NMR and X-ray crystallographic studies of the conformation of a 3,4,6-triphenyl-δ-lactone

Article abstract of DOI:10.1021/jo0155963

1-Oxa-3S,4S,6R-triphenyl-2-cyclohexanone and its enantiomer were synthesized, and the structure was determined by NMR and X-ray crystallography. The X-ray crystal structure showed that the δ-lactone adopts a boat conformation in the solid. The X-ray data showed a shortened C-O bond between the carbonyl carbon and the ether oxygen, consistent with delocalization involving the ester group. ¹H and ¹³C NMR measurements in acetone-d₆ showed that the lactone is biased in favor of a boat conformation. In the less polar solvent chloroform-d₁, changes in the ¹H NMR coupling constants indicate a shift in the equilibrium in favor of a less rigid twist-boat conformation. The IR absorption of the lactone carbonyl at 1740 cm^-1 would suggest a half-chair conformation inconsistent with the dominance of the boat forms shown by NMR and X-ray.

Full text of DOI:10.1021/jo0155963

J . Org. Chem. 2002, 67, 27-31
27
NMR a n d X-r a y Cr ysta llogr a p h ic Stu d ies of th e Con for m a tion of a
3,4,6-Tr ip h en yl-δ-La cton e
J ean A. Fuller-Stanley,* J ames H. Loehlin, Kimberly A. Bolin, Genevieve Fairbrother, and
Fausta Nazaire
Department of Chemistry, Wellesley College, 106 Central Street, Wellesley, Massachusetts 02481
jfullers@wellesley.edu
Received February 27, 2001
1-Oxa-3S,4S,6R-triphenyl-2-cyclohexanone and its enantiomer were synthesized, and the structure
was determined by NMR and X-ray crystallography. The X-ray crystal structure showed that the
δ-lactone adopts a boat conformation in the solid. The X-ray data showed a shortened C-O bond
between the carbonyl carbon and the ether oxygen, consistent with delocalization involving the
1
ester group. H and 13C NMR measurements in acetone-d6 showed that the lactone is biased in
favor of a boat conformation. In the less polar solvent chloroform-d1, changes in the 1H NMR coupling
constants indicate a shift in the equilibrium in favor of a less rigid twist-boat conformation. The
IR absorption of the lactone carbonyl at 1740 cm-1 would suggest a half-chair conformation
inconsistent with the dominance of the boat forms shown by NMR and X-ray.
1
In tr od u ction
Combined 13C and H NMR analysis provides valuable
evidence about the conformation of various six-membered
ring systems, in particular δ-lactones and closely related
molecules.4,8 Previous studies of a related δ-lactone,
namely, 1-oxa-4,5,6-triphenyl-2-cyclohexanone, charac-
terized three configurational isomers.4b The NMR evi-
dence, in particular the 1H coupling constants, supported
the existence of two different lactone conformations.4b
Two of these isomers, the all-trans and the all-cis,
adopted half-chair conformations. However, in the trans-
cis isomer, (axial phenyl at C-6) the boat conformation
proved to be more stable.4b Our previous studies on the
all-trans 1-oxa-3,4,5-triphenyl-2-cyclohexanone revealed
a half-chair conformation.9 This suggests that when
substituents are attached to the carbons that are part of
the ester moiety, their orientation directly influences the
conformation that δ-lactones adopt. However, the orien-
tation of substituents at the other two carbons of the
δ-lactone is apparently less influential to the conforma-
tion adopted. We wanted to probe this concept further
and now report our results.
It has been known for some time that the atoms
comprising the δ-lactone grouping C-C(O)-O-C are
almost coplanar.1 For δ-lactones, this gives rise to two
possible conformations: either the half-chair or the boat.
Crystallographic evidence shows that both forms exist
in the solid state.2 Molecular mechanics (MM2) calcula-
tions on the unsubstituted δ-lactone showed the half-
chair and boat conformations both occupying energy
minima with the half-chair more stable by about 0.54
kcal/mol.3 There is also evidence from NMR analysis to
support both forms in solution.4 Formerly, attempts were
made to correlate the conformations of δ-lactones with
their infrared carbonyl absorptions; where frequencies
in the range 1730-1750 cm-1 have been attributed to
the half-chair form, those in the range 1758-1765 cm-1
are ascribed to the boat form.5 However, many examples
are now known in which the above frequency ranges have
proved to be unreliable in determining conformations.4b,6
In addition, steric requirements of certain groups are
known to force the lactone moiety out of planarity, thus
making other conformations energetically viable.7,8a
Some studies have shown that δ-lactones can adopt
conformations other than the half-chair or boat, namely,
twist-boat, sofa, and other undefined forms.7,8 Since no
correlation with infrared frequency has been shown for
these forms, and the proposed ones for half-chair and boat
conformations have proved to be unreliable,4b,6-8 it is
important to develop a more robust method for assigning
δ-lactone conformations. We decided to use a combined
13C and 1H NMR analysis to do a systematic study on
nonfused δ-lactones to establish the conformations. While
the conformation that a molecule adopts in the solid is
not necessarily the same as that in solution, crystal
structure information with its greater detail and preci-
sion frequently complements structures determined for
molecules in more mobile states. In this study, we
(1) Carroll, F. I.; Blackwell, J . T. Tetrahedron Lett. 1970, 4173 and
references therein.
(2) (a) McConnell, J . F.; Mathieson, A. McL.; Schoenborn, B. P.
Tetrahedron Lett. 1962, 445. (b) Mathieson, A. McL. Tetrahedron Lett.
1963, 445. (c) J effrey, G. A.; Kim, S. H. J . Chem. Soc., Chem. Commun.
1966, 211. (d) Sheppard, R. C.; Turner, S. J . Chem. Soc., Chem.
Commun. 1968, 77.
(3) Philip, T.; Cook, R. L.; Mallory, T. B., J r. ; Allinger, N. L.; Chang,
S.; Yuh, Y. J . Am. Chem. Soc. 1981, 110, 2151.
(4) (a) Carroll, F. I.; Mitchell, G. N.; Blackwell, J . T.; Sobti, A.; Meck,
R. J . Org. Chem. 1974, 39, 3890. (b) Stanley, J . A.; Matallana, A.;
Kingsbury, C. A. J . Phys. Org. Chem. 1990, 3, 419. (c) Axiotis, S.;
Dreux, J .; Perrin, M.; Royer, J . Tetrahedron 1982, 38, 499.
(5) Cheung, K. K.; Overton, K. H.; Sim, G. A. J . Chem. Soc. Chem.
Commun. 1965, 664.
(6) (a) J urczak, M.; Rabiczko, J .; Socha, D.; Chmielewski, M.;
Cardona, F.; Goti, A.; Brandi, A. Tetrahedron: Asymmetry 2000, 11,
2015. (b) Morimoto, Y.; Shirahama, H. Tetrahedron 1997, 53, 2013.
(7) Thomas, S. A. J . Crystallogr. Spectrosc. Res. 1985, 15, 115.
(8) (a) A¨ yra¨s, P.; Pihlaja, K. Tetrahedron 1973, 29, 1311, 3369. (b)
Fronza, G.; Fuganti, C.; Grasselli, P. J . Chem. Soc., Perkin Trans. 1
1982, 885.
(9) Stanley, J . A.; Dakin, S.; Szabo, L.; Posaw, L.; Lee, C.; Hou, W.
M. Org. Prep. Proced. Int. 1991, 23, 193.
10.1021/jo0155963 CCC: $22.00 © 2002 American Chemical Society
Published on Web 12/14/2001

28 J . Org. Chem., Vol. 67, No. 1, 2002
Fuller-Stanley et al.
The magnitude of the coupling constants for the
diastereotopic protons at C-4 with H3 also supported
restricted rotation about the C3-C4 bond. Newman
projections of the three stable conformers (3d -f) due to
rotation about the C3-C4 bond are shown in Scheme 3.
Two of these conformers, 3e and 3f, are consistent with
the large (9.7 Hz) and small (3.7 Hz) coupling constant
observed for J 34. Of these only 3e, with the carbonyls in
a gauche position, has the appropriate position for the
hydride transfer during the internal Cannizzaro reaction.
F igu r e 1. Possible conformations: boat (6a ), half-chair (6b),
and twist-boat (6c) based on stereochemistry obtained from
X-ray data and 1H NMR coupling constants.
Thus, the stereochemistry of the lactone formed ap-
pears to be dominated by the dipolar carbonyl interaction
in the keto aldehyde 3. This preferred stereochemical
arrangement of the keto aldehyde 3 gives credence to the
dominance of lactone 6 as the major configurational
isomer as shown in Scheme 4.
compare the conformations obtained from solution NMR
with those from X-ray crystallography.
Resu lts a n d Discu ssion
Scheme 4 rationalizes the major configurational isomer
isolated and depicts the hydride transfer occurring from
the same side as the phenyl at C-3. If the hydride transfer
were to occur from the bottom, as shown in Scheme 5,
the configurational isomer with phenyl up at C-6 would
dominate. In this situation, the OCH3 group would be
on top and would encounter nonbonded steric hindrance
with the phenyl at C-3. In fact, this was not the major
isomer isolated. Thus, the model for steric approach
control is supported rather than the model for product
development control.11
Single-crystal X-ray diffraction analysis of the tri-
phenyl-δ-lactone was obtained and clearly showed the
boat conformation. A sketch of the boat conformation 6a
is shown in Figure 1. Dihedral angles C3-C4-C5-C6 and
C3-C2-O1-C6 were found to be 7 and 4°, respectively.
These compare very favorably with X-ray data of another
similarly substituted δ-lactone with a boat conformation.4c
Likewise, bond angles C2-O1-C6 and O1-C2-C3 of 117.5
and 116.1°, respectively, were found, similar to other boat
conformations.4c The shortened C-O bond length be-
tween the carbonyl carbon and ether oxygen is consistent
with delocalized pi bonding between the carbonyl group
and the adjacent ring oxygen. The X-ray data exhibit an
orderly intermolecular dipolar arrangement of the car-
bonyl groups. The lactones pack in such a way that the
carbonyl oxygen of one molecule is in close proximity to
the ether oxygen of its neighbor. The essentially planar
ester group found in the crystal structure further sup-
ports the delocalization model for ester electrons.
Con figu r a tion a l a n d Con for m a tion a l Assign m en t
fr om NMR An a lysis. The δ-lactone, 1-oxa-3S,4S,6R-
triphenyl-2-cyclohexanone 6, and its enantiomer were
synthesized by the condensation of 2-phenylethanal 1 and
chalcone 2 using the method of Meerwein.10 In Scheme
1, the synthesis is outlined and the numbering system
shown for compounds 3 and 6. The resulting keto
aldehyde 3 was isolated, purified, and characterized by
1H and 13C NMR. This keto aldehyde 3 was then
subjected to an internal Cannizzaro reaction involving a
hydride transfer, which finally produced lactone 6. The
same lactone 6 was also obtained by oxidation of 3 to the
ketoacid 4 followed by reduction to the hydroxy acid 5,
which cyclized when heated in a vacuum.
The yield of keto aldehyde 3 was fairly high (greater
than 75%) in our study. The proton NMR of 3 displayed
a large coupling constant of 10.7 Hz for J 23, which is
consistent with restricted rotation about the C2-C3
bond. Newman projections of the three most stable
conformers 3a -c are shown in Scheme 2. The large
coupling constant J 23 is indicative of the dominance of
conformer 3a . In this arrangement, H2 and H3 are anti,
consistent with the large coupling constant. Also worthy
of note is the proximity of the two carbonyl groups
(gauche) in this conformer. Thus, it appears that the
stereochemistry of the keto aldehyde in solution is
dominated by dipolar interaction of the carbonyl groups
rather than by steric hindrance.
Other isomers are possible, but due to steric hindrance,
the hydride transfer seems to occur only from the top (the
same side as the phenyl at C-3). This results in lactone
6 with the configuration as shown in Scheme 4. The 13C
NMR spectrum of the mother liquor showed at least two
other carbonyl compounds. No attempts were made to
isolate other configurational isomers from the mother
liquor. The yield of lactone from the keto aldehyde was
small (approximately 25%) in our study. The 13C NMR
spectrum of this sample did show evidence for two
compounds, possibly two lactones (ratio of 23:1). The
minor product was not identified, but peaks appear in
regions expected for another lactone isomer.
In the oxidation of 3 to the ketoacid 4, neither attempts
to purify the ketoacid nor configurational assignments
were made. The 13C NMR spectrum was used to deter-
mine effective completion of the reaction. The ketoacid 4
was reduced using sodium borohydride to produce the
hydroxy acid 5. The yield was low. We did not attempt
to quantify the isolated products 4 and 5 or assign
configuration. From the 1H and 13C NMR data, the
lactone isolated after heating in a vacuum was identical
to that obtained from the internal Cannizzaro reaction.
Thus, it appears that the hydride addition from the
borohydride was also guided by steric approach control,
similar to the hydride transfer in the Cannizzaro reac-
tion. The lactone isolated from this latter path (heating
in a vacuum) showed no signs of other isomers, unlike
that from the Cannizzaro path.
The configuration of lactone 6 was clearly established
from the X-ray analysis and showed a trans relationship
between H3 and H4. In acetone, the large coupling
constant of 11.5 Hz (J 34) can be best accommodated by
three conformations: boat 6a , half-chair 6b, and twist-
(11) Lowry, T. H.; Richardson, K. S. In Mechanism and Theory in
Organic Chemistry, 2nd ed.; Harper and Row: New York, 1981; pp
620-625.
(10) Meerwein, H. J . Prakt. Chem. 1918, 97, 225.

Conformation of a 3,4,6-Triphenyl-δ-Lactone
J . Org. Chem., Vol. 67, No. 1, 2002 29
Sch em e 1
Sch em e 2
basis of the magnitude of vicinal proton coupling con-
stants. However, the adjustments due to the electrone-
gativities of attached atoms are still imprecise. In our
study, the coupling constant of 8.7 Hz observed for J 5b6
is much less than the 11.5 Hz observed for J 34. This
difference in itself is not a measure of the extent to which
the dihedral angles (H3-C3-C4-H4 and H5b-C5-C6-
H6) differ; the presence of the electronegative oxygen on
C-6 is an important factor in that difference. Although
it is known that the presence of electronegative atoms
will lower the coupling constant, the 8.7 Hz observed for
J 5b6 is much smaller than expected for a dihedral angle
close to 180°, even after accounting for electronegativity.
In the boat conformation (6a ), the vicinal protons H5b
and H6 would have a dihedral angle close to 180°; the
twist-boat (6c) and half-chair (6b) conformations would
have much lower values for the corresponding dihedral
angles. In fact, in 6b, the protons at C-5 are bisected by
H6 with angles close to 60° and thus would be expected
Sch em e 3
to show much smaller coupling constants for J 5a6 and J 5b6
.
The observed value of 8.7 Hz for J 5b6 supports an
equilibrium mixture of the three conformations 6a -c
with a strong bias toward 6a .
Sch em e 4
The coupling constants of 6.6 and 7.8 Hz observed for
J 45a and J 45b, respectively, also support an equilibrium
biased toward 6a . Conformer 6a would have dihedral
angles H4-C4-C5-H5a and H4-C4-C5-H5b close to
120 and 0°, respectively, while 6b and 6c would have
respective dihedral angles close to 180 and 60°. Thus, one
of these coupling constants would be expected to be much
greater than the 7.8 Hz observed. Coupling constants
close to 8.0 Hz are associated with dihedral angles close
to zero, as exhibited by boat conformations.4b,14 This
further supports an equilibrium heavily biased toward
the boat conformation, 6a . NOE experiments on lactone
6 indicate a bias toward the boat conformation in acetone.
Irradiation of H3 yielded NOE at H6 (4% difference);
similarly, irradiation of H6 yielded NOE at H3 (5%
difference). The indicated close proximity of H3 to H6
again supports a boat conformation. Finally, irradiation
of H5b yielded NOE at H4 (7% difference), indicating the
close proximity of these protons, consistent with a boat
conformation.
Sch em e 5
boat 6c (Figure 1). Bucourt12a and others have used the
term planar to indicate the presence in a ring of a
dihedral angle of zero. Thus, δ-lactones in the boat form
are normally defined as diplanar; however, a perfect boat
is rarely observed. The diplanar angles normally deviate
from zero by (10° and occasionally by greater amounts.
The half-chair is normally defined as monoplanar, while
the twist conformation, often referred to as twist-boat or
skew-boat, is best described as nonplanar.
When the solvent was changed from acetone-d6 to
chloroform-d1, there were small but definite changes in
The use of modified Karplus equations13 continues to
be an important tool for assigning dihedral angles on the
1
the H NMR chemical shifts and coupling constants. In
(13) (a) Haasnoot, C. A. G.; de Leeuw, F. A. A. M.; Altona, C.
Tetrahedron 1980, 36, 2783 and references therein. (b) Colucci, W. J .;
Gandour, R. D.; Mooberry, E. A. J . Am. Chem. Soc. 1986, 108, 7142.
(14) (a) Nagao, Y.; Tohjo, T.; Ochiai, M.; Shiro, M. Chem Lett. 1992,
335. (b) Han, S.; J oullie, M.; Petasis, N.; Bigorra, J .; Corbera, J .; Font,
J .; Ortuno, R. Tetrahedron 1993, 49, 349.
(12) (a) Bucourt, R. In Topics in Stereochemistry; Eliel, E. L.,
Allinger, N. L., Eds.; Interscience Publication Wiley and Sons: New
York, 1974; Vol. 8, pp 159-218. (b) Kellie, G. M.; Riddell, F. G. In
Topics in Stereochemistry; Eliel, E. L., Allinger, N. L., Eds.; Interscience
Publication Wiley and Sons: New York, 1974; 8, pp 225-269.

30 J . Org. Chem., Vol. 67, No. 1, 2002
Fuller-Stanley et al.
and conformational elucidation.4,8,16,17 We observed only
a minor chemical shift change when the solvent was
changed from acetone-d6 to chloroform-d1. Most notice-
able was the upfield shift of 3 ppm for C-5. This could be
due to increased steric interaction between C-2 and C-5
as the conformation shifts from a boat to a twist-boat.
Molecular models show that, as this conformational shift
occurs, C-5 is brought into closer proximity with the
carbonyl carbon.
Sch em e 6
particular, J 34 changed from 11.5 to 9.5 Hz; to a lesser
degree, J 56 couplings changed from 8.7 and 4.4 Hz to 7.2
and 5.1 Hz, respectively. These changes suggest either a
shift in the conformational equilibrium or a widening of
dihedral angles.12 In a study of substituted 4-oxo-1,3-
dioxans, A¨ yra¨s8a determined that significant changes in
the sum of J trans + J cis for the fragment -CH2-CHR-
can be used as a measure of shift in the conformational
equilibrium. In our study of δ-lactones, slight changes
in the sum J 5a6 + J 5b6 in acetone and CDCl3 of 13.1 and
12.3 Hz, respectively, were measured. A shift in the
equilibrium in favor of more flexible forms, twist-boat
and/or half-chair conformations, would be consistent with
the observed change in coupling constants. 1H NMR
experiments were carried out between 297 and 247 K in
acetone-d6 and in chloroform-d1. No conformational
changes as a function of temperature were observed.
While conformational mobility cannot be ruled out,
particularly in chloroform-d1, the major forms present in
the two solvents are somewhat different.
Lambert’s R-value method for six-membered ring
compounds has been used as another indicator of con-
formational effects.15 Lambert showed that the value of
the ratio R (R ) J trans/J cis) for the fragment -CH2-CHR-
can be used as a measure of conformational bias. He
showed that for perfect chairs and boats, the ring
dihedral angle, æ, as shown in Scheme 6 is observed to
be 56 ( 2° while the angle for twist-boats and half-chairs
will be outside that range. The values of the proton
dihedral angles H5-C-C-H6 are directly influenced by
this change in ring dihedral angle.
Con clu sion s
The X-ray data showed the boat conformation with 3,4-
trans and 4,6-trans configurations, which was supported
by both the 1H and 13C NMR data in acetone. The
magnitude of the coupling constants and the positive
NOE observed between H3:H6 and H4:H5 are indicative
of their close proximity. In chloroform, the equilibrium
shifts in favor of the more flexible conformations, twist-
boat or half-chair. The structure of the δ-lactone deduced
from the NMR data in acetone, the more polar solvent,
is consistent with that found in the solid, indicating a
more ordered arrangement. In the solid, the X-ray data
showed the lactone molecules arranged in an orderly
pattern consistent with intermolecular dipolar attraction
of the carbonyl groups. It is possible that, in acetone, the
solvent molecules are able to replace lactone molecules
and still maintain a boat conformation. In chloroform,
the solvent molecules are unable to maintain the dipolar
interaction and thus shift to less rigid conformations
dominated by the twist-boat. On the basis of the previous
literature, the IR absorption at 1740 cm-1 would be more
consistent with the half-chair form.5 Morimoto6b has also
found IR conformation correlations that are inconsistent
with literature expectations.5 We suggest that the normal
IR range for δ-lactones should be revised to be 1730-
1750 cm-1 irrespective of conformation. Other factors
such as internal or external steric interactions may be
responsible for those δ-lactones with IR absorptions
outside that range.
Lambert found that for conformations biased toward
the boat or chair, an R-value of 2.0 ( 0.2 is normally
expected. An R-value of 1.2 ( 0.2, on the other hand, is
normally associated with twist-boat or half-chair confor-
mations.15 Note that a perfect chair is not a viable
conformation for δ-lactones; thus, only the boat form will
be considered for R-values close to 2.0. In our study of
δ-lactone 6, we applied Lambert’s R-value method to the
fragment -CH2-CH-O-. For J 5a6/J 5b6 in acetone, we
calculated an R-value of 1.98, indicating a bias toward
the boat, while in CDCl3, the R-value was 1.41, support-
ing a twist-boat or an equilibrium of all three conforma-
tions dominated by the twist-boat. The R-value of 1.4 is
at the upper limit of the flexible forms, as predicted for
the twist-boat. In CDCl3, the equilibrium is most likely
biased toward the twist-boat because the steric hindrance
that the phenyl at C-6 would experience in the half-chair
form is alleviated. A¨ yra¨s8a also found a shift away from
the half-chair in favor of the twist-boat to relieve steric
interactions between axial groups at C-6 and nonbonded
interactions with groups at C-4. Kellie and Riddell12b
noted that one of the energy advantages of the twist-boat
is relief of strains due to 1,3-diaxial interactions that
would exist in the half-chair forms.
Exp er im en ta l Section
Gen er a l Com m en ts. Chalcone 1 and phenylacetaldehyde
2 were obtained from Aldrich Chemical Co. and were used
without further purification. All melting points were taken in
capillary tubes and are uncorrected. IR spectra were recorded
on a Perkin-Elmer 1310 instrument as thin films on NaCl
plates. Samples for IR were typically made by dissolving the
compound in acetone and then placing a small amount on a
NaCl plate and allowing the solvent to evaporate, thus forming
a thin film. All NMR spectra were recorded on a Bruker NR/
200 FT (200 MHz) spectrometer in CDCl3 solution (except
where noted) with TMS as the internal standard. In a typical
13C NMR spectrum, the transformed peaks were referenced
to CDCl3 taken as 77 ppm. The coupling constants for 6 were
determined from a spectrum run in acetone-d6, as the CDCl3
spectrum had unresolved peaks, particularly of the methylene
protons. Coupling constants were also obtained by proton
decoupling experiments. Assignments of the 13C signals were
aided by DEPT and 13C{1H} NOE experiments. Samples for
NOE experiments were deoxygenated by passing nitrogen
through the NMR sample until half the original volume of
acetone-d6 was evaporated.
13C NMR chemical shifts are very sensitive to molec-
ular geometry and have been useful for stereochemical
(15) (a) Romers, C.; Altona, C.; Buys, H. R.; Havinga, E. In Topics
in Stereochemistry; Eliel, E. L., Allinger, N. L., Eds.; Interscience
Publication, Wiley and Sons: New York, 1969; Vol. 4, pp 39-93. (b)
Lambert, J oseph B. J . Am. Chem. Soc. 1967, 89, 1836.
(16) Gasis, M. J .; Djarmati, Z.; Pelletier, S. W. J . Org. Chem. 1976,
41, 1219.
(17) Wehrli, F. W.; Wirthlin, T. In Interpretation of Carbon-13 NMR
Spectra; Heyden & Son, Ltd.: 1980, 37.

Conformation of a 3,4,6-Triphenyl-δ-Lactone
J . Org. Chem., Vol. 67, No. 1, 2002 31
5-Oxo-2,3,5-tr ip h en ylp en ta n a l 3. Compound 3 was pre-
pared by the method of Meerwein:10 mp 148-149 °C (lit.10 not
isolated); IR (cm-1) 3060, 3030, 2900, 2700, 1725, 1685, 1600,
CCl4/toluene was 1.22 g/cm3. Density calculated from X-ray-
determined lattice constants was 1.230(1) g/cm3. The crystals
belong to the space group P21/c with Z ) 4. Lattice constants
were a 12.835(3) Å, b 5.977(1) Å, c 23.210(3) Å, and â 95.20(1)°.
The crystal selected for intensity measurements was prismatic
with dimensions 0.61 x 0.35 x 0.29 mm. Using Mo KR radiation
(λ ) 0.71073 Å) with a graphite monochromator on a Syntex
P21 diffractometer, 3136 unique reflections were measured of
which 2285 had F2 > 3σ(F2), and these were used in determin-
ing and refining the structure. Lorentz and polarization
corrections as well as an empirical absorption correction based
on psi scans were made on all data. The structure was solved
using the MULTAN78 program.18 The XTAL version 3.219
software was used for the remaining crystallographic pro-
grams. Hydrogen atom positions were calculated (C-H ) 0.96
Å) after each refinement cycle, given an assumed isotropic
displacement parameter U ) 0.038, and were not refined. All
non-hydrogen atoms were refined anisotropically by full-matrix
least squares on the basis of F2; 227 parameters were refined,
including secondary extinction. The final agreement factors
based on F were R ) 0.043 and wR ) 0.040 where 1/w ) σF2
+ (0.015 F)2. The average and maximum shift/error ratios in
the final refinement cycle were 0.005 and 0.022. Discrepancies
in the final Fourier difference map ranged from -0.26 to +0.25
electrons/Å3. The refined bond lengths and angles can be found
in the CIF file. Most deviate only slightly from typical reference
values.20 The X-ray numbering system differs from that used
in this article.
1
1580, 1500, 1450, 1230, 760, 700; H NMR δ 3.1 and 3.3 (m,
CH2, J ) -13.6 Hz, 9.7 Hz, 3.7 Hz, 2H), 3.9 (dd, H2, J ) 10.7
Hz, 3.0, 1H), 4.3 (m, H3, J ) 10.7 Hz, 9.7 Hz, 3.7 Hz, 1H),
6.8-7.8 (aromatic, 15H), 9.6 (d, H1, J ) 3.0, 1H); 13C NMR δ
42 (C-3), 43 (C-4), 64 (C-2), 128-142 (aromatic), 198 (C-5), 200
(C-1).
5-Oxo-2,3,5-tr ip h en ylp en ta n oic Acid 4. Compound 4 was
prepared by oxidation of 3 with a known procedure4b,10 and
by using KMnO4 as described. The keto aldehyde 3 (0.5 g) was
added to 8 mL of water and the mixture heated to ap-
proximately 73 °C. KMnO4 (0.5 g) in 10 mL of water was added
over a 10 min period with stirring. The solution was heated
for an additional 20 min until the color changed from purple
to blackish brown. The hot solution was gravity filtered and
HCl added to the cooled filtrate. A white solid precipitated from
the acidified solution: 13C NMR (DMSO-d6) δ 42 (C-3), 44 (C-
4), 58 (C-2), (124-142) aromatic, 174 (C-1), 198 (C-5).
5-Hyd r oxy-2,3,5-tr ip h en ylp en ta n oic Acid 5. Compound
5 was prepared by reduction of 4 with NaBH4 according to a
modified method:4b mp 144-145 °C (lit.10 143-143.5 °C); IR
(cm-1) 3500, 3030, 1710, 1600, 1500, 1460, 1370, 1310, 1230,
1
1180, 1070, 1020, 980, 910, 750, 725, 700; H NMR (acetone-
d6) δ 2.4 (CH2, 2H), 3.1 (H3, 1H), 3.8 (H2, 1H), 4.0 (OH, 1H),
4.3 (H5, 1H), 11.0 (COOH, 1H); 13C NMR (acetone-d6) δ 44.2
(C-4), 46.6 (C-3), 59.2 (C-2), 73.4 (C-5), 126-146 (aromatic),
174.0 (C-1).
1-Oxa -3S,4S,6R-tr ip h en yl-2-cycloh exa n on e (a n d En a n -
tiom er ) 6. Compound 6 was prepared by two different
pathways. Lactone 6 was prepared from 3 by a modification
of Meerwein’s reaction10 as follows. The aldehyde 3 (8.02 g)
was added to freshly prepared NaOMe (2.00 g Na in 100 mL
of ice-cold MeOH) and refluxed for 2 h. After reflux, ap-
proximately one-half of the solvent was evaporated. The cooled
solution was acidified with 6 M HCl while being stirred. The
mixture was covered and allowed to stand at room temperature
for 48 h. The crude crystals were filtered and rinsed with cold
MeOH. The solid was recrystallized from EtOH: mp 135-137
°C. Lactone 6 was also prepared by heating the hydroxy acid
Ack n ow led gm en t. We thank Bruce Foxman (Bran-
deis University) for the use of his diffractometer. This
work was made possible in part by support from the
Howard Hughes Medical Institute grants to Wellesley
College. We also thank the Brachman Hoffman Fund
of Wellesley College for support.
Su p p or tin g In for m a tion Ava ila ble: X-ray CIF file for
lactone 6 has been deposited with the Cambridge Crystal-
lographic Data Center, ref # CCD171882; 13C NMR data for
1
compounds 3-6, H NMR data for 3 and 6, and ORTEP plots
5 in a vacuum:10 mp 137-138 °C (lit.10 138-139 °C); IR (cm-1
)
of lactone 6. This material is available free of charge via the
3040, 1740, 1600, 1500, 1460, 1370, 1310, 1230, 1180, 1070,
1020, 980, 910, 750, 725, 700; 1H NMR (acetone-d6) δ 2.5-2.7
(m, CH2, J ) -14.6 Hz, 8.7 Hz, 7.8 Hz, 6.6 Hz, 4.4 Hz, 2H),
3.5 (m, H4, J ) 11.5 Hz, 7.8 Hz, 6.6 Hz, 1H), 4.4 (d, H3, J )
11.5 Hz, 1H), 6.0 (q, H6, J ) 8.7 Hz, 4.4 Hz, 1H), 7.0-7.6
(aromatic, 15H); 13C NMR (acetone-d6) δ 39.4 (CH2), 43.8 (C-
4), 53.8 (C-3), 79.0 (C-6), 126-144 (aromatic), 172.0 (C-2).
X-r a y Cr ysta llogr a p h ic Deter m in a tion . Crystals of the
δ-lactone 6 were grown from 95% ethanol that was slowly
cooled from 40 °C to room temperature at about 2.5 °C per
day. Density measured by the neutral buoyancy method in
Internet at http://pubs.acs.org.
J O0155963
(18) Main, P.; Hull, S. E.; Lessinger, L.; Germain, G.; Declercq, J .-
P.; Woolfson, M. M. MULTAN78; Universities of York, England, and
Louvain, Belgium, 1978.
(19) Hall, S. R., Fleck, H. D., Stewart, J . M., Eds. XTAL 3.2 Users
Manual; Universities of Western Australia, Geneva, and Maryland,
1992.
(20) International Tables for X-ray Crystallography; Kynoch Press:
England, 1985; Vol. III, p 276.