Rapid determination of enantiomeric excess of α-chiral aldehydes using circular dichroism spectroscopy

Article abstract of DOI:10.1016/j.tet.2013.11.086

A method for enantiodiscrimination of α-chiral aldehydes is reported. The method utilizes circular dichroism (CD) spectroscopy and a sensing ensemble composed of 2-(1-methylhydrazinyl) pyridine (1) and Fe(II)(TfO)₂. Aldehydes react rapidly with hydrazine (1) to form chiral imines, which form complexes with Fe(II). By monitoring the CD bands above 320 nm, one can determine the enantiomeric excess (ee) values of α-chiral aldehydes with an average absolute error of ±5%. The analysis was fast, and thus can have potential applications in high-throughput screening (HTS) of catalytic asymmetric induction.

Full text of DOI:10.1016/j.tet.2013.11.086

Tetrahedron 70 (2014) 1357e1362
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Rapid determination of enantiomeric excess of
using circular dichroism spectroscopy
a
-chiral aldehydes
,
,
Sanmitra Barman a y, Eric V. Anslyn b
*
a University of Texas at Austin, Austin, TX 78712, USA
b Department of Chemistry, University of Texas at Austin, Austin, TX 78746, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
A method for enantiodiscrimination of
a
-chiral aldehydes is reported. The method utilizes circular di-
Received 15 September 2013
Received in revised form 21 November 2013
Accepted 25 November 2013
Available online 7 December 2013
chroism (CD) spectroscopy and a sensing ensemble composed of 2-(1-methylhydrazinyl) pyridine (1) and
Fe(II)(TfO)2. Aldehydes react rapidly with hydrazine (1) to form chiral imines, which form complexes
with Fe(II). By monitoring the CD bands above 320 nm, one can determine the enantiomeric excess (ee)
values of
a
-chiral aldehydes with an average absolute error of ꢀ5%. The analysis was fast, and thus can
have potential applications in high-throughput screening (HTS) of catalytic asymmetric induction.
Keywords:
Enantiomeric excess
Ó 2013 Elsevier Ltd. All rights reserved.
Exciton coupled circular dichroism
High-throughput screening
Metal to ligand charge transfer
1. Introduction
groups are exploring optical techniques for the determination of ee
in HTS.8 Moreover, to speed up the analysis time during screening,
Asymmetric synthesis is a well-recognized method for the
synthesis of enantiomerically enriched compounds.1 However, the
process of finding the best catalyst for a particular asymmetric re-
action can be time consuming and depends heavily on trial and
error to find the best catalyst and suitable reaction conditions.
Combinatorial chemistry, combined with parallel synthesis, is an
alternate tool for finding an optimal catalyst and reaction condi-
tions, as this technique can explore a large number of candidates in
a short time span.2 However, the determination of each reaction’s
ee value is a slow process. The most popular techniques to de-
termine the ee of an asymmetric reaction are chromatographic
techniques, such as chiral HPLC and GC.3 Although these techniques
are very accurate, the time required by serial chromatographic
techniques restricts their use in high-throughput screening (HTS).
Although NMR has been implemented in HTS, it also suffers from
being a serial technique.4
optical techniques can be carried out in a microwell plate format. In
recent years, our group and others have focused on developing
assays for determining the ee of chiral molecules containing car-
boxylic acids, ketones, amines, and alcohols by various optical
techniques.9e12
2. Results and discussions
Here, we describe the determination of ee for the
dehydes using CD spectroscopy. No optical methods are reported in
the literature for the determination of the ee of -chiral aldehydes,
in part due to their propensity to racemize. However, -chiral al-
a-chiral al-
a
a
dehydes are building blocks for many pharmaceuticals, hence
creating an assay to determine their handedness could be generally
useful.13 An analyte binding event that would induce CD signals in
wavelengths longer than 320 nm was sought as most organic
functional groups are CD silent in this region.10 This would allow
determination of the ee values of crude reaction mixtures, and
hence, can make this technique rapid and useful for HTS.
To create an assay for chiral aldehydes, we have combined the
best aspects of two protocols we have previously reported for chiral
amines and ketones.10,11 Both protocols used CD active bands cre-
ated upon metal complexation of imines. For example, with chiral
ketones a condensation with 2-(1-methylhydrazine) pyridine (1)
gave bidentate imines (2), which were then mixed with a chiral
Cu(I) complex giving rise to structures, such as 3 (Scheme 1). These
For HTS of ee values, optical signaling techniques, such as
fluorescence, UVevis spectroscopy, and colorimetric analysis are
well suited due to their speed of analysis compared to chromato-
graphic techniques.5e7 Due to this advantage, many research
* Corresponding author. Tel.: þ1 512 471 0068; fax: þ1 202 513 8667; e-mail
addresses:
sanmitrab@gmail.com
(S.
Barman),
anslyn@austin.utexas.edu
(E.V. Anslyn).
y
Tel.: þ1 785 341 8553.
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.11.086

1358
S. Barman, E.V. Anslyn / Tetrahedron 70 (2014) 1357e1362
O
R
*
N
N
N
or
N
N
R =
NH2
*
R
2
1
N
N
N
-
-
PF6
PF6
R
*
(Ph)2
P
P
(Ph)2
N
N
NCCH3
NCCH3
P
P
CuI
CuI
N
(Ph)2
(Ph)2
R
*
3
Scheme 1. Our previously reported system for chiral ketones: CD active charge-transfer band is present in the receptor and modulated upon binding of the imine.10
structures possess CD active metal to ligand charge transfer (MLCT)
bands, whose intensities can be used to determine the ee of the
chiral ketones. While this method was successful, the detriment
was weak CD signals that were only slightly different for the en-
antiomers of 2. In contrast, a different strategy for chiral amines
gave large CD signals with equal and opposite spectra. This assay
also relies on a condensation to make bidentate imines, but the
electrophilic and nucleophilic partners are exchanged (Scheme 2).
Condensation of chiral amines with aldehyde 4, followed by mixing
the resulting imine with Fe(II) triflate gives the octahedral com-
a range of chemical space representing both aromatic and aliphatic
moieties (Fig. 1). All these chiral aldehydes were synthesized from
their alcohol precursors. After perusal of the literature (SciFinder)
search, we found that 2-phenyl propanol, 2-methoxy-2-phenyl
ethanol, and 2-methyl butanol, are the only chiral alcohols com-
mercially available for oxidation to
a-chiral aldehydes and for
which both the enantiomers are sold. The synthesis scheme in-
volves oxidation to the aldehyde with the mild oxidizing agent
DesMartin Periodinane (Scheme 3).14 Imine bond formations with
pyridine 2-(1-methylhydrazinyl, 1) was completed in 30 min after
2TfO-
R*
OH
O
N
OH
ECCD and
FeII(TfO-)2
CH3CN
CH3CN
N
enantiomeric
excess
R*-NH2
OH
FeII
N
N
determination
N
R*
3
4
5
R* =
Scheme 2. Our previously reported system for chiral amines: exciton coupled circular dichroism (ECCD) spectrum was generated when chiral imine analyte bind to the Fe(II) center,
thereby facilitating the determination of ee of chiral amines.11
plexes represented by 5. Both MLCT and exciton coupled circular
dichroism (ECCD) bands could be used to determine the ee of the
chiral amines.
Herein, we show that by using compound 1 with chiral alde-
hydes, followed by the addition of Fe(II) triflate, we can create
O
O
O
relatively large CD signals for the determination of the ee values of
the chiral aldehydes. The preparatory work for our current ap-
proach is faster than the previous two cases because we demon-
strate that making a very quick and simple derived calibration
curve, consisting of just three points, gives the same ultimate error
in ee values as our previous approaches.10
O
2-phenylpropanal
2-methylbutanal
2-methoxy-2-phenylacetaldehyde
N
N
N
N
N
N
N
N
N
2.1. Choice of chiral aldehydes
O
Because no
synthesized a handful from commercially available chiral alcohols.
The chiral aldehydes 2-phenylpropanal, 2-methoxy-2-
phenylacetaldehyde, and 2-methyl butanal were chosen to span
a-chiral aldehydes are commercially available, we
L1
L2
L3
Fig. 1. Structures of (top) aldehydes studied, and (bottom) L1, L2, and L3 created by
reaction with 2-(1-methylhydrazinyl) pyridine (1).

S. Barman, E.V. Anslyn / Tetrahedron 70 (2014) 1357e1362
1359
NH2
N
Des-Martin
periodinane
R1
R2
O
O
R1
R2
4 Å MS
N
R2
N
N
N
N
N
N
CH2Cl2
25 °C, 1 h
CH3CN
0.5 h, 25 °C
R1
R1
R2
E
Z (not observed)
(R)
(S)
(R)
(S)
Racemic
Racemic
(ee was determined
from NMR titration
Analyte L1, R1 = Ph, R2 = CH3, ee = 74% (R), and 80% (S)
Analyte L2, R1 = Ph, R2 = OCH3, ee = 95% or more (R), and 95% or more (S)
Analyte L3, R1 = CH2CH3, R2 = CH3, ee = 95% or more (R), and 95% or more (S)
with chiral Yb complex)
Scheme 3. Synthesis of the imine derivatives of a
-chiral aldehydes (no Z isomer was observed in the 1H NMR spectrum).
the addition of 4 A molecular sieves. The 1H NMR spectra for the
derivatized analytes (L1, L2, and L3) showed essentially only one
diastereomer, with the hydrazone linkage in a Z-form, and the
imine being the E isomer. These conformational preferences likely
result due to the minimization of steric interactions. Complexation
of the bidentate imines (L1eL3) with Fe(II) was performed in
acetonitrile, resulting in complexes represented by 6 (Scheme 4).
saturation.10 As long as the assays are performed above saturation,
the ee calibration curve developed at a single concentration can be
used to determine the unknown’s ee at any concentration. Satura-
tion also generates the maximum signal-to-noise ratio and mini-
mizes the contributions of 1:1 and 1:2 metal:analyte species,
thereby simplifying the stereochemical interpretation of the CD
data. As previously reported from our group for the determination of
the ee of chiral amines (Scheme 2), we find saturation at 3 equiv
analyte (L1, L2 or L3) to 1 equiv of Fe(II) (Fig. 2).11 Analyte L2 does not
show as clear an end point as that for L1 and L3. This can be at-
tributed to a lower affinity of L2 for Fe(II), which is possibly due to
increased strain in the 1:3 (metal:analyte) complex as a result of the
larger methoxy group compared to methyl in L1 and L3, re-
spectively. As previously observed,11 the binding curves have sig-
moidal shapes, reflecting the 1:3 stoichiometry of the system.
ꢀ
2TfO-
N
FeII(TfO-)2
N
N
N
FeII
N
CH3CN
N
R*
R*
3
6
L1-L3
Scheme 4. Complexation of the imine derivative with FeII(TfOꢁ
)
in acetonitrile.
2.3. Stereoisomerism
2
The dominant species in solution with an Fe(II) to imine stoi-
chiometry of 1:3 is an octahedral complex, which can exist in two
2.2. Determining saturation via UVevis titrations
helical isomers (
D and L) and two configurational isomers (fac and
UVevis titrations were performed to determine the equivalents
of analytes L1, L2, and L3 to Fe(II) required to reach signal saturation
(Fig. 2). The determination of the equivalents to reach saturation is
important as it allows one to create concentration independent
calibration curves for enantiomeric excess at concentrations beyond
mer) (Fig. 3). Hence for an enantiomerically pure aldehyde sample,
N
N
RR/RS
N
RS/RR
N
N
N
N
N
FeII
FeII
N
RR/RS
N
RR/RS
N
N
N
N
N
N
RS/RR
RR/R
SN
N
Δ
Λ
fac
RS/RR
RR/RS
N
N
RR/RS
RS/RR
N
N
N
N
N
N
N
N
N
FeII
FeII
N
RR/RS
N
RR/RS
N
N
N
N
N
Λ
Δ
Fig. 2. Changes in absorption as a function of the number of equivalents of imine ti-
trated into an acetonitrile solution of 1 mM Fe(II) at 334, 330, and 345 nm for L1, L2,
and L3, respectively. The number of equivalents is defined as the concentration of
imine divided by the concentration of Fe(II).
mer
Fig. 3.
D and L stereoisomers of the fac and the mer configurational isomers with
enantiomerically pure imines.

1360
S. Barman, E.V. Anslyn / Tetrahedron 70 (2014) 1357e1362
four possible stereoisomers exist in solution. For aldehydes that are
not enantiomerically pure, there are eight possible stereoisomers
for the fac isomer and 16 possible isomers for the mer isomer, giving
a total of 24 possible stereoisomers (see Supplementary data for all
the isomeric forms). Complexity may arise while determining the
ee of chiral aldehydes when a mixture of R and S isomers were
added to a solution of Fe(II) due to the formation of this large
number of stereoisomers. However, as long as all the isomers are in
equilibria and rapidly exchanging, the CD spectra will be consistent
and indicative of the ee value of the aldehydes.
complexes between chiral imines and Fe(II). The CD spectra were
recorded above saturation after reaching equilibria, and hence are
concentration independent.
For analytes L1 and L3, the first Cotton effect observed at 334
and 345 nm, respectively, are positive for the R isomer and negative
for the S isomer. However, for analyte L2, the sign of the first Cotton
effect at 330 nm is reversed for the R and the S isomers, and the
intensity of the CD signal is much higher than analytes L1 and L3.
The difference of sign of the CD signals for analyte L2 as a function
of R/S nomenclature is attributed simply to the priority of the
groups around the stereocenter. Looking at the chiral center, L2
contains methoxy, phenyl, and hydrogen whereas L1 and L3 con-
tain methyl, phenyl, and hydrogen. Clearly methoxy has higher
priority than phenyl in L2 whereas phenyl and ethyl have higher
priority in L1 and L3, respectively. Hence this phenomenon ex-
plains the difference in sign of the CD signals for the three analytes.
The larger intensity CD signal for analyte L2 compared to L3 can be
attributed to the larger steric interactions from the bulky phenyl
rings of the aldehyde compared to small alkyl groups in analyte L3,
forcing a larger twist and thereby the higher CD signal. However,
the larger intensity CD signal for analyte L2 compared to L1 can be
attributed simply to the higher enantiomeric excess of L2. The
peaks from 330 to 345 nm for all three analytes are attributed to
2.4. Ee determination of the imines with chiral ytterbium tris
[3-(trifluoromethylhydroxymethylene)-(D) camphorate]
complex
As chiral aldehydes are prone to racemize, and the formation of
the imines may lead to racemization, we measured the ee of the
imines with the chiral shift reagent Ytterbium tris[3-(tri-
fluoromethylhydroxymethylene)-(þ) camphorate] via 1H NMR.15
We performed NMR titrations by adding progressively increasing
equivalents of the chiral shift reagent to the chiral imines in CDCl3
and monitored the methyl or the methoxy resonances in analytes
L1, L2, and L3 (Fig. 1). For the racemic imines, we observed two
resonances with equal intensity for the methyl or the methoxy
groups for all three analytes. Whereas for enantio-enriched R and S
isomers, the intensity of the same peaks either varied from 1:1, or
we could only observe one peak for the methyl or the methoxy
group, suggesting that the enantiomeric excess to be more than
95%. For analyte L1, the ee of the R and the S isomers were 74 and
80%, respectively, whereas for analytes L2 and L3; the ee were
found to be ꢂ95% for both the R and the S isomers.
a single strong electric-dipole-allowed
pep* transition, localized
on the 2-iminopyridine chromophore and directed approximately
along the bond between the imine and 2-pyridine carbon atoms
after complexation (Fig. 3).11
2.6. Building a calibration curve for the ee determination of
unknown a-chiral aldehydes
To demonstrate the assay’s ability to determine the ee values of
unknown samples, a calibration curve was generated by plotting the
molar ellipticities at 334, 330, and 345 nm for analytes L1, L2, and L3,
respectively, versus the ee for each of these analytes. Obviously, the
racemic sample showed zero molar ellipticity and ee. Using only
three values for each analyte found by the NMR chiral shift analysis
and CD analysis, we generated calibration curves for each of the
aldehydes (Fig. 5). Unknown samples were prepared for the three
aldehydes by varying the enantiomeric excess at concentrations
above saturation. Errors were calculated for each sample by taking
the absolute difference between the actual and the experimentally
determined ee. The average absolute error for the assay was calcu-
lated and determined to be ꢀ5% for all the aldehydes. In the present
2.5. CD analysis stereoisomerism
All the Fe(II) octahedral complexes showed CD spectra, with the
R and the S isomers of the original aldehydes giving mirror image
spectra (Fig. 4). We postulated that the appearance of the CD signal
in the imine-Fe(II) complex is due to the helical twist imparted by
the three imine ligands in the octahedral geometry. No CD signals
are observed at wavelengths longer than 290 nm for the enantio
enriched alcohols or aldehydes, nor any signal at wavelengths
longer than 300 nm were observed for the imines alone. Hence, any
signal observed above 300 nm is produced by the formation of the
Fig. 5. Calibration curve for analytes L1, L2, and L3. Molar ellipticities for L1, L2, and L3
at 334, 330 and 345 nm, respectively, from Fig. 4, versus enantiomeric excess values as
determined from 1H NMR titrations.
Fig. 4. CD spectra for analytes L1, L2, and L3 (each 0.6 mM) in acetonitrile with 0.2 mM
Fe(II) in a 0.1 cm quartz cell from 200 to 600 nm.

S. Barman, E.V. Anslyn / Tetrahedron 70 (2014) 1357e1362
1361
scenario, the total time required to analyze the ee of 96 samples of
3.3. General procedure for the synthesis of imines
a particular aldehyde is not more than 1 h considering the de-
rivatization, then complexation, followed by CD analysis. However,
one might argue that the present system needs the calibration curve
for each aldehyde takes another 2e3 h. Considering these factors,
we still could analyze nearly 2400 samples of a particular aldehyde
sample in 24 h, and hence this fits the definition of high-throughput
analysis. Unknown samples containing both very high as well as
verylowchiral puritygenerated an absolute error within limit (ꢀ5%)
as well. Hence, although only three points are used in the calibration
curve, this study shows no loss of accuracy relative to previous
studies. Because the calibration curves are linear, and three points
defines a line, this is not necessarily surprising, but it is gratifying for
the ultimate desire of minimizing the amount of preparatory work
before measuring samples with unknown ee values.
ꢀ
To a 50 mL round bottom flask, charged with 4 A molecular
sieves, pyridine 2(1-methyl hydrazinyl) (1) (1 mmol), R/S/Racemic
aldehyde (1 mmol) and dry acetonitrile (5.0 mL) were added and
stirred under nitrogen for 30 min at room temperature. The reaction
mixture was filtered through Celite and the solvent was removed in
vacuo to afford the analytes L1, L2, and L3 as oil with 70e80% yield.
3.3.1. (E)-1-Methyl-2-(2-phenylpropylidene)-1-(pyridine-2-yl)hydra-
zine (L1). 1H NMR (CDCl3, 400 MHz)
d
ppm: 1.56 (d, J¼4.8 Hz, 3H),
3.42 (s, 3H), 3.79 (m,1H), 6.71 (t, J¼4.2 Hz,1H), 7.02 (d, J¼4.6 Hz,1H),
7.20e7.40 (m, 5H), 7.56e7.60 (m, 2H), 8.18 (d, J¼3.8 Hz,1H). 13C NMR
(CDCl3, 100 MHz)
d ppm: 19.9, 29.1, 44.0, 109.9, 114.8, 126.6, 128.0,
128.8, 137.8, 140.4, 142.0, 146.2, 158.0. HR-MS (MþH)þ1: 240.14952
(calcd), 240.14933 (obsd) (error ꢁ0.8 ppm).
In summary, using commercially available Fe(II)(TfO)2, pyridine
2-(1-methylhydrazinyl), and a fast straight forward condensation
3.3.2. (E)-2-(2-Methoxy-2-phenylethylidene)-1-methyl-1-(pyridine-2-
reactions with the
a-chiral aldehydes, we created an assay for the
yl)hydrazine (L2). 1H NMR (CDCl3, 400 MHz)
d ppm: 3.39 (s, 3H), 3.41
determination of the enantioselectivity of some
a-chiral aldehydes
(s, 3H), 4.84 (d, J¼4.2 Hz, 1H), 6.68 (t, J¼4.0 Hz, 1H), 6.82 (d, J¼4.6 Hz,
using circular dichroism spectroscopy. The speed at which CD
operates is advantageous for high-throughput screening of asym-
metric catalysts/auxiliaries. The calibration curve based upon only
three points was linear, and allowed for determination of the en-
antiomeric excesses of a series of chiral aldehydes. We have dem-
onstrated this system’s ability to differentiate the enantiomers of
1H), 7.24 (m, 1H), 7.32 (m, 5H), 7.49 (m, 3H), 8.10 (d, J¼3.8 Hz, 1H). 13
C
NMR (CDCl3, 100 MHz):
d ppm: 29.8, 57.0, 83.9, 110.0, 115.8, 127.0,
128.0, 129.1, 136.2, 138.0, 140.0, 146.4, 157.9. HR-MS (MþH)þ1
:
256.14444 (calcd), 256.14424 (obsd) (error ꢁ0.76 ppm).
3.3.3. (E)-1-Methyl-2-(2-methylbutylidene)-1-(pyridin-2-yl)hydra-
three derivatized a-chiral aldehydes, determining the enantiomeric
zine (L3). 1H NMR (CDCl3, 400 MHz)
d
ppm: 0.93 (t, J¼4.6 Hz, 3H),
excess of unknown samples with approximately ꢀ5% absolute
1.14 (d, J¼4.2 Hz, 3H), 1.40e1.55 (m, 1H), 1.55e1.62 (m, 1H),
2.30e2.44 (m, 1H), 3.42 (s, 3H), 6.62 (t, J¼3.6 Hz, 1H), 6.81 (d,
J¼3.4 Hz, 1H), 7.42e7.52 (m, 2H), 8.16 (d, J¼1.8 Hz, 1H). 13C NMR
error.
3. Experimental section
(CDCl3, 100 MHz)
d ppm: 11.9, 18.2, 28.0, 29.4, 38.6, 109.9, 114.8,
137.9, 142.8, 146.5, 158.0. HR-MS (MþH)þ: 192.14952 (calcd),
192.14920 (obsd) (error ꢁ1.67 ppm).
3.1. General experimental procedure
All commercially obtained reagents were used as received. A
Varian Mercury 400 MHz, and a Varian Inova 400 MHz spec-
trometer were used to obtain 1H and 13C NMR spectra, which
were referenced using the solvent residual peak. Chemical shifts
are given in parts per million (ppm). Signals are reported as m
(multiplet), s (singlet), d (doublet), t (triplet), q (quartet), br s
(broad singlet), br m (broad multiplet). LCeMS data was recor-
ded on an Agilent 6130 Quadrupole instrument. High resolution
mass spectrometry was performed with a Varian 9.4T QFT-ESI
ICR system. Circular dichroism spectra were obtained on a CD-
Jasco-815 CD spectrophotometer using a temperature control-
ler at 25 ꢃC in a Starna 1 mm quartz cuvette. Syntheses of al-
dehydes from alcohols were carried out by published procedure.
All solvents were removed by rotary evaporation under vacuum
using a standard rotavapor equipped with a dry ice condenser.
All filtrations were performed with a vacuum. Flash chroma-
3.4. General experimental details on ee determination of
imines
In an NMR tube around 10 mg of analyte (L1, L2, and L3) was
dissolved in CDCl3. Then progressively with an increment of 5%,
Ytterbium tris[3-(trifluoromethylhydroxymethylene)-(þ) cam-
phorate] complex was added starting from 5% (wt/wt) up to 150%.
After each addition, the entire solution was sonicated and allowed
to stand for 30 min prior to obtaining 1 H NMR spectra. At 30% (wt/
wt) addition, the 1H NMR peak of the methyl, methoxy and methyl
at the chiral center for analytes L1, L2, and L3, respectively, showed
clear characteristic splitting pattern with 1:1 intensity for racemic
and with various ratios for the R and the S isomers for all the
analytes. The ee for each isomer was determined from the in-
tegration of the methyl peak.
ꢀ
tography was performed using Sorbtech 60 A 230X400 mesh
silica gel.
Acknowledgements
3.2. General procedure for the synthesis of the aldehydes
We gratefully acknowledge the financial support from the Na-
tional Institute of Health (R01 GM077437) and Welch Foundation
(F-1151).
To a 50 mL round bottom flask, chiral alcohol (1 mmol) was
dissolved in 10 mL of dry dichloromethane under nitrogen atmo-
sphere and was cooled to 0 ꢃC. Sodium bicarbonate (1.2 equiv) and
Des-Martin Periodinane (1.2 equiv) were added and the reaction
mixture was allowed to warm to room temperature. The reaction
mixture was stirred for 1 h and was hydrolyzed by the addition of
a 1:1 mixture of Na2S2O3 (satd aqueous) and NaHCO3 (satd aqu-
eous). The aqueous phase was extracted with dichloromethane and
the organic phase was subsequently washed with NaHCO3
(satd aqueous) then dried over anhydrous sodium sulfate. After
removal of the organic solvent under reduced pressure, a colorless
oily pure product was obtained as the product (yield 75e85%).
Supplementary data
Experimental procedures, 1H, 13C NMR, HR-MS, UVevis, and
CD spectral data are available. Supplementary data associated
with this article can be found in the online version, at http://
dx.doi.org/10.1016/j.tet.2013.11.086. These data include MOL files
and InChiKeys of the most important compounds described in
this article.

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E. Chem. Cat. Chem. 2009, 1, 445e448; (c) Truppo, M. D.; Rozzell, J. D.; Moore, J.
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