Addition reactions of sulfenyl and sulfinyl chlorides with 3-phenyl-1-azabicyclo[1.1.0]butane

Article abstract of DOI:10.1002/hlca.200890154

The reactions of 3-phenyl-1-azabicyclo[1.1.0]butane with α-chlorosulfenyl chlorides and sulfinyl chlorides lead to the corresponding sulfenamides and sulfinamides, respectively, which possess an azetidine ring. It is proposed that a two-step mechanism occurs involving an intermediate carbenium ion, which is formed by the addition of the electrophile at the N-atom and cleavage of the N(1)-C(3) bond. The structures of 9b and 10b are established by X-ray crystallography.

Full text of DOI:10.1002/hlca.200890154

Helvetica Chimica Acta – Vol. 91 (2008)
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Addition Reactions of Sulfenyl and Sulfinyl Chlorides with 3-Phenyl-1-
azabicyclo[1.1.0]butane
by Grzegorz Mloston´* and Marta Woznicka1)
´
´
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´
University of Łodz, Department of Organic and Applied Chemistry, Narutowicza 68, PL-90-136 Łodz
(phone: þ 48426355761; fax: þ 48426355380; e-mail: gmloston@uni.lodz.pl)
and Jo´zef Drabowicz
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of
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Heteroorganic Chemistry, Sienkiewicza 112, PL-90-063 Łodz
and Anthony Linden and Heinz Heimgartner*
Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich
(phone: þ 41446354282; fax: þ 41446356812; e-mail: heimgart@oci.uzh.ch)
The reactions of 3-phenyl-1-azabicyclo[1.1.0]butane with a-chlorosulfenyl chlorides and sulfinyl
chlorides lead to the corresponding sulfenamides and sulfinamides, respectively, which possess an
azetidine ring. It is proposed that a two-step mechanism occurs involving an intermediate carbenium ion,
which is formed by the addition of the electrophile at the N-atom and cleavage of the N(1)ÀC(3) bond.
The structures of 9b and 10b are established by X-ray crystallography.
1. Introduction. – Strained 1-azabicyclo[1.1.0]butanes 1 easily undergo cleavage of
the N(1)ÀC(3) bond in the presence of reagents of type EX (E ¼ electrophile, X ¼
halogen, azide, acetate, etc.) to give azetidine derivatives 3 via a carbenium ion 2,
which combines with the nucleophile X [1 – 4] (Scheme 1). In the case of TsN3 or TsCl,
the cation 2 can be intercepted in a competitive reaction by a second molecule of 1 to
form biazetidine derivatives 5 [5][6]. Similarly, the formation of ꢀdimericꢁ products was
reported for the reaction of 1a with butyl nitrite in AcOH [7] and of 1b with N2O4 in
the presence of atmospheric O2 [8]. On the other hand, treatment of 1a with
triethyloxonium tetrafluoroborate led to the formation of polymeric products [9].
In the case of the unsubstituted 1-azabicyclo[1.1.0]butane (1, R ¼ H), the addition
of TsCl was reported to yield exclusively the 1:1 adduct [10].
Prompted by the results obtained with sulfonyl chlorides, we decided to investigate
corresponding reactions with other S electrophiles, such as sulfenyl chlorides and
sulfinyl chlorides. Whereas sulfinyl chlorides are relatively well-known and widely
applied in organic synthesis [11a], sulfenyl chlorides are less well-known, and only a
limited number of stable representatives are accessible [11b,c], including a-chloro-
sulfenyl chlorides, which only recently were prepared by chlorination of sterically
crowded thioketones [12][13].
1
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)
Part of the Ph.D. thesis of M.W., University of Łodz, 2007.
ꢂ 2008 Verlag Helvetica Chimica Acta AG, Zürich

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Scheme 1
Sulfinyl and sulfenyl chlorides are known to react with N-nucleophiles to yield
sulfinamides and sulfenamides (sulfanyl-amines), respectively [11a,b][14]. They are
formed via a substitution reaction in which HCl is eliminated. According to the
reactions presented in Scheme 1, it could be expected that their reactions with 1 will
lead, however, to azetidine derivatives of type 3, which are 1,3-addition products. To the
best of our knowledge, neither sulfinyl nor sulfanyl amides derived from azetidine have
been reported to date. Sulfinamides are versatile building blocks [15] in asymmetric
synthesis [16] and organocatalysis [17]. Furthermore, some of them have also invoked
interest in medicinal chemistry [18][19]. In addition, in the case of sulfenamides,
diverse applications are known, e.g., in the rubber industry [20].
2. Results and Discussion. – 2.1. Reactions with a-Chlorosulfenyl Chlorides.
Treatment of thioketones 6a and 6b with PCl5 in boiling CCl4 afforded a-chlorosulfenyl
chlorides 7a and 7b [12][13], respectively, which, without further purification, were
used for the reaction with 1a in benzene or CH2Cl2 (Scheme 2). In the case of 6c, the
obtained mixture of nearly equal amounts of cis-7c and trans-7c was used without
Scheme 2

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1421
separation. The reactions with 1a were carried out at ca. 58, and, after 30 min, no
1
starting materials could be detected by H-NMR spectroscopy.
1
In the case of 7a, the H-NMR spectrum of the reaction mixture showed the
presence of two sharp singlets for Me groups at 1.30 and 1.37 ppm, as well as a broad
singlet at 4.37 ppm, which can be attributed to the two CH2 groups of the azetidine ring.
The pure product was isolated as a crystalline material and identified as the
sulfenamide 8a (Scheme 2). The 13C-NMR spectrum of 8a showed, along with signals
of Me groups (21.5 and 24.0 ppm) and CH2 groups (74.7 ppm), signals for two
quaternary C-atoms at 68.1 and 89.8 ppm, which were attributed to C(3) and C(3’). The
C¼O group absorbed at 217.3 ppm.
The analogous product 8b was obtained from the reaction of 7b and 1a. For the
reaction of cis/trans-7c, 2 mol-equiv. of 1a were used, leading to the formation of a 1:2
adduct 8c as a mixture of approximately equal amounts of the cis- and trans-isomers.
The attempted separation of the diastereoisomers, either by crystallization or by
1
preparative TLC, failed. As expected from the molecular symmetry, the H-NMR
spectrum of the cis-isomer showed two signals for Me groups at 1.40 and 1.58 ppm,
whereas trans-8c is characterized by the presence of only one Me signal at 1.50 ppm. In
contrast to the reaction of 1a with TsN3 [5], formation of biazetidine derivatives or
oligomeric materials was not observed.
The crystalline sulfenamides 8a and 8b were sequentially oxidized by treatment
with meta-chloroperbenzoic acid (mCPBA) in CH2Cl2 at room temperature. Using 1
mol-equiv. of mCPBA, they were smoothly converted into the corresponding
sulfinamides 9a and 9b, respectively (Scheme 3).
Scheme 3
1
It is interesting to note that characteristic changes of the H-NMR spectrum are
observed when the conversion 8b ! 9b occurs, i.e., the four Me groups at the
cyclobutane ring gave four signals at 1.40, 1.49, 1.67, and 1.82 ppm, and the CH2 groups
of the azetidine ring appeared as an AB system at 4.30 and 4.82 ppm (JAB ¼ 9.3 Hz) and
a singlet at 4.45 ppm. This pattern indicates that the molecule of 9b, in contrast to 8b,
does not possess a symmetry plane. In the IR spectrum (KBr), a strong absorption

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band at 1112 cmÀ1 was attributed to the S¼O group. In addition, the MS and elemental
analyses evidenced 9b as the mono-oxidation product of 8b. Finally, crystallization
from petroleum ether gave colorless crystals suitable for an X-ray crystal-structure
determination, which established the proposed structure of 9b (Figure).
Figure. ORTEP Plots [21] of the molecular structures of a) 9b and b) 10b (arbitrary atom numbering;
50% probability ellipsoids)
Treatment of 8a and 8b with 2 mol-equiv. of mCPBA in CH2Cl2 gave, after longer
reaction time at room temperature, the sulfonamides 10a and 10b, respectively. The
1H-NMR spectra showed that the molecules are symmetric and, therefore, only two Me
signals (1.55 and 1.75 mm for 10b) and an AB system for two CH2 groups (4.53 and
4.78 ppm, J ¼ 8.8, for 10b) were displayed. Two intense absorption bands at 1341 and
1156 cmÀ1 were in accordance with the values expected for sulfonamides [22]. Finally,
the structure of 10b was established by X-ray crystallography (Figure).
2.2. Reactions with Sulfinyl Chlorides. Sulfinyl chlorides 11a – 11d, which are easily
accessible according to known protocols [23], were used for the reaction with 3-phenyl-

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1423
1-azabicyclo[1.1.0]butane (1a). The experiments were performed in CH2Cl2 at 0 – 58 in
the presence of pyridine in order to avoid polymerization of 1a induced by traces of
HCl. After 1 h, the reactions were complete, and the 1H-NMR spectra of the mixtures
showed that 1a was completely consumed. Instead of the two CH2 multiplets of 1a,
located at 1.50 and 2.77 ppm (CDCl3), in all products, two AB systems appeared
between 3.3 and 5.0 ppm. After chromatographic workup, sulfinamides 12 were
obtained as crystalline materials, which are stable at room temperature (Scheme 4).
Whereas the non-equivalency of the two CH2 groups in 12a was apparent only in the
1H-NMR spectrum (AB systems at 4.47 and 4.66 ppm, JAB ¼ 8.8 and 9.9 Hz, resp.), the
non-equivalency in the products 12b – 12d was also confirmed by the appearance of two
CH2 signals in the 13C-NMR spectra (e.g., for 12b: 58.3 and 61.2 ppm).
Scheme 4
It is worth mentioning that, in the 1H-NMR spectra of sulfinamides obtained from
11c and diethyl or dimethylamine, the N-alkyl groups are equivalent at room
temperature [24][25]. Moreover, according to the studies of Moriarty, the rotation
barrier in N,N-dimethylmethanesulfinamide is so low that even at À 608 both MeN
groups appear as a singlet [26]. These observations suggest that, in the series of new
sulfinamides 12 derived from azetidines, the rotation barrier of the SÀN bond is
significantly higher, i.e., the double-bond character of the S,N bond increases.
The S-atom of a sulfinamide is a stereogenic center and, therefore, sulfinamides are
chiral compounds [15]. In a tentative experiment, a CDCl3 solution of sulfinamide 12d
at room temperature was treated with an equimolar amount of (þ)-(R)-(tert-butyl)
(phenyl)thiophosphonic acid. The 1H-NMR spectrum of this mixture showed that the
low-field-shifted part of one AB system at 3.88 ppm has split into four lines with equal
intensities within each part. This result confirmed the presence of two enantiomers of
12d in the solution. Additional support came from the analytical HPLC experiment
with a sample of racemic 12d on a chiral solid phase (Chiralpak AS), in which two
separated peaks with equal intensities were observed.
The isolated sulfinamides 12c and 12d were treated with mCPBA at room
temperature to yield the expected sulfonamides 13a and 13b, respectively, in good
yields (Scheme 5). As is characteristic for sulfonamides derived from azetidine (e.g.,
1
10a and 10b), the two CH2 groups appear in the H-NMR spectrum as an AB system
between 4.3 and 4.8 ppm. In the 13C-NMR spectrum, these groups appear as a single
signal at 66.5 and 66.1 ppm for 13a and 13b, respectively. The characteristic strong
bands for the sulfonamide group in the IR spectrum were found at 1315/1136 and 1352/
1172 cmÀ1, respectively.

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Scheme 5
3. Conclusions. – The strained 3-phenyl-1-azabicyclo[1.1.0]butane (1a) reacts
smoothly with sulfenyl and sulfinyl chlorides to give the expected sulfenamides and
sulfinamides, respectively, with an azetidine residue. In contrast to similar reactions
with sulfonyl chlorides, no oligomerization of 1a was observed. As previously proposed
for the addition reaction of EX with 1-azabicyclo[1.1.0]butanes (see Scheme 1), the
reactions with sulfenyl chlorides 7 and sulfinyl chlorides 9 occur stepwise via the initial
formation of an ion pair of type 2. Subsequent addition of the ClÀ ion to the azetidinium
ion leads to the final product. The 1H-NMR analysis of the crude product mixture gave
no indication for the competitive formation of a 2-azete derivative via deprotonation of
the intermediate 2.
The NMR data of the sulfinamides 12 clearly indicate that the rotation about the
SÀN bond in these compounds is much more hindered than in the known N,N-dialkyl-
substituted analogues. Most likely, this is the result of the incorporation of the N-atom
into a strained four-membered ring.
´
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The authors thank the Rector of the University of Łodz for a grant and F. Hoffmann-La Roche AG,
Basel, for financial support. The skilful help of Mrs. Małgorzata Celeda in performing some of the
experiments and Mr. Adrian Zaja˛c for preliminary experiments are acknowledged.
Experimental Part
1. General. M.p.: in capillary with a Meltemp 2 apparatus; uncorrected. IR Spectra: in KBr pellets
.
with a Nexus FT-IR spectrophotometer; in cmÀ1 1H- and 13C-NMR Spectra: Tesla BS 687 (80 and
20 MHz, resp.) or Bruker 300 spectrometer (300 and 75 MHz, resp.) with Me4Si (¼0 ppm) as internal
standard; d in ppm, J in Hz, the multiplicity of 13C signals was determined by DEPTexperiments. MS (EI
or CI): Finnigan Mat-90 or Finnigan SSQ-700 spectrometer; CI with isobutane or NH3; in m/z (rel. %).
Elemental analyses were performed in the Analytical Laboratory of the University of Zürich and the
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Laboratory of the Polish Academy of Sciences (CBMiM) in Łodz.
2. Starting Materials. 3-Phenyl-1-azabicyclo[1.1.0]butane (1a) was prepared from trimethylsulfonium
iodide, BuLi, and 3-phenyl-2H-azirine according to a known protocol [27]. 2,2,4,4-Tetramethyl-3-
thioxocyclobutanone (6a) [28], 3,3-dichloro-2,2,4,4-tetramethylcyclobutanethione (6b) [13], and 2,2,4,4-
tetramethylcyclobutane-1,3-dithione (6c) [29] were synthesized from 2,2,4,4-tetramethylcyclobutane-1,3-
dione (for 6a and 6c) and 3,3-dichloro-2,2,4,4-tetramethylcyclobutanone (for 6b) by thionation using P2S5
in pyridine soln. at 1308. 1-Chloro-2,2,4,4-tetramethyl-3-oxocyclobutanesulfenyl chloride (7a) [12], 1,3,3-
trichloro-2,2,4,4-tetramethylcyclobutanesulfenyl chloride (7b) [13], and cis/trans-1,3-dichloro-2,2,4,4-
tetramethylcyclobutane-1,3-bis(sulfenyl chloride) (cis/trans-7c) [12] were obtained from thioketones 6a –
6c by chlorination using PCl5 in CCl4 soln. according to known protocols. Methanesulfinyl chloride (11a),
ethanesulfinyl chloride (11b), 2,2-dimethylethanesulfinyl chloride (11c), and benzenesulfinyl chloride
(11d) were synthesized according to literature protocols [23].
3. Reactions of 1a with a-Chlorosulfenyl Chlorides 7a – 7c. General Procedure. To a magnetically
stirred soln. of 7 (1 mmol) in 2 ml of benzene (7a and 7c) or in 0.5 ml of CH2Cl2 (7b) at r.t., a soln. of 1a

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(131 mg, 1 mmol in the case of 7a and 7b, and 262 mg, 2 mmol in the case of 7c) in benzene (1 ml) or
CH2Cl2 (0.5 ml) was added, and stirring was continued for 30 min. Then, the solvent was evaporated, and
the residue was washed with Et2O, and filtered. The filtrate was evaporated to dryness, and the oily
residue was crystallized from hexane (for 8a) or Et2O (for 8b) after cooling the soln. in a dry ice box.
3-Chloro-3-[(3-chloro-3-phenylazetidin-1-yl)sulfanyl]-2,2,4,4-tetramethylcyclobutanone (8a). Yield:
259 mg (72%). Colorless crystals. M.p. 101 – 1028 (hexane, À 708). IR (KBr): 3000s, 1780vs (C¼O),
1450s, 1060s, 1020s, 715s, 695s. 1H-NMR (CDCl3): 1.30 (s, 2 Me); 1.37 (s, 2 Me); 4.37 (s, 2 CH2); 7.13 – 7.43
(m, 5 arom. H). 13C-NMR (CDCl3): 21.6 (2 Me); 24.0 (2 Me); 63.7 (CqCl); 68.1 (2 Cq); 74.7 (2 CH2); 89.8
(CqS); 125.7 (2 arom. CH); 128.5 (arom. CH); 129.1 (2 arom. CH); 142.5 (arom. C); 217.3 (C¼O). EI-
MS: 359 (18), 357 (26, Mþ. ), 191 (57), 149 (93), 131 (100), 120 (79), 103 (63), 77 (58), 42 (56). Anal. calc.
for C17H21Cl2NOS (358.33): C 56.98, H 5.91, N 3.91; found: C 56.62, H 5.95, N 4.04.
3-Chloro-3-phenyl-1-[(1,3,3-trichloro-2,2,4,4-tetramethylcyclobutyl)sulfanyl]azetidine (8b). Yield:
80 mg (19%). Colorless crystals. M.p. 52 – 558 (Et2O, À 708). IR (KBr): 3022m, 2941m, 2845m, 1471vs,
1447vs, 1072m, 871s, 833s, 823m, 804s, 758vs, 697vs, 619s. 1H-NMR (CDCl3): 1.46 (s, 2 Me); 1.54 (s, 2 Me);
4.39 (s, 2 CH2); 7.29 – 7.46 (m, 5 arom. H). 13C-NMR (CDCl3): 25.1 (2 Me); 27.6 (2 Me); 58.9 (2 Cq); 63.5
(CqCl); 74.4 (2 CH2); 92.1 (CqS); 98.8 (CqCl2); 125.4 (2 arom. CH); 128.2 (arom. CH); 128.7 (2 arom.
CH); 142.2 (arom. C). CI-MS: 416 (17), 414 (34), 412 (26, [M þ 1]þ), 168 (10), 133 (11), 132 (100). Anal.
calc. for C17H21Cl4NS (413.24): C 49.41, H 5.12, N 3.39, S 7.76; found: C 49.28, H 5.21, N 3.26, S 7.60.
cis/trans-1,3-Dichloro-1,3-bis[(3-chloro-3-phenylazetidin-1-yl)sulfanyl]-2,2,4,4-tetramethylcyclobu-
tane (cis/trans-8c, ratio ca. 1:1). Yield: 422 mg (73%). Colorless oil; melts at r.t. after crystallization from
pentane at À 788. IR (film): 2980m, 2960m, 2860m, 1440s, 1370m, 1310m, 1260m, 1160m, 1075s, 990m,
800s, 710s, 680vs. 1H-NMR (CDCl3): cis-8: 1.40 (s, 2 Me); 1.58 (s, 2 Me); 4.40 (br. s, 4 CH2); 7.21 – 7.50 (m,
10 arom. H); trans-8: 1.50 (s, 4 Me); 4.40 (br. s, 4 CH2); 7.21 – 7.50 (m, 10 arom. H). 13C-NMR (CDCl3):
23.6, 28.9 (4 Me, cis-8c); 26.4 (4 Me, trans-8c); 56.1, 56.6 (2 Cq, cis- and trans-8c); 63.8, 65.5 (2 CqCl, cis-
and trans-8c); 74.3, 74.4 (4 CH2, cis- and trans-8c); 93.0, 93.8 (2 CqS, cis- and trans-8c); 125.4 (4 arom. CH,
cis- and trans-8c); 128.1 (2 arom. CH, cis- and trans-8c); 128.7 (4 arom. CH, cis- and trans-8c); 142.2 (2
arom. Cq, cis- and trans-8c). CI-MS (isobutane): 579 (2), 578 (3), 577 (3), 576 (4), 574 (3, [M þ 1]þ), 543
(8), 541 (14), 539 (13, [M À Cl]þ), 342 (74), 306 (100), 270 (34), 132 (42).
4. Oxidation of 8a and 8b with mCPBA. General Procedure. A magnetically stirred soln. of 8
(1 mmol) in CH2Cl2 (5 ml) was cooled in an ice-water bath, and a portion of mCPBA (1 mmol for the
synthesis of 9a and 9b, or 6 mmol for the synthesis of 10a and 10b) was added in small portions. Stirring
was continued for 15 min (for 9a and 9b) or 12 h (for 10a and 10b). Then, the soln. was diluted with
CH2Cl2 (10 ml), and washed with a sat. aq. soln. of NaHCO3, 2 – 5% NaOH, and brine. The org. layer was
separated and dried, and the solvent was evaporated. Pure samples were obtained by crystallization from
the appropriate solvent.
3-Chloro-3-[(3-chloro-3-phenylazetidin-1-yl)sulfinyl]-2,2,4,4-tetramethylcyclobutanone (9a). Yield:
230 mg (61%). Colorless crystals. M.p. 102 – 1048 (petroleum ether). IR (KBr): 1794s (C¼O), 1781m,
1105s (S¼O), 1060m, 698m. 1H-NMR (CDCl3): 1.29, 1.37, 1.55, 1.70 (4s, 4 Me); 4.29, 4.90 (AB, JAB ¼ 9.3,
CH2); 4.50 (s, CH2); 7.34 – 7.48 (m, 5 arom. CH). 13C-NMR (CDCl3): 21.1, 21.7, 21.9, 22.1 (4 Me); 62.7, 64.5
(2 CH2); 65.8 (CqCl); 66.9, 67.1 (2 Cq); 91.7 (CqS); 125.3 (2 arom. CH); 128.6 (arom. CH); 128.9 (2 arom.
CH); 141.2 (arom. C); 214.7 (C¼O). CI-MS (isobutane): 378 (12), 376 (65), 374 (100, [M þ 1]þ), 214
(10), 131 (13). Anal. calc. for C17H21Cl2NO2S (374.33): C 54.55, H 5.65, N 3.74, S 8.57; found: C 54.62, H
5.87, N 3.78, S 8.61.
3-Chloro-3-phenyl-1-[(1,3,3-trichloro-2,2,4,4-tetramethylcyclobutyl)sulfinyl]azetidine (9b). Yield:
179 mg (42%). Colorless crystals. M.p. 115 – 1178 (petroleum ether). IR (KBr): 1449m, 1112s (S¼O),
1080m, 1071m, 886m, 796m, 716m, 694m, 616m. 1H-NMR (CDCl3): 1.40, 1.49, 1.68, 1.82 (4s, 4 Me); 4.24,
4.84 (AB, JAB ¼ 9.4, CH2); 4.44 (s, CH2); 7.32 – 7.38 (m, 5 arom. H). 13C-NMR (CDCl3): 24.6, 25.0, 25.1,
25.6 (4 Me); 57.6, 57.8 (2 Cq); 62.5, 64.4 (2 CH2); 65.9 (CqCl); 94.4 (CqS); 98.0 (CqCl2); 125.3 (2 arom.
CH); 128.6 (arom. CH); 128.8 (2 arom. CH); 141.2 (arom. C). CI-MS (isobutane): 434 (10), 432 (65), 430
(100), 428 (73, [M þ 1]þ). Anal. calc. for C17H21Cl4NOS (429.24): C 47.57, H 4.93, N 3.26, S 7.47; found: C
47.63, H 5.01, N 3.31, S 7.51.
3-Chloro-3-[(3-chloro-3-phenylazetidin-1-yl)sulfonyl]-2,2,4,4-tetramethylcyclobutanone (10a).
Yield: 170 mg (44%). Colorless crystals. M.p. 94 – 988 (petroleum ether/CH2Cl2). IR (KBr): 1793s

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(C¼O), 1774m, 1337s (S¼O), 1156s (S¼O), 1115m, 719m, 655m, 632m, 618m. 1H-NMR (CDCl3): 1.49
(s, 2 Me); 1.62 (s, 2 Me); 4.59, 4.81 (AB, JAB ¼ 9.5, 2 CH2); 7.36 – 7.44 (m, 5 arom. H). 13C-NMR (CDCl3):
20.6 (2 Me); 24.8 (2 Me); 61.4 (2 Cq); 67.3 (2 CH2); 91.0 (CqS); 125.3 (2 arom. CH); 128.9 (arom. CH);
129.0 (2 arom. CH); 140.7 (arom. C); 213.3 (C¼O); signal for CqCl missing. 13C-NMR (C6D6): 21.4
(2 Me); 25.4 (2 Me); 62.6 (CqCl); 67.8 (2 CH2); 68.2 (2 Cq); 92.2 (CqS); 126.2 (2 arom. CH); 129.0 (arom.
CH); 129.7 (2 arom. CH); 141.7 (arom. C); 212.6 (C¼O). CI-MS (isobutane): 392 (64), 390 (94, [M þ
1]þ), 354 (100, [M À Cl]þ), 131 (22). Anal. calc. for C17H21Cl2NO3S (390.33): C 52.31, H 5.42, N 3.59, S
8.22; found: C 52.14, H 5.49, N 3.64, S 8.11.
3-Chloro-3-phenyl-1-[(1,3,3-trichloro-2,2,4,4-tetramethylcyclobutyl)sulfonyl]azetidine (10b). Yield:
289 mg (65%). Colorless crystals. M.p. 119 – 1218 (hexane/CH2Cl2). IR (KBr): 1341s (S¼O), 1156s
(S¼O), 1112m, 695m, 663s, 622m. 1H-NMR (CDCl3): 1.55 (s, 2 Me); 1.75 (s, 2 Me); 4.53, 4.78 (AB, JAB
¼
8.8, 2 CH2); 7.40 (s, 5 arom. H). 13C-NMR (CDCl3): 25.3 (2 Me); 27.0 (2 Me); 58.3 (2 Cq); 61.3 (CqCl);
67.3 (2 CH2); 94.7 (CqS); 97.7 (CqCl2); 125.3 (2 arom. CH); 128.8 (1 arom. CH); 129.0 (2 arom. CH); 140.7
(arom. C). 13C-NMR (C6D6): 26.3 (2 Me); 27.6 (2 Me); 59.3 (2 Cq); 62.6 (CqCl); 67.9 (2 CH2); 95.7 (CqS);
99.2 (CCl2); 126.2 (2 arom. CH); 129.0 (arom. CH); 129.7 (2 arom. CH); 141.7 (arom. C). CI-MS
(isobutane): 450 (4), 448 (19), 446 (37), 444 (27, [M þ 1]þ), 412 (45), 410 (100), 408 (85, [M À Cl]þ), 376
(48), 374 (62), 346 (37), 344 (39), 340 (26), 338 (28), 132 (38), 130 (67). Anal. calc. for C17H21Cl4NO2S
(445.24): C 45.86, H 4.75, N 3.15, S 7.20; found: C 45.79, H 4.83, N 3.09, S 7.10.
5. Reactions of 1a with Sulfinyl Chlorides 11a – 11d. General Procedure. A magnetically stirred soln.
of 11 (1 mmol) and dry pyridine (158 mg, 2 mmol) in CH2Cl2 (1 ml) was cooled in an ice-water bath, a
soln. of 1a (131 mg, 1 mmol) in CH2Cl2 (1 ml) was added in small portions, and stirring was continued for
1 h. Then, the soln. was diluted with CH2Cl2 (10 ml), washed with H2O, and the org. layer was dried
(MgSO4). The solvent was evaporated, and pure products were obtained after prep. TLC (for 12a and
12d) or crystallization (for 12b and 12c).
3-Chloro-1-(methylsulfinyl)-3-phenylazetidine (12a). Yield: 100 mg (44%). Colorless crystals. M.p.
67 – 698 (Et2O, À 208) IR (KBr): 1073m (br.), 1055m, 909s, 731s, 647m, 622m. 1H-NMR (CDCl3): 2.45 (s,
Me); 4.14, 4.71 (AB, JAB ¼ 8.8, CH2); 4.38 (s, CH2); 7.30 – 7.52 (m, 5 arom. H). 13C-NMR (CDCl3): 38.9
(Me); 57.8, 60.7 (2 CH2); 63.2 (CqCl); 125.4 (2 arom. CH); 128.5 (arom. CH); 128.8 (2 arom. CH); 141.3
(arom. C). CI-MS (isobutane): 232 (34), 231 (11), 230 (100, [M þ 1]þ), 194 (16), 166 (18), 131 (29).
Anal. calc. for C10H12ClNOS (229.73): C 52.28, H 5.27, N 6.10, S 13.96; found: C 52.20, H 5.25, N 6.07, S
14.01.
3-Chloro-1-(ethylsulfinyl)-3-phenylazetidine (12b). Yield: 62 mg (25%). Colorless crystals. M.p. 71 –
728 (Et2O, À 208). IR (KBr): 1075s, 1061m, 1052m, 1025m, 725m, 703m, 624m. 1H-NMR (CDCl3): 1.25 (t,
J ¼ 7.6, MeCH2); 2.60 (q, J ¼ 7.6, MeCH2); 4.12, 4.72 (AB, JAB ¼ 8.5, CH2); 4.40 (s, CH2); 7.34 – 7.46 (m, 5
arom. H). 13C-NMR (CDCl3): 7.5 (MeCH2); 46.7 (MeCH2); 58.3, 61.2 (2 CH2); 63.6 (CqCl); 125.4 (2
arom. CH); 128.4 (arom. CH); 128.7 (2 arom. CH); 141.4 (arom. C). CI-MS: 246 (31), 244 (100, [M þ
1]þ). Anal. calc. for C11H14ClNOS (243.76): C 54.20, H 5.79, N 5.75, S 13.16; found: C 54.27, H 5.65, N
5.68, S 13.49.
3-Chloro-1-[(1,1-dimethylethyl)sulfinyl]-3-phenylazetidine (12c). Yield: 170 mg (63%). Colorless
crystals. M.p. 87 – 908 (Et2O, À 708). IR (KBr): 2959m, 2928m, 1451m, 1363m, 1178m (br.), 1066vs,
1051s, 1021m, 728s, 705m, 621m. 1H-NMR (CDCl3): 1.19 (s, 3 Me); 4.10, 4.76 (AB, JAB ¼ 9.0, CH2); 4.34,
4.48 (AB, JAB ¼ 8.8, CH2); 7.30 – 7.46 (m, 5 arom. CH). 13C-NMR (CDCl3): 23.2 (3 Me); 57.4 (Cq); 61.6,
64.2 (2 CH2); 64.9 (CqCl); 125.4 (2 arom. CH); 128.3 (arom. CH); 128.7 (2 arom. CH); 141.8 (arom. C).
CI-MS (NH3): 291 (3), 289 (10, [M þ NH4]þ), 274 (35), 273 (15), 272 (100, [M þ 1]þ). Anal. calc. for
C13H18ClNOS (271.81): C 57.45, H 6.67, N 5.15, S 11.80; found: C 57.58, H 6.42, N 4.92, S 11.79.
3-Chloro-3-phenyl-1-(phenylsulfinyl)azetidine (12d). Yield: 185 mg (63%). Colorless thick oil. IR
(film): 1444m, 1096s, 1075m, 1062s, 753m, 697s, 623m, 591s, 580s. 1H-NMR (CDCl3): 3.82, 4.56 (AB, JAB
¼
8.8, CH2); 4.30, 4.44 (AB, JAB ¼ 8.8, CH2); 7.30 – 7.77 (m, 10 arom. H). 13C-NMR (CDCl3): 58.5, 60.6
(2 CH2); 62.8 (CqCl); 125.2 (2 arom. CH); 125.3 (2 arom. CH); 128.2 (arom. CH); 128.5 (2 arom. CH);
128.7 (2 arom. CH); 131.0 (arom. CH); 141.2, 142.0 (2 arom. C). CI-MS (isobutane): 294 (32), 293 (15),
292 (100, [M þ 1]þ), 132 (11), 131 (12). Anal. calc. for C15H14ClNOS (291.80): C 61.74, H 4.84, N 4.80, S
10.99; found: C 61.85, H 4.95, N 4.72, S 10.83.

Helvetica Chimica Acta – Vol. 91 (2008)
1427
6. Oxidation of 12c and 12d with mCPBA. General Procedure. A magnetically stirred soln. of 12
(1 mmol) in CH2Cl2 (12 ml) was cooled in an ice-water bath, mCPBA (345 mg, 2 mmol) was added in
small portions, and stirring was continued for 15 min. Then, the soln. was diluted with CH2Cl2 (10 ml),
and washed with a sat. aq. soln. of NaHCO3, 2% NaOH, and brine. The org. layer was separated, dried
(MgSO4), and the solvent was evaporated. Pure products were obtained after crystallization.
3-Chloro-1-[(1,1-dimethylethyl)sulfonyl]-3-phenylazetidine (13a). Yield: 183 mg (64%). Colorless
crystals. M.p. 137 – 1398 (hexane/CH2Cl2). IR (KBr): 1315vs (S¼O), 1136vs (S¼O), 1102m, 730m, 693s,
616m. 1H-NMR (CDCl3): 1.40 (s, 3 Me); 4.45, 4.68 (AB, JAB ¼ 10.1, 2 CH2); 7.40 (s, 5 arom. H). 13C-NMR
(CDCl3): 23.8 (3 Me); 60.1 (Cq); 61.5 (CqCl); 66.5 (2 CH2); 125.4 (2 arom. CH); 128.7 (arom. CH); 129.0
(2 arom. CH); 141.3 (arom. C). CI-MS (isobutane): 290 (19), 288 (58, [M þ 1]þ), 254 (12), 252 (100,
[M À Cl]þ), 132 (37). Anal. calc. for C13H18ClNO2S (287.81): C 54.25, H 6.30, N 4.87, S 11.14; found: C
54.19, H 6.25, N 4.81, S 11.05.
Table. Crystallographic Data for Compounds 9b and 10b
9b
10b
Crystallized from
Empirical formula
Formula weight
Crystal color, habit
Crystal dimensions [mm]
Temperature [K]
Crystal system
Space group
petroleum ether
C17H21Cl4NOS
429.23
colorless, prism
0.15 ꢀ 0.15 ꢀ 0.20
160(1)
hexane/CH2Cl2
C17H21Cl4NO2S
445.23
colorless, plate
0.05 ꢀ 0.08 ꢀ 0.28
160(1)
monoclinic
P21/n
monoclinic
P21/n
Z
4
4
Reflections for cell determination
2q Range for cell determination [8]
Unit cell parameters
a [Š]
71996
4 – 55
27149
4 – 55
13.5031(2)
6.2927(1)
23.1262(4)
97.048(1)
1950.21(5)
1.462
0.718
f and w
55
7.3150(2)
13.1977(2)
20.9374(6)
98.439(1)
1999.44(9)
1.479
b [Š]
c [Š]
b [8]
V [Š3]
Dx [g cmÀ3
]
m(MoKa) [mmÀ1
Scan type
]
0.707
w
2q(max) [8]
55
Transmission factors [min; max]
Total reflections measured
Symmetry independent reflections
Reflections with I > 2s(I)
Reflections used in refinement
Parameters refined; restraints
Final R(F) [I > 2s(I) reflections]
wR(F2) (all data)
0.849; 0.900
42318
4425
3711
4424
221
0.0395
0.1005
0.0358; 2.5269
1.103
0.892; 0.968
18106
4496
3518
4496
231
0.0359
0.0858
0.0347; 1.0875
1.028
Weighting parameters [a; b]a)
Goodness-of-fit
Secondary extinction coefficient
–
0.0051(7)
0.001
0.37; À 0.44
Final Dmax/s
D1 (max; min) [e Š
0.001
0.63; À 0.56
À3
]
a) wÀ1 ¼ s2(F2o ) þ (aP)2 þ bP where P ¼ (F o2 þ 2F 2c )/3.

1428
Helvetica Chimica Acta – Vol. 91 (2008)
3-Chloro-3-phenyl-1-(phenylsulfonyl)azetidine (13b). Yield: 292 mg (95%). Colorless crystals. M.p. 87 –
908 (hexane/CH2Cl2). IR (KBr): 1448m, 1352vs (S¼O), 1172vs (S¼O), 1112s, 754m, 724s, 699m, 653s,
591m, 580s. 1H-NMR (CDCl3): 4.33, 4.51 (AB, JAB ¼ 9.6, 2 CH2); 7.31 – 8.08 (m, 10 arom. H). 13C-NMR
(CDCl3): 60.7 (CqCl); 66.1 (2 CH2); 125.2 (2 arom. CH); 128.3 (2 arom. CH); 128.7 (arom. CH); 128.8 (2
arom. CH); 129.3 (2 arom. CH); 133.7 (arom. CH); 133.8, 140.6 (2 arom. C). CI-MS: 310 (18), 308 (48,
[M þ 1]þ), 274 (25), 272 (100, [M À Cl]þ). Anal. calc. for C15H14ClNO2S (307.80): C 58.53, H 4.58, N 4.55,
S 10.42; found: C 58.21, H 4.69, N 4.53, S 10.35.
7. X-Ray Crystal-Structure Determination of 9b and 10b (Table and Figure)2). All measurements
were performed on a Nonius KappaCCD diffractometer [30] 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 the Figure. Data
reduction was performed with HKL Denzo and Scalepack [31]. The intensities were corrected for
Lorentz and polarization effects, and absorption corrections based on the multi-scan method [32] were
applied. Each structure was solved by direct methods using SIR92 [33], 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 displacement parameter with a value equal to 1.2 Ueq of its parent C-atom (1.5 Ueq for the
Me groups). The refinement of each structure was carried out on F2 using full-matrix least-squares
procedures, which minimized the function Sw(F2o À Fc2 )2. A correction for secondary extinction was
applied in the case of 10b. In the case of 9b, one reflection, whose intensity was considered to be an
extreme outlier, was omitted from the final refinement. Neutral-atom scattering factors for non-H-atoms
were taken from [34a], and the scattering factors for H-atoms were taken from [35]. Anomalous
dispersion effects were included in Fc [36]; the values for f ’ and f ’’ were those of [34b]. The values of the
mass attenuation coefficients are those of [34c]. All calculations were performed using the SHELXL97
[37] program.
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Received March 13, 2008