Stereoselective access to γ-nitro carboxylates, precursors for highly functionalized γ-lactams

Article abstract of DOI:10.1002/hlca.200390063

A straightforward synthesis of the enantiomerically pure nitro derivatives 31 and epi-32, which are particularly useful intermediates for the synthesis of highly functionalized γ-lactams, is presented. (+)-(R)-3-Hydroxy-3-phenylpropanoic acid (20) and its ethyl ester 25 were prepared from (+)-L-mandelic acid (21). Condensation of 20 with pivalaldehyde furnished the novel enantiomerically pure 1,3-dioxan-4-one 17, the absolute configuration of which was established by X-ray crystal-structure analysis. Treating the lithium enolate of 17 with the nitro alkene 18 led, in a Michael-type addition, to a 1:1 mixture of two diastereoisomeric products. The stereocontrol of the addition was limited to the novel stereogenic center next to the lactone function. When the lithium enolate of 25 was treated with 18, the same selectivity was observed but with a lower chemical yield. Very facile separation of the isomers was achieved later in the synthetic sequence, when one isomer cyclized selectively to the nitro lactone 31, while the other one was isolated as hydroxy ester epi-32. The relative configuration of racemic epi-32 could be established by X-ray crystal-structure analysis.

Full text of DOI:10.1002/hlca.200390063

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Helvetica Chimica Acta Vol. 86 (2003)
Stereoselective Access to g-Nitro Carboxylates, Precursors for Highly
Functionalized g-Lactams
by Christian Meisterhans1), Anthony Linden, and Manfred Hesse*
Organisch-chemisches Institut der Universit‰t Z¸rich, Winterthurerstrasse 190, CH-8057 Z¸rich
(tel.: ‡41-1-6354195; fax: ‡41-1-635 6812; e-mail: mhesse@oci.unizh.ch)
A straightforward synthesis of the enantiomerically pure nitro derivatives 31 and epi-32, which are
particularly useful intermediates for the synthesis of highly functionalized g-lactams, is presented. (‡)-(R)-3-
Hydroxy-3-phenylpropanoic acid (20) and its ethyl ester 25 were prepared from (‡)-l-mandelic acid (21).
Condensation of 20 with pivalaldehyde furnished the novel enantiomerically pure 1,3-dioxan-4-one 17, the
absolute configuration of which was established by X-ray crystal-structure analysis. Treating the lithium enolate
of 17 with the nitro alkene 18 led, in a Michael-type addition, to a 1:1 mixture of two diastereoisomeric products.
The stereocontrol of the addition was limited to the novel stereogenic center next to the lactone function. When
the lithium enolate of 25 was treated with 18, the same selectivity was observed but with a lower chemical yield.
Very facile separation of the isomers was achieved later in the synthetic sequence, when one isomer cyclized
selectively to the nitro lactone 31, while the other one was isolated as hydroxy ester epi-32. The relative
configuration of racemic epi-32 could be established by X-ray crystal-structure analysis.
Introduction.
In the course of our investigations on the total synthesis of
caesalpinine A (1; Scheme 1) [1], a cyclic spermidine alkaloid [2], we were interested in
finding an easy access to the lactam 2. The nitro ester 3 was assumed to be a useful
precursor to 2, as it should undergo lactamization as soon as the NO2 group is reduced.
¬
In 1979, Frater had found that b-hydroxybutyrate 4 can be alkylated with high
diastereoselectivity, when its corresponding enolate is treated with alkyl bromides
(Scheme 2) [3]. Seebach and co-workers applied this method for nitro alkenes 5 as
alkylating agents [4]. Subsequent hydrogenation of the NO2 groups afforded the
corresponding g-lactams through spontaneous cyclization of the in situ formed amino
esters. The configuration of the novel stereogenic center in the a-position to the ester
¬
was in agreement with the findings of Frater. The stereoselectivity can be explained by
Scheme 1
Ph
OH
H
O
Ph
OPG
Ph
H
OPG
H
O
H
O
N
H
OEt
H
N
BnO
HO
Ph
N
H
H
NH
O
NO2
3
1
2
PG = protecting group
1
)
Part of the Ph.D. thesis of C. M., University of Z¸rich, 2002.

Helvetica Chimica Acta Vol. 86 (2003)
645
Scheme 2
OH
O
OH
O
OH
O
H
H
a)
+
H3C
OEt
H3C
OEt
H3C
OEt
R
R
(S)-4
R = alkyl
95% erythro
5% threo
OH
O
OH
O
OH
H
O
H
c)
b)
H3C
OEt
H3C
OEt
H3C
NH
NO2
R
R
H
(R)-4
H
NO2
R
two diastereoisomers in the ratio 1 : 1
OLi
5, R = alkyl, aryl
Et
O
Li
O
H3C
6
a) 1. 2.0 equiv. LiN(i-Pr)2 (LDA), THF, hexamethylphosphoric triamide (HMPTA), À 208. 2. Alkyl bromide,
À 20 to ‡ 258; 80%. b) 1. 2.0 equiv. LDA, THF, À788; 2. 5, À 788; 38to 81%. c) H 2, Raney-Ni; 43 to 87%.
the dianion 6, which forms a lithium chelate and, thus, favors a trans-substitution
relative to the Me group. A synthetic equivalent for b-hydroxy esters are dioxanones
like 7, which can be obtained by the condensation of the b-hydroxy acid 8 with
pivalaldehyde (Scheme 3) [5 7]. These dioxanones and their enolates are conforma-
tionally stable due to their cyclic structure and, at the same time, give high chemical
yields even with less reactive alkylating agents. In 1994, Seebach and co-workers
investigated the addition of the enolate of 9 to nitro alkenes and observed the
diastereoselectivities shown in Scheme 3 [8]. The hydrogenation of 10 in the presence
of Raney-Ni afforded the g-lactam 11. Liebscher and co-workers followed a slightly
different route to the same class of products. They prepared the alkylidene or arylidene
dioxanones 12 by a formal aldol condensation of 13 with aldehydes (Scheme 4) [5]. In
the next step, the Michael addition of MeNO2 afforded the nitro lactones 14 with the
selectivities shown in Scheme 4 [9]. Upon hydrogenation, the preferred products
yielded the cis-configured g-lactams 15. We now wanted to apply the method of
Seebach and co-workers [8] for the synthesis of 16, and two new aspects had to be
considered: first, we were interested to determine if the Ph-substituted dioxanone 17
would give the same selectivities for substitution in the a-position (Scheme 5), second,
the nitro alkene 18 bears a BnO group, which needs to be converted to an amino group
later in the synthesis, and it was unknown how such a function would influence the
diastereoselectivity at the second novel stereogenic center of 19.

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Helvetica Chimica Acta Vol. 86 (2003)
Scheme 3
O
O
OH
O
a) or
b)
H3C
O
H3C
OH
8
7
c)
O
O
O
O
O
O
H
H
H
H
+
F3C
O
F3C
O
F3C
O
R
R
9
10
NO2
NO2
NO2
R = Bu
R = Ph
:
:
6
2
1
1
R
5
d)
R = Ph
OH
O
H
F3C
NH
Ph
H
11
a) Pivalaldehyde, pyridinium toluene-4-sulfonate, benzene, 808. b) 1. Me3SiCl, Et3N, CH2Cl2, r.t., 2. pivalalde-
hyde, Me3Si-triflate, CH2Cl2, À 788. c) 1. t-BuLi, THF, À 758; 2. addition of 5, À 758, 3 h; 97%. d) 1 bar H2,
EtOH, Raney-Ni, 12 h, r.t.; 41%.
Results and Discussion. Synthesis of the Hydroxy Acid 20 andthe Hydroxy Ester
25. The preparation of (‡)-(R)-3-hydroxy-3-phenylpropanoic acid (20) was achieved
by a C1-homologization of (‡)-l-mandelic acid (21): according to [10], reduction of 21
followed by tosylation furnished 22 (Scheme 6). The nucleophilic substitution of the
TsO group in 22 by CN produced the intermediate 23, which was isolated in addition to
the desired nitrile 24, when the reaction was stopped prematurely. Base hydrolysis of 24
afforded the hydroxy acid 20, and esterification according to [11] yielded the ethyl ester
25.
Synthesis andStructure of the Dioxanone 17. Direct condensation of 20 with
pivalaldehyde in benzene by azeotropic removal of H2O [6] gave only mediocre yields

Helvetica Chimica Acta Vol. 86 (2003)
647
Scheme 4
a)
O
O
O
R
O
H3C
O
H3C
O
13
12
b)
OH
O
R
O
O
R
O
c)
O
H
H
H
H
H
+
H3C
H3C
O
H3C
O
NH
R
H
NO2
NO2
15
14
:
R = alkyl
R = Ph
4
6
1
1
:
a) 1. LDA, THF, À 788; 2. RCHO, THF, À 788, 1 h; 3. MeCl, pyridine, 4-(dimethylamino)pyridine (DMAP),
r.t., 30 min; 4. Et3N, CHCl3, 618, 24 h; 42 to 54%. b) MeNO2, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU),
CH2Cl2, À 308, 4 h; r.t., 16 h. c) 1 bar H2, MeOH, Raney-Ni, r.t., 20 h.
Scheme 5
O
O
Si
Ph
O
O
O
O
O
H
H
H
17
Ph
Ph
O
NH
+
H
OH
BnO
NO2
BnO
NO2
16
19
18
of the dioxanone 17, so it was prepared in two steps from 20 according to the method of
Tsunoda et al. (Scheme 6) [7]. The hydroxy acid 20 could be transformed into the
doubly silylated 26. Then, 26 was condensed with pivalaldehyde at À 788 to furnish 17.

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Helvetica Chimica Acta Vol. 86 (2003)
Scheme 6
OH
OH
OH
OH
O
[10]
a)
b)
OH
OTs
CN
Ph
Ph
Ph
Ph
OR
O
O
21
22
24
20
R = H
via:
Ph
[11]
23
25 R = Et
RO
O
O
O
d)
Ph
OR
Ph
O
26 R = Me3Si
20 R = H
17
c)
e)
f)
O
BnO
NO2
BnO
NO2
BnO
OH
28
H
18
27
a) KCN, MeOH, 6 d, r.t.; 76%. b) 5m aq. NaOH, H2O2, 238; 57%. c) Me3SiCl, Et3N, CH2Cl2; 69%.
d) pivalaldehyde, Me3Si-triflate, CH2Cl2, À 788; 75%. e) MeNO2, KOH in MeOH, r.t.; 88%. f) MsCl, Et3N,
DMAP, CH2Cl2, r.t.; 82%.
After recrystallization from THF, 17 was submitted to X-ray crystal-structure
elucidation (Fig. 1). The configuration of the new stereogenic center at C(2) was estab-
lished as (S) relative to the known (R)-configuration at C(6). This arrangement corre-
sponds to our expectations that both substituents would be attached to the ring in an
equatorial orientation. Moreover, Fig. 1 clearly shows how the Re-face of the ring (with
respect to the lactone) is sterically blocked by the Ph substituent. Therefore, it can be
assumed that a substituent at C(5) would be introduced in trans-orientation to the Ph ring.
Synthesis of the Nitro Alkene 18. The nitro alkene 18 was prepared by condensation
of the corresponding aldehyde 27 with MeNO2 (Scheme 6) analogously to [12].
Aldehyde 27 was synthesized as described in [13]. In basic methanolic solution, MeNO2
and 27 formed the nitro alcohol 28, which, upon treatment with MsCl and Et3N, was
converted to the desired nitro alkene 18.
Addition of the Enolates of 17 and 25 to 18. The dioxanone 17 was treated with LDA
to generate its lithium enolate (Scheme 7). Addition of a THF solution of 18 at À 758
furnished in 86% yield the diastereoisomers 19 and epi-19 in the ratio 1:1. As found for
the trifluoromethyl derivatives 10 by Seebach and co-workers [8], the dioxanone
system properly induced the trans-configuration between the new substituent and the

Helvetica Chimica Acta Vol. 86 (2003)
649
Fig. 1. ORTEP Plot of the molecular structure of 17 (with 50% probability ellipsoids)
Ph ring. On the other hand, no selectivity was observed for the formation of the second
stereogenic center. This means that the two faces of 18 are not distinguished by the
enolate; Re attack leads to 19 and Si attack to epi-19. Due to their apolar character, the
diastereoisomers showed very similar chromatographic properties, so they were not
separated before the next steps. The mixture 19/epi-19 was submitted to acid-catalyzed
esterification in EtOH (Scheme 7), so, in one step, the pivaloyl group could be removed
and the ethyl ester introduced to obtain 29 and epi-29 in 69% yield. The quite low yield
can be explained by partial elimination of H2O, leading to a cinnamic acid derivative. In
analogy to [3] and [4], direct alkylation of the b-hydroxy ester 25 was performed by
treatment with 2 equiv. of LDA at À 60 to À 108 in THF and adding 1.1 equiv. of 18 at
À 78 (Scheme 7). A 1:1 mixture of the two diastereoisomers 29 and epi-29 was isolated
in 53% yield, as well as ca. 20% of starting material 25. When 1.5 equiv. of 18 were
added, the yield dropped to ca. 40%, probably due to O-alkylation of 25. The
secondary OH groups in 29 and epi-29 had to be protected with a stable group for the
rest of the synthesis, and we chose the (t-Bu)Me2SiO group, as it can be introduced and
removed specifically and under mild conditions. The protection was carried out with (t-
Bu)Me2Si-triflate, which is more reactive than the corresponding chloride. The very
nonpolar silylated 30 and epi-30 could be separated by repeated chromatography.
Cleavage of the BnO groups of 30 and epi-30 by Catalytic Hydrogenation. It was
originally planned to convert the NO2 groups of 30 and epi-30 to NH2 groups, and to
remove the BnO groups at once by catalytic hydrogenation. During the search for

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Helvetica Chimica Acta Vol. 86 (2003)
Scheme 7
O
O
OH
O
H
H
H
a)
b)
c)
Ph
O
Ph
OEt
17
25
H
BnO
NO2
BnO
NO2
29 + epi-29
19 + epi-19
d)
TBDMSO
Ph
TBDMSO
O
TBDMSO
Ph
O
O
H
H
H
H
e)
Ph
OEt
OEt
O
+
H
H
NO2
HO
NO2
BnO
NO2
(TBDMS = (t-Bu)Me2Si)
31
epi-32
30 + epi-30
a) 1. LDA, THF, À 758; 2. 18, THF, À 758, 86%. b) EtOH, conc. H2SO4, 788, 17 h; 69%. c) 1. 2 equiv. LDA,
THF, À 60 to À 108; 2. 1.1 equiv. 18, THF, À 7 to ‡ 148, 2 h; 53%. d) (t-Bu)Me2Si-triflate, DMF/CH2Cl2, 08,
7 h; 93%. e) 3.5 bar H2, AcOH/CH2Cl2/CHCl3 70 :5 :0.5, 10% Pd/C, 24 h; 94%.
suitable conditions, we discovered that the hydrogenation of 30 and epi-30 in the
presence of 10% Pd/C in AcOH with ca. 10% chlorinated solvents (CH2Cl2 and traces
of CHCl3) at 3.5 bar H2 pressure cleaved the BnO groups selectively (Scheme 7). The
NO2 groups were not affected at all, while, under different conditions, at least partial
reduction to the hydroxylamines was observed. The chemical yield of ca. 90% was
reached only with a special lot of catalyst, different lots seem to vary in their activity.
Unexpectedly, one of the formed hydroxy esters spontaneously cyclized to the lactone
31, whereas the product emerging from epi-30 did not show any tendency to cyclize and
could be isolated as hydroxy ester epi-32. Based on the dramatic differences in polarity,
31 (Rf 0.70) and epi-32 (Rf 0.42) could be very easily separated by column
chromatography (CH2Cl2/AcOEt 20 :1).
Configurations of epi-32 and 31. The relative configuration of epi-32 could be
elucidated by X-ray crystal-structure analysis of racemic epi-32 crystallized from
EtOH. In the crystal, (Æ)-epi-32 is present in two conformations A and B in the ratio
63 :37, but they differ only in the orientation of the (t-Bu)Me2Si and NO2 groups
(Fig. 2). The two halves of the molecule linked by the C(2)ÀC(3) bond show a
staggered conformation. For the torsion angle C(1)ÀC(2)ÀC(3)ÀC(4), the value
À 71.4(4)8 was found, which corresponds almost with À 608, the theoretical value for
perfect staggering. Knowing that the (R)-configuration at C(1') originated from (‡)-l-

Helvetica Chimica Acta Vol. 86 (2003)
651
mandelic acid, the absolute configuration of the enantiomerically pure epi-32 could be
assigned as (1'R,2S,3R). This enabled us to determine the configuration of epi-30, the
precursor of epi-32, and the configurations of 30 and 31. The reason for different
cyclization behaviors of the two hydroxy esters 32 and epi-32 may be explained by their
different relative configurations.
Fig. 2. ORTEP Plot of the two disordered conformations in the molecular structure of (Æ)-epi-32 (with 50%
probability ellipsoids)
Conclusions. The enantiomerically pure nitro derivatives 31 and epi-32, which are
particularly useful intermediates for the synthesis of highly functionalized g-lactams,
are readily accessible by a straightforward synthesis. In the key step, the enolate of the
b-hydroxy ester 25 or its dioxanone derivative 17 are added in a Michael-type addition
to the nitro alkene 18 to form a 1:1 mixture of two diastereoisomers. The stereo-
selectivity with respect to the novel stereogenic centre in the a-position to the ester
group is controlled by the cyclic structures of both the ester and the dioxanone enolate.
Furthermore, later in the synthesis, one of the two isomers underwent lactonization,
while its epimer could be isolated as a hydroxy ester. This chemoselectivity allows a
very facile separation by simple column chromatography.
We thank the analytical departments of our institute for excellent services, the Kanton Z¸rich and the Swiss
National Science Foundation for generous financial support.
Experimental Part
General. All commercially available reagents were used without further purification. Solvents were either
puriss. p.a. grade (Fluka) or distilled prior to use. THF for the reaction with LDA was dried over Na-
benzophenone and freshly distilled before use. Reactions were normally not carried out under N2, unless stated
otherwise; they were monitored by TLC on Merck precoated plates Kieselgel 60 F254. All extracts were dried

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Helvetica Chimica Acta Vol. 86 (2003)
before evaporation over MgSO4, unless stated otherwise. Column chromatography (CC): Kieselgel 60 (230
400 mesh ASTM) from Merck. M.p.: Mettler Fp 5. IR [cmÀ1]: in CHCl3 (Fluka for IR spectroscopy); Perkin-
Elmer 781. Optical rotations (‰aŠ21): in CHCl3 (filtrated over Alox I), except stated otherwise; Perkin-Elmer 241
D
polarimeter. NMR Spectra: in CDCl3, except stated otherwise; 1H-NMR: Bruker ARX-300 (300 MHz) or
Bruker DRX-600 (600 MHz); 13C-NMR: Bruker ARX-300 (75 MHz) or Bruker DRX-600 (150 MHz); chemical
shifts d in ppm rel. to Me4Si as internal standard; coupling constants J in Hz. MS: Finnigan SSQ-700 for chemical
ionization (CI) with NH3, Finnigan MAT-90 for electron impact (EI, 70 eV), and Finnigan TSQ-700 for
electrospray ionization (ESI); m/z (rel. intensity in %). Hydrogenation: Parr-Instruments Company Inc.
(3.5 bar H2).
(‡)-(R)-3-Hydroxy-3-phenylpropanenitrile (24). A soln. of 40.44 g (138mmol) of (‡)-(S)-2-hydroxy-2-
phenylethyl 4-methylbenzenesulfonate (22, prepared according to [10], m.p. 70.0 72.48 (t-BuOMe), [a]D
ˆ
‡51.5 (c ˆ 2.365, CHCl3)), in 500 ml of MeOH was treated with 8.99 g (138 mmol) of KCN dissolved in ca. 50 ml
of MeOH and stirred at r.t. for 8.5 h and, later, another 8.09 g (124 mmol) of KCN was added. After 6 d, the dark
blue mixture was evaporated, the residue was poured into H2O and extracted with CH2Cl2. High-vacuum
distillation afforded 15.40 g (76%) of 24 as a colorless oil. Upon storage at r.t., the product acquired a deep blue
color, so it was kept under Ar at À 188. [a]D ˆ ‡50.4 (c ˆ 4.945, MeOH). IR (CHCl3): 3590m, 3400m (br.),
3000m, 2890m, 2250m, 1950w, 1875w, 1810w, 1700w, 1600m, 1490m, 1450m, 1410m, 1310m, 1280m, 1170m,
1
1080m, 1050s, 1025m, 935m, 910m, 8 65m, 690m, 630m. H-NMR (300 MHz): 7.40 7.31 (m, 5 H); 4.99 (dt, J ˆ
6.2, 3.8, 1 H); 2.84 (d, J ˆ 3.8, 1 H); 2.72 (d, J ˆ 6.0, 2 H). 13C-NMR (75 MHz): 141.0 (s); 128.8 (d); 128.7 (d);
‡
125.5 (d); 117.2 (s); 70.0 (d); 27.9 (t). CI-MS: 165 ([M ‡ 18] ).
(S)-2-Phenyloxirane (23). A sample of 21.1 g (72 mmol) of 22 was dissolved in 300 ml of MeOH, then
8.93 g (137 mmol) of KCN and a few grains of 4-(dimethylamino)pyridine (DMAP) were added, and the
mixture was stirred at r.t. for 23 h. The mixture was evaporated and poured into H2O, extracted with CH2Cl2,
and purified by CC (CH2Cl2/AcOEt 20 :1) to give 3.74 g (43%) of 23 and 4.19 g (39.5%) of 24. 1H-NMR
(300 MHz) of 23: 7.37 7.24 (m, 5 H); 3.84 (dd, J ˆ 4.2, 2.7, 1 H); 3.13 (dd, J ˆ 5.4, 4.0, 1 H); 2.79 (dd, J ˆ 5.7, 2.7,
1 H). 13C-NMR (75 MHz): 137.6 (s); 128.4 (d); 128.1 (d); 125.5 (d); 52.3 (d); 51.1 (t).
(‡)-(R)-3-Hydroxy-3-phenylpropanoic Acid (20). A soln. of 4.15 g (28.2 mmol) of 24 in 100 ml of aq. 5m
NaOH was treated with 40 ml of 32% H2O2, whereby the temp. rose to 358. After stirring at r.t. for 6.5 h, the
mixture was poured into 100 ml of 40% aq. H3PO4 and extracted with CH2Cl2. Recrystallization from 80 ml of t-
BuOMe/hexane 1 :1 at À 188 afforded 2.69 g (57.4%) of 20. Colorless needles. M.p. 115.5 117.08. [a]D ˆ ‡22.4
(c ˆ 4.135, MeOH). IR (KBr): 3293m, 2921m, 2654m, 1699s, 1496w, 1456m, 1417m, 1353w, 1273m, 1211m,
1177m, 1084m, 1054m, 1017m, 925w, 8 8w6, 8 37w, 766m, 703s, 611m, 532w. 1H-NMR (300 MHz; DMSO; d ˆ
2.54 ppm): 7.47 7.30 (m, 5 H); 5.04 (t, J ˆ 6.9, 1 H); 2.63 (d, J ˆ 6.9, 2 H). 13C-NMR (75 MHz; DMSO; d ˆ
.
‡
39.7 ppm): 172.4 (s); 145.2 (s); 128.2 (d); 127.1 (d); 126.0 (d); 69.7 (d); 44.7 (t). EI-MS: 166 (40, M ), 107 (100),
‡
106 (30), 105 (28), 79 (89), 77 (64). CI-MS: 218 (8), 184 (100, [M ‡ 18] ), 166 (17).
Trimethylsilyl (R)-3-Phenyl-3-[(trimethylsilyl)oxy]propanoate (26). A suspension of 2.62 g (15.8mmol)
of 20 in 20 ml of CH2Cl2 was chilled with an ice-bath, then 4.83 ml (37.7 mmol) of Et3N and 4.39 ml (34.7 mmol)
of Me3SiCl were added slowly. Stirring at r.t. was maintained for 5 d, and the thick suspension was liquefied
from time to time by adding CH2Cl2. The mixture was diluted with 20 ml of pentane, filtered, and the cake was
washed with pentane and t-BuOMe, followed by washing the filtrate with aq. 1m HCl and H2O. High-vacuum
distillation yielded 3.384 g (69%) of 26 as a colorless oil, which was stored under Ar at À 188. 1H-NMR
(300 MHz): 7.35 7.22 (m, 5 H); 5.11 (dd, J ˆ 9.0, 4.4, 1 H); 2.72 (dd, J ˆ 15.1, 9.0, 1 H); 2.57 (dd, J ˆ 15.1, 4.4,
1 H); 0.26 (s, 18 H). 13C-NMR (75 MHz): 172.6 (s); 143.9 (s); 128.2 (d); 127.4 (d); 125.9 (d); 72.0 (d); 47.6 (t);
0.0 (q).
(‡)-(2S,6R)-2-(tert-Butyl)-6-phenyl-1,3-dioxan-4-one (17). In a flame dried-vessel under Ar, 7.59 g
(24.4 mmol) of 26 was dissolved in 50 ml of CH2Cl2. At À 708, 2.96 ml (26.9 mmol) of pivalaldehyde and,
80 min later at À 608, 220 ml (1.23 mmol) of Me3Si-triflate were added. The mixture was stirred for 7 h at À 708,
then the reaction was stopped by addition of 200 ml of pyridine and slow warming to r.t. Another 50 ml CH2Cl2
was poured into the mixture, before it was washed twice with sat. aq. NaHCO3 soln. The product was purified by
crystallization (t-BuOMe/hexane 1:1) to give 4.307 g (75%) of 17. Colorless needles. M.p.: 135.4 139.88. [a]D
ˆ
‡93.7 (c ˆ 1.965, CHCl3). IR (CHCl3): 2980m, 2960m, 2910w, 2880w, 1740s, 1600w, 1485m, 1450w, 1410w, 1370m,
1
1345m, 1315w, 1280m, 1110m, 1070w, 990s, 700w. H-NMR (300 MHz): 7.41 7.32 (m, 5 H); 5.11 (s, 1 H); 4.93
(dd, J ˆ 10.8, 4.5, 1 H); 2.95 (dd, J ˆ 17.6, 4.5, 1 H); 2.69 (dd, J ˆ 17.6, 10.8, 1 H); 1.06 (s, 9 H). 13C-NMR
(75 MHz): 167.6 (s); 139.4 (s); 128.8 (d); 128.5 (d); 125.3 (d); 108.4 (d); 75.4 (d); 38.1 (t); 35.5 (s); 24.0 (q).
.
‡
EI-MS: 234 (6, M ), 205 (4), 177 (25), 131 (100), 107 (30), 104 (90), 79 (15), 78(20), 77 (25), 57 (60). CI-MS:

Helvetica Chimica Acta Vol. 86 (2003)
653
‡
‡
252 (100, [M ‡ 18] ), 235 (14, [M ‡ 1] ), 166 (59), 148(5), 131 (7), 104 (9). Crystals suitable for X-ray crystal-
structure analysis were obtained from THF.
(Æ)-3-(Benzyloxy)-1-nitropropan-2-ol (28). A soln. of 6.034 g (40 mmol) of 27 [13] in 21.5 ml (400 mmol)
of MeNO2 was treated dropwise with 3 ml of a 3m methanolic KOH soln., which induced a remarkable warming.
After 1.5-h stirring at r.t., 70 drops conc. H2SO4 were added. The mixture was poured into H2O, extracted twice
with t-BuOMe, the org. phase was washed with aq. sat. NaHCO3 soln. and brine: 7.40 g (88%) 28. An anal.
sample was obtained by CC (CH2Cl2/AcOEt 20 :1). 1H-NMR (300 MHz): 7.40 7.29 (m, 5 H); 4.60 4.44
(m, 5 H); 3.56 3.55 (m, 2 H); 2.91 (br. s, 1 H). 13C-NMR (75 MHz): 137.1 (s); 128.5 (d); 128.1 (d); 127.8( d);
78.0 (t); 73.6 (t); 70.4 (t); 67.7 (d).
3-(Benzyloxy)-1-nitroprop-1-ene (18). At r.t., 4.66 ml (60 mmol) of MsCl and a few grains of DMAP were
added to a soln. of 7.40 g (35 mmol) of crude 28 in 75 ml of CH2Cl2. Upon dropwise addition of 11.2 ml
(80 mmol) of Et3N, the soln. warmed up until boiling. After stirring for 1 h at r.t., the mixture was poured into
H2O and extracted with CH2Cl2. The product was purified by CC (CH2Cl2): 5.55 g (82%) of 18. Yellow oil.
Storage under Ar at À 188. IR (CHCl3): 3120w, 3000w, 2860m, 1660m, 1635w, 1525s, 1495m, 1450m, 1355s,
1275w, 1120s, 1020m, 930s, 8 25w, 690w. 1H-NMR (300 MHz): 7.41 7.20 (m, 7 H); 4.60 (s, 2 H); 4.27 4.25
(m, 2 H). 13C-NMR (75 MHz): 139.7 (d); 138.3 (d); 137.0 (s); 128.6 (d); 128.1 (d); 127.7 (d); 73.3 (t); 65.5 (t). CI-
‡
MS: 211 (100, [M ‡ 18] ), 177 (51), 147 (27), 108(38).
(2S,5S,6R)-5-[(S)-2-(Benzyloxy)-1-(nitromethyl)ethyl]-2-(tert-butyl)-6-phenyl-1,3-dioxan-4-one (19) and
(2S,5S,6R)-5-[(R)-2-(Benzyloxy)-1-(nitromethyl)ethyl]-2-(tert-butyl)-6-phenyl-1,3-dioxan-4-one (epi-19). In a
flame-dried bottle under Ar, a soln. of 310 ml (2.2 mmol) of (i-Pr)2NH in 2 ml of THF was treated at À 708 with
1.4 ml (2.2 mmol) of a 1.6m BuLi soln. in hexane. The cooling was removed for 5 min, and, after the temp. of the
soln. had reached À 708 again, a soln. of 468mg (2.0 mmol) of ( ‡)-17 in 4 ml of THF was added during 3 min.
The temp. rose to À 608 during stirring, and, after 45 min, it was cooled to À 958, and a soln. of 510 ml
(3.0 mmol) of 18 in 2 ml of THF was added dropwise over 3 min. Stirring was maintained at À 758 for another
45 min, then the mixture was poured into 20 ml of aq. sat. NH4Cl soln. and extracted with t-BuOMe. CC
(pentane/t-BuOMe 3 :1) of the crude product afforded 739 mg (86%) of 19/epi-19 in a 1 :1 ratio according to the
1H-NMR spectra. IR (CHCl3): 2960m, 2900w, 2870m, 1730s, 1550s, 1480m, 1450m, 1405m, 1375m, 1365m,
1345m, 1315m, 1280m, 1100s, 1025w, 990s, 950w, 935w, 910w, 8 45w, 690w. 1H-NMR (600 MHz): 7.42 7.20
(m, 20 H); 5.01 (s, 1 H); 4.90 (d, J ˆ 10.5, 1 H); 4.81 (s, 1 H); 4.69 (d, J ˆ 11.0, 1 H); 4.64 (dd, J ˆ 13.5, 7.0, 1 H);
4.56 (dd, J ˆ 13.5, 7.0, 1 H); 4.52 (d, J ˆ 11.2, 1 H); 4.46 (d, J ˆ 11.2, 1 H); 4.37 (AB, 2 H); 4.25 4.23 (m, 2 H);
3.70 3.68( m, 1 H); 3.66 3.62 (m, 3 H); 3.55 3.52 (m, 1 H); 3.12 3.09 (m, 1 H); 3.00 (dd, J ˆ 11.0, 1.8, 1 H);
2.76 (dd, J ˆ 10.5, 1.4, 1 H); 2.72 2.69 (m, 1 H); 0.97 (s, 9 H); 0.91 (s, 9 H). 13C-NMR (150 MHz): 168.8 (s);
168.7 (s); 137.8( s); 137.7 (s); 137.2 (s); 137.1 (s); 129.5 (d); 129.2 (d); 129.0 (d); 128.9 (d); 128.6 (d); 128.5 (d);
128.2 (d); 128.1 (d); 127.9 (d); 127.7 (d); 127.4 (d); 127.1 (d); 108.5 (d); 108.1 (d); 80.0 (d); 79.1 (d); 76.8( t); 74.7
(t); 73.9 (t); 73.1 (t); 69.5 (t); 68.0 (t); 48.2 (d); 47.9 (d); 36.3 (d); 35.4 (s); 35.3 (d); 35.2 (s); 23.9 (q). CI-MS: 445
‡
(94, [M ‡ 18] ), 359 (100), 315 (38), 206 (87).
Ethyl (2S,3S)- and(2 S,3R)-4-(Benzyloxy)-2-[(R)-hydroxy(phenyl)methyl]-3-(nitromethyl)butanoate (29
and epi-29, resp.). a) By Transesterification of 19 and epi-19. Ten drops of conc. H2SO4 were added to a soln. of
19/epi-19 (ratio 1:1) in 15 ml of EtOH. The mixture was heated to reflux during 17 h, the solvent was
evaporated, and the residue was poured into H2O and extracted with CH2Cl2. Purification by CC (CH2Cl2/
AcOEt 20 :1) yielded 449 mg (69%) of a 1:1 mixture 29/epi-29.
b) By Addition of the Enolate of 25 to 18. In a flame-dried bottle under Ar, a soln. of 1.23 ml (8.7 mmol) of
(i-Pr)2NH in 2 ml of THF was treated at 08 with 5.45 ml (8.7 mmol) of a 1.6m BuLi soln. in hexane, and the
mixture was cooled to À 608. After the dropwise addition of a soln. of 847 mg (4.36 mmol) of ethyl (‡)-(R)-3-
hydroxy-3-phenylpropanoate (25, prepared according to [11], [a]D ˆ ‡51.6 (c ˆ 1.105, CHCl3)) in 2 ml of THF,
the mixture was allowed to warm slowly. When the temp. had reached À 78 (after 2 h), a soln. of 820 ml
(4.8mmol) of 18 in 2 ml of THF was added, whereby the temp. rose to 08. Another 2 h later, the temp. reached
‡ 148, and the mixture was poured into sat. aq. NH4Cl soln. and extracted with CH2Cl2. CC (CH2Cl2/AcOEt
20 :1) yielded 900 mg (53%) of a 1 :1 mixture 29/epi-29. IR (CHCl3): 3600w, 3500w (br.), 3090w, 3060w, 2980w,
2900w, 2870m, 1720s, 1555s, 1495m, 1455m, 1430m, 1395m, 1375s, 1330m, 1180s, 1115m, 1095s, 1060m, 1020m,
910w, 8 70w, 8 30w, 695m. 1H-NMR (300 MHz): 7.38 7.25 ( m, 20 H); 5.04 (br. t, J ˆ 6.8, 1 H); 4.95 (br. t, J ˆ 6.4,
1 H); 4.69 (d, J ˆ 6.2, 2 H); 4.64 4.42 (m, 6 H); 4.04 3.90 (m, 4 H); 3.69 (dd, J ˆ 10.0, 4.4, 1 H); 3.58 3.51
(m, 3 H); 3.38(br. d, J ˆ 7.8, 1 H); 3.21 (br. d, J ˆ 7.5, 1 H); 3.07 3.00 (m, 2 H); 2.90 2.78( m, 2 H); 1.03 (t, J ˆ
7.1, 3 H); 1.03 (t, J ˆ 7.1, 3 H ) . 13C-NMR (75 MHz): 173.0 (s); 141.2 (s); 140.8( s); 137.4 (s); 128.6 (d); 128.5 (d);
128.1 (d); 127.9 (d); 127.8( d); 127.7 (d); 125.9 (d); 125.7 (d); 75.0 (t); 74.8( t); 73.4 (t); 72.4 (d); 72.3 (d) 68.2 (t);

654
Helvetica Chimica Acta Vol. 86 (2003)
‡
67.8( t); 61.1 (t) 51.7 (d); 51.1 (d); 37.9 (d); 37.7 (d); 13.8( q). CI-MS: 405 (100, [M ‡ 18] ), 387 (90), 370 (19),
358(15), 318(16), 299 (30), 294 (22), 278(52).
Ethyl (À)-(2S,3S)- and( ‡)-(2S,3R)-4-(Benzyloxy)-2-[(R)-{[(tert-butyl)dimethylsilyl]oxy}(phenyl)meth-
yl]-3-(nitromethyl)butanoate (30 and epi-30, resp.). To a 1:1 mixture of 724 mg (1.87 mmol) of 29/epi-29,
dissolved in 3.5 ml of DMF and 3.5 ml of CH2Cl2, 330 ml (2.83 mmol) of 2,6-lutidine, and 515 ml of (t-Bu)Me2Si-
triflate were added at 08. The mixture was stirred during 7.5 h, poured into H2O, and extracted with CH2Cl2. The
org. phase was washed twice with aq. CuSO4 soln. and with aq. NH4Cl soln., and evaporated. After CC (pentane/
t-BuOMe 9 :1), 872 mg (93%) of 30/epi-30 were obtained. The two diastereoisomeric products could be
separated without loss by repeated CC.
Data of 30: [a]D ˆ À4.6 (c ˆ 1.00, CHCl3). IR (CHCl3): 2950m, 2930m, 2890w, 2860m, 1725s, 1555s, 1495w,
1470w, 1460w, 1455m, 1430w, 1380m, 1360m, 1295w, 1255m, 1180m, 1080s, 1025w, 1005w, 940w, 915w, 8 95w, 8 8 5w,
870w, 8 40s, 695w. 1H-NMR (600 MHz): 7.36 7.25 (m, 10 H); 4.95 (d, J ˆ 9.4, 1 H); 4.45 (dd, J ˆ 13.6, 6.2, 1 H);
4.40 4.38( m, 2 H); 4.27 (dd, J ˆ 13.6, 7.6, 1 H); 4.14 (q, J ˆ 7.2, 2 H); 3.56 (dd, J ˆ 10.0, 4.4, 1 H); 3.40 (dd, J ˆ
10.0, 7.7, 1 H); 2.93 (dd, J ˆ 9.4, 4.1, 1 H); 2.42 2.39 (m, 1 H); 1.26 (t, J ˆ 7.2, 3 H); 0.78( s, 9 H); À 0.01 (s, 3 H);
À 0.34 (s, 3 H). 13C-NMR (150 MHz): 171.8( s); 140.9 (s); 137.6 (s); 128.6 (d); 128.5 (d); 128.4 (d); 127.8( d);
127.6 (d); 127.2 (d); 75.6 (t); 74.9 (d); 73.1 (t); 67.0 (t); 60.8( t) 53.7 (d); 36.6 (d); 25.5 (q); 17.9 (s); 14.2 (q); À 4.6
‡
(q); À 5.4 (q). CI-MS: 519 (27, [M ‡ 18] ), 387 (81), 370 (26), 295 (8), 278 (100).
Data of epi-30: [a]D ˆ ‡42.2 (c ˆ 0.925, CHCl3). IR (CHCl3): 2950m, 2930m, 2890w, 2860m, 1725s,
1555s, 1495w, 1470w, 1460w, 1455m, 1430w, 1395w, 1380m, 1360m, 1330w, 1255m, 1180m, 1090s, 1025w,
1
1005w, 940w, 915w, 8 40s, 695w. H-NMR (600 MHz): 7.38 7.23 ( m, 10 H); 4.85 (d, J ˆ 9.6, 1 H); 4.68( dd, J ˆ
13.5, 3.2, 1 H); 4.62 (dd, J ˆ 13.5, 9.7, 1 H); 4.38 4.36 ( m, 2 H); 4.11 3.99 (m, 2 H); 3.39 (dd, J ˆ 9.8, 4.9,
1 H); 3.32 (dd, J ˆ 9.8, 4.6, 1 H); 3.01 (dd, J ˆ 9.5, 3.4, 1 H); 2.35 2.28( m, 1 H); 1.21 (t, J ˆ 7.2, 3 H);
0.80 (s, 9 H); À 0.02 (s, 3 H); À 0.32 (s, 3 H). 13C-NMR (150 MHz): 172.5 (s); 141.2 (s); 137.6 (s); 128.7 (d);
128.5 (d); 128.3 (d); 127.7 (d); 127.5 (d); 127.0 (d); 75.3 (d); 74.0 (t); 73.2 (t); 70.0 (t); 60.8( t) 55.3 (d); 36.7 (d);
‡
25.5 (q); 17.9 (s); 14.0 (q); À 4.7 (q); À 5.5 (q). CI-MS: 519 (37, [M ‡ 18] ), 387 (100), 370 (12), 278 (14), 219
(7).
Ethyl (‡)-(2S,3R)-2-[(R)-{[(tert-Butyl)dimethylsilyl]oxy}(phenyl)methyl]-4-hydroxy-3-(nitromethyl)bu-
tanoate (epi-32). In a 500-ml flask for the Parr apparatus, 215 mg (0.43 mmol) of epi-30 were dissolved in
70 ml of AcOH, 5 ml of CH2Cl2 and 0.5 ml of CDCl3. After addition of 95 mg of 10% Pd/C, the mixture was
hydrogenated during 24 h under 3.5 bar H2 pressure. Filtration, evaporation, and CC (CH2Cl2/AcOEt 50 :1)
afforded 152 mg (86%) oily epi-32. [a]D ˆ ‡56.0 (c ˆ 1.15, CHCl3). IR (CHCl3): 2960m, 2930m, 2890w, 2860m,
1725s, 1555s, 1470w, 1460w, 1455w, 1395m, 1380m, 1360m, 1330w, 1255m, 1085s, 1020w, 1005w, 970w, 940w, 915w,
1
870w, 8 40s, 700w. H-NMR (600 MHz): 7.38 7.30 ( m, 5 H); 4.87 (d, J ˆ 9.6, 1 H); 4.65 (dd, J ˆ 13.5, 3.2, 1 H);
4.52 (dd, J ˆ 13.5, 9.8, 1 H); 4.18 (q, J ˆ 7.2, 2 H); 3.53 (d, J ˆ 5.3, 2 H); 3.02 (dd, J ˆ 9.6, 3.4, 1 H); 2.20 2.17
(m, 1 H); 1.85 (br. s, 1 H); 1.30 (t, J ˆ 7.2, 3 H); 0.80 (s, 9 H); À 0.02 (s, 3 H); À 0.33 (s, 3 H). 13C-NMR
(150 MHz): 172.6 (s); 141.0 (s); 128.7 (d); 128.6 (d); 126.9 (d); 75.0 (d); 73.7 (t); 62.9 (t); 61.0 (t) 54.9 (d); 38.3
‡
(d); 25.5 (q); 17.8( s); 14.1 (q); À 4.7 (q); À 5.5 (q). CI-MS: 429 (6, [M ‡ 18] ), 383 (6), 297 (100), 251 (13).
From racemic epi-32, which was prepared from (Æ)-17, crystals suitable for X-ray crystal-structure analysis could
be obtained from EtOH (m.p. 83.5 86.58).
(‡)-(3S,4S)-3-[(R)-{[(tert-Butyl)dimethylsilyl]oxy}(phenyl)methyl]-2,3,4,5-tetrahydro-4-(nitromethyl)furan-
2-one (31). Analogously to the preparation of epi-32, reaction of 30 (165 mg, 0.33 mmol) and 10% Pd/C (71 mg)
in 80 ml of AcOH, 5 ml of CH2Cl2, and 0.5 ml of CDCl3 in a Parr apparatus (3.5 bar H2 pressure) yielded, after
CC (CH2Cl2/AcOEt 50 :1), colorless crystals of 31 (96 mg, 80%). M.p. 69.5 71.68 (AcOEt). [a]D ˆ ‡41.0 (c ˆ
1.01, CHCl3). IR (CHCl3): 2950m, 2930m, 2880w, 2860m, 1775s, 1720w, 1610w, 1555s, 1460w, 1450w, 1430w,
1375m, 1255m, 1160m, 1090m, 1060m, 1025m, 1005w, 940w, 900w, 8 3s5. 1H-NMR (600 MHz): 7.37 7.32
(m, 5 H); 5.44 (d, J ˆ 3.9, 1 H); 4.83 (dd, J ˆ 13.6, 4.7, 1 H); 4.47 (dd, J ˆ 13.6, 9.7, 1 H); 4.03 (dd, J ˆ 9.6, 8.1,
1 H); 3.95 (dd, J ˆ 9.6, 7.5, 1 H); 3.17 3.09 (m, 1 H); 2.90 (dd, J ˆ 8.7, 3.8, 1 H); 0.93 (s, 9 H); 0.10 (s, 3 H); À
0.03 (s, 3 H). 13C-NMR (150 MHz): 173.8( s); 139.1 (s); 128.6 (d); 128.4 (d); 126.3 (d); 76.6 (t); 72.9 (d); 69.4 (t);
‡
51.3 (d) 34.5 (d); 25.7 (q); 18.1 (s); À 4.9 (q); À 5.3 (q). CI-MS: 748(46, [2 M ‡ 18] ), 616 (6), 471 (10), 383
‡
(100, [M ‡ 18] ), 308(13), 251 (6).
Hydrogenation of a Mixture 30/epi-30. In a 500-ml flask of a Parr apparatus, 300 mg (0.60 mmol) of a
mixture epi-30/30 27:73 was dissolved in 70 ml of AcOH, 5 ml of CH2Cl2, and 0.5 ml of CDCl3. After addition of
130 mg of 10% Pd/C, the mixture was hydrogenated during 27 h under 3.5 bar H2 pressure. Filtration,
evaporation, and CC (CH2Cl2/AcOEt 50 :1) afforded 146 mg (0.40 mmol, 67%) of 31 and 66 mg (0.16 mmol,
27%) of epi-32. The total yield of the two very easily separable products was 94%.

Helvetica Chimica Acta Vol. 86 (2003)
655
Crystal-Structure Determinations of 17 and( Æ)-epi-322). All measurements were conducted on a Nonius
KappaCCD diffractometer with graphite-monochromated MoKa radiation (l ˆ 0.71073 ä). The intensities
were corrected for Lorentz and polarization effects, but not for absorption. The data collection and refinement
parameters are given in the Table, and views of the molecules are shown in Figs. 1 and 2. For 17, the structure was
solved by direct methods using SHELXS97 [14]. The non-H-atoms were refined anisotropically. All of the H-
atoms were fixed in geometrically calculated positions (d(CÀH) ˆ 0.95 ä), and each was assigned a fixed
isotropic displacement parameter with a value equal to 1.2Ueq of its parent C-atom. The absolute configuration
could not be determined crystallographically due to the absence of significant anomalous scatterers in the
compound. Instead, the enantiomer used in the refinement was based on the known (R)-configuration at the Ph-
substituted C-atom which was derived from the (‡)-l-mandelic acid used in the synthesis. For (Æ)-epi-32, the
structure was solved by direct methods with SIR92 [15]. The Si-atom and its attached Me and t-Bu groups are
disordered. Two positions were defined for each of the affected atoms. The best results were obtained when the
site occupation factor of the major conformation was set to 0.63, although some of the CÀC distances in the
Table. Crystallographic Data for Compounds 17 and( Æ)-epi-32
17
(Æ)-epi-32
Crystallized from
THF
EtOH
Empirical formula
Formula weight [g molÀ1
Crystal color, habit
Crystal dimensions [mm]
Temp. [K]
C14H18O3
234.29
colorless, prism
0.20 Â 0.23 Â 0.23
298(1)
C20H33NO6Si
411.56
colorless, prism
0.13 Â 0.25 Â 0.25
160(1)
]
Crystal system
Space group
orthorhombic
P212121
orthorhombic
Pbca
Z
4
8
Reflections for cell determination
1762
4565
2q Range for cell determination [8]
5
55
4 50
Unit cell parameters a [ä]
5.9263(1)
10.2524(2)
21.3223(4)
1295.52(4)
1.201
0.0831
f and w
55
11.2988(2)
10.6558(1)
38.0316(6)
4578.9(1)
1.194
0.135
f and w
50
b [ä]
c [ä]
V [ä3]
Dx [g cmÀ3
]
m(MoKa) [mmÀ1
Scan type
]
2q(max) [8]
Total reflections measured
Symmetry independent reflections
Reflections used [I > 2s(I)]
Parameters refined
21650
2979
2388
155
44013
4042
2462
264
Final R
0.0416
0.0529
0.023
0.0736
0.0739
0.010
wR
Weights: p in w ˆ [s2(Fo) ‡ (pFo)2]À1
Goodness-of-fit
1.472
3.484
Secondary extinction coefficient
Final Dmax/s
D1 (max; min) [e äÀ3
9(1) Â 10À6
0.0002
0.001
0.33; À 0.31
]
0.14; À 0.14
2
)
Crystallographic data (excluding structure factors) for the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as supplementary publication No. CCDC-
181625 and 181626 for 17 and (Æ)-epi-32, resp. Copies of the data can be obtained, free of charge, on
application to the CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax: ‡44-(0)-1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk).

656
Helvetica Chimica Acta Vol. 86 (2003)
model for the disordered region of the molecule are quite poor, particularly for the minor conformation. The O-
atoms of the NO2 group are also disordered over two positions, with the major conformation again having a site
occupation factor of 0.63. The non-H-atoms were refined anisotropically, except for the disordered C-atoms of
both conformations and the disordered O-atoms of the minor conformation, which were refined only
isotropically. All of the H-atoms were fixed in geometrically calculated positions (d(CÀH) ˆ 0.95 ä), and each
was assigned a fixed isotropic displacement parameter with a value equal to 1.2Ueq of its parent atom. The
orientation of the OH group was defined so that the idealized OÀH vector pointed in the direction of a peak
located in a difference electron-density map.
The refinement of each structure was carried out on F by full-matrix least-squares procedures which
minimized the function Sw(j Fo jÀj Fc j)2. A correction for secondary extinction was applied only in the case of
17. Neutral-atom-scattering factors for non-H-atoms were taken from [16], and the scattering factors for H-
atoms from [17]. Anomalous dispersion effects were included in Fc [18]; the values for f' and f'' were those of
Creagh and McAuley [19], and the values of the mass-attenuation coefficients were those of [20]. All
calculations were performed using the teXsan crystallographic software package [21], and the crystallographic
diagrams were drawn with ORTEPII [22].
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M. Hesse, in −The Alkaloids×, Vol. 58, Ed. G. A. Cordell, Academic Press, 2003, p. 83.
¬
[3] G. Frater, Helv. Chim. Acta 1979, 62, 2825.
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¡
[6] P. Aeyras, K. Pihlaja, Tetrahedron Lett. 1970, 4095.
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[12] J. Knight, P. J. Parsons, J. Chem. Soc., Perkin Trans. 1 1989, 979.
[13] J. A. Marshall, J. D. Trometer, B. E. Blough, T. D. Crute, J. Org. Chem. 1988, 53, 4274.
[14] G. M. Sheldrick, −SHELXS97, Program for the Solution of Crystal Structures×, University of Gˆttingen,
Germany, 1997.
[15] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M. C. Burla, G. Polidori, M. Camalli, J. Appl.
Crystallogr. 1994, 27, 435.
[16] E. N. Maslen, A. G. Fox, M. A. O×Keefe, in −International Tables for Crystallography×, Ed. A. J. Wilson,
Kluwer Academic Publishers, Dordrecht, 1992, Vol. C, Table 6.1.1.1, p. 477.
[17] R. F. Steward, E. R. Davidson, W. T. Simpson, J. Chem. Phys. 1965, 42, 3175.
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ReceivedOctober 8, 2002