scheme 3) [6–9]. These and related ylides are important building
blocks for cycloadditions and other reactions [8][10], including conversions with
amines [11], alkenes [12][13], and metal-organic compounds such as PhLi [14] or
RMgBr [15]. In general, sulfinimides are reactive intermediates, which easily undergo
further reactions. However, in a few cases, the isolation of a sulfinimide is possible when
it is further stabilized by p-acceptor groups, as in compound 10 [16].
2
)
It was not possible to apply other purification techniques, as decomposition occurred during chroma-
tography on either SiO2 or Al2O3, as well as by the attempted microdistillation.

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Helvetica Chimica Acta – Vol. 89 (2006)
Fig. 1. ORTEP Plots [5] of the molecular structures of a) 6a and b) 7a (arbitrary numbering of
atoms; 50% probability ellipsoids)
Scheme 3
Sulfinimides are also accessible via the reaction of the corresponding sulfanyl chlor-
ides with silylated amines [17]. They display a characteristic absorption at 480–500 nm,

Helvetica Chimica Acta – Vol. 89 (2006)
1045
and some examples exist as red or orange crystals [18–20]. Furthermore, they can often
be identified by specific MS fragmentations [21].
The compounds 2 and 3 were treated with 3 or more equiv. of a primary amine. To
avoid a reaction of the amine with 2 equiv. of the electrophile, the chlorosulfanyl com-
pound was added to a solution of the amine in the corresponding solvent. Unfortu-
nately, the expected sulfinimides of type 9 could not be isolated from any of the reac-
t
tions with BuNH2, cyclohexylamine, PhCH2NH2 or PhNH2. In all experiments, mix-
tures of compounds were formed that could neither be separated nor identified, and
several variations of the reaction conditions did not improve the result. On the other
hand, a hint for the intermediate formation of 9 may be the coloration of the reaction
mixture.
Therefore, we tried to trap the reactive intermediate in the reaction with tBuNH2 in
analogy to the procedures applied with thiocarbonyl ylides [22–24]. In this experiment,
MeOHwas added to the mixture after 1 min, and workup after 1 h gave compound 11,
which actually points to the intermediary occurrence of the sulfinimide [3] (Scheme 4).
Scheme 4
Most likely, 11 was formed by the addition of MeOHto sulfinimide 9a. A nucleo-
philic substitution of Cl at C(2) of the intermediate of type 8 by MeOHaccording to an
SN2 mechanism can be excluded, as such reactions are not known in similar sterically
crowded cyclobutanone derivatives. However, a reaction via an SN1 mechanism is fea-
sible, but the thereby formed sulfonium ion equals the protonated form of sulfinimide
9a. Under the basic reaction conditions, it is most likely that deprotonation to give 9a
occurs very fast. On the other hand, the addition of MeOHcould take place already at
the protonated intermediate. A direct formation of the thiaziridine by cyclization of the
primarily formed cation can be excluded, because, to the best of our knowledge, there
are no experimental data available for a ring opening of thiaziridines to give thiocar-
bonyl S-imides. All known reactions which are formulated via intermediate thiaziri-
dines proceed by elimination of S (cleavage of the S,N and S,C bonds) or via rearrange-
ment to give a thionitrone (cleavage of the S,C bond) [25].
In some cases, sulfinimides react further to the corresponding thiaziridines, which
easily form imines by elimination of sulfur [22] (see Scheme 5). Therefore, as a second,
more significant indication of an intermediate sulfinimide, we attempted to trap 9a with
adamantanethione in a 1,3-dipolar cycloaddition, in analogy to related reactions [26].
t
For this purpose, the reaction with BuNH2 and 2 was carried out as usual, and, after

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Helvetica Chimica Acta – Vol. 89 (2006)
Scheme 5
a short time, adamantanethione was added to the mixture. After usual workup, the
known imine 12 and trithiolane 14 were obtained, but not the desired [2+3] cycload-
duct. A plausible mechanistic explanation for the formation of these compounds is
shown in Scheme 5. The key-step is the S-transfer reaction from the intermediate thia-
ziridine onto adamantanethione to give 12 and adamantane S-sulfide (13, a thiosulfine)
[25]. The latter undergoes a spontaneous [2+3] cycloaddition with adamantanethione
to give the 1,2,4-trithiolane 14.
The reaction of 2 with PhCH2NH2 was expected to give rise to a 1,4-Hshift in the
intermediate 1,3-dipole of type 9 (see [27]); however, no corresponding product was
obtained. The analogous reaction of 3 with tBuNH2 was accomplished without any com-
plication. As, in this case, a HCl elimination in the initially formed substitution product
15 is not possible, 15a was obtained in good yield (Scheme 6). Similarly, the reaction of 3
with PhNH2 yielded the corresponding product 15b.
Scheme 6
In summary, reactions of chlorosulfanyl derivative 2 and chlorodisulfanyl derivative
3 with secondary amines proceeded smoothly leading to products 6 and 7, respectively,
which can be isolated in good yield and in a relatively pure state. As a result of their
instability, further purification by chromatography or distillation was not possible,
and therefore, no correct elemental analyses could be obtained. Similarly, the reactions
of 3 with tBuNH2 and PhNH2 yielded the substitution products 15. On the other hand,
we were unable to isolate pure products of the reactions of 2 with primary amines.

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However, two different quenching experiments indicate the interim formation of
sulfinimides of type 9 by elimination of HCl from the initially formed substitution prod-
G
uct 8.
2.2. Reactions of 2 and 3 with O Nucleophiles. Some reactions of chlorosulfanyl com-
pounds with O nucleophiles, in most cases aliphatic alcohols [28–30] or phenols [31],
are described to occur via substitution of Cl. For the reactions with 2 and 3, we
chose some alcohols and phenols, as well as AcOHand H O. The conversions of 2
2
with MeOH, EtOH, and phenol in CH2Cl2 in the presence of Et3N proceeded smoothly
U
at room temperature and gave the crude substitution products 16 in high yields (Scheme
7). Unfortunately, these oily compounds decomposed during the attempted chromato-
1
graphic purifications. Therefore, their yields were determined by H-NMR measure-
ments with 1,1,2,2-tetrachloroethane as an internal standard.
Scheme 7
i
t
The reactions with PrOHand BuOH, as well as with their alkoxides, led to com-
plex mixtures of mainly decomposition products, and the spectroscopic analysis of
the crude mixture gave no hint for the presence of the expected products of type 16.
With 2,4,6-trimethylphenol as the nucleophile, the conversion proceeded again with
a high yield of the crude solid product 16d, which was purified by crystallization. Fur-
thermore, its structure was established by X-ray crystallography (Fig. 2).
Fig. 2. ORTEP Plot [5] of the molecular structure of 16d (arbitrary numbering of atoms; 50% proba-
bility ellipsoids)

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Helvetica Chimica Acta – Vol. 89 (2006)
The reaction of 2 with H2O, using THF as the solvent instead of the usually applied
CH2Cl2, led to the expected sulfine 18, which was formed by consecutive substitution of
Cl at the S-atom to give 17, followed by HCl elimination (Scheme 8). The known 18
[32], a thiocarbonyl S-oxide, was purified by crystallization.
Scheme 8
With AcOHand 2 in CH2Cl2, no reaction was observed at room temperature. At
higher temperature, i.e., in boiling CH2Cl2, 18 was formed again as the main product,
probably via elimination of AcCl from the initially formed substitution product 19
(Scheme 9).
Scheme 9
Of special interest are the conversions of 2 with allyl and propargyl alcohols
(Scheme 10). In these cases, the initially formed substitution products of type 20, i.e.,
allyl and allenyl sulfenates, respectively, could undergo a [2,3]-sigmatropic rearrange-
ment to give the corresponding sulfoxides. Such reactions using simple sulfanyl chlor-
ides, have been published by Raj et al. [33], and Scheufler and Maier [34] (for earlier
work see refs. cit. in [33][34], and e.g., [35][36]).
Indeed, the reactions of 2 with allyl alcohol, propargyl alcohol, and 3-phenylprop-2-
yn-1-ol led to the rearranged products, the sulfoxides 21, 22a, and 22b, respectively3)
(Scheme 10). After purification by either chromatography or crystallization, the prod-
ucts were obtained as colorless oils or crystals. Due to the newly formed stereogenic
center at the S-atom, the cyclobutane core bears, instead of pair-wise diastereotopic
Me groups of the starting material or the primary substitution product, four diastereo-
topic Me groups. Therefore, the rearranged products are easily distinguishable from the
initially formed substitution products by NMR spectroscopy.
In a second series of experiments, chlorodisulfanyl compound 3 was reacted with
three representative O nucleophiles. With MeOH, the reaction proceeded smoothly
to give 23a as a colorless oil (Scheme 11). Due to decomposition during the purification
process, the yield could only be determined by NMR measurement with an internal
standard. As in the case of 2, the reaction of 3 with 2,4,6-trimethylphenol occurred
3
)
With cinnamyl alcohol as the nucleophile, a mixture of decomposition products was obtained.

Helvetica Chimica Acta – Vol. 89 (2006)
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Scheme 10
smoothly to yield 23b as a colorless solid, which was purified by recrystallization. On
the other hand, the attempted conversion of 3 with propargyl alcohol to give the corre-
sponding rearranged product (cf. Scheme 10) was unsuccessful, as neither one of the
expected products, i.e., the primarily formed substitution products of type 23
(R=HCꢀCÀCH2) and its rearranged disulfanyl S-monoxide, could be detected4).
Scheme 11
2.3. Reactions of 2 and 3 with P Nucleophiles. Reactions of P nucleophiles with sim-
ple sulfanyl chlorides are well-known. Among others, conversions with dialkyl [38], tri-
alkyl [39][40], disilyl [41], and trisilyl phosphites [42], as well as with related com-
pounds [43][44], have been described. In the present study, dialkyl (or diaryl) and tri-
alkyl phosphites were used as nucleophiles in the reactions with 2 and 3. Both types of
nucleophiles should lead to the same products, as has already been shown with a sul-
fanyl chloride, which is similar to 2 [45].
Dialkyl (or diaryl) phosphites may exist in two tautomeric forms, in one of which
the P-atom bears a lone electron pair. It, therefore, possesses nucleophilic properties
and can attack the S-atom of the sulfanyl chlorides by replacing Cl in a SN2 reaction.
After deprotonation of the phosphonium ion 24, the corresponding thiophosphate 25
is formed (Scheme 12).
4
)
Several disulfanyl S-monoxides have been isolated as stable compounds (see, e.g., [37]).

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Scheme 12
The reaction of 2 in CH2Cl2 at 08 was carried out with dimethyl, diethyl, and
diphenyl phosphites. In the first two cases, a quantitative conversion to the expected
products 25a and 25b was observed, and they could be isolated in good yields after crys-
tallization (Scheme 12). It is worth mentioning that no base is needed for a complete
conversion. The reaction of 2 with diphenyl phosphite proceeded less smoothly, how-
ever, and 25c was obtained in 35% yield after crystallization.
When trialkyl phosphites were used instead of the dialkyl derivatives, the same
products 25 were obtained. Their formation follows a similar reaction pathway via
intermediate 26 as found for the Michaelis–Arbuzov reaction. The reaction with tri-
methyl and triethyl phosphites gave 25a and 25b, again in high yields (Scheme 12).
However, the yield of the product of the reaction with triisopropyl phosphite, 25d,
was significantly lower. This product could be purified by recrystallization, and its struc-
ture was established by X-ray crystallography (Fig. 3).
Similar reactions were carried out with chlorodisulfanyl compound 3, but, in these
cases, only mixtures of compounds were formed that could neither be separated nor
identified. Although the reaction conditions were varied significantly, no products
could be isolated. Only in one experiment with a tenfold excess of triethyl phosphite,
one main product was formed, which could be isolated by crystallization. Unexpectedly,
this product proved to be 25b, identical with the product of the reaction of triethyl phos-
phite with 2 (Scheme 13).
This result can be explained by the following mechanism: upon substitution of Cl by
the phosphite, the corresponding phosphonium ion 27 is formed. Two pathways are pos-
sible for the stabilization of this compound: a) attack of Cl at one of the EtO groups
would lead to the Michaelis–Arbuzov product, in analogy to the reaction with 2; b)
an additional phosphite molecule may attack the second S-atom, in analogy to the ini-
tial reaction of Ph3P with dipyridyl disulfide in the Corey–Nicolaou lactonization
U

Helvetica Chimica Acta – Vol. 89 (2006)
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Fig. 3. ORTEP Plot [5] of the molecular structure of 25d (arbitrary numbering of atoms; 50% proba-
bility ellipsoids)
Scheme 13
[46][47] and similar reactions, and triethoxy thiophosphate is released as the leaving
group. Stabilization of the newly formed phosphonium ion 26b now occurs in an
Michaelis–Arbuzov reaction, as depicted in Scheme 12. The mass spectrum of the
crude reaction mixture indeed confirmed the presence of the proposed triethyl thio-
phosphate. This reaction pathway is certainly favored by the huge excess of the phos-
phite.
2.4. Reactions of 2 and 3 with S Nucleophiles. The reaction of sulfanyl chlorides with
S nucleophiles represents a standard method for the elongation of the S-chain in poly-
sulfanes [48][49]. The application of thiocarbonyl compounds as nucleophiles has been
described recently [50][51], and the reaction of thioacetic S-acid with 2 and 3 [2], as
well as with a similar sulfanyl chloride [45], was already mentioned in the introduction

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(Scheme 1). The resulting esters were used for the synthesis of S-rich heterocycles.
Therefore, only a few reactions should be performed in this study to elucidate if SH
compounds are appropriate nucleophiles for reactions with 2 and 3.
A thiol and a thiophenol, EtSHand PhSH, respectively, have been selected as
reagents. Both reactions with either 2 or 3 proceeded very smoothly and led, in quan-
titative yield, to almost pure products. An additional purification by means of chroma-
tography was not possible due to decomposition; however, crystallization was success-
ful in the cases of 28b and 29b (Scheme 14). In conclusion, thioles and thiophenols are
convenient nucleophiles in reactions with 2 and 3 to give the corresponding di- and tri-
sulfanes, respectively.
Scheme 14
2.5. Attempted Reactions of 2 and 3 with C Nucleophiles. In the last section, reac-
tions of 2 and 3 with selected C nucleophiles were investigated. For this purpose, orga-
nolithium and Grignard compounds, silyl enol ethers, enolates of carbonyl and b-dicar-
bonyl compounds, cyanide, and CH2N2 have been applied. Silyl enol ethers should be
convenient enol equivalents to react with 2 and 3, as no bases are required. As a refer-
ence reaction, the trimethylsilyl enol ether of acetophenone was treated with commer-
cially available o-nitrophenylsulfanyl chloride. Even without the addition of a Lewis
acid, the expected product 30 was obtained in good yield [52] (Scheme 15).
Scheme 15
Under the same conditions, 2 did not undergo a reaction. Additional experiments
with different Lewis acids and under various conditions only led to the formation of
acetophenone and decomposition products, but not to the desired sulfane. Unfortu-
nately, the result could not be improved by using other C nucleophiles. The desired sul-

Helvetica Chimica Acta – Vol. 89 (2006)
1053
fane could not be isolated with NaCN, CH2N2, MeMgBr, (trifluoromethyl)trimethylsi-
lane (Ruppertꢁs reagent [53–55]) nor with the enolates of N-methyl-N-phenylacet-
amide or b-dicarbonyl compounds (dimethyl malonate, acetylacetone). Besides uncon-
verted starting material, only decomposition or side products (e.g., 1 and 18) were
obtained in small amounts5). The analogous reactions with 3 led to similar results
and only decomposition products were obtained. Therefore, chlorosulfanyl compounds
2 and 3 are not appropriate substrates to react with C nucleophiles.
3. Conclusions. – It has been shown that the chlorosulfanyl compounds 2 and 3
undergo substitution reactions at the S-atom with various nucleophiles and, therefore,
are convenient building blocks for the synthesis of several organosulfur compounds. In
the case of 2, the reactions with N, O, S, and P nucleophiles occur smoothly, and the
products are stable if no subsequent HCl elimination is possible. In the reactions
with primary amines and H2O, HCl elimination in the initially formed substitution
products leads to reactive thiocarbonyl S-imides and the stable thiocarbonyl S-oxide
(a sulfine), respectively. The intermediate thiocarbonyl S-imides formed in the reac-
tions with primary amines can be detected by interception with either MeOHor ada-
mantanethione. Unexpectedly, the reactions of 2 and 3 with C nucleophiles do not lead
to the expected substitution products.
Experimental Part
1. General. See [57]. M.p.: Mettler-FP-5 or Büchi B-450 apparatus; uncorrected. IR Spectra: Perkin-
Elmer 781 or Perkin-Elmer 1600-FT-IR spectrophotometer. 1H- and 13C-NMR spectra: Bruker AC-300 or
Bruker ARX-300 instrument (300 and 75.5 MHz, resp.) or Bruker DRX-600 instrument (600 and 150.9
MHz, resp.), in CDCl3; multiplicities of the C-atoms determined with DEPT technique. MS: Finnigan
MAT-90 or Finnigan SSQ-700 instrument (CI (NH3)). Elemental analyses were performed by the Mik-
roanalytisches Laboratorium des Organisch-Chemischen Instituts der Universität Zürich.
2. Reactions of 2 and 3 with NNucleophiles. 2.1. Reactions with Secondary Amines. General Proce-
dure. To a soln. of 3-chloro-3-(chlorosulfanyl)-2,2,4,4-tetramethylcyclobutanone (2; 113.5 mg, 0.5 mmol)
or 3-chloro-3-(chlorodisulfanyl)-2,2,4,4-tetramethylcyclobutanone (3; 130 mg, 0.5 mmol) in Et2O (3 ml)
U
at 08 was added the respective secondary amine (1 mmol). The yellow color of the mixture disappeared
immediately, and a precipitate formed. After stirring for 60 min, the inorg. salts were removed by filtra-
tion, and the solvent was evaporated to yield the product as an oily substance. If possible, the oil was fur-
ther purified by trituration and crystallization.
3-Chloro-2,2,4,4-tetramethyl-3-[(morpholin-4-yl)sulfanyl]cyclobutanone (6a). Reaction of 2 with
morpholine. Yield: 97 mg (70%). Colorless crystals. M.p. 63–658 (hexane). IR (neat): 2966m, 2915m,
1
2858s, 2338m, 1788vs, 1465w, 1453w, 1138w, 1111s, 1095m, 909w, 833w. H-NMR: 1.34 (s, 2 Me); 1.35
(s, 2 Me); 3.10 (t, J=4.6, 2 CH2N); 3.62 (t, J=4.7, 2 CH2O). 13C-NMR: 22.0 (q, 2 Me); 23.3 (q, 2 Me);
57.5 (t, 2 CH2N); 67.5 (t, 2 CH2O); 69.5 (s, 2 Me2C); 84.3 (s, SCCl); 217.1 (s, C=O). CI-MS: 280 (36,
[M(37Cl)+1]+), 278 (97, [M(35Cl)+1]+), 242 (75, [MÀCl]+), 88 (100, [C4H9NO+1]+).
Suitable crystals for the X-ray crystal-structure determination were obtained from hexane at À408.
3-Chloro-2,2,4,4-tetramethyl-3-[(piperidin-1-yl)sulfanyl]cyclobutanone (6b). Reaction of 2 with
piperidine. Yield: 85 mg (62%). Colorless oil. IR (neat): 2997m, 2974m, 2938s, 2912m, 1789m, 1468vs,
1
1385s, 1370s, 1112w, 1089m, 1049m, 976w, 954w, 916w, 827s, 801m. H-NMR: 1.39 (s, 2 Me); 1.45 (s, 2
5
)
In a control experiment, the known reaction of o-nitrophenylsulfanyl chloride with diethyl malonate
[56] was successfully repeated.

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Helvetica Chimica Acta – Vol. 89 (2006)
Me); 1.56–1.61 (m, 3 CH2); 3.12 (t, J=5.3, 2 CH2N). 13C-NMR: 22.0 (q, 2 Me); 23.2 (q, 2 Me); 23.5 (t,
CH2); 27.0 (t, 2 CH2); 58.8 (t, 2 CH2N); 68.0 (s, 2 Me2C); 89.7 (s, SCCl); 217.8 (s, C=O). CI-MS: 276
(60, [M(35Cl)+1]+), 240 (100, [MÀCl]+), 86 (10, [C5H11N+1]+).
3-Chloro-2,2,4,4-tetramethyl-3-[(pyrrolidin-1-yl)sulfanyl]cyclobutanone (6c). Reaction of 2 with pyr-
rolidine. Yield: 110 mg (84%). Colorless oil. IR (neat): 2997w, 2967m, 2935s, 2869m, 1785vs, 1465m,
1
1382w, 1365w, 1173w, 1137w, 1028m, 980w, 915w, 887w, 834w. H-NMR: 1.39 (s, 2 Me); 1.43 (s, 2 Me);
1.78–1.82 (m, 2 CH2); 3.19–3.23 (m, 2 CH2N). 13C-NMR: 21.7 (q, 2 Me); 23.2 (q, 2 Me); 25.6 (t, 2
CH2); 57.4 (t, 2 CH2N); 67.7 (s, 2 Me2C); 89.5 (s, SCCl); 217.8 (s, C=O). CI-MS: 262 (83,
[M(35Cl)+1]+), 226 (100, [MÀCl]+), 70 (10).
3-Chloro-3-[(diethylamino)sulfanyl]-2,2,4,4-tetramethylcyclobutanone (6d). Reaction of
2 with
Et2NH. Yield: 102 mg (78%). Colorless oil. IR (neat): 2997w, 2964w, 2932m, 2867m, 1785vs, 1465m,
A
1
1382w, 1366w, 1170w, 1027m, 917w, 834w. H-NMR: 1.05 (t, J=7.1, 2 MeCH2); 1.28 (s, 2 Me); 1.37 (s,
2 Me); 3.09 (q, J=7.1, 2 CH2N). 13C-NMR: 13.1 (q, 2 MeCH2); 21.4 (q, 2 Me); 21.7 (q, 2 Me); 51.3 (t,
2 CH2N); 66.9 (s, 2 Me2C); 89.3 (s, SCCl); 217.1 (s, C=O). CI-MS: 264 (54, [M(35Cl)+1]+), 228 (100,
[MÀCl]+), 74 (6, [C4H11N+1]+).
3-Chloro-2,2,4,4-tetramethyl-3-[(morpholin-4-yl)disulfanyl]cyclobutanone (7a). Reaction of 3 with
morpholine. Yield: 119 mg (79%). Colorless crystals. M.p. 58–608 (hexane). IR (neat): 2973m, 2921m,
1
2859s, 2338m, 1786vs, 1465w, 1453w, 1382w, 1138w, 1366w, 1112s, 1098m, 931w, 838w. H-NMR: 1.42 (s,
2 Me); 1.43 (s, 2 Me); 3.04 (t, J=4.8, 2 CH2N); 3.70 (t, J=4.8, 2 CH2O). 13C-NMR: 23.3 (q, 2 Me);
23.4 (q, 2 Me); 56.2 (t, 2 CH2N); 67.0 (t, 2 CH2O); 69.2 (s, 2 Me2C); 84.0 (s, SCCl); 216.5 (s, C=O). CI-
MS: 310 (4, [M(35Cl)+1]+), 278 (5), 242 (5), 88 (65, [C4H9NO+1]+), 86 (100, C4
N
N
Suitable crystals for the X-ray crystal-structure determination were obtained from hexane at À408.
3-Chloro-2,2,4,4-tetramethyl-3-[(piperidin-1-yl)disulfanyl]cyclobutanone (7b). Reaction of 3 with
piperidine. Yield: 103 mg (67%). Colorless oil. IR (neat): 2999m, 2972m, 2938s, 2910m, 2870w, 1793m,
1469vs, 1383s, 1370s, 1112w, 1098m, 1048m, 972w, 953w, 916w, 829s, 802m. 1H-NMR: 1.41 (s, 2 Me);
1.43 (s, 2 Me); 1.59–1.66 (m, 3 CH2); 3.02 (t, J=5.6, 2 CH2N). 13C-NMR: 22.6 (t, CH2); 23.4 (q, 2 Me);
23.5 (q, 2 Me); 26.8 (t, 2 CH2); 58.0 (t, 2 CH2N); 69.2 (s, 2 Me2C); 84.1 (s, SCCl); 217.1 (s, C=O). CI-
MS: 308 (31, [M(35Cl)+1]+), 240 (25), 84 (100, C5
N
N
3-Chloro-2,2,4,4-tetramethyl-3-[(pyrrolidin-1-yl)disulfanyl]cyclobutanone (7c). Reaction of 3 with
pyrrolidine. Yield: 118 mg (80%). Colorless oil. IR (neat): 2998w, 2965m, 2934s, 2868m, 1786vs,
1465m, 1383w, 1364w, 1174w, 1136w, 1029m, 980w, 915w, 889w, 835w. 1H-NMR: 1.42 (s, 4 Me);
1.80–1.84 (m, 2 CH2); 3.12–3.14 (m, 2 CH2N). 13C-NMR: 23.4 (q, 4 Me); 25.7 (t, 2 CH2); 55.3 (t, 2
CH2N); 69.1 (s, 2 Me2C); 84.3 (s, SCCl); 217.0 (s, C=O). CI-MS: 294 (7, [M(35Cl)+1]+), 226 (6), 70
(100, C
3-Chloro-3-[(diethylamino)disulfanyl]-2,2,4,4-tetramethylcyclobutanone (7d). Reaction of 3 with
2NH. Yield: 128 mg (87%). Colorless oil. IR (neat): 2996w, 2971m, 2935m, 2868m, 1785vs, 1465m,
A
G
Et
ACHTREUNG
1
1382m, 1365w, 1168w, 1027m, 914w, 829w. H-NMR: 1.20 (t, J=7.1, 2 MeCH2); 1.42 (s, 2 Me); 1.44 (s,
2 Me); 3.01 (q, J=7.1, 2 CH2N). 13C-NMR: 13.7 (q, 2 MeCH2); 23.3 (q, 2 Me); 23.5 (q, 2 Me); 52.0 (t,
2 CH2N); 69.1 (s, 2 Me2C); 84.2 (s, SCCl); 217.1 (s, C=O). CI-MS: 296 (2, [M(35Cl)+1]+), 228 (2), 72
(100, C
N
N
2.2. Reactions with Primary Amines. 3-{[(tert-Butyl)amino]sulfanyl}-3-methoxy-2,2,4,4-tetramethyl-
t
cyclobutanone (11). To a soln. of 2 (113.5 mg, 0.5 mmol) in CH2Cl2 (3 ml) at 08 was added BuNH2 (73
mg, 1 mmol). After stirring for 10 min at 08, 0.5 ml of MeOHwas added, and stirring was continued
for 60 min at r.t. Then, the solvent was evaporated, and, after addition of of Et2O (5 ml), the insoluble
G
residue was removed by filtration. Evaporation of the solvent yielded 111 mg (86%) of 11. Colorless
oil. 1H-NMR: 1.19 (s, 3 Me); 1.34 (s, 2 Me); 1.35 (s, 2 Me); 2.12 (s, NH); 3.52 (s, MeO). 13C-NMR:
20.9 (q, 2 Me); 21.2 (q, 2 Me); 29.8 (q, 3 Me); 53.9 (s, MeO); 66.3 (s, 2 Me2C); 96.0 (s, SCOMe); 220.4
t
(s, C=O). CI-MS: 260 (11, [M(35Cl)+1]+), 187 (100, [MÀ BuNH]+).
t
Reaction of 2 with BuNH2 in the presence of Adamantanethione. To a soln. of 2 (113.5 mg, 0.5 mmol)
in CH2Cl2 (3 ml) at 08 was added tBuNH2 (73 mg, 1 mmol). After stirring for 10 min at 08, adamantane-
t
thione (166 mg, 1 mmol) and BuNH2 (37 mg, 0.5 mmol) were added, and stirring was continued for 60
min at r.t. Then, the solvent was evaporated, and the mixture was separated by prep. TLC (SiO2,
CH2Cl2/hexane 1:1). Only 14 (80 mg, 44%) [24] and decomposition products were obtained.

Helvetica Chimica Acta – Vol. 89 (2006)
1055
3-{[(tert-Butyl)amino]disulfanyl}-3-chloro-2,2,4,4-tetramethylcyclobutanone (15a). To a soln. of 3
t
(130 mg, 0.5 mmol) in Et2O (3 ml) at 08 was added BuNH2 (73 mg, 1 mmol). The color of the mixture
G
changed from yellow to red, and a precipitate formed. After stirring for 60 min, the inorg. salts were
removed by filtration, and the solvent was evaporated to yield 15a (102 mg, 69%). Colorless oil. IR
(neat): 3368m, 2994w, 2973m, 2933m, 2868m, 1788vs, 1464m, 1385m, 1365w, 1167w, 1025m, 915w,
1
829w. H-NMR: 1.21 (s, 3 Me); 1.41 (s, 2 Me); 1.46 (s, 2 Me); 3.60 (s, NH). 13C-NMR: 22.7 (q, 2 Me);
23.5 (q, 2 Me); 29.5 (q, 3 Me); 56.0 (s, Me3C); 69.1 (s, 2 Me2C); 91.0 (s, SCCl); 217.1 (s, C=O). CI-MS:
298 (42, [M(37Cl)+1]+), 296 (100, [M(35Cl)+1]+), 175 (18), 74 (15, [C4H11N+1]+).
3-Chloro-2,2,4,4-tetramethyl-3-[(phenylamino)disulfanyl]cyclobutanone (15b). Analogous to the
reaction with tBuNH2, 3 was treated with PhNH2 (93 mg, 1 mmol), leading to 15b (112 mg, 71%). Yellow
oil. IR (neat): 3368m, 2973m, 2923m, 2868w, 1789vs, 1610s, 1553s, 1474m, 1389w, 1352w, 1293w, 1248m,
1172w, 1039m, 913w, 843w. 1H-NMR: 1.40 (s, 2 Me); 1.43 (s, 2 Me); 5.60 (s, NH); 7.33–6.94 (m, 5
arom. H). 13C-NMR: 22.9 (q, 2 Me); 23.4 (q, 2 Me); 69.2 (s, 2 Me2C); 89.9 (s, SCCl); 116.9, 122.1,
129.2 (3d, 5 arom. CH); 144.6 (s, arom. C); 216.4 (s, C=O). CI-MS: 318 (14, [M(37Cl)+1]+), 316 (35,
[M(35Cl)+1]+), 280 (100, [MÀCl]+ ), 94 (21, [C6H7N+1]+).
3. Reactions of 2 and 3 with O Nucleophiles. General Procedure. To a soln. of 2 (113.5 mg, 0.5 mmol)
or 3 (130 mg, 0.5 mmol) in CH2Cl2 (3 ml) at 08 was added the respective O nucleophile (0.5 mmol). After
stirring for 10 min at r.t., Et
ACHTREUNG
min. Then, the solvent was evaporated, and, after addition of 5 ml of Et
AHCTREUNG
removed by filtration. Evaporation of the solvent yielded the product as an oily substance.
3-Chloro-3-[(methoxy)sulfanyl]-2,2,4,4-tetramethylcyclobutanone (16a). Reaction of 2 with MeOH.
1
Yield: 92% (estimated by H-NMR with 1,1,2,2-tetrachloroethane as internal standard). Colorless oil.
IR (neat): 2978s, 2937m, 2873m, 1789vs, 1770m, 1464s, 1381w, 1362w, 1246w, 1178m, 1134m, 1028s,
1
917m, 887m, 838m, 793w, 742w. H-NMR: 1.37 (s, 2 Me); 1.45 (s, 2 Me); 3.89 (s, MeO). 13C-NMR: 20.2
(q, 2 Me); 24.0 (q, 2 Me); 67.3 (q, MeO); 68.6 (s, 2 Me2C); 89.1 (s, SCCl); 216.3 (s, C=O). CI-MS: 187
(100, [MÀCl]+), 188 (10), 155 (8).
3-Chloro-3-[(ethoxy)sulfanyl]-2,2,4,4-tetramethylcyclobutanone (16b). Reaction of 2 with EtOH.
1
Yield: 88% (estimated by H-NMR with 1,1,2,2-tetrachloroethane as internal standard). Colorless oil.
IR (neat): 2975vs, 2934s, 2868m, 1790vs, 1464s, 1383m, 1366w, 1245w, 1169m, 1135m, 1026s, 914m,
884m, 836m, 792w, 738w. 1H-NMR: 1.27 (t, J=7.0, MeCH2); 1.39 (s, 2 Me); 1.45 (s, 2 Me); 4.01 (q,
J=7.0, MeCH2O). 13C-NMR: 16.1 (q, MeCH2); 20.3 (q, 2 Me); 24.4 (q, 2 Me); 68.5 (s, 2 Me2C); 75.8
(t, MeCH2O); 89.1 (s, SCCl); 216.4 (s, C=O). CI-MS: 239 (36, [M(37Cl)+1]+), 237 (100,
[M(35Cl)+1]+), 201 (47), 191 (47), 166 (21), 163 (20), 131 (19).
3-Chloro-2,2,4,4-tetramethyl-3-[(phenoxy)sulfanyl]cyclobutanone (16c). Reaction of 2 with PhOH.
1
Yield: 84% (estimated by H-NMR with 1,1,2,2-tetrachloroethane as internal standard). Colorless oil.
IR (neat): 3383s (br.), 2973s, 2932m, 1784s, 1598s, 1583s, 1493vs, 1463s, 1381w, 1365m, 1263m, 1026w,
917m, 826s, 755w. 1H-NMR: 1.43 (s, 2 Me); 1.44 (s, 2 Me); 7.06–7.31 (m, 5 arom. H). 13C-NMR: 20.4
(q, 2 Me); 23.8 (q, 2 Me); 68.7 (s, 2 Me2C); 88.4 (s, SCCl); 117.5, 123.4, 129.2 (3d, 5 arom. CH); 160.4
(s, Ph); 215.9 (s, C=O). CI-MS: 249 (100, [MÀCl]+), 250 (16).
3-Chloro-2,2,4,4-tetramethyl-3-{[(2,4,6-trimethylphenyl)oxy]sulfanyl}cyclobutanone (16d). Reaction
of 2 with 2,4,6-trimethylphenol. Yield: 104 mg (64%). Colorless crystals. M.p. 53–558 (hexane). IR
(ATR): 2980w, 2964m, 2930m, 1785vs, 1769s, 1473m, 1458s, 1380w, 1364m, 1242w, 1190s, 1124vs,
1
1027m, 953w, 887w, 854s, 803vs, 781m, 741m, 676w. H-NMR: 1.41 (s, 2 Me); 1.48 (s, 2 Me); 2.21 (s, p-
MeC6H2); 2.37 (s, 2 o-MeC6H2); 6.76 (s, 2 arom. H). 13C-NMR: 15.8 (q, 2 o-MeC6H2); 20.4 (q, 2 Me);
20.6 (q, p-MeC6H2); 24.4 (q, 2 Me); 68.9 (s, 2 Me2C); 87.8 (s, SCCl); 129.5 (s, 2 arom. C); 129.6 (d, 2
arom. CH); 133.9, 155.2 (2s, 2 arom. C); 216.0 (s, C=O). CI-MS: 291 (27, [MÀCl]+), 287 (39), 191
(21), 153 (23), 152 (53), 135 (100), 136 (61).
Suitable crystals for the X-ray crystal-structure determination were obtained from hexane at À408.
3-Chloro-2,2,4,4-tetramethyl-3-[(propa-1,2-dien-1-yl)sulfanyl]cyclobutanone S-Oxide (22a). Reac-
tion of 2 with propargyl alcohol. Yield: 27 mg (11%). Colorless crystals. M.p. 74–758 (hexane). IR
(ATR): 3047m, 2963m, 1931m, 1772vs, 1456s, 1443m, 1383w, 1366m, 1247w, 1167m, 1139m, 1114w,
1
1065s, 1052vs, 1022s, 929w, 889s, 853m, 845m, 796m, 760w. H-NMR: 1.34 (s, Me); 1.39 (s, Me); 1.44 (s,
Me); 1.78 (s, Me); 5.2–5.4 (m, CH2=C); 6.30 (t, J=6.3, CH=C). 13C-NMR: 21.1 (q, Me); 21.3 (q,

1056
Helvetica Chimica Acta – Vol. 89 (2006)
Me); 22.4 (q, Me); 22.9 (q, Me); 65.9 (q, Me2C); 69.0 (s, Me2C); 82.0 (t, CH2=C); 90.1 (s, SCCl); 96.5 (d,
CH=C); 209.4 (s, CH=C=CH2); 214.2 (s, C=O). CI-MS: 266 (38, [M(37Cl)+NH4]+), 264 (100,
[M(35Cl)+NH4]+), 247 (13, [M(35Cl)+1]+), 190 (11).
3-Chloro-2,2,4,4-tetramethyl-3-[(1-phenylpropa-1,2-dien-1-yl)sulfanyl]cyclobutanone S-Oxide (22b).
Reaction of 2 with 3-phenylprop-2-yn-1-ol. Yield: 103 mg (57%). Colorless crystals. M.p. 54–588 (hex-
ane). IR (ATR): 3059m, 2986m, 2972m, 2906w, 2866w, 1958m, 1922w, 1788vs, 1489m, 1463m, 1443s,
1425m, 1382m, 1365m, 1243m, 1170m, 1136w, 1109w, 1080s, 1019s, 979m, 935w, 912m, 875s, 828w, 765s,
707s, 700s, 660m. 1H-NMR: 1.34 (s, Me); 1.41 (s, Me); 1.46 (s, Me); 1.87 (s, Me); 5.61, 5.72 (AB,
J=13.6, CH2=C); 7.31–7.48 (m, 5 arom. H). 13C-NMR: 22.4 (q, Me); 22.5 (q, Me); 22.8 (q, Me); 23.9
(q, Me); 65.9 (q, Me2C); 69.9 (s, Me2C); 85.4 (t, CH2=C); 87.8 (s, SCCl); 93.6 (d, CH=C); 128.3,
128.8, 129.2 (3d, 5 arom. CH); 131.6 (s, arom. C); 209.4 (s, CH=C=CH2); 214.2 (s, C=O). CI-MS: 323
(12, [M(35Cl)+1]+), 287 (100, [MÀCl]+), 259 (22), 132 (24), 115 (18).
3-Chloro-2,2,4,4-tetramethyl-3-[(prop-2-enyl)sulfanyl]cyclobutanone S-Oxide (21). Reaction of 2
with allyl alcohol. Yield: 76 mg (61%). Colorless crystals. M.p. 56–578 (hexane). IR (ATR): 3088w,
2976m, 2936w, 2871w, 1791vs, 1777vs, 1637w, 1463m, 1447m, 1420w, 1382m, 1368m, 1247w, 1174w,
1
1083m, 1046vs, 1022m, 987m, 961w, 931m, 891w, 864m, 835w, 793w, 724w. H-NMR: 1.36 (s, Me); 1.39
(s, Me); 1.47 (s, Me); 1.78 (s, Me); 3.35–3.42, 3.66–3.73 (2m, CH2S); 5.49–5.52 (m, CH2=CH);
5.93–6.07 (m, CH2=CH). 13C-NMR: 21.2 (q, Me); 21.5 (q, Me); 22.1 (q, Me); 22.8 (q, Me); 55.9 (t,
CH2S); 65.7 (q, Me2C); 69.2 (s, Me2C); 89.7 (s, SCCl); 123.8 (t, CH2=CH); 126.3 (d, CH2=CH); 213.9
(s, C=O). CI-MS: 266 (15, [M(35Cl)+NH4]+), 251 (37, [M(37Cl)+1]+), 250 (12), 249 (100,
[M(35Cl)+1]+). Anal. calc. for C11H17ClO2S (248.77): C 53.11, H6.89, S 12.89; found: C 53.06, H6.68,
S 12.67.
Reaction of 2 with H2O. To a soln. of 2 (113.5 mg, 0.5 mmol) in THF (3 ml) at r.t. was added H2O (3
ml). After stirring for 45 min at r.t., CH
N
N
of the org. phase (MgSO4) and evaporation of the solvent, the residue was purified by prep. TLC (SiO2;
CH2Cl2/hexane 1:1). Subsequent recrystallization from hexane yielded 18 (67 mg, 79%) [31].
Reaction of 2 with AcOH. To a soln. of 2 (113.5 mg, 0.5 mmol) in CH2Cl2 (3 ml) at r.t. was added
AcOH(30.3 mg, 0.5 mmol), and the mixture was heated under reflux for 6 h. After cooling to r.t., the
solvent was evaporated. Purification of the residue by prep. TLC (SiO2; CH2Cl2/hexane 1:1) yielded
18 (66 mg, 78%).
3-Chloro-3-(methoxydisulfanyl)-2,2,4,4-tetramethylcyclobutanone (23a). Reaction of 3 with MeOH.
1
Yield: 74% (estimated by H-NMR with 1,1,2,2-tetrachloroethane as internal standard). Colorless oil.
IR (neat): 2975s, 2939s, 2877m, 1787vs, 1773m, 1466s, 1380w, 1363w, 1243w, 1180m, 1133m, 1030s,
1
916m, 889m, 840w, 795w, 744w. H-NMR: 1.42 (s, 2 Me); 1.46 (s, 2 Me); 3.66 (s, MeO). 13C-NMR: 22.8
(q, 2 Me); 23.4 (q, 2 Me); 63.5 (q, MeO); 68.6 (s, 2 Me2C); 86.7 (s, SCCl); 216.4 (s, C=O). CI-MS: 272
(27, [M(35Cl)+NH4]+), 219 (100, [MÀCl]+), 191 (17), 159 (84).
3-Chloro-2,2,4,4-tetramethyl-3-{[(2,4,6-trimethylphenyl)oxy]disulfanyl}cyclobutanone (23b). Reac-
tion of 3 with 2,4,6-trimethylphenol. Yield: 95 mg (53%). Colorless solid. M.p. 98–1008 (hexane). IR
(KBr): 2972s, 2932s, 2865w, 1762s, 1603m, 1490s, 1449m, 1312m, 1201s, 1151m, 1027m, 921m, 834m,
737w. 1H-NMR: 1.45 (s, 2 Me); 1.46 (s, 2 Me); 2.20 (s, p-MeC6H2); 2.22 (s, 2 o-MeC6H2); 6.94 (s, 2
arom. H). 13C-NMR: 15.9 (q, 2 o-MeC6H2); 20.4 (q, 2 Me); 22.4 (q, 2 Me); 23.7 (q, p-MeC6H2); 69.3 (s,
2 Me2C); 89.5 (s, SCCl); 123.3, 127.9 (2s, 3 arom. C); 129.6 (d, 2 arom. CH); 151.9 (s, arom. C); 216.9
(s, C=O). CI-MS: 323 (56, [MÀCl]+), 152 (48), 153 (100). Anal. calc. for C17H23ClO2S2 (358.95): C
56.88, H6.46, S 17.87; found: C 56.61, H6.38, S 17.66.
4. Reactions of 2 and 3 with P Nucleophiles. General Procedure. To a soln. of 2 (113.5 mg, 0.5 mmol)
or 3 (130 mg, 0.5 mmol) in CH
N
N
stirring for 60 min, the solvent was evaporated yielding the product as an oil, which was further purified
by crystallization.
S-(1-Chloro-2,2,4,4-tetramethyl-3-oxocyclobutyl) O,O-Dimethyl Thiophosphate (25a). Reaction of 2
with (MeO)
ACHTREUNG
Reaction of 2 with (MeO)3
AHCTREUNG
from hexane. Colorless crystals. M.p. 48–498 (hexane). IR (KBr): 2996m, 2974m, 2937m, 2871w,
1
1790vs, 1768m, 1465s, 1379w, 1364w, 1273vs, 1180m, 1043vs, 918m, 841s, 552s. H-NMR: 1.42 (s, 2 Me);

Helvetica Chimica Acta – Vol. 89 (2006)
1057
1.58 (s, 2 Me); 3.87 (d, J(H,P)=12.8, 2 MeO). 13C-NMR: 21.7 (q, 2 Me); 23.8 (q, 2 Me); 54.3 (dq, J(C,
P)=6.9, 2 MeO); 69.8 (d, J(C,P)=4.9, 2 Me2C); 82.4 (d, J(C,P)=5.8, SCCl); 216.5 (s, C=O). CI-MS:
320 (37, [M(37Cl)+NH4]+), 318 (100, [M(35Cl)+NH4]+), 301 (11, [M(35Cl)+1]+). Anal. calc. for
C10H18ClO4PS (300.74): C 39.94, H6.03, S 10.66; found: C 39.75, H5.83, S 10.42.
S-(1-Chloro-2,2,4,4-tetramethyl-3-oxocyclobutyl) O,O-Diethyl Thiophosphate (25b). Reaction of 2
with (EtO)
ACHTREUNG
Reaction of 2 with (EtO)
AHCTREUNG
from hexane. Colorless crystals. M.p. 30–328 (hexane). IR (KBr): 2985s, 2938m, 2907m, 1789s, 1468s,
1
1384m, 1265s, 1165m, 1021m, 926w, 833w, 745w, 559s. H-NMR: 1.39 (td, J(H,H)=7.1, J(H,P)=0.8, 2
MeCH2); 1.43 (s, 2 Me); 1.58 (s, 2 Me); 4.13–4.31 (m, MeCH2
O). 13C-NMR: 15.9 (dq, J(C,P)=7.4, 2
G
Me); 21.7 (q, 2 Me); 23.8 (q, 2 Me); 64.3 (td, J(C,P)=7.1, MeCH2O); 69.8 (d, J(C,P)=4.7, 2 Me2C);
82.5 (d, J(C,P)=5.8, SCCl); 216.7 (s, C=O). CI-MS: 348 (38, [M(37Cl)+NH4]+), 346 (100,
[M(35Cl)+NH4]+), 331 (26, [M(37Cl)+1]+), 329 (66, [M(35Cl)+1]+). Anal. calc. for C12H22ClO4PS
(328.79): C 43.84, H6.74, S 9.75; found: C 43.73, H6.48, S 9.55.
S-(1-Chloro-2,2,4,4-tetramethyl-3-oxocyclobutyl) O,O-Diphenyl Thiophosphate (25c). Reaction of 2
with (PhO)2POH. Yield: 203 mg (92%) of crude 25c; 78 mg (35%) after crystallization from hexane. Col-
G
orless crystals. M.p. 57–598 (hexane). IR (KBr): 2990m, 2928w, 2875w, 1789vs, 1588s, 1489vs, 1257s, 1204s,
1
1177s, 1156s, 1021s, 938vs, 827w, 774s, 690s, 616w. H-NMR: 1.40 (s, 2 Me); 1.42 (s, 2 Me); 7.13–7.37 (m,
10 arom. H). 13C-NMR: 21.9 (q, 2 Me); 23.6 (q, 2 Me); 70.2 (d, J(C,P)=5.3, 2 Me2C); 82.9 (d, J(C,P)=6.1,
SCCl); 120.9 (dd, J(C,P)=4.8, 4 arom. CH); 125.8 (dd, J(C,P)=4.9, 4 arom. CH); 129.8 (d, 2 arom. CH);
150.1 (d, J(C,P)=9.5, 2 arom. CH); 216.2 (s, C=O). CI-MS: 442 (51, [M(35Cl)+NH4]+), 344 (15), 252
(100). Anal. calc. for C20H22ClO4PS (424.88): C 56.54, H5.22; found: C 56.10, H5.29.
S-(1-Chloro-2,2,4,4-tetramethyl-3-oxocyclobutyl) O,O-Diisopropyl Thiophosphate (25d). Reaction of
2 with (iPrO)3
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
Me); 23.9 (q, 2 Me); 69.9 (d, J(C,P)=4.7, 2 Me2C); 73.5 (dd, J(C,P)=7.1, Me2CH); 82.7 (d,
J(C,P)=6.0, SCCl); 217.0 (s, C=O). CI-MS: 376 (14, [M(37Cl)+NH4]+), 374 (36, [M(35Cl)+NH4]+),
359 (39, [M(37Cl)+1]+), 357 (100, [M(35Cl)+1]+).
Suitable crystals for the X-ray crystal-structure determination were obtained from hexane at À408.
Reaction of 3 with (EtO)3P. After usual workup and crystallization from hexane 25b was obtained: 44
mg (34%). Colorless crystals. M.p. 30–328 (hexane).
5. Reactions of 2 and 3 with S Nucleophiles. General Procedure. To a soln. of 2 (113.5 mg, 0.5 mmol)
or 3 (130 mg, 0.5 mmol) in CH2Cl2 (3 ml) at 08 was added the respective S nucleophile (0.5 mmol). After
stirring for 10 min at r.t., Et3
ACHTREUNG
min. Then, the solvent was evaporated, and, after addition of Et
AHCTREUNG
removed by filtration. Evaporation of the solvent yielded the product as an oily substance. Where pos-
sible, this was further purified by crystallization.
3-Chloro-3-(ethyldisulfanyl)-2,2,4,4-tetramethylcyclobutanone (28a). Reaction of 2 with EtSH. Yield:
99% (estimated by 1H-NMR with 1,1,2,2-tetrachloroethane as internal standard). Colorless oil. IR
(neat): 2973vs, 2932s, 2869m, 1789vs, 1464s, 1455s, 1381m, 1366w, 1249m, 1131m, 1095w, 1026m, 915w,
1
830m. H-NMR: 1.33 (t, J=7.4, MeCH2); 1.43 (s, 2 Me); 1.48 (s, 2 Me); 2.99 (q, J=7.4, MeCH2
A
NMR: 14.0 (q, MeCH2); 22.3 (q, 2 Me); 23.5 (q, 2 Me); 33.8 (t, MeCH2S); 69.0 (s, 2 Me2C); 89.0 (s,
SCCl); 216.6 (s, C=O). CI-MS: 218 (12), 217(100, [MÀCl]+), 189 (52).
3-Chloro-2,2,4,4-tetramethyl-3-(phenyldisulfanyl)cyclobutanone (28b). Reaction of 2 with PhSH.
Yield: 127 mg (84%). Colorless crystals. M.p. 47–488 (hexane). IR (KBr): 2973s, 2932m, 1784s, 1598s,
1
1583s, 1493vs, 1463s, 1381w, 1365m, 1263m, 1026w, 917m, 826s, 755w. H-NMR: 1.39 (s, 2 Me); 1.45 (s,
2 Me); 7.21–7.34 (m, 3 arom. H); 7.59–7.62 (m, 2 arom. H). 13C-NMR: 22.5 (q, 2 Me); 23.4 (q, 2 Me);
69.1 (s, 2 Me2C); 87.9 (s, SCCl); 127.6, 128.8, 129.6 (3d, 5 arom. CH); 136.8 (s, arom. C); 216.2 (s,
C=O). CI-MS: 267 (19), 266 (17), 265 (100, [MÀCl]+). Anal. calc. for C14H17ClOS2 (300.89): C 55.89,
H5.70, S 21.32; found: C 56.02, H5.50, S 21.05.

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Helvetica Chimica Acta – Vol. 89 (2006)
Table. Crystallographic Data for Compounds 6a, 7a, 16d, and 24d
6a
7a
16d24d
Crystallized from
Empirical formula
Formula weight
Crystal color, habit
Crystal dimensions [mm]
Temp. [K]
hexane
hexane
hexane
hexane
C14H26ClO4
356.84
C12
G
G
U
C12
G
G
E
A
G
S
G
G
G
277.81
309.87
colorless, prism colorless, prism colorless, prism colorless, prism
0.15”0.15”0.23 0.25”0.30”0.30 0.22”0.25”0.28 0.15”0.25”0.28
160(1)
monoclinic
P21/n
160(1)
monoclinic
C2/c
160(1)
orthorhombic
Pca21
160(1)
monoclinic
P21/c
Crystal system
Space group
Z
4
8
4
4
Reflections for cell
determination
2q Range for cell
determination [8]
Unit cell parameters a [Š]
b [Š]
13595
21144
45294
29614
4–60
4–55
4–60
4–60
6.1117(2)
13.5317(4)
16.8950(6)
100.208(2)
1375.13(8)
1.342
0.420
f and w
60
20.2280(3)
13.3852(3)
14.4498(3)
130.3281(9)
2982.6(1)
1.380
0.530
f and w
55
24.3189(3)
6.1656(1)
11.2385(2)
90
1685.11(5)
1.288
12.0776(2)
10.8647(1)
15.1497(2)
111.7564(9)
1846.33(4)
1.284
0.417
f and w
60
c [Š]
b [8]
V [Š3]
Dx [g cmÀ3
]
m(MoKa) [mmÀ1
Scan type
]
0.352
w
2q(max) [8]
60
Transmission factors [min; max]
Total reflections measured
Symmetry independent
reflections
0.844; 0.946
24256
4009
0.801; 0.879
33254
3421
0.797; 0.929
42276
4901
0.842; 0.942
51692
5406
Reflections with I>2s(I)
Reflections used in refinement
Parameters refined; restraints
2702
4009
158
2962
3419
167
4367
4897
197; 1
0.0343
4508
5405
199
Final
R(F) [I>2s (I)
reflections]
0.0442
0.0326
0.0342
wR(F2) (all data)
0.1174
0.0774
0.0864
0.0919
Weighting parameters [a; b]a)
Goodness-of-fit
0.0576; 0.2756 0.0310; 3.1386 0.0413; 0.5216 0.0473; 0.5655
1.032
–
1.066
–
1.039
–
1.047
0.010(1)
Secondary extinction
coefficient
Final Dmax/s
D1 (max; min) [e Š
0.001
0.36; À0.59
0.001
0.42; À0.37
0.001
0.26; À0.34
0.002
0.47; À0.58
À3
]
a) wÀ1 =s 2(F2o)+(aP)2 +bP where P=(Fo2 +2F2c )/3.
3-Chloro-3-(ethyltrisulfanyl)-2,2,4,4-tetramethylcyclobutanone (29a). Reaction of 3 with EtSH.
1
Yield: 97% (estimated by H-NMR with 1,1,2,2-tetrachloroethane as internal standard). Colorless oil.
IR (neat): 2973vs, 2932s, 2869m, 1787vs, 1464s, 1381m, 1366w, 1253m, 1131m, 1026m, 915m, 885w,
830m, 739w. 1H-NMR: 1.39 (t, J=7.3, MeCH2); 1.43 (s, 2 Me); 1.46 (s, 2 Me); 2.93 (q, J=7.3,
MeCH2S). 13C-NMR: 14.0 (q, MeCH2); 22.3 (q, 2 Me); 23.5 (q, 2 Me); 33.8 (t, MeCH2S); 69.0 (s, 2
Me2C); 89.0 (s, SCCl); 216.6 (s, C=O). CI-MS: 218 (12), 217(100, [MÀCl]+), 189 (52).
3-Chloro-2,2,4,4-tetramethyl-3-(phenyltrisulfanyl)cyclobutanone (29b). Reaction of 3 with PhSH.
Yield: 114 mg (68%). Colorless crystals. M.p. 42–438 (hexane). IR (ATR): 2976m, 2934w, 1786vs,

Helvetica Chimica Acta – Vol. 89 (2006)
1059
1767s, 1574w, 1475w, 1451s, 1435m, 1377w, 1361w, 1020m, 908m, 886w, 828m, 733vs, 686vs. 1H-NMR: 1.39
(s, 2 Me); 1.44 (s, 2 Me); 7.25–7.38 (m, 3 arom. H); 7.56–7.59 (m, 2 arom. H). 13C-NMR: 22.9 (q, 2 Me);
23.3 (q, 2 Me); 69.1 (s, 2 Me2C); 87.3 (s, SCCl); 128.2, 129.1, 129.9 (3d, 5 arom. CH); 136.7 (s, arom. C);
215.9 (s, C=O). CI-MS: 297 (18, [MÀCl]+), 265 (21), 218 (100). Anal. calc. for C14H17ClOS3 (332.95): C
50.51, H5.15, S 28.89; found: C 56.49, H5.02, S 28.73.
6. X-Ray Crystal-Structure Determination of 6a, 7a, 16d, and 25d (Table and Figs. 1–3)6). All meas-
urements were performed on a Nonius KappaCCD diffractometer [58] using graphite-monochromated
MoKa radiation (l 0.71073 Š) and an Oxford Cryosystems Cryostream 700 cooler. The data collection
and refinement parameters are given in the Table, and views of the molecules are shown in Figs. 1–3.
Data reduction was performed with HKL Denzo and Scalepack [59]. The intensities were corrected
for Lorentz and polarization effects, and absorption corrections based on the multi-scan method [60]
were applied. Equivalent reflections, other than the Friedel pairs for 16d, were merged. The structures
were solved by direct methods using SIR92 [61], which revealed the positions of all non-H-atoms. The
non-H-atoms were refined anisotropically. All of the H-atoms were placed in geometrically calculated
positions and refined using a riding model where each H-atom was assigned a fixed isotropic displace-
ment parameter with a value equal to 1.2 Ueq of its parent C-atom (1.5 Ueq for the Me groups). The refine-
ment of each structure was carried out on F 2 using full-matrix least-squares procedures, which minimized
the function Sw(Fo2 ÀF2c )2. A correction for secondary extinction was applied in the case of 25d. In 7a,
16d, and 25d, two, four, and one reflections, resp., whose intensities were considered to be extreme out-
liers, were omitted from the final refinement. Refinement of the absolute structure parameter [62] of 16d
yielded a value of À0.05(5), which confidently confirms that the refined coordinates correspond with the
true absolute structure. Neutral atom scattering factors for non-H-atoms were taken from [63a], and the
scattering factors for H-atoms were taken from [64]. Anomalous dispersion effects were included in Fc
[65]; the values for f’ and f’’ were those of [63b]. The values of the mass attenuation coefficients are
those of [63c]. All calculations were performed using the SHELXL97 [66] program.
REFERENCES
´
[1] K. N. Koch, G. Mloston, A. Senning, Eur. J. Org. Chem. 1999, 83.
´
[2] G. Mloston, A. Majchrzak, A. Senning, I. Sotøfte, J. Org. Chem. 2002, 67, 5690.
[3] K. Oka, S. Hara, Tetrahedron Lett. 1977, 8, 695.
[4] C. D. Gabbutt, J. D. Hepworth, B. M. Heron, M. Kanjia, Tetrahedron 1994, 50, 827.
[5] C. K. Johnson, ꢂORTEP IIꢁ, Report ORNL-5138, Oak Ridge National Laboratory, Oak Ridge, Ten-
nessee, 1976.
[6] I. El-Sayed, M. F. Abdel-Megeed, S. M. Yassin, A. Senning, Phosphorus, Sulfur, Silicon 1994, 86,
239.
[7] L. N. Markovskii, V. M. Timoshenko, Yu. G. Shermolovich, Zh. Org. Khim. 1995, 31, 161; Chem.
Abstr. 1996, 124, 116274.
[8] H. W. Roesky, A. May, M. Noltemeyer, J. Fluorine Chem. 1993, 62, 77.
´
´
[9] G. Mloston, J. Romanski, A. Linden, H. Heimgartner, Helv. Chim. Acta 1993, 76, 2147.
[10] T. Saito, S. Motoki, J. Org. Chem. 1977, 42, 559.
[11] S. Tamagaki, K. Sakaki, S. Oae, Bull. Chem. Soc. Jpn. 1974, 47, 3084.
[12] T. Saito, S. Motoki, Chem. Lett. 1978, 591.
[13] T. Saito, S. Motoki, J. Org. Chem. 1979, 44, 2493.
[14] S. Holm, J. A. Boerma, N. H. Nilsson, A. Senning, Chem. Ber. 1976, 109, 1069.
[15] T. Saito, M. Nakane, S. Motoki, Bull. Chem. Soc. Jpn. 1984, 57, 1429.
[16] I. Crossland, Acta Chem. Scand. B 1977, 10, 890.
[17] A. May, H. Roesky, D. Stalke, F. Pauer, G. M. Sheldrick, Chem. Ber. 1990, 123, 1475.
[18] S. Tamagaki, K. Sakaki, S. Oae, Bull. Chem. Soc. Jpn. 1973, 46, 2608.
6
)
CCDC-600725–600728 contain the supplementary crystallographic data for this paper. These data
can be obtained free of charge from the Cambridge Crystallographic Data Centre, via
www.ccdc.cam.ac.uk/data_request/cif.
U

1060
Helvetica Chimica Acta – Vol. 89 (2006)
[19] K. Oka, S. Hara, Tetrahedron Lett. 1977, 2939.
[20] E. M. Burgess, H. R. Penton, J. Am .Chem. Soc. 1973, 95, 279.
[21] T. Saito, S. Motoki, J. Org. Chem. 1977, 42, 3922.
´
[22] G. Mloston, J. Fabian, Pol. J. Chem. 1999, 73, 683.
´
[23] R. Huisgen, G. Mloston, E. Langhals, Helv. Chim. Acta 2001, 84, 1805.
´
´
[24] G. Mloston, J. Romanski, A. Linden, H. Heimgartner, Pol. J. Chem. 1996, 70, 880.
´
[25] G. Mloston, M. Celeda, H. W. Roesky, E. Parisini, J.-T. Ahlemann, Eur. J. Org. Chem. 1998, 459.
´
´
[26] G. Mloston, J. Romanski, H. Heimgartner, Pol. J. Chem. 1996, 70, 437.
´
´
[27] G. Mloston, J. Romanski, A. Linden, H. Heimgartner, Helv. Chim. Acta 1995, 78, 1067.
[28] S. Braverman, D. Ytzhak, Tetrahedron 1990, 46, 2975.
[29] M. E. Sitzmann, W. H. Gilligan, J. Org. Chem. 1983, 48, 3354.
[30] E. O. John, J. M. Shreeve, J. Fluorine Chem. 1987, 36, 429.
[31] W. G. Phillips, K. W. Ratts, J. Org. Chem. 1972, 37, 1526.
[32] B. Zwanenburg, A. Wagenaar, L. Thijs, J. Strating, J. Chem. Soc., Perkin Trans. 1 1973, 73.
[33] C. P. Raj, N. A. Dhas, M. Cherkinski, A. Gedanken, S. Braverman, Tetrahedron Lett. 1998, 39, 5413.
[34] F. Scheufler, M. E. Maier, Eur. J. Org. Chem. 2000, 3945.
[35] P. Bickart, F. W. Carson, J. Jacobus, E. G. Miller, K. Mislow, J. Am. Chem. Soc. 1968, 90, 4869; R.
Tang, K. Mislow, J. Am. Chem. Soc. 1970, 92, 2100.
[36] D. A. Evans, G. C. Andrews, C. L. Sims, J. Am. Chem. Soc. 1971, 93, 4956.
[37] E. Block, S. Naganathan, D. Putman, S. H. Zhao, Pure Appl. Chem. 1993, 65, 625; R. Bauer, W.
Breu, H. Wagner, W. Weigand, J. Chromatogr. 1991, 541, 464.
´
[38] J. Michalski, B. Mlotkowska, A. Skowronska, J. Chem. Soc., Perkin Trans. 1 1974, 319.
[39] D. C. Morrison, J. Am. Chem. Soc. 1955, 77, 181.
[40] A. K. Bhattacharya, G. Thyagarajan, Chem. Rev. 1981, 81, 415.
[41] M. G. Blackburn, T. W. Maciej, J. Chem. Soc., Perkin Trans. 1 1985, 1419.
[42] J. Chojnowski, M. Cypryk, W. Fortuniak, J. Michalski, Synthesis 1977, 683.
´
´
´
[43] A. Skowronska, R. Dembinski, R. Kaminski, J. Michalski, Tetrahedron Lett. 1987, 28, 4209.
[44] K. A. Petrov, N. K. Bliznyuk, V. A. Savostenok, Zh. Obshch. Khim. 1961, 31, 1361; Chem. Abstr.
1961, 55, 23317e.
´
[45] G. Mloston, A. Majchrzak, M. Rutkowska, M. Woznicka, A. Linden, H. Heimgartner, Helv. Chim.
Acta 2005, 88, 2624.
[46] E. J. Corey, K. C. Nicolaou, J. Am. Chem. Soc. 1974, 96, 5614; E. J. Corey, K. C. Nicolaou, L. S. Mel-
vin Jr., J. Am. Chem. Soc. 1975, 97, 653 and 654.
[47] E. J. Corey, D. J. Brunelle, Tetrahedron Lett. 1976, 3409; T. Sasaki, M. Inoue, M. Hirama, Tetrahe-
dron Lett. 2001, 42, 5299.
[48] R. Steudel, Chem. Rev. 2002, 102, 3905.
[49] R. Steudel, K. Hassenberg, V. Münchow, O. Schumann, J. Pickard, Eur. J. Inorg. Chem. 2000, 92, 921.
´
[50] A. Majchrzak, A. Janczak, G. Mloston, A. Linden, H. Heimgartner, Helv. Chim. Acta 2003, 86, 2272.
´
[51] A. Majchrzak, G. Mloston, A. Linden, H. Heimgartner, Helv. Chim. Acta 2004, 87, 790.
[52] I. L. Finar, A. J. Montgomery, J. Chem. Soc. 1961, 367.
[53] R. P. Singh, J. M. Shreeve, Tetrahedron 2000, 56, 7613.
[54] G. K. S. Prakash, A. K. Yudin, Chem. Rev. 1997, 97, 757.
´
[55] G. Mloston, G. K. S. Prakash, G. A. Olah, H. Heimgartner, Helv. Chim. Acta 2002, 85, 1644.
[56] I. V. Koval, T. G. Panasenko, Zh. Org. Khim. 1989, 25, 1677; Chem. Abstr. 1990, 112, 197734.
´
´
[57] G. Mloston, J. Romanski, H. Heimgartner, Pol. J. Chem. 2001, 75, 975
[58] R. Hooft, KappaCCD Collect Software, Nonius BV, Delft, The Netherlands, 1999.
[59] Z. Otwinowski, W. Minor, in ꢂMethods in Enzymologyꢁ, Vol. 276, ꢂMacromolecular Crystallogra-
phyꢁ, Part A, Eds. C. W. Carter Jr., R. M. Sweet, Academic Press, New York, 1997, p. 307.
[60] R. H. Blessing, Acta Crystallogr., Sect. A 1995, 51, 33.
[61] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M. C. Burla, G. Polidori, M. Camalli,
SIR92, J. Appl. Crystallogr. 1994, 27, 435.
[62] H. D. Flack, G. Bernardinelli, Acta Crystallogr., Sect. A 1999, 55, 908; H. D. Flack, G. Bernardinelli,
J. Appl. Crystallogr. 2000, 33, 1143.

Helvetica Chimica Acta – Vol. 89 (2006)
1061
[63] a) E. N. Maslen, A. G. Fox, M. A. OꢁKeefe, in ꢂInternational Tables for Crystallographyꢁ, Ed. A. J. C.
Wilson, Kluwer Academic Publishers, Dordrecht, 1992 Vol. C, Table 6.1.1.1, p. 477; b) D. C. Creagh,
W. J. McAuley, in ꢂInternational Tables for Crystallographyꢁ, Ed. A. J. C. Wilson, Kluwer Academic
Publishers, Dordrecht, 1992 Vol. C, Table 4.2.6.8, p. 219; c) D. C. Creagh, J. H. Hubbell, in ꢂInterna-
tional Tables for Crystallographyꢁ, Ed. A. J. C. Wilson, Kluwer Academic Publishers, Dordrecht,
1992 Vol. C, Table 4.2.4.3, p. 200.
[64] R. F. Stewart, E. R. Davidson, W. T. Simpson, J. Chem. Phys. 1965, 42, 3175.
[65] J. A. Ibers, W. C. Hamilton, Acta Crystallogr. 1964, 17, 781.
[66] G. M. Sheldrick, SHELXL97, Program for the Refinement of Crystal Structures, University of Gçt-
tingen, Germany, 1997.
Received March 14, 2006