New highly efficient aziridine-functionalized tridentate sulfinyl catalysts for enantioselective diethylzinc addition to carbonyl compounds

Article abstract of DOI:10.1016/j.tetasy.2009.09.012

New tridentate enantiomerically pure heteroorganic catalysts, containing hydroxyl, sulfinyl, and aziridine moieties, have proven to be highly efficient in the enantioselective diethylzinc addition to aryl and alkyl aldehydes to give the desired products in very high yields (up to 99%) and with ee's up to 97%. The influence of the stereogenic centers located on the sulfinyl sulfur atom and in the aziridine moiety on the stereochemical course of the reaction are discussed.

Full text of DOI:10.1016/j.tetasy.2009.09.012

Tetrahedron: Asymmetry 20 (2009) 2311–2314
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
New highly efficient aziridine-functionalized tridentate sulfinyl catalysts
for enantioselective diethylzinc addition to carbonyl compounds
a,
a,b
a
b,
*
*
´
´
Stanisław Lesniak , Michał Rachwalski , Ewelina Sznajder , Piotr Kiełbasinski
a
´
´
Department of Organic and Applied Chemistry, University of Łódz, Narutowicza 68, 90-131 Łódz, Poland
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Heteroorganic Chemistry, Sienkiewicza 112, 90-363 Łódz, Poland
b
´
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 June 2009
Revised 7 September 2009
Accepted 10 September 2009
Available online 28 October 2009
New tridentate enantiomerically pure heteroorganic catalysts, containing hydroxyl, sulfinyl, and aziri-
dine moieties, have proven to be highly efficient in the enantioselective diethylzinc addition to aryl
and alkyl aldehydes to give the desired products in very high yields (up to 99%) and with ee’s up to
97%. The influence of the stereogenic centers located on the sulfinyl sulfur atom and in the aziridine moi-
ety on the stereochemical course of the reaction are discussed.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
by attaching an enantiomeric amine.6 However, the newly synthe-
sized ligands, containing chiral open-chain amines turned out to be
The asymmetric diethylzinc addition to aldehydes is one of the
most intensely investigated reactions leading to the formation of
C–C bonds and serves as a test model for newly developed cata-
lysts. Although over 20 years have already passed since the first re-
port on the asymmetric addition of diethylzinc to benzaldehyde in
the presence of leucinol, the search for new catalysts for this reac-
tion still continues. The last comprehensive overview in this field
was in 2001,1 and has been followed by a number of new original
reports. An inspection of the types of compounds that exhibit the
best catalytic activity in this reaction clearly shows that the most
efficient are chiral aminoalcohols. In most cases the stereogenic
centers, which serve as a source of chirality, are located on carbon
atoms, or the catalyst molecule is built on the basis of an axially
chiral substrate. Although the stereogenic sulfinyl moiety is known
to exert high asymmetric induction,2 particularly when used as a
chiral auxiliary, only a few catalysts have been used, which possess
a stereogenic center located on the sulfur.3–5 Moreover, in those
cases only hydroxy sulfoximines3 and hydroxy sulfoxides4,5 were
applied and proved to be rather poor catalysts.
quite inefficient as catalysts and led to the product of the diethyl-
zinc addition to benzaldehyde in yields of up to 55% and with ee’s
not exceeding 50%.6
In order to improve the efficiency of those catalysts via the
introduction of other types of chiral amines, we turned our atten-
tion to enantiomeric aziridines, which are readily available from
the corresponding amino alcohols obtained, in turn, by reduction
of the appropriate natural aminoacids or their opposite enantio-
mers.7 It is noteworthy that variously substituted aziridines have
already been found to be very good catalysts for the title reac-
tion.8–13 Moreover, aziridines are known to efficiently coordinate
organozinc compounds.14–16 Therefore, we decided to apply the
methodology developed by us earlier6 to the synthesis of the
new type of sulfinyl catalyst containing achiral and chiral
aziridines.
2. Results and discussion
2.1. Synthesis of tridentate catalysts from monoacetate 1
Taking into account the findings that amino alcohols were the
most efficient catalysts for this type of reaction, we decided to con-
struct molecules which would have the structure of amino alcohols
and bear an additional stereogenic sulfinyl group. To this end, we
have recently synthesized a series of tridentate ligands, containing
hydroxyl, sulfinyl, and amine moieties, via an enzyme-promoted
desymmetrization of a prochiral bis-hydroxy sulfoxide, followed
The synthesis of tridentate catalysts 4a–d comprised of three
steps (Scheme 1). First, enantiomerically pure monoacetate 1 was
mesylated with methanesulfonic anhydride in dichloromethane
in the presence of triethylamine to form the mesyl derivative 2
in quantitative yield.6 Mesylate 2 was then reacted with a series
of enantiomerically pure aziridines7 in chloroform in the presence
of triethylamine leading to the products 3a–d in chemical yields of
80–92%. Finally, the crude compounds 3a–d were subjected to
deacetylation with sodium methoxide in methanol to give prod-
ucts 4a–d in yields 90–95%. The results are shown in Table 1.
* Corresponding authors. Tel.: +48 42 6355765; fax: +48 42 6655162 (S.L.), tel.:
+48 42 6815832; fax: +48 42 6803260 (P.K.).
E-mail addresses: slesniak@chemul.uni.lodz.pl (S. Les´niak), piokiel@bilbo.
cbmm.lodz.pl (P. Kiełbasin´ ski).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.09.012

´
S. Lesniak et al. / Tetrahedron: Asymmetry 20 (2009) 2311–2314
2312
AcO
OSO2Me
AcO
OH
O
O
S
S
(MeSO2)2O
Et3N, CH2Cl2, rt
(+)-(R)-1
R1
R2
(+)-(S)-2
R1
N
HO
R1
N
AcO
N
H
O
R2
O
R2
MeONa/MeOH
S
S
Et3N, CHCl3, rt
3
4
Aziridines
Pri
Me
Me
H
Me
H
Pri
N
H
H
N
N
H
N
H
H
c
a
d
b
Scheme 1. Synthesis of chiral aziridine-substituted tridentate catalysts.
Table 1
Synthesis of products 3 and 4
Entry
Aziridine
Products 3
Products 4
R1
R2
Yield (%)
Yield (%)
[a
]
D
Absolute configuration
a
Symbol
1
2
3
4
a
b
c
Me
i-Pr
H
Me
H
i-Pr
H
80
90
88
92
95
93
91
90
À1.8
+2.3
À2.0
+3.5
(RS)
(RSSC)
(RSRC)
(RSSC)
d
Me
a
In chloroform (c 1).
2.2. The use of catalysts 4 in the asymmetric addition of
diethylzinc to aldehydes
mode of chelation of diethylzinc must be different in each catalyst
type. Thus, the aziridine moiety must coordinate diethylzinc much
more strongly than the open-chain amine fragment, simulta-
neously lowering the involvement of the hydroxy group, yet coop-
erating with the sulfinyl part of the catalyst molecule. This is in
agreement with the next results, in which two diastereomeric cat-
alysts 4b and 4c, constructed from opposite enantiomers of 2-iso-
propylaziridine, lead to the formation of the opposite enantiomers
of alcohols 5 with high enantiomeric excess. The small differences
in their ee values may be explained in terms of ‘match’ and ‘mis-
match’ interactions with the stereogenic sulfinyl center. Interest-
ingly, the original aziridines, when deprived of the sufinyl and
hydroxy moieties, did not catalyze the title reaction at all.
Optically active compounds 4a–d constitute enantiomerically
pure diastereomeric tridentate ligands/catalysts, and their three
nucleophilic centers can bind organometallic reagents in a stereo-
selective manner. Therefore, it seemed reasonable to assume that
they would effectively catalyze the asymmetric addition of diethyl-
zinc to aldehydes (Scheme 2). The results are shown in Table 2.
Inspection of Table 2 reveals several interesting findings. First,
the formation of enantiomerically enriched alcohols 5 in the pres-
ence of the catalyst 4a, containing achiral 2,2-dimethylaziridine,
means that the stereogenic sulfinyl moiety must exert asymmetric
induction (though moderate), since it is the sole source of chirality
in this catalyst (entries 1, 5 and 9). However, if compared with the
catalysts containing open-chain amine moieties described previ-
ously,6 catalyst 4a leads to the formation of the opposite enantio-
mer of the product 5 (R = Ph). This allows us to conclude that the
When considering the unusual ability of the aziridine ring to ex-
ert the observed high asymmetric induction, it seems reasonable to
take into account its capability of forming relatively stable inver-
tomers. Thus, although the inversion process is very fast for simple
amines, it is much slower in aziridines,17 whose invertomers can in
certain cases be even physically separated.18 The inversion barrier
for aziridine is
DG
# = 17.2 kcal/mol.19 Interestingly, in the case of
H
the adducts containing the 2,2-dimethylaziridine ring (both ligand
4a and its O-acetyl precursor 3a), their 1H and 13C NMR spectra
clearly indicate the presence of both invertomers: a high inversion
barrier around the nitrogen atom causes non-equivalence of both
the methyl groups and the ring hydrogen atoms (see Section 4).
A similar phenomenon has already been reported.20 However, in
case of the adducts containing 2-monosubstituted aziridine rings
OH
Et
O
C
catalyst
4
R
Et2Zn
+
benzene
R
H
5
Scheme 2. Asymmetric addition of diethylzinc to aldehydes.

´
2313
S. Lesniak et al. / Tetrahedron: Asymmetry 20 (2009) 2311–2314
Table 2
Asymmetric addition of diethylzinc to aldehydes in the presence of 4
Entry
R
Catalyst
Alcohol 5
eeb (%)
a
Yield (%)
[a
]
D
Absolute configuration
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
4a
4b
4c
4d
4a
4b
4c
4d
4a
4b
4c
4d
50
99
99
95
46
94
95
92
40
89
87
84
À22
50
97
93
94
48
96
96
92
45
90
90
82
(S)
(S)
(R)
(S)
(S)
(S)
(R)
(S)
(S)
(S)
(R)
(S)
À45.7
+44.0
À44.2
À25.1
À50.4
+50.4
À48.1
+3.2
2-MeOC6H4
2-MeOC6H4
2-MeOC6H4
2-MeOC6H4
n-Pr
n-Pr
n-Pr
n-Pr
10
11
12
+6.4
À6.4
+5.8
a
In chloroform (c 1).
Determined using chiral HPLC.
b
3b–d and 4b–d the inversion barrier is not that high; hence, the
presence of both invertomers is not so clearly observable. More-
over, the pyramidal inversion at the aziridine nitrogen can be
halted by metal complexation, for example, by zinc.21 This may re-
sult in the stereoinduced formation of an additional stereogenic
center on nitrogen, enhancing the stereoselectivity of the diethyl-
zinc addition to carbonyl compounds. The work aimed at the isola-
tion and determination of the structure of zinc complexes with
ligands 4, which could allow us to gain more information in this
matter, are currently in progress in our laboratories.
2 h. After this time, water was added and both phases were sepa-
rated. The aqueous phase was extracted with dichloromethane
(3Â). After drying over anhydrous magnesium sulfate and evapora-
tion of solvent, the mesyl derivative 2 was obtained (1.257 g, 100%,
[a]
D = +12.4). 1H NMR (CDCl3): d = 1.93 (s, 3H), 2.92 (s, 3H), 5.33
(AB, 2H), 5.47 (s, 2H), 7.59–7.86 (m, 8H). MS (CI): m/z 383
(M+H). HRMS (CI) calcd for C17H19O6S2: 383.4512; found 383.4587.
Mesylate 2 (0.5 mmol) was dissolved in chloroform (10 mL) and
triethylamine (0.5 mmol) and corresponding aziridine (0.5 mmol)
was added. The mixture was stirred at room temperature for
72 h. After this time chloroform was evaporated and the residue
was purified via preparative TLC (chloroform/methanol 20:1) to
give derivatives 3a–d. Their chemical purity was determined on
the basis of TLC, 1H NMR, and 13C NMR spectra. They were sub-
jected to ensuing deacetylation without further analysis and
purification.
3. Conclusions
The chiral tridentate ligands, containing two stereogenic cen-
ters, one located on the sulfinyl sulfur atom, the other on the car-
bon atom in the aziridine moiety, were found to be very efficient
catalysts for the enantioselective diethylzinc addition to alde-
hydes. Each enantiomer of the product may be obtained by using
easily available diastereomeric ligands. The stereogenic centers lo-
cated on the aziridine moieties exerted a decisive influence on the
absolute configuration of the products. However, the influence of
the sulfinyl stereogenic center cannot be neglected, since the reac-
tion is stereoselective even if the ligand bears an achiral aziridine
moiety. The mode of chelation of the diethylzinc molecule must
be different for the aziridine-containing ligands when compared
with those containing open-chain amine moieties.
4.2.1. Compound 3a (as a mixture of invertomers)
1H NMR (CDCl3): d = 1.10–1.30 (m, 7H), 1.66, 1.78 (2s, 1H), 1.79,
2.00 (2s, 3H), 3.60–3.80 (m, 2H), 5.10–5.45 (m, 2H), 7.35–7.85 (m,
8H). 13C NMR (CDCl3): d = 16.58 (CH3), 20.46 (CH3CO), 26.06 (CH3),
36.44, 36.75 (2C), 40.55, 40.81 (2CH2), 52.82, 53.34 (2CH2N), 62.14,
62.34 (2CH2O), 125.81, 125.96 (2Car), 126.54, 126.62 (2Car), 127.66,
127.69 (2Car), 128.06, 128.21 (2Car), 129.34, 129.37 (2Car), 129.44,
129.59 (2Car), 131.22, 131.22 (2Car), 131.34, 131.40 (2Car), 134.51,
134.74 (2C), 139.19, 139.43 (2C), 140.26, 140.82 (2C), 142.00,
142.37 (2C), 170.28 (C@O).
4. Experimental
4.1. General
4.2.2. Compound 3b
1H NMR (CDCl3): d = 0.79 (d, J = 6.4 Hz, 3H), 0.80 (d, J = 6.2 Hz,
3H), 1.08–1.16 (m, 1H), 1.19–1.28 (m, 2H), 1.50 (d, J = 3.4 Hz,
1H), 3.30–3.48 (m, 2H), 5.20 (d, J = 3.1 Hz, 1H), 5.35 (d, J = 3.1 Hz,
1H), 7.35–7.55 (m, 6H), 7.60–7.80 (m, 2H). 13C NMR (CDCl3):
d = 19.30 (CH3), 20.29 (CH3CO), 20.57 (CH3), 30.90 (CH), 32.70
(CH), 46.91 (CH2), 61.45 (CH2N), 62.38 (CH2O), 125.97 (Car),
126.65 (Car), 128.13 (Car), 129.21 (Car), 129.36 (Car); 129.42 (Car),
131.07 (Car), 131.19 (Car), 134.74 (C), 138.41 (C), 141.75 (C),
142.65 (C), 170.21 (C@O).
NMR spectra were recorded on a Bruker instrument at 200 MHz
with CDCl3 and CD3OD as solvents. Optical rotations were mea-
sured on a Perkin–Elmer 241 MC polarimeter (c 1). Column chro-
matography was carried out using Merck 60 silica gel. TLC was
performed on Merck 60 F254 silica gel plates. The enantiomeric ex-
cess (ee) values were determined by chiral HPLC (KNAUER, Chir-
alpak AS).
Aziridines a–d were synthesized according to the procedure re-
4.2.3. Compound 3c
ported in the literature.7
1H NMR (CDCl3): d = 0.68 (d, J = 6.4 Hz, 3H), 0.79 (d, J = 6.6 Hz,
3H), 1.03–1.15 (m, 1H), 1.12–1.25 (m, 1H), 1.29 (d, J = 6.1 Hz,
1H), 1.61 (d, J = 3.0 Hz, 1H), 1.94 (s, 3H), 3.43 (d, J = 14.1 Hz, 1H),
3.64 (d, J = 14.1 Hz, 1H), 5.14 (d, J = 13.0 Hz, 1H), 5.30 (d,
J = 13.0 Hz, 1H), 7.35–7.53 (m, 5H), 7.55–7.85 (m, 3H). 13C NMR
(CDCl3): d = 19.28 (CH3), 20.34 (CH3CO), 20.58 (CH3), 31.03 (CH),
32.76 (CH), 46.97 (CH2), 60.61 (CH2N), 62.38 (CH2O), 126.03 (Car),
126.43 (Car), 126.72 (Car), 128.16 (Car), 129.40 (2Car), 129.53 (Car),
4.2. Synthesis of tridentate ligands 4a–d—general procedure
Enantiomerically pure monoacetate 1 ([a]D = +60, ee >99, 1 g,
3.29 mmol) was dissolved in dichloromethane (20 mL) and trieth-
ylamine (0.4 g, 3.95 mmol) and mesyl anhydride (0.69 g, 3.95 mol)
were added. The mixture was stirred at room temperature during

´
S. Lesniak et al. / Tetrahedron: Asymmetry 20 (2009) 2311–2314
2314
131.25 (Car), 134.48 (C), 138.59 (C), 141.32 (C), 142.47 (C), 170.26
(C@O).
131.71 (Car), 137.70 (C), 139.84 (C), 142.20 (C), 143.43 (C). MS
(CI): m/z = 302 (M+H). HRMS (FAB) calcd for C17H20NO2S:
302.1214; found 302.1216.
4.2.4. Compound 3d
1H NMR (CDCl3): d = 1.15 (d, J = 6.0 Hz, 3H), 1.25–1.60 (m, 3H),
1.98 (s, 3H), 3.40–3.60 (m, 2H), 5.18–5.45 (m, 2H), 7.35–7.85 (m,
8H). 13C NMR (CDCl3): d = 17.80 (CH3), 20.65 (CH3CO), 34.61 (CH),
35.25 (CH2), 60.68 (CH2N), 62.48 (CH2O), 126.18 (Car), 126.63
(Car), 128.04 (Car), 128.62 (Car), 129.56 (2Car), 131.32 (2Car),
134.70 (C), 138.57 (C), 141.22 (C), 142.58 (C), 170.40 (C@O).
Compound 3 (0.15 mmol) was dissolved in methanol (2 mL)
after which sodium (0.15 mmol) was slowly added. The mixture
was stirred at room temperature for 0.5 h. After this time methanol
was evaporated and the residue was separated by preparative TLC
(chloroform/methanol 10:1) to give chiral tridentate ligands 4a–d.
4.3. Asymmetric addition of diethylzinc to aldehydes—general
procedure
Chiral catalysts 4a–d (0.1 mmol) and benzene (10 mL) were
placed in a flask. To ensure dryness, 5 mL of benzene were distilled
off. The mixture was cooled to 0 °C and a solution of diethylzinc
(1.0 M solution in hexane, 3 mmol) was added under an argon
atmosphere. After stirring for 0.5 h, an aldehyde (1 mmol) was
added at 0 °C and the mixture was stirred at room temperature
for 12 h. After this time, a 5% aqueous solution of hydrochloric acid
was added to the mixture. Both layers were separated and the
aqueous layer was extracted with diethyl ether (4Â). The com-
bined organic layers were washed with brine (10 mL) and dried
over MgSO4. The solvents were evaporated to give the crude alco-
hols 5, which were purified by preparative TLC (ethyl acetate/hex-
ane 1:7). They were identified by comparison of their 1H NMR
spectra with those reported in the literature. Their absolute config-
urations were determined in the same way: for the alcohol 5
(R = Ph),6 for 5 (R = 2-MeOC6H4)22 and for 5 (R = n-Pr).23
4.2.5. Compound 4a (as a mixture of invertomers)
1H NMR (CDCl3): d = 1.05–1.45 (m, 7H), 1.70, 1.88 (2s, 1H),
3.05–3.70 (m, 1.5H), 4.00–4.85 (m, 2.5H), 6.00 (s, br, 1H), 7.15–
7.65 (m, 7H), 7.90–8.20 (m, 1H). 13C NMR (CDCl3): d = 17.49,
17.99 (2CH3), 25.36, 26.31 (2CH3), 38.22, 38.60 (2Cq), 40.38,
40.94 (2CH2), 52.79, 54.21 (2CH2N), 61.65, 61.87 (2CH2O), 125.84,
126.13 (2Car), 126.53, 128.10 (2Car), 127.79, 128.33 (2Car), 129.33,
129.57 (2Car), 129.62, 129.73 (2Car), 129.84, 130.20 (2Car), 130.68,
130.93 (2Car), 131.68, 131.74 (2Car), 138.35, 138.99 (2C), 139.93,
140.24 (2C), 142.48, 142.60 (2C), 143.29, 144.05 (2C). MS (CI): m/
z = 316 (M+H). HRMS (FAB) calcd for C18H22NO2S: 316.1371; found
316.1372.
Acknowledgments
Financial support by the Polish Ministry of Science and Higher
Education, Grant No. PBZ-KBN-126/T09/03 (for P.K.), is gratefully
acknowledged.
4.2.6. Compound 4b
1H NMR (CDCl3): d = 0.63 (d, J = 6.5 Hz, 3H), 0.88 (d, J = 6.6 Hz,
3H), 1.05–1.15 (m, 1H), 1.50–1.65 (m, 1H), 1.69 (d, J = 6.6 Hz,
1H), 1.83 (d, J = 3.8 Hz, 1H), 2.69 (d, J = 12.5 Hz, 1H), 4.10 (d,
J = 13.0 Hz, 1H), 4.44 (d, J = 13.0 Hz, 1H), 4.97 (d, J = 12.5 Hz, 1H),
6.90 (s, br, 1H), 7.20–7.60 (m, 7H), 8.20–8.35 (m, 1H). 13C NMR
(CDCl3): d = 19.46 (CH3), 20.50 (CH3), 30.97 (CH), 32.77 (CH),
48.19 (CH2), 60.73 (CH2N), 61.77 (CH2O), 125.66 (Car), 127.96
(Car), 128.15 (Car), 129.78 (Car), 129.92 (Car), 130.45 (Car), 130.69
(Car), 131.58 (Car), 137.62 (C), 139.52 (C), 142.48 (C), 143.88 (C).
MS (CI): m/z = 330 (M+H). HRMS (FAB) calcd for C19H24NO2S:
330.1528; found 330.1527.
References
1. Pu, L.; Yu, H.-B. Chem. Rev. 2001, 101, 757–824.
2. Mikołajczyk, M.; Drabowicz, J.; Kiełbasin´ ski, P. Chiral Sulfur Reagents:
Applications in Asymmetric and Stereoselective Synthesis; CRC Press: Boca
Raton, 1997.
3. Bolm, C.; Muller, J.; Schlingloff, G.; Zehnder, M.; Neuburger, M. J. Chem. Soc.,
Chem. Commun. 1993, 182–183.
4. Carreno, M. C.; Garcia Ruano, J. L.; Maestro, R. C.; Cabrejas, L. M. M. Tetrahedron:
}
Asymmetry 1993, 4, 727–734.
5. Kiełbasin´ ski, P.; Albrycht, M.; Mikołajczyk, M.; Wieczorek, M. W.; Majzner, W.
R.; Filipczak, A.; Ciołkiewicz, P. Heteroat. Chem. 2005, 16, 93–103.
6. Rachwalski, M.; Kwiatkowska, M.; Drabowicz, J.; Kłos, M.; Wieczorek, W. M.;
Szyrej, M.; Sieron´ , L.; Kiełbasin´ ski, P. Tetrahedron: Asymmetry 2008, 19, 2096–
2101.
7. Xu, J. Tetrahedron: Asymmetry 2002, 13, 1129–1134.
8. Tanner, D.; Korne, H. T.; Guijarro, D.; Andersson, P. G. Tetrahedron 1998, 54,
14213–14232.
9. Zwanenburg, B.; Lawrence, C. F.; Nayak, S. K.; Thijs, L. Synlett 1999, 1571–1572.
10. ten Holte, P.; Wijgergangs, J.-P.; Thijs, L.; Zwanenburg, B. Org. Lett. 1999, 1,
1095–1097.
11. Page, P. C. B.; Allin, S. M.; Maddocks, S. J.; Elsegood, M. R. J. J. Chem. Soc., Perkin
Trans. 1 2002, 2827–2832.
4.2.7. Compound 4c
1H NMR (CDCl3): d = 0.58 (d, J = 6.4 Hz, 3H), 0.81 (d, J = 6.6 Hz,
3H), 0.98–1.15 (m, 1H), 1.35–1.50 (m, 1H), 1.59 (d, J = 6.6 Hz,
1H), 1.73 (d, J = 3.8 Hz, 1H), 2.68 (d, J = 12.6 Hz, 1H), 4.09 (d,
J = 13.0 Hz, 1H), 4.37 (d, J = 13.0 Hz, 1H), 4.77 (d, J = 12.6 Hz, 1H),
6.75 (s, br, 1H), 7.15–7.70 (m, 7H), 8.10–8.20 (m, 1H). 13C NMR
(CDCl3): d = 19.85 (CH3), 20.42 (CH3), 30.81 (CH), 32.70 (CH),
47.97 (CH2), 60.51 (CH2N), 61.59 (CH2O), 125.51 (Car), 128.06
(Car), 129.00 (Car), 129.35 (Car), 129.73 (Car), 130.11 (Car), 130.43
(Car), 131.55 (Car), 138.13 (C), 139.49 (C), 142.20 (C), 143.51 (C).
MS (CI): m/z = 330 (M+H). HRMS (FAB) calcd for C19H24NO2S:
330.1528; found 330.1526.
12. Braga, A. L.; Milani, P.; Paixao, M. W.; Zeni, G.; Rodriguez, O. E. D.; Alves, E. F.
Chem. Commun. 2004, 2488–2489.
13. Bulut, A.; Aslan, A.; Izgu, E. C.; Dogan, O. Tetrahedron: Asymmetry 2007, 18,
1013–1016.
14. Faure, R.; Loiseleur, H.; Bartnik, R.; Les´niak, S.; Laurent, A. Cryst. Struct.
Commun. 1981, 10, 515–519.
15. Bartnik, R.; Lesniak, S.; Laurent, A. Tetrahedron Lett. 1981,
´
4811–4812.
16. Bartnik, R.; Les´niak, S.; Laurent, A. J. Chem. Res. 1982, 287, 2701–2709.
17. Anet, F. A. L. J. Am. Chem. Soc. 1985, 107, 4335.
18. Bois, S. J. J. Am. Chem. Soc. 1968, 90, 508–509.
4.2.8. Compound 4d
1H NMR (CDCl3): d = 1.25 (d, J = 5.5 Hz, 3H), 1.52 (d, J = 4.0 Hz,
1H), 1.59 (d, J = 6.5 Hz, 1H), 1.75–1.95 (m, 1H), 2.74 (d,
J = 13.0 Hz, 1H), 4.13 (d, J = 13.0 Hz, 1H), 4.52 (d, J = 13.0 Hz, 1H),
4.80 (d, J = 13.0 Hz, 1H), 6.70 (s, br, 1H), 7.20–7.60 (m, 7H), 8.10–
8.25 (m, 1H). 13C NMR (CDCl3): d = 17.12 (CH3), 34.60 (CH), 35.32
(CH2), 60.87 (CH2N), 61.58 (CH2O), 125.77 (Car), 127.84 (Car),
128.32 (Car), 129.56 (Car), 129.74 (Car), 130.18 (Car), 130.76 (Car),
19. Nakanishi, H.; Yamamoto, O. Tetrahedron 1974, 30, 2115–2121.
20. Kostyanovski, R. G.; Leshchinskaya, V. P.; Alekperov, R. K.; Kadorkina, G. K.;
Shustova, L. L.; Elnatanov, Y. I.; Gromova, G. L.; Alyev, A. E.; Ciervin, U. N. Izv.
Akad. Nauk SSSR, Ser. Khim. 1988, 11, 2566–2575.
21. Davies, M. W.; Clarke, A. J.; Clarkson, G. J.; Shipman, M.; Tucker, J. H. R. Chem.
Commun. 2007, 5078–5080.
22. Cardellicchio, C.; Ciccarella, G.; Naso, F.; Perna, F.; Tortorella, P. Tetrahedron
1999, 55, 14685–14692.
23. Cere, V.; Peri, F.; Pollicino, S. J. Org. Chem. 1997, 62, 8572–8574.