Aza-MIRC Reactions of Sulfonyl-Activated Hydroxycarbamates with α,β-Difunctionalised Acrylates

Article abstract of DOI:10.1002/ejoc.200300425

Highly functionalised aziridines are readily obtained in high yields (up to 95%) under mild conditions from the reaction of trisubstituted olefins bearing different groups with nosyloxy-carbamates in the presence of calcium oxide. We propose a possible explanation for the different reactivities observed between these olefins and the aminating agents. Reagent-controlled stereoselective amination reactions led to the expected products with high conversions and purities. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200300425

FULL PAPER
Aza-MIRC Reactions of Sulfonyl-Activated Hydroxycarbamates with
α,β-Difunctionalised Acrylates
Stefania Fioravanti,*[a] Alberto Morreale,[a] Lucio Pellacani,*[a] and Paolo A. Tardella*[a]
Keywords: Amination / Diastereoselectivity / Michael addition / Nitrogen heterocycles / Small-ring systems
Highly functionalised aziridines are readily obtained in high
yields (up to 95%) under mild conditions from the reaction of
between these olefins and the aminating agents. Reagent-
controlled stereoselective amination reactions led to the ex-
trisubstituted olefins bearing different groups with nosyloxy- pected products with high conversions and purities.
carbamates in the presence of calcium oxide. We propose a
possible explanation for the different reactivities observed
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Sulfonyl-activated hydroxycarbamates[1] can be used suc- reported.[8] Moreover, the formation of isocyanate species
cessfully in direct aziridination reactions. Lwowski was the may take place in some cases.[9] Recently, we reported the
first to introduce ethyl nosyloxycarbamate (NsONHCO2Et) direct synthesis of imidazolidin-2-ones from β-keto esters,
as an alternative source of (ethoxycarbonyl)nitrene probably through
a
multicomponent reaction of
(NCO2Et) with respect to the corresponding azide. Other NsONϪCO2tBu and tert-butoxy isocyanate (tBuOϪNϭ
authors have used these kinds of reagents for some time.[2]
We have found that both NsONHCO2Et and
CϭO).[10]
Aziridines[11] are versatile intermediates in organic syn-
TsONHCO2Et, used in conjunction with inorganic bases,[3] thesis and can be considered as valuable building blocks for
are suitable aziridination agents either for electron-rich or the synthesis of a variety of natural[12] and pharmacologi-
electron-poor olefins and, in the latter case, we have pro- cally active compounds,[13] and for selective organic trans-
posed, on the basis of experimental evidence, a mechanism formations. Moreover, they can be used as scaffolds for the
involving an intermediate aza-anion (NsONϪCO2Et) as the construction of a library of useful building blocks.[14] Aziri-
reactive species (Scheme 1).[4]
dine moieties are often introduced after multi-step synth-
eses and, thus, direct aziridination is a goal of considerable
importance in organic chemistry.
To obtain polyfunctionalised aziridines, we considered
using α,β-disubstituted acrylates as starting materials. Sub-
strates 1Ϫ4 are commercially available; we synthesised the
trisubstituted olefins 5Ϫ7 in high yields using a reported
procedure.[15] These substrates were reacted with two differ-
ent NsONHCO2R reagents in CH2Cl2, in the presence of
CaO at room temperature (Scheme 2). Molar ratios, reac-
tion times, products, and yields are displayed in Table 1.
Scheme 1
To be successful, this reaction, which can be considered
as an aza-MIRC (Michael-Initiated Ring Closure) pro-
cess,[5] requires activation of the CϭC bond. Good results
have been observed when using α-nitro olefins and several
olefins that carry two geminal electron-withdrawing
groups.[6] Inversely, the amination of fumarates and male-
ates does not proceed as satisfactorily under a variety of
conditions.[7]
tert-Butyl arylsulfonyloxycarbamates (ArSO3NHCO2-
tBu) undergo aza-MIRC reactions with electron-poor olef-
ins, but electrophilic amination reactions have rarely been
Scheme 2
We observed only traces of products when a phenyl group
is present in the β-position (1, 2), even with high excesses
of reactants. GC/MS analyses display molecular ions and
fragmentations that are compatible with those expected for
aziridines. The effect of a phenyl group in lowering the reac-
[a]
`
Dipartimento di Chimica, Universita degli Studi di Roma La
Sapienza,
P.le Aldo Moro 2, 00185 Roma, Italy
Fax: (internat.) ϩ 39-06-490631
E-mail: lucio.pellacani@uniroma1.it
Eur. J. Org. Chem. 2003, 4549Ϫ4552
DOI: 10.1002/ejoc.200300425
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4549

S. Fioravanti, A. Morreale, L. Pellacani, P. A. Tardella
FULL PAPER
Table 1. Direct aziridination of α,β-disubstituted acrylates with NsONHCO2R
Olefin
Y
EWG
Molar ratios[a]
R
Reaction times [h]
Product
Yields (%)[b]
1
2
3
4
5
6
7
5
6
7
Ph
Ph
EtO
EtO
CO2Et
CN
COCH3
CO2Et
CN
CO2Et
CN
CO2Et
CN
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
1:10:8
1:10:8
1:8:6
Et
Et
Et
Et
Et
Et
Et
Bn
Bn
Bn
48
48
24
24
2
2
2
1
1
1
traces
traces
8
Ϫ[c]
Ϫ[c]
36
52
94
91
92
95
88
1:8:6
9
1:2:1.2
1:2:1.2
1:2:1.2
1:2:1.2
1:2:1.2
1:2:1.2
10
11
12
13
14
COCH3
15
92
[a]
[b]
[c]
Ratio of substrate/CaO/NsONHCO2R.
collected almost quantitatively.
After flash chromatography on silica gel.
After workup, the unchanged substrate was
tivity has been already observed by us[4] and others[7a]. The conversions and purities, as confirmed by 1H and 13C NMR
β-ethoxyacrylates 3 and 4 display enhanced reactivity and spectra, and in good isolated yields.
the corresponding aziridines 8 and 9 were obtained after
flash chromatography on silica gel in 36 and 52% yield,
respectively; we found these compounds to be unstable
upon storing them at room temperature. In these reactions,
parallels exist with our findings on push-pull olefins.[16] The
best results were obtained for the reactions of olefins bear-
ing an additional electron-withdrawing group. In these
cases (5Ϫ7), the products 10Ϫ12 were obtained cleanly un-
der milder conditions. As expected, good Michael acceptors
undergo the aza-MIRC reaction. Thus, the substrates 5Ϫ7
Scheme 3
reacted rapidly, very likely by trapping the intermediate aza-
anion and, after immediate ring-closure with elimination of
the NsOϪ group, we isolated polyfunctionalised aziridines
in almost quantitative yields. The same alkenes reacted
quantitatively with a new carbamate, benzyl nosyloxycarba-
mate (NsONHCO2Bn), which we synthesised using stand-
ard procedures (see Exp. Sect.). The results obtained for the
aziridination of the alkenes 5Ϫ7 (Table 1) show that
NsONHCO2Bn exhibits almost the same reactivity as that
of NsONHCO2Et.[17]
In contrast, attempts to perform reactions with
NsONHCO2tBu failed. It is probable that aziridine forma-
tion is precluded by steric hindrance, as a result of the pres-
ence of the bulky tert-butyl group or because of competitive
conversion into the isocyanate.
Thus, the outcome of these direct aziridinations is
strongly influenced not only by the substituents on the al-
kenes, but also by the nature of the alkyl and/or aryl groups
of the arylsulfonyloxycarbamates. Our first attempts to im-
prove the yields and rates for the reactions of alkenes 1, 3,
5, and 7, by using ionic liquids[18] such as [bmim]BF4
instead of CH2Cl2, did not give better results (bmim ϭ
1-butyl-3-methylimidazolium.
We attempted some experiments in which we tried to in-
duce diastereoselectivity. Reagent-controlled stereoselective
amination reactions were performed with the olefins 5Ϫ7
using the chiral nosyloxycarbamate derived from Helmch-
en’s auxiliary.[19] These reactions, which we performed using
the same molar ratios of substrate:CaO:NsONHCO2R*,
The diastereoisomeric ratios (dr) were determined by
NMR spectroscopy and HPLC analyses performed on the
crude mixtures. While the values of the diastereomeric ex-
cesses for the aziridines 16 and 18 were similar to those
found in analogous reactions promoted by the same chiral
noxyloxycarbamate,[20] the reasons for the lack of diastereo-
selectivity observed for 17 are not clear. In all cases, we
obtained the aziridines as optically pure compounds when
purified by HPLC (eluent: hexane/EtOAc, 70:30; flow rate:
1.3 mL/min). The aziridines 17 also can be separated suc-
cessfully by flash chromatography on silica gel.
In conclusion, we report a direct synthetic approach to
multi-functionalised aziridines by an aza-MIRC pathway,
which is improved by the presence of EWGs on the starting
alkenes. These substituents on the aziridines are potential
new reactive sites for further chemoselective transform-
ations. Moreover, functional groups are known to play a
critical role in the biological activity of several aziridines.[21]
Experimental Section
GC analyses were performed with an HP 5890 Series II gas chro-
matography system equipped with a capillary column (methyl sili-
cone, 12.5 m ϫ 0.2 mm). GC-MS analyses were carried out with
an HP G1800A GCD System equipped with a capillary column
(phenyl methyl silicone, 30 m ϫ 0.25 mm). IR: PerkinϪElmer 1600
led to the expected products (Scheme 3) after 5 h with high Series FTIR spectrophotometer. NMR: Varian Mercury 300 and
4550  2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2003, 4549Ϫ4552

Aza-MIRC Reactions of Sulfonyl-Activated Hydroxycarbamates
FULL PAPER
Gemini 200, using CDCl3 as the solvent and CHCl3 as the in-
ternal standard.
111 (31), 110 (23) 101 (12), 94 (11), 68 (14), 67 (59), 66 (100), 56
(36). C12H16N2O6 (284.101): calcd. C 50.70, H 5.67, N 9.85; found
C 50.64, H 5.65, N 9.87.
Synthesis of Benzyl Nosyloxycarbamate (NsONHCO2Bn): Com-
mercially available (Aldrich) benzyl N-hydroxycarbamate (1.67 g, Triethyl 3-Acetylaziridine-1,2,2-tricarboxylate (12): Viscous oil
10.0 mmol) was reacted with equimolar amounts of nosyl chloride
(2.22 g) and freshly distilled triethylamine (1.01 g, 1.4 mL) in anhy-
drous diethyl ether (300 mL) at 0 °C. After 3 h, the title compound
was obtained in 81% yield (2.85 g, 8.1 mmol) as a pale-yellow solid.
M.p. 92Ϫ93 °C (from CH2Cl2/pentane). IR (CCl4): ν˜ ϭ 3341, 1778,
(0.554 g, 1.84 mmol, 92% yield). IR (CCl4): ν˜ ϭ 1770, 1725 cmϪ1
.
1H NMR (CDCl3): δ ϭ 1.19Ϫ1.31 (m, 9 H), 2.20 (s, 3 H), 3.74 (s,
1 H), 4.10Ϫ4.33 (m, 6 H) ppm. 13C NMR (CDCl3): δ ϭ 13.8 (two
signals), 14.1, 27.8, 49.9, 50.6, 62.9, 63.9, 64.0, 157.3, 162.6, 163.4,
198.8 ppm. GC/MS: m/z (%) ϭ 301 (9) [Mϩ], 228 (10), 156 (100),
128 (52), 110 (83). C13H19NO7 (301.116): calcd. C 51.82, H 6.36,
N 4.65; found C 51.72, H 6.34, N 4.63.
1
1609 cmϪ1. H NMR (CDCl3): δ ϭ 4.98 (s, 2 H), 7.10Ϫ7.18 (m, 2
H), 7.27Ϫ7.38 (m, 3 H), 8.04Ϫ8.10 (m, 2 H), 8.13Ϫ8.19 (m, 2 H),
8.90 (s, 1 H) ppm. 13C NMR (CDCl3): δ ϭ 68.8, 123.8, 128.4,
128.5, 130.7, 134.0, 138.6, 150.9, 155.1 ppm. ESI-MS: m/z ϭ 353
[M ϩ 1]ϩ. C14H12N2O7S (352.315).
1-Benzyl 2,2,3-Triethyl Aziridine-1,2,2,3-tetracarboxylate (13): Vis-
cous oil (0.747 g, 1.90 mmol, 95% yield). IR (CCl4): ν˜ ϭ 1744 cmϪ1
.
1H NMR (CDCl3): δ ϭ 1.18 (t, J ϭ 7.2 Hz, 3 H), 1.27 (t, J ϭ
7.2 Hz, 3 H), 1.29 (t, J ϭ 7.2 Hz, 3 H), 3.77 (s, 1 H), 4.13 (q, J ϭ
7.2 Hz, 2 H), 4.21 (t, J ϭ 7.2 Hz, 2 H), 4.21 (t, J ϭ 7.2 Hz, 2 H),
General Procedure for the Synthesis of Aziridines: CaO and
NsONHCO2R were added portionwise at room temperature, in the
molar ratios reported in Table 1, to a stirred solution of substrate 5.14 (d, J ϭ 12.3 Hz, 1 H), 5.18 (d, J ϭ 12.3 Hz, 1 H), 7.34 (s, 5
(2 mmol) in 3 mL of CH2Cl2. The reaction was monitored by TLC
and GC, and CH2Cl2/pentane (20:80) were added to the crude mix-
ture upon completion. After filtration and solvent evaporation un-
der reduced pressure, the residue was purified by flash chromatog-
raphy on silica gel (hexane/ethyl acetate, 70:30).
H) ppm. 13C NMR (CDCl3): δ ϭ 13.8, 13.9, 14.0, 44.8, 50.0, 62.3,
62.4, 63.6, 69.1, 128.3, 128.4 (four signals), 134.6, 157.1, 162.3,
163.3, 164.4 ppm. GC/MS: m/z (%) ϭ 276 (Ͻ 1) [M Ϫ 117]ϩ, 214
(62), 168 (39), 91 (100). C19H23NO8 (393.142): calcd. C 58.01, H
5.89, N 3.56; found C 57.99, H 5.89, N 3.56.
Triethyl 3-Ethoxyaziridine-1,2,2-tricarboxylate (8): Viscous oil
1-Benzyl 2,2-Diethyl 3-Cyanoaziridine-1,2,2-tricarboxylate (14):
(0.218 g, 0.72 mmol, 36% yield). IR (CCl4): ν˜ ϭ 1751, 1738 cmϪ1
.
Viscous oil (0.609 g, 1.76 mmol, 88% yield). IR (CCl4): ν˜ ϭ 2257,
1H NMR (CDCl3): δ ϭ 1.24Ϫ1.38 (m, 12 H), 3.79 (q, J ϭ 7.2 Hz, 1758 cmϪ1. H NMR (CDCl3): δ ϭ 1.21 (t, J ϭ 7.2 Hz, 3 H), 1.35
1
2 H), 4.11Ϫ4.45 (m, 6 H), 6.35 (s, 1 H) ppm. 13C NMR (CDCl3):
(t, J ϭ 7.2 Hz, 3 H), 3.76 (s, 1 H), 4.04Ϫ4.23 (m, 2 H), 4.38 (q,
δ ϭ 14.1, 14.2, 14.3, 14.4, 59.6, 62.4, 62.5 (two signals), 63.3, 98.4, J ϭ 7.2 Hz, 2 H), 5.15 (d, J ϭ 12.3 Hz, 1 H), 5.22 (d, J ϭ 12.3 Hz,
154.4, 164.6, 165.0 ppm. GC/MS: m/z (%) ϭ 231 (9) [M Ϫ
1 H), 7.36 (s, 5 H) ppm. 13C NMR (CDCl3): δ ϭ 13.8, 14.0, 32.1,
49.4, 63.4, 64.2, 69.8, 112.6, 128.5 (two signals), 128.6 (two signals),
CO2Et]ϩ, 215 (12), 214 (100), 186 (50), 142 (70), 127 (25), 122 (21),
115 (34), 114 (40), 100 (11), 99 (15), 98 (20), 90 (11), 87 (17), 81 128.7, 134.1, 155.9, 161.2, 162.2 ppm. GC/MS: m/z (%) ϭ 300 (Ͻ
(13), 77 (14), 71 (39), 70 (82), 62 (24), 56 (82). C13H21NO7 1) [M Ϫ 46]ϩ, 107 (39), 91 (100). C17H18N2O6 (346.116): calcd. C
(303.132): calcd. C 51.48, H 6.98, N 4.62; found C 51.44, H 6.96,
N 4.63.
58.96, H 5.24, N 8.09; found C 58.99, H 5.23, N 8.11.
1-Benzyl 2,2-Diethyl 3-Acetylaziridine-1,2,2-tricarboxylate (15):
Diethyl 2-Cyano-3-ethoxyaziridine-1,2-dicarboxylate (9): Viscous oil
Viscous oil (0.668 g, 1.84 mmol, 92% yield). IR (CCl4): ν˜ ϭ 1748
1
(0.266 g, 1.04 mmol, 52% yield). IR (CCl4): ν˜ ϭ 2222, 1765, 1735 cmϪ1. H NMR (CDCl3): δ ϭ 1.36 (t, J ϭ 7.2 Hz, 3 H), 1.45 (t,
cmϪ1
.
1H NMR (CDCl3): δ ϭ 1.18Ϫ1.46 (m, 9 H), 3.70 (q, J ϭ
J ϭ 7.2 Hz, 3 H), 2.39 (s, 3 H), 3.98 (s, 1 H), 4.28 (q, J ϭ 7.2 Hz,
7.2 Hz, 2 H), 4.14Ϫ4.75 (m, 4 H), 6.45 (s, 1 H) ppm. 13C NMR 2 H), 4.44 (q, J ϭ 7.2 Hz, 2 H), 5.32 (d, J ϭ 12.3 Hz, 1 H), 5.36
(CDCl3): δ ϭ 14.0, 14.3, 14.9, 58.4, 63.3, 63.5, 64.3, 98.7, 112.2,
(d, J ϭ 12.3 Hz, 1 H), 7.51 (s, 5 H) ppm. 13C NMR (CDCl3): δ ϭ
13.8, 13.9, 27.9, 50.0, 50.7, 62.7, 63.7, 69.1, 128.4 (four signals),
151.9, 161.0 ppm. GC/MS: m/z (%) ϭ 257 (15) [M ϩ 1]ϩ, 158 (21),
103 (100), 100 (13), 75 (42), 56 (10), 47 (34). C11H16N2O5 (256.106): 128.5, 134.6, 157.3, 162.6, 163.4, 198.8 ppm. GC/MS: m/z (%) ϭ
calcd. C 51.56, H 6.29, N 10.93; found C 51.58, H 6.26, N 10.95.
363 (1) [Mϩ], 246 (11), 140 (10), 110 (11), 91 (100). C18H21NO7
(363.132): calcd. C 59.50, H 5.83, N 3.85; found C 59.45, H 5.84,
N 3.88.
Tetraethyl Aziridine-1,2,2,3-tetracarboxylate (10): Viscous oil
(0.622 g, 1.88 mmol, 94% yield). IR (CCl4): ν˜ ϭ 1764, 1739 cmϪ1
.
1H NMR (CDCl3): δ ϭ 1.12Ϫ1.38 (m, 12 H), 3.69 (s, 1 H), Synthesis of Aziridines 16؊18: The chiral nosyloxycarbamate
4.08Ϫ4.40 (m, 8 H) ppm. 13C NMR (CDCl3): δ ϭ 13.7, 13.8 (two (NsONHCO2R*) was prepared according to ref.[20]. For the syn-
signals), 14.0, 44.6, 49.8, 62.2, 62.3 (two signals), 63.5, 157.2, 162.5,
thesis of the following aziridines, we followed the general procedure
above. The molar ratios, reaction times, and yields are reported
163.5, 164.6 ppm. GC/MS: m/z (%) ϭ 331 (Ͻ 1) [Mϩ], 214 (20),
187 (10), 186 (100), 185 (13), 168 (36), 158 (23), 157 (30), 140 (94), in Scheme 3.
130 (13), 129 (19), 111 (45), 85 (30), 68 (14), 57 (11). C14H21NO8
16 (Major Diastereoisomer): [α]D ϭ Ϫ31.78 (c ϭ 4.5, CHCl3). IR
(331.127): calcd. C 50.75, H 6.39, N 4.23; found C 50.70, H 6.37,
N 4.22.
(CCl4): ν˜ ϭ 1754, 1745, 1736, 1609, 1596 cmϪ1. 1H NMR (CDCl3):
δ ϭ 0.57 (s, 3 H), 0.74 (s, 3 H), 0.94 (s, 3 H), 1.06Ϫ1.18 (m, 1 H),
1.26Ϫ1.36 (m, 9 H), 1.46Ϫ1.58 (m, 1 H), 1.62Ϫ1.76 (m, 2 H), 1.85
Triethyl 3-Cyanoaziridine-1,2,2-tricarboxylate (11): Viscous oil
(0.517 g, 1.82 mmol, 91% yield). IR (CCl4): ν˜ ϭ 2222, 1769, 1739 (d, J ϭ 3.9 Hz, 1 H), 2.03 (s, 3 H), 2.28 (s, 3 H), 4.01 (d, J ϭ
1
cmϪ1. H NMR (CDCl3): δ ϭ 1.29 (t, J ϭ 7.2 Hz, 3 H), 1.33 (t, 7.2 Hz, 1 H), 4.22Ϫ4.38 (m, 6 H), 4.50 (s, 1 H), 5.10 (d, J ϭ 7.2 Hz,
J ϭ 7.2 Hz, 3 H), 1.37 (t, J ϭ 7.2 Hz, 3 H), 3.77 (s, 1 H), 4.24 (q,
1 H), 5.77 (s, 1 H), 6.85 (s, 1 H), 7.08 (s, 1 H), 7.30Ϫ7.52 (m, 5 H)
J ϭ 7.2 Hz, 2 H), 4.33 (q, J ϭ 7.2 Hz, 2 H), 4.40 (q, J ϭ 7.2 Hz, ppm. 13C NMR (CDCl3): δ ϭ 11.5, 14.0, 14.3, 29.9, 21.1, 21.3,
2 H) ppm. 13C NMR (CDCl3): δ ϭ 13.7, 13.8, 14.0, 31.9, 49.2, 28.2, 32.1, 44.6, 47.3, 48.3, 50.0, 50.8, 62.0, 62.2, 63.3, 66.9, 85.1,
63.2, 64.1, 64.2, 112.6, 155.8, 161.2, 162.1 ppm. GC/MS: m/z (%) ϭ
285 (Ͻ 1) [MHϩ], 212 (12), 211 (12), 184 (35), 167 (13), 166 (25), 165.2 ppm. ESI-MS: m/z
157 (21), 156 (63), 155 (16), 139 (31), 138 (68), 129 (48), 112 (13), (698.823).
128.0, 128.3, 129.4, 132.3, 137.3, 138.0, 156.2, 163.0, 163.1,
ϭ
700 [M
ϩ
1]ϩ. C36H46N2O10S
Eur. J. Org. Chem. 2003, 4549Ϫ4552
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4551

S. Fioravanti, A. Morreale, L. Pellacani, P. A. Tardella
FULL PAPER
[4]
[5]
[6]
S. Fioravanti, L. Pellacani, S. Stabile, P. A. Tardella, R. Ballini,
Tetrahedron 1998, 54, 6169Ϫ6176.
17 (Major Diastereoisomer): [α]D ϭ Ϫ18.71 (c ϭ 3.1, CHCl3). IR
1
(CCl4): ν˜ ϭ 2255, 1757, 1609, 1596 cmϪ1. H NMR (CDCl3): δ ϭ
R. D. Little, J. R. Dawson, Tetrahedron Lett. 1980, 21,
2609Ϫ2612.
0.59 (s, 3 H), 0.85 (s, 3 H), 0.96 (s, 3 H), 1.05Ϫ1.18 (m, 1 H), 1.30
(t, J ϭ 7.2 Hz, 3 H), 1.38 (t, J ϭ 7.2 Hz, 3 H), 1.48Ϫ1.62 (m, 1
H), 1.64Ϫ1.77 (m, 2 H), 1.86 (d, J ϭ 4.5 Hz, 1 H), 1.99 (s, 3 H),
2.36 (s, 3 H), 3.97 (d, J ϭ 7.2 Hz, 1 H), 4.34 (q, J ϭ 7.2 Hz, 2 H),
4.43 (q, J ϭ 7.2 Hz, 2 H), 7.78 (s, 1 H), 5.05 (d, J ϭ 7.2 Hz, 1 H),
5.62 (s, 1 H), 6.87 (s, 1 H), 7.16 (s, 1 H), 7.28Ϫ7.41 (m, 4 H),
7.47Ϫ7.55 (m, 1 H) ppm. 13C NMR (CDCl3): δ ϭ 11.5, 14.0, 14.1,
20.8, 21.0, 21.3, 21.4, 28.0, 32.0, 47.4, 48.1, 49.3, 50.9, 63.1, 63.7,
67.2, 85.7, 113.5, 128.0, 128.8, 129.5, 131.9, 132.5, 136.7, 136.9,
137.5, 138.4, 155.1, 161.5, 162.1 ppm. ESI-MS: m/z ϭ 653 [M ϩ
1]ϩ. C34H41N3O8S (651.770).
[6a] S. Fioravanti, A. Morreale, L. Pellacani, P. A. Tardella, Syn-
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been achieved in the presence of a chiral auxiliary. See: S.
Fioravanti, A. Morreale, L. Pellacani, P. A. Tardella, J. Org.
Chem. 2002, 67, 4972Ϫ4974.
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[7b]
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ˆ
[9] [9a]
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18 (Major Diastereoisomer): [α]D ϭ Ϫ27.30 (c ϭ 3.7, CHCl3). IR
(CCl4): ν˜ ϭ 1754, 1740, 1732, 1609, 1596 cmϪ1. 1H NMR (CDCl3):
δ ϭ 0.57 (s, 3 H), 0.76 (s, 3 H), 0.96 (s, 3 H), 1.04Ϫ1.16 (m, 1 H),
1.30 (t, J ϭ 7.2 Hz, 3 H), 1.31 (t, J ϭ 7.2 Hz, 3 H), 1.46- 1.58 (m,
1 H), 1.62Ϫ1.76 (m, 2 H), 1.81 (d, J ϭ 4.2 Hz, 1 H), 2.00 (s, 3 H),
2.30 (s, 3 H), 2.43 (s, 3 H), 3.97 (d, J ϭ 7.2 Hz, 1 H), 4.25Ϫ4.37
(m, 4 H), 4.63 (s, 1 H), 5.08 (d, J ϭ 7.2 Hz, 1 H), 5.64 (s, 1 H),
6.86 (s, 1 H), 7.00 (s, 1 H), 7.31Ϫ7.53 (m, 5 H) ppm. 13C NMR
(CDCl3): δ ϭ 11.5, 14.0, 20.8, 21.1, 21.4, 28.1, 28.5, 32.1, 47.3,
48.3, 49.9, 50.3, 50.9, 62.4, 63.3, 67.2, 85.2, 128.0, 128.2, 129.4,
132.4, 137.2, 137.9, 156.8, 163.1, 163.3, 199.9 ppm. ESI-MS: m/z ϭ
670 [M ϩ 1]ϩ. C35H44N2O9S (668.797).
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Acknowledgments
This research was carried out within the framework of the National
Project ‘‘Stereoselezione in Sintesi Organica. Metodologie ed Ap-
plicazioni’’, supported by the Italian Ministero dell’Istruzione
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`
`
dell’Universita e della Ricerca (MIUR) and by the Universita degli
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Received July 9 2003
4552
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4549Ϫ4552