Molecular geometry and optical activity of N-nitroso-2,2,6,6-tetramethylpiperidines generated by spontaneous crystallization and inclusion complexation with optically active diols

Article abstract of DOI:10.1016/j.tetasy.2009.05.008

Three sterically strained N-nitrosamines and their inclusion complexes with optically active diols (TADDOLs) were obtained and their solid state crystal structures are described. Owing to the formation of N-nitroso-4-hydroxy-2,2,6,6-tetramethylpiperidine 2 as spontaneously resolvable conglomerate crystals (space group P3₂) its solid state CD was measured. The crystal structures of the inclusion complexes revealed that in all cases the guest nitrosamines assume chiral conformations as seen by their chiroptical spectra. The optically active nitrosamines are configurationally labile and rapidly racemize in solution. The solid state structures revealed that in order to avoid an allylic 1,3-strain [A^(1,3)], caused by an interaction of the nitrosamino group with the methyl substituents, the piperidine ring in 1 and 2 assumes a chair conformation significantly flattened at the amino nitrogen whereas in the 4-oxo derivative 3 the piperidine ring assumes a twist-boat conformation.

Full text of DOI:10.1016/j.tetasy.2009.05.008

Tetrahedron: Asymmetry 20 (2009) 1308–1313
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Molecular geometry and optical activity of N-nitroso-2,2,6,6-tetramethyl-
piperidines generated by spontaneous crystallization and inclusion
complexation with optically active diols
a
b
a,
*
´
Teresa Olszewska , Maria Gdaniec , Tadeusz Połonski
a
´
Department of Chemistry, Technical University, 80-952 Gdansk, Poland
b Faculty of Chemistry, A. Mickiewicz University, 60-780 Poznan´, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Three sterically strained N-nitrosamines and their inclusion complexes with optically active diols (TADD-
OLs) were obtained and their solid state crystal structures are described. Owing to the formation of N-
nitroso-4-hydroxy-2,2,6,6-tetramethylpiperidine 2 as spontaneously resolvable conglomerate crystals
(space group P32) its solid state CD was measured. The crystal structures of the inclusion complexes
revealed that in all cases the guest nitrosamines assume chiral conformations as seen by their chiroptical
spectra. The optically active nitrosamines are configurationally labile and rapidly racemize in solution.
The solid state structures revealed that in order to avoid an allylic 1,3-strain [A(1,3)], caused by an inter-
action of the nitrosamino group with the methyl substituents, the piperidine ring in 1 and 2 assumes a
chair conformation significantly flattened at the amino nitrogen whereas in the 4-oxo derivative 3 the
piperidine ring assumes a twist-boat conformation.
Received 20 April 2009
Accepted 11 May 2009
Available online 8 June 2009
Ó 2009 Elsevier Ltd. All rights reserved.
O
OH
Ph2COH
1. Introduction
R1
R2
O
H
N-Nitrosamines have attracted considerable interest over the
past two decades since many compounds of this class are known
to be potential carcinogens and mutagenic agents.1 Since the
molecular geometry and conformational properties critically influ-
ence the biological activity, the stereochemistry of N-nitrosamines
has been the subject of many experimental and theoretical inves-
tigations.2 In the case of piperidines a substitution of the nitrogen
with an NO group strongly affects the conformation of the six-
membered ring and the orientation of substituents. Due to so
H
O
N
N
N
NO
1
NO
3
NO
2
Ph2COH
4, R1 = R2 = CH3
R1 = R2 = (CH2)5
5
,
The introduction of the NO group at the nitrogen atom low-
ers the symmetry of the secondary amines and in the absence
of any improper symmetry axis, N-nitrosamines 1–3 are chiral
and may exist in two enantiomeric forms. Their chirality results
from a hindered rotation about the partial double N–N bond
and interconversion between the enantiomers may occur by
rotation of the NO group or, as in case of 1 and 3, by inversion
of the six-membered ring. A chiral discrimination occurring dur-
ing the complexation of N-nitrosamines with the optically active
diols (R,R)-4 and (R,R)-5 allowed us to obtain the compounds 1–
3 in the optically active forms and measure their solid state CD
spectra. Furthermore, the 4-hydroxy derivative 2 crystallizes as
called allylic 1,3-strain [A(1,3) 3,4
caused by an interaction of the
]
planar N-nitrosamine system with the nearly coplanar equatorial
substituents at C-2 and C-6 of N-nitroso-cis-2,6-dimethylpiperi-
dine, this compound exists in solution almost exclusively in a diax-
ial conformation.5 Similarly, its 2,6-diphenyl analogue prefers the
sterically constrained diaxial conformation in the solid state as
well as in solution, to relieve the more severe A(1,3) strain.6
However, in the case of N-nitroso-2,2,6,6-tetramethylpiperidine
1, the A(1,3) strain cannot be avoided by inversion of the ring but in-
stead the molecule may assume a non-chair conformation and/or
increase a pyramidal character of the amino nitrogen. Continuing
an interest in the stereochemistry and spectroscopy of N-nitrosa-
mines,4,7 we performed structural and spectroscopic studies on
the sterically overcrowded compounds 1–3.
a
conglomerate that leads to spontaneous generation of
chirality.8
2. Results and discussion
N-Nitrosamines 1–3 were prepared by nitrosation of the corre-
sponding amines with HNO2.
* Corresponding author. Tel.: +48 58 3471528; fax: +48 58 3472694.
E-mail address: tadpol@chem.pg.gda.pl (T. Połon´ ski).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.05.008

T. Olszewska et al. / Tetrahedron: Asymmetry 20 (2009) 1308–1313
1309
Compound 1 is a liquid at ambient temperature but 2 and 3 are
solids. The diffraction quality crystals of 2, which were grown from
water–methanol, belong to the enantiomorphous space group P32
(or P31). Usually this means that during crystallization, the racemic
mixture forms a conglomerate, that is, a mechanical mixture of
homochiral crystals where each single crystal contains only one
enantiomer.8
Spontaneous generation of chirality is a rare phenomenon that
receives considerable attention due to it being one of the simplest
and least expensive methods for the preparation of enantiomeri-
cally pure compounds.8 It may also be responsible for the prebiotic
origin of chirality.9 The crystal structure of 2 revealed that the
piperidine ring adopts an intermediate conformation between
the chair and sofa, as evidenced by the Cremer and Pople puckering
parameters10 and the hydroxyl group occupies an equatorial posi-
tion. The ring is significantly flattened at the amino nitrogen, which
shifts the equatorial methyl substituents out of the plane of the
nitrosamino group and minimizes the A(1,3) strain (Fig. 1). The
strain is further diminished by a pyramidalization of the amino
nitrogen as shown by its displacement of 0.130 (4) Å from the
plane formed by three neighbouring atoms. The O–HꢀꢀꢀO hydrogen
bonds between the hydroxyl groups assemble the molecules of 2
into a helical structure running along the three-fold screw axis of
the crystal.
The optical activity of the single crystals of 2 was confirmed by
the solid state CD spectrum taken in a KBr disk (Fig. 2), which
shows a strong Cotton effect near 400 nm corresponding to the
*
p electronic transition of the NNO chromophore. It is notewor-
n–
thy that compound 2 absorbs at ca. 30 nm longer wavelengths than
simple nitrosamines.11,12 Apparently the non-planarity of the chro-
*
mophore is responsible for a bathochromic shift of the n–
transition.
p
Our earlier results have shown that the resolution of racemic
nitrosamines can be achieved by inclusion complexation with chi-
ral hosts.7a–c Particularly useful as host compounds were the diols
(R,R)-4 and (R,R)-5 known as TADDOLs (a,a, ,
a0 a0-tetraphenyl-1,3-
dioxolane-4,5-dimethanols) which are easily accessible from (+)-
tartaric acid.13 The inclusion complexes of compounds 1–3 with
(R,R)-4 and (R,R)-5 were obtained by co-crystallization of equimo-
lar amounts of the components from toluene and hexane at room
*
p absorption band remains
temperature. Since the nitrosamine n–
far outside the absorption range of hosts 4 and 5, the optical activ-
ity of the guest molecules can be easily detected by CD measure-
ments of the complexes. Thus the solid state CD of the complex
2ꢀ4 exhibits a strong positive Cotton effect at 404 nm (Fig. 2). The
spectrum closely resembles that one shown by the crystals of the
pure guest 2. According to our helicity rule for N-nitrosopiperi-
dines,7b the positive n–
p
Cotton effect indicates an (R)-configura-
*
tion for guest molecule 2 (Scheme 1). Unfortunately, complex 2ꢀ4
does not form crystals suitable for X-ray analysis and this assign-
ment cannot be verified by the crystal structure.
Due to the rapid racemization of the title nitrosamines, at-
tempts to measure the CD of 2ꢀ4 in solution at room temperature
failed. However, upon dissolution of the complex in toluene at
ꢁ20 °C,
a relatively strong Cotton effect was detected near
410 nm. Its intensity gradually decreases and vanished completely
after ca. 2 h (Fig. 3). In an analogous experiment performed at 5 °C,
complete racemization occurred after 15 min. The first-order rate
constant k of racemization at ꢁ20 °C was derived from the linear
regression of h(t) = exp(ꢁ2kt) of 0.0005 sꢁ1 and corresponds to
Figure 1. An ORTEP representation of 2 showing the piperidine ring conformation.
the N–N rotation energy barrier
D
Gà of 77.6 kJ molꢁ1. This value
Figure 2. Solid state CD spectra of the nitrosamine 2 and the complex 2ꢀ4 taken in KBr disks (solid and broken line, respectively) and UV-vis spectrum of 2 measured in
methanol.

1310
T. Olszewska et al. / Tetrahedron: Asymmetry 20 (2009) 1308–1313
N
N
N
N
O
O
(+)
( )
Scheme 1.
is significantly lower than that found for 1 (82 kJ molꢁ1) from the
1H NMR measurements.14,15 These values are unusually low in
comparison with typical nitrosamines such as N-nitrosopiperidine
(93.0 kJ molꢁ1),15 that results from the significant deviation of the
nitrosamino chromophore from planarity
Figure 4. An ORTEP drawing of the guest molecule (pR)-1 in the inclusion
compound 1ꢀ5.
The non-planarity of the nitrosamino chromophore in 1 is sug-
*
gested by a bathochromic shift of its n–
p
transition (kmax 397 nm
The crystal structure of 3 revealed that the nitrosamine mole-
cules are disordered and that each site in the crystal is occupied
by two enantiomers in an 88:12 ratio. The piperidine ring assumes
a twisted-boat conformation that diminishes the interaction be-
tween the methyl substituents and the nearly planar nitrosamine
moiety. The two components occupying the same site in the crystal
show the enantiomeric piperidine ring conformations whereas the
N-nitroso group is common to both components (Fig. 6).
Boat-type conformations of the guest molecule 3 were also de-
tected in the crystal structure of the inclusion complex 3ꢀ52ꢀH2O
(Fig. 7). The N–NO group is disordered over two positions and
the occupancy factors of the two orientations are close to 0.5. For
in cyclohexane). Although 1 is itself a liquid, it forms a crystalline
complex with (R,R)-5. Thus the geometrical parameters of the
guest molecule 1 trapped in the chiral host lattice were determined
by X-ray structural analysis (Fig. 4).
In the asymmetric unit there is one molecule of (R,R)-5 and one
molecule of 1 forming a host–guest pair via hydrogen bond be-
tween the hydroxy group of the host and the nitroso group of
the guest molecule. The piperidine ring of 1 assumes a conforma-
tion intermediate between the chair and sofa (Fig. 5). The absolute
configuration of the guest 1 embedded in the host matrix of (R,R)-5
was determined as pS (planar chirality).16 The solid state CD spec-
trum of 1ꢀ5 shown in Figure 5 exhibited a positive Cotton effect at
375 nm that according to the helicity rule also points to the (pR)-
configuration of the guest molecule. In the case of 1, the racemiza-
tion can occur not only by rotation of the nitroso group, but also by
inversion of the piperidine ring. Since the energy barrier of the sec-
this reason, the solid state CD spectrum does not show a measur-
*
p transition,
able Cotton effect in the region of the nitrosamine n–
however, it exhibits a relatively strong CD band with a pronounced
*
vibronic structure at 265 nm corresponding to the ketone n–
p
ond process is much lower (less than 25 kJ molꢁ1 17
the first one, the CD cannot be measured in solution.
)
than that of
excitation (Fig. 8). Its sign is determined by the geometry of the
six-membered ring and thus the absolute conformation of the
Figure 3. Decay of the CD signal of the complex 2ꢀ4 at ꢁ20 °C in toluene.

T. Olszewska et al. / Tetrahedron: Asymmetry 20 (2009) 1308–1313
1311
Figure 5. Solid state CD spectrum of the complex 1ꢀ5 taken in KBr disks and UV–vis spectrum of 1 measured in cyclohexane.
avoid the allylic 1,3-strain (A(1,3)), caused by an interaction of the
nitrosamino group with the methyl substituents, the piperidine
ring in 1 and 2 assumes a chair conformation significantly flattened
at the amino nitrogen whereas in the 4-oxo derivative 3, the piper-
idine ring assumes boat-type conformations. All three nitrosa-
mines easily form crystalline inclusion complexes with optically
active diols (TADDOLs) in which the guest nitrosamines assume
chiral conformations that was manifested by their CD spectra in
the solid state. Furthermore, in the case of 2 during the crystalliza-
tion of the compound as a conglomerate, a spontaneous generation
of chirality occurs. Due to the rotation of the N–NO group or inver-
sion of the piperidine ring, the optically active nitrosamines rapidly
racemize in solution.
Figure 6. A twisted-boat conformation of 3 viewed along the piperidine N1–C2
bond. The disordered minor component is shown with empty lines (notice an
approximately mirror-plane relationship between the two disordered piperidine
rings connected to a common nitroso group).
4. Experimental
4.1. General
guest molecule can be easily predicted by the simple octant rule
(Scheme 2).18 The N–N rotation energy barrier
D
Gà assigned by
the variable temperature 1H NMR measurements in DMSO-d6 is
of 93.1 kJ molꢁ1
.
The N-nitrosamine 1 was obtained following the literature
method.19 The N-nitrosamines 1 and 2 were prepared by N-nitro-
sation of the corresponding amines with HNO2.20 1H and 13C
NMR spectra were obtained with Varian Unity Plus spectrometer
at 500 and 125 MHz, respectively. The deuteriated solvents were
used as an internal lock for 1H and 13C NMR. The solid state CD
3. Conclusion
In conclusion, the crystal structures of the sterically congested
N-nitroso-2,2,6,6-tetramethylpiperidines revealed that in order to
Figure 7. Two conformers of 3 occupying the same site in crystals of 3ꢀ52 ꢀ H2O.

1312
T. Olszewska et al. / Tetrahedron: Asymmetry 20 (2009) 1308–1313
Figure 8. Solid state CD spectrum of the complex 3ꢀ52ꢀH2O taken in KBr disk.
61.1, 54.0, 51.7, 31.5, 26.3. Anal. Calcd for C9H16N2O2 (184.24): C,
58.67; H, 8.75; N, 15.21. Found: C, 58.66; H, 8.81; N, 15.20.
4.4. X-ray structure analysis
O
N
X-ray data were collected with a KM4CCD diffractometer. The
crystal structures were solved by direct methods with SHELXS9722
and refined by full-matrix least-squares with SHELXL97.22 The H
atoms attached to carbon atoms were positioned geometrically.
The H atoms from OH groups were located in difference Fourier
maps. All structural drawings were prepared with the program OR-
TEP-III for Windows.23 In the absence of significant anomalous
scattering, Friedel pairs were merged for 1ꢀ5, 2 and 3ꢀ52ꢀH2O.
Crystal data for C9H18N2O2 2, M = 186.25, trigonal, space group
P32, a = b = 12.133(3), c = 5.804(2) Å, V = 739.9(4) Å3, T = 100 K,
N
O
Scheme 2.
spectra were taken with freshly prepared KBr disks and recorded
with a Jasco J-715 dichrograph. A mixture of 2–5 mg of the sample
and 250 mg of dried KBr was ground and formed into a disk
0.5 mm thick and with radius of 15 mm. The disk was rotated
around the optical axis and the CD recordings were made for sev-
eral positions in order to check a reproducibility of the spectra.
Caution: All nitrosamines are potential chemical carcinogens,
and special care should be taken in the handling and disposal of
these substances.21
Z = 3,
q , l(Mo Ka
x = 1.254 g cmꢁ3 ) = 0.089 mmꢁ1, k = 0.71073 Å,
3949 reflections measured, 857 unique (Rint = 0.0524). Final resid-
uals for 122 parameters were R1 = 0.0482, wR2 = 0.0772 for 780
reflections with I > 2r(I), and R1 = 0.0587, wR2 = 0.0807 for all data.
In the absence of significant anomalous scattering, the absolute
structure was arbitrary assigned.
Crystal data for C9H16N2O2 3, M = 184.24, monoclinic, space
group P21/n, a = 6.0613(8), b = 16.489(2), c = 10.2529(13) Å,
4.2. N-Nitroso-4-hydroxy-2,2,6,6-tetramethylpiperidine 2
b = 91.166(11)°, T = 180 K,
V = 1024.5(2) Å3,
Z = 4,
qx =
1.194 g cmꢁ3 ) = 0.085 mmꢁ1, k = 0.71073 Å, 5023 reflec-
,
l(Mo Ka
Mp 96–97 °C (methanol/water); 1H NMR (CDCl3) d 4.15 (m, 1H),
2.26 (br s, 1H), 2.17 (ddd, J = 2.6 Hz, 4.8 Hz and 13.3 Hz, 1H), 1.91
(ddd, J = 2.4 Hz, 4.4 Hz and 13.7 Hz, 1H), 1.83 (dd, J = 10.0 Hz and
13.4 Hz, 1H), 1.77 (s, 3H), 1.70 (m, 1H), 1.56 (s, 3H), 1.54 (s, 3H),
1.36 (s, 3H); 13C NMR (CDCl3) d 63.1, 62.1, 61.7, 50.1, 47.7, 33.1,
32.1, 29.8, 24.0. Anal. Calcd for C9H18N2O2 (186.25): C, 58.04; H,
9.74; N, 15.04. Found: C, 58.07; H, 9.88; N, 15.00.
tions measured, 1797 unique (Rint = 0.0139). Final residuals for
143 parameters were R1 = 0.0427, wR2 = 0.1106 for 1441 reflections
with I > 2r(I), and R1 = 0.0538, wR2 = 0.1178 for all data. The mole-
cule is disordered over two sites with the occupation ratio 88:12.
The atoms which are common for both positions of 3 are O2, N2,
N1, C2, C6, C7, C8. On cooling, at ca. 157 K a phase transition occurs
ꢀ
to a twinned triclinic P1 form with Z = 16 and the unit cell param-
eters a = 11.7354(7), b = 17.5461(11), c = 20.9962(14) Å,
a =
4.3. N-Nitroso-2,2,6,6-tetramethyl-4-piperidinone 3
72.333(6)°, b = 88.839(5)°, = 80.015 (5)°.
c
Mp 71–72 °C (toluene/hexane); 1H NMR (CDCl3) d 2.69 (d,
J = 4.4 Hz, 4H), 1.72 (s, 6H), 1.49 (s, 6H); 13C NMR (CDCl3) d 61.8,
Crystal data for C9H18N2OꢀC34H35O4 1ꢀ5, M = 1215.48, ortho-
rhombic, space group P212121, a = 9.3865(4), b = 18.1507(7),

T. Olszewska et al. / Tetrahedron: Asymmetry 20 (2009) 1308–1313
1313
2. (a) Rao, C. N. R.; Bhaskar, K. R. In Spectroscopy of the Nitroso Group, Part I; Patai,
S., Feuer, H., Eds.; Wiley: Chichester, 1970. Chapter 3; (b) Challis, B. C.; Challis, J.
A. In The Chemistry of Amino, Nitroso, and Nitro Compounds and Their Derivatives;
Supplement F; Patai, S., Ed.; Wiley: New York, 1982. Part 2, Chapter 26.
3. (a) Johnson, F.; Malhotra, S. K. J. Am. Chem. Soc. 1965, 87, 5492; (b) Malhotra, S.
K.; Johnson, F. J. Am. Chem. Soc. 1965, 87, 5493; For review see: (c) Johnson, F.
Chem. Rev. 1968, 68, 375; (d) Broeker, J. L.; Hoffman, R. W.; Houk, K. N. J. Am.
Chem. Soc. 1991, 113, 5006.
c = 22.0090(8) Å,
x = 1.199 g cmꢁ3
reflections measured, 3709 unique (Rint = 0.0495). Final residuals
V = 3749.7(3) Å3,
(Mo K
) = 0.078 mmꢁ1, k = 0.71073 Å, 26,765
T = 130 K,
Z = 4,
q
,
l
a
for 463 parameters were R1 = 0.0396, wR2 = 0.0699 for 3157 reflec-
tions with I > 2
Crystal data for C9H16N2O2ꢀ2(C34H35O4)ꢀH2O 3ꢀ52ꢀH2O, M =
1215.48, monoclinic, space group P21, a = 9.3808(5),
b = 34.0461(17), c = 10.2416(6) Å, b = 94.782(5)°, V = 3259.6(3) Å3,
T = 100 K, Z = 2, (Mo
x = 1.238 g cmꢁ3 ) = 0.082 mmꢁ1
r(I), and R1 = 0.0548, wR2 = 0.0754 for all data.
´
4. (a) Gdaniec, M.; Milewska, M. J.; Połonski, T. J. Org. Chem. 1995, 60, 7411; (b)
Połon´ ski, T.; Pham, M.; Milewska, M. J.; Gdaniec, M. J. Org. Chem. 1996, 61,
3766; (c) Gdaniec, M.; Pham, M.; Połon´ ski, T. J. Org. Chem. 1996, 61, 3766.
5. (a) Chow, Y. L.; Colon, C. J.; Tam, J. N. S. Can. J. Chem. 1968, 46, 2821; (b) Fraser,
R. R.; Grindley, T. B.; Passananti, S. Can. J. Chem. 1975, 53, 2473.
q
,
l
Ka
,
k = 0.71073 Å, 19,222 reflections measured, 5820 unique
(Rint = 0.0822). Final residuals for 806 parameters were
R1 = 0.0476, wR2 = 0.0853 for 2672 reflections with I > 2r(I), and
´
6. Gdaniec, M.; Milewska, M. J.; Połonski, T. Pol. J. Chem. 1996, 70, 607.
7. (a) Olszewska, T.; Milewska, M. J.; Gdaniec, M.; Połon´ ski, T. Chem. Commun.
1999, 1385; (b) Olszewska, T.; Milewska, M. J.; Gdaniec, M.; Małuszyn´ ska, H.;
Połon´ ski, T. J. Org. Chem. 2001, 66, 501; (c) Gdaniec, M.; Milewska, M. J.;
Połon´ ski, T. Angew. Chem., Int. Ed. 1999, 38, 392; (d) Szyrszyng, M.; Nowak, E.;
R1 = 0.1325, wR2 = 0.1082 for all data. The guest molecule is disor-
dered over two positions with the ratio of the occupancy factors of
53:47. The two residual highest peaks in the difference Fourier
map were interpreted as two water molecules, each with the half
occupancy. H atoms of these molecules were not located.
Crystallographic data (excluding structure factors) for the struc-
tures in this paper have been deposited with the Cambridge Crystal-
lographic Data Centre as supplementary publication numbers CCDC
726779–726782. Copies of the data can be obtained, free of charge,
on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK
[fax: +44(0)-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].
´
Gdaniec, M.; Milewska, M. J.; Herman, A.; Połonski, T. J. Org. Chem. 2001, 66,
7380.
8. (a) Jacques, J.; Collet, A.; Wilen, S. M. Enantiomers, Racemates, and Resolutions;
Wiley: New York, 1981; (b) Eliel, E.; Wilen, S. H. Stereochemistry of Organic
Compounds; Wiley: New York, 1994. Chapter 7.2.
9. Addadi, L.; Lahav, M. In Origins of Optical Activity in Nature; Walker, D. C., Ed.;
Elsevier: Amsterdam, 1979. Chapter 14.
10. Cremer, D.; Pople, J. A. J. Am. Chem. Soc. 1975, 97, 1354.
11. Jaffe, H. H.; Orchin, M. Theory and Applications of Ultraviolet Spectroscopy;
Wiley: New York, 1962. p 188.
12. Sarker, H.; Greer, M. L.; Blackstock, S. C. J. Org. Chem. 1996, 61, 3177.
13. (a) Serbach, D.; Beck, A. K.; Imwinkelried, R.; Roggo, S.; Wonnacott, A. Helv.
Chim. Acta 1987, 70, 954; (b) Toda, F.; Tanaka, K. Tetrahedron Lett. 1988, 29, 551.
14. Harris, K.; Pryce-Jones, T.; Swinbourne, F. J. J. Chem. Soc., Perkin Trans. 2 1980,
476.
Acknowledgement
15. Lunazzi, L.; Cerioni, G.; Ingold, K. U. J. Am. Chem. Soc. 1976, 98, 7484.
16. Chapter 14.8 of Ref. 8b.
17. Lunazzi, L.; Macciantelli, D. J. Chem. Soc., Perkin Trans. 2 1981, 604.
18. (a) Moffitt, W.; Woodward, R. B.; Moscowitz, A.; Klyne, W.; Djerassi, C. J. Am.
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We are indebted to Dr. J. Frelek (IChO PAN, Warsaw) for CD
measurements with use of her JASCO J-715 instrument.
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