Stereoselective 1,3-dipolar cycloadditions of thioketones to carbohydrate-derived nitrones

Article abstract of DOI:10.1016/j.tetasy.2016.08.007

A series of cycloaliphatic thioketones was reacted with selected enantiopure nitrones bearing carbohydrate-derived moieties leading to 1,4,2-oxathiazolidine derivatives in a highly stereoselective manner. Analysis of spectroscopic data supplemented by X-r

Full text of DOI:10.1016/j.tetasy.2016.08.007

Tetrahedron: Asymmetry 27 (2016) 973–979
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Stereoselective 1,3-dipolar cycloadditions of thioketones
to carbohydrate-derived nitrones
a
a
b
a,
⇑
Grzegorz Mlosto n´ , Aleksandra Michalak , Andrzej Fruzi n´ ski , Marcin Jasi n´ ski
a
Faculty of Chemistry, University of Łód ´z , Tamka 12, 91-403 Łód ´z , Poland
Institute of General and Ecological Chemistry, Łód ´z University of Technology, Zeromskiego 115, 90-924 Łód ´z , Poland
b
_
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of cycloaliphatic thioketones was reacted with selected enantiopure nitrones bearing carbohy-
drate-derived moieties leading to 1,4,2-oxathiazolidine derivatives in a highly stereoselective manner.
Analysis of spectroscopic data supplemented by X-ray diffraction analysis of the major products con-
Received 16 July 2016
Accepted 2 August 2016
Available online 28 August 2016
firmed the anti-configuration in the series derived from
nitrones bearing a sugar moiety at the C atom. In the case of the model benzaldehyde-derived nitrone
decorated at the N atom with carbohydrate auxiliary, and also for a -erythrose-derived cyclic nitrone,
D-glyceraldehyde and L-erythrose-functionalized
L
in the reaction with sterically crowded 2,2,4,4-tetramethyl-3-thioxocyclobutanone the exclusive forma-
tion of single diastereoisomeric products was observed indicating an excellent steric match of the sub-
1
strates. Dissociation constants of selected (3+2)-cycloadducts were determined by H NMR spectroscopy.
Ó 2016 Elsevier Ltd. All rights reserved.
1
. Introduction
Over the last few decades, both aromatic and cycloaliphatic
On the other hand, carbohydrate-derived nitrones are attractive
chiral 1,3-dipoles widely applied not only for the (3+2)-cycloaddi-
tions but also for other reactions leading to N,O-heterocycles with
7
thioketones have attracted considerable attention as extremely
reactive dipolarophiles (so-called ‘‘superdipolarophiles”) towards
diverse 1,3-dipoles such as diazoalkanes, thiocarbonyl S-metha-
diverse ring size. In addition, they are useful starting materials for
reactions with nucleophiles, particularly with Grignard reagents
8
and lithiated organyls. To the best of our knowledge, (3+2)-
1
nides, and nitrones. It is well documented, that they react with
cycloadditions of enantiopure nitrones with thioketones have not
been reported. Thus, in continuation of our studies aimed at the
synthesis and applications of thioketones in organic synthesis9
we became interested in chiral 1,4,2-oxathiazolidines. Herein we
report on the highly stereoselective additions of selected cycloali-
phatic thioketones 1a–d depicted in Figure 1 with a model enan-
1
,3-dipoles yielding the corresponding five-membered sulfur
2
heterocycles. For example, 1,3-dithiolanes, 1,2,4-trithiolanes,
,4,2-dithiazolidines, 1,3-oxathiolanes, and 1,3-thiazolidines are
1
available by (3+2)-cycloaddition reactions, which are believed to
occur via a concerted pathway. However, in recent publications
the reactions of aryl/hetaryl and dihetaryl thioketones with some
diazoalkanes and with thiocarbonyl ylides were shown to proceed
via diradical stepwise mechanisms. Reactions of thioketones with
nitrones have been studied, and 1,4,2-oxathiazolidines are
reported as products formed with complete regioselectivity.
However, this type of products derived from c-aryl/alkyl nitrones
undergo dissociation in solution and form an equilibrium with
tiopure
D-glyceraldehyde and L-erythrose-derived nitrones.
3
2
. Results and discussion
4
–6
For the test experiments with cycloaliphatic thioketones 1,
enantiopure -glyceraldehyde derived nitrone 2 was selected as a
model compound (Fig. 2). In a typical procedure, a solution of
a in THF was added dropwise to a slight excess of 2 (1.1 equiv)
D
1
0
4
a
the starting materials as reported by Black and Watson, and
1
also by Huisgen et al.1a Only in the case of fluorinated nitrones
5
in dry THF, at room temperature, and after only a few minutes,
the characteristic red colour of starting thioketone 1a completely
disappeared indicating the end of reaction. The crude reaction mix-
6
and their analogues bearing a diphenylphosphinoyl moiety was
a remarkable stability of the cycloadducts observed.
1
ture was examined by H NMR which showed two sets of signals
located at 4.33 (dbr, J ꢀ 9.1 Hz) ppm and 4.26 (d, J = 8.7 Hz) ppm
attributed to C(3)-H of the expected 1,4,2-oxathiazolidine products
of type 6 as a diastereomeric mixture in a 96:4 ratio (Scheme 1,
⇑
Corresponding author.
E-mail address: mjasinski@uni.lodz.pl (M. Jasi n´ ski).
http://dx.doi.org/10.1016/j.tetasy.2016.08.007
957-4166/Ó 2016 Elsevier Ltd. All rights reserved.
0

9
74
G. Mlosto n´ et al. / Tetrahedron: Asymmetry 27 (2016) 973–979
values of J = 8.5 Hz (3.95 ppm, for syn-9a), and of J = 9.9 Hz
S
Cl
Cl
(4.10 ppm, for anti-9a) were observed (Fig. 4). As expected for con-
certed processes, no influence of the solvents used on the reaction
outcome could be observed; thus, similar results with respect to
the chemical yield and to the ratio of isomers were noticed for
S
O
S
S
1
a
1b
1c
1d
2 2
the reactions performed at ambient conditions in THF, CH Cl ,
Figure 1. Thioketones 1a–d selected for the study on (3+2)-cycloadditions with
enantiopure nitrones.
and toluene. On the other hand, some impact of the reaction tem-
perature on the diastereomeric ratio was observed. Whereas the
reaction performed in refluxing THF provided anti-/syn-configured
products in 71:29 ratio, slightly enhanced diastereoselectivity
Table 1). Similar excellent facial selectivity (97:3 ratio) was noticed
for the reactions of thioketone 1b and adamantanethione 1c. More-
over, the sterically crowded di-tert-butyl thioketone 1d also pro-
vided the corresponding product, however only in a ca. 3:1 ratio,
after a remarkably longer reaction time of 30 min. It is a rather
unexpected result as this bulky thioketone reacts only with small
(
7
83:17) was observed for the reaction run at ꢁ10 °C (Table 1, entry
).
In continuation, benzaldehyde-derived nitrone 1014 functional-
ized at the N atom with a carbohydrate auxiliary was reacted with
thioketones 1a and 1b to afford the corresponding products 11a
and 11b, respectively, in excellent yield and diastereoselectivity
of >99:1 (Scheme 2). Similar to our previous report on the applica-
tion of the aforementioned nitrone in the synthesis of 1,2-oxazi-
1
,3-dipoles such as diazomethane.11 Major components of the
crude 1,4,2-oxathiazolidines 6a–d were easily separated by stan-
dard column chromatography, and isolated as colourless materials,
fairly stable in the pure state. Although the structure of new
enantiopure 1,4,2-oxathiazolidines 6 were confirmed by NMR
techniques supplemented by MS and elemental analysis, the abso-
lute configurations of the newly generated stereogenic centers
could not be assigned by spectroscopic analysis. Fortunately, the
absolute configuration of anti-6c was confirmed by a single crystal
X-ray structure measurements (Fig. 3). Since characteristic shift
1
5
nes, the signals of the benzylic protons assigned to C(3) of the
1
5
,4,2-oxathiazolidine ring appear as singlets (at 6.03 and
.89 ppm for 11a and 11b, respectively). Hence, due to unhindered
rotation of the auxiliary moiety the absolute configuration could
not be assigned by NOE experiments. Fortunately, the X-ray anal-
ysis of 11a unambiguously indicated the 7(S)-configuration of the
product (Fig. 5). Again, the absolute configuration in dichloro-ana-
logue 11b was assumed based on the characteristic patterns in the
NMR spectra of the series. Finally, the reaction of selected cyclic
1
13
patterns in H and C NMR spectra for both series of diastereoiso-
meric products 6a–d were observed, the anti-configuration of
major components could be assigned as well.
1
6
nitrone 12 with model thioketone 1a was performed to afford
,4,2-oxathiazolidine 13a as sole products in 92% yield. Apparently,
In order to gain more insight into the influence of steric hin-
drance caused by substituents attached to 1,3-dioxolane moiety
1
the presence of the fused 1,3-oxolane moiety in 12 favours exclu-
sive addition of the thioketone from the less hindered back side.
The presence of an uncoupled signal (singlet at 4.91 ppm) in the
H NMR spectrum of 13a, attributed to 3b -H of the polycyclic
skeleton strongly supports the proposed absolute configuration
at the newly generated stereogenic center.
of the nitrone on the stereochemical outcome, a series of
throse-derived nitrones 3–5 was selected for further studies. The
parent -erythrose-derived N-glycosylhydroxylamine, a known
masked nitrone’ 3, was prepared by condensation of the respective
lactol with neat N-benzylhydroxylamine as described. Subse-
quent trapping of the hydroxyl group in 3 under standard silylation
conditions, performed in the presence of DMAP and imidazole,
afforded nitrones 4 and 5 in fair yields of ca. 70%.13 Attempted syn-
thesis of 1,4,2-oxathiazolidine 7a under standard reaction condi-
tions using nitrone 3 and thioketone 1a provided after 30 min a
complex mixture of desired products (anti-/syn-configured prod-
ucts in a 55:45 ratio), contaminated with unconsumed substrates
L-ery-
L
1
0
‘
12
Almost all tested reactions went virtually to completion as evi-
denced by the loss of the coloured thioketone (with the exception
of that with nitrone 3 and 1a), and fairly stable cycloadducts were
1
isolated. However, partial cycloreversion was observed by H NMR
3
for CDCl solutions stored for a longer time at room temperature.
For example, a sample of enantiomerically pure anti-6a reached
equilibrium after 24 h, and the initial mixture of 1,4,2-oxathiazo-
lidines 6a (anti-/syn- 96:4 ratio) accompanied by a small amounts
of the starting materials was formed. Similar monitoring of pure
anti-9a and syn-9a showed, that each of diastereomers provided
the initial mixture of anti-9a/syn-9a (81:19 ratio) after only a few
(
ca. 26%). Neither longer reaction times (up to 24 h at rt) nor
decrease of the reaction temperatures led to completion of the
reaction, which indicates a mismatch of the substrates resulting
in significant shift of the equilibrium towards the reaction part-
ners. In contrast, the reactions of both silylated analogues 4 and
1
a,6
days. By analogy to previous reports,
selected (3+2)-cycloadducts were determined by
spectroscopy and the results are summarized in Table 2. The
collected data for the -glyceraldehyde series revealed, that
adamantane-derived product 6c is more stable than
-oxocyclobutane derivative 6a and its dichloro analogue 6b by
dissociation constants of
5
provided target compounds 8a and 9a in excellent yields
1
H
NMR
(
>97%) and high anti-diastereoselectivity (dr ratio 81:19; Table 1,
entries 6 and 7). Apparently, the steric pressure by cis-substitution
at the backbone 1,3-oxolane moiety of the starting nitrones 4 and 5
has some negative effect on the stereoselectivity. The absolute con-
figurations at the newly generated stereogenic centers in 7–9 was
tentatively assigned based on the NMR spectra; the characteristic
shift patterns of the signals attributed to the 1,4,2-oxathiazolidine
D
3
factors of 3.7 and 2.5, respectively. On the other hand, the
dissociation constant of 6d is two orders of magnitude higher
than those determined for 6a–c. Presumably, the presence of two
tert-butyl groups in 6d favours cycloreversion process due to
and the 1,3-dioxolane moieties nicely matched to those observed
1
for products in
D
-glyceraldehyde series. For example, in the
H
NMR spectra of 9a, the diagnostic shifts and coupling constant
R'
R'
S
1a-d
THF, rt
Bn
N
O
O
O
N
O
O
O
R
O
N
O
N
R
R'
Bn
Bn
S
Bn
R'
OR
2
3 R = H
2-5
6-9
4
5
R = TBS
R = TBDPS
Scheme 1. (3+2)-Cycloadditions of thioketones 1 to nitrones 2–5 leading to 1,4,2-
oxathiazolidine derivatives 6–9.
Figure 2. D-Glyceraldehyde and L-erythrose-derived nitrones 2 and 3–5.

G. Mlosto n´ et al. / Tetrahedron: Asymmetry 27 (2016) 973–979
975
Table 1
Synthesis of 1,4,2-oxathiazolidines 6–9; reaction conditions: thione 1a–d (1.0 mmol), nitrone 2–5 (1.1 mmol), THF, rt, 5–30 min
Entry
anti-/syn-a
Products
Bn
N
Bn
N
O
O
O
O
O
O
S
S
1
96:4
O
O
anti-6a (88%)b
syn-6a (4%)c
Bn
Bn
N
O
O
N
O
O
O
O
Cl
S
Cl
S
2
3
4
97:3
97:3
76:24
Cl
Cl
anti-6b (92%)b
syn-6b (3%)c
Bn
Bn
N
S
O
N
S
O
O
O
O
O
anti-6c (83%)b
syn-6c (3%)c
Bn
Bn
N
S
O
N
S
O
O
O
O
O
anti-6d (11%)b (60%)c
syn-6d (19%)c
Bn
Bn
N
S
O
N
O
O
O
O
O
S
5
6
7
55:45d
O
O
OH
OH
anti-7a (39%)c
syn-7a (32%)
c
Bn
Bn
N
S
O
N
S
O
O
O
O
O
81:19
O
O
O
O
OTBS
anti-8a (51%)b
OTBS
syn-8a (18%)c
Bn
Bn
N
S
O
N
S
O
O
O
O
O
e
7
8
8
1:29
1:19
f
g
OTBDPS
OTBDPS
3:17
anti-9a (74%)b
syn-9a (9%)b
a
b
c
d
e
f
Ratio of anti-/syn-products in a crude reaction mixture.
Yield of isolated purified material.
Yield estimated by 1H NMR spectroscopic analysis of crude reaction mixture.
In an equilibrium with starting materials: 7a:3:1a in ca. 6:1:1 ratio.
THF, reflux, 5 min.
THF, rt, 20 min.
THF, ꢁ10 °C, 30 min.
g
remarkable steric repulsion, which in the case of 6a and 6b is to
some extent overcompensated for by decrease of the cyclobutane
ring strain. Finally, the analysis of Kdiss in 3-oxocyclobutane series
a demonstrate that the stability of (3+2)-cycloadducts follows the
order 6a > 13a > 11a, which very likely relates to increase of the
ring strain in tricyclic system, and to the steric hindrance around
the S,O-acetal group caused by chiral auxiliary, respectively.
with cycloaliphatic thioketones to give 1,4,2-oxathiazolidines with
complete regioselectivity, high yield, and good to excellent
diastereoselectivity. Chromatographic separation of crude prod-
ucts enabled isolation of the major diastereomers, and in two cases,
the absolute configuration at the newly generated stereogenic
centers was unambiguously established by means of single-crystal
X-ray diffraction analysis. Remarkably, isolated products are stable
3
in the pure state, however, in CDCl solutions at room temperature,
an equilibration with starting materials was evidenced. These
enantiomerically pure products are the first examples of chiral
3
. Conclusions
1
,4,2-oxathiazolidines prepared by (3+2)-cycloaddition with
The presented study showed that enantiopure carbohydrate-
derived nitrones smoothly undergo (3+2)-cycloaddition reactions
thioketones, and nicely supplements earlier reports on this topic.

9
76
G. Mlosto n´ et al. / Tetrahedron: Asymmetry 27 (2016) 973–979
Ph
O
O
O
S
1
a,b
O
N
THF, rt
Ph
N
O
O
O
O
10
Cl
O
Cl
(7S)-11a (76%)
(7S)-11b (83%)
H
N
O
O
O
O
1
a
S
O
THF, rt
O
N
O
13a (92%)
12
Scheme 2. Synthesis of 1,4,2-oxathiazolidines (7S)-11a,b and 13a.
Figure 3. A view of the molecular structure of compound anti-6c. Displacement
ellipsoids are drawn at the 50% probability level. X-ray data collected at the
ambient temperature 100 K.
4
4
. Experimental
.1. General
Solvents were purchased and used as received without further
1
0
12
13
14
16
purification. Nitrones 2, 3, 4–5, 10, and 12 were prepared
following the literature reports. 2,2,4,4-Tetramethyl-3-thioxocy-
clobutanone 1a, 3,3-dichloro-2,2,4,4-tetramethylcyclobutanethione
1
b, and adamantanethione 1c were obtained by thionation of the
corresponding ketones with P 10 in pyridine according to litera-
ture; for di(tert-butyl)thioketone 1d a protocol involving reaction
2
S
17
of di(tert-butyl)ketimine lithium salt with CS
2
was applied.1 Prod-
8
ucts were purified by standard chromatography column on silica
gel (230–400 mesh, Merck or Fluka) or by flash chromatography
using Reveleris X2 (Grace) system. Unless stated otherwise, yields
refer to analytically pure samples. NMR spectra were recorded
with Bruker AVIII 600 instrument. Chemical shifts are reported rel-
Figure 5. A view of the molecular structure of compound (7S)-11a. Displacement
ellipsoids are drawn at the 50% probability level. X-ray data collected at the
ambient temperature 293 K.
1
13
ative to solvent residual peaks ( H NMR: d = 7.26 ppm [CDCl
NMR: d = 77.0 ppm [CDCl ]). For detailed peak assignments 2D
spectra were measured (COSY, HMQC, HMBC). IR spectra were
3
];
C
measured with a FTIR NEXUS spectrometer (as KBr pellets or thin
films). MS were performed with a Finnigan MAT-95 or with a
Varian 500-MS LC Ion Trap instruments. Optical rotations were
3
Figure 4. Diagnostic part of the 1H NMR spectra of syn-9a (upper) and anti-9a (bottom).

G. Mlosto n´ et al. / Tetrahedron: Asymmetry 27 (2016) 973–979
977
0
0
0
0
0
Table 2
4.1.3. (4 R,7R)-6-Benzyl-2,2-dichloro-7-(2 ,2 -dimethyl-1 ,3 -di-
a
Dissociation constants of cycloadducts 6a–d, 11a, and 13a
0
oxolan-4 -yl)-1,1,3,3-tetramethyl-5-oxa-8-thia-6-azaspiro[3.4]
octane anti-6b
min; crude product (433 mg, 97%) containing mixture of anti-
and syn-products in a 97:3 ratio, respectively, was purified on
chromatography column (SiO , petroleum ether/EtOAc 15:1) to
give anti-6b (411 mg, 92%) as a colourless solid; mp 111–113 °C;
5
ꢁ1
Entry
Adduct(s)
K
diss ꢂ 10 [mol L
]
5
1
2
3
4
5
6
6a
6b
6c
6d
11a
13a
0.827
0.561
0.223
75.86
24.25
4.784
2
20
1
[
1
a
]
D
= ꢁ80.4 (c 0.86, CHCl
3 3
); H NMR (CDCl , 600 MHz): d = 1.05,
), 1.34, 1.36, 1.42, 1.43 (4 s, 3H each, 1-
), 3.72 (dd, J = 4.8, 8.9 Hz, 1H, 5 -H), 3.96–3.99 (m, 1H,
0
.29 (2 s, 3H each, 2 -Me
2
a
1
Determined by H NMR at 25 °C; initial concentration of starting materials
0
Me
2
, 3-Me
2
ꢁ
1
c = 0.050 mol L
.
0
4
5
7
-H), 3.98 (d, J = 11.9 Hz, 1H, CH
-H), 4.14 (d, J = 11.9 Hz, 1H, CH
.26–7.29, 7.31–7.34, 7.38–7.42 (3 m, 1H, 2H, 2H, Ph) ppm;
2
Ph), 4.03 (dd, J = 6.5, 8.9 Hz, 1H,
Ph), 4.23 (d, J = 9.1 Hz, 1H, 7-H),
0
2
13
C
NMR (CDCl
3
, 151 MHz): d = 23.0, 24.6, 25.4, 28.0 (4 q, 4 Me),
determined with an Anton Paar MCP 500 polarimeter at the tem-
peratures indicated. Elemental analyses were obtained with a
Vario EL III (Elementar Analysensysteme GmbH) instrument. Melt-
ing points were determined in capillaries with a MEL-TEMP II
0
2
6
6.0, 26.6 (2 q, 2 -Me
7.2 (t, C-5 ), 76.0 (d, C-7), 76.8 (d, C-4 ), 98.4 (s, C-2), 105.5 (s,
2
), 59.4, 59.7 (2 s, C-1, C-3), 61.1 (t, CH
2
Ph),
0
0
0
C-4), 110.6 (s, C-2 ), 127.9, 128.4, 129.7, 135.4 (3 d, s, Ph) ppm;
IR (KBr):
m = 3065–2855 (@CAH, CAH), 1450, 1255, 1225, 1145,
apparatus (Aldrich) or with
Opta-Tech), and are uncorrected. Single crystal X-ray data were
collected with a Bruker SMART APEX II CCD diffractometer (Cu K
radiation, k = 1.54178 Å, 30 W Incoatec Microfocus Source I S with
a polarizing optical microscope
ꢁ
1
+
1
9
1
070 (CAO) cm ; ESI-MS (m/z): 447 (21, [M+H] ), 446 (100,
(
+
[
5
M] ); elemental analysis calcd (%) for C21
6.50, H 6.55, N 3.14, S 7.18; found: C 56.36, H 6.65, N 3.07, S 7.31.
Selected data for syn-6b (in a mixture with anti-6b): 1H NMR
CDCl , 600 MHz): d = 1.18, 1.32, 1.38, 1.47 (4 s, 3H each), 3.33
2 3
H29Cl NO S (446.4): C
a
l
Montel optics); the structure solution and refinement was per-
formed by using Shelxs-9720 and Shelxl-2014.
21
(
(
3
0
0
dd, J = 5.6, 8.8 Hz, 1H, 5 -H), 3.77 (dt, J ꢀ 5.9, 8.8 Hz, 1H, 5 -H),
3
.82, 4.01 (2 d, J = 11.7 Hz, 1H each, CH
2
Ph) ppm, other signals
C NMR (CDCl3, 151 MHz):
1
3
4
.1.1. General procedure for the synthesis of 1,4,2-oxathiazolidines
overlap with those of anti-6b;
To a solution of the respective nitrone (1.1 mmol) in dry THF
d = 23.1, 25.0, 25.1, 25.9, 26.7, 28.3 (6 q, 6 Me), 59.6, 59.9 (2 s, C-
1, C-3), 61.5 (t, CH Ph), 67.8 (t, C-5 ), 75.9, 77.3 (2 d, C-7, C-4 ),
), 128.8, 129.1, 129.5,
(
3 mL) a solution of thione 1 (1.0 mmol) in THF (1 mL) was added
dropwise and the stirring was continued at room temperature until
the starting thione was fully consumed (TLC monitoring, SiO , pet-
0
0
2
0
100.0 (s, C-2), 106.7 (s, C-4), 109.6 (s, C-2
135.2 (3 d, s, Ph) ppm.
2
roleum ether/EtOAc 20:1). The solvent was removed under
reduced pressure, and the resulting was filtered through short sil-
0
R,400R)-Spiro{adamantane-2,5
0
0
0
-(200,200-dimethyl-
4.1.4. (3
00 ,300 -dioxolan-400 -yl)-[1,4,2]oxathiazolidine} anti-6c
1
-[2
-benzyl-3
ica gel pad (SiO
2
, hexanes/EtOAc 3:1). Crude 1,4,2-oxathiazolidine
derivative was purified on chromatography column.
20 min; crude product (374 mg, 93%) containing mixture of
anti- and syn-products in a 97:3 ratio, respectively, was purified
on chromatography column (SiO , petroleum ether/EtOAc 20:1)
to give anti-6c (333 mg, 83%) as a colourless solid; mp 89–91 °C;
0
0
0
0
0
0
2
4
1
.1.2. (4 R,7R)-6-Benzyl-7-(2 ,2 -dimethyl-1 ,3 -dioxolan-4 -yl)-
,1,3,3-tetramethyl-5-oxa-8-thia-6-azaspiro[3.4]octan-2-one
20
1
[a
]
D
= ꢁ78.3 (c 0.44, CHCl
3
); H NMR (CDCl
3
, 600 MHz): d = 1.14,
anti-6a
0
0
1
2
5
.30 (2 s, 3H each, 2 -Me
2
), 1.53–1.62, 1.68–1.94, 2.04–2.10 (3 m,
5
min; crude product (377 mg, 96%) containing mixture of anti-
H, 8H, 3H, Ad), 2.23 (m
-H), 4.06 (dd, J = 6.5, 8.9 Hz, 1H, 5 -H), 4.21 (d, J = 13.0 Hz, 1H,
Ph), 4.26 (ddd, J = 5.4, 6.5, 9.1Hz, 1H, 4 -H), 4.33 (d, J = 9.1 Hz,
H, 3 -H), 4.40 (d, J = 13.0 Hz, 1H, CH
.41–7.44 (3 m, 1H, 2H, 2H, Ph) ppm;
51 MHz): d = 25.5, 26.6 (2 q, 2 Me), 26.0, 26.7, 34.1, 34.7, 37.2,
8.0, 38.1, 41.9, 42.2 (2 d, 5 t, 2 d, Ad), 61.8 (t, CH
), 76.91 (d, C-4 ), 76.95 (d, C-3 ), 106.5 (s, spiro-C), 110.5 (s, C-
), 127.3, 128.2, 129.1, 137.2 (3 d, s, Ph) ppm; IR (KBr):
c
, 1H, Ad), 3.72 (dd, J = 5.4, 8.9 Hz, 1H,
and syn-products in a 96:4 ratio, respectively, was purified on
0
0
00
chromatography column (SiO
2
, petroleum ether/EtOAc 10:1) to
0
0
CH
2
2
0
give anti-6a (343 mg, 88%) as a thick colourless oil; [
a
]
D
= ꢁ78.5
0
1
7
1
3
5
2
m
2
Ph), 7.23–7.26, 7.29–7.33,
1
0
(
c 0.88, CHCl
3
); H NMR (CDCl
3
, 600 MHz): d = 1.08 (s, 3H, 2 -Me),
13
3
C NMR (CDCl ,
0
1
.22, 1.24, 1.29, 1.31 (4 s, 3H each, 1-Me
2
, 3-Me
2
), 1.31 (s, 3H, 2 -
0
0
Me), 3.76 (dd, J = 4.6, 8.9 Hz, 1H, 5 -H), 3.97–4.04 (m, 1H, 4 -H),
2
Ph), 67.6 (t, C-
0
4
4
7
.01 (d, J = 11.9 Hz, 1H, CH
.20 (d, J = 11.9 Hz, 1H, CH
.28–7.31, 7.33–7.36, 7.41–7.43 (3 m, 1H, 2H, 2H, Ph) ppm;
2
Ph), 4.07 (dd, J = 6.5, 8.9 Hz, 1H, 5 -H),
0
0
0
0
00
0
2
Ph), 4.33 (dbr, J ꢀ 9.1 Hz, 1H, 7-H),
13
C
= 3085–2860 (@CAH, CAH), 1450, 1370, 1225, 1065 (CAO)
NMR (CDCl
3
, 151 MHz): d = 18.5, 20.5, 22.4, 25.0 (4 q, 4 Me),
ꢁ1
+
+
cm ; ESI-MS (m/z): 424 (100, [M+Na] ), 402 (11, [M] ); elemental
analysis calcd (%) for C23 S (401.6): C 68.79, H 7.78, N 3.49, S
.99; found: C 68.71, H 7.75, N 3.47, S 8.03. Suitable crystals for an
0
2
6
5.4, 26.5 (2 q, 2 -Me
2
), 61.3 (t, CH
2
Ph), 65.5, 66.6 (2 s, C-1, C-3),
H31NO
3
0
0
7.3 (t, C-5 ), 76.2 (d, C-7), 77.1 (d, C-4 ), 103.8 (s, C-4), 110.7 (s,
7
0
C-2 ), 128.0, 128.5, 129.7, 135.4 (3 d, s, Ph), 219.6 (C@O) ppm; IR
X-ray crystal structure determination were obtained from hexane
(
1
film):
070, 1030 (CAO) cm ; ESI-MS (m/z): 414 (100, [M+Na] ); ele-
mental analysis calcd (%) for C21 S (391.5): C 64.42, H
.47, N 3.58, S 8.19; found: C 64.15, H 7.43, N 3.46, S 7.90.
Selected data for syn-6a (in a mixture with anti-6a): 1H NMR
CDCl , 600 MHz): d = 1.24, 1.28, 1.32, 1.33, 1.37 (5 s, 3H each),
m = 3085–2865 (@CAH, CAH), 1790 (C@O), 1455, 1390,
solution by slow evaporation of the solvent.
ꢁ1
+
Selected data for syn-6c (in a mixture with anti-6c): 1H NMR
H29NO
4
0
0
(
CDCl
3
, 600 MHz): d = 1.25, 1.29 (2 s, 3H each, 2 -Me
J = 5.1, 8.8 Hz, 1H, 5 -H), 4.01 (dd, J = 6.2, 8.8 Hz, 1H, 5 -H), 4.13
ddd, J = 5.1, 6.2, 8.7 Hz, 1H, 4 -H) ppm, other signals overlap with
those of anti-6c; C NMR (CDCl
2
), 3.49 (dd,
7
0
0
00
0
0
(
(
3
13
3
, 151 MHz): selected signals
0
0
3
.50 (dd, J = 6.5, 8.8 Hz, 1H, 5 -H), 3.89 (dt, J ꢀ 5.8, 8.8 Hz, 1H, 5 -
Ph), 4.26 (d,
J = 8.7 Hz, 1H, 7-H) ppm, other signals overlap with those of anti-
0
0
0
d = 63.0 (t, CH
2
Ph), 67.8 (t, C-5 ), 77.8 (d, C-3 ), 108.7, 109.5 (2 s,
H), 3.95, 4.12 (2 d, J = 11.7 Hz, 1H each, CH
2
0
0
spiro-C, C-2 ), 127.9, 128.5, 129.3, 136.6 (3 d, s, Ph) ppm.
1
3
6
3
a; C NMR (CDCl , 151 MHz): d = 18.6, 20.8, 22.3, 25.1, 25.2,
0
0
0
0
0
0
4
.1.5. (3R,4 R)-2-Benzyl-3-(2 2 -dimethyl-1 ,3 -dioxolan-4 -yl)-5,
-bis(tert-butyl)-[1,4,2]oxathiazolidine anti-6d
0 min; crude product was filtered through a short silica gel
plug (petroleum ether/EtOAc 10:1) to give 6d (311 mg, 79%) as a
2
6.7 (6 q, 6 Me), 61.5 (t, CH
2
Ph), 65.6, 66.7 (2 s, C-1, C-3), 67.7 (t,
5
0
0
0
C-5 ), 76.1, 77.7 (2 d, C-7, C-4 ), 104.5 (s, C-4), 109.6 (s, C-2 ),
3
1
28.3, 128.8, 129.5, 135.2 (3 d, s, Ph), 219.7 (C@O) ppm.

9
78
G. Mlosto n´ et al. / Tetrahedron: Asymmetry 27 (2016) 973–979
mixture of anti- and syn-products in a 76:24 ratio, respectively.
Attempted separation by standard column chromatography
enabled isolation of a small sample of anti-6d (42 mg, 11%) as a
Selected data for syn-8a (in a mixture with anti-8a): 1H NMR
(CDCl
, 600 MHz): d = ꢁ0.09, ꢁ0.03, 0.82 (3 s, 3H, 3H, 9H, TBS),
3
1.20, 1.28, 1.32, 1.33 (4 s, 3H each, 4 Me), 3.28 (dd, J = 5.7,
2
0
1
0
0
colourless oil; [
a
]
D
= ꢁ41.2 (c 0.23, CHCl
3
); H NMR (CDCl
3
,
11.3 Hz, 1H, 5 -CH
2
O), 3.61 (dd, J = 3.8, 11.3 Hz, 1H, 5 -CH
2
O),
0
6
00 MHz): d = 1.08, 1.16 (2 s, 9H each, 2 tBu), 1.37, 1.46 (2 s, 3H
3.96 (dd, J = 2.4, 5.7 Hz, 1H, 5 -H), 3.97 (d, J = 12.5 Hz, 1H, CH
2
Ph),
0
each,
2
Me), 3.79 (dd, J = 7.2, 8.4 Hz, 1H, 5 -H), 3.85 (d,
4.85 (d, J = 8.6 Hz, 1H, 7-H) ppm, other signals overlap with those
J = 13.8 Hz, 1H, CH
2
0
Ph), 4.06 (d, J = 7.9 Hz, 1H, 3-H), 4.07 (dd,
of anti-8a.
0
J = 6.4, 8.4 Hz, 1H, 5 -H), 4.35 (ddd, J = 6.4, 7.2, 7.9 Hz, 1H, 4 -H),
.56 (d, J = 13.8 Hz, 1H, CH Ph), 7.23–7.27, 7.29–7.32, 7.38–7.41
4
2
4.1.8. Synthesis of 1,4,2-oxathiazolidines 9a
13
(
3 m, 1H, 2H, 2H, Ph) ppm; C NMR (CDCl
3
, 151 MHz): d = 25.7,
20 min; crude products (647 mg, 98%, anti/syn 81:19) were sep-
2
6.7 (2 q, 2 Me), 29.8, 30.5, 43.7, 44.5 (2 q, 2 s, 2 tBu), 61.2 (t, CH
2
-
2
arated by flash chromatography (SiO , petroleum ether/EtOAc
95:5) to give syn-9a (59 mg, 9%, first eluted) and anti-9a (488 mg,
74%, second eluted) as a colourless oils.
0
0
Ph), 68.3 (t, C-5 ), 75.8 (d, C-3), 76.3 (d, C-4 ), 107.4 (s, C-5), 110.2
0
(
s, C-2 ), 126.9, 127.8, 129.7, 137.6 (3 d, s, Ph) ppm; IR (film):
m
= 3080–2865 (@CAH, CAH), 1450, 1370, 1220, 1070 (CAO)
ꢁ
1
+
0
0
0
0
0
cm ; CI-MS (m/z): 394 (71, [M+H] ), 292 (100); elemental analysis
calcd (%) for C22 S (393.2): C 67.14, H 8.96, N 3.56, S 8.15;
4.1.9. (4 S,5 S,7R)-6-Benzyl-7-[2 ,2 -dimethyl-5 -(tert-butyldi-
0
0
0
H35NO
3
methylsiloxymethyl)-1 ,3 -dioxolan-4 -yl]-1,1,3,3-tetramethyl-
found: C 67.13, H 8.93, N 3.45, S 8.08.
5-oxa-8-thia-6-azaspiro[3.4]octan-2-one syn-9a
Selected data for syn-6d (in a mixture with anti-6d): 1H NMR
[
a
]
= ꢁ28.5 (c 0.95, CHCl
1
D
3 3
); H NMR (CDCl , 600 MHz):
(
(
CDCl
3
, 600 MHz): d = 1.05, 1.17 (2 s, 9H each, 2 tBu), 1.25, 1.36
d = 1.02 (s, 9H, tBu), 1.12, 1.23, 1.26, 1.31 (4 s, 3H each, 1-Me
2
, 3-
0
2 s, 3H each, 2 Me), 3.81 (d, J = 13.7 Hz, 1H, CH
2
Ph), 4.15 (dd,
Me
2
), 1.34, 1.42 (2 s, 3H each, 2 -Me
2
), 3.47 (dd, J = 6.1, 11.2 Hz,
0
0
0
J = 6.6, 8.1 Hz, 1H, 5 -H), 4.31–4.35 (m, 2H, 3-H, 5 -H), 4.42 (d,
1H, 5 -CH
11.2 Hz, 1H, 5 -CH
J = 13.3, 1H, CH
2
O), 3.73 (d, J = 13.3, 1H, CH
2
Ph), 3.85 (dd, J = 3.8,
0
0
0
J = 13.7 Hz, 1H, CH
nals overlap with those of anti-6d; C NMR (CDCl
2
Ph), 4.49 (td, J ꢀ 2.9, 7.0 Hz, 1H, 4 -H), other sig-
2
O), 3.95 (dd, J = 6.1, 8.5 Hz, 1H, 4 -H), 3.99 (d,
1
3
0
3
, 151 MHz):
2
Ph), 4.21 (td, J = 3.8, 6.1 Hz, 1H, 5 -H), 4.76 (d,
d = 24.8, 26.2 (2 q, 2 Me), 29.6, 30.4, 43.9, 44.2 (2 q, 2 s, 2 tBu),
J = 8.5 Hz, 1H, 7-H), 7.11–7.15, 7.18–7.21, 7.24–7.29, 7.33–7.36,
0
0
6
1.7 (t, CH
2
Ph), 65.4 (t, C-5 ), 72.8 (d, C-3), 74.6 (d, C-4 ), 106.8 (s,
7.39–7.42, 7.58–7.60, 7.63–7.65 (7 m, 3H, 2H, 2H, 3H, 1H, 2H,
0
13
C-5), 109.1 (s, C-2 ), 127.0, 127.9, 129.4, 137.5 (3 d, s, Ph) ppm.
2H, 3 Ph) ppm; C NMR (CDCl
3
, 151 MHz): d = 18.7, 26.9 (s, q,
0
tBu), 19.2, 20.9, 22.1, 24.9 (4 q, 1-Me
2
2
, 3-Me ), 25.3, 27.7 (2 q, 2 -
0
4
.1.6. Synthesis of 1,4,2-oxathiazolidines 7a
0 min; crude reaction mixture (99% recovery of the mass) was
2
Me ), 61.2 (t, CH
2
Ph), 62.5 (t, 5 -CH
2
O), 65.6, 66.8 (2 s, C-1, C-3),
0
0
3
74.6 (d, C-7), 77.8 (d, C-4 ), 78.2 (d, C-5 ), 104.1 (s, C-4), 108.3 (s,
C-2 ), 127.56, 127.58, 127.7, 128.5, 128.7, 129.63, 129.65, 133.2,
1
0
analyzed by NMR spectroscopy; the H NMR spectrum taken in
CDCl revealed the presence of an equilibrated mixture containing
3
133.5, 135.4, 135.67, 135.71 (7 d, 3 s, 2 d, 3 Ph), 220.2 (s, C@O)
starting materials (1a and 3, ꢃ13% each) and the products anti-7a
and syn-7a (74%, in ca. 55:45 ratio, respectively). Attempted sepa-
ration of the products by chromatography techniques was in vain.
ppm; IR (film):
m = 3070–2860 (@CAH, CAH), 1790 (C@O), 1460,
ꢁ1
1380, 1250, 1215, 1115 (CAO) cm ; ESI-MS (m/z): 682 (100, [M
+
+
+Na] ), 660 (12, [M] ); elemental analysis calcd (%) for C38
5
H49NO -
+
+
+
ESI-MS (m/z): 422 (3, [M+H] ), 266 (54, [Mꢁ1a] ), 91 (100, [Bn] );
SSi (659.3): C 69.16, H 7.48, N 2.12; found: C 69.25, H 7.54, N 1.95.
1
Selected data for anti-7a (in a mixture with syn-7a, 1a, and 3): H
0
0
0
0
0
0
NMR (CDCl
3
, 600 MHz): d = 3.68 (dd, J = 5.3, 12.0 Hz, 1H, 5 -CH
2
O),
4.1.10. (4 S,5 S,7S)-6-Benzyl-7-[2 ,2 -dimethyl-5 -(tert-butyldi-
0
0
0
0
3
.76 (dd, J = 3.9, 12.0 Hz, 1H, 5 -CH
2
O), 4.57 (d, J = 9.8 Hz, 1H, 7-H)
methylsiloxymethyl)-1 ,3 -dioxolan-4 -yl]-1,1,3,3-tetramethyl-
ppm; Selected data for syn-7a (in a mixture with anti-7a, 1a, and
5-oxa-8-thia-6-azaspiro[3.4]octan-2-one anti-9a
[a] = +19.6 (c 1.00, CHCl ); H NMR (CDCl , 600 MHz): d = 1.00
D 3 3
(s, 9H, tBu), 1.20, 1.22, 1.27, 1.30 (4 s, 3H each, 1-Me
1
20
1
3
5
): H NMR (CDCl
3
, 600 MHz): d = 2.94 (dd, J = 6.7, 11.9 Hz, 1H,
0
0
2
-CH O), 3.24 (dd, J = 4.8, 11.9 Hz, 1H, 5 -CH
2
O), 4.71 (d,
2
, 3-Me
2
), 1.21,
0
0
J = 10.0 Hz, 1H, 7-H) ppm.
1.34 (2 s, 3H each, 2 -Me
2
), 3.69 (dd, J = 3.7, 11.5 Hz, 1H, 5 -CH
2
O),
0
3
.75 (dd, J = 5.3, 11.5 Hz, 1H, 5 -CH
2
O), 4.10 (dd, J = 5.9, 9.9 Hz, 1H,
0
0
0
0
0
0
0
4
.1.7. (4 S,5 S,7S)-6-Benzyl-7-[2 ,2 -dimethyl-5 -(tert-butyldimethyl-
4 -H), 4.14 (ddd, J = 3.7, 5.3, 5.9 Hz, 1H, 5 -H), 4.14, 4.18 (d,
J = 12.2 Hz, 1H each, CH Ph), 4.74 (d, J = 9.9 Hz, 1H, 7-H), 7.27–
7.32, 7.33–7.44, 7.61–7.63, 7.68–7.70 (4 m, 3H, 8H, 2H, 2H, 3 Ph)
0
0
0
siloxymethyl)-1 ,3 -dioxolan-4 -yl]-1,1,3,3-tetramethyl-5-oxa-8-
2
thia-6-azaspiro[3.4]octan-2-one anti-8a
1
3
2
0 min; crude reaction mixture was filtered through short silica
gel plug (CH Cl ) and the solvents were removed to give 8a
520 mg, 97%) as a mixture of anti- and syn-products in a 81:19
ratio, respectively. Major product anti-8a (273 mg, 51%) was iso-
lated by column chromatography (SiO , petroleum ether/Et
ppm; C NMR (CDCl
3
, 151 MHz): d = 18.6, 26.8 (s, q, tBu), 19.1,
0
2
2
20.4, 22.2, 25.2 (4 q, 1-Me
2
, 3-Me
2
), 25.5, 27.6 (2 q, 2 -Me
2
), 61.2
0
(
(t, CH
2
Ph), 62.6 (t, 5 -CH
2
O), 65.2, 66.6 (2 s, C-1, C-3), 72.6 (d, C-
0
0
0
7), 77.3 (d, C-5 ), 78.6 (d, C-4 ), 102.2 (s, C-4), 108.9 (s, C-2 ),
127.6, 127.7, 127.8, 128.4, 129.5, 129.6, 129.7, 132.9, 133.0,
135.70, 135.73, 135.75 (7 d, 2 s, d, s, d, 3 Ph), 220.0 (s, C@O)
2
2
O
2
0
5
CHCl
3
:1) as a colourless solid; mp 66–68 °C; [
a]
D
= +56.7 (c 0.55,
1
3
); H NMR (CDCl
3
, 600 MHz): d = ꢁ0.05, ꢁ0.02, 0.84 (3 s,
ppm; IR (film):
m = 3075–2850 (@CAH, CAH), 1785 (C@O), 1460,
ꢁ1
H, 3H, 9H, TBS), 1.22, 1.23, 1.26, 1.28, 1.30, 1.34 (6 s, 3H each, 6
1380, 1250, 1220, 1215, 1115, 1080 (CAO) cm ; ESI-MS (m/z):
682 (100, [M+Na] ); elemental analysis calcd (%) for C38H49NO SSi
5
0
0
0
+
Me), 3.67–3.73 (m, 2H, 5 -CH
2
O), 4.05–4.11 (m, 3H, 4 -H, 5 -H, CH
2
-
Ph), 4.19 (d, J = 12.1 Hz, 1H, CH
2
Ph), 4.67 (d, J = 9.5 Hz, 1H, 7-H),
(659.3): C 69.16, H 7.48, N 2.12, S 4.26; found: C 69.04, H 7.49, N
2.10, S 4.15.
13
7
1
1
3
.25–7.32, 7.39–7.42 (2 m, 3H, 2H, Ph) ppm; C NMR (CDCl ,
51 MHz): d = ꢁ5.6, ꢁ5.4 (2 q, 2 Me, TBS), 18.3, 25.9 (s, q, tBu),
0
0
0
0
0
8.7, 20.5, 22.1, 25.2, 25.6, 27.6 (6 q, 6 Me), 61.0 (t, CH
2
Ph), 61.7
4.1.11. (3a S,4 S,6a S,7S)-6-(2 ,2 -Dimethyltetrahydrofuro[3,4-d]
0
0
(
t, 5 -CH
2
O), 65.3, 66.6 (2 s, C-1, C-3), 72.6 (d, C-7), 77.3, 78.5 (2
[1,3]dioxol-4 -yl)-1,1,3,3-tetramethyl-7-phenyl-5-oxa-8-thia-6-
0
0
0
d, C-4 , C-5 ), 102.2 (s, C-4), 108.7 (s, C-2 ), 127.8, 128.4, 129.5,
35.7 (3 d, s, Ph), 220.1 (s, C@O) ppm; IR (KBr): = 3060–2855
@CAH, CAH), 1790 (C@O), 1250, 1145, 1030 (CAO) cm ; ESI-
azaspiro[3.4]octan-2-one (7S)-11a
1
(
m
10 min; crude product (7S/7R >99:1) was filtered through short
ꢁ1
silica gel plug (petroleum ether/EtOAc 15:1) to give (7S)-11a
+
+
20
MS (m/z): 537 (42, [M+H] ), 536 (100, [M] ); elemental analysis
calcd (%) for C28 SSi (535.8): C 62.76, H 8.47, N 2.61, S
.98; found: C 62.53, H 8.43, N 2.73, S 5.81.
(319 mg, 76%) as a colourless solid; mp 115–116 °C; [
a]
D
= ꢁ54.5
1
H45NO
5
(c 0.78, CHCl
3
); H NMR (CDCl
3
, 600 MHz): d = 0.84, 0.92, 1.26,
5
1.36 (4 s, 3H each, 1-Me
2 2
, 3-Me ), 1.36, 1.50 (2 s, 3H each,

G. Mlosto n´ et al. / Tetrahedron: Asymmetry 27 (2016) 973–979
979
0
0
0
2
-Me
2
), 4.00–4.04 (m, 2H, 6 -H
2
), 4.71 (s, 1H, 4 -H), 4.93 (dd,
References
0
0
J = 3.2, 6.1 Hz, 1H, 6a -H), 5.13 (d, J = 6.1 Hz, 1H, 3a -H), 6.03 (s,
1.
(a) Huisgen, R.; Fišera, L.; Giera, H.; Sustmann, R. J. Am. Chem. Soc. 1995, 117,
9671–9678; (b) Huisgen, R.; Rapp, J. Tetrahedron 1997, 53, 939–960; (c)
Huisgen, R.; Langhals, E. Tetrahedron Lett. 1989, 30, 5369–5372; (d) Huisgen, R.;
Li, X.; Giera, H.; Langhals, E. Helv. Chim. Acta 2001, 84, 981–999; (e) Huisgen, R.;
Langhals, E. Heteroatom. Chem. 2006, 17, 433–442.
1
H, 7-H), 7.23–7.27, 7.30–7.34, 7.47–7.49 (3 m, 1H, 2H, 2H, Ph)
1
3
ppm; C NMR (CDCl
3
, 151 MHz): d = 18.3, 20.1, 22.6, 24.5 (4 q,
), 24.9, 26.3 (2 q, 2 -Me
0
1
7
-Me
2
, 3-Me
2
2
), 64.9, 67.1 (2 s, C-1, C-3),
0
0
0
2.3 (d, C-7), 74.1 (t, C-6 ), 80.4 (d, C-6a ), 83.5 (d, C-3a ), 96.8 (d,
0
0
2. (a) Fišera, L.; Huisgen, R.; Kalwinsch, I.; Langhals, E.; Li, X.; Mlosto n´ , G.; Polborn,
K.; Rapp, J.; Sicking, W.; Sustmann, R. Pure Appl. Chem. 1996, 68, 789–798; (b)
Mlosto n´ , G.; Heimgartner, H. In Synthetic Applications of 1,3-Dipolar
Cycloaddition Chemistry Toward Heterocycles and Natural Products; Padwa, A.,
Pearson, W. H., Eds.; Wiley: New York, 2002; pp 315–360; (c) Mlosto n´ , G.;
Heimgartner, H. In Targets in Heterocyclic Systems; Attanasi, O. A., Spinelli, D.,
Eds.; Italian Society of Chemistry, 2006; Vol. 10, pp 266–300; (d) Verani, G.;
Garau, A. Chalcogene C = E compounds (E = S, Se, Te) In Handbook of Chalcogen
Chemistry, New Perspectives in Sulfur, Selenium and Tellurium; Devillanova, F. A.,
du Mont, W.-W., Eds.; The Royal Society of Chemistry: Dorchester, 2013; Vol. 1,
pp 123–136. Chapter 2.3.
C-4 ), 104.4 (s, C-4), 112.3 (s, C-2 ), 127.0, 127.7, 128.1, 140.0 (3
d, s, Ph), 220.1 (s, C@O) ppm; IR (KBr): = 3090–2880 (@CAH,
CAH), 1795 (C@O), 1455, 1380, 1210, 1095, 1050, 1035 (CAO)
cm ; ESI-MS (m/z): 442 (100, [M+Na] ); elemental analysis calcd
%) for C22 S (419.2): C 62.98, H 6.97, N 3.34, S 7.64; found:
C 62.85, H 6.97, N 3.26, S 7.46. Suitable crystals for an X-ray crystal
structure determination were obtained from petroleum ether solu-
tion by slow evaporation of the solvent.
m
ꢁ1
+
(
H29NO
5
3
.
(a) Mlosto n´ , G.; Pipiak, P.; Heimgartner, H. Beilstein J. Org. Chem. 2016, 12, 716–
724; (b) Mlosto n´ , G.; Hamera-Fałdyga, R.; Linden, A.; Heimgartner, H. Beilstein J.
Org. Chem. 2016, 12, 1421–1427.
(a) Black, D. S. C.; Watson, K. G. Aust. J. Chem. 1973, 26, 2491–2504; (b) Giera,
H.; Huisgen, R. Liebigs Ann. Recueil 1997, 1685–1689. For the reactions of
nitrones with thioaldehydes, see; (c) Schaumann, E.; Ruhter, G. Tetrahedron
Lett. 1985, 26, 5265–5268. For the reactions of nitrones with bis
0
0
0
0
0
4
[
.1.12. (3a S,4 S,6a S,7S)-6-(2 ,2 -Dimethyltetrahydrofuro[3,4-d]
0
1,3]dioxol-4 -yl)-1,1,3,3-tetramethyl-7-phenyl-5-oxa-8-thia-6-
4.
azaspiro[3.4]octan-2-one (7S)-11b
0 min; crude product (7S/7R >99:1) was filtered through short
silica gel plug (petroleum ether/EtOAc 15:1) to give (7S)-11b
394 mg, 83%) as a colourless solid; mp 129–131 °C; [
c 0.80, CHCl
1
(
trifluoromethyl)thioketene, see; (d) Raasch, M. S. J. Org. Chem. 1970, 35,
2
0
(
(
1
Me
6
a]
D
= ꢁ58.5
3470–3483. for the reaction of thioketones with nitronates, see; (e) Vedejs, E.;
Perry, D. A. J. Org. Chem. 1984, 49, 575–576.
1
3
); H NMR (CDCl
3
, 600 MHz): d = 0.90, 1.10, 1.40,
), 1.37, 1.50 (2 s, 3H each, 2 -
0
5. (a) Mlosto n´ , G.; Obijalska, E.; Celeda, M.; Mittermeier, V.; Linden, A.;
Heimgartner, H. J. Fluorine Chem. 2014, 165, 27–32; (b) Emamian, S. RSC Adv.
2015, 5, 72959–72970.
6. Shioji, K.; Mastumoto, A.; Takao, M.; Kurauchi, Y.; Shigetomi, T.; Yokomori, Y.;
Okuma, K. Bull. Chem. Soc. Jpn. 2007, 80, 743–746.
.49 (4 s, 3H each, 1-Me , 3-Me
2
2
0
0
2
), 4.01 (m
c
, 2H, 6 -H
2
), 4.62 (s, 1H, 4 -H), 4.91-4.93 (m, 1H,
0
0
a -H), 5.11 (dbr, J ꢀ 6.1 Hz, 1H, 3a -H), 5.89 (s, 1H, 7-H), 7.23–
1
3
7
.26, 7.29–7.32, 7.42–7.45 (3 m, 1H, 2H, 2H, Ph) ppm; C NMR
7.
(a) Koumbis, A. E.; Gallos, J. K. Curr. Org. Chem. 2003, 7, 771–797; b) Fišera, L.
Top. Heterocycl. Chem. 2007, 7, 287–323; (c) Grigorev, I. A. Nitrones: Novel
Strategies in Synthesis. In Nitrile Oxides Nitrones and Nitronates in Organic
Synthesis; Feuer, H., Ed.; John Wiley & Sons: Hoboken, 2008; pp 129–434; (d)
Stecko, S.; Pieczykolan, M.; Ulikowski, A.; Kabala, K.; Wołosewicz, K.; Maciejko,
M.; Grzeszczyk, B.; Jurczak, M.; Chmielewski, M.; Furman, B. Curr. Org. Chem.
2014, 18, 1716–1730.
(
CDCl
3
, 151 MHz): d = 22.5, 26.3, 26.8, 27.5 (4 q, 1-Me
4.0, 25.0 (2 q, 2 -Me
4.2 (t, C-6 ), 80.6 (d, C-6a ), 83.1 (d, C-3a ), 96.9 (d, C-4 ), 98.7 (s,
C-2), 106.1 (s, C-4), 112.3 (s, C-2 ), 127.1, 127.8, 128.2, 139.6 (3 d,
2
, 3-Me
2
),
0
2
7
2
), 58.9, 60.4 (2 s, C-1, C-3), 72.1 (d, C-7),
0
0
0
0
0
s, Ph) ppm; IR (KBr):
m
= 3085–2870 (@CAH, CAH), 1380, 1210,
ꢁ
1
+
8. (a) Merino, P.; Castillo, E.; Franco, S.; Merchan, F. L.; Tejero, T. Tetrahedron:
Asymmetry 1998, 9, 1759–1769; (b) De Risi, C.; Dondoni, A.; Perrone, D.; Pollini,
G. P. Tetrahedron Lett. 2001, 42, 3033–3036; (c) Toyao, A.; Tamura, O.; Takagi,
H.; Ishibashi, H. Synlett 2003, 35–38; (d) Marradi, M.; Cicchi, S.; Delso, J. I.; Rosi,
L.; Tejero, T.; Merino, P.; Goti, A. Tetrahedron Lett. 2005, 46, 1287–1290; (e)
Helms, M.; Schade, W.; Pulz, R.; Watanabe, T.; Al-Harrasi, A.; Fišera, L.;
Hlobilová, I.; Zahn, G.; Reissig, H.-U. Eur. J. Org. Chem. 2005, 1003–1019.
9. (a) Gebert, A.; Jasi n´ ski, M.; Mlosto n´ , G.; Heimgartner, H. Helv. Chim. Acta 2014,
97, 931–938; (b) Jasi n´ ski, M.; Mlosto n´ , G.; Stolarski, M.; Costa, W.; Domínguez,
M.; Reissig, H.-U. Chem. Asian J. 2014, 9, 2641–2648; (c) Mlosto n´ , G.; Pipiak, P.;
Linden, A.; Heimgartner, H. Helv. Chim. Acta 2015, 98, 462–473; (d) Mlosto n´ , G.;
Urbaniak, K.; Pawlak, A.; Heimgartner, H. Heterocycles 2016, 93. http://dx.doi.
org/10.3987/COM-15-S(T)8.
1
(
(
2
095, 1055 (CAO) cm ; ESI-MS (m/z): 497 (13, [M+Na] ), 474
+
100, [M] ); elemental analysis calcd (%) for
474.4): C 55.69, H 6.16, N 2.95, S 6.76; found: C 55.70, H 6.35, N
22 2 4
C H29Cl NO S
.75, S 6.97.
0
0
0
4
.1.13. (3a S,3b R,7a S)-Spiro[(1,1,3,3-tetramethyl-2-oxocyclo-
0
0
0
0
0
0
0
butane)-4,5 -[2 ,2 -dimethyl-tetrahydro-1 ,3 ,6 -trioxa-4 -thia-
a -azacyclopenta[a]pentalene] 13a
5 min; crude product was purified by column on silica gel
petroleum ether/EtOAc 6:1) to give 13a (288 mg, 92%) as a single
0
6
1
(
2
0
10. Merino, P.; Franco, S.; Merchan, F.; Tejero, T. Tetrahedron: Asymmetry 1997, 8,
diastereoisomer; colourless solid; mp 45–47 °C; [
a]
D
= +118.0 (c
3489–3496.
1
0
.62, CHCl
3
); H NMR (CDCl
3
, 600 MHz): d = 1.24, 1.26, 1.27 (3 s,
1
1. (a) Mlosto n´ , G.; Huisgen, R. Tetrahedron Lett. 1989, 30, 7045–7048; (b) Huisgen,
R.; Mlosto n´ , G.; Giera, H.; Langhals, E.; Polborn, K.; Sustmann, R. Eur. J. Org.
Chem. 2005, 1519–1531.
2. Dondoni, A.; Giovannini, P. P.; Perrone, D. J. Org. Chem. 2002, 67, 7203–7214.
3. Maciaszczyk, J.; Jasi n´ ski, M. Tetrahedron: Asymmetry 2015, 26, 510–515.
0
6
H, 3H, 3H, 4 Me), 1.32, 1.52 (2 s, 3H each, 2 -Me
2
), 3.28 (dd,
0
0
J = 5.1, 11.4 Hz, 1H, 7 -H), 3.47 (dbr, J ꢀ 11.4 Hz, 1H, 7 -H), 4.80
1
1
0
0
(
d
br, J ꢀ 6.6 Hz, 1H, 3a -H), 4.91 (pseudo-t, J ꢀ 6.4 Hz, 1H, 7a -H),
0
13
4
2
6
.91 (s, 1H, 3b -H) ppm; C NMR (CDCl
3
, 151 MHz): d = 19.0,
14. Cicchi, S.; Marradi, M.; Goti, A.; Brandi, A. Tetrahedron Lett. 2001, 42, 6503–
0
0
6505.
0.0, 23.0, 24.0 (4 q, 4 Me), 24.9, 26.4 (2 q, 2 -Me
4.6, 67.4 (2 s, C-1, C-3), 78.6 (d, C-7a ), 80.1 (d, C-3b ), 80.9 (d,
2
), 59.7 (t, C-7 ),
1
1
5. Jasi n´ ski, M.; Lentz, D.; Reissig, H.-U. Beilstein J. Org. Chem. 2012, 8, 662–674.
6. Cicchi, S.; Marradi, M.; Vogel, P.; Goti, A. J. Org. Chem. 2006, 71, 1614–1619.
0
0
0
0
C-3a ), 104.8 (s, spiro-C), 112.3 (s, C-2 ), 219.3 (s, C@O) ppm; IR
KBr): = 2990–2860 (@CAH, CAH), 1780 (C@O), 1460, 1380,
205, 1060, 1030, 1010 (CAO) cm ; CI-MS (m/z): 314 (2, [M
H] ), 158 (100), 142 (36); elemental analysis calcd (%) for
S (313.1): C 57.48, H 7.40, N 4.47, S 10.23; found: C
7.54, H 7.48, N 4.46, S 10.21.
17. (a) Greidanus, J. W. Can. J. Chem. 1970, 48, 3530–3536; (b) Mlosto n´ , G.;
Majchrzak, A.; Rutkowska, M.; Wo z´ nicka, M.; Linden, A.; Heimgartner, H. Helv.
Chim. Acta 2005, 88, 2624–2636.
8. Barton, D. H. R.; Guziec, F. S.; Shahak, J. J. Chem. Soc., Perkin Trans. 1 1974, 1794–
1799.
9. CCDC-1471383 (anti-6c) and CCDC-1471385 ((7S)-11a) contains the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from the Cambridge Crystallographic Data Centre via
http://www.ccdc.cam.ac.uk/data_request/cif.
(
1
+
C
m
ꢁ1
1
+
1
15 4
H23NO
5
Acknowledgements
20. Sheldrick, G. M. Acta Cryst. A 2008, 64, 112–122.
1. Sheldrick, G. M. Acta Cryst. C 2015, 71, 3–8.
2
Support of this work by the National Science Center, Cracow,
Poland, in the framework of the Maestro grant (project number
2
012/06A/ST5/00219) is gratefully acknowledged.