Assessing chiral self-recognition using chiral stationary phases

Article abstract of DOI:10.1016/j.tet.2011.06.103

Chiral stationary phases were synthesized and their ability to separate racemic precursors from which they were derived was assessed. Taken in conjunction with homochiral recognition previously observed in the solid state, the results of this study reveal

Full text of DOI:10.1016/j.tet.2011.06.103

Tetrahedron 67 (2011) 7143e7147
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Assessing chiral self-recognition using chiral stationary phases
Wonjae Lee c, Seth E. Snyder b, Phillip I. Volkers b, William H. Pirkle b, David A. Engebretson e,
,
William A. Boulanger d, Huei-Shian Lin a, Bin-Syuan Huang a, James R. Careya
*
a Department of Applied Chemistry, National University of Kaohsiung, 700 Kaohsiung University Rd., Kaohsiung 811, Taiwan
b Department of Chemistry, University of Illinois at Urbana Champaign, 601 South Goodwin Avenue, Urbana, IL 61801, United States
c Chosun University, College of Pharmacy, Gwangju 501-759, Republic of Korea
d Obiter Research, Urbana, IL 61801, United States
e Department of Chemistry, Oklahoma City University, Oklahoma City, OK, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Chiral stationary phases were synthesized and their ability to separate racemic precursors from which
they were derived was assessed. Taken in conjunction with homochiral recognition previously observed
Received 16 February 2011
Received in revised form 28 June 2011
Accepted 29 June 2011
in the solid state, the results of this study reveal that a geometrically controlling
pep interaction has
a profound influence on molecular recognition.
Available online 5 July 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Molecular recognition
Homochiral
Chiral stationary phases
Self-assembly
pep Interaction
1. Introduction
In the course of our studies on small-molecule chiral chroma-
tography, we have observed that several of our and related CSPs
derived from amide and ester derivatives of 3,5-dinitrobenzoyl
(DNB) amino acids can effectively separate the racemic precursors
of these CSPs.25,26 In all cases, the enantiomer forming the homo-
chiral diastereomeric complex with the CSP is more retained on the
chromatography column. Furthermore, enantiomerically enriched
samples of the DNB-leucine amides show self-induced chemical shift
nonequivalence.27 Based on these studies, we proposed that a chiral
recognition mechanism exists in solution involving three essential
points of interaction: two hydrogen-bonding interactions and
An important but relatively unexplored area of small-molecule
chiral recognition involves enantioselective self-assembly, often
referred to as self-recognition.1e8 Several important examples of
weak small-molecule chiral self-recognition in solution involving
hydrogen-bonded dimers have been reported.9 For instance, Hara
has shown that an enantioenriched sample of N-acetyl-S-valine
tert-butyl ester exhibits self-induced NMR nonequivalence, the
intensity of the signals is reflective of the enantiomeric ratio in
solution.10 Furthermore, chiral stationary phases (CSPs) derived
from N-acetyl-S-valine tert-butyl ester and several related amino
acid esters were used to show that chiral self-recognition can be
used for chiral chromatographic separations, albeit with weak
enantiodiscrimination.11e13 In contrast to the weak self-association
of small molecules, significant levels of enantioselective self-
assembly have been reported for supramolecular constructs, such
as hydrogen-bonded assemblies,14e19 metal/ligand complexes,20e23
and supramolecular polymers.24 This difference reflects the larger
number of intermolecular interactions composing the supramo-
lecular assemblies relative to the small-molecule complexes.
a controlling multipoint offset
pep interaction between the aro-
matic moieties. Recently, we have provided strong evidence to con-
firm this hypothesis through X-ray crystallographic analysis (Fig.1).28
Significantly, the model not only explains the high level of chiral
self-association but also reveals that the offset pep interaction can
play a prominent role in the chiral recognition of small chiral
molecules. Herein, we explore the chiral self-recognition phe-
nomenon further through chiral chromatographic analysis. The
difference in free energy (DDG) of association between the homo-
chiral complex and the heterochiral complex can be derived simply
from chromatographic separation factors
(a
).3 Hence, chiral
chromatography provides an effective means of studying self-
recognition. Although dual hydrogen bonding drives the
dimerization of ‘like’ molecules, we postulate that the presence of
* Corresponding author. Tel.: þ886 7 591 9778; fax: þ886 7 591 9348; e-mail
address: jcarey@nuk.edu.tw (J.R. Carey).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.06.103

7144
W. Lee et al. / Tetrahedron 67 (2011) 7143e7147
O2N
O2N
O
O
N
H
N
O
O
OEt
O2N
O
O
(CH2)3
Si
N
(CH2)11
N
H
Si
EtO
H
O
O
NO2
(3S, 4R)-CSP 2
(S)-CSP 1
Me
(CH2)3Si
O
Me
O
O
O
Me
Si
Me
O2N
O2N
N
(CH2)11
N
O
N
H
(CH2)3Si
N
H
MeMe
O
O
NO2
NO2
(S)-CSP 4
(S)-CSP 3
O
O
N
O2N
O
O2N
O
N
H
O
H
N
H
NO2
NO2
Fig. 1. X-ray structure of the diethyl amide of DNB leucine. Two hydrogen-bonding
interactions and an offset
( )-6
( )-5
pep
interaction account for the chiral recognition.28
O
the offset
pep interaction orients the molecules and promotes
(CH2)9
O
N
O
O
strong enantioselectivity. The results of these studies have impor-
tant implications for future CSP and catalyst design as the offset
pep interaction is much more general than the p-stacking in-
O2N
(CH2)9
N
H
O2N
N
N
H
NO2
teraction between a
p-acid and a p-base, an interaction designed
NO2
into the majority of selector/substrate complexes.3e5 Moreover, the
results can potentially be applied to rational drug design.
( )-8
( )-7
2. Results and discussion
O
O
O2N
O
N
H
The structures of the CSPs and the racemic analytes used in this
study are shown in Fig. 2. Notably, single enantiomers from the
racemates in Fig. 2 are precursors to the four CSPs shown, requiring
hydrosilyation prior to tethering to the silica support. Preparations
of three commercially available CSPs (1, 2, and 4)29,30 and com-
pounds 5e1031 have been described earlier. The synthesis of
(S)-CSP 3 is shown in Scheme 1. All four CSPs were initially designed
O2N
O
N
H
N
N
NO2
NO2
( )-10
( )-9
Fig. 2. CSPs and racemic analytes utilized in this study.
to separate the enantiomers of p-basic racemic analytes suspected
to interact with the CSPs through a well-established chiral recog-
nition mechanism.31 In each case, the essential functionalities
thought to be responsible for chiral recognition are located
in similar places on the backbone. CSPs 2 and 3, derived from
counterpart (ꢀ)-5, consistent with many of the previous studies
involving -donor/
-acceptor systems.31 This result implicates the
p
p
carbonyl oxygen as a hydrogen bonding acceptor in the chiral
recognition mechanism owing to the increased basicity of the
amide carbonyl oxygen relative to the carbonyl oxygen of the butyl
ester. Furthermore, the DNB tertiary amides (ꢀ)-9 and (ꢀ)-10 give
tert-butyl
b-lactam and 3-caprolactam, respectively, are cyclized
versions of CSPs 1 and 4 and were designed to provide a more
conformationally rigid backbone, thus removing a degree of free-
dom at the stereocenter. Prior studies indicate that CSP 2 and CSP 4
give the highest enantioselectivities for separation of a series of
larger
a
values than the secondary n-butyl amide (ꢀ)-5. In the later
case, an additional hydrogen-bonding interaction from the sec-
ondary amide hydrogen may provide a competing achiral mode of
interaction that increases retention and thus diminishes enantio-
selectivity. The length of the alkyl chains on the N,N-dialkyl amides
also affects enantioselectivity showing a modest increase from the
diethyl amide (ꢀ)-9 to the dipropyl amide (ꢀ)-10 but then de-
creasing as the alkyl chains are lengthened further (data not
shown). Similar effects of the length of alkyl substituents on
enantioselectivity have been noted earlier and attributed to in-
tercalation of these groups between the strands of bonded phase.32
Separations of other racemic DNB amino acids can be accomplished
on all four CSPs.
p-basic racemic analytes including napthylenecarboxamides, nap-
roxen derivatives, and benzodiazepines, while CSP 3 shows the
poorest performance in all cases.25
The four
arating the enantiomers of all of the
study. Chromatographic (HPLC) analysis was performed on each of
the four -acidic CSPs using a mobile phase of 20% 2-propanol in
hexane (flow rate 2 mL/min). Chromatographic separation factors
) for these racemic analytes are displayed in Table 1, with entries
p-acidic CSPs shown in Fig. 2 are also capable of sep-
p-acidic analytes used in this
p
(a
involving chiral self-recognition marked in bold. In all cases, the
enantiomer forming the homochiral adsorbate is the more retained
on the column. The butyl ester of DNB-leucine (ꢀ)-6 shows sig-
Interestingly, the
outperforms the other CSPs for chromatographic resolutions of the
p-acidic racemates shown in Fig. 2, despite typically giving the
3-caprolactam derived (S)-CSP 3 generally
nificantly reduced
a
values relative to its secondary amide

W. Lee et al. / Tetrahedron 67 (2011) 7143e7147
7145
H
N
O
O
O
H2N
b, c, d
H
O
a
N
N
O
11
( )-12
O
O
Me
Si
Me
(CH2)9
O2N
N
(CH2)11
O2N
N
O
e, f
N
N
H
O
H
NO2
NO2
( )-13
(S)-CSP 3
Scheme 1. Synthesis of (S)-CSP 3. Reagents and conditions: (a) Phthalic anhydride, cat.Uncap triethylamine, reflux (b) Sodium hydride, 10-undecenyl mesylate (c) Ethanolic
hydrazine solution, reflux (d) 3,5-Dinitrobenzoyl chloride, triethylamine (e) Resolution on (S)-N-(1-naphthyl)leucine(siloxyundecylester) column (f) Hydrosilylation and bonding to
silica.
substituents on the stereogenic centers. This cross hydrogen bonding
Table 1
is sufficient to explain dimerization of DNB leucine amides in solu-
tion27,34 and in the solid state.28 Furthermore, the offset
pep
Examples of chiral self-recognition of racemic analytes on several amino acid
derived CSPs
interaction between aromatic rings controls enantioselective di-
merization by providing a third point of interaction and orienting the
Analyte
(S)-CSP 1
(3S,4R)-CSP 2
(S)-CSP 3
(S)-CSP 4
a a
,
[
a
]
D
a a
,
[a
]
D
a a
,
[
a
]
D
a a
,
[a]
b
k01
c
b
k01
c
b
k01
c
b
k01
c
molecules with respect toeachother. The offset
pepinteraction is not
D
as geometrically restricted as the -stacking interaction seen in many
p
(ꢀ)-5
(ꢀ)-6
(ꢀ)-7
1.50, 0.96, (S)
1.29, 0.99, (S)
1.88, 1.41,
2.03, 1.33, (S)
1.57, 1.61, (S)
3.73, 1.41,
3.32, 0.66, (S)
1.89, 1.26, (S)
7.11, 1.55,
3.04, 1.37, (S)
2.21, 1.06, (S)
3.72, 1.54,
CSP/analyte interactions, henceproviding a largerdegree of rotational
and translational space for the molecules to move while still main-
taining the essential three points of interaction. These added degrees
of freedom might explain the surprisingly high separation factors of
the racemic DNB analytes on the conformationally rigid and sterically
cumbersome CSP 3.
(3S,4R)
(3S,4R)
(3S,4R)
(3S,4R)
(ꢀ)-8
(ꢀ)-9
(ꢀ)-10
2.48, 2.41, (S)
2.04, 1.38, (S)
2.21, 1.01, (S)
4.03, 3.73, (S)
3.02, 1.61, (S)
3.60, 1.53, (S)
2.54, 2.33, (S)
4.34, 1.00, (S)
4.63, 0.83, (S)
4.05, 2.32, (S)
5.39, 2.01, (S)
6.05, 2.22, (S)
a
Chromatographic separation factor.
Retention factor (see experimental) for the first eluted enantiomer using 20%
b
2-propanol/80% hexane as the mobile phase at a flow rate of 2 mL/min.
3. Conclusion
c
Absolute configuration of the more strongly retained enantiomer.
Entries involving chiral self-recognition are marked in bold.
We have described the chromatographic resolution of a series of
racemic amino acids derivates containing an electron-deficient
aromatic ring. Consistent with results obtained in the solid state,
the results presented here provides evidence suggesting that the
origin of homochiral enantioselective control is determined by
head-to-head dual hydrogen bonding and a geometrically con-
poorest performance for resolution of
striking example in Table 1 involves the resolution of (ꢀ)-7, which
has an value of 7.11 on CSP 3, nearly twice that of CSP 2 and CSP 4.
p A
-basic racemates.25
a
The chiral recognition mechanisms are clearly different in each
case. The large enantioselectivity indicates that the molecular
surfaces of (S)-CSP 3 and (3S,4R)-7 display a high degree of com-
plementarity. Conformational rigidity of a CSP will enhance enan-
tioselectivity when one enantiomer of the analyte closely conforms
to the molecular shape of the CSP. A rigid backbone reduces the
likelihood of multiple conformations contributing to the chiral
recognition process.
trolling offset
pep interaction. Factors, such as rigidity and shape
complementarity also appear to affect the magnitude of enantio-
selective discrimination.
4. Experimental section
4.1. General methods
On the other hand, a rigid CSP will impose severe steric re-
quirements on chiral recognition, particularly when the interacting
surfaces are not well suited to each other. These opposing factors
J values are given in hertz. The various CSPs and racemic analytes
used in this study were previously described unless otherwise
noted.30e34 CSP 1 was obtained from Regis Technologies (Morton
Grove, IL). The 1H NMR spectra were obtained on a Varian XL-200
using tetramethylsilane as an internal reference. Low-resolution
mass spectra were obtained on a Varian MAT CH-5 mass spec-
trometer with 70 eV electron impact ionization. High-resolution
mass spectra were obtained on a Varian 731 mass spectrometer.
Microelemental analyses were performed by the University of Illi-
nois Microanalytical Service. Optical rotations were determined
at room temperature with a Rudolph Autopol III polarimeter and a
1 dm polarimetric cell. Chromatography was performed using
a Rainin HPX solvent delivery system and pressure monitor,
likely explain the disparity between p-basic and p-acidic analytes
on CSP 3. The results presented here suggest that shape comple-
mentarity plays a critical role in self-recognition and, more gener-
ally, in chiral discrimination.
Despite several reports of weak small-molecule self-recognition
through hydrogen-bonded dimers (see Introduction),9 the preference
for the homochiral dimer has not been explained sufficiently. Hara’s
proposed chiral recognition mechanism for self-discrimination of
N-acyl amino acid esters involves two parallel edge-to-edge hydro-
gen-bonding interactions in a head-to-tail approach generating
a anti-b
-sheet-like structure.33 The head-to-tail alignment does not
satisfy the minimized steric repulsion interaction between sub-
stituents on the stereogenic center and hence fails to explain the
stability differences between the diastereomeric complexes. Alter-
natively, a head-to-head approach from cross, dual hydrogen bonding
(Fig. 1) minimizes steric interactions between the two alkyl
a Rheodyne 7125 injector with a 20 ml sample loop, a Milton Roy LDC
Monitor D fixed wavelength detector opening at 254 nm and a Kipp
and Zonen BD 41 recorder. Chromatographic runs were conducted
at ambient temperature with a flow rate of 2 mL/min. The void
volume was determined by using 1,3,5-tert-butylbenzene. The

7146
W. Lee et al. / Tetrahedron 67 (2011) 7143e7147
retention factor (k01) was calculated using the following equation:
k01¼(tnꢁt0)/t0 where tn is the retention time of the analyte and t0
is the retention time of 1,3,5-tert-butylbenzene. The separation
showed (NMR analysis) no remaining vinyl group on the starting
material. The excess of dimethylchlorosilane was removed by dis-
tillation. Residual dimethylchlorosilane was removed by three
successive distillations after the addition of small portions of
dichloromethane. A mixture of 2 mL of dry triethylamine and 3 mL
of absolute ethanol was added to the crude chlorosilane with 15 mL
of dry dichloromethane at 0 ꢂC and the reaction mixture was stirred
for 30 min at room temperature. After concentration of the reaction
mixture, 10 mL of anhydrous diethyl ether was added. The insoluble
triethylamine hydrochloride was removed by filtration, and the
filtrate was evaporated. The crude product was purified on silica gel
factor (a) is a ratio of the retention factors of the two enantiomers.
4.2. Detailed synthetic protocols
4.2.1. (N-3,5-Dinitrobenzoyl)-3-amino-N-10-undecenyl-3-caprolac-
tam (13). Compound 11 was purchased from (Sigma, St. Louis MO),
and 12 was synthesized as described previously.35 Sodium hydride
(60%) dispersion in mineral oil, 506 mg (12.6 mmol), in 50 mL of dry
benzene and 3.8 mL of dry DMSO were stirred with the phthali-
producing pure ethoxysilane oil (762 mg, 86.4%). [
a
]
þ62.90 (c
D
mido-
3
-caprolactam (12) at 60 ꢂC for 20 min. A mixture of 10-
0.97 in CH2Cl2); 1H NMR (CDCl3):
d
0.03 (s, 6H), 0.47e0.60 (m, 2H),
undecenyl mesylate, 3.16 g (12.7 mmol), and tetrabutylammo-
nium bromide, 0.750 g (2.33 mmol), in dry benzene were added to
the reaction mixture at room temperature. After refluxing for 7 h,
the benzene was evaporated the product was diluted with 100 mL
of dichloromethane. After washing with 100 mL (3ꢃ) of water, the
organic layer was dried over MgSO4 and concentrated in vacuo. The
crude product was purified by flash chromatography to afford
3.68 g of pure product. An ethanolic 1 M solution of hydrazine
1.05e1.35 (br s, 16H), 1.12 (t, J¼6.9 Hz, 3H), 1.40e1.65 (m, 2H),
1.80e2.20 (m, 5H), 3.20e3.50 (m, 4H), 3.50e3.70 (m, 1H), 3.60 (q,
J¼7.0 Hz, 2H), 4.83 (dd, J¼10 and 6.4 Hz, 1H), 8.66 (d, J¼6.2 Hz, 1H),
8.90 (d, J¼1.8 Hz, 2H), 9.06 (t, J¼2.1 Hz, 1H); mass spectrum: m/z
(relative intensity) 578 (2.59%), 459 (29.0), 307 (30.8), 195 (51.0),
103 (100), 75 (76.3), 55 (61.6), 44 (96.0); HR-MS (FAB) (found:
[MþH]þ, 578.3137. C28H46N4O7Si requires m/z 578.3136). Chiral
stationary phase (þ)-(S)-N-11-Dimethylethoxyundecyl-(N-3,5-dini-
hydrate (8.8 mL) was added to N-alkylated-
3
-caprolactam, 3.3 g
trobenzoyl)-3-amino-3-caprolactam. The ethoxysilane (762 mg)
(8.0 mmol), suspended in 100 mL of 95% ethanol. After refluxing for
6 h, the solvent was evaporated and the contents were diluted with
dichloromethane. After removal of the insoluble solid by filtration,
from the previous step was added to dichloromethane slurry of
4.4 g of Rexchrom silica (5 mm, 100 A) from Regis Technologies that
had been previously dried by azeotropic water removal with ben-
zene. The resulting slurry was evaporated to dryness under reduced
ꢀ
2.26 g of 3-amino-10-undecenyl-3-caprolactam (crude oil product)
€
was isolated and used without further purification. In the next step,
3,5-dinitrobenzoyl chloride, 2.42 g (9.5 mmol), in 20 mL of dry
dichloromethane was added to a dichloromethane solution (40 mL)
pressure, then mechanically rocked in a Kugelrohr oven under re-
duced pressure (0.3 Torr) at 100 ꢂC for 30 h. The modified silica was
washed with methanol and packed into a 4.6ꢃ250 mm stainless
steel HPLC column by conventional methods. The residual silane
groups were endcapped using 2 mL of hexamethyldisilazane in
50 mL of dichloromethane.
of the 3-amino-10-undecenyl-3-caprolactam, 2.26 g (8.0 mmol),
and triethylamine, 1.5 mL (10.8 mmol), in an ice-bath. The reaction
mixture was stirred at room temperature for 30 min and washed
twice with 40 mL of 2 N NaOH and 50 mL of brine. The organic layer
was dried over MgSO4 and concentrated under reduced pressure.
The crude product was chromatographed on silica gel to afford
(3.6 g, 94%) of the pure product. Rf¼0.3 (hexane/ethyl acetate¼3/1);
Acknowledgements
This work was financially supported by the National Science
Mp: 102e104 ꢂC; 1H NMR (CDCl3):
d 1.20e1.50 (br s,12H),1.40e1.70
Council of Taiwan.
(m, 2H), 1.80e2.30 (m, 7H), 3.05e3.70 (m, 5H), 4.72e4.85 (m, 1H),
4.87e5.07 (m, 2H), 5.70e5.92 (m, 1H), 8.64 (d, J¼6.4 Hz, 1H), 8.99
References and notes
(d, J¼2.4 Hz, 2H), 9.15 (m, 1H); 13C NMR (CDCl3):
d 27.461, 28.171,
1. For excellent reviews on this subject, see: Acc. Chem. Res. 2004, 37, 487e631.
2. Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2001, 40, 3726e3748.
3. Pirkle, W. H.; Pochapsky, T. C. Adv. Chromatogr. 1987, 27, 73e127.
4. Pirkle, W. H.; Pochapsky, T. C. Chem. Rev. 1989, 89, 347e362.
5. Welch, C. J. J. Chromatogr., A 1994, 666, 3e26.
6. Pirkle, W. H.; Snyder, S. E. Org. Lett. 2001, 3, 1821e1823.
7. Snyder, S. E.; Pirkle, W. H. Org. Lett. 2002, 4, 3283e3286.
8. Snyder, S. E.; Carey, J. R.; Pirkle, W. H. Tetrahedron 2005, 61, 7562e7567.
9. (a) Alkorta, I.; Elguero, J. J. Am. Chem. Soc. 2002, 124, 1488e1493; (b) Matsu-
zawa, A.; Nojiri, A.; Kumagai, N.; Shibasaki, M. Chem.dEur. J. 2010, 16,
5036e5042.
28.346, 28.544, 29.460, 29.636, 29.941, 29.956, 30.025, 32.147,
32.344, 49.463, 49.783, 53.805, 114.720, 121.462, 127.831, 138.446,
139.736, 149.214, 161.929, 172.613; nmax/cmꢁ1 (KBr): 3257.57
(NeH), 3080.26 (C]C), 2926.85 (C]C arom.), 2853.75 (NO2), 2854
(C]O),1627.67 (meta-benzene),1659 (NO2 arom.),1300.21,1265.25
(NO2); mass spectrum: m/z (relative intensity) 474 (55.9%), 307
(73.7), 195 (98.8), 149 (49.1), 97 (70.2), 55 (98,8), 41 (100); (found:
C, 60.66; H, 7.22. C24H34N4O6 requires: C, 60.74; H, 7.22).
10. Dobashi, A.; Saito, N.; Motoyama, Y.; Hara, S. J. Am. Chem. Soc.1986,108, 307e308.
11. Dobashi, A.; Hara, S. Anal. Chem. 1983, 55, 1805e1806.
12. Dobashi, A.; Oka, K.; Hara, S. J. Am. Chem. Soc. 1980, 102, 7122e7123.
13. Hara, S.; Dobashi, A. J. Liq. Chromatogr. 1979, 2, 883e889.
14. Russell, K. C.; Lehn, J. M.; Kyritsakas, N.; DeCian, A.; Fischer, J. New J. Chem. 1998,
22, 123e128.
15. Prins, L. J.; Huskens, J.; De Jong, F.; Timmerman, P.; Reinhoudt, D. N. Nature
1999, 398, 498e502.
16. Shi, X.; Fettinger, J. C.; Cai, M.; Davis, J. T. Angew. Chem., Int. Ed. 2000, 39,
3124e3127.
4.2.2. (þ)-(S)-(N-3,5-Dinitrobenzoyl)-3-amino-N-10-undecenyl-
3-
caprolactam ((S)-13). Enantiomerically pure samples of 13 were
obtained by preparative medium pressure liquid chromatography of
the respective enantiomers on a 100ꢃ3000 column containing a (S)-N-
(1-naphthyl)leucine-derived CSP bonded to 60 m
m irregular silica.25
The
caprolactam elutes second, the enantiomeric purity being greater
than 99%. The NMR spectrum is identical to that of the racemate. [
(þ)-(S)-(N-3,5-dinitrobenzoyl)-3-amino-N-10-undecenyl-
3-
17. Murguly, E.; McDonald, R.; Branda, N. R. Org. Lett. 2000, 2, 3169e3172.
18. Shi, X.; Fettinger, J. C.; Davis, J. T. J. Am. Chem. Soc. 2001, 123, 6738e6739.
19. Ten Cate, A. T.; Dankers, P. Y. W.; Kooijman, H.; Spek, A. L.; Sijbesma, R. P.;
Meijer, E. W. J. Am. Chem. Soc. 2003, 125, 6860e6861.
a
]
D
þ55.04 (c 4.98 in CH2Cl2). The solvent choice for the specific rotation
was based solely on solubility.
20. Masood, A. M. E.; Eric, J.; Stack, T. D. P. Angew. Chem., Int. Ed. 1998, 37, 928e932.
21. Enemark, E. J.; Stack, T. D. P. Angew. Chem., Int. Ed. 1998, 37, 932e935.
22. Xu, J.; Parac, T. N.; Raymond, K. N. Angew. Chem., Int. Ed. 1999, 38, 2878e2882.
23. Vincent, J.-M.; Philouze, C.; Pianet, I.; Verlhac, J.-B. Chem.dEur. J. 2000, 6,
3595e3599.
24. Ishida, Y.; Aida, T. J. Am. Chem. Soc. 2002, 124, 14017e14019.
25. Lee, W. Ph.D. Thesis, Univ. of Illinois, Urbana-Champaign, 1994.
26. Hyun, M. H.; Kim, Y. D.; Han, S. C.; Lee, J. B. J. High Resolut. Chromatogr. 1998, 21,
464e470.
4.2.3. (þ)-(S)-N-11-Dimethylethoxyundecyl-(N-3,5-dinitrobenzoyl)-
3-amino-
3
-caprolactam (CSP-3). Compound (S)-13, 0.93
g
(2.0 mmol), and 15 mL of dimethylchlorosilane were dissolved in
15 mL of dry dichloromethane. After addition of chloroplatinic acid
(44 mg), the reaction mixture was heated to reflux under a nitrogen
atmosphere. After 100 min, an aliquot of the reaction mixture

W. Lee et al. / Tetrahedron 67 (2011) 7143e7147
7147
27. Pirkle, W. H.; Pochapsky, T. C. J. Am. Chem. Soc. 1987, 109, 5975e5982.
28. Snyder, S. E.; Volkers, P. I.; Engebretson, D. A.; Lee, W.; Pirkle, W. H.; Carey, J. R.
Org. Lett. 2007, 9, 2341e2343.
29. (a) U.S. Patent 5,290,440, 1994; (b) . U.S. Patent 5,578,212, 1996.
30. (a) Pirkle, W. H.; Pochapsky, T. C.; Mahler, G. S.; Field, R. E. J. Chromatogr. 1985,
348, 89e96; (b) Pirkle, W. H.; Lee, W. Bull. Korean Chem. Soc. 2010, 31,
621e623.
31. Pirkle, W. H.; Pochapsky, T. C.; Mahler, G. S.; Corey, D. E.; Reno, D. S.; Alessi, D.
M. J. Org. Chem. 1986, 51, 4991e5000.
32. Pirkle, W. H.; Hyun, M. H.; Bank, B. J. Chromatogr. 1984, 316, 585e604.
33. Dobashi, A.; Hara, S. Tetrahedron Lett. 1983, 24, 1509e1510.
34. Snyder, S. E.; Carey, J. R.; Shvets, A. B.; Pirkle, W. H. J. Org. Chem. 2005, 70,
4073e4081.
35. Belyaev, A. Tetrahedron Lett. 1995, 36, 439e440.