Assignment of the absolute configuration of β-chiral primary alcohols by NMR: Scope and limitations

Article abstract of DOI:10.1021/ja972550b

The prediction of the absolute configuration of β-chiral primary alcohols from the ¹H NMR spectra of their esters with (R)- and (S)- 9-anthrylmethoxyacetic acids (9-AMA, 3) is discussed. Low-temperature NM experiments, MM, semiempirical, ab initio, and aromatic shielding effect calculations allowed the identification of the main conformers and showed that, in all alcohols for which the calculated ΔE(ag) (CVff) is in the range of 0.7-1.5 kcal/mol, conformer a/a is the most stable. A simple model for the assignment of the absolute configuration from NMR data is presented and its reliability corroborated with alcohols (8-20) of known configuration. Nevertheless, cyclic alcohols 21-23 have much higher ΔE(ag) values (2.2-3.1 kcal/mol) due to their different conformational composition, and their absolute configuration cannot be reliably predicted by this method.

Full text of DOI:10.1021/ja972550b

J. Am. Chem. Soc. 1998, 120, 4741-4751
4741
Assignment of the Absolute Configuration of â-Chiral Primary
Alcohols by NMR: Scope and Limitations
Shamil K. Latypov,† Mar´ıa J. Ferreiro, Emilio Quin˜oa´, and Ricardo Riguera*
Contribution from the Departamento de Qu´ımica Orga´nica, Facultad de Qu´ımica, and the Instituto de
Acuicultura, UniVersidad de Santiago de Compostela, 15706 Santiago de Compostela, Spain
ReceiVed July 28, 1997
Abstract: The prediction of the absolute configuration of â-chiral primary alcohols from the 1H NMR spectra
of their esters with (R)- and (S)-9-anthrylmethoxyacetic acids (9-AMA, 3) is discussed. Low-temperature
NMR experiments, MM, semiempirical, ab initio, and aromatic shielding effect calculations allowed the
identification of the main conformers and showed that, in all alcohols for which the calculated ∆Eag (CVff) is
in the range of 0.7-1.5 kcal/mol, conformer a/a is the most stable. A simple model for the assignment of the
absolute configuration from NMR data is presented and its reliability corroborated with alcohols (8-20) of
known configuration. Nevertheless, cyclic alcohols 21-23 have much higher ∆Eag values (2.2-3.1 kcal/
mol) due to their different conformational composition, and their absolute configuration cannot be reliably
predicted by this method.
Introduction
The determination of the absolute configuration of organic
compounds by NMR constitutes a research area of increasing
interest due to the general availability of the instruments, the
small amount of sample needed, and the simplicity of the
method. Although many papers have been published on this
topic, so far only two classes of substrate and one type of
auxiliary reagent have been fully investigated.1 The former are
secondary alcohols and primary amines with the asymmetric
center at the R-carbon, and the latter are arylmethoxyacetic acids
(AMAAs).2 The method is based on the derivatization of the
alcohol or amine with the (R)- and (S)-enantiomers of the
Figure 1. Selective influence of the aryl ring on both sides of the
secondary alcohol moiety depending on the absolute configuration of
the AMAA.
1
AMAA reagent followed by the comparison of the H NMR
spectra of the resulting diastereomers. The chemical shifts of
the L1/L2 substituents at the asymmetric center of the substrate
in the (R)- and (S)-derivatives reflect the influence of the aryl
ring, and therefore, a correlation can be established between
the spatial position of the aryl ring (known absolute configu-
ration of the auxiliary reagent) and the position of the L1/L2
substituents of the substrate (unknown absolute configuration)
(Figure 1).
of a large number of substrates of known stereochemistry.
These studies have also indicated that the difference in chemical
shifts observed for L1/L2 in the (R)-and (S)-AMAA derivatives
(measured as ∆δRS)4 is determined by the strength of the
aromatic shielding effect and by the conformational composition
(structure and relative abundance of the conformers). The merits
and limitations of the classical MPA (1) and MTPA (2) reagents5
(see Chart 1) and the advantages of new and more efficient
reagents such as 9-AMA (3) have been discussed.2c,3 Simple
models that are useful to predict the absolute configuration of
secondary alcohols and amines by NMR have been developed.2
It would be beneficial to extend the use of this methodology
to other functional groups. Primary alcohols are interesting
candidates for such studies because they are frequently found
in nature in chiral form. If a correlation between the NMR
properties of appropiate derivatives and stereochemistry were
found, the assignment of the absolute configuration (and that
This methodology has been fully supported by extensive
conformational analysis and comparison of experimental and
calculated shielding effects3 and substantiated by examination
* To whom correspondence should be addressed.
† Present address: The Institute of Organic and Physical Chemistry of
The Russian Academy of Sciences, Kazan, 4200.1383, Tatarstan, Russian
Federation.
(1) For a review on the use of NMR for assignment of absolute
configuration and ee measurements see: Uray, G. Houben-Weyl: Methods
in Organic Chemistry; Helchen, G., Hoffmann, R. W., Mulzer, J.,
Schaumann, E., Eds.; Thieme: Stuttgart, New York, 1996; Vol. 1, p 253.
(2) (a) Trost, B. M.; O’Krongly, D.; Belletire, J. L. J. Am. Chem. Soc.
1980, 102, 7595-7596. (b) Trost, B. M.; Bunt, R. C.; Pulley, Sh. R. J.
Org. Chem. 1994, 59, 4202-4205. (c) Seco, J. M.; Latypov, Sh. K.; Quin˜oa´,
E.; Riguera, R. Tetrahedron Lett. 1994, 35, 2921-2924. (d) Latypov, Sh.
K.; Seco, J. M.; Quin˜oa´, E.; Riguera, R. J. Org. Chem. 1995, 60, 1538-
1545. (e) Seco, J. M.; Latypov, Sh. K.; Quin˜oa´, E.; Riguera, R. Tetrahe-
dron: Asymmetry 1995, 6, 107-110. (f) Kouda, K.; Kusumi, T.; Ping, X.;
Kan, Y.; Hashimoto, T.; Asakawa, Y. Tetrahedron Lett. 1996, 37, 4541-
4544.
(3) (a) Latypov, Sh. K.; Seco, J. M.; Quin˜oa´, E.; Riguera, R. J. Org.
Chem. 1995, 60, 504-515. (b) Seco, J. M.; Latypov, Sh. K.; Quin˜oa´, E.;
Riguera, R. Tetrahedron 1997, 53, 8541-8564.
(4) ∆δRS represents the difference between the chemical shift of the same
group of the alcohol in the (R)- and (S)-derivatives (∆δRS ) δR - δS).
(5) Latypov, Sh. K.; Seco, J. M.; Quin˜oa´, E.; Riguera, R. J. Org. Chem.
1996, 61, 8569-8577.
S0002-7863(97)02550-X CCC: $15.00 © 1998 American Chemical Society
Published on Web 05/02/1998

4742 J. Am. Chem. Soc., Vol. 120, No. 19, 1998
LatypoV et al.
Chart 1
Figure 2. Main rotamers in the alcohol moiety of an AMA ester of a
â-chiral primary alcohol by rotation around (a) the O-C1′ and (b) the
C1′-C2′ bonds.
corresponding (R/S)-9-AMA esters. A preliminary account has
of potential precursors, such as carboxylic acids and aldehydes)
would be easily attained.
recently been published.7
Conformational Analysis of AMAA Esters of Primary
Alcohols and the Aromatic Shielding Effect
However, a number of intrinsic difficulties can be seen due
to the nature of primary alcohols: (1) The asymmetric center
is, at best, at beta (â) or gamma (γ) positions with regard to
the OH group. (2) The distance between groups L1/L2 of the
substrate and the aryl ring of the auxiliary reagent is obviously
larger than in secondary alcohols, and in addition, the longer
chain between the chiral center and the auxiliary reagent should
reduce the conformational preference. As a result, the ∆δRS
values in primary alcohols would be smaller and less reliable
than those usually obtained from secondary alcohols.
The NMR parameters of flexible molecules depend on the
structure and relative population of the main conformers.
Therefore, in the case of the AMAA esters of a primary alcohol
with a chiral carbon at the â position (C2′), we have to analyze
the rotation around the CR-CO, CO-O, O-C1′, and C1′-C2′
bonds. To keep this study within practical limits, we simplified
this situation by considering the rotational mobility around the
CR-CO and CO-O bonds to be very low and considered those
skeletal fragments to be almost rigid (Figure 2). Experimental
data supporting restricted rotation around the CO-O bond has
been provided by DNMR8 and complemented by aromatic
shielding calculations and ab initio data.9 Similarly, the
existence of a preferred sp rotamer around the CR-CO bond in
the 9-anthryl derivative is well documented.3
The remaining two bonds (O-C1′ and C1′-C2′) are very
flexible. Each bond can give rise to three low-energy rotamers
(two gauche and one anti, Figure 3), and therefore the overall
number of main rotamers that can be expected is 9. To study
the behavior of this skeletal fragment in depth, isobutyl formate
(7) was selected as the simplest model to perform molecular
mechanics calculations (CVff). The results are presented in
Figures 3 and 4.
Figure 3 shows the structures of the nine main conformers
obtained by rotation around the O-C1′ (vertical axis) and the
C1′-C2′ bonds (horizontal axis). The corresponding energy map
is presented in Figure 4. It shows that the rotamers that have
the C2′-C1′-O-C(O)-H bonds in the same plane (g+/a, a/a,
and g-/a, middle row, Figure 3) are the most stable ones and,
therefore, those obtained by rotation around the O-C1′ bond
(columns) do not need to be considered. A similar precedent
was previously observed in secondary alcohols, where rotation
around the C1′-O bond leads to a preferred gauche relationship
between the C1′-H and the O-C(O) bonds.3
The low conformational preference found in the esters of
secondary alcohols,5 together with the unfavorable orientation
of the phenyl ring when facing L1/L2, suggests that neither MPA
(1) or MTPA (2) would be good reagents for this purpose.
We have recently established3 that the conformational equi-
librium around the CO-CR bond is strongly dependent on the
nature of the aryl ring. Ab initio calculations and DNMR
experiments on the 9-AMA (3) ester of a secondary alcohol
have shown that (a) there is a strong conformational preference
for the synperiplanar conformer (sp)6 and (b) that the anthryl
ring is oriented in such a way that L1/L2 remain well within the
aromatic magnetic cone (maximum shielding zone). Therefore,
we may reasonably expect a reduction in the flexibility of the
ester and a greater efficiency in the transformation of the
aromatic shielding into high-field shifts when using 9-AMA.
1
To test this supposition we studied the H NMR spectra of
the MPA, MTPA, and 9-AMA esters of 2-methylpropan-1-ol
(compounds 4-6, respectively), where the diastereotopic methyl
groups are the L1/L2 substituents, and assessed the ability of
each reagent to separate the L1/L2 signals. In fact, it was only
in the case of ester 6 that completely separated signals were
found (∆δ ) 0.033). Ester 4 showed only a slight separation
(overlapped doublets, ∆δ ) 0.002), while no noticeable
discrimination was detected in ester 5.
In this paper we describe our results on the assignment of
the absolute configuration of primary alcohols with the asym-
metric center at the â position by 1H NMR spectroscopy of the
(7) Ferreiro, M. J.; Latypov, Sh. K.; Quin˜oa´, E.; Riguera, R. Tetrahe-
dron: Asymmetry 1996, 7, 2195-2198.
(8) (a) Drakenberg, T.; Forsen, S. J. Phys. Chem. 1972, 76, 3582-3586.
(b) Grindley, T. B. Tetrahedron Lett. 1982, 23, 1757-1760.
(9) (a) Ohtani, I.; Kusumi, T.; Kashman, Yo.; Kakisawa, H. J. Am. Chem.
Soc. 1991, 113, 4092-4096. (b) Tucker, J. A.; Houk, K. N.; Trost, B. M.
J. Am. Chem. Soc. 1990, 112, 5465-5471.
(6) The sp conformer is defined by the synperiplanar conformation of
the CR-OMe and CdO groups.

Configuration of â-Chiral Primary Alcohols
J. Am. Chem. Soc., Vol. 120, No. 19, 1998 4743
Table 1. Comparison of Semiempirical and Nonempirical Data
(in kcal/mol) for the Main Conformers of Compound 7
conformer
MM (CVff)12
AM113
ab initioa
gauche (g-/a, g+/a)
anti (a/a)
0.00
0.87
0.00
0.87
0.10
0.00
a RHF/3-21G//RHF/3-21G.14
Table 2. Calculated Shielding Incrementsa for the Methyl Groups
in the Main Conformers of 2-Methylpropan-1-ol 9-AMA Ester (6)
conformer
Me(1′)
Me(2′)
g+/a
a/a
g-/a
ca. 0.14
ca. 0.82
ca. -0.1
ca. 0.55
ca. -0.05
ca. 0.1
a Semiclassical model. See refs 3 and 21.
between the substituents at C2′ and the oxygen atom are
considered (the methyl groups in 7 should destabilize the anti
a/a form). However, other studies, including statistical me-
chanical Monte Carlo simulations, have indicated that the anti
form (a/a) should be more stable than the gauche ones.11 To
assess the extent of this discrepancy and its consequences, we
decided to check the accuracy of our MM and AM1 predictions
by carrying out the energy calculations at a higher level.
Table 1 shows the RHF/3-21G//RHF/3-21G ab initio calcula-
tions on ester 7. These calculations show a slight preference
for the anti as opposed to the gauche rotamers. This difference
between the ab initio and the approximate methods can be
ascribed to an underestimation of the stability of the anti form
by MM and AM1 calculations of about 1 kcal/mol.
Figure 3. Low-energy conformers of isobutyl formate (7) as calculated
by MM. The squares under each drawing contain two symbols that
identify each conformer. The symbol on the left side defines the C1′-
C
2′ bond: a means C2′-H anti to O-C1′; g+ or g- means a 120° turn
(clockwise or counterclockwise, respectively) from the a position. The
symbol on the right side defines the O-C1′ bond: a means C1′-C2′
anti to O-CHO; g+ or g- means a 120° turn (clockwise or
counterclockwise, respectively) from the a position.
Once the existence of the three main conformations was
established, the next goal was to estimate the participation of
each conformer in the average NMR chemical shift. To this
end, we carried out aromatic shielding effect calculations
(semiclassical model) on the 9-AMA ester of 2-methylpropan-
1-ol (6) following the previously established methodology.3
Table 2 shows the expected shielding on the methyl groups
of 6 considering the conformers g+/a, g-/a, and a/a. The
results indicate that both methyl groups are subject to very
different shielding in the g+/a and a/a conformers, while no
appreciable difference is produced in conformer g-/a. The
greatest separation between Me(1′) and Me(2′) occurs in
conformer a/a (0.82 vs -0.05), and this, therefore, becomes
the most significant in terms of NMR spectroscopy. Conformer
a/a is, in addition, the most populated one. Therefore, the
average shielding is dominated by this conformer15 and the
relative chemical shifts of Me(1′) and Me(2′) can be effectively
Figure 4. Energy contour map of ester 7 calculated by MM as a
function of the dihedral angles around the O-C1′ and C1′-C2′ bonds.
Experimental evidence of this conclusion was obtained by
low-temperature NMR. We observed that at lower temperatures
the NMR spectra of 7 showed the signals due to the protons at
C1′ shifted to higher field than at room temperature (3.875 ppm
at 300 K and 3.847 ppm at 193 K) as a result of the shielding
generated by the carbonyl group. This observation is in good
agreement with an increase in the relative populations of
conformers g-/a, a/a, and g+/a,10 and these should therefore
be the most stable ones.
(11) (a) Shimanouchi, T.; Ogawa, Y.; Ohta, M.; Matsuura, H.; Harada,
I. Bull. Chem. Soc. Jpn. 1976, 49, 2990-3008. (b) Ogawa, Y.; Ohta, M.;
Sakakibaba, M.; Matsuura, H.; Harada, I.; Shimanouchi, T. Bull. Chem.
Soc. Jpn. 1977, 50, 650-660. (c) Andersson, M.; Karlstrom, G. J. Phys.
Chem. 1985, 89, 4957-4962. (d) Hoppilliard, Y.; Solgadi, D. Tetrahedron
1980, 36, 377-380.
(12) Roberts, V. A.; Osguthorpe, D. I.; Wolff, J.; Genest, M.; Hagler,
A. T. Proteins: Struct., Funct., Genet. 1988, 4, 31.
As for the C1′-C2′ bond, Figure 4 shows that no clear
preference is found in the equilibrium around the C1′-C2′ bond,
around which interconversion between the g-/a, a/a, and g+/a
conformers occurs (middle row in Figure 3). The MM derived
energy map suggests that rotamers g-/a and g+/a are a little
more stable than rotamer a/a. AM1 semiempirical calculations
reiterate those results (Table 1), and therefore, we may conclude
that the gauche g+/a and g-/a forms are the preferred ones.
This preference seems reasonable when steric considerations
(13) (a) Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P.
J. Am. Chem. Soc. 1985, 107, 3902-3909. (b) Havel, T. F. Prog. Biophys.
Mol. Biol. 1991, 56, 43-78. (c) Stewart, J. J. P. J. Comput. Chem. 1989,
10, 209-220. (d) Komorinski, A.; McIver, W., Jr. J. Am. Chem. Soc. 1973,
95, 4512-4517.
(14) Frisch, M. J.; Trucks, G. W.; Head-Gordon, M.; Gill, P. M. W.;
Wrong, M. W.; Foresman, J. B.; Johnson, B. G.; Schhlegel, H. B.; Robb,
M. A.; Replogle, E. S.; Gomperts, R.; Andres, J. L.; Raghavachari, K.;
Binkley, J. S.; Gonzalez, C.; Martin, R. L.; Fox, D. J.; Defrees, D. J.; Baker,
J.; Stewart, J. J. P.; Pople, J. A. GAUSSIAN 92, revision D.1; Gaussian:
Pittsburgh, PA, 1992.
(15) Inspection of the aromatic shielding effects values shown in Table
2 indicates that conformer a/a would be the NMR significant one even if
the three conformers were equally populated.
(10) Balasubrahamanyam, S. N.; Bharathi, S. N.; Usga, G. Org. Magn.
Reson. 1983, 21, 474-481.

4744 J. Am. Chem. Soc., Vol. 120, No. 19, 1998
LatypoV et al.
Figure 5. ∆Eag (CVff, in kcal/mol) and ∆δRS values for the 9-AMA esters of compounds 8-20. Selected ∆δRS values for some MPA (compounds
24, 26, and 28) and MTPA (compounds 25, 27, and 29) esters are also shown.
predicted from their position relative to the aryl group in
conformer a/a [i.e. Me(1′) is shielded in the (R)-ester and Me-
(2′) is shielded in the (S)-ester].
NMR Results
Experimental evidence confirming that the a/a form is both
the most populated and NMR significant one in compounds
8-20 was obtained from the low-temperature 1H NMR spectra
of the (R)- and (S)-9-AMA esters of (S)-(-)-2-methylbutan-1-
ol (8). For instance, Me(4′) in the (S)-9-AMA ester and Me-
(5′) in the (R)-9-AMA ester show upfield shifts (by 0.038 and
0.008 ppm, respectively) at low temperature (183 K), relative
to the signals at room temperature, in agreement with their
position under the shielding cone of the anthryl ring in the a/a
form, but they shift to lower field [by 0.047 ppm for Me(4′) in
the (R)- and 0.103 ppm for Me(5′) in the (S)-ester] when they
are located in the nonshielding cone area.
To see if the above conclusions on model compound 6 can
be applied generally to allow the establishment of a secure and
reliable NMR connection between the absolute configuration
at the asymmetric center of the auxiliary reagent and that of
the alcohol, we carried out MM calculations (CVff) on primary
alcohols 8-23, of known absolute configuration. Their struc-
tures are shown in Figures 5 and 6 along with the calculated
energy difference between the gauche and anti forms (∆Eag
Ea - Eg).
)
Compounds 8-20 (Figure 5) show ∆Eag values in the range
0.72-1.51 kcal/mol. These are close to the calculated values
for model 6 and should clearly also be affected by the
underestimation of the stability of the anti form associated with
the MM method. Nevertheless, the preference for the a/a form
shown by ab initio calculations can be easily restored in all
cases by the introduction of a correction factor of -1.4 kcal/
mol (to be added to the CVff value). In contrast, MM
calculations on compounds 21-23 (Figure 6) produce much
higher ∆Eag values (2.20-3.08 kcal/mol) due to excessive
destabilization of the a/a form, which in 21-23 is no longer
the preferred one, with g-/a and g+/a forms now making a
very significant contribution.
A crude evaluation of the experimental shielding increments
suffered by Me(4′) in 8, for example, can be obtained as the
difference between its chemical shift in the 9-AMA esters and
in the free alcohol 8, [ca. 0.392 ppm in the (R)-9-AMA and
0.359 ppm in the (S)-9-AMA]. Comparison with the calculated
values for conformer a/a in model compound 6 (ca. 0.82 ppm,
Table 2) points to the aromatic shielding effect of the anthryl
group as being responsible for the observed high-field shift and
confirms 9-AMA to be a very efficient shielding reagent. In
addition, this comparison suggests that the conformer that
produces shielding amounts to ca. 44-48% of the population
in the 9-AMA ester. In terms of energy, this corresponds to a
preference for the a/a form of about 0.27-0.37 kcal/mol at 183
K, a value which is in good general agreement with the results
of ab initio calculations.
The above results clearly indicate that, among all the primary
alcohols studied, two different groups can be distinguished:
compounds 8-20, which are conformationally similar to model
6 and have ∆Eag ) 0.72-1.51, and compounds 21-23, which
behave in a different way and show much higher ∆Eag values
(2.20-3.08).
Comparison of the NMR spectra of 8 and its esters with both
enantiomers of 9-AMA, MPA, and MTPA (Figure 7) illustrates
these results very well: while in the MPA and MTPA
derivatives, Me(4′) and Me(5′) resonate at virtually the same
chemical shift as in the free alcohol, in the 9-AMA ester the

Configuration of â-Chiral Primary Alcohols
J. Am. Chem. Soc., Vol. 120, No. 19, 1998 4745
calculations. The structures shown for the (R)- and (S)-9-AMA
esters of 8 combine both the a/a conformer of the alcohol moiety
(discussed in this work) and the most stable sp conformer
previously deduced for the acid substructure.3,5 For instance,
Me(5′) lies on the same side as the aryl ring in the (R)- ester
and, therefore, its signal is shifted to higher field than that in
the (S)-ester (negative ∆δRS). The opposite is observed for the
ethyl substituent [i.e. Me(4′)], which is closer to the aryl ring
in the (S)-ester (positive ∆δRS). As a conclusion, and in
accordance with the a/a and sp conformers, the absolute
configuration of 8 must be (S).
Figure 6. ∆Eag (CVff, in kcal/mol) and ∆δRS values for the 9-AMA
esters of compounds 21-23.
This correlation between the signs of ∆δRS and the absolute
configuration of the alcohol works well in all the compounds
shown in Figure 5. The sign of ∆δRS is consistently positive
or negative for all protons located on a certain side of the
asymmetric center and indicates that the absolute configuration
of these primary alcohols can be determined by interpretation
of the chemical shifts of L1/L2 in the (R)- and (S)-9-AMA esters
in the light of the conformational model shown in Figure 9,
where the MeO-CR-CO-O-C1′-C2′-H bonds are in the
same plane.
In this way, identification of substituent L1 as the one that
resonates at higher field in the (R)-9-AMA ester than in the
(S)-ester (negative ∆δRS; Figure 9) and of L2 as the substituent
that resonates at higher field in the (S)- than in the (R)-ester
(positive ∆δRS) allows the spatial location of L1 and L2 around
C2′ to be established and makes the assignment of the absolute
configuration a simple task.
However, the NMR spectra of compounds 21-23 show that
they do not conform to the model discussed above, and their
high preference for gauche forms leads to signs of ∆δRS which
are in disagreement with the above reasoning. Indeed, it must
be stressed that the configuration deduced in this way is not
reliable.
1
Figure 7. Partial H NMR spectra (3:1 CS2-CD2Cl2) of (a) 2-meth-
ylbutan-1-ol (8); (b) (R)-MTPA ester; (c) (S)-MTPA ester; (d) (R)-
MPA ester; (e) (S)-MPA ester; (R)-9-AMA and (S)-9-AMA esters (88:
12) (f) at room temperature and (g) at 183 K.
Scope and Limitations
shielding produced by the anthryl ring effectively shifts Me(4′)
and Me(5′) upfield by ∆δ ) 0.25-0.40 in relation to the free
alcohol. Analogous results were obtained when the comparison
was extended to alcohols 9 and 10 (Figure 5), confirming that
9-AMA (3) is a good reagent for producing shielding for primary
alcohols. However, no useful ∆δRS values or a general trend
in the signs was observed when MPA (1) and MTPA (2) were
used as derivatizing agents, as shown in Figure 5 for derivatives
24-29.
Inspection of the structures of compounds 8-20 indicates
that the model shown in Figure 9 can be applied to a wide
variety of â-chiral primary alcohols with a diverse range of
functions and substitution patterns and that the presence of polar
groups does not adversely affect its reliability. At the same
time, we have reported that it cannot be used with compounds
21-23 because of their different conformational composition.
It is very important to point out that the model has worked
correctly for all the alcohols in which the chiral center was not
part of (i.e. 8, 10, 12, 13-17) and in most cases in which it is
part of a cyclic system (i.e. 9, 11, 18-20).
Model for the Determination of the Absolute
Configuration of â-Chiral Primary Alcohols from the H
1
NMR of Their 9-AMA Esters
Clearly, it is imperative to define clear criteria to distinguish
those primary alcohols whose stereochemistry can be investi-
gated by this method and those that are not suitable due to their
different conformational composition. This could surely be
performed by ab initio calculations (Table 1), but these are time-
consuming and simpler methods would be certainly cheaper.
MM is an alternative which could be considered. It is fast,
and the ∆Eag values obtained for 8-20 are coherent within the
whole series and are significantly different from those obtained
for 21-23. These facts make it a suitable method to be used
to distinguish between the two groups of compounds. Unfor-
tunately, the CV force field produces a systematic excess of
gauche over anti conformers that has to be corrected by about
-1.4 kcal/mol to restore the preference (anti forms are more
stable than gauche forms by about 0.3 kcal/mol) indicated by
ab initio and NMR results obtained on 8-20.
All the information presented to this point strongly suggests
that a correlation exists between the spatial location of the
anthryl ring at the asymmetric center of the reagent and that of
substituents L1/L2 around the asymmetric center of the alcohol
and, therefore, that the absolute configuration at the asymmetric
center of the acid (CR) can be correlated to that of the alcohol
(C2′) by NMR.
Experimental evidence was obtained from the 1H NMR
spectra of the alcohols of known absolute configuration shown
in Figure 5. The ∆δRS values obtained are sufficiently large
(and well outside the experimental error) that they are of
practical use, and their signs are homogeneously distributed in
accordance with the spatial arrangement of the substituents in
relation to the anthryl ring.
Figure 8 illustrates the reasoning outlined above for com-
pound 8, showing the full accordance between the experimental
NMR data and the low-energy conformers deduced from the
To see if other force fields would be more advantageous, we
carried out MM calculations on compounds 6-23 with other

4746 J. Am. Chem. Soc., Vol. 120, No. 19, 1998
LatypoV et al.
Figure 8. Low-energy conformers of the 9-AMA esters of 8 with selected NMR data.
in MM calculations show the difference between the two types
of compounds, but PCff is the best and it can be safely used as
an alternative to ab initio calculations to predict the suitability
of a primary alcohol for this method. Greater values than those
observed for compounds 6-20 are an indication of a different
conformational composition and, therefore, that the assignment
of the absolute configuration will be unreliable.
Experimental Section
Computational Methods. Molecular mechanics (employing the
PC91 force field17) and AM1 (PM3) calculations were performed using
the Insight II package on a Silicon Graphics Iris (SGI) computer. Initial
molecular geometries were originated from the Builder Module of
Insight II; 3D coordinates were then generated from the bond lengths,
bond angles, and dihedral angles using the DG-II package.20 The
conformational space of each compound was scanned by MM
optimization of the sterically allowed conformations around key single
bonds. The MM simulations were carried out in Vacuo. Analysis of
conformational transitions, identification of the low-energy conformers,
and calculation of the energy barriers between these conformers were
all carried out by MM. The energies of conformations were minimized
in Cartesian coordinate space by the block diagonal Newton-Raphson
method; minima corresponded to rms energy gradients < 0.001 kcal/
(mol Å). The ground-state energies of the geometries were then
calculated by AM1 (PM3) using the MOPAC 6.0 program. For all
compounds, full geometry optimization used the Broyden-Fletcher-
Goldfarb-Shanno (BFGS) method and the PRECISE option.13 Ab
initio electronic structure calculations (at the restricted Hartree-Fock
level of theory) were performed using GAUSSIAN 92.14 During the
ab initio calculations all internal coordinates were optimized by Berny
algorithm and convergence was tested against criteria for the maximum
force component, root-mean-square force, maximum step component,
and root-mean-square step. No symmetry options were implemented.
Shielding effects calculations based on the semiclassical model of
Bovey and Johnson21 were carried out using an SGI computer. No
corrections for local anisotropic contributions21d,e were implemented.
Calculations were performed with π-current loops separation of 1.39
Å.21b,f
Figure 9. Conformational model for the determination of the absolute
configuration of â-chiral primary alcohols by NMR spectroscopy.
options.16 The data contained in Table 3 show PCff9117 as the
method that best reproduces the existence of two groups of
compounds (set 6-20, where the a/a conformer is more stable
than the gauche conformers, and set 21-23, in which the
behavior is the other way round) and give the ∆Eag values
closest to the real ones (ab initio and NMR).
The force fields Amber18 and CVff12 produce overstabilization
of the gauche forms; nevertheless, the ∆Eag values obtained
allow a distinction to be made between set 6-20 [small
stabilization of gauche, ∆Eag) 0.5-2.3 (Amber), 0.7-1.4
(CVff)] and set 21-23, where the overstabilization is very large
[∆Eag) 3.8 (Amber), 2.2-3.1 (CVff)].
Finally, MMX19 calculations give results similar to Amber
and CVff, but the parametrization is not good enough to
adequately reproduce all the structural features of 6-23, and
some energy values are out of range.
Conclusions
In conclusion, the absolute configuration of almost all â-chiral
1
primary alcohols can be safely assigned by H NMR spectro-
scopy of the (R)- and (S)-9-AMA esters, employing the model
shown in Figure 9. If the chiral center is part of a ring, or
when strong steric interactions could be in operation, ab initio
or MM calculations must be performed in order to ensure that
the anti form is the most stable one. All the force fields used
NMR Spectroscopy. 1H and 13C NMR spectra of samples in 4:1
CS2/CD2Cl2 or CDCl3 (ca. 2-3 mg in 0.5 mL) were recorded on a
AMX 500, AMX 300, or WM 250 NMR spectrometer. Chemical shifts
(ppm) are internally referenced to the tetramethylsilane signal (0 ppm)
(16) For a recent comparative study see: Gundertofte, K.; Liljefors, T.;
Norrby, P.; Ptterson, I. J. Comput. Chem. 1996, 17, 429-449.
(17) Maple, J. R.; Dinur, U.; Hagler, A. T. Proc. Natl. Acad. Sci. U.S.A.
1988, 85, 5350-5354.
(18) Kollman, P. A.; Weiner, S.; Seibel, G.; Lybrand, T.; Singh, U. Ch.;
Caldwell, J.; Rao, Sh. N. Ann. N. Y. Acad. Sci. 1986, 482, 234-244.
(19) Gajewski, J. J.; Gilbert, K. E.; Mckelvey, J. AdV. Mol. Model. 1990,
2, 65-92.
(20) Cioslowski, J.; Kertesz, M. QCPE Bull. 1987, 7, 159.
(21) (a) Waugh, J. S.; Fessenden, R. W. J. Am. Chem. Soc. 1957, 79,
846-849. (b) Johnson. C. E.; Bovey, F. A. J. Chem. Phys. 1958, 29, 1012-
1014. (c) Jonathan, N.; Gordon, S.; Dailey, B. P. J. Chem. Phys. 1962, 36,
2443-2448. (d) Dailey, B. P. J. Chem. Phys. 1964, 41, 2304-2310. (e)
Musher, J. I. J. Chem. Phys. 1965, 42, 4081-4083. (f) Haigh, C. W.;
Mallion, R. B. Ring current theories in NMR. Progress in NMR spectros-
copy; Pergamon Press: London, 1980; Vol. 13, pp 303-344.

Configuration of â-Chiral Primary Alcohols
J. Am. Chem. Soc., Vol. 120, No. 19, 1998 4747
Table 3. Conformational Energy Distribution (in kcal/mol) around the C1′-C2′ Bond for Alcohols 7-23 Obtained in the Framework of
Several Force Fields
amber
CVff
PCff91
MMXa
a
g+
g-
a
g+
g-
a
g+
g-
a
g+
g-
7
8
9
0.54
0.42
2.34
1.07
1.08
b
0.90
0.00
0.86
0.87
0.00
0.48
1.04
0.00
c
0.00
0.00
0.00
0.01
0.00
b
0.00
0.47
0.00
0.00
0.69
0.00
0.00
1.14
0.00
0.00
b
0.87
0.72
1.37
1.25
1.07
0.73
1.21
0.89
1.00
1.23
0.47
0.80
1.51
0.10
2.20
3.08
2.45
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.21
1.04
0.69
0.05
0.80
0.72
0.52
0.89
0.34
0.75
0.29
0.45
0.34
1.00
0.10
0.98
0.00
0.00
0.10
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00d
2.71
0.96
0.39
0.54
0.00
0.26
0.06
0.56
0.64
0.02
0.52
0.24
0.04
0.06
0.59
0.03
0.55d
0.00
0.00
0.64
0.46
0.52
0.21
1.43
0.52
0.67
0.25
0.69
0.30
1.35
0.00
0.69
0.63
1.58
4.83
2.40
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
2.07
0.00
0.00
0.00
0.00
0.00
0.11
1.89
0.14
0.11
b
1.88
1.55
1.86
1.19
0.19
0.29
0.62
1.36
1.67
0.22
b
0.55
0.39
0.43
0.17
0.80
6.89
7.34
6.75
7.21
6.71
0.34
6.76
0.61
0.30d
0.40
0.79
0.10
0.21
0.42
0.18
0.34
0.36
1.74
0.58
0.18
0.31
2.44
0.21
0.34
0.33
0.24
1.95
10
11
12
13
14
15
16
17
18
19
20
21
22
23
3.82
b
a pc4.41. b The potential type cannot be assigned. c Unstable structure. d A full set of force fields is not available.
in all cases. One- and two-dimensional NMR spectra were measured
with standard pulse sequences. 2D homo- (COSY) and heteronuclear
(HMQC) shift correlation experiments were carried out using pulsed
field gradient technique. Apodization with a shifted sine bell and
baseline correction was implemented to process 2D spectra.
(ppm) 0.51 (d, J ) 6.7 Hz, 3H), 0.54 (d, J ) 6.7 Hz, 3H), 1.62 (m,
1H), 3.43 (s, 3H), 3.82 (d, J ) 6.7 Hz, 2H), 6.29 (s, 1H), 7.54 (m,
4H), 8.02 (d, J ) 8.3 Hz, 2H), 8.48 (s, 1H), 8.58 (d, J ) 8.9 Hz, 2H);
UV λmax 260 nm (CHCl3); MS (EI) m/z 322 (M+); HRMS (EI) C21H22O3
found 322.15740, calcd 322.15690, ∆m -0.50 mu.
1
1D H NMR Spectra. Size 32 K, pulse length 2.8 ms (30°), 16
acquisitions.
(S)-(-)-2-Methylbutyl (R)-(-)-2-(9-anthryl)-2-methoxyacetate ((R)-
8): HPLC tR ) 21.83 min (hexanes-ethyl acetate, 96:4, 2 mL/min,
1
2D COSY Spectra. Sequence: D1-90-t1-G1-90-G2-AQ;
relaxation delay D1 ) 1 s, 90° pulse 8.5 µs, gradient ratio 1:1.
2D TOCSY Spectra. Relaxation delay D1 ) 2 s; mixing time 41.3
ms; 90° pulse 8.5 µs; TPPI-mode, NS ) 64.
2D Proton-Detected Heteronuclear Multiple Quantum Correla-
tion (HMQC) Experiments. Sequence: D190(1H)-D2-90(13C)-t1/
2-G1-180(1H)-G2-t1/2-90(13C)-G3-D2-AQ (GARP(13C)), re-
laxation delay D1 ) 2s; D2 ) 3.45 ms; 90° pulse (1H) 8.5 µs; 90°
pulse (13C) 10.5 µs, gradient ratio 5:3:4.
For DNMR spectroscopy, the probe temperature was controlled by
a standard unit calibrated using a methanol reference; samples were
allowed to equilibrate for 15 min at each temperature before recording
spectra.
General Methods. Preparation of diastereomeric esters 4-29 from
the corresponding primary alcohols and (R/S)-9-anthrylmethoxyacetic
acid (9-AMA) was carried out with DCC and DMAP.22 Final
purification was achieved by HPLC (µ-Porasil 3 mm × 250 mm or
Spherisorb S5W 5 mm, hexanes-ethyl acetate). The N-BOC-amino
alcohols were obtained from the corresponding Boc-protected amino
acids by reduction with BH3‚THF at 0 °C.23 Retention of configuration
was observed in all cases.
2-Methylpropyl (R)-(-)-2-methoxy-2-phenylacetate ((R)-4): [R]
) -79.0 (c ) 0.012, CHCl3); 1H NMR (300.13 MHz, CDCl3) δ (ppm)
0.81 (d, J ) 6.7 Hz, 3H), 0.82 (d, J ) 6.7 Hz, 3H), 1.87 (m, 1H), 3.41
(s, 3H), 3.90 (d, J ) 6.8 Hz, 2H), 4.77 (s, 1H), 7.33 (m, 3H), 7.43 (m,
2H); UV λmax 242 nm (CHCl3); MS (EI) m/z 222 (M+); HRMS (EI)
C13H18O3 found 222.11262, calcd 222.11256, ∆m -0.06 mu.
2-Methylpropyl (R)-(-)-2-methoxy-2-(trifluoromethyl)-2-phen-
ylacetate: ((R)-5): [R] ) +11.6 (c ) 0.005, CHCl3); 1H NMR (300.13
MHz, CDCl3) δ (ppm) 0.93 (d, J ) 6.7 Hz, 6H), 2.00 (m, 1H), 3.55 (s,
3H), 4.06 (dd, J ) 6.5, 10.6 Hz, 1H), 4.15 (dd, J ) 6.5, 10.6 Hz, 1H),
7.41 (m, 3H), 7.51 (m, 2H); UV λmax 232 nm (CHCl3); MS (EI) m/z
290 (M+); HRMS (EI) C14H17O3F3 found 290.11300, calcd 290.11298,
∆m -0.02 mu.
µ-porasil); [R] ) -61.6 (c ) 0.005, EtOH); H NMR (500.13 MHz,
CDCl3) δ (ppm) 0.41 (d, J ) 6.7 Hz, 3H), 0.53 (t, J ) 7.6 Hz, 3H),
0.75 (m, 1H), 0.93 (m, 1H), 1.34 (m, 1H), 3.37 (s, 3H), 3.79 (dd, J )
6.8, 10.8 Hz, 1H), 3.86 (dd, J ) 6.0, 10.8 Hz, 1H), 6.23 (s, 1H), 7.40
(dd, J ) 6.8, 8.1 Hz, 2H), 7.47 (dd, J ) 6.5, 7.9 Hz, 2H), 7.94 (d, J
) 8.6 Hz, 2H), 8.39 (s, 1H), 8.53 (d, J ) 8.9 Hz, 2H); 13C NMR (75.47
MHz, CDCl3) δ (ppm) 10.8, 15.8, 25.6, 33.7, 57.5, 69.6, 77.2, 124.5,
125.0, 126.4, 127.4, 129.1, 130.5, 131.4, 171.4; UV λmax 260 nm
(CHCl3); MS (EI) m/z 336 (M+); HRMS (EI) C22H24O3 found
336.17293, calcd 336.17254, ∆m -0.39 mu. Anal. Calcd for
C22H24O3: C, 78.53; H, 7.2. Found: C, 78.89; H, 7.12.
(S)-(-)-2-Methylbutyl (S)-(+)-2-(9-anthryl)-2-methoxyacetate ((S)-
8): HPLC tR ) 23.11 min (hexanes-ethyl acetate, 96:4, 2 mL/min,
µ-porasil); [R] ) +154.4 (c ) 0.0025, EtOH); 1H NMR (500.13 MHz,
CDCl3) δ (ppm) 0.42 (d, J ) 6.7 Hz, 3H), 0.45 (t, J ) 7.4 Hz, 3H),
0.67 (m, 1H), 0.75 (m, 1H), 1.31 (m, 1H), 3.36 (s, 3H), 3.80 (d, J )
6.3 Hz, 2H), 6.21 (s, 1H), 7.40 (dd, J ) 7.4, 8.3 Hz, 2H), 7.47 (dd, J
) 6.4, 8.7 Hz, 2H), 7.94 (d, J ) 8.6 Hz, 2H), 8.40 (s, 1H), 8.50 (d, J
) 9.0 Hz, 2H); 13C NMR (75.47 MHz, CDCl3) δ (ppm) 10.8, 15.9,
25.5, 33.8, 57.5, 69.6, 77.2, 124.4, 125.0, 126.4, 127.4, 129.1, 130.5,
131.4, 171.4; UV λmax 260 nm (CHCl3); MS (EI) m/z 336 (M+); HRMS
(EI) C22H24O3 found 336.17285, calcd 336.17254, ∆m -0.31 mu.
D-r,â-Isopropylidenegliceryl (R)-(-)-2-(9-anthryl)-2-methoxyac-
etate ((R)-9): HPLC tR ) 27.53 min (hexanes-ethyl acetate, 80:20, 2
mL/min, Spherisorb S5W 5µm); [R] ) -30.4 (c ) 0.0025, EtOH); 1H
NMR (500.13 MHz, CDCl3) δ (ppm) 0.94 (s, 3H), 1.09 (s, 3H), 2.91
(dd, J ) 6.3, 8.4 Hz, 1H), 3.36 (dd, J ) 6.3, 8.4 Hz, 1H), 3.37 (s, 3H),
3.90 (m, 1H), 3.98 (dd, J ) 5.4, 11.5 Hz, 1H), 4.07 (dd, J ) 4.2, 11.6
Hz, 1H), 6.23 (s, 1H), 7.40 (m, 2H), 7.47 (m, 2H), 7.95 (d, J ) 8.6
Hz, 2H), 8.42 (s, 1H), 8.46 (d, J ) 8.9 Hz, 2H); 13C NMR (75.47
MHz, CDCl3) δ (ppm) 25.3, 26.1, 57.5, 64.1, 65.5, 72.8, 77.2, 109.3,
124.2, 125.0, 126.7, 129.2, 129.4, 130.6, 131.5, 171.2; UV λmax 260
nm (CHCl3); MS (EI) m/z 380 (M+); HRMS (EI) C23H24O5 found
380.16202, calcd 380.16237, ∆m 0.35 mu. Anal. Calcd for
C23H24O5: C, 72.60; H, 6.36. Found: C, 72.91; H, 6.18.
2-Methylpropyl (R)-(-)-2-(9-anthryl)-2-methoxyacetate ((R)-6):
1
[R] ) -23.2 (c ) 0.033, CHCl3); H NMR (300.13 MHz, CDCl3) δ
D-r,â-Isopropylidenegliceryl (S)-(+)-2-(9-anthryl)-2-methoxyac-
etate ((S)-9): HPLC tR ) 30.21 min (hexanes-ethyl acetate, 80:20, 2
mL/min, Spherisorb S5W 5µm); [R] ) +28.7 (c ) 0.0055, EtOH); 1H
NMR (500.13 MHz, CDCl3) δ (ppm) 0.97 (s, 3H), 1.01 (s, 3H), 3.20
(dd, J ) 5.7, 8.4 Hz, 1H), 3.35 (s, 3H), 3.53 (dd, J ) 5.7, 8.3 Hz, 1H),
(22) Trost, B. M.; Belletire, J. L.; Godleski, S.; McDougal, P. G.;
Balkovec, J. M. J. Org. Chem. 1986, 51, 2370-2374.
(23) Stanfield C. F.; Parker J. E.; Kanellis P. J. Org. Chem. 1981, 46,
4799-4800.

4748 J. Am. Chem. Soc., Vol. 120, No. 19, 1998
LatypoV et al.
3.89 (m, 2H), 4.11 (m, 1H), 6.23 (s, 1H), 7.39 (m, 2H), 7.46 (m, 2H),
7.93 (d, J ) 8.4 Hz, 2H), 8.40 (s, 1H), 8.47 (d, J ) 9.0 Hz, 2H); 13C
NMR (62.97 MHz, CDCl3) δ (ppm) 25.2, 26.1, 57.4, 64.8, 66.0, 72.9,
77.1, 109.4, 124.3, 125.0, 126.6, 129.2, 129.4, 130.6, 131.5, 171.1;
UV λmax 260 nm (CHCl3); MS (EI) m/z 380 (M+); HRMS (EI) C23H24O5
found 380.16248, calcd 380.16237, ∆m -0.11 mu.
Methyl 3-[(((R)-9-anthryl(methoxy)methyl)carbonyl)oxy]-2-(R)-
methylpropanoate ((R)-10): HPLC tR ) 55.81 min (hexanes-ethyl
acetate, 90:10, 2 mL/min, Spherisorb S5W 5 µm); [R] ) -33.5 (c )
0.0055, EtOH); 1H NMR (500.13 MHz, CDCl3) δ (ppm) 0.69 (d, J )
7.1 Hz, 3H), 2.46 (m, 1H), 3.19 (s, 3H), 3.35 (s, 3H), 4.08 (m, 2H),
6.20 (s, 1H), 7.40 (m, 2H), 7.47 (m, 2H), 7.94 (d, J ) 8.4 Hz, 2H),
8.41 (s, 1H), 8.46 (d, J ) 9.0 Hz, 2H); 13C NMR (75.47 MHz, CDCl3)
δ (ppm) 13.1, 38.7, 51.4, 57.5, 66.0, 77.1, 124.4, 125.0, 126.5, 127.0,
129.2, 130.5, 131.4, 170.9, 173.5; UV λmax 260 nm (CHCl3); MS (EI)
m/z 366 (M+); HRMS (EI) C22H22O5 found 366.14624, calcd 366.14672,
∆m 0.48 mu. Anal. Calcd for C22H22O5: C, 72.1; H, 6.06. Found:
C, 72.33; H, 5.89;
3H), 1.70 (m, 1H), 2.65 (d, J ) 5.2 Hz, 2H), 3.38 (s, 3H), 3.82 (dd, J
) 7.3, 11.2 Hz, 1H), 4.04 (dd, J ) 5.2, 11.0 Hz, 1H), 6.24 (s, 1H),
7.41 (m, 2H), 7.49 (m, 2H), 7.95 (d, J ) 8.5 Hz, 2H), 8.41 (s, 1H),
8.50 (d, J ) 9.3 Hz, 2H); 13C NMR (75.47 MHz, CDCl3) δ (ppm)
15.1, 34.4, 35.9, 57.5, 67.0, 77.1, 124.3, 125.0, 126.6, 129.2, 129.3,
130.5, 131.4, 171.1; UV λmax 260 nm (CHCl3); MS (EI) m/z 400 (M+);
HRMS (EI) C21H21O3Br found 400.06753, calcd 400.06741, ∆m -0.12
mu.
Boc-L-Alanyl (R)-(-)-2-(9-anthryl)-2-methoxyacetate ((R)-13):
HPLC tR ) 31.89 min (hexanes-ethyl acetate, 85:15, 3 mL/min,
µ-porasil); [R] ) -114.9 (c ) 0.0285, CHCl3); 1H NMR (500.13 MHz,
CDCl3) δ (ppm) 0.54 (d, J ) 6.8 Hz, 3H), 1.27 (s, 9H), 3.36 (s, 3H),
3.56 (br, 1H), 3.78 (br, 1H), 3.89 (dd, J ) 4.1, 10.6 Hz, 1H), 3.96 (br,
1H), 6.22 (s, 1H), 7.40 (m, 2H), 7.48 (m, 2H), 7.94 (d, J ) 8.4 Hz,
2H), 8.40 (s, 1H), 8.49 (d, J ) 9.2 Hz, 2H); 13C NMR (75.47 MHz,
CDCl3) δ (ppm) 17.0, 28.3, 57.5, 67.4, 77.2, 124.3, 125.1, 126.7, 127.2,
129.2, 129.3, 130.5, 131.4, 154.8, 171.1; UV λmax 258 nm (CHCl3);
MS (EI) m/z 423 (M+); HRMS (EI) C25H29O5N found 423.20440, calcd
423.20457, ∆m 0.17 mu. Anal. Calcd for C25H29O5N: C, 70.9; H,
6.9; N, 3.31. Found: C, 71.23; H, 6.68; N, 3.52
Methyl 3-[(((S)-9-anthryl(methoxy)methyl)carbonyl)oxy]-2-(R)-
methylpropanoate ((S)-10): HPLC tR ) 57.45 min (hexanes-ethyl
acetate, 90:10, 2 mL/min, Spherisorb S5W 5µm); [R] ) +8.0 (c )
Boc-L-Alanyl (S)-(+)-2-(9-anthryl)-2-methoxyacetate ((S)-13):
HPLC tR ) 32.79 min (hexanes-ethyl acetate, 85:15, 3 mL/min,
1
0.002, EtOH); H NMR (500.13 MHz, CDCl3) δ (ppm) 0.79 (d, J )
1
7.1 Hz, 3H), 2.36 (m, 1H), 3.09 (s, 3H), 3.34 (s, 3H), 4.08 (dd, J )
7.4, 10. Hz, 2H), 6.19 (s, 1H), 7.39 (m, 2H), 7.46 (m, 2H), 7.93 (d, J
) 8.4 Hz, 2H), 8.39 (s, 1H), 8.46 (d, J ) 9.2 Hz, 2H); 13C NMR (75.47
MHz, CDCl3) δ (ppm) 13.3, 38.6, 51.3, 57.5, 66.0, 77.1, 124.4, 125.0,
126.5, 127.0, 129.2, 130.5, 131.4, 170.9, 173.6; UV λmax 260 nm
(CHCl3); MS (EI) m/z 366 (M+); HRMS (EI) C22H22O5 found
366.14668, calcd 366.14672 ∆m 0.04 mu.
µ-porasil); [R] ) +50.0 (c ) 0.01, CHCl3); H NMR (500.13 MHz,
CDCl3) δ (ppm) 0.49 (br, 3H), 1.30 (s, 9H), 3.39 (s, 3H), 3.63 (br,
1H), 3.88 (dd, J ) 4.4, 10.9 Hz, 1H), 3.96 (br, 2H), 6.24 (s, 1H), 7.41
(m, 2H), 7.48 (m, 2H), 7.95 (d, J ) 8.4 Hz, 2H), 8.41 (s, 1H), 8.50 (d,
J ) 9.2 Hz, 2H); 13C NMR (75.47 MHz, CDCl3) δ (ppm) 16.8, 28.2,
57.5, 67.6, 77.2, 124.3, 125.0, 126.6, 127.1, 129.1, 129.2, 130.4, 131.4,
154.8, 171.0; UV λmax 258 nm (CHCl3); MS (EI) m/z 423 (M+); HRMS
(EI) C25H29O5N found 423.20406, calcd 423.20457, ∆m 0.51 mu.
Boc-L-Valyl (R)-(-)-2-(9-anthryl)-2-methoxyacetate ((R)-14): HPLC
tR ) 21.91 min (hexanes-ethyl acetate, 85:15, 3 mL/min, µ-porasil);
(+)-trans-Myrtanyl (R)-(-)-2-(9-anthryl)-2-methoxyacetate ((R)-
11): HPLC tR ) 22.93 min (hexanes-ethyl acetate, 96:4, 2 mL/min,
1
µ-porasil); [R] ) -58.8 (c ) 0.01, EtOH); H NMR (500.13 MHz,
1
CDCl3) δ (ppm) 0.36 (s, 3H), 0.79 (s, 3H), 0.86 (m, 2H), 0.96 (td, J )
5.7, 1.0 Hz, 1H), 1.14 (m, 1H), 1.40 (m, 1H), 1.47 (m, 1H), 1.56 (m,
2H), 1.80 (m, 1H), 3.34 (s, 3H), 3.60 (dd, J ) 8.4, 10.5 Hz, 1H), 3.89
(dd, J ) 6.0, 10.5 Hz, 1H), 6.18 (s, 1H), 7.38 (m, 2H), 7.45 (m, 2H),
7.93 (d, J ) 8.4 Hz, 2H), 8.38 (s, 1H), 8.47 (d, J ) 9.0 Hz, 2H); 13C
NMR (75.47 MHz, CDCl3) δ (ppm) 17.3, 19.6, 22.9, 23.7, 26.2, 33.9,
38.6, 40.4, 41.6, 57.4, 68.0, 77.2, 124.4, 125.0, 126.4, 127.4, 129.1,
130.5, 131.4, 171.4; UV λmax 260 nm (CHCl3); MS (EI) m/z 402 (M+);
HRMS (EI) C27H30O3 found 402.21962, calcd 402.21950 ∆m -0.12
mu. Anal. Calcd for C27H30O3: C, 80.55; H, 7.52. Found: C, 80.73;
H, 7.37.
[R] ) -80.4 (c ) 0.005, CHCl3); H NMR (500.13 MHz, CDCl3) δ
(ppm) 0.44 (d, J ) 6.7 Hz, 3H), 0.49 (d, J ) 6.8 Hz, 3H), 0.98 (m,
1H), 1.29 (s, 9H), 3.25 (m, 1H), 3.38 (s, 3H), 3.79 (d, J ) 9.7 Hz,
1H), 4.00 (m, 2H), 6.21 (s, 1H), 7.41 (m, 2H), 7.49 (m, 2H), 7.96 (d,
J ) 8.4 Hz, 2H), 8.42 (s, 1H), 8.48 (d, J ) 9.3 Hz, 2H); 13C NMR
(75.47 MHz, CDCl3) δ (ppm) 17.9, 19.0, 28.3, 29.1, 54.5, 57.5, 64.9,
77.2, 79.1, 124.3, 125.0, 126.6, 127.2, 129.2, 130.5, 131.4, 155.4, 171.1;
UV λmax 258 nm (CHCl3); MS (EI) m/z 451 (M+); HRMS (EI)
C27H33O5N found 451.23519, calcd 451.23587, ∆m 0.68 mu. Anal.
Calcd for C27H33O5N: C, 71.82; H, 7.37; N, 3.1. Found: C, 71.98; H,
7.13; N, 2.88.
(+)-trans-Myrtanyl (S)-(+)-2-(9-anthryl)-2-methoxyacetate ((S)-
11): HPLC tR ) 22.75 min (hexanes-ethyl acetate, 96:4, 2 mL/min,
Boc-L-Valyl (S)-(+)-2-(9-anthryl)-2-methoxyacetate ((S)-14):
HPLC tR ) 22.82 min (hexanes-ethyl acetate, 85:15, 3 mL/min,
1
1
µ-porasil); [R] ) +89.7 (c ) 0.007, EtOH); H NMR (500.13 MHz,
µ-porasil); [R] ) +28.0 (c ) 0.016, CHCl3); H NMR (500.13 MHz,
CDCl3) δ (ppm) 0.46 (s, 3H), 0.79 (m, 1H), 0.83 (m, 1H), 0.85 (s,
3H), 1.07 (m, 2H), 1.39 (m, 1H), 1.48 (m, 1H), 1.57 (m, 2H), 1.85 (m,
1H), 3.35 (s, 3H), 3.73 (dd, J ) 6.4, 10.6 Hz, 1H), 3.80 (dd, J ) 7.3,
10.6 Hz, 1H), 6.18 (s, 1H), 7.38 (m, 2H), 7.45 (m, 2H), 7.93 (d, J )
8.4 Hz, 2H), 8.38 (s, 1H), 8.47 (d, J ) 9.2 Hz, 2H); 13C NMR (62.97
MHz, CDCl3) δ (ppm) 17.4, 19.8, 22.9, 23.6, 26.2, 34.0, 38.7, 40.4,
41.9, 57.4, 68.6, 77.2, 124.5, 125.0, 126.4, 127.5, 129.1, 130.6, 131.5,
171.5; UV λmax 260 nm (CHCl3); MS (EI) m/z 402 (M+); HRMS (EI)
C27H30O3 found 402.21934, calcd 402.21950, ∆m 0.16 mu.
3-Bromo-2-(R)-(-)-methylpropyl (R)-(-)-2-(9-anthryl)-2-meth-
oxyacetate ((R)-12): HPLC tR ) 24.81 min (hexanes-ethyl acetate,
94:6, 1 mL/min, Spherisorb S5W 5µm); [R] ) +30.9 (c ) 0.0065,
EtOH); 1H NMR (500.13 MHz, CDCl3) δ (ppm) 0.43 (d, J ) 6.8 Hz,
3H), 1.73 (m, 1H), 2.65 (dd, J ) 5.5, 10.2 Hz, 1H), 2.74 (dd, J ) 6.0,
10.5 Hz, 1H), 3.34 (s, 3H), 3.89 (m, 2H), 6.21 (s, 1H), 7.36 (m, 2H),
7.44 (m, 2H), 7.89 (d, J ) 8.4 Hz, 2H), 8.36 (s, 1H), 8.46 (d, J ) 9.2
Hz, 2H); 13C NMR (62.97 MHz, CDCl3) δ (ppm) 14.9, 34.2, 35.8,
57.4, 66.9, 77.1, 124.2, 125.0, 126.6, 127.2, 129.2, 130.5, 131.4, 171.1;
UV λmax 260 nm (CHCl3); MS (EI) m/z 400 (M+); HRMS (EI)
C21H21O3Br found 400.06732, calcd 400.06741, ∆m 0.09 mu. Anal.
Calcd for C21H21O3Br: C, 62.99; H, 5.29. Found: C, 63.25; H, 5.07.
3-Bromo-2-(R)-(-)-methylpropyl (S)-(+)-2-(9-anthryl)-2-meth-
oxyacetate ((S)-12): HPLC tR ) 27.85 min (hexanes-ethyl acetate,
94:6, 1 mL/min, Spherisorb S5W 5µm); [R] ) -40.0 (c ) 0.003,
EtOH); 1H NMR (500.13 MHz, CDCl3) δ (ppm) 0.60 (d, J ) 6.8 Hz,
CDCl3) δ (ppm) 0.30 (d, J ) 6.7 Hz, 3H), 0.39 (d, J ) 6.7 Hz, 3H),
0.76 (m, 1H), 1.31 (s, 9H), 3.28 (m, 1H), 3.41 (s, 3H), 3.95 (d, J ) 9.7
Hz, 1H), 3.98 (m, 2H), 6.22 (s, 1H), 7.40 (m, 2H), 7.48 (m, 2H), 7.94
(d, J ) 8.4 Hz, 2H), 8.40 (s, 1H), 8.50 (d, J ) 9.2 Hz, 2H); 13C NMR
(75.47 MHz, CDCl3) δ (ppm) 18.1, 18.6, 28.2, 29.1, 54.2, 57.6, 65.2,
77.2, 79.1, 124.3, 125.0, 126.6, 127.1, 129.1, 130.4, 131.4, 155.3, 170.9;
UV λmax 258 nm (CHCl3); MS (EI) m/z 451 (M+); HRMS (EI)
C27H33O5N found 451.23570, calcd 451.23587, ∆m 0.17 mu.
Boc-L-Leucyl (R)-(-)-2-(9-anthryl)-2-methoxyacetate ((R)-15):
HPLC tR ) 17.33 min (hexanes-ethyl acetate, 85:15, 3 mL/min,
1
µ-porasil); [R] ) -87.0 (c ) 0.008, CHCl3); H NMR (500.13 MHz,
CDCl3) δ (ppm) 0.39 (m, 1H), 0.40 (d, J ) 6.7 Hz, 3H), 0.48 (d, J )
6.7 Hz, 3H), 0.51 (m, 1H), 1.10 (m, 1H), 1.28 (s, 9H), 3.38 (s, 3H),
3.44 (m, 1H), 3.58 (d, J ) 8.9 Hz, 1H), 3.81 (dd, J ) 3.9, 11.2 Hz,
1H), 4.08 (dd, J ) 4.7, 11.2 Hz, 1H), 6.22 (s, 1H), 7.41 (m, 2H), 7.49
(m, 2H), 7.96 (d, J ) 8.4 Hz, 2H), 8.42 (s, 1H), 8.49 (d, J ) 9.2 Hz,
2H); 13C NMR (75.47 MHz, CDCl3) δ (ppm) 21.6, 22.5, 24.1, 28.3,
39.9, 47.6, 57.5, 66.5, 77.2, 79.2, 124.3, 125.1, 126.7, 129.2, 130.4,
131.5, 155.0, 166.4, 171.0; UV λmax 258 nm (CHCl3); MS (EI) m/z
465 (M+); HRMS (EI) C28H35O5N found 465.25122, calcd 465.25152,
∆m 0.30 mu. Anal. Calcd for C28H35O5N: C, 72.23; H, 7.58; N, 3.01.
Found: C, 72.53; H, 7.23; N, 2.93.
Boc-L-Leucyl (S)-(+)-2-(9-anthryl)-2-methoxyacetate ((S)-15):
HPLC tR ) 17.48 min (hexanes-ethyl acetate, 85:15, 3 mL/min,
1
µ-porasil); [R] ) +17.0 (c ) 0.014, CHCl3); H NMR (500.13 MHz,

Configuration of â-Chiral Primary Alcohols
J. Am. Chem. Soc., Vol. 120, No. 19, 1998 4749
CDCl3) δ (ppm) 0.32 (m, 1H), 0.34 (d, J ) 6.7 Hz, 3H), 0.40 (m, 1H),
0.44 (d, J ) 6.7 Hz, 3H), 0.98 (m, 1H), 1.30 (s, 9H), 3.40 (s, 3H),
3.52 (br, 1H), 3.76 (d, J ) 8.9 Hz, 1H), 3.91 (dd, J ) 3.9, 11.2 Hz,
1H), 3.97 (dd, J ) 3.8, 11.2 Hz, 1H), 6.24 (s, 1H), 7.41 (m, 2H), 7.48
(m, 2H), 7.95 (d, J ) 8.7 Hz, 2H), 8.41 (s, 1H), 8.52 (d, J ) 8.9 Hz,
2H); 13C NMR (75.47 MHz, CDCl3) δ (ppm) 21.8, 22.2, 24.2, 28.3,
39.8, 47.4, 57.6, 66.7, 77.2, 79.2, 124.4, 125.0, 126.6, 129.2, 130.4,
131.4, 155.0, 166.4, 170.9; UV λmax 258 nm (CHCl3); MS (EI) m/z
465 (M+); HRMS (EI) C28H35O5N found 465.25158, calcd 465.25152,
∆m -0.06 mu.
δ (ppm) 22.6, 27.0, 57.6, 65.5, 76.3, 76.8, 124.0, 125.2, 126.7, 126.9,
129.2, 129.4, 130.4, 131.3, 171.0, 176.2; UV λmax 266 nm (CHCl3);
MS (EI) m/z 364 (M+); HRMS (EI) C22H20O5 found 364.13114, calcd
364.13107, ∆m -0.07 mu. Anal. Calcd for C22H20O5: C, 72.51; H,
5.53. Found: C, 72.78; H, 5.27.
(R)-γ-Hydroxymethyl-γ-butyrolactone (S)-(+)-2-(9-anthryl)-2-
methoxyacetate ((S)-18): HPLC tR ) 23.65 min (hexanes-ethyl
acetate, 40:60, 1 mL/min, Spherisorb S5W 5µm); [R] ) +50.1 (c )
0.034, CHCl3); 1H NMR (500.13 MHz, CDCl3) δ (ppm) 1.48 (m, 1H),
1.81 (m, 1H), 1.85 (m, 1H), 2.05 (m, 1H), 3.34 (s, 3H), 4.03 (dd, J )
5.2, 12.2 Hz, 1H), 4.13 (dd, J ) 3.5, 12.2 Hz, 1H), 4.26 (m, 1H), 6.23
(s, 1H), 7.38 (m, 2H), 7.45 (m, 2H), 7.93 (d, J ) 8.3 Hz, 2H), 8.40 (s,
1H), 8.43 (d, J ) 9.0 Hz, 2H); 13C NMR (75.47 MHz, CDCl3) δ (ppm)
23.3, 27.3, 57.5, 65.6, 76.5, 76.9, 124.0, 125.0, 126.7, 129.2, 129.5,
130.4, 131.4, 170.9, 175.8; UV λmax 266 nm (CHCl3); MS (EI) m/z
364 (M+); HRMS (EI) C22H20O5 found 364.13117, calcd 364.13107,
∆m -0.10 mu.
(S)-5-(Hydroxymethyl)-2-pyrrolidinone (R)-(-)-2-(9-anthryl)-2-
methoxyacetate ((R)-19): [R] ) -39.7 (c ) 0.0175, CHCl3); 1H NMR
(500.13 MHz, CDCl3) δ (ppm) 1.42 (m, 1H), 1.90 (m, 1H), 2.04 (m,
2H), 3.42 (s, 3H), 3.47 (m, 1H), 3.80 (dd, J ) 7.9, 11.2 Hz, 1H), 4.16
(dd, J ) 3.9, 11.2 Hz, 1H), 5.65 (br, 1H), 6.35 (s, 1H), 7.49 (m, 2H),
7.55 (m, 2H), 8.03 (d, J ) 7.9 Hz, 2H), 8.50 (s, 1H), 8.53 (d, J ) 9.0
Hz, 2H); 13C NMR (75.47 MHz, CDCl3) δ (ppm) 22.5, 29.0, 52.3,
57.4, 67.4, 76.8, 124.0, 125.1, 126.8, 129.3, 129.5, 130.4, 131.4, 171.1,
177.4; UV λmax 264 nm (CHCl3); MS (EI) m/z 363 (M+); HRMS (EI)
C22H21O4N found 363.14696, calcd 363.14705, ∆m 0.09 mu. Anal.
Calcd for C22H21O4N: C, 72.71; H, 5.82; N, 3.85. Found: C, 72.83;
H, 5.69; N, 3.56.
(S)-5-(Hydroxymethyl)-2-pyrrolidinone (S)-(+)-2-(9-anthryl)-2-
methoxyacetate ((S)-19): [R] ) +135.3 (c ) 0.027, CHCl3); 1H NMR
(500.13 MHz, CDCl3) δ (ppm) 1.20 (m, 1H), 1.76 (m, 2H), 1.94 (m,
1H), 3.42 (s, 3H), 3.58 (m, 1H), 3.83 (dd, J ) 6.0, 11.4 Hz, 1H), 4.10
(dd, J ) 4.0, 11.3 Hz, 1H), 6.01 (br, 1H), 6.32 (s, 1H), 7.47 (m, 2H),
7.55 (m, 2H), 8.02 (d, J ) 7.8 Hz, 2H), 8.49 (s, 1H), 8.52 (d, J ) 8.9
Hz, 2H); 13C NMR (75.47 MHz, CDCl3) δ (ppm) 22.5, 29.0, 52.2,
57.4, 67.1, 76.8, 124.0, 125.1, 126.7, 129.2, 129.4, 130.4, 131.3, 171.2,
177.7; UV λmax 264 nm (CHCl3); MS (EI) m/z 363 (M+); HRMS (EI)
C22H21O4N found 363.14708, calcd 363.14705, ∆m -0.03 mu.
2,3-O,O′-Isopropilidene-D-ribono-1,4-lactone (R)-(-)-2-(9-anthryl)-
2-methoxyacetate ((R)-20): HPLC tR ) 19.45 min (hexanes-ethyl
acetate, 60:40, 2 mL/min, Spherisorb S5W 5µm); [R] ) -67.3 (c )
0.0295, CHCl3); 1H NMR (500.13 MHz, CDCl3) δ (ppm) 1.17 (s, 3H),
1.28 (s, 3H), 3.30 (d, J ) 5.8 Hz, 1H), 3.41 (s, 3H), 4.09 (dd, J ) 2.2,
12.2 Hz, 1H), 4.29 (d, J ) 5.8 Hz, 1H), 4.44 (dd, J ) 2.5, 12.0 Hz,
1H), 4.46 (t, J ) 2.4 Hz, 1H), 6.30 (s, 1H), 7.50 (m, 2H), 7.56 (m,
2H), 8.07 (d, J ) 7.7 Hz, 2H), 8.42 (d, J ) 8.9 Hz, 2H), 8.55 (s, 1H);
13C NMR (62.97 MHz, CDCl3) δ (ppm) 25.1, 26.4, 57.4, 63.9, 74.0,
76.6, 76.9, 78.9, 113.3, 123.3, 125.1, 127.0, 129.6, 129.9, 130.3, 131.3,
170.4, 172.1; UV λmax 260 nm (CHCl3); MS (EI) m/z 436 (M+); HRMS
(EI) C25H24O7 found 436.15209, calcd 436.15220, ∆m 0.11 mu. Anal.
Calcd for C25H24O7: C, 68.8; H, 5.54. Found: C, 69.12; H, 5.28.
2,3-O,O′-Isopropilidene-D-ribono-1,4-lactone(S)-(+)-2-(9-anthryl)-
2-methoxyacetate ((S)-20): HPLC tR ) 16.49 min (hexanes-ethyl
acetate, 60:40, 2 mL/min, Spherisorb S5W 5µm); [R] ) +68.9 (c )
0.024, CHCl3); 1H NMR (500.13 MHz, CDCl3) δ (ppm) 0.85 (s, 3H),
1.20 (s, 3H), 2.15 (d, J ) 5.8 Hz, 1H), 3.24 (d, J ) 5.8 Hz, 1H), 3.48
(s, 3H), 4.17 (dd, J ) 2.1, 12.5 Hz, 1H), 4.27 (dd, J ) 1.8, 12.5 Hz,
1H), 4.39 (t, J ) 1.9 Hz, 1H), 6.27 (s, 1H), 7.53 (m, 2H), 7.60 (m,
2H), 8.06 (d, J ) 7.9 Hz, 2H), 8.42 (d, J ) 8.5 Hz, 2H), 8.56 (s, 1H);
13C NMR (62.97 MHz, CDCl3) δ (ppm) 24.4, 26.2, 57.7, 64.2, 73.7,
76.2, 76.7, 79.0, 113.0, 123.3, 125.5, 126.5, 127.5, 129.4, 129.5, 130.3,
131.2, 170.7, 172.5; UV λmax 260 nm (CHCl3); MS (EI) m/z 436 (M+);
HRMS (EI) C25H24O7 found 436.15204, calcd 436.15220, ∆m 0.16 mu.
(2R,3R)-trans-3-Phenyloxirane-2-methyl (R)-(-)-2-(9-anthryl)-2-
methoxyacetate ((R)-21): HPLC tR ) 11.45 min (hexanes-ethyl
acetate, 75:25, 2 mL/min, µ-porasil); [R] ) -56.7 (c ) 0.030, EtOH);
1H NMR (500.13 MHz, CDCl3) δ (ppm) 2.77 (m, 1H), 3.27 (d, J )
1.9 Hz, 1H), 3.34 (s, 3H), 4.05 (dd, J ) 5.2, 12.2 Hz, 1H), 4.26 (dd,
J ) 3.8, 12.2 Hz, 1H), 6.25 (s, 1H), 6.87 (m, 2H), 7.14 (m, 3H), 7.38
(m, 4H), 7.91 (d, J ) 8.3 Hz, 2H), 8.38 (s, 3H), 8.45 (d, J ) 8.8 Hz,
Boc-L-Isoleucyl (R)-(-)-2-(9-anthryl)-2-methoxyacetate ((R)-16):
HPLC tR ) 15.25 min (hexanes-ethyl acetate, 85:15, 3 mL/min,
1
µ-porasil); [R] ) -75.8 (c ) 0.010, CHCl3); H NMR (500.13 MHz,
CDCl3) δ (ppm) 0.40 (d, J ) 6.3 Hz, 3H), 0.46 (t, J ) 7.4 Hz, 3H),
0.63 (m, 2H), 0.94 (m, 1H), 1.29 (s, 9H), 3.29 (m, 1H), 3.38 (s, 3H),
3.73 (d, J ) 9.3 Hz, 1H), 3.98 (dd, J ) 4.5, 11.5 Hz, 1H), 4.06 (dd, J
) 4.3, 11.5 Hz, 1H), 6.22 (s, 1H), 7.41 (m, 2H), 7.49 (m, 2H), 7.95 (d,
J ) 8.4 Hz, 2H), 8.41 (s, 1H), 8.48 (d, J ) 9.2 Hz, 2H); 13C NMR
(75.47 MHz, CDCl3) δ (ppm) 11.0, 14.9, 24.7, 28.2, 35.6, 53.4, 57.5,
64.7, 77.1, 79.1, 124.2, 125.0, 126.6, 127.2, 129.1, 130.4, 131.4, 155.2,
171.0; UV λmax 258 nm (CHCl3); MS (EI) m/z 465 (M+); HRMS (EI)
C28H35O5N found 465.25144, calcd 465.25152, ∆m 0.08 mu. Anal.
Calcd for C28H35O5N: C, 72.23; H, 7.58; N, 3.01. Found: C, 72.23;
H, 7.58; N, 2.57.
Boc-L-Isoleucyl (S)-(+)-2-(9-anthryl)-2-methoxyacetate ((S)-16):
HPLC tR ) 15.43 min (hexanes-ethyl acetate, 85:15, 3 mL/min,
1
µ-porasil); [R] ) +15.2 (c ) 0.015, CHCl3); H NMR (500.13 MHz,
CDCl3) δ (ppm) 0.15 (d, J ) 6.7 Hz, 3H), 0.35 (m, 1H), 0.41 (t, J )
7.3 Hz, 3H), 0.58 (m, 1H), 0.91 (m, 1H), 1.31 (s, 9H), 3.31 (m, 1H),
3.42 (s, 3H), 3.92 (d, J ) 9.6 Hz, 1H), 3.96 (dd, J ) 4.5, 11.5 Hz,
1H), 4.01 (dd, J ) 4.2, 11.3 Hz, 1H), 6.23 (s, 1H), 7.41 (m, 2H), 7.48
(m, 2H), 7.95 (d, J ) 8.3 Hz, 2H), 8.41 (s, 1H), 8.51 (d, J ) 9.2 Hz,
2H); 13C NMR (75.47 MHz, CDCl3) δ (ppm) 10.8, 14.4, 24.7, 28.2,
35.4, 53.1, 57.5, 65.0, 77.1, 79.0, 124.2, 124.9, 126.5, 127.0, 129.0,
130.3, 131.3, 155.2, 170.8; UV λmax 258 nm (CHCl3); MS (EI) m/z
465 (M+); HRMS (EI) C28H35O5N found 465.25168, calcd 465.25152,
∆m -0.16 mu.
Boc-L-phenylalanyl (R)-(-)-2-(9-anthryl)-2-methoxyacetate ((R)-
17): HPLC tR ) 21.20 min (hexanes-ethyl acetate, 85:15, 2 mL/min,
1
µ-porasil); [R] ) -73.8 (c ) 0.025, CHCl3); H NMR (500.13 MHz,
CDCl3) δ (ppm) 1.34 (s, 9H), 1.71 (m, 1H), 2.06 (m, 1H), 3.48 (s,
3H), 3.71 (m, 2H), 3.82 (m, 1H), 4.17 (m, 1H), 6.32 (s, 1H), 6.46 (d,
J ) 7.1 Hz, 2H), 7.02 (m, 2H), 7.05 (m, 1H), 7.50 (m, 2H), 7.60 (m,
2H), 8.04 (d, J ) 8.4 Hz, 2H), 8.50 (s, 1H), 8.59 (d, J ) 8.9 Hz, 2H);
13C NMR (62.97 MHz, CDCl3) δ (ppm) 28.2, 36.6, 50.5, 57.6, 64.5,
77.1, 79.3, 124.3, 125.2, 126.4, 126.9, 127.5, 128.3, 128.8, 129.0, 129.4,
130.5, 131.5, 136.7, 154.9, 171.1; UV λmax 262 nm (CHCl3); MS (EI)
m/z 499 (M+); HRMS (EI) C31H33O5N found 499.23572, calcd
499.23587, ∆m 0.15 mu. Anal. Calcd for C31H33O5N: C, 74.51; H,
6.66; N, 2.8. Found: C, 74.62; H, 6.50; N, 2.85.
Boc-L-phenylalanyl (S)-(+)-2-(9-anthryl)-2-methoxyacetate ((S)-
17): HPLC tR ) 22.00 min (hexanes-ethyl acetate, 85:15, 2 mL/min,
µ-porasil); [R] ) +54.2 (c ) 0.0145, CHCl3); 1H NMR (500.13 MHz,
CDCl3) δ (ppm) 1.37 (s, 9H), 1.65 (m, 1H), 2.11 (m, 1H), 3.49 (s,
3H), 3.75 (br, 1H), 3.81 (dd, J ) 3.4, 11.3 Hz, 1H), 3.95 (m, 1H), 4.18
(m, 1H), 6.25 (d, J ) 7.0 Hz, 2H), 6.37 (s, 1H), 6.89 (t, J ) 7.6 Hz,
2H), 7.00 (t, J ) 7.4 Hz, 1H), 7.51 (m, 2H), 7.60 (m, 2H), 8.05 (d, J
) 8.4 Hz, 2H), 8.52 (s, 1H), 8.64 (d, J ) 8.7 Hz, 2H); 13C NMR (62.97
MHz, CDCl3) δ (ppm) 28.2, 36.9, 50.3, 57.6, 64.9, 77.3, 79.5, 124.4,
125.2, 126.3, 126.8, 127.3, 128.2, 128.8, 129.4, 129.5, 130.5, 131.6,
136.7, 154.9, 170.7; UV λmax 262 nm (CHCl3); MS (EI) m/z 499 (M+);
HRMS (EI) C31H33O5N found 499.23574, calcd 499.23587, ∆m 0.13
mu.
(R)-γ-Hydroxymethyl-γ-butyrolactone (R)-(-)-2-(9-anthryl)-2-
methoxyacetate ((R)-18): HPLC tR ) 22.50 min (hexanes-ethyl
acetate, 40:60, 1 mL/min, Spherisorb S5W 5µm); [R] ) -93.0 (c )
1
0.0145, CHCl3); H NMR (500.13 MHz, CDCl3) δ (ppm) 0.89 (m,
1H), 1.15 (m, 1H), 1.62 (m, 1H), 1.79 (m, 1H), 3.38 (s, 3H), 4.00 (dd,
J ) 3.1, 12.2 Hz, 1H), 4.19 (dd, J ) 2.9, 12.2 Hz, 1H), 4.39 (m, 1H),
6.25 (s, 1H), 7.42 (m, 2H), 7.50 (m, 2H), 7.96 (d, J ) 8.3 Hz, 2H),
8.43 (s, 1H), 8.45 (d, J ) 9.0 Hz, 2H); 13C NMR (75.47 MHz, CDCl3)

4750 J. Am. Chem. Soc., Vol. 120, No. 19, 1998
LatypoV et al.
2H); 13C NMR (62.97 MHz, CDCl3) δ (ppm) 56.2, 57.5, 58.5, 64.6,
77.0, 124.3, 125.1, 125.6, 126.7, 126.9, 128.3, 128.4, 129.2, 129.5,
130.6, 131.5, 136.0, 171.2; UV λmax 260 nm (CHCl3); MS (EI) m/z
398 (M+); HRMS (EI) C26H22O4 found 398.15222, calcd 398.15185,
∆m 0.37 mu. Anal. Calcd for C26H22O4: C, 78.36; H, 5.57. Found:
C, 78.61; H, 5.24.
131.5, 171.3; UV λmax 264 nm (CHCl3); MS (EI) m/z 508 (M+); HRMS
(EI) C29H32O8 found 508.20996, calcd 508.20971, ∆m -0.25 mu.
(S)-(-)-2-Methylbutyl (R)-(-)-2-methoxy-2-phenylacetate ((R)-
24): HPLC tR ) 21.45 min (hexanes-ethyl acetate, 96:4, 2 mL/min,
1
Spherisorb S5W 5µm); [R] ) -68.2 (c ) 0.009, EtOH); H NMR
(500.13 MHz, CDCl3) δ (ppm) 0.82 (m, 6H), 1.09 (m, 1H), 1.30 (m,
(2R,3R)-trans-3-Phenyloxirane-2-methyl (S)-(+)-2-(9-anthryl)-2-
methoxyacetate ((S)-21): HPLC tR ) 11.62 min (hexanes-ethyl
acetate, 75:25, 2 mL/min, µ-porasil); [R] ) +85.7 (c ) 0.015, EtOH);
1H NMR (500.13 MHz, CDCl3) δ (ppm) 2.98 (m, 1H), 3.18 (d, J )
2.2 Hz, 1H), 3.36 (s, 3H), 4.04 (dd, J ) 4.2, 12.5 Hz, 2H), 4.37 (dd,
J ) 3.2, 12.5 Hz, 1H), 6.27 (s, 1H), 6.80 (m, 2H), 7.16 (m, 3H), 7.40
(m, 2H), 7.47 (m, 2H), 7.95 (d, J ) 8.4 Hz, 2H), 8.42 (s, 1H), 8.50 (d,
J ) 8.9 Hz, 2H); 13C NMR (75.47 MHz, CDCl3) δ (ppm) 55.7, 57.5,
58.8, 63.5, 77.0, 124.3, 125.0, 125.5, 126.7, 126.8, 128.3, 128.4, 129.2,
129.5, 130.5, 131.5, 135.9, 171.0; UV λmax 260 nm (CHCl3); MS (EI)
m/z 398 (M+); HRMS (EI) C26H22O4 found 398.15185, calcd 398.15185,
∆m 0.00 mu.
1H), 1.66 (m, 1H), 3.42 (s, 3H), 3.96 (m, 2H), 4.77 (s, 1H), 7.37 (m,
3H), 7.45 (m, 2H); H NMR (500.13 MHz, CS2 + CD2Cl2 (4:1)) δ
1
(ppm) 0.78 (d, J ) 6.8 Hz, 3H), 0.83 (t, J ) 7.5 Hz, 3H), 1.08 (m,
1H), 1.28 (m, 1H), 1.59 (m, 1H), 3.32 (s, 3H), 3.80 (dd, J ) 6.6, 10.7
Hz, 1H), 3.90 (dd, J ) 6.0, 10.7 Hz, 1H), 4.62 (s, 1H), 7.20-7.32 (m,
5H); 13C NMR (62.97 MHz, CDCl3) δ (ppm) 10.9, 16.0, 25.8, 34.0,
57.3, 69.6, 82.7, 127.2, 128.6, 128.7, 136.5, 170.9; UV λmax 242 nm
(CHCl3); MS (EI) m/z 236 (M+); HRMS (EI) C14H20O3 found
236.14125, calcd 236.14125, ∆m 0.00 mu. Anal. Calcd for
C14H20O3: C, 71.16; H, 8.53. Found: C, 71.50; H, 8.25.
(S)-(-)-2-Methylbutyl (S)-(+)-2-methoxy-2-phenylacetate ((S)-
24): HPLC tR ) 21.57 min (hexanes-ethyl acetate, 96:4, 2 mL/min,
(-)-Isolongifolyl (R)-(-)-2-(9-anthryl)-2-methoxyacetate ((R)-22):
HPLC tR ) 20.77 min (hexanes-ethyl acetate, 93:7, 2 mL/min,
1
Spherisorb S5W 5µm); [R] ) +72.0 (c ) 0.028, EtOH); H NMR
(500.13 MHz, CDCl3) δ (ppm) 0.81 (m, 6H), 1.07 (m, 1H), 1.28 (m,
1
Spherisorb S5W 5µm); [R] ) -75.4 (c ) 0.016, EtOH); H NMR
1H), 1.64 (m, 1H), 3.42 (s, 3H), 3.95 (m, 2H), 4.76 (s, 1H), 7.35 (m,
(500.13 MHz, CDCl3) δ (ppm) 0.13 (s, 3H), 0.55 (m, 1H), 0.61 (s,
3H), 0.72 (m, 1H), 0.82 (s, 3H), 1.1 (m, 6H), 1.32 (m, 2H), 1.63 (br,
1H), 1.72 (br, 1H), 1.81 (m, 1H), 3.41 (s, 3H), 4.03 (m, 2H), 6.26 (s,
1H), 7.42 (m, 2H), 7.50 (m, 2H), 7.96 (d, J ) 8.3 Hz, 2H), 8.41 (s,
1H), 8.58 (d, J ) 8.9 Hz, 2H); 13C NMR (62.97 MHz, CDCl3) δ (ppm)
21.3, 22.4, 25.7, 29.2, 32.6, 33.0, 39.6, 40.0, 41.1, 43.3, 45.5, 57.4,
61.6, 64.6, 77.1, 124.7, 125.0, 126.4, 127.3, 127.5, 129.1, 130.7, 131.6,
171.1; UV λmax 260 nm (CHCl3); MS (EI) m/z 470 (M+); HRMS (EI)
C32H38O3 found 470.28142, calcd 470.28210, ∆m 0.68 mu. Anal. Calcd
for C32H38O3: C, 81.65; H, 8.14. Found: C, 81.91; H, 8.01.
1
3H), 7.44 (m, 2H); H NMR (500.13 MHz, CS2 + CD2Cl2 (4:1)) δ
(ppm) 0.79 (d, J ) 6.8 Hz, 3H), 0.81 (t, J ) 7.4 Hz, 3H), 1.06 (m,
1H), 1.27 (m, 1H), 1.58 (m, 1H), 3.32 (s, 3H), 3.81 (ddd, J ) 1.3, 6.6,
10.7 Hz, 1H), 3.87 (ddd, J ) 1.0, 5.9, 10.7 Hz, 1H), 4.62 (s, 1H),
7.20-7.32 (m, 5H); 13C NMR (62.97 MHz, CDCl3) δ (ppm) 10.9, 16.0,
25.7, 34.0, 57.2, 69.5, 82.6, 127.1, 128.5, 128.6, 136.5, 170.8; UV λmax
242 nm (CHCl3); MS (EI) m/z 236 (M+); HRMS (EI) C14H20O3 found
236.14120, calcd 236.14125, ∆m -0.05 mu.
(S)-(-)-2-Methylbutyl (R)-(-)-2-methoxy-2-(trifluoromethyl)-2-
phenylacetate ((R)-25): HPLC tR ) 22.79 min (hexanes-ethyl acetate,
96:4, 2 mL/min, Spherisorb S5W 5µm); [R] ) +54.0 (c ) 0.03,
CHCl3); 1H NMR (500.13 MHz, CS2 + CD2Cl2 (4:1)) δ (ppm) 0.89 (t,
J ) 7.4 Hz, 3H), 0.91 (d, J ) 6.7 Hz, 3H), 1.17 (m, 1H), 1.37 (m,
1H), 1.72 (m, 1H), 3.47 (s, 3H), 4.07 (d, J ) 6.1 Hz, 2H), 7.30-7.42
(m, 5H); 13C NMR (75.47 MHz, CDCl3) δ (ppm) 11.0, 16.3, 25.8,
34.0, 55.4, 70.9, 84.6 (J ) 27.9 Hz), 117.6, 121.4, 125.3, 127.3, 128.4,
129.5, 132.4, 166.7; UV λmax 232 nm (CHCl3); MS (EI) m/z 304 (M+);
HRMS (EI) C15H19O3F3 found 304.12863, calcd 304.12862, ∆m -0.01
mu. Anal. Calcd for C15H19O3F3: C, 59.2; H, 6.29. Found: C, 59.47;
H, 6.56.
(-)-Isolongifolyl (S)-(+)-2-(9-anthryl)-2-methoxyacetate ((S)-22):
HPLC tR ) 21.77 min (hexanes-ethyl acetate, 93:7, 2 mL/min,
1
Spherisorb S5W 5µm); [R] ) +14.2 (c ) 0.023, EtOH); H NMR
(500.13 MHz, CDCl3) δ (ppm) 0.31 (s, 3H), 0.38 (m, 1H), 0.38 (s,
3H), 0.55 (m, 1H), 0.65 (s, 3H), 0.70 (m, 2H), 0.87 (m, 5H), 1.01 (m,
1H), 1.16 (m, 2H), 1.51 (m, 2H), 3.29 (s, 3H), 3.73 (dd, J ) 7.6, 10.9
Hz, 1H), 4.12 (dd, J ) 8.1, 10.8 Hz, 1H), 6.12 (s, 1H), 7.29 (m, 2H),
7.37 (m, 2H), 7.83 (d, J ) 8.5 Hz, 2H), 8.28 (s, 1H), 8.43 (d, J ) 8.8
Hz, 2H); 13C NMR (75.47 MHz, CDCl3) δ (ppm) 21.2, 22.2, 25.6,
29.1, 32.5, 32.9, 39.4, 39.8, 40.9, 43.1, 45.3, 45.4, 57.3, 61.4, 64.5,
77.3, 124.5, 124.8, 126.3, 127.3, 128.9, 130.4, 131.4, 170.9; UV λmax
260 nm (CHCl3); MS (EI) m/z 470 (M+); HRMS (EI) C32H38O3 found
470.28230, calcd 470.28210, ∆m -0.20 mu.
(S)-(-)-2-methylbutyl (S)-(+)-2-methoxy-2-(trifluoromethyl)-2-
phenylacetate ((S)-25): HPLC tR ) 21.57 min (hexanes-ethyl acetate,
96:4, 2 mL/min, Spherisorb S5W 5µm); [R] ) -43.0 (c ) 0.035,
CHCl3); 1H NMR (500.13 MHz, CS2 + CD2Cl2 (4:1)) δ (ppm) 0.89 (t,
J ) 7.5 Hz, 3H), 0.90 (d, J ) 6.8 Hz, 3H), 1.18 (m, 1H), 1.39 (m,
1H), 1.71 (m, 1H), 3.47 (s, 3H), 4.00 (dd, J ) 6.6, 10.7 Hz, 1H), 4.15
(dd, J ) 5.7, 10.7 Hz, 1H), 7.30-7.42 (m, 5H); 13C NMR (75.47 MHz,
CDCl3) δ (ppm) 11.0, 16.2, 25.8, 33.9, 55.4, 70.9, 84.6 (J ) 27.9 Hz),
117.6, 121.4, 125.3, 127.3, 128.3, 129.5, 132.4, 166.6; UV λmax 232
nm (CHCl3); MS (EI) m/z 304 (M+); HRMS (EI) C15H19O3F3 found
304.12868, calcd 304.12862, ∆m -0.06 mu.
1,2:3,4-Di-O,O′,O′′,O′′′-isopropylidene-r-D-galactopyranosyl (R)-
(-)-2-(9-anthryl)-2-methoxyacetate ((R)-23): HPLC tR ) 39.69 min
(hexanes-ethyl acetate, 85:15, 2 mL/min, Spherisorb S5W 5µm); [R]
) -133.0 (c ) 0.008, CHCl3); 1H NMR (500.13 MHz, CDCl3) δ (ppm)
1.06 (s, 3H), 1.13 (s, 3H), 1.24 (s, 3H), 1.35 (s, 3H), 3.43 (s, 3H), 3.65
(dq, J ) 1.9, 4.1 Hz, 1H), 3.77 (dd, J ) 1.9, 7.9 Hz, 1H), 4.06 (dd, J
) 4.1, 11.6 Hz, 1H), 4.18 (dd, J ) 2.5, 4.9 Hz, 1H), 4.34 (dd, J ) 7.7,
11.6 Hz, 1H), 4.39 (dd, J ) 2.5, 7.9 Hz, 1H), 5.42 (d, J ) 4.9 Hz,
1H), 6.32 (s, 1H), 7.46 (m, 2H), 7.54 (m, 2H), 8.00 (d, J ) 7.1 Hz,
2H), 8.46 (s, 1H), 8.69 (d, J ) 8.9 Hz, 2H); 13C NMR (62.97 MHz,
CDCl3) δ (ppm) 24.1, 24.9, 25.6, 25.8, 57.6, 64.4, 66.0, 70.4, 70.5,
70.8, 77.4, 96.0, 108.6, 109.5, 124.8, 125.0, 126.5, 129.0, 129.2, 130.6,
131.5, 171.0; UV λmax 264 nm (CHCl3); MS (EI) m/z 508 (M+); HRMS
(EI) C29H32O8 found 508.21007, calcd 508.20971 ∆m -0.36 mu. Anal.
Calcd for C29H32O8: C, 68.49; H, 6.34. Found: C, 68.73; H, 6.27.
1,2:3,4-Di-O,O′,O′′,O′′′-isopropylidene-R-D-galactopyranosyl (S)-
(+)-2-(9-anthryl)-2-methoxyacetate ((S)-23): HPLC tR ) 34.41 min
(hexanes-ethyl acetate, 85:15, 2 mL/min, Spherisorb S5W 5µm); [R]
) +77.2 (c ) 0.012, CHCl3); 1H NMR (500.13 MHz, CDCl3) δ (ppm)
0.99 (s, 3H), 1.19 (s, 3H), 1.22 (s, 3H), 1.27 (s, 3H), 3.09 (d, J ) 7.9
Hz, 1H), 3.42 (s, 3H), 3.63 (dt, J ) 1.6, 6.8 Hz, 1H), 3.97 (dd, J )
7.0, 10.9 Hz, 1H), 4.07 (dd, J ) 2.3, 4.9 Hz, 1H), 4.11 (dd, J ) 2.3,
7.9 Hz, 1H), 4.24 (dd, J ) 6.7, 10.9 Hz, 1H), 5.28 (d, J ) 4.9 Hz,
1H), 6.24 (s, 1H), 7.42 (m, 2H), 7.48 (m, 2H), 7.96 (d, J ) 7.7 Hz,
2H), 8.42 (s, 1H), 8.50 (d, J ) 8.9 Hz, 2H); 13C NMR (62.97 MHz,
CDCl3) δ (ppm) 23.7, 24.8, 25.6, 25.8, 57.6, 63.0, 64.5, 69.8, 70.2,
70.4, 77.1, 96.0, 108.5, 109.0, 124.4, 125.1, 126.7, 129.1, 129.2, 130.6,
D-r,â-Isopropylidenegliceryl (R)-(-)-2-methoxy-2-phenylacetate
((R)-26): HPLC tR ) 18.15 min (hexanes-ethyl acetate, 75:25, 2 mL/
1
min, Spherisorb S5W 5µm); [R] ) -46.0 (c ) 0.0075, EtOH); H
NMR (250.13 MHz, CDCl3) δ (ppm) 1.28 (s, 3H), 1.32 (s, 3H), 3.37
(s, 3H), 3.53 (dd, J ) 5.6, 8.3 Hz, 1H), 3.88 (dd, J ) 5.8, 8.4 Hz, 1H),
4.16 (m, 3H), 4.77 (s, 1H), 7.29-7.43 (m, 5H); 13C NMR (62.97 MHz,
CDCl3) δ (ppm) 25.3, 26.5, 57.3, 64.7, 66.1, 73.3, 82.5, 110.0, 127.3,
128.7, 128.8, 136.2, 170.5; UV λmax 260 nm (CHCl3); MS (EI) m/z
280 (M+). HRMS (EI) C15H20O5 found 280.13101, calcd 280.13101,
∆m 0.00 mu. Anal. Calcd for C15H20O5: C, 64.27; H, 7.19. Found:
C, 64.53; H, 7.02.
D-r,â-Isopropylidenegliceryl (S)-(+)-2-methoxy-2-phenylacetate
((S)-26): HPLC tR ) 18.47 min (hexanes-ethyl acetate, 75:25, 2 mL/
min, Spherisorb S5W 5µm); [R] ) +67.0 (c ) 0.06, EtOH); 1H NMR
(250.13 MHz, CDCl3) δ (ppm) 1.31 (s, 3H), 1.34 (s, 3H), 3.39 (s, 3H),
3.60 (m, 1H), 3.93 (m, 1H), 4.1 (m, 1H), 4.21 (m, 2H), 4.79 (s, 1H),
7.34 (m, 3H), 7.43 (m, 2H); 13C NMR (62.97 MHz, CDCl3) δ (ppm)
25.2, 26.4, 57.2, 65.0, 66.1, 73.1, 82.3, 109.7, 127.1, 128.6, 128.8, 136.0,

Configuration of â-Chiral Primary Alcohols
J. Am. Chem. Soc., Vol. 120, No. 19, 1998 4751
170.5; UV λmax 260 nm (CHCl3); MS (EI) m/z 280 (M+); HRMS (EI)
C15H20O5 found 280.13103, calcd 280.13101, ∆m -0.02 mu.
D-r,â-Isopropylidenegliceryl (R)-(-)-2-methoxy-2-(trifluorom-
ethyl)-2-phenylacetate ((R)-27): HPLC tR ) 11.32 min (hexanes-
ethyl acetate, 85:15, 2 mL/min, Spherisorb S5W 5µm); [R] ) +36.0
1H), 3.39 (s, 3H), 3.53 (s, 3H), 4.23 (m, 2H), 4.74 (s, 1H), 7.30-7.42
(m, 5H); 13C NMR (75.47 MHz, CDCl3) δ (ppm) 13.5, 38.7, 51.6,
57.2, 65.8, 82.2, 127.0, 128.4, 128.6, 136.0, 170.2, 173.7; UV λmax
236 nm (CHCl3); MS (EI) m/z 266 (M+); HRMS (EI) C14H18O5 found
266.11543, calcd 266.11542, ∆m -0.01 mu.
(-)-Methyl D-â-hydroxyisobutyrate (R)-(-)-2-methoxy-2-(tri-
fluoromethyl)-2-phenylacetate ((R)-29): HPLC tR ) 16.10 min
(hexanes-ethyl acetate, 85:15, 2 mL/min, Spherisorb S5W 5µm); [R]
) +23.5 (c ) 0.0165, CHCl3); 1H NMR (300.13 MHz, CDCl3) δ (ppm)
1.21 (d, J ) 7.2 Hz, 3H), 2.87 (m, 1H), 3.52 (s, 3H), 3.63 (s, 3H),
4.43 (m, 2H), 7.37-7.51 (m, 5H); 13C NMR (75.47 MHz, CDCl3) δ
(ppm) 13.7, 38.7, 51.9, 55.4, 67.3, 84.5 (J ) 27.9 Hz), 117.4, 121.3,
125.1, 127.3, 128.4, 129.6, 132.1, 166.3, 173.6; UV λmax 232 nm
(CHCl3); MS (EI) m/z 334 (M+); HRMS (EI) C15H17O5F3 found
334.10270, calcd 334.10280, ∆m 0.10 mu. Anal. Calcd for
C15H17O5F3: C, 53.89; H, 5.13. Found: C, 54.11; H, 5.45.
1
(c ) 0.0045, CHCl3); H NMR (300.13 MHz, CDCl3) δ (ppm) 1.34
(s, 3H), 1.38 (s, 3H), 3.56 (s, 3H), 3.73 (dd, J ) 5.3, 8.5 Hz, 1H), 4.04
(dd, J ) 6.0, 8.6 Hz, 1H), 4.35 (m, 3H), 7.38-7.55 (m, 5H); 13C NMR
(75.47 MHz, CDCl3) δ (ppm) 25.2, 26.4, 55.5, 66.0, 66.2, 72.9, 84.7
(J ) 27.9 Hz), 109.9, 117.5, 121.3, 125.1, 127.3, 128.4, 129.7, 132.1,
166.4; UV λmax 232 nm (CHCl3); MS (EI) m/z 348 (M+); HRMS (EI)
C16H19O5F3 found 348.11843, calcd 348.11845, ∆m 0.02 mu. Anal.
Calcd for C16H19O5F3: C, 55.17; H, 5.5. Found: C, 55.43; H, 5.28.
D-r,â-Isopropylidenegliceryl (S)-(+)-2-methoxy-2-(trifluorom-
ethyl)-2-phenylacetate ((S)-27): HPLC tR ) 11.64 min (hexanes-
ethyl acetate, 85:15, 2 mL/min, Spherisorb S5W 5µm); [R] ) -37.2
(c ) 0.026, CHCl3); 1H NMR (300.13 MHz, CDCl3) δ (ppm) 1.34 (s,
3H), 1.38 (s, 3H), 3.55 (s, 3H), 3.72 (m, 1H), 4.01 (m, 1H), 4.36 (m,
3H), 7.36-7.55 (m, 5H); 13C NMR (75.47 MHz, CDCl3) δ (ppm) 25.2,
26.4, 57.2, 65.0, 66.1, 72.8, 84. (J ) 27.9 Hz), 109.8, 117.5, 121.3,
125.1, 127.3, 128.4, 129.7, 132.0, 166.3; UV λmax 232 nm (CHCl3);
MS (EI) m/z 348 (M+); HRMS (EI) C16H19O5F3 found 348.11844, calcd
348.11845, ∆m 0.01 mu.
(-)-Methyl D-â-hydroxyisobutyrate (S)-(+)-2-methoxy-2-(tri-
fluoromethyl)-2-phenylacetate ((S)-29): HPLC tR ) 15.81 min
(hexanes-ethyl acetate, 85:15, 2 mL/min, Spherisorb S5W 5µm); [R]
) -41.0 (c ) 0.0305, CHCl3); 1H NMR (300.13 MHz, CDCl3) δ (ppm)
1.20 (d, J ) 7.2 Hz, 3H), 2.87 (m, 1H), 3.52 (s, 3H), 3.64 (s, 3H),
4.38 (dd, J ) 5.6, 10.9 Hz, 1H), 4.49 (dd, J ) 7.0, 10.8 Hz, 1H),
7.37-7.52 (m, 5H); 13C NMR (75.47 MHz, CDCl3) δ (ppm) 13.6, 38.7,
51.9, 55.3, 67.3, 84.6 (J ) 27.9 Hz), 84.8, 117.5, 121.3, 125.1, 127.3,
128.4, 129.6, 132.0, 166.2, 173.5; UV λmax 232 nm (CHCl3); MS (EI)
m/z 334 (M+); HRMS (EI) C15H17O5F3 found 334.10235, calcd
334.10280, ∆m 0.45 mu.
(-)-Methyl D-â-hydroxyisobutyrate (R)-(-)-2-methoxy-2-phe-
nylacetate ((R)-28): HPLC tR ) 29.03 min (hexanes-ethyl acetate,
1
85:15, 2 mL/min, µ-porasil); [R] ) -67.3 (c ) 0.0485, CHCl3); H
NMR (300.13 MHz, CDCl3) δ (ppm) 1.07 (d, J ) 7.2 Hz, 3H), 2.75
(m, 1H), 3.39 (s, 3H), 3.57 (s, 3H), 4.17 (dd, J ) 5.7, 10.9 Hz, 1H),
4.28 (dd, J ) 7.3, 10.8 Hz, 1H), 4.74 (s, 1H), 7.28-7.42 (m, 5H); 13
C
Acknowledgment. This work was financially supported by
grants from the CICYT (MAR95-1-33-CO2-O2 and PM95-
0135) and from the Xunta de Galicia (XUGA-20901B95 and
XUGA-20910B96). S.K.L. acknowledges the Spanish Ministry
for Education and Science for a postdoctoral research grant.
M.J.F. thanks the Xunta de Galicia and Fundacio´n “Gil Da´vila”
for a grant.
NMR (75.47 MHz, CDCl3) δ (ppm) 13.3, 38.7, 51.6, 57.1, 65.8, 82.2,
126.9, 128.4, 128.5, 136.0, 170.1, 173.6; UV λmax 236 nm (CHCl3);
MS (EI) m/z 266 (M+); HRMS (EI) C14H18O5 found 266.11541, calcd
266.11542, ∆m 0.01 mu. Anal. Calcd for C14H18O5: C, 63.15; H,
6.81. Found: C, 63.43; H, 6.49.
(-)-Methyl D-â-hydroxyisobutyrate (S)-(+)-2-methoxy-2-phenyl-
acetate ((S)-28): HPLC tR ) 19.9 min (hexanes-ethyl acetate, 85:15,
1
3 mL/min, µ-porasil); [R] ) +30.5 (c ) 0.0415, CHCl3); H NMR
(300.13 MHz, CDCl3) δ (ppm) 1.09 (d, J ) 7.2 Hz, 3H), 2.71 (m,
JA972550B