Reactive extraction of enantiomers of 1,2-amino alcohols via stereoselective thermodynamic and kinetic processes

Article abstract of DOI:10.1021/jo800670t

(Chemical Equation Presented) (R)-Amino alcohol with an enantiomeric excess of >95% was resolved by reactive extraction processes from 2 equiv of racemic alcohol using a chiral receptor 2 as an enantioselective extractant. One resolution cycle is composed of three extractions: a stereoselective reversible imine formation, a stereoselective irreversible imine hydrolysis, and the recovery of 2 and enantiomeric amino alcohols.

Full text of DOI:10.1021/jo800670t

applicable substrates, and sometimes tedious conditions in
releasing substrates. Steensma et al. tested several tens of
selectors for enantioselective separation of a number of chemi-
cally related amino alcohols and amines by solvent extraction.5
They reported the enantioselectivity of azophenolic crown ether
of Hirose6 to be 5.0 as the highest among those tested and most
promising enantioselective extractor.5
Reactive Extraction of Enantiomers of 1,2-Amino
Alcohols via Stereoselective Thermodynamic and
Kinetic Processes
Lijun Tang,† Sujung Choi,† Raju Nandhakumar,†
Hyunjung Park,† Hyein Chung,† Jik Chin,‡ and
Kwan Mook Kim*,†
Recently, we demonstrated7 that a chiral receptor 1 recognizes
the chirality of 1,2-amino alcohols (aa) based on reversible
imine formation and multiple hydrogen bonding including
resonance assisted hydrogen bond (RAHB).8 Receptor 1 showed
moderate stereoselectivity (KR/KS) of 3-5. Considering the
origin of the stereoselectivity of 1, strong hydrogen bond donors
in the receptor will enhance the stereoselectivity. In this context,
we developed a new receptor 2 derivatized with a guanidinium
group which provides a charge-reinforced hydrogen bond9 as a
protonated form over a wide pH range.10
DiVision of Nano Sciences, Ewha Womans UniVersity,
Seoul 120-750, South Korea, and Department of Chemistry,
80 St. George Street, UniVersity of Toronto,
Toronto, Ontario, Canada M5S 3H6
kkmook@ewha.ac.kr
ReceiVed April 03, 2008
Scheme 1 describes the synthesis of receptor 2 from (S)-2,2′-
dihydroxy-1,1′-binaphthyl-3-carboxaldehyde,7 through selective
monoprotection of the hydroxyl group followed by several steps
including a PCC oxidation and deprotection. All the compounds
were confirmed by spectroscopic data and are in good agreement
with the presented structures. It is noteworthy that compound
2 is highly soluble in organic solvents such as chloroform and
dichloromethane but not soluble in water even as Cl- salt form,
which is an important requisite as an extractor.
(R)-Amino alcohol with an enantiomeric excess of >95%
was resolved by reactive extraction processes from 2 equiv
of racemic alcohol using a chiral receptor 2 as an enanti-
oselective extractant. One resolution cycle is composed of
three extractions: a stereoselective reversible imine formation,
a stereoselective irreversible imine hydrolysis, and the
recovery of 2 and enantiomeric amino alcohols.
Partial 1H NMR spectra for the enantioselective recognition
of 2-amino-1-butanol (ab) by receptor 2 in CDCl3 are shown
in Figure 1. The aldehyde peak at 9.98 ppm (Figure 1a)
disappears on addition of (S)-ab with a rapid complete formation
of an imine (2-S-ab) C-H signal at 8.76 ppm (Figure 1b).
Enantioselective recognition of amino alcohols has been
extensively studied1 because of their importance as a chiral pool
in the ligand design for stereoselective catalysts and as biologi-
cally active molecules.2,3 The resolution of enantiomers by
solvent extraction has been of interest4 and currently appears
to be a time-saving and cost-effective process. However,
industrial scale application of most extractors so far developed
is limited due to low enantioselectivity, narrow range of
(4) (a) Eliel, E. L.; Wilen, S. H. In Stereochemistry of Organic Compounds;
Wiley, New York, 1994; pp 416-421. (b) Tang, K.; Chen, Y.; Huang, K.; Liu,
J. Tetrahedron: Asymmetry 2007, 18, 2399–2408. (c) Dzygiel, P.; Monti, C.;
Piarulli, U.; Gennari, C. Org. Biomol. Chem. 2007, 5, 3464–3471. (d) Lacour,
J.; Goujon-Ginglinger, C.; Torche-Haldimann, S.; Jodry, J. J. Angew. Chem.
2000, 112, 3830-3832; Angew. Chem., Int. Ed. 2000, 39, 3695-3697. (e)
Andrisano, V.; Gottarelli, G.; Masiero, S.; Heijne, E. H.; Pieraccini, S.; Spada,
G. P. Angew. Chem. 1999, 111, 2543-2544; Angew. Chem., Int. Ed. 1999, 38,
2386-2388.
† Ewha Womans University.
‡ University of Toronto.
(1) (a) Wang, X. Q.; Chen, L.; Tao, L.; Wang, D.; Xiao, Q. Y.; Pu, L. J.
Org. Chem. 2007, 72, 97–101. (b) Ishii, Y.; Onda, Y.; Kubo, Y. Tetrahedron
Lett. 2006, 47, 8221–8225. (c) Eelkema, R.; Feringa, B. L. J. Am. Chem. Soc.
2005, 127, 13480–13481. (d) Tsubaki, K.; Tanima, D.; Nuruzzaman, M.;
Kusumoto, T.; Fuji, K.; Kawabata, T. J. Org. Chem. 2005, 70, 4609–4616. (e)
Liu, L.; Zhou, W.; Chruma, J.; Breslaw, R. J. Am. Chem. Soc. 2004, 126, 8136–
8137. (f) Escuder, B.; Rowan, A. E.; Feiters, M. C.; Nolte, R. J. M. Tetrahedron
2004, 60, 291–300. (g) Kim, S. G.; Kim, K. H.; Kim, Y. H.; Shin, S. K.; Ahn,
K. H. J. Am. Chem. Soc. 2003, 125, 13819–138214. (h) Lee, S. J.; Lin, W.
J. Am. Chem. Soc. 2002, 124, 4554–4555.
(5) Steensma, M.; Kuipers, N. J. M.; de Haan, A. B.; Kwant, G. Chirality
2006, 18, 314–328.
(6) Naemura, K.; Nishioka, K.; Ogasahara, K.; Nishikawa, Y.; Hirose, K.;
Tobe, Y. Tetrahedron: Asymmetry 1998, 9, 563–574.
(7) Kim, K. M.; Park, H.; Kim, H. J.; Chin, J.; Nam, W. Org. Lett. 2005, 7,
3525–3527.
(8) (a) Chin, J.; Mancin, F.; Thavarajah, N.; Lee, D.; Lough, A.; Chung,
D. S. J. Am. Chem. Soc. 2003, 125, 15276–15277. (b) Gilli, P.; Bertolasi, V.;
Ferretti, V.; Gilli, G. J. Am. Chem. Soc. 2000, 122, 10405–10417.
(9) Mazik, M.; Cavga, H. J. Org. Chem. 2007, 72, 831–838.
(10) (a) Schmuck, C.; Schwegmann, M. J. Am. Chem. Soc. 2005, 127, 3373–
3379. (b) Wiskur, S. L.; Lavign; J, J.; Metzer, A.; Tobey, S. L.; Lynch, V.;
Anslyn, E. V. Chem.sEur. J. 2004, 10, 3792–3804. (c) Beer, P. D.; Gale, P. A.
Angew. Chem. 2001, 113, 502-532. Angew. Chem., Int. Ed. 2001, 40, 485-
516.
(2) (a) Coppola, G. M.; Schuster, H. F., Asymmetric Synthesis. Construction
of Chiral Molecules Using Amino Acids; Wiley: New York, 1987. (b) Zheng,
Y. S.; Zhang, C. Org. Lett. 2004, 6, 1189–1192. (c) Bergmeier, S. C. Tetrahedron
2000, 56, 2561–2576.
(3) (a) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336–345. (b)
Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. ReV. 1996, 96, 835–876.
5996 J. Org. Chem. 2008, 73, 5996–5999
10.1021/jo800670t CCC: $40.75 2008 American Chemical Society
Published on Web 07/04/2008

SCHEME 1. Synthesis of 2a
FIGURE 2. The resolution of the (R)-enantiomer of ape by reactive
1
extraction using 2 as an extractor. (a) H NMR of the CDCl3 layer in
a Reagents: (a) MOMCl, NaH/DMF; (b) 3-nitrobenzylbromide, NaH/
DMF; (c) NaBH4/CH3OH; (d) Fe, NH4Cl, C2H5OH/dioxane/H2O, reflux;
(e) 1,3-bis-BOC-2-methyl-2-thiopseudourea, TEA, HgCl2/DMF; (f) PCC/
CH2Cl2; (g) HCl in diethyl ether.
equilibrium with the D2O layer, where 2 and ape are in 1:2 ratio. (b-d)
1
Change of H NMR in the CDCl3 layer in contact with 0.1 N DCl/
D2O. (e) 1H NMR of the CDCl3 layer after hydrolysis of (d) with 1 N
DCl/D2O, which proves complete imine hydrolysis and clean recovery
of 2. (f) Increase of de value upon the hydrolysis.
TABLE 1. Stereoselective Imine Formation (KR/KS) of 1 and 2
a
1
Measured by H NMR Study
KR/KS
amines
17
2
methylbenzylamine
2-amino-1-propanol
2-amino-1-butanol
2-amino-2-phenylethanol
phenyl alaninol
valinol
1.0
3.7
3.1
4.8
3.7
1.0
11
15
9.8
8.3
12
7.4
leucinol
a The solvents used are benzene-d6 and CDCl3 for
1 and 2,
respectively. The error range is related to NMR integration error.
SCHEME 2. Different Steric Repulsions between
2-R-(Amino Alcohol) and 2-S-(Amino Alcohol) around The
Imine Bond
1
FIGURE 1. Partial H NMR (250 MHz, CDCl3) spectra of (a) 2, (b)
2-S-ab, (c) 2-R-ab, and (d) mixture of 2 and 2.0 equiv of racemic
2-amino-1-butanol (ab).
Likewise, addition of (R)-ab to 2 results in the increase of an
imine (2-R-ab) C-H signal at 8.88 ppm (Figure 1c). Further-
more, the diastereotopic benzylic CH2 signals between 4.7 and
5.3 ppm provide prominent information to differentiate 2-S-ab
fold larger than the azophenolic crown ether of Hirose.5 To the
best of our knowledge, 2 represents one of the highly stereo-
selective small organic receptors for a wide range of underiva-
tized 1,2-amino alcohols.
1
and 2-R-ab. Figure 2d shows the H NMR spectrum for a
mixture of 2-S-ab and 2-R-ab formed by addition of 2.0 equiv
of racemic ab to 2. The integration of imine C-H signals gives
the ratio of 2-S-ab to 2-R-ab to be 3.9:1 at equilibrium, which
demonstrates that the imine formation constant for 2-R-ab (KR)
is greater than that of 2-S-ab (KS) by a factor of about 3.92 )
15.11 Although 2-S-ab is first formed by the addition of 1 equiv
of (S)-ab, the above equilibrium ratio is obtained within minutes
upon addition of 1 equiv of (R)-ab. The stereoselectivities (KR/
KS) of 2 for five different amino alcohols are compared with
receptor 1 in Table 1. Though both receptors 1 and 2 bind all
amino alcohols with the same sense of stereoselectivity, receptor
2 has higher selectivity. Moreover, the selectivity of 2 is 2-3-
Scheme 2 illustrates different steric repulsion between the
imines 2-R-aa and 2-S-aa, a key origin of the stereoselective
imine formation. The steric energy due to the repulsion between
hydrogen and alkyl/aryl around the imine bond in 2-S-aa is
greater than that in 2-R-aa where the interaction is only between
the hydrogen atoms. Both the receptors, 1 and 2, do not bind
methylbenzylamine with noticeable stereoselectivity. The ste-
reoselectivity of the receptors toward the amino alcohols is
almost completely lost in polar DMSO-d6. These clearly indicate
that the H-bond between the receptor and guest plays an
important role in the chiral discrimination. The charge-reinforced
stronger H-bonding between the guanidinium motif and OH
induces rigidity in the three-dimensional structure of the imine
(11) KR ) [2-R-aa]/([2][R-aa]) and KS ) [2-S-aa]/([2][S-aa]), where aa )
amino alcohol. KR/KS ) ([2-R-aa][S-aa])/([2-S-aa][R-aa]) ) ([2-R-aa]/[2-S-aa])2
when [2]0 ) [R-aa]0 ) [S-aa]0.
J. Org. Chem. Vol. 73, No. 15, 2008 5997

and thus higher enantioselectivity of 2 compared to that of uryl-
based receptor 1.
We tried reactive extraction of racemic amino alcohol by
using 2 as a chiral extractor in the CDCl3/D2O bilayer. A 10
mM CDCl3 solution of 2 and a 20 mM D2O solution of racemic
2-amino-2-phenylethanol (ape) were prepared. Ethylene glycol
was added to D2O solution as an integral standard in order to
assess the amount of ape distribution between aqueous and
organic layers. Equal volumes of CDCl3 and D2O solutions were
mixed and shaken for 10 min in a small vial, which was enough
for the biphasic system to reach the equilibrium. The pD value
of the D2O layer was adjusted to 7-8 with DCl so that free
amino alcohol exists almost exclusively in the aqueous layer.
FIGURE 3. Conceptual diagrams representing the (R)-aa resolution
via stereoselective imine formation and hydrolysis in reactive extraction
of amino alcohols with a chiral extractor 2.
1
Figure 2a shows the H NMR spectrum for the CDCl3 layer,
where the aldehyde (2) was completely reacted to form imine,
and the ratio of 2-R-ape/2-S-ape was 3.1. Comparison of peaks
of ape and ethylene glycol in the 1H NMR spectrum of the D2O
layer represents that the amount of ape in the D2O layer
decreased to half of its initial number. Therefore, it is safe to
say that the ratio of R-ape/S-ape in the D2O layer is 1/3.1. The
thermodynamic equilibrium established between the two layers
corresponds to the stereoselectivity of 3.12 ) 9.6, which is
actually another way to prove the selectivity (KR/KS) listed in
Table 1. Eventually, the amino alcohol in the D2O layer is
stereoselectively extracted into the CDCl3 layer, giving 2-R-
ape domination in the organic layer with the diastereomeric
excess (de) value of 52%.
processes, which could be cost-effective and time-saving ones,
using 2 as a chiral extractor.
Experimental Section
Compound 4. To an ice-cooled solution of (S)-1,1′-bi-2-
naphtholaldehyde 3 (3.9 g, 12.42 mmol) in DMF was added and
stirred NaH (0.447 g, 11.18 mmol) for 1 h. Chloromethyl methyl
ether (1.08 mL, 12.42 mmol) in DMF was added to the above
mixture (ca. 4 h). After stirring overnight, the reaction mixture was
quenched and extracted with ethyl acetate several times. The organic
layer was dried, evaporated, and triturated with chloroform/hexane
to give a pale yellow solid 4 (2.31 g, 52%): mp 164 °C; 1H NMR
(CDCl3, 250 MHz) δ 10.59 (s, 1H), 8.62 (s, 1H), 8.09 (d, 1H, J )
8.0 Hz), 7.99-7.88 (m, 2H), 7.54-7.27 (m, 6H), 7.07 (d, 1H, J )
8.0 Hz), 5.08 (s, 1H), 4.74 (dd, 2H), 3.03 (s, 3H); 13C NMR (CDCl3,
63 MHz) δ 154.4, 151.5, 136.7, 133.6, 132.9, 130.7, 130.4, 130.0,
129.1, 128.9, 128.2, 127.1, 126.6, 125.7, 124.6, 124.1, 123.7, 118.0,
114.5, 100.4, 57.4; HRMS (EI) calcd for C23H18O4 358.1205; found
358.1201; [R]D ) -108.17 (c 0.42, CHCl3).
Furthermore, the de value in the CDCl3 layer of Figure 2a
could be enhanced by second reactive extraction with 0.1 N
DCl/D2O. The hydrolysis is quite slow, irreversible, and
stereoselective. The spectra in Figure 2b–d show the changes
occurring in the CDCl3 layer according to the imine hydrolysis.
As the hydrolysis proceeds, the NMR peaks corresponding to
2 are growing, and the ratio of 2-R-ape/2-S-ape is remarkably
increasing. The increase of de upon the hydrolysis is displayed
in Figure 2f as it approaches >95%. When the hydrolysis obeys
first-order rate law, ln([2-S-ape]0/[2-S-ape]) ) (kS/kR)ln([2-R-
ape]0/[2-R-ape]), where kS and kR are hydrolysis rate constant
for 2-S-ape and 2-R-ape, respectively. Using this relation, we
can obtain kS/kR ) 6.4 ( 0.4 from the data of Figure 2f.
Finally, acid hydrolysis of the CDCl3 layer of Figure 2d by
1 N DCl/D2O solution led to fast and clean recovery of receptor
2 in the organic layer as shown in Figure 2e. The amino alcohol
released was transferred to the aqueous layer, where the
enantiomeric excess (ee) of ape must be consistent with the de
of the imine form of Figure 2d. In this representative reactive
extraction of one cycle with 2, we could have obtained (R)-
amino alcohol of >95% ee from 2 equiv of racemic amino
alcohol with ∼48% yield.
Compound 5. To a stirred ice-cold solution of 4 (0.6 g, 1.67
mmol) in DMF was added NaH (0.081 g, 2.0 mmol). After stirring
for 10 min, 3-nitrobenzylbromide (0.434 g, 2.0 mmol) was added
and stirred for 4 h. The reaction mixture was quenched and extracted
with ethyl acetate several times. The EA layer was dried and
evaporated, and column chromatography with EA/hexane (1:3, v/v)
1
gave 5 as pale yellow solids (0.783 g, 95%): mp 71 °C; H NMR
(CDCl3, 250 MHz) δ 10.65 (s, 1H), 8.64 (s, 1H), 8.07-7.87 (m,
5H), 7.53-7.23 (m, 9H), 5.22 (dd, 2H), 4.77 (dd, 2H), 2.93 (s,
3H); 13C NMR (CDCl3, 63 MHz) δ 139.2, 138.9, 133.9, 132.7,
131.9, 130.6, 130.4, 130.2, 129.5, 129.3, 129.3, 129.1, 128.2, 127.2,
126.8, 126.1, 125.8, 128.3, 124.4, 122.6, 121.7, 119.3, 114.8, 100.4,
69.7, 57.1; HRMS (EI) calcd for C30H23NO6 493.1525; found
493.1520; [R]D ) -16.03 (c 1.69, CHCl3).
Compound 6. Sodium borohydride (60 mg, 1.56 mmol) was
added to a stirred solution of 5 (0.643 g, 1.3 mmol) in methanol at
rt. After being stirred overnight, the mixture was quenched and
extracted with EA, dried, and evaporated to give compound 6
quantitatively as an amorphous solid: mp 155 °C; 1H NMR (CDCl3,
250 MHz) δ 8.09-7.78 (m, 6H), 7.42-7.12 (m, 9H), 5.13 (dd,
2H), 4.96 (s, 2H), 4.55 (dd, 2H), 3.63 (br, 1H), 3.10 (s, 3H); 13C
NMR (CDCl3, 63 MHz) δ 153.5, 153.1, 148.1, 139.2, 134.6, 134.0,
133.6, 132.8, 131.2, 130.3, 129.5, 129.2, 129.1, 128.3, 128.2, 127.2,
126.4, 125.5, 125.3, 125.2, 124.4, 122.6, 121.7, 120.4, 115.1, 99.4,
69.8, 61.9, 57.1; HRMS (EI) calcd for C30H25NO6 495.1682; found
495.1678; [R]D ) +10.53 (c 0.95, CHCl3).
Figure 3 depicts conceptually the processes of three extrac-
tions of this work which are controlled by pH conditions. The
first one is a stereoselective reversible imine formation (ther-
modynamic process); the second one is stereoselective irrevers-
ible imine hydrolysis (kinetic and slow process), and the last
one is the recovery of 2 and enantiomeric amino alcohol (kinetic
and fast process).
Compound 7. Nitro compound 6 (0.646 g, 1.3 mmol) was
dissolved in a cosolvent of ethanol/dioxane/water with 1/1/1 volume
ratio, and iron powder (0.504 g, 9.1 mmol) and ammonium chloride
(0.126 g, 2.34 mmol) were added and refluxed overnight. The
mixture was filtered and extracted with methylene chloride, and
column chromatography with EA/hexane 1:1 mixture gave 7 (0.575
In summary, we have developed a highly enantioselective
receptor 2 for 1,2-amino alcohols based on charge-reinforced
hydrogen bonds between guanidinium motif and alcoholic OH.
More interestingly, we have demonstrated that enantiomers of
general 1,2-amino alcohols can be resolved by extraction
5998 J. Org. Chem. Vol. 73, No. 15, 2008

1
g, 95%) as pale yellow solids: mp 79 °C; H NMR (CDCl3, 250
10.62 (s, 1H), 10.14 (s, 1H), 8.59 (s, 1H), 8.06-7.85 (m, 3H), 7.60
(d, 1H, J ) 8.2 Hz), 7.48-7.09 (m, 9H), 6.79 (d, 1H, J ) 7.6 Hz),
5.10 (dd, 2H), 4.71 (dd, 2H), 2.93 (s, 3H), 1.58 (s, 9H), 1.49 (s,
9H); 13C NMR (CDCl3, 63 MHz) δ 137.8, 137.0, 136.8, 133.8,
131.1, 130.2, 130.2, 129.2, 129.1, 129.0, 128.9, 128.1, 127.0, 128.8,
126.0, 125.9, 125.1, 124.0, 123.2, 121.9, 120.4, 118.8, 115.0, 100.3,
83.8, 79.7, 70.6, 57.1, 28.2, 28.1; HRMS (EI) calcd for C41H43N3O8
705.3050; found 705.3045; [R]D ) -21.79 (c 0.78, CHCl3).
Compound 2. A solution of 9 in methylene chloride was treated
with trifluoroacetic acid (2.0 mL) at 0 °C and stirred for 12 h at rt.
After neutralization with aqueous NaOH, the organic layer was
acidified with dry HCl. The whole evaporation of the solvent
MHz) δ 7.95-7.79 (m, 4H), 7.40-7.16 (m, 7H), 6.87 (m, 1H),
6.37 (m, 2H), 6.06 (s, 1H), 4.98-4.86 (m, 4H), 4.66 (dd, 2H), 3.52
(br, 3H), 3.04 (s, 3H); 13C NMR (CDCl3, 63 MHz) δ 154.3, 153.1,
146.6, 138.4, 134.7, 134.0, 133.9, 131.2, 130.1, 129.3, 129.1, 128.8,
128.2, 128.1, 127.0, 126.3, 126.0, 125.7, 125.4, 125.2, 124.1, 119.8,
116.6, 115.4, 114.4, 113.5, 99.3, 70.8, 62.0, 57.1; HRMS (EI) calcd
for C30H27NO4 465.1940; found 465.1935; [R]D ) -3.88 (c 1.80,
CHCl3).
Compound 8. To a stirred solution of 7 (0.454 g, 0.98 mmol)
and 1,3-bis-BOC-2-methyl-2-thiopseudourea (0.298 g, 1.03 mmol
in dry DMF at 0 °C under nitrogen) were added triethylamine (0.54
mL, 3.92 mmol) and HgCl2 (0.291 g, 1.08 mmol). The resulting
suspension was stirred at 0 °C for 3 h and at rt overnight. The
mixture was diluted with EA and filtered through Celite. Evapora-
tion of the solvent followed by silica column chromatography (EA/
hexane, 1:3) gave 8 (0.586 g, 85%) as white solids: mp 118 °C; 1H
NMR (CDCl3, 250 MHz) δ 11.68 (s, 1H), 10.12 (s, 1H), 8.01-7.86
(m, 4H), 7.60 (d, 1H, J ) 7.9 Hz), 7.46-7.06 (m, 8H), 6.80 (d,
1H, J ) 7.6 Hz), 5.09 (dd, 2H), 4.94 (s, 2H), 4.57 (dd, 2H), 3.53
(br s, 1H), 3.18 (s, 3H), 1.59 (s, 9H), 1.50 (s, 9H); 13C NMR (CDCl3,
63 MHz) δ 163.5, 153.9, 153.5, 153.1, 137.9, 136.6, 134.3, 133.9,
133.7, 131.0, 129.9, 129.2, 129.1, 128.9, 128.0, 127.9, 126.9, 126.3,
125.7, 125.4, 125.3, 125.1, 124.0, 123.3, 122.0, 120.5, 119.9, 115.4,
99.3, 83.7, 79.7, 70.7, 62.1, 57.1, 28.1, 27.9; HRMS (EI) calcd for
C41H45N3O8 707.3207; found 707.3204; [R]D ) +6.26 (c 0.96,
CHCl3).
1
afforded 2 quantitatively as yellow solids: mp 170 °C; H NMR
(CDCl3, 250 MHz) δ 10.38 (s, 1H), 10.10 (s, 1H), 9.64 (s, 1H),
8.29 (s, 1H), 7.77-7.92 (m, 4H), 7.31-6.72 (m, 9H), 6.47 (s, 2H),
6.28 (s, 1H), 4.83 (s, 2H); 13C NMR (DMSO-d6, 63 MHz) δ 155.6,
153.7, 152.8, 139.0, 136.8, 134.9, 133.2, 130.2, 129.8, 129.4, 128.9,
128,1, 127.2, 126.7, 124.7, 124.3, 124.2, 123.8, 122.8, 122.6, 117.5,
117.4, 115.3, 69.1; HRMS (FAB) calcd for C29H24N3O3 462.1818;
found 462.1812; [R]D ) -65.81 (c 0.94, CHCl3).
Acknowledgment. This work was supported by a grant from
the Ministry of Science and Technology of Korea through NRL,
SRC program of MOST/KOSEF at Ewha Womans University
(R11-2005-008-000000), and Korea Research Foundation (KRF-
2004-005-C00093).
Supporting Information Available: 1H NMR and 13C NMR
spectra for 2-9, and details of the data analysis on the rate
constants. This material is available free of charge via the
Internet at http://pubs.acs.org.
Compound 9. PCC (0.305 g, 1.42 mmol) was added to
compound 8 (0.5 g, 0.71 mmol) in methylene chloride at rt. After
12 h, the mixture was passed through a short pad of Celite. The
filtrate was concentrated and purified by column chromatography
with EA/hexane 1:3 mixture to give 11 (0.46 g, 92%) as white
1
solids: mp 158 °C; H NMR (CDCl3, 250 MHz) δ 11.66 (s, 1H),
JO800670T
J. Org. Chem. Vol. 73, No. 15, 2008 5999