Kinetic and thermodynamic aspects in the 1,3-dipolar cycloaddition of five-membered cyclic nitrones to α,β-unsaturated γ- and δ-lactones

Article abstract of DOI:10.1016/j.tetasy.2007.04.015

The 1,3-dipolar cycloaddition of five-membered ring nitrones to the α,β-unsaturated δ-lactones is kinetically controlled, whereas the same reactions involving γ-lactones, upon heating and prolonged reaction times, display visible reversibility of the reac

Full text of DOI:10.1016/j.tetasy.2007.04.015

Tetrahedron: Asymmetry 18 (2007) 1085–1093
Kinetic and thermodynamic aspects in the 1,3-dipolar cycloaddition of
five-membered cyclic nitrones to a,b-unsaturated c- and d-lactones
´
´
Sebastian Stecko, Konrad Pasniczek, Margarita Jurczak, Zofia Urbanczyk-Lipkowska and
Marek Chmielewski*
Institute of Organic Chemistry of the Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
Received 16 March 2007; accepted 18 April 2007
Available online 29 May 2007
Abstract—The 1,3-dipolar cycloaddition of five-membered ring nitrones to the a,b-unsaturated d-lactones is kinetically controlled,
whereas the same reactions involving c-lactones, upon heating and prolonged reaction times, display visible reversibility of the reaction
and as the consequence, the formation of the more stable, thermodynamic products can be observed. Owing to this and to the high ste-
reoselectivity of the cycloaddition, d-lactones can be used for kinetic resolution of racemic nitrones whereas c-ones cannot. In addition
the reversibility of the cycloaddition, as well as racemization of 5-substituted 2-(5H)-furanones (c-lactones), complicates the composition
of the post-reaction mixtures and may lead to the formation of partially racemic adducts. The possible asymmetric transformation of
cycloaddition involving c-lactones, which eventually provide the most stable thermodynamic products in high yield, cannot be performed
due to the low stability of cyclic nitrones which undergo decomposition.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
served, with the exception of the formation of a small
amount of the endo adduct reported by Font et al.7 for
compound 7, c-lactones 5 and 6 can add nitrone in both
the exo and endo mode. Recently Langlois et al.8 have re-
ported the endo approach of oxazoline N-oxide and unsat-
urated d-lactone in the mismatched pair and explained that
by the interaction between the positively charged imino-
ether fragment in the nitrone and the lactone carbonyl
group. The endo addition of the reactants is energetically
more demanding than the exo addition and might occur
if none of the substituents present in the lactone or nitrone
hinders such approach and when there is an additional sec-
ondary interaction that favors the endo transition state.
Recently we have reported that the 1,3-dipolar cycloaddi-
tion of nitrones 1–4 to a,b-unsaturated c-5, 6 and d-lac-
tones 7–10 constitutes an interesting example of a double
asymmetric induction, where the chirality elements of each
reactant may influence stereoselectivity either in concert or
in opposite manner.1–5 Although, in general, 1,3-dipolar
cycloaddition involving nitrones is thermally reversible,6
the results of our investigations have been interpreted on
the assumption that the cycloaddition is kinetically
controlled. In the case of d-lactones, such an assumption
appeared reasonable since we have never observed any
reversibility of these reactions. In the case of c-lactones,
however, upon heating and prolongation of the reaction
time, the reversibility of the cycloaddition has been ob-
served, and the presence of more stable thermodynamic
products has been detected. Moreover, in the case of c-lac-
tone 6, a partial racemization can occur and consequently
adducts derived from 6 and ent-6 are formed.
The high preference of the anti addition to the terminal
acetoxymethyl group in the d-lactones 8–10 and to the
3-tert-butoxy group of the nitrones 2 and 3 has been
observed. The 4-tert-butoxy substituent present in 3 played
a secondary role. In the case of mismatched pairs, the con-
figuration of the 4-O-acetoxy substituent in lactones 9 and
10 becomes the decisive factor controlling the outcome of
the addition.4
Contrary to the corresponding additions involving d-lac-
tones, where only the exo approach of reactants was ob-
The cycloaddition of 2 mol equiv of racemic d-lactones 8/
ent-8 and nitrones 2 or 3 showed significant kinetic resolu-
tions.1,2 In the case of the nitrone 2, D-glycero lactone 8
was less reactive and could be isolated in 95% yield and
*
Corresponding author. Tel./fax: +48 22 632 66 81; e-mail: chmiel@
icho.edu.pl
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.04.015

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S. Stecko et al. / Tetrahedron: Asymmetry 18 (2007) 1085–1093
81% ee,2 whereas in the case of nitrone 3, L-glycero lactone
ent-8 is less reactive and was isolated in 86% yield and 77%
ee.1
Table 1. Cycloaddition of 2 and 5 in toluene solution under reflux
Entry
Time (h)
Yield (%)
Cycloadducts ratioa
(%)
13
14
15
Ot-Bu
t-BuO
t-BuO
Ot-Bu
1
2
3
4
5
48
96
120
196
48b
73
67
65
56
75
17
12
8
4
25
64
67
46
35
75
19
29
46
58
—
+
+
+
+
N
N
N
N
O -
O -
O -
O -
1
3
4
2
a All data are average of five runs.
b Reaction performed at room temperature.5
RO
O
O
O
O
the proportion of 13:14:15 was found to be 1:6:6 whereas
after 7 days it was 1:9:14, respectively (Scheme 1). At the
same time the yield of the reaction was decreased to 65%
and 56%. Under the same condition the exo-anti adduct
14 underwent slow rearrangement to the exo-syn 15; after
7 days of reflux the mixture contained 40% of 14 and
60% of 15 (Table 2). It shows that the adduct exo-syn 15,
not observed under kinetic control of the reaction, is ther-
modynamically the most stable one (Tables 1 and 2). It
should be stressed that our results throw a new light on
the work of the Brandi et al. published in a review article,11
which for the cycloaddition of the nitrone 2 and the lactone
5 reported the formation of two exo adducts 14 and 15 in a
ratio of about 5:1, respectively; the endo adduct 13 has not
been found. The configuration of adducts 13–15 was estab-
lished by NMR spectra and confirmed by X-ray analysis
(Fig. 1).12
6 (R=H)
5
12 (R=TBDPS)
AcO
O
O
O
O
O
O
OAc
7
8
ent-8
AcO
AcO
AcO
O
O
O
O
AcO
10
9
O
O
O
O
O
O
O
O
O
O
+
+
3
2
4
N
N
1a
H
H
H
H
H
H
H
H
H
4a
4b
O -
11
O -
2 + 5
+
+
O1
8N
O
O
Ot-Bu
Ot-Bu
Ot-Bu
N
N
5
6
11ent
7
exo-anti
exo-syn
endo-anti
The lack of the endo approach of reactants in the case of d-
lactones 8–10 suggested the examination of the cycloaddi-
tion involving racemic nitrone 11/ent-11. One would expect
an effective kinetic resolution of 11/ent-11 using both d-lac-
tones 9, 10 and c-lactone 12. Moreover, in the case of mis-
matched pairs at higher temperature, or under high
pressure, due to steric reasons, one could expect the endo
addition even for d-lactones.
13
15
14
Scheme 1.
Table 2. Isomerization of 14 (exo-anti) in toluene
Entry
Time
Ratio of 14/15a
1
2
3
4
5
6
24 h
48 h
90 h
7 d
12 d
16 d
93:7
63:37
48:52
39:61
30:61
40:60
The stereocontrolled formation of the desired configuration
of the cycloadduct will allow us to design an efficient target-
oriented synthesis. Recently, using nitrones 2 and 3, and
lactones 7 and 10, we have demonstrated a convenient
approach to indolizidine3,9 and pyrrolizidine10 alkaloids.
a All data are average of three runs.
A similar transformation was observed for the adducts of
the mismatched pair, nitrone 2 and lactone 6 (Table 3).
The previously reported standard reaction in toluene solu-
tion (47 h at room temperature followed by 1 h reflux )
provided a mixture of three products 16–18 in a ratio of
about 21:27:52 (Scheme 2). The prolongation of the reac-
tion time to 96 h under reflux showed 4% of 19. The endo
2. Results and discussion
Reaction between lactone 5 and nitrone 2 in toluene solu-
tion at room temperature afforded two adducts endo-anti
13 and exo-anti 14 in a ratio of about 1:3, respectively,
and in 75% yield (Table 1).5 The same reaction in boiling
toluene revealed after 48 h the presence of exo-syn adduct
15. Prolongation of the reaction time led to a reduction
of the content of the endo compound 13. After 5 days,
Examination of 1-h reflux of the reaction mixture did not show any
change of the adducts’ ratio.

S. Stecko et al. / Tetrahedron: Asymmetry 18 (2007) 1085–1093
1087
Figure 1. Molecular structures of the compounds 13–15 with the crystallographical numbering scheme.12
Table 3. Cycloaddition of nitrone 2 to the lactone 6
Entry
Solvent
Additive
Time
Yield (%)
Cycloadducts ratioa (%)
16
17
18
19
1
2
3
4
5
6
7
PhMe
PhMe
PhMe
PhMe
Et3N
—
—
47 h (rt) 1 h (reflux)
48 h (reflux)
54 h (rt), 1 h (reflux)
60 h (reflux)
9 d (rt)
89
72
66
75
90
66
41
21
23
18
11
—
8
27
23
24
15
11
15
—
52
48
43
39
25
42
20
—
6
Et3N (10%)
Et3N (10%)
—
15
35
64
35
80
Et3N
Et3N
—
5 d (reflux)
7 d (rt)
H2O (5%)
—
a All data are average of five runs.
adduct 18 which was the main product of the cycloaddi-
tion, refluxed in toluene solution for 24 h showed the unre-
acted substrate and two new products: the exo-anti adduct
17 and the cycloadduct 19 in a ratio of about 8:1:3, respec-
tively. Observation of the formation of the adduct 19 which
should be thermodynamically the most stable (the matched
approach of 2 and ent-6) suggested a possible shift of the
reaction towards 19 as the sole product upon prolongation
of the reaction time. As a consequence of such an asymmet-
ric transformation, lactone 6 could be used in both enantio-
meric forms or as a racemate since the configuration of the
final product would be determined by the configuration of
nitrone 2. To accelerate the racemization of lactone 6,13 tri-
ethylamine was added. The highest content of 19 (19:18
equal 4:1) was found for the use of triethylamine in the
presence of a small amount of water as the solvent (Table
3). The overall yield of the transformation, however, was
decreased significantly to afford products in 41% only. It
was shown that upon prolongation of heating and in the
presence of a base, both reactants (the nitrone and the lac-
tone) underwent decomposition.
Racemic nitrone 11/ent-11 was obtained from D-arabinose
following known procedure.14 The reaction sequence pro-
ceeds via an intermediate that belongs to Cs symmetry
point group. Enantiomerically pure nitrone 11 can be
obtained by an alternative way involving intramolecular
alkylation of an oxime.15–17
In the case of cycloaddition between racemic nitrone 11/
ent-11 and lactones 8 and 10 one could expect that matched
pairs, involving 11, should approach almost exclusively in
the anti-exo mode to provide adducts 20 and 21, respec-
tively, whereas mismatched pairs involving ent-11 could
react via both exo and endo mode.
HO
HO
HO
O
N
O
N
O
N
O
H
O
O
H
+
H
H
H
+
H
H
H
2 + 6
The cycloaddition of lactone 8 to 2 equiv of the racemate
11/ent-11 at room temperature for 5 days resulted in a vis-
ible kinetic resolution and exclusively afforded adduct 20 in
79% yield and unreacted nitrone ent-11 with 64% ee in 60%
yield (Table 4). Reaction between 8 and 1 equiv of 11/ent-
11 in boiling toluene for 4 days gave besides 20 (92%)
adduct 22 (8%) in low 22% yield. The reaction of enantio-
merically pure nitrone ent-11 with 8 under the same condi-
tions showed two products, adducts 22 and 24, in the ratio
of about 4:1, respectively, in 51% yield; product of the endo
approach 26 was not found.
H
O
O
O
Ot-Bu
Ot-Bu
Ot-Bu
exo-anti
exo-syn
endo-anti
16
17
18
HO
HO
HO
O
O
O
N
O
O
O
+
H
H
H
H
H
H
H
H
H
O
N
O
N
O
Ot-Bu
Ot-Bu
Ot-Bu
exo-anti
endo-anti
exo-anti
Similar results were obtained for lactone 10 and the race-
mate 11/ent-11. 1:2 Proportion of reactants, after 6 days,
afforded adduct 21 as a sole product in 82% yield and the
17
19
18
Scheme 2.

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S. Stecko et al. / Tetrahedron: Asymmetry 18 (2007) 1085–1093
Table 4. Kinetic resolution of nitrones 11/11ent by lactones 8, 10 and 12
Entry
Lactone
Nitrone
Lactone/nitrone ratio
Temperature
Time
Yield (%)
Diastereoisomers’ ratio (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
8
11/11ent
11/11ent
11/11ent
11ent
1:2
1:1
1:1
1:1
1:2
1:1
1:1
1:2
1:1
1:1
1:1
1:1
1:1
1:2
1:2
1:1
1:1
rt
rt
Reflux
Reflux
rt
rt
Reflux
rt
5 d
6 d
4 d
5 d
7 d
8 d
3 d
6 d
7 d
5 d
24 h
7 d
7 d
7 d
7 d
14 d
5 d
79
36
22
51
79
36
51
82
65
33
74
68
49
95
72
84
64
100(20)
100(20)
92(20), 8(24)
80(22), 20(24)
95(28), 5(29)
67(28), 33(29)
64(28), 36(29)
100(21)
82(21), 12(25), 6(23)
67(25), 33(21)
67(25), 33(23)
71(30), 23(32), 6(31)
57(30), 41(32), 2(31)
76(30), 24(32)
58(30), 28(32), 14(31)
80(32), 20(31)
95(rac-30), 2(rac-32), 3(rac-31)
8
8
8
9
11/11ent
11/11ent
11ent
9
9
10
11/11ent
11/11ent
11/11ent
11ent
10
10
10a
rt
Reflux
50 ꢁC
rt
Reflux
rt
Reflux
rt
rt
12
12
11/11ent
11/11ent
11/11ent
11/11ent
11ent
12
12
12
12/12entb
1/11ent
a Reaction performed under high pressure (11 kbar).
b Obtained via racemization of 12 under basic condition (Et3N in aq EtOH, 1 h).13
Figure 2. Molecular structure of the compounds 20 and 28 with the crystallographical numbering scheme.3
AcO
R
AcO
O
R
AcO
R
unreacted nitrone ent-11 in 53% yield (Table 4). Optically
pure nitrone ent-11 was obtained when the cycloaddition
involved 1.6 equiv of the racemate 11/ent-11. Under the
same conditions, 1:1 proportion of reactants, besides 21,
led to unseparable mixture of two other adducts 23 and
25, in the ratio of about 82:12:6, respectively, in 65% yield.
Reaction of enantiomerically pure nitrone ent-11 with 10 at
50 ꢁC for 24 h showed two products, adduct 23 and 25 in
the ratio of about 2:1, respectively, in 74% yield. In the case
of both mismatched pairs 8/ent-11 and 10/ent-11 cycload-
dition proceeded in lower yields than in corresponding
matched pairs 8/11 and 10/11 providing exo adducts only
(Table 4). The formation of endo adducts 26 and 27 was
not observed. The configuration of compounds 20–25
was proven by 1H NMR, coupling constants between
H-1a, H-2, H-5a, H-5b and H-6 protons and NOEs. Addi-
tionally the structure and configuration of 20 was con-
firmed by X-ray crystal structure determination (Fig. 2).12
O
5
1a
5a
5b
O
3
4
2
O
O
O
H
H
H
H
H
H
H
H
H
O1
O
O
N
O
N
O
N
O
6
7
8
O
O
O
24: R=H
25: R=OAc
20: R=H
21: R=OAc
22: R=H
23: R=OAc
AcO
AcO
AcO
AcO
AcO
R
O
O
O
O
O
O
H
H
H
H
H
H
H
H
H
O
O
O
N
O
N
O
N
O
O
O
O
28
29
26: R=H
27: R=OAc
Cycloaddition of D-erythro lactone 9 with 2 equiv of race-
mic nitrone 11/ent-11 at room temperature for 7 days affor-
ded two adducts 28 and 29 in a ratio of about 95:5,
respectively, and 79% yield.
Under the same conditions and a 1:1 ratio of both reac-
tants, adducts 28 and 29 were formed in a ratio of

S. Stecko et al. / Tetrahedron: Asymmetry 18 (2007) 1085–1093
1089
about 2:1, respectively; the yield of the reaction dropped to
36%. Cycloaddition of 9 with 1 equiv of 11/ent-11 in
boiling toluene for 3 days provided 28 and 29 in a ratio
of about 2:1 and in 51% yield. The structure and configu-
ration of 28 was proven by X-ray crystallography
(Fig. 2).12
example, heating of the mixture of adducts 32 and 31 (in
the ratio 4:1) in toluene solution revealed the formation
of ent-30 after 3 days to give an ent-30:31:32 ratio equal
to 12:67:21, respectively. The prolongation of the reaction
time, however, decreased the content of 31 and 32, whereas
it did not significantly increase the content of ent-30. This
was caused by the decomposition of the nitrone ent-11,
formed via retro-cycloaddition, and testified that its
decomposition was faster than the cycloaddition to both
enantiomeric forms of the lactone 12/ent-12. The presence
of ent-30 was detected by NMR spectra and by HPLC on
the chiral columnà and compared with the chromatogram
of the racemic adduct 30/ent-30 obtained by cycloaddition
of both racemic nitrone and lactone.
TBDPSO
TBDPSO
TBDPSO
O
N
O
N
O
N
O
H
O
O
H
H
H
H
H
H
H
H
O
O
O
O
O
O
O
O
O
31
32
30
TBDPSO
3. Conclusions
TBDPSO
O
N
O
N
O
O
H
The results we have reported herein show that d-lactones
are attractive dipolarophiles which can be used for the ki-
netic resolution of a racemic nitrone. This resulted from
the fact that cycloadditions involving d-lactones are not
reversible and usually form one predominating adduct, or
in many cases, produce a single product. The correspond-
ing transformations involving c-lactones are more compli-
cated. As we showed, cycloadditions to c-lactones
proceeded with lower diastereoselectivity, when compared
with the cycloaddition to six-membered ones because of
the possible formation of endo adducts. Moreover, the
reversibility of cycloaddition, as well as racemization of
5-substituted 2-(5H)-furanones, additionally complicates
the composition of the post-reaction mixtures and may
lead to the formation of partially racemic products. The
possible asymmetric transformation, which eventually
would provide the most stable thermodynamic product,
cannot be performed effectively due to the low stability of
cyclic nitrones. As a result, c-lactones are less attractive
in target-oriented synthesis.
H
H
H
H
H
O
O
O
O
O
O
ent-31
ent-30
In order to increase the stability of dipolarophile, for the
investigation of the cycloaddition between racemic nitrone
11/ent-11 and a chiral c-lactone, we decided to use tert-
butyldiphenylsilyl-protected compound 12. Bearing in
mind the results of the cycloaddition of 2 and 6, presented
above, one could expect that the cycloaddition of the c-lac-
tone 12 with racemic nitrone 11/ent-11 under kinetic con-
trol would lead to an interesting kinetic resolution
providing the exo adduct 30 with 11 and the endo one 32
with ent-11.
Cycloaddition of lactone 12 to 1 equiv of the racemate 11/
ent-11 at room temperature for 7 days led to the formation
of three adducts 30–32 in a ratio of about 71:6:23, respec-
tively, in 68% overall yield (Table 4).
4. Experimental
4.1. General
Under reflux for 7 days, the content of the endo adduct 32
raised significantly and only trace amounts of compound
31 were detected (Table 4). The yield, however, dropped
to 49%. Cycloaddition of 12 with 2 equiv of racemic nit-
rone 11/ent-11 at room temperature for 7 days afforded
two adducts 30 and 32 in a ratio of about 3:1, respectively.
Under reflux in toluene solution the content of adducts de-
rived from ent-11 was increased. Reaction of 12 with ent-11
provided adducts 32 and 31 in a ratio of 4:1, respectively.
The proportions of stereoisomers 30–32 were determined
by HPLC. One can expect, however, that reversibility of
the cycloaddition and racemization of the lactone 12 can
provide enantiomeric forms of adducts: 30ent by epimer-
ization of 31 at C-2 and 31ent by similar epimerization of
30. Both processes should eventually result in the decrease
of enantiomeric excess of 30 and 31. The process of racemi-
zation of 31 cannot be observed due to the low content of
this stereoisomer in the reaction mixture and the highest
stability of the adduct 30. The first process, however, the
formation of ent-30 from 31 can be easily observed. For
Melting points were determined by using Ko¨fler hot-stage
apparatus with microscope and are uncorrected. Proton
and carbon NMR spectra were recorded on a Bruker
DRX 500 Avance Spectrometer at 500 MHz and
125 MHz, respectively, using deuterated solvents and
TMS as an internal standard. Chemical shifts are reported
as d values in ppm and coupling constants are in Hertz.
Infrared spectra were obtained on an FT IR-1600 Per-
kin–Elmer spectrophotometer. The optical rotations were
measured with a JASCO J-1020 digital polarimeter. High
resolution mass spectra were recorded on ESI-TOF Mari-
ner spectrometer (Perspective Biosystem). X-ray analysis
was performed on Nonius MACH3 diffractometer. HPLC
chromatography was recorded on Merck LaChrom
à HPLC: column Chiralcelꢂ OD-H, hexane:i-propanol 90:10, 1 mL/min,
retention times: 15.7 min 30, 27.3 min 30ent.

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S. Stecko et al. / Tetrahedron: Asymmetry 18 (2007) 1085–1093
chromatograph equipped with Hitachi Pump L-2130 and
Hitachi Diode Array Detector L-2450.
4.4. Cycloaddition of lactone 8 to nitrone ent-11
4.4.1. General procedure. Lactone 8 (34 mg, 0.2 mmol)
and nitrone 11ent (31 mg, 0.2 mmol) were dissolved in
dry toluene (5 mL) and refluxed for 5 days under a nitrogen
atmosphere. The reaction progress was monitored by TLC
chromatography (hexane–ethyl acetate 1:4). After the sol-
vent was evaporated, the residue was chromatographed
(ethyl acetate–hexane 70:30 v/v) to afford 22 (27 mg,
41%, Rf = 0.28) and 24 (7 mg, 10%, Rf = 0.45).
Thin layer chromatography (TLC) was performed on alu-
minium sheets silica gel 60 F254 (20 · 20 · 0.2) from Merck.
Column chromatography (CC) was carried out using
Merck silica gel 230–400 mesh. The TLC spots were visual-
ized by treatment with alcoholic solution of ninhydrine
(spray) and heating.
All solvents were dried and purified by the standard
techniques.
4.4.2. (1aR,3S,5aR,5bS,6S,7R)-3-Acetoxymethyl-hexahy-
dro-6,7-O-isopropylidenedioxy-pyrrolo[1,2-b]-pyrano[3,4-d]-
isoxazol-5(3H)-one 20. Mp 100–102 ꢁC; [a]D = +37.3 (c
Nitrone 2,18 lactones 519 and 620 were obtained following
literature procedure. Silylated lactone 12 were prepared
according to literature procedure.21 Racemic nitrone 11/
ent-11 was obtained from D-arabinose following known
procedure.14 Enantiomerically pure nitrones 11 and ent-
11 were obtained by intramolecular alkylation of
corresponding 2,3-O-isopropylidene-D- and L-erythrose
oxime.15–17
0.9, CH2Cl2); IR(film): m 1740, 1234 cmꢀ1 1H NMR
;
(500 MHz, CDCl3) d: 4.89 (ddd, 1H, J 6.6, 5.2, 1.0 Hz,
H-7), 4.86 (d, 1H, J 6.6 Hz, H-6), 4.80 (dddd, 1H, J 11.3,
5.4, 3.6, 2.0 Hz, H-3), 4.74 (ddd, 1H, J 8.8, 3.7, 2.0 Hz,
H-1a), 4.26 (dd, 1H, J 12.2, 3.6 Hz, CHHOAc), 4.20 (dd,
1H, J 12.2, 5.4 Hz, CHHOAc), 3.86 (d, 1H, J 7.9 Hz, H-
5b), 3.50 (dd, 1H, J 12.3, 1.0 Hz, H-8), 3.23 (dd, 1H, J
8.8, 7.9 Hz, H-5a), 2.97 (dd, 1H, J 12.3, 5.2 Hz, H-80),
2.10 (s, 3H, OAc), 2.00 (dt, 1H, J 15.1, 2.0 Hz, H-2), 1.91
(ddd, 1H, J 11.3, 3.7 Hz, H-20), 1.50, 1.31 (2s, 6H,
C(CH3)2); 13C NMR (125 MHz, CDCl3) d: 170.4, 168.7,
112.3, 81.4, 78.5, 76.4, 73.0, 72.6, 64.8, 58.3, 49.2, 29.7,
26.2, 24.7, 20.6; MS HR (ESI) m/z [M+Na]+, Calcd for
C15H21NO7Na: 350.1210. Found: 350.1227.
4.2. Cycloaddition of lactones 5 and 6 to nitrone 2
General procedure:
A solution of lactone 5 or 6
(0.375 mmol) and nitrone 2 (78.5 mg, 0.500 mmol) in sol-
vent (Table 1; 5 mL) was stirred under nitrogen for periods
of time as shown in Table 1. Subsequently, the solvent was
evaporated and the product isolated by chromatography
using hexane–ethyl acetate 1:2 v/v as an eluent. Two frac-
tions were collected; the first one contained both exo-
adducts.§ (TLC, Rf 0.5, ethyl acetate–hexane 2:1) while
the second fraction contained endo-adduct (TLC, Rf 0.3,
ethyl acetate–hexane 2:1).
4.4.3. (1aS,3S,5aS,5bR,6R,7S)-3-Acetoxymethyl-hexahy-
dro-6,7-O-isopropylidenedioxy-pyrrolo[1,2-b]-pyrano[3,4-d]-
isoxazol-5(3H)-one 22. Colourless crystals; mp 158–
161 ꢁC; [a]D = ꢀ3.7 (c 0.4, CH2Cl2); IR(film): m 1747,
1241 cmꢀ1 1H NMR (500 MHz, CDCl3) d: 4.92 (ddd,
;
1H, J 6.5, 5.5, 2.5 Hz, H-7), 4.86 (dd, 1H, J 6.5, 1.9 Hz,
H-6), 4.67 (ddd, 1H, J 10.3, 9.5, 6.7 Hz, H-1a), 4.40 (dddd,
1H, J 11.8, 5.9, 3.6, 1.5 Hz, H-3), 4.26 (dd, 1H, J 12.1,
4.3. Isomerization of 14 (exo-anti)
3.6 Hz, CHHOAc), 4.22 (dd, 1H,
J 12.1, 5.9 Hz,
CHHOAc), 4.07 (dd, 1H, J 5.9, 1.9 Hz, H-5b), 3.43 (dd,
1H, J 13.1, 2.5 Hz, H-8), 3.28 (dd, 1H, J 9.5, 5.9 Hz, H-
5a), 3.18 (dd, 1H, J 13.1, 5.5 Hz, H-80), 2.22 (ddd, 1H, J
13.7, 6.7, 1.5 Hz, H-2), 2.10 (s, 3H, OAc), 1.77 (ddd, 1H,
J 13.7, 11.8, 10.3 Hz, H-20), 1.52, 1.32 (2s, 6H, C(CH3)2);
13C NMR (125 MHz, CDCl3) d: 170.6, 169.4, 113.1, 83.5,
79.5, 74.7, 73.5, 72.4, 65.0, 59.9, 49.6, 30.3, 26.6, 24.9,
20.7; HR MS (ESI) m/z [M+Na]+, Calcd for C15H21NO7-
Na: 350.1210. Found: 350.1231.
4.3.1. General procedure. Solution of 30 mg of adduct 14
(0.124 mmol) in 5 mL of dry toluene was heated at reflux
under nitrogen for appropriate period of time (Table 2).
Subsequently, the solvent was evaporated and mixture of
14/15 was isolated by chromatography on silica gel using
hexane–ethyl acetate 1:2 v/v as an eluent.
4.3.2. (1aS,4aR,4bS,5S)-5-tert-Butoxy-hexahydrofuro[3,4-
d]pyrrolo[1,2-b]isoxazol-4(3H)-one 15. Mp 102–103 ꢁC
(benzene–diethyl ether 1:1); [a]D = +1.2 (c 0.4, CH2Cl2);
4.4.4. (1aR,3S,5aR,5bS,6R,7S)-3-Acetoxymethyl-hexahy-
dro-6,7-O-isopropylidenedioxy-pyrrolo[1,2-b]-pyrano[3,4-d]-
isoxazol-5(3H)-one 24. Colourless oil; [a]D = +20.5 (c 0.1,
IR (film): m 1771 cmꢀ1 1H NMR (500 MHz, C6D6) d:
;
4.13 (1H, ddd, J 7.1, 5.3, 1.7 Hz, H-1a), 4.03 (1H, dd, J
10.4, 1.7 Hz, H-2), 3.74 (1H, dd, J 7.3, 1.3 Hz, H-4b),
3.59–3.54 (2H, m, H-20, H-5), 3.35 (1H, dd, J 7.1, 1.3 Hz,
H-4a), 3.11 (1H, ddd, J 13.3, 7.7, 3.6 Hz, H-7), 2.58 (1H,
ddd, J 13.3, 10.0, 7.0 Hz, H-70), 1.64 (1H, dddd, J 12.8,
10.0, 7.7, 5.9 Hz, H-6), 1.46 (1H, dddd, J 12.8, 7.2, 7.0,
3.6 Hz, H-60), 0.97 (9H, s, t-Bu); 13C NMR (125 MHz,
C6D6) d: 177.1, 77.6, 73.9, 73.7, 72.5, 71.5, 53.2, 50.1,
34.1, 28.2; HR MS (ESI) m/z [M+H]+ Calcd for
C12H20NO4 242.1387. Found 242.1379.
CH2Cl2); IR(film): 1739, 1733, 1229 cmꢀ1
;
1H NMR
(500 MHz, CDCl3) d: 5.08 (dddd, 1H, J 11.2, 5.5, 3.4,
2.1 Hz, H-3), 4.86 (ddd, 1H, J 6.3, 5.3, 1.0 Hz, H-7), 4.80
(dd, 1H, J 6.3, 5.3 Hz, H-6), 4.65 (ddd, 1H, J 8.0, 3.4,
3.2 Hz, H-1a), 4.27 (dd, 1H, J 12.2, 3.4 Hz, CHHOAc),
4.20 (dd, 1H, J 12.2, 5.5 Hz, CHHOAc), 3.88 (dd, 1H, J
8.0, 1.2 Hz, H-5a), 3.77 (dd, 1H, J 5.3, 1.2 Hz, H-5b),
3.63 (br d, 1H, J 15.5 Hz, H-8), 3.05 (dd, 1H, J 15.5,
5.3 Hz, H-80), 2.10 (s, 3H, OAc), 2.05 (ddd, 1H, J 14.5,
3.2, 2.1 Hz, H-2), 1.84 (ddd, 1H, J 14.5, 11.2, 3.4 Hz, H-
20), 1.49, 1.33 (2s, 6H, C(CH3)2); HR MS (ESI) m/z
§ The 14:15 ratio was determined by NMR spectra in benzene-d6.

S. Stecko et al. / Tetrahedron: Asymmetry 18 (2007) 1085–1093
1091
[M+Na]+, Calcd for C15H21NO7Na: 350.1210. Found
350.1222.
5.6 Hz, CHHOAc), 3.46 (dd, 1H, J 3.3, 2.7 Hz, H-5b),
3.11 (dd, 1H, J 13.8, 3.8 Hz, H-8), 3.00 (dd, 1H, J 13.8,
5.8 Hz, H-80), 2.53 (ddd, 1H, J 7.9, 3.3, 2.0 Hz, H-5a),
1.56, 1.53 (2s, 6H, 2 · OAc), 1.46, 1.16 (2s, 6H,
C(CH3)2); 13C NMR (125 MHz, CDCl3) taken for the mix-
ture 23 and 25, d: 170.3, 169.7, 169.5, 114.3, 85.5, 80.7,
75.8, 74.1, 72.8, 67.7, 61.8, 60.4, 51.0, 26.9, 24.8, 20.7,
20.7; HR MS (ESI) m/z [M+Na]+ taken for the mixture
23 and 25, Calcd for C17H23NO9Na: 408.1265. Found:
408.1265.
4.5. Kinetic resolution of 11/ent-11
4.5.1. General procedure. Lactone 10 (228 mg, 1.0 mmol)
and racemic nitrone 11/ent-11 (267 mg, 1.6 mmol) were dis-
solved in dry toluene (40 mL) and the reaction was carried
out for 6 days at room temperature (under nitrogen). The
reaction was monitored by TLC chromatography (hex-
ane–ethyl acetate 1:1, Rf = 0.28). After this, the solvent
was evaporated and residue purified by column chromato-
graphy—at first cycloadduct 21 was eluted by using a mix-
ture of hexane–ethyl acetate (1:1 v/v) and then residue on
column was eluted by a mixture of methylene chloride–
methanol (90:10 v/v) affording 110 mg of pure ent-11
(39%) as colourless crystals. The optical purity of (+)-ent-
11 was confirmed by chiral HPLC chromatography. Chiral
HPLC chromatography: Chiralpak ASꢂ, i-propanol
(100%), sample concentration 1 mg/mL, flow rate
0.3 mL/min, retention times: 66.0 min (ꢀ)-11 and
72.6 min (+)-ent-11.
4.5.5. (1aS,2R,3R,5aR,5bS,6R,7S)-2-Acetoxy-3-acetoxy-
methyl-hexahydro-6,7-O-isopropylidenedioxy-pyrrolo[1,2-b]-
pyrano[3,4-d]isoxazol-5(3H)-one 25. 1H NMR (500 MHz,
C6D6) taken for the mixture 23 and 25, d: 5.30 (ddd, 1H, J
6.8, 5.4, 1.4 Hz, H-3), 5.28 (dd, 1H, J 3.5, 1.4 Hz, H-2), 4.58
(dd, 1H, J 8.2, 3.5 Hz, H-1a), 4.23 (dd, 1H, J 11.7, 6.8 Hz,
CHHOAc), 4.14 (dd, 1H, J 11.7, 5.4 Hz, CHHOAc), 4.10
(dd, 1H, J 6.3, 5.3 Hz, H-7), 4.00 (d, 1H, J 8.2 Hz, H-5a),
3.96 (dd, 1H, J 6.3, 5.2 Hz, H-6), 3.53 (d, 1H, J 15.7 Hz,
H-8), 3.24 (d, 1H, J 5.2 Hz, H-5b), 2.35 (dd, 1H, J 15.7,
5.3 Hz, H-80), 1.57, 1.44 (2s, 6H, 2 · OAc), 1.37, 1.06 (2s,
6H, C(CH3)2); 13C NMR (125 MHz, CDCl3) taken for
the mixture 23 and 25, d: 170.3, 169.6, 169.4, 113.2, 82.9,
82.0, 75.2, 75.2, 74.3, 66.6, 62.1, 59.8, 47.3, 26.2, 23.9,
20.7, 20.7.
4.5.2. (+)-3,4-Isopropylidenodioxypyrroline-1-oxide ent-
30
11. Mp 101.5–102.5 ꢁC; ½aꢁD ¼ þ26:1 (c 0.56, CH2Cl2);
20
Ref. 14b ½aꢁD ¼ þ27:7 (c 0.46, CH2Cl2); for 11: Ref. 14b
20
26
½aꢁD ¼ ꢀ28 (c 0.46, CH2Cl2); Ref. 15 ½aꢁD ¼ ꢀ26:3 (c
0.50, CH2Cl2); Ref. 16 [a]D = ꢀ26.5 (c 0.83, CH2Cl2);
IR(film): m 1580 cmꢀ1 1H NMR (500 MHz, CDCl3) d:
;
4.5.6.
(1aS,2S,3R,5aR,5bS,6S,7R)-2-Acetoxy-3-acetoxy-
methyl-hexahydro-6,7-O-isopropylidenedioxy-pyrrolo[1,2-b]-
pyrano[3,4-d]isoxazol-5(3H)-one 28. Colourless crystals;
mp 63–65 ꢁC; [a]D = +95.2 (c 0.8, CH2Cl2); IR(film): m
6.89 (q, 1H, J 1.6 Hz, H-2), 5.30 (br d, 1H, J 6.4 Hz, H-
3), 4.92 (ddd, 1H, J 6.5, 5.2, 1.3 Hz, H-4), 4.14 (ddd, 1H,
J 15.2, 5.4, 1.9 Hz, H-5), 4.06 (dq, 1H, J 15.2, 1.3 Hz, H-
50), 1.46, 1.39 (2s, 6H, C(CH3)2); 13C NMR (125 MHz,
CDCl3) d: 132.5, 112.2, 79.8, 73.6, 67.9, 27.2, 25.7; HR
MS (ESI) m/z [M+H]+, Calcd for C7H12NO3: 158.0812.
Found: 158.0804; HPLC: retention time 72.6 min.
1746, 1218 cmꢀ1 1H NMR (500 MHz, CDCl3) d: 5.10
;
(dd, 1H, J 9.4, 3.4 Hz, H-2), 4.99 (ddd, 1H, J 9.4, 3.9,
2.6 Hz, H-3), 4.94 (ddd, 1H, J 6.6, 5.6, 3.1 Hz, H-7), 4.76
(dd, 1H, J 6.6, 2.7 Hz, H-6), 4.74 (dd, 1H, J 8.4, 3.4 Hz,
H-1a), 4.37 (dd, 1H, J 12.6, 3.9 Hz, CHHOAc), 4.28 (dd,
1H, J 12.6, 2.6 Hz, CHHOAc), 3.92 (dd, 1H, J 4.9,
2.7 Hz, H-5b), 3.56 (dd, 1H, J 8.4, 4.9 Hz, H-5a), 3.38
(dd, 1H, J 13.6, 3.1 Hz, H-8), 3.32 (dd, 1H, J 13.6,
5.6 Hz, H-80), 2.12, 2.08 (2s, 6H, 2 · OAc), 1.50, 1.32 (2s,
6H, C(CH3)2); 13C NMR (125 MHz, CDCl3) d: 170.3,
169.6, 167.3, 113.7, 83.3, 79.8, 77.3, 73.4, 72.0, 66.3, 61.4,
60.2, 50.8, 26.6, 24.8, 20.7, 20.6; HR MS (ESI) m/z
[M+Na]+, Calcd for C17H23NO9Na: 408.1265. Found:
408.1272.
4.5.3. (1aS,2R,3R,5aR,5bS,6S,7R)-2-Acetoxy-3-acetoxy-
methyl-hexahydro-6,7-O-isopropylidenedioxy-pyrrolo[1,2-b]-
pyrano[3,4-d]isoxazol-5(3H)-one 21. Colourless crystals;
mp 106–108 ꢁC; [a]D = +30.7 (c 0.8, CH2Cl2); IR(film): m
1747, 1223 cmꢀ1 1H NMR (500 MHz, CDCl3) d: 5.08
;
(dd, 1H, J 2.6, 1.1 Hz, H-2), 4.93 (dd, 1H, J 6.2, 1.1 Hz,
H-3), 4.91 (ddd, 1H, J 6.6, 5.5, 2.1 Hz, H-7), 4.80 (dd,
1H, J 6.6, 1.8 Hz, H-6), 4.51 (dd, 1H, J 8.6, 2.6 Hz, H-
1a), 4.23 (m, 2H, CH2OAc), 3.85 (dd, 1H, J 6.5, 1.8 Hz,
H-5b), 3.44 (dd, 1H, J 13.0, 2.1 Hz, H-8), 3.38 (dd, 1H, J
8.6, 6.5 Hz, H-5a), 3.08 (dd, 1H, J 13.0, 5.5 Hz, H-80),
2.11, 2.09 (2s, 6H, 2 · OAc), 1.50, 1.31 (2s, 6H,
C(CH3)2); 13C NMR (125 MHz, CDCl3) d: 170.2, 169.3,
167.4, 113.1, 82.4, 79.1, 76.5, 75.1, 73.7, 65.8, 61.8, 59.3,
48.6, 26.4, 24.7, 20.6, 20.6; HR MS (ESI) m/z [M+Na]+,
Calcd for C17H23NO9Na: 408.1265. Found: 408.1284.
4.5.7. (1aR,2S,3R,5aS,5bR,6R,7S)-2-Acetoxy-3-acetoxy-
methyl-hexahydro-6,7-O-isopropylidenedioxy-pyrrolo[1,2-b]-
pyrano[3,4-d]isoxazol-5(3H)-one 29. Colourless oil; [a]D =
ꢀ2.9 (c 0.2, CH2Cl2); IR(film): m 1745, 1203 cmꢀ1
;
1H
NMR (500 MHz, CDCl3) d: 5.22 (dd, 1H, J 9.1, 7.6 Hz,
H-2), 4.96 (ddd, 1H, J 6.6, 5.8, 3.8 Hz, H-7), 4.76 (dd,
1H, J 6.6, 3.2 Hz, H-6), 4.49 (dd, 1H, J 9.6, 7.6 Hz, H-
1a), 4.43 (ddd, 1H, J 9.1, 5.1, 2.5 Hz, H-3), 4.38 (dd, 1H,
J 12.4, 5.1 Hz, CHHOAc), 4.22 (dd, 1H, J 12.4, 2.5 Hz,
CHHOAc), 4.10 (dd, 1H, J 3.8, 3.2 Hz, H-5b), 3.64 (dd,
1H, J 9.6, 3.8 Hz, H-5a), 3.42 (dd, 1H, J 13.9, 5.8 Hz, H-
8), 3.32 (dd, 1H, J 13.9, 3.8 Hz, H-80), 2.11, 2.08 (2s, 6H,
2 · OAc), 1.52, 1.33 (2s, 6H, C(CH3)2); 13C NMR
(125 MHz, CDCl3) d: 170.5, 168.9, 167.8, 114.1, 84.7,
80.6, 76.3, 75.5, 74.7, 67.0, 61.2, 60.4, 50.2, 26.9, 24.9,
4.5.4. (1aR,2R,3R,5aS,5bR,6R,7S)-2-Acetoxy-3-acetoxy-
methyl-hexahydro-6,7-O-isopropylidenedioxy-pyrrolo[1,2-b]-
pyrano[3,4-d]isoxazol-5(3H)-one 23. 1H NMR (500 MHz,
C6D6) taken for the mixture 23 and 25, d: 4.84 (dd, 1H, J
2.0, 1.1 Hz, H-2), 4.78 (ddd, 1H, J 6.9, 5.6, 1.1 Hz, H-3),
4.43 (ddd, 1H, J 6.6, 5.8, 3.8 Hz, H-7), 4.28 (d, 1H, J
7.9 Hz, H-1a), 4.18 (dd, 1H, J 6.6, 2.7 Hz, H-6), 4.09 (dd,
1H, J 11.6, 6.9 Hz, CHHOAc), 4.05 (dd, 1H, J 11.6,

1092
S. Stecko et al. / Tetrahedron: Asymmetry 18 (2007) 1085–1093
20.7, 20.6; HR MS (ESI) m/z [M+Na]+, Calcd for
C17H23NO9Na: 408.1265. Found: 408.1276.
ꢀ5.6 (c 0.2, CH2Cl2); IR(film): m 1775, 1112 cmꢀ1
;
1H
NMR (500 MHz, C6D6, without aromatic protons) d:
5.38 (dd, 1H, J 6.5, 1.8 Hz, H-5), 4.71 (ddd, 1H, J 6.5,
5.7, 2.8 Hz, H-6), 4.48 (d, 1H, J 6.8 Hz, H-1a), 4.08 (dd,
1H, J 2.9, 1.9 Hz, H-2), 3.94 (dd, 1H, J 8.8, 1.8 Hz, H-
4b), 3.58 (dd, 1H, J 11.5, 2.9 Hz, CHHOSiPh2t-Bu), 3.46
(dd, 1H, J 8.8, 6.8 Hz, H-4a), 3.41 (dd, 1H, J 13.3,
2.9 Hz, H-7), 3.15 (dd, 1H, J 13.3, 5.7 Hz, H-70), 3.10
(dd, 1H, J 11.5, 1.9 Hz, CHHOSiPh2t-Bu), 1.49, 1.14 (2s,
6H, C(CH3)2), 1.02 (s, 9H, t-Bu); 13C NMR (125 MHz,
C6D6) d: 175.1, 112.6, 83.1, 83.1, 80.3, 79.9, 74.4, 64.2,
61.6, 52.1, 27.0, 26.8, 24.9, 19.2; HR MS (ESI) m/z
[M+Na]+, Calcd for C28H35NO6NaSi: 532.21259. Found:
532.2109.
4.6. Synthesis of lactone 12
4.6.1. (5S)-5-(tert-Butyldiphenylsiloxymethyl)-2(5H)-fura-
none 12. To a solution of 6 (1.016 g, 8.9 mmol) and imid-
azole (0.864 g, 12.7 mmol) in CH2Cl2 (20 mL) at 0 ꢁC was
added tert-butyldiphenylsilyl chloride (3.143 g, 2.9 mL,
11.4 mmol). After 45 min, the reaction was quenched by
addition of water (20 mL). The layers were separated and
the aqueous layer was extracted with CH2Cl2
(3 · 10 mL). The combined organic extracts were dried
over sodium sulfate. Evaporation of the solvent followed
by chromatographical purification yielded 12 (2.923 g,
97%) as colourless crystals: mp 79–81 ꢁC (diethyl ether–
4.7.4. (1aR,2R,4aS,4bR,5R,6S)-2-tert-Butyldiphenyl-siloxy-
methyl-hexahydro-5,6-O-isopropylidenedioxy-pyrrolo[1,2-b]-
furo[3,4-d]isoxazol-4(3H)-one 31. Colourless oil; [a]D =
25
benzene 1:1), Ref. 22 79–80 ꢁC; ½aꢁD ¼ ꢀ80:6 (c 1.33,
22
CH2Cl2), Ref. 22 ½aꢁD ¼ ꢀ83:0 (c 1.6, CH2Cl2); IR(film):
1
m 1755 cmꢀ1; H NMR (500 MHz, C6D6 without aromatic
1
ꢀ11.5 (c 0.25, CH2Cl2); IR(film): m 1775, 1112 cmꢀ1; H
protons) d: 6.40 (dd, 1H, J 5.7, 1.6 Hz, H-3), 5.63 (dd, 1H,
J 5.7, 2.0 Hz, H-4), 4.31 (dddd, 1H, J 4.4, 4.3, 2.0, 1.6 Hz,
H-5), 3.52 (dd, 1H, J 11.0, 4.3 Hz, CHHOSiPh2t-Bu), 3.37
(dd, 1H, J 11.0, 4.4 Hz, CHHOSiPh2t-Bu), 1.07 (s, 9H, t-
Bu); 13C NMR (125 MHz, C6D6) d: 171.9, 152.7, 122.7,
82.7, 63.5, 26.9, 19.4; HR MS (ESI) m/z [M+Na]+, Calcd
for C21H24O3NaSi: 375.13869. Found: 375.13859.
NMR (500 MHz, CDCl3, without aromatic protons) d:
4.97 (ddd, 1H, J 6.5, 6.0, 4.5 Hz, H-6), 4.80 (dd, 1H, J
7.2, 5.2, Hz, H-1a), 4.60 (dd, 1H, J 6.5, 4.9 Hz, H-5),
4.58 (ddd, 1H, J 6.6, 6.0, 5.2 Hz, H-2), 4.03 (dd, 1H, J
10.9, 6.0 Hz, CHHOSiPh2t-Bu), 3.99 (dd, 1H, J 10.9,
6.6 Hz, CHHOSiPh2t-Bu), 3.88 (d, 1H, J 4.9 Hz, H-4b),
3.68 (d, 1H, J 7.2 Hz, H-4a), 3.54 (dd, 1H, J 14.6,
6.0 Hz, H-7), 3.14 (dd, 1H, J 14.6, 4.5 Hz, H-70), 1.52,
1.33 (2s, 6 H, C(CH3)2), 1.06 (s, 9H, t-Bu); 13C NMR
(125 MHz, C6D6) d: 174.1, 114.7, 85.4, 82.8, 82.0, 76.0,
75.9, 62.0, 61.1, 53.6, 27.2, 27.0, 25.1, 19.5; HR MS (ESI)
m/z [M+Na]+, Calcd for C28H35NO6NaSi: 532.21259.
Found: 532.2146.
4.7. Cycloaddition of lactone 12 to racemic nitrone 11/ent-11
4.7.1. General procedure. Solution of lactone 12 and nit-
rone 11/ent-11 in dry toluene (10 mL) was stirred at ambi-
ent temperature under nitrogen (for reagents’ ratio see
Table 4). The reaction progress was monitored by HPLC
chromatography (LiChrospher Si60ꢂ, hexane–isopropanol
97:3 v/v, flow rate 1 mL/min, sample concentration 1 mg/
mL, retention times: 9.1 min 30, 9.5 min 32, 12.5 min 12
and 28.4 min 31). After that solvent was evaporated, the
adducts were isolated by chromatography on silica gel by
using mixture of hexane and ethyl acetate as a eluent (5:1
v/v).
Acknowledgement
This work was supported by the Ministry of Science and
Informatics Grant # 3 T09A 025 28.
References
4.7.2. (1aS,2R,4aR,4bS,5S,6R)-2-tert-Butyldiphenylsiloxy-
methyl-hexahydro-5,6-O-isopropylidenedioxy-pyrrolo-[1,2-
1. Jurczak, M.; Rabiczko, J.; Socha, D.; Chmielewski, M.;
Cardona, F.; Goti, A.; Brandi, A. Tetrahedron: Asymmetry
2000, 11, 2015–2022.
b]-furo[3,4-d]isoxazol-4(3H)-one 30. Colourless oil; [a]D
=
+22.5 (c 0.4, CH2Cl2); IR(film): m 1776, 1113 cmꢀ1 1H
;
2. Socha, D.; Jurczak, M.; Frelek, J.; Klimek, A.; Rabiczko, J.;
NMR (500 MHz, C6D6, without aromatic protons) d:
4.62 (ddd, 1H, J 6.7, 6.0, 4.5 Hz, H-6), 4.49 (dd, 1H, J
7.5, 1.3 Hz, H-1a), 4.30 (ddd, 1H, J 2.9, 2.3, 1.3 Hz, H-
2), 4.26 (dd, 1H, J 6.7, 4.1 Hz, H-5), 4.03 (dd, 1H, J 4.1,
1.6 Hz, H-4b), 3.54 (dd, 1H, J 11.4, 2.9 Hz, CHHO-
SiPh2t-Bu), 3.43 (dd, 1H, J 7.5, 1.6 Hz, H-4a), 3.34 (dd,
1H, J 14.2, 6.0 Hz, H-7), 3.26 (dd, 1H, J 11.4, 2.3 Hz,
CHHOSiPh2t-Bu), 3.08 (dd, 1H, J 14.2, 4.5 Hz, H-70),
1.38, 1.16 (2s, 6H, C(CH3)2), 1.06 (s, 9H, t-Bu); 13C
NMR (125 MHz, C6D6) d: 174.9, 114.5, 85.8, 85.0, 81.8,
78.7, 76.6, 64.3, 60.8, 54.2, 27.2, 26.9, 25.2, 19.3; HR MS
(ESI) m/z [M+H]+, Calcd for C28H36NO6Si: 510.23064.
Found: 510.2311.
´
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