Synthesis and structure of condensed heterocycles derived from intramolecular 1,3-dipolar cycloaddition of transient and enantiomerically pure α-allylamino nitrones and nitrile oxides in a high level of diastereoselectivity

Article abstract of DOI:10.1055/s-2000-6334

A series of typical nitrone and nitrile oxide derivatives was generated in situ from the corresponding sulfonylated α-allylamino aldehydes and aldoximes, which afforded isoxazolidine and isoxazoline fused heterocycles by intramolecular 1,3-dipolar cycloaddition reactions with a high degree of diastereoselectivity. The structure as well as the absolute stereochemistry of the products were confirmed by extensive 2D-NMR spectroscopy and single crystal X-ray analyses and the reasons for the observed selectivity were explained by the energy calculations of the transition states using semiemprical (MOPAC AM1 and MOPAC PM3) and ab initio methods (3-21G* and 6- 31G*).

Full text of DOI:10.1055/s-2000-6334

PAPER
365
Synthesis and Structure of Condensed Heterocycles Derived from
Intramolecular 1,3-Dipolar Cycloaddition of Transient and Enantiomerically
Pure a-Allylamino Nitrones and Nitrile Oxides in a High Level of
Diastereoselectivity
Md. Jashim Uddin,a Minoru Kikuchi,a Ken Takedatsu,a Ken-Ichi Arai,a Tetsuya Fujimoto,a Jiro Motoyoshiya,b Akikazu
Kakehi,c Ryozo Iriye,d Hirofusa Shirai,a Iwao Yamamoto*a
a Department of Functional Polymer Science, Shinshu University, Ueda, Nagano 386-8567, Japan
b Department of Material Creation Chemistry, Shinshu University, Ueda, Nagano 386-8567, Japan
c Department of Chemistry and Material Engineering, Shinshu University, Wakasato, Nagano 380-8553, Japan
d Department of Bioscience and Biotechnology, Shinshu University, Kami-Ina, Nagano 399-4598, Japan
Fax +81(268)215494; E-mail: ganchan@giptc.shinshu-u.ac.jp
Received 27 August 1999; revised 7 October 1999
their potential as latent synthetic equivalents has only re-
Abstract: A series of typical nitrone and nitrile oxide derivatives
cently begun to be realized.16 On the other hand, the
dipolarophilic activity of the C-C double, triple or hetero-
multiple bonds depends significantly on the belonging
was generated in situ from the corresponding sulfonylated a-allyl-
amino aldehydes and aldoximes, which afforded isoxazolidine and
isoxazoline fused heterocycles by intramolecular 1,3-dipolar cy-
cloaddition reactions with a high degree of diastereoselectivity. The substituents and the introduction of electron-donating or
structure as well as the absolute stereochemistry of the products
electron-withdrawing substituents on the dipole or the
alkene can alter the relative frontier orbital energies,17-18
were confirmed by extensive 2D-NMR spectroscopy and single
crystal X-ray analyses and the reasons for the observed selectivity
which could influence the reactivity as well as the selec-
were explained by the energy calculations of the transition states us-
tivity of the process.19
ing semiemprical (MOPAC AM1 and MOPAC PM3) and ab initio
methods (3-21G* and 6-31G*).
Key words: 1,3-dipolar cycloaddition, nitrones, nitrile oxides, tran-
sition states, diastereoselectivity
Recently, we have described a series of chiral auxiliary
controlled diastereoselective intramolecular Diels-Alder
reactions of sulfonyl-substituted trienes.20 In this paper,
we report a series of intramolecular 1,3-dipolar cycloaddi-
Reactions in which the formation of a new carbon-carbon
or carbon-heteroatom bond provide new stereogenic cen-
ters with a high level of enantio- and diastereoselectivity
are of special interest for asymmetric synthesis.1 The 1,3-
dipolar cycloaddition is such a reaction, which conserves
the stereochemistry of the alkene, and in which, a stereo-
center on the dipole is often able to influence the relative
stereochemistry of the newly formed stereogenic centers
in the product.2 Even greater stereocontrol is possible
when both reactants are a part of the same molecule, the
intramolecular nature, which often enhances the stereose-
lectivity of the cyclization process.3,4 As a result, this type
of cyclization could be applied to the synthesis of targeted
macromolecules, for example, sugar derivatives,5 b-lac-
tams,6 amino acids,7 alkaloids8 and other interesting
classes of compounds. Also, considerable attention has
been paid to a basic survey of this process but the general
rules for the regio- and stereoselectivities are still ob-
scure.9 Among the other 1,3-dipolar cycloadditions, the
intramolecular nitrone olefin cycloaddition and intramo-
lecular nitrile oxide olefin cycloaddition have been of
considerable synthetic and mechanistic interest,10,11 espe-
cially since the resulting heterocycles can serve as precur-
sors of synthetic equivalents,12 such as amino alcohols,13
and hydroxy ketones,14 or other functional groups.15 More
closely, while isoxazoli(di)nes are very readily available,
tion reaction of nitrones and nitrile oxides with alkenes
having an electron-withdrawing substituent and which
contain a chiral auxiliary at the allylic position. In addi-
tion, the transition state energy of conformers responsible
for producing the selective stereoisomers, the stereochem-
istry of the cycloadducts, and the subsequent ring opening
reaction to synthetic equivalents are discussed.
As the nitrones 2a-d are very unstable species (Scheme
1), they were generated in situ from the corresponding a-
allylamino aldehydes20 1a-d in anhydrous diethyl ether at
room temperature and smoothly cyclized to afford the bi-
cyclic heterocycles 3a-d in good yields (Table 1).
The oximation2 of 1a-d by hydroxylammonium chloride
in aqueous ethanol in the presence of sodium hydroxide
gave a-allylamino aldoximes 4a-d, which were also cat-
alytically tautomerized into their nitrones 5a-d by zinc
chloride in an in situ fashion (Scheme 2) in boiling ben-
zene and were intramolecularly cyclized17 to produce con-
densed heterocycles 6a-d (Table 2).
The structural assignment of all the diastereomerically
1
pure new molecules were ascertained by IR, H and 13C
NMR, DEPT, 2D-COSY, HMQC, 2D-NOESY, and
HRMS spectra and confirmed by a single crystal X-ray
analysis of (S,S,S)-3a (Figure 1).
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366
M. J. Uddin et al.
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Table 2 Diastereoselective Synthesis of Compounds 6
R
R
Ph
N
R
Ph
H
[a]2D5
dea
O
Product
R
Yield
(%)
BnN
N
O
i
BnN
(c=1.0, CHCl3) (%)
BnN
O
40-97%
(S,S,S)-6a
(S,S,S)-6b
(S,S,S)-6c
(S,S,S)-6d
(R,R,R)-6b
Bn
66
55
60
45
77
+156.9c
+137.6
+238.7
+101.9
–131.3
70
>96b
77
SO2Ph
(S)-1a-d
SO2Ph
Me
i-Pr
i-Bu
Bn
SO2Ph
(S)-2a-d
(S,S,S)-3a-d
82
Bn
>96b
Bn
Ph
N
Bn
Ph
H
O
BnN
a The de values were determined by 1H NMR spectroscopy (Bruker
DRX 500 MHz spectrometer).
N
O
i
BnN
BnN
O
54%
b In 1H NMR spectrum there were no peaks corresponding to the
other isomers.
SO2Ph
(R)-1a
SO2Ph
(R,R,R)-3a
SO2Ph
(R)-2a
c Recorded at 26∞C.
Reagents and conditions: i) PhNHOH/CaCl2/Et2O, 0°C to r. t.
Scheme 1
R
R
H
N
R
H
H
NOH
BnN
N
i
O
BnN
BnN
O
45-66%
SO2Ph
(S)-4a-d
SO2Ph
(S,S,S)-6a-d
SO2Ph
(S)-5a-d
Me
Me
H
N
Me
H
H
NOH
BnN
N
i
O
BnN
BnN
O
77%
SO2Ph
(R)-4b
SO2Ph
SO2Ph
(R)-5b
(R,R,R)-6b
Figure 1 X-ray crystal structure of (S,S,S)-3a.
Reagents and conditions: i) ZnCl2/benzene, reflux
Selected bond lengths (Å) and bond angles (°): N1-C1 1.470 (8),
O1-N1 1.440 (7), O1-C2 1.415 (8), C2-C3 1.550 (9), C3-C4 1.576
(9), C1-C3 1.533 (8), N2-C4 1.460 (8), N2-C5 1.469 (8), C1-C5
1.563 (8), O1-N1-C1 105.7 (5), N1-O1-C2 106.9 (5), O1-C2-C3
106.2 (5), C2-C3-C4 114.3 (6), C1-C3-C2 101.7 (5), C1-C3-C4
104.7 (5), C4-N2-C5 107.1 (5), N2-C4-C3 107.1 (5), N2-C5-C1
106.4 (5), C3-C1-C5 105.7 (5), N1-C1-C3 107.6 (5).36
Scheme 2
Table 1 Diastereoselective Synthesis of Compounds 3
Product
R
Yield
(%)
[a]2D5
dea
(c=1.0, CHCl3) (%)
(S,S,S)-3a
(S,S,S)-3b
(S,S,S)-3c
(S,S,S)-3d
(R,R,R)-3a
(S,R,S)-3e
Bn
Me
i-Pr
i-Bu
Bn
77
63
40
97
54
65
+176.2c
+158.9d
+230.7
+148.0e
–173.4d
+ 54.4
>96b
>96b
>96b
>96b
>96b
>96b
The cis-selectivity can be explained by calculation of each
transition state (TS) energy by CAChe MOPAC AM1 cal-
culations (Figure 2), according to which, the heat of for-
mation belonging to the endo-re (TS 1, 57.33 kcal/mol)
conformer was 0.48 kcal/mol less than that of the endo-si
facial congener (TS 2, 57.81 kcal/mol). On the other hand,
the energy difference between the exo-re (TS 3) and exo-
si (TS 4) facial conformers was 3.47 kcal/mol, but the
mean difference between the energy of the two sets of
transition states was considerable, i.e. the endo-set was
10.47 kcal/mol less than that of corresponding exo-set.
Therefore, the endo-re facial transition state (TS 1) should
be responsible for the observed selectivity. As the energy
difference between endo-re (TS 1) and endo-si (TS 2) was
very small, the absolute energy level of the endo-set was
further calculated using ab initio methods (6-31G*) based
(CH2)3
a The de values were determined by 1H NMR spectroscopy (Bruker
DRX 500 MHz spectrometer).
b In 1H NMR spectrum there were no peaks corresponding to the
other isomers.
c Recorded at 27∞C.
d Recorded at 26∞C.
e Recorded at 23∞C.
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Synthesis and Structure of Condensed Heterocycles
367
(R,R,R)-6b, respectively. The optical characteristics of the
cycloadducts having potentially opposite configurations
were confirmed by the specific rotation and their circular
dichroism spectra. The AM1 results would be due to the
different appreciation of the steric repulsion between the
oxygen of the nitrone and the substituent on the chiral cen-
ter, which were more closer to TS 2 compared to TS 1, as
confirmed by the space filling model of individual transi-
tion states (Figure 3).
Figure 3 Space filling models of TS-1 and TS-2
The chiral nitrile oxides 7a-c were generated21 from the
oximes 4a-c using NBS in THF in the presence of a cat-
alytic amount of pyridine at room temperature in the same
fashion. The cyclization21 was performed in the presence
of triethylamine in boiling toluene to give diastereomeri-
cally pure isoxazoline derivatives 8a-c (Scheme 3, Table
3) in good yields.
R
R
R
NOH
i, ii
BnN
N
O
BnN
N
BnN
O
60-72%
SO2Ph
(S)-4a-c
SO2Ph
(S,S)-8a-c
SO2Ph
(S)-7a-c
Figure 2 Transition state (TS) energies as calculated by MOPAC
AM 1
Me
Me
Me
NOH
BnN
N
i, ii
O
BnN
N
BnN
O
64%
SO2Ph
(R)-4b
SO2Ph
(R,R)-8b
SO2Ph
(R)-7b
on the structures located by AM1. The energies of TS 1
and TS 2 were estimated as -1463.0041051 and
-1462.998336 Hartree respectively, from such values the
difference in energies between TS 1 and TS 2 was calcu-
lated to be 0.0058 Hartree (3.58 kcal/mol), which is large
enough to control the p-facial (si- face) selectivity. In a
similar way, the facially identical conformers were as-
sumed to be involved in the intramolecular cycloaddition
of nitrone (R)-2a and (R)-5b to afford (R,R,R)-3a and
Reagents and conditions: i) NBS/pyridine/THF, r.t.; ii) Et3N/toluene,
reflux
Scheme 3
A detailed analysis of the 1H NMR spectra of the cycload-
ducts disclosed the coupling patterns which were con-
firmed by the 2D-COSY experiments. In fact, we have
Synthesis 2000, No. 3, 365–374 ISSN 0039-7881 © Thieme Stuttgart · New York

368
M. J. Uddin et al.
PAPER
and dipolarophile takes place in two parallel planes24,25
and that an endo transition state is preferred in the absence
of obvious steric interactions.26-29
Table 3 Diastereoselective Synthesis of Compounds 8
Product
R
Yield (%)
dea (%)
(S,S)-8a
(S,S)-8b
(S,S)-8c
(R,R)-8b
Bn
65
60
72
64
73b
>96c
>96c
>96c
Me
i-Pr
Me
PhO2S
R
Ph
N
a The de values were determined by 1H NMR spectroscopy (Bruker
DRX 500 MHz spectrometer).
O
N
R
O
N
H
H
b Determined by Bruker DRX 400 MHz 1H NMR spectrometer.
c In 1H NMR spectrum there were no peaks corresponding to the other
isomers.
N
SO2Ph
Ph
exo-TS
endo-TS
Figure 5 Transition states of nitrile oxide olefin cycloaddition
often seen measurable coupling constants between the hy-
drogens located on the carbons a to an sp2 center. The ste-
reochemical information present in the dipolarophile was
found to be retained in the cycloadducts confirmed by the
2D-NOESY spectra. In particular, irradiation of the H-10
signal (d = 3.96) of (S,S)-8c resulted in a positive interac-
tion of the signal for the Ph (ortho H) (d = 7.53) group of
SO2Ph located at C-5 taken together with the absence of
any such interaction between H-8 and SO2Ph, suggesting
a cis-relation among them (Figure 4). Thus it was clear
that in the current reaction, the stereocenter at the a-posi-
tion to the nitrogen functionality can effectively control
the formation of the new contiguous stereocenters and can
regulate the process to produce one of the four possible
stereoisomers in a selective fashion. We were pleased to
observe the formation of the desired isoxazoline fused
heterocyclic systems under a one-pot procedure by adapt-
ing the procedure of Kim et al.21 with slight modifications.
Subsequently, the analogs (S,S)-8a, (S,S)-8b and (R,R)-8b
could be assigned as cis, based on their characteristic cou-
pling patterns and NOESY behaviors. In general, the ste-
reochemistry between the alkyl groups at C-8 and C-5 in
the five membered rings fused to isoxazolines is predom-
inantly cis; this observation has often been supported by
energy calculations,22,23 and examination of the molecular
models reveals that the formation of pyrrolidine fused
isoxazolines having cis-stereochemistry could take place
via an endo transition state (Figure 5). This is in accord
with the widely accepted view that approach of the dipole
The reaction30 of methyl L-prolinate hydrochloride [(S)-
11e] with vinylsulfonyl chloride31 in the presence of tri-
ethylamine at room temperature gave methyl N-(vinylsul-
fonyl) L-prolinate (S)-12e in 40% yield. A DIBAL
reduction of (S)-12e in toluene at -78°C afforded N-vi-
nylsulfonyl L-prolinal [(S)-13e] in 32% yield. The nitrone
(S)-14e has been generated in situ from the reaction of (S)-
13e with phenylhydroxylamine in THF in the presence of
calcium chloride at room temperature and an intramolec-
ular 1,3-dipolar cycloaddition which gave a tricyclic isox-
azolidine derivative (S,R,S)-3e in 65% yield (Scheme 4
and Table 1).
ii
i
N
N
CHO
COOMe: HCl
N
H
COOMe: HCl
32%
40%
O2S
O2S
(S)-13e
Ph
(S)-11e
(S)-12e
H
Ph
N
iii
N
N
N
O
O
65%
O2S
O2S
(S,R,S)-3e
(S)-14e
H
Reagents and conditions: i) vinylsulfonyl chloride/Et3N/CH2Cl2, r.t.;
ii) DIBAL/toluene, -78°C; iii) PhNHOH/CaCl2/THF, -10°C to r.t.
Scheme 4
H3C
H3C
The structure of all the intermediate compounds were elu-
H10
1
cidated based on their IR, H and 13C NMR and DEPT
H8
spectra. The stereochemical courses of the cycloaddition
of (S)-14e is comparable with the cycloaddition of analo-
gous species (S)-2a because, in both cases the transition
states afforded N-Ph substituted isoxazolidine systems,
therefore, this can be assumed to have identical geome-
tries, as it was confirmed by 2D-NOESY correlations for
(S,R,S)-3e, which was further confirmed by a single crys-
tal X-ray analysis (Figure 6). In addition, the transition
state energy calculation is consistent with the observed
N
NOE
N
O
H6b
H6a
H4a
SO2
H4b
H
Figure 4 H-H NOE correlations of (S,S)-8c.
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PAPER
Synthesis and Structure of Condensed Heterocycles
369
experimental results. Accordingly, the heat of formation
of re-re and si-si facial transition states (Figure 7) differed
by 3.68 kcal/mole, which was large enough to control the
p-facial (si-face) selectivity. The reductive cleavage of the
N-O bond of (S,S,S)-3a by Raney Ni (W-2) in anhydrous
ethanol at room temperature afforded the g-amino alcohol
(S,S,S)-9a in good yield (Scheme 5). The presence of NH
and OH groups was identified by the IR absorptions at n =
3250 and at 3350 cm-1, respectively. Furthermore, as ex-
pected, the stereochemical features acquired in the cy-
cloaddition process have been retained in compound
(S,S,S)-9a, as confirmed by the coupling constants and
NOE experiments. In addition, the reductive desulfuriza-
tion of (S,S,S)-3a by LiAlH4 in THF at room temperature
gave (S,R,S)-10a in 88% yield (Scheme 5), where the ab-
sorptions of NH and OH was not observed in the IR spec-
trum of 10a.
Bn
Bn
Bn
Ph
Ph
Ph
NH
OH
H
H
H
H
N
N
i
ii
BnN
BnN
BnN
O
O
88%
77%
SO2Ph
(S,S,S)-3a
SO2Ph
(S,S,S)-9a
(S,R,S)-10a
Reagents and conditions: i) LiAlH4/THF, reflux; ii) Raney Ni (W-2)/
EtOH, r.t.
Scheme 5
Figure 7 Transition state (TS) energies as calculated by MOPAC
PM3
the concerted mechanism. In the present study, the inter-
atomic distances of the involved atoms at transition state
TS 1 were 1.732Å for C-O and 2.870Å for C-C and their
observed difference was 1.138Å. The difference between
the C-O and C-C distance was too large for a concerted
process. Furthermore, the electronic charges of the a-car-
bon of the sulfone in TS 1 calculated by a Mulliken Pop-
ulation analysis (Table 4) were -0.692736 (3-21G*) and
-0.479634 (6-31G*), and those of the b-carbon were esti-
mated as -0.165666 (3-21G*) and -0.588774 (6-31G*),
suggest that the reactions would proceed in a Michael ad-
dition manner, and not in a concerted pathway.
Figure 6 X-ray crystal structure of (S,R,S)-3e. Selected bond
lengths (Å) and bond angles (°): S(1)-N(2) 1.660(6), N(2)-C(6)
1.491(8), C(6)-C(7) 1.549(8), C(2)-C(7) 1.565(8), N(1)-C(7)
1.460(8), O(1)-N(1) 1.430(7), O(1)-C(1) 1.465(8), C(1)-C(2)
1.52(1), S(1)-C(2) 1.773(6), S(1)-C(2)-(1) 114.6(5), N(2)-S(1)-
C(2) 94.2(3), C(2)-C(7)-(6) 107.7(5), N(1)-C(7)-C(2) 104.3(5),
S(1)-N(2)-C(6) 108.8(4), N(2)-C(6)-C(7) 109.1(5), N(1)-C(7)-
C(6) 110.1(6), O(1)-N(1)-C(7) 104.1(4), N(1)-O(1)-C(1)
106.0(5).36
Table 4 Electronic Charges of TS 1 Calculated by Mulliken Popu-
lation Analysis
According to the basic investigation of Robb et al.32 and
Nguyen et al.33 by ab initio studies, the intermolecular 1,3-
dipolar cycloaddition of a simple nitrone and ethylene
proceeded as a concerted process. Furthermore, Pascal
and his co-workers34 reported the semiempirical studies of
the reactions. Their results were in good agreement with
Elements
3-21G*
6-31G*
a-Carbon of sulfone
b-Carbon of sulfone
Carbon of nitrone
Nitrogen of nitrone
Oxygen of nitrone
–0.692736
–0.165666
+0.360877
–0.453827
–0.479241
–0.479634
–0.087086
+0177413
–0.1090914
–0.588774
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M. J. Uddin et al.
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Solvents and reagents were distilled from drying agents as follows:
THF, Et2O (Na-benzophenone); benzene, toluene (Na); CH2Cl2
(P2O5); MeOH (Mg), Et3N (KOH). 1,3-Dichloro-2-phenylsulfonyl-
propane,35 vinylsulfonyl chloride31 and phenylhydroxylamine were
prepared according to the reported procedures. Column chromatog-
raphy was performed by using 230-400 mesh silica gel. Melting
points were measured with a Yanagimoto micro melting apparatus.
IR spectra were recorded as films on NaCl plates or as KBr pellets
on a Jasco A-100 spectrometer. 1H NMR and 13C NMR spectra were
recorded on Jeol FX-90, Bruker DRX-400 and Bruker DRX-500
Preparation of Compounds 3; General Procedure
A solution of aldehyde 1 (5.77 mmol) in anhyd Et2O (10 mL) was
added to a mixture of phenylhydroxylamine (6.35 mmol) and CaCl2
(2.31 mmol) in anhyd Et2O (35 mL) at 0°C. The resultant mixture
was stirred at r.t. for 2-3 d under N2, after which CaCl2 was filtered,
the filtrate concentrated in vacuo and the residue chromatographed
on silica gel (CH2Cl2) to give 3 as white to yellow crystals (Table
1), which were then analyzed (Table 5) for the determination of the
structure and stereochemistry.
1
spectrometers. H and 13C chemical shifts are reported in (d) ppm
Preparation of Compounds 6; General Procedure
from TMS and coupling constants are in Hz. DEPT-13C, HMQC,
2D-COSY, 2D-NOESY spectra were also measured on Bruker
DRX-400 and Bruker DRX-500 spectrometers. Optical rotations
were determined by a Jasco DIP 370 digital polarimeter. Mass spec-
tra were taken with a Jeol JMS-DX303 spectrometer.
A solution of aldoxime 4 (1.38 mmol) in anhyd benzene (138 mL)
containing a catalytic amount of ZnCl2 (0.36 mmol) was refluxed
for 6-16 h. The mixture was then cooled to r.t and quenched with
5% aq NH3 (30 mL). The benzene layer was separated and washed
several times with H2O, then with saturated brine. After drying
(Na2SO4), the benzene was evaporated in vacuo and the resultant
Table 5 Spectroscopic Data of the Cycloadducts 3a-e
Product
IR (KBr/Neat) 1H NMR (500 MHz, CDCl3/TMS)
13C NMR (125.76 MHz, CDCl3/TMS) HRMS (FAB), m/z, (M)
n (cm-1
)
d, J (Hz)
d
calcd
found
(S,S,S)-3aa 3060, 3030,
2950, 2885,
2.57 (d, 1H, J = 11.0), 3.01 (dd, 1 H, J =
34.93 (CH2), 56.35 (CH2), 58.70
510.1963
510.1963
14.3, 14.3), 3.09 (dd, 1 H, J = 14.3, 14.3), 510.1977 (CH2), 69.79 (CH), 72.49
3.18-3.16 (m, 1 H), 3.30 (d, 1 H, J = 13.4), (CH2) 75.91 (CH), 82.58 (C-SO2),
3.61 (d, 1 H, J = 11.0), 3.94 (d, 1 H, J = 9.3), 133.88-114.96 (Ph), 136.47 (PhN),
4.06 (d, 1 H, J = 13.4), 4.41 (s, 1 H), 4.42 137.79 (PhCH2), 148.77 (PhSO2)
(d, 1 H, J = 4.7), 7.53-6.45 (m, 20 H)
1600, 1480,
1467, 1300,
1150, 1073,
760, 680
(S,S,S)-3bb 2940, 1590
1450, 1290,
1.29 (d, 3 H, J = 6.1), 2.43 (d, 1 H, J = 11.3), 16.64 (CH3), 59.96 (CH2), 56.51 (CH2), 434.1702
2.52-2.69 (m, 1 H), 3.03 (d, 1 H, J = 13.0), 65.14 (CH), 72.16 (CH2) 80.09 (CH),
434.1663
462.2019
1130, 960,
910, 740,
720, 680
3.53 (d, 1 H, J = 11.4), 3.86 (d, 1 H, J =
82.52 (C-SO2), 133.88-114.09 (Ph),
13.0), 3.92 (d, 1 H, J = 9.2), 4.35 (d, 1 H, 137.10 (PhN), 137.75 (PhCH2), 149.00
J = 6.7), 4.52 (d, 1 H, J = 9.2), 6.91-7.72 (PhSO2)
(15 H, m)
(S,S,S)-3cc 3060, 2950,
2790, 1590,
0.90 (d, 3 H, J = 6.88), 1.07 (d, 3 H, J =
15.75 (CH3), 19.28 (CH3), 26.71 (CH2), 462.1975
7.11), 2.38 (d, 1 H, J = 11.36), 2.18-2.15 56.63 (CH2), 60.63 (CH2) 71.91 (CH),
(m, 1 H), 3.18-3.16 (m, 1 H), 2.54 (dd, 1H, 72.27 (CH2), 73.22 (CH) 82.10 (C-
1480, 1440,
1360, 1300
1210, 1140,
1080, 1020,
J = 7.45, 7.44), 3.57 (d, 1 H, J = 11.33),
SO2),133.89-114.03 (Ph), 148.24
2.86 (d, 1 H, J = 13.06), 3.86 (d, 1 H, J = (PhSO2)
9.08), 4.45 (d, 1 H,J = 9.10), 3.91 (d, 1 H,
J = 13.09), 4.69 (d, 1 H, J = 7.48), 6.94-
7.62 (m, 15 H)
800, 670
(S,S,S)-3dd 3060, 2990
2750, 1600,
1500, 1460,
1380, 1320,
1270, 1150,
1100, 1030,
960, 880,
0.95 (d, 3 H, J = 6.10), 0.97 (d, 3 H, J =
6.20), 1.99-1.97 (m, 3 H), 2.39 (d, 1 H,
J = 11.30), 2.76-2.56 (m, 1 H), 2.98 (d,
1H, J = 13.0), 3.52 (d, 1 H, J = 11.30), 2.86 82.92 (C-SO2), 133.83-114.44 (Ph),
(d, 1 H, J = 9.0), 3.97 (d, 1 H, J = 13.10), 137.45 (PhN), 138.08 (PhCH2), 148.85
4.40 (d, 1 H, J = 9. 10), 4.56 (d, 1 H, J =
6.80), 8.84-7.84 (m, 15 H)
22.82 (CH3), 24.21 (CH3), 25.07 (CH), 476.2131
41.17 (CH2), 56.93 (CH2), 60.37 (CH2),
68.11 (CH), 72.42 (CH2), 78.62 (CH),
476.2147
(PhSO2)
760, 730
(S,R,S)-3ee 3050,2950
1600,1500,
1450,1300,
1230,1150,
1050,1000,
900,800,
2.06-1.98 (m, 2 H), 2.12-2.09 (m, 1 H),
24.37 (CH2), 31.26 (CH2), 47.58 (CH2), 280.0880
280.0881
2.32-2.30 (m, 1 H), 3.28-3.23 (m, 1 H), 66.21 (CH), 66.66 (CH) 69.23 (CH2),
3.73-3.96 (m, 1 H),3.91 (dd, 1 H, J = 2.82, 74.38 (CH), 129.45-114.85 (Ph)
2.83), 4.08-4.07 (m, 1 H), 4.16 (dd, 1 H,
J = 7.77, 7.79), 4.49 (dd, 1 H, J = 6.43,
6.45) 4.66 (dd, 1 H, J = 1.54, 1.55), 7.30-
6.99 (m, 5 H)
750,680
a White prisms, mp 108-109°C.
b Pale yellow solid, mp 98-99°C.
c White crystals, mp 100-101°C.
d Pale yellow solid, mp 120-121°C.
e Yellow needles, mp 130-131°C.
Synthesis 2000, No. 3, 365–374 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis and Structure of Condensed Heterocycles
371
gummy mass was chromatographed on silica gel (hexane/EtOAc,
1:1) to give 6 as colored syrups or amorphous solids (Table 2),
which were then analyzed (Table 6).
in vacuo to give a white solid, which was recrystallized from isopro-
pyl alcohol to afford (S,S,S)-9a as white needles (77%); mp 180-
181°C.
HRMS (FAB): m/z (M + 1) calcd for C31H33N2O3S: 513.2211,
found: 513.2221.
Preparation of Compounds 8; General Procedure
A solution of aldoxime 4 (0.65 mmol) in anhyd THF (2 mL) was
added to a solution of NBS (0.67 mmol) in anhyd THF (2 mL) con-
taining a catalytic amount of pyridine (0.03 mmol) and stirred at r.t.
for 10 min under N2. A solution of Et3N (0.69 mmol) in anhyd THF
(2 mL) was then added followed by distilled toluene (20 mL), and
the mixture was subjected to reflux for 12-16 h. The cooled mixture
was quenched with H2O (15 mL). The organic layer was separated
and washed several times with brine. After drying (Na2SO4), the
solvent was evaporated and the residue was chromatographed on
silica gel (hexane/EtOAc, 1:1) to afford 8 as colored syrups (Table
3), which were then analyzed (Table 7)
IR(KBr): n = 3480(OH) 3410(NH), 1605, 1455, 1150(N-O), 1080,
750, 690 cm-1.
1H NMR (500MHz, CDCl3/TMS): d = 2.59 (d, 1 H, J = 11.9 Hz),
2.64 (q, 1 H, J =18.34 Hz), 2.76 (dd, 1 H, J = 14.0, 14.0 Hz), 2.89
(dd, 1 H, J = 14.0, 14.0 Hz), 3.06 (d, 1 H, J = 13.0 Hz), 3.20 (s, 1
H), 3.34 (d, 1 H, J = 11.9 Hz), 3.54 (d, 1 H, J = 12.0), 4.02 (d, 1 H,
J = 13.0), 4.09 (d, 1 H, J = 12.1 Hz), 4.43 (t, 1 H, J = 15.50 Hz),
7.66-6.47 (m, 20 H).
13C NMR (125.76MHz, DEPT, CDCl3): d = 35.70 (CH2), 56.92
(CH2), 57.22 (CH2), 62.29 (CH), 62.59 (CH2), 72.88 (CSO2), 73.68
(CH), 133.61-114.96 (Ph), 137.31 (PhN), 146.68 (PhSO2).
Reductive Ring Opening of (S,S,S)-3a; (2S, 3S, 4S)-3-Anilino-
1,2-dibenzyl-4-hydroxymethyl-4-phenylsulfonylpyrrolidine
(9a)
A solution of Raney Ni (W-2) (3.30 mL) in anhyd EtOH 10 mL)
was added dropwise to a solution of (S,S,S)-3a (1.60 mmol) in an-
hyd EtOH (30 mL) at 25°C, which was stirred at r.t. for 17 h under
N2 (Scheme 5). The white crystals that appeared were dissolved in
EtOAc and the solution was filtered. The filtrate was concentrated
Reductive Desulfurization of (S,S,S)-3a; (1S,5R,8S)-7,8-Diben-
zyl-2-phenyl-3-oxa-2,7-diazabicyclo[3,3,0]octane (10a)
A solution of (S,S,S)-3a (0.80 mmol) in anhyd THF (10 mL) was
slowly added to a slurry of LiAlH4 (3.20 mmol) in THF (10 mL) at
10°C, which was then refluxed for 72 h under N2 (Scheme 5). To the
ice-cold reaction mixture was added dropwise 10% aq KOH solu-
Table 6 Spectroscopic Data of the Cycloadducts 6a-d
Product
IR (KBr/Neat) 1H NMR (500 MHz, CDCl3/TMS)
13C NMR (125.76 MHz, CDCl3/TMS) HRMS (FAB), m/z, (M + 1)
n (cm-1
)
d, J (Hz)
d
calcd
found
(S,S,S)-6aa 3400, 3075
3025, 2925,
1.25 (s, 2 H), 2.25 (d, 1 H, J = 11.33),
29.36 (CH2), 36.06 (CH2), 60.39
435.1742
435.1729
3.32 (d, 1 H, J = 11.30), 2.88 (d, 1 H, J = (CH2), 70.12 (CH2), 70.89 (CH) 77.02
5.60), 3.50 (d, 1 H, J = 9.99), 4.06 (d, 1 H, (CH), 81.73 (C-SO2), 126.48-137.65
J = 10.0), 4.16 (d, 1 H, J = 5.40), 4.28 (dd, (Ph), 146.13 (PhSO2)
1 H, J = 7.80, 7.78), 5.55 (s, 1 H), 7.66-
2800, 1600,
1580, 1500,
1450, 1300,
1140, 1080,
7.11 (m, 15 H)
740, 680
(S,S,S)-6bb 3425, 3070
3050, 2950,
1.15 (d, 3 H, J = 6.05), 2.26 (d, 1 H, J = 17.22 (CH3), 58.07 (CH2), 60.32
11.0), 3.43 (d, 1 H, J = 11.40), 2.28-2.32 (CH2), 65.35 (CH), 76.81 (CH) 77.02
(m, 1 H), 2.86 (d, 1 H, J = 13.22), 3.78 (CH2), 80.90 (C-SO2), 136.94-127.17
(d, 1 H, J = 13.10), 3.95 (d, 1 H,J = 6.5), (Ph), 147.77 (PhSO2)
4.05 (d, 1 H, J = 9.30), 4.27 (d, 1 H, J =
359.1429
359.1429
387.1737
401.1899
2925, 2850,
2800, 1580,
1450, 1300,
1020, 820,
9.0), 5.62 (s, 1 H), 7.72-6.80 (m, 10 H)
740, 680
(S,S,S)-6cc 3450, 3075,
3025, 2975,
0.70 (d, 1 H, J = 6.85), 0.85 (d, 3 H, J = 15.37 (CH), 20.16 (CH3), 26.50 (CH3), 387.1742
5.50), 1.02 (d, 3 H, J = 7.05), 1.25 (s,
2 H), 2.30 (dd, 1 H, J = 14.65, 14.40),
26.70 (CH2), 56.70 (CH2), 60.44 (CH),
69.69 (CH), 76.77 (CH2) 80.90 (C-
2925, 2850,
1360, 1300,
1210, 1140,
1080, 1020,
2.78 (d, 1 H, J = 12.92), 3.83 (d, 1 H, J = SO2),134.00-125.11 (Ph), 137.06
12.80), 4.07 (d, 1 H, J = 9.10), 4.26 (d, (PhN),137.78 (PhCH2), 150.22
1 H, J = 9.30), 4.14 (m, 1 H), 5.29 (s,
1 H), 6.93-7.82 (m, 10 H)
(PhSO2)
800, 670
(S,S,S)-6dd 3450, 3075
3050, 2975,
2950, 2875,
1590, 1500,
1450, 1380,
1150, 1090,
950, 840,
0.88 (d, 3 H, J = 6.50), 0.92 (d, 3 H, J = 22.47 (CH3), 24.35 (CH3), 24.83 (CH), 401.1963
7.65), 0.94 (m, 1 H), 1.28 (d, 2 H, J = 29.71 (CH2), 52.77 (CH2), 56.80
13.70), 2.87 (d, 1 H, J = 13.35), 3.84 (d, (CH2), 60.50 (CH2), 67.95 (CH), 75.49
1 H, J = 13.0), 3.42 (d, 2 H, J = 7.32) 4.04 (CH), 81.37 (C-SO2), 137.94-127.12
(d, 2 H, J = 16.51), 4.10 (d, 1 H, J = 6.70), (Ph), 148.85 (PhSO2)
4.23 (d, 1 H, J = 14.33), 5.62 (s, 1 H),
7.97-6.99 (m, 10 H)
760, 690
a Brown amorphous solid, mp 75-76°C.
b Pale yellow syrup.
c Yellow syrup.
d Brown syrup.
Synthesis 2000, No. 3, 365–374 ISSN 0039-7881 © Thieme Stuttgart · New York

372
M. J. Uddin et al.
PAPER
Table 7 Spectroscopic Data of the Cycloadducts 8a-c
Producta IR (KBr/Neat) 1H NMR (500 MHz, CDCl3/TMS)
13C NMR (125.76 MHz, CDCl3/TMS) HRMS (FAB), m/z, (M + 1)
n (cm-1)
d, J (Hz)
d
calcd
found
(S,S)-8a
3075, 2950
2925, 2850,
2800, 1660,
1580, 1500,
1450, 1300,
1140, 1080,
740, 680
1.24 (t, 1 H, J = 8.00), 3.10 (d, 2 H, J = 38.60 (CH2), 57.10 (CH2), 58.40 (CH2), 433.1585
12.00), 3.45 (d, 2 H, J = 12.00), 3.80 (d, 61.40 (CH), 77.40 (CH2) 84.90 (C-
1 H, J = 12.00), 4.11 (d, 1 H, J = 8.00), SO2), 128.50-137.50 (Ph), 150.50
4.87 (d, 1 H, J = 8.00), 7.52-6.81 (m, (PhSO2), 164.90 (C=N)
15 H)
433.1561
(S,S)-8b
(S,S)-8c
3090, 3070
3050, 2950,
2925, 2850,
2800, 1680,
1550, 1300
740, 680
1.14 (d, 3 H, J = 6.03), 2.27 (d, 1 H, J = 17.09 (CH3), 53.43 (CH2), 56.47 (CH2), 357.1272
11.24), 2.85 (d, 1 H, J = 13.40), 3.41 (d, 76.79 (CH), 77.25(CH2) 80.90 (C-
1 H, J = 11.48), 3.76 (d, 1 H, J = 13.19), SO2),137.71-127.10 (Ph),143.89
3.96 (d, 1 H, J = 9.00), 3.98-4.00 (m, (PhSO2), 163.08
1 H) 4.26 (d, 1 H, J = 8.99), 7.76-6.87
357.1309
385.1576
(m, 10 H) (C=N)
3075, 2990
2980, 2950,
2925, 2850,
1660, 1600,
1210, 1140,
1030, 750
1.08 (d, 3 H, J = 6.85), 1.17 (d, 3 H, J = 216.19 (CH3),18.54 (CH3), 29.25 (CH), 385.1585
6.90), 2.14-2.19 (m, 1 H), 3.20 (d, 1 H, 53.99 (CH2), 58.93 (CH2), 64.34
J = 12.80), 3.52 (d, 1 H, J = 12.85),
3.92-3.96 (m, 1 H), 4.06 (d, 1 H, J = 137.54-127.01 (Ph), 150.32 (PhSO2),
9.90), 4.10 (s, 2 H), 4.72 (d, 1 H, J =
10.12), 7.89-7.17 (m, 10 H)
(CH),76.34(CH2),85.09 (C-SO2),
164.53 (C=N)
a All compounds are colored syrups.
b 400 MHz NMR spectrum.
tion (0.5 mL) followed by H2O (0.5 mL). The mixture was then re-
fluxed again for 15 min and the solids that appeared were filtered
after cooling. After drying (MgSO4), the solvent was removed and
the resultant mass was chromatographed on silica gel (CH2Cl2) and
the product obtained was recrystallized from isopropyl alcohol to
afford the isoxazolidine derivative (S,R,S)-10a as white crystals
(88%); mp 112-113°C.
(2) Hassner, A.; Maurya, R.; Friedman, O; Gottlieb, H.E. J. Org.
Chem. 1993, 58, 4539.
For general reviews on 1,3-dipolar cycloaddition, see:
Kozikowski, A.P. Acc. Chem. Res. 1984, 32, 1.
Kanemasa, S; Tsuge, O. Heterocycles 1990, 30, 719.
Carruthers, W. Cycloaddition Reactions in Organic
Synthesis, Pergamon: Oxford, 1990, p 285.
Wade, P.A. Comprehensive Organic Synthesis, Trost, B.M.,
Ed.; Pergamon: Oxford, 1991,, Vol. 4; p 1111.
Little, R.D. Comprehensive Organic Synthesis, Trost, B.M.,
Ed.; Pergamon: Oxford, 1991, Vol. 5; p 239.
(3) (a) Padwa, A. Angew. Chem., Int. Ed. Engl. 1976, 15, 123.
(b) Padwa, A.; Schoffstall, A.M. Adv. Cycloadd. 1990; 2, 1.
(c) Rai, K.M.L., Hassner, A. Heterocycles 1990, 30, 817.
(4) (a) Oppolzer, W.; Angew. Chem.,Int. Ed. Engl. 1977,16, 10.
(b) Confalone, P. N.; Huie, E. M. Org. React. 1988, 36, 1.
(c) Terao, Y.; Aono, M.; Achiwa, K. Heterocycles 1988, 27,
981.
HRMS (FAB): m/z (M + 1) calcd for C25H27N2O: 371.2123, found:
371.2122.
IR(KBr): n = 3020 (CH, C6H5), 2950 (aliphatic CH), 1592 (C=C,
C6H5),1488 (Ph), 1460 (Ph), 1082 (C-N), 1080, 750, 690 cm-1.
1H NMR (500MHz, CDCl3/TMS): d = 2.16-2.14 (m, 1 H), 2.93-
2.90 (m, 1 H),3.01 (d, 1 H, J = 5.65 Hz), 3.23-3.11 (m, 3), 3.28 (dd,
1 H, J = 14.6, 14.6 Hz), 3.71 (m, 2 H), 4.05 (m, 1 H), 4.15 (d, 1 H,
J = 13.0 Hz), 7.43-6.68 (m, 15 H).
13C NMR (125.76MHz, DEPT, CDCl3): d = 37.45 (CH2), 46.13
(CH), 57.97 (CH), 58.94 (CH2), 70.03 (CH), 71.08 (CH2), 75.61
(CH), 129.92-114.41 (Ph), 138.61 (PhN), 150.73 (PhSO2).
(5) De Shong, P.; Leginus, J. M.; Lander, S. W. J. Org. Chem.
1986, 51, 574.
(6) Kametani, T.; Chu, S.-D. T. J. Chem. Soc. Perkin. Trans. 1
1988, 1598.
(7) Annunziata, R.; Cinquini, M.; Cozzi, F.; Raimondi, L.;
Tetrahedron 1987, 43, 4051
Crystal Data for 3a and 3e
See Tables 8 and 9, respectively.
(8) (a) Tufariello, J. J. Acc. Chem. Res. 1979, 11, 369.
(b) Ali, S. A.; Khan, J. H.; Wazeer, M. I. M. Tetrahedron
1988, 44, 5911.
Acknowledgement
We wish to thank Mr. Kouichi Mizuki of Yoshitomi Pharmaceutical
Co., Ltd., for the HRMS measurements. This work was supported
by Grant-in Aid for COE Research (10CE 2003) by the Ministry of
Education, Science, Sports and Culture of Japan.
(c) Hall, A.; Meldrum, K. P.; Therond, P.R.; Wightman, R. H.
Synlett 1997, 123.
(d) Goti, A.; Fedi, V.; Nanneli, L.; De Sarlo, F.; Brandi, A.
Synlett 1997, 577.
(9) Moriyama, S.; Vallée, Y. Synthesis 1998, 4, 393.
(10) (a) Padwa, A. In 1,3-Dipolar Cycloaddition Chemistry,
Padwa, A., Ed.; Wiley-Interscience: New York, 1984; Vol 2.
(b) Tufariello, J. Acc. Chem. Res. 1979, 12, 396.
References
(1) Rossiter, B.F.; Swingle, N. M. Chem.Rev. 1992, 92, 771.
Synthesis 2000, No. 3, 365–374 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis and Structure of Condensed Heterocycles
373
Table 8 Summary of Data Collection, Structure solution and Refinement Details for (1S,5S,8S)-(+)-7,8-Dibenzyl-2-phenyl-5-phenylsulfo-
nyl-3-oxa-2,7-diazabicyclo-[3,3,0]octane (3a)
Crystal Data
Emperical Formula C31H30N2O3S
Data Acquisition
Rigaku AFC5S
Structure Solution and Refinement
Diffractometer
Radiation
Structure Solution
Direct Methods
Full-matrix
Formula Weight
Appearance
510.65
MoKa (l = 0.71069Å) Refinement
20°C
white prisms
Temperature
Least-squares
Crystal Dimension
(mm)
0.360 × 0.420 × 0.562 Attenuator
Ni foil (factors:
2.3,5.2,11.7)
Function Minimized ∑ w(|Fo|-|Fc|)2
Crystal System
orthorhombic
Take-off Angle
6.0°
Least-squares
Weights
4Fo2/s2(Fo2)
0.03
No. Reflections Used
for Unit
Detector Aperture
6.0 mm horizontal
p-factor
Cell Determination
(2q) range
25 (33.6-37.4°)
6.0 mm vertical
Anomalous
Dispersion
All non-hydrogen
atoms
Omega Scan Peak
Width
Crystal to Detector
Distance
40 cm
at Half-height
0.14
Scan Type
Scan Rate
w
No. Observations
Lattice Parameters:
a = 10.114 (4)Å
16.0°/min (in omega) [|>2.00s(|)]
(2 rescans)
1868
334
B = 25.387 (5)Å
C = 10.055 (4)Å
V = 2582 (2)Å
Scan Width
2qmax
(1.01+0.30 tan q)°
55.0°
No. Variables
Reflection/Parameter
Ratio
No. of Reflection
Measured
Total: 3380
5.59
Space Group
P212121 (#19)
Unique: 3379
(Rint =0.899)
Residuals R:Rw
0.063:0.060
Z value
Dcalc
4
Correlations
Lorentz-polarization Goodness of Fit
Indicator
1.314 g/cm3
1080
1.59
F000
Max Shift/Error in
Final
m(MoKa)
1.53 cm–1
Cycle
0.03
Maximum Peak in
Final Diff. Map
Minimum Peak in
0.32e-/Å3
(11) Confalone, P.N.; Pizzolato, G.; Confalone, D. L.; Uskokovic,
M. R. J. Am. Chem. Soc. 1980, 102, 1954.
(19) Gothelf, K. V.; Joergensen, K. A. Chem. Rev. 1998, 98, 863,
and references cited therein.
(12) Baraldi, P. G.; Fabio, M.; Pollini, G. P.; Simoni, D.; Barco, A.;
Simonetta, B. J. Chem. Soc.,Perkin. Trans. 1. 1982, 2983.
(13) Jäger, V.; Ground, H.; Bub, V.; Schwab, W.; Muller, I. Bull.
Chem. Soc. Belg. 1983, 92, 1039.
(20) Takeuchi, H.; Fujimoto, T.; Kakehi, A.; Yamamoto, I. J.
Org.Chem. 1998, 63, 7172.
(21) Kim, B. H.; Chung, Y. J.; Keum, G.; Kim, J.; Kim, K.
Tetrahedron Lett. 1992, 33, 6811.
(14) Jäger, V.; Schohe, R.; Franz, R.; Ehrler, R. Lect. Hetercycl.
Chem. 1985, 8, 79.
(15) Jäger, V.; Schwab, W. Tetrahedron Lett. 1978, 3129.
(16) Curran, D. P. Adv. Cycloadd. 1988, 1, 133.
(17) Abiko, A.; Liu, J. F.; Wang, F. Q.; Masamune, S. Tetrahedron
Lett. 1997, 38, 3261.
(22) Hassner, A.; Murthy, K. S. K; Padwa, A.; Chiacchio, U.;
Dean, D. C.; Schoffstall, A. M. J. Org. Chem. 1989, 54, 5277.
(23) Brown, F. K.; Raimondi, L.; Wu, Y-D.; Houk, K. N.
Tetrahedron Lett. 1992, 33, 4405.
(24) Huisgen, R.; Grashey, R.; Hauck, H.; Seidl, H. Chem. Ber.
1968, 101, 2043.
(18) Frederickson, M. Tetrahedron 1997, 53, 403.
Synthesis 2000, No. 3, 365–374 ISSN 0039-7881 © Thieme Stuttgart · New York

374
M. J. Uddin et al.
PAPER
Table 9 Summary of Data Collection, Structure Solution and Refinement Details for 3e
Crystal Data
Emperical Formula C13H16N2O3S
Formula Weight 280.34
Data Acquisition
Rigaku AFC5S
Structure Solution and Refinement
Diffractometer
Radiation
Structure Solution
Refinement
Direct Methods
Full-matrix
MoKa
(l = 0.71069Å)
Crystal Color, Habit yellow, needle
Temperature
23°C
Least-squares
Crystal Dimension
(mm)
0.040 × 0.240 × 0.680 Attenuator
Ni foil (factors:
2.3,5.2,11.7)
Function Minimized ∑ w(|Fo|-|Fc|)2
Crystal System
monoclinic
Take-off Angle
6.0°
Least-squares
Weights
4Fo2/s2(Fo2)
0.03
No. Reflections Used
for Unit
Detector Aperture
6.0 mm horizontal
6.0 mm vertical
40 cm
p-factor
Cell Determination
(2q) range
25(36.4-39.8°)
Anomalous
Dispersion
All non-hydrogen
atoms
Omega Scan Peak
Width
Crystal to Detector
Distance
at Half-height
0.14
Scan Type
Scan Rate
w-2q
No. Observations
Lattice Parameters:
a = 8.250 (9)Å
16.0°/min (in omega) 8|>2.00s(|)]
1158
171
(2 rescans)
B = 5.660 (6)Å
C = 13.918(4)Å
V = 647.5 (8)Å3
Scan Width
2qmax
(1.311 + 0.30 tan q)° No. Variables
55.0°
Reflection/Parameter
No. of Reflection
Measured
Total : 1753
Ratio
6.77
Space Group
P21 (#4)
Unique : 1642
(Rint = 0.049)
Residuals R:Rw
0.064 : 0.063
Z value
Dcalc
2
Correlations
Lorentz-polarization Goodness of Fit
Indicator
1.438g/cm3
296
1.72
F000
Max Shift/Error in
Final
m(MoKa)
2.44 cm-1
Cycle
0.05
Maximum Peak in
Final Diff. Map
0.52e-/Å3
(25) Leroy, G.; Nguyen, M. T.; Sana, M. Tetrahedron 1978, 34,
2459.
(33) Nguyen, M. T.; Chandra, A. K.; Sakai, S.; Morokuma, K. J.
Org. Chem. 1999, 64, 65.
(26) Tufariello, J. J.; Ali, Sk. A. Tetrahedron Lett. 1978, 19, 4647.
(27) Tufariello, J. J.; Puglis, J. M. Tetraherdrn Lett. 1986, 27,
1265.
(28) Burdisso, M.; Gandolfi, R.; Grounanger, P.; Rastelli, A. J.
Org. Chem. 1990, 55, 3427.
(29) Jung, M. E.; Gervay, J. Chemtracts 1990, 3, 284.
(30) Metz, P.; Seng, D.; Fröhlich, R.; Wibbeling, B. Synlett 1996,
741.
(34) Pascal, Y. L.; Chanet-Ray, J.; Vessiere, R.; Zeroual, A.
Tetrahedron 1992, 7197
(35) Anzeveno, P. B.; Mathews, D. P.; Barney, C. L.; Barbuch, R.
J. J. Org. Chem. 1984, 49, 3134.
(36) Further details of the crystal structure determination are
available on request from Cambridge Crystallographic Data
Centre; CCDC-133125 for the compound (S,S,S)-3a and
CCDC-133126 for (S,R,S)-3e.
(a)Goldberg, A. A. J. Chem. Soc. 1945, 464.
(b)Rondestvedt, Jr. C. S. J. Am. Chem. Soc. 1954, 76, 1926.
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Article Identifier:
1437-210X,E;2000,0,03,0365,0374,ftx,en;F05399SS.pdf
Synthesis 2000, No. 3, 365–374 ISSN 0039-7881 © Thieme Stuttgart · New York