Total synthesis of (-)- and (+)-tedanalactam

Article abstract of DOI:10.1021/jo901143b

(Chemical Equation Presented) The first stereoselective route providing access to both enantiomers of tedanalactam, a naturally occurring piperidone, has been developed. The stereogenic centers were generated by the use of Sharpless asymmetric dihydroxyla

Full text of DOI:10.1021/jo901143b

pubs.acs.org/joc
leaves of Piper crassinervium (piperaceae). It displays pro-
Total Synthesis of (-)- and (þ)-Tedanalactam
mising fungicidal activity. The core structure containing
an epoxy-δ-lactam derivative (Figure 1) is also found in
piplaroxide 2, an ant-repellant alkaloid5a isolated from
Piper tuberculatum, 3,4-epoxy-8,9-dihydropiplartine 3 iso-
lated from leaves5b and twigs of Piper verrucosum, and
3,4-epoxy-5-pipermethystine 4 from roots5c of the kava
shrub (Piper methysticum). The kava shrub is a source of
traditional beverage for many South Pacific Island people.
So far there are no reports on the synthesis of these epoxy
piperidones, nor is their absolute stereochemistry described.
Our ongoing interest in the synthesis of small molecules,6 and
potential anticancer activity of epoxy piperidines7 prompted
us to devise the synthesis of tedanalactam. Herein, we report
the first total synthesis of (-)- and (þ)-tedanalactam em-
ploying Sharpless dihydroxylation as the source of chirality.
Retrosynthetic analyses (Scheme 1) of tedanalactam 1 lead
to 3-tosyloxy-4-hydroxy-2-piperidone 5 as a suitable pre-
cursor, which can be assembled from δ-amino ester 6. The
required monotosyl ester 6 could be prepared from the
corresponding dihydroxy ester 7 to be obtained by Sharpless
asymmetric dihydroxylation of the unsaturated ester 8.
With the above objective in mind, 3-amino-1-propanol 9
was subjected to N-protection by using Boc anhydride and
subsequently transformed into olefin 8 by tandem oxidation-
Wittig reaction,6e,8 using PCC/NaOAc and phosphorane.
Exclusively E-olefin was formed during this step (Scheme 2).
Following Scheme 3, cis dihydroxylation of R,β-unsatu-
rated ester 8 in the presence of OsO4 and NMO as co-oxidant
gave a rac-diol 7. Enantioselective Sharpless dihydroxylation
with the AD-mix R catalyst (NH2SO2CH3, t-BuOH:H2O
(1/1), 0 °C) afforded diol 7a in 77% yield and 91% ee as
determined by the HPLC analyses, whereas reverse selecti-
vity was obtained when the AD-mix β catalyst was used.
Thus, diol 7b was prepared by employing the AD-mix β as
catalyst with 94% ee and 71% yield. The absolute stereo-
chemistry of diols was assumed from the predictable facial
selectivity rule (mnemonic rule) suggested by Sharpless et al.9
To test the viability of the proposed route, rac-2,3-dihy-
droxy ester 7 was used for our initial studies. Regioselective
monotosylation10 at the 2-position of rac-2,3-dihydroxy
ester 7 worked well to give the monotosylated ester 6
(Scheme 4). Conversion of rac-6 to rac-1 required N-depro-
tection, followed by the corresponding cyclization to the
Mahesh S. Majik,† Perunninakulath S. Parameswaran,‡ and
Santosh G. Tilve*,†
†Department of Chemistry, Goa University, Taleigao Plateau,
Goa 403 206, India, and ‡National Institute of Oceanography,
Dona Paula, Goa 403 004, India
stilve@unigoa.ac.in
Received May 29, 2009
The first stereoselective route providing access to both
enantiomers of tedanalactam, a naturally occurring
piperidone, has been developed. The stereogenic centers
were generated by the use of Sharpless asymmetric dihy-
droxylation. Tandem oxidation-Wittig reaction and
one-pot deprotection, lactamization, and oxirane ring
formation are the other key elements.
The piperidine motif is widely encountered in naturally
occurring alkaloids, displaying a wide range of biological
activities.1 Piperidones are key synthetic intermediates2 for
the synthesis of the piperidine ring due to the presence of the
keto function, which allows the introduction of other groups.
Piperidones are also known for their therapeutic usage and a
few are isolated as natural products.
Tedanalactam, a cis-3,4-epoxy-2-piperidone 1, was first
isolated from sponge Tedania ignis in 1994 by Cronan and
Cardellina.3 Recently in 2007, Lago and Kato4 found it in
(5) (a) Capron, M. A.; Weimer, D. F. J. Nat. Prod. 1996, 59, 794. (b)
Seeram, N. P.; Lewis, P. A.; Jacobs, H. J. Nat. Prod. 1996, 59, 436. (c)
Dragull, K.; Yoshida, W. Y.; Tang, C. Phytochemistry 2003, 64, 555.
(6) (a) Majik, M. S.; Parameswaran, P. S.; Tilve, S. G. J. Org. Chem. 2009,
74, 3591. (b) Patre, R.; Gawas, S.; Sen, S.; Parameswaran, P. S.; Tilve, S. G.
Tetrahedron Lett. 2007, 48, 3517. (c) Parvatkar, P.; Parameswaran, P. S.;
Tilve, S. G. Tetrahedron Lett. 2007, 48, 7870. (d) Majik, M. S.; Shet, J. B.;
Tilve, S. G.; Parameswaran, P. S. Synthesis 2007, 663. (e) Shet, J.; Desai, V.;
Tilve, S. G. Synthesis 2004, 1859.
(7) Miyashita, K.; Park, M.; Adachi, S.; Seki, S.; Obika, S.; Imanishi, T.
Bioorg. Med. Chem. Lett. 2002, 12, 1075.
(8) Taylor, R. J. K.; Reid, M.; Foot, J.; Raw, S. A. Acc. Chem. Res. 2005,
38, 851.
(1) (a) Pei, Z.; Li, X.; von Geldern, T. W.; Longenecker, K.; Pireh, D.;
Stewart, K. D.; Backes, B. J.; Lai, C.; Lubben, T. H.; Ballaron, S. J.; Beno, B.
W. A.; Kempf-Grote, A. J.; Sham, H. L.; Trevillyan, J. M. J. Med. Chem.
2007, 50, 1983. (b) Elworthy, T. R.; Brill, E. R.; Caires, C. C.; Kim, W.; Lach,
L. K.; Tracy, J. L.; Chiou, S.-S. Biorg. Med. Chem. Lett. 2005, 15, 2523.
(c) Yu, Y. K.; Nagimoxa, A. D.; Praliev, K. D.; Shin, S. N.; De kempe, N.
Pharm. Chem. J. 2002, 36, 382. (d) Watson, P. S.; Jiang, B.; Scott, B. Org.
Lett. 2000, 23, 3679.
(2) (a) Godineau, E.; Schenk, K.; Landais, Y. J. Org. Chem. 2008, 73, 6983
and references cited therein. (b) Buffat, M. G. P. Tetrahedron 2004, 60, 1701. (c)
Weintraub, P. M.; Sabol, J. S.; Kane, J. M.; Borcherding, D. R. Tetrahedron 2003,
59, 2953. (d) Mitchinson, A.; Nadin, A. J. Chem. Soc., Perkin Trans. 1 2000,
2862. (e) Laschat, S.; Dickner, T. Synthesis 2000, 1781.
(9) (a) Becker, H.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl. 1996, 35,
448. (b) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev.
1994, 94, 2483.
(3) Cronan, J. M., Jr.; Cardellina, J. H. II Nat. Prod. Lett. 1994, 5, 85.
(4) Lago, J. H.; Kato, M. J. Nat. Prod. Res. 2007, 21, 910.
(10) Fleming, P. R.; Sharpless, K. B J. Org. Chem. 1991, 56, 2869.
6378 J. Org. Chem. 2009, 74, 6378–6381
Published on Web 07/09/2009
DOI: 10.1021/jo901143b
r
2009 American Chemical Society

Majik et al.
JOCNote
SCHEME 3. Synthesis of Diol 7
FIGURE 1. Examples of epoxy-2-piperidone.
SCHEME 1. Retrosynthesis of Tedanalactam 1
aDetermined by chiral HPLC, using a Chiralpak AD column.
SCHEME 4. Synthesis of Tedanalactam 1
SCHEME 2. Synthesis of Olefin 8
Reagents and conditions: (a) TsCl, Et3N, CH2Cl2, 0 °C, 72 h (65-
66%); (b) (1) TFA, CH2Cl2, 0 °C to rt, 2 h; (2) aq NH3 (72-77%).
achieved successfully by treatment of 6a and 6b with TFA
followed by aq NH3 to give (-)-tedanalactam 1a having
[R]30 -7.60 (c 0.130, MeOH) [lit3 [R]30 -8.90 (c 0.3,
D
D
MeOH)] in 91% ee and (þ)-tedanalactam 1b in 94% ee
(determined by HPLC analyses). The sign of specific
rotation of (-)-tedanalactam is consistent with that of
the natural tedanalactam, which reveals the presence of
(3S,4S) configuration at the epoxy ring of the natural
product.
In conclusion, the first total synthesis of (-)-tedanalactam
with 91% ee and (þ)-tedanalactam with 94% ee has been
completed in a simple way from 3-amino-1-propanol in five
steps. Sharpless asymmetric dihydroxylation was employed
as the source of chirality. The tandem processes used in our
synthetic endeavors such as oxidation-Wittig reaction,
deprotection-lactamization-epoxidation are the highlights
of this synthesis. Moreover, our successful asymmetric total
synthesis of both enantiomers of 1 also suggests the 1a
(3S,4S) configuration of the natural isomer.
lactam ring and epoxidation without formation of the pyr-
rolidine ring11 by nucleophilic displacement of the tosyl
group. This was achieved via one-pot strategy employing
the acid-mediated Boc deprotection (TFA, CH2Cl2, 0 °C)
and lactamization-epoxidation sequence promoted by basic
medium (aq NH3). The basic features involved in this step are
the occurrence of three reactions in one pot in tandem
fashion to furnish tedanalactam 1 in 74% yield. The overall
yield of 1 from 9 is 21%.
Having secured the route in terms of relative stereochem-
istry, we focused our effort on completing an enantioselec-
tive synthesis of tedanalactam. To this end, the diol 7a
prepared with AD-mix R and the diol 7b prepared with
AD-mix β was subjected to selective monotosylation at the
2-position by using TsCl, Et3N at 0 °C for 72 h to provide the
corresponding monotosylates 6a and 6b in good yield
(Scheme 4). To complete the total asymmetric synthesis,
final steps of deprotection, cyclization, and epoxidation were
Experimental Section
General Remarks. Column chromatography was performed
by using Merck silica gel 60/120 mesh size. 1H (300 MHz) and
13C (75 MHz) NMR spectra were recorded on a Bruker 300
(11) The steric crowding is inhibiting the nucleophilic displacement of the
tosyl group to form the pyrrolidine ring.
J. Org. Chem. Vol. 74, No. 16, 2009 6379

Majik et al.
JOCNote
instrument. Chemical shifts are expressed in δ relative to tetra-
methylsilane (TMS), the coupling constant J are given in Hz.
Chiral HPLC analyses was executed by using a Jasco HPLC
model MX-2080-31 instrument.
stirring for 30 min at rt. CH3SO2NH2 (0.264 g, 2.78 mmol) was
added and the mixture was cooled to 0 °C. Olefin 8 (0.850 g,
2.78 mmol) was added and the heterogeneous slurry was stirred
vigorously for 15 h at 0 °C and then 8 h at rt. Na2SO3 (3.2 g) was
added and the mixture was further stirred for 1 h. EtOAc
(30 mL) was added and the aq layer was extracted with EtOAc
(3ꢀ20 mL). The combined organic layer was washed with 5%
KOH (2ꢀ20 mL), dried over anhyd Na2SO4, concentrated, and
purified by column chromatography on silica gel (hexanes:
EtOAc=6:4) to give the corresponding diol 7a or 7b. IR and
1H and 13C NMR data for 7a and 7b were identical with those
of rac-diol 7 described above.
tert-Butyl (3-Hydroxypropyl)carbamate (10). The Boc2O
(5.83 g, 0.026 mol) was added dropwise to a stirred solution of
3-amino-1-propanol 9 (1.744 g, 0.023 mol) in dry THF (40 mL)
at 0 °C. Then Et3N (5.882 g, 0.058 mol) was added dropwise to
the mixture. The reaction mixture was then stirred at rt for 12 h.
THF was removed under vacuum, then water (30 mL) was
added and extracted in CH2Cl2 (3ꢀ30 mL). The organic layer
was washed with 5% aq HCl (2ꢀ20 mL), 5% aq NaHCO3 (2ꢀ
20 mL), sat. NaCl (20 mL), and then water (30 mL), dried over
anhyd Na2SO4, and concentrated in vacuum. Purification of the
oily crude product by column chromatography on silica gel
(hexanes:EtOAc = 4:6) afforded tert-butyl (3-hydroxypropyl)-
carbamate (10) (2.929 g, 72%) as a thick colorless liquid. IR
Benzyl (2R,3S)-5-[(tert-Butoxycarbonyl)amino]-2,3-dihydrox-
ypentanoate (7a). Product 7a was obtained as a white semisolid
(0.730 g, 77% yield), using AD-mix R; [R]31 -3.93 (c 0.891,
D
CHCl3); HPLC of diol 7a: 91% ee (Rt=16.0 min for the major
enantiomer, Rt=12.5 min for the minor one; column: Chiralpak
AD, UV detector, 254 nm, 20% 2-propanol in n-hexane; flow
rate: 0.7 mL/min).
1
(neat) 3612-3115, 1703 cm-1. H NMR (300 MHz, CDCl3) δ
1.46 (s, 9H), 1.66-1.70 (m, 2H), 2.97 (br s, 1H), 3.30 (q, J=6.0
Hz, 2H), 3.68 (t, J=6.0 Hz, 2H), 4.79 (br s, 1H). 13C NMR
(75 MHz, CDCl3) δ 28.3, 34.4, 37.0, 59.7, 79.6, 157.1. HRMS
m/z [M þ Na]þ calcd for C8H17NO3Na 198.1106, found
198.1104.
Benzyl (2S,3R)-5-[(tert-Butoxycarbonyl)amino]-2,3-dihydroxy-
pentanoate (7b). Product 7b (0.388 g, 71%) as a white semisolid
was obtained from olefin 8 (0.492 g) by using AD-mix β;
[R]31 þ4.16 (c 0.721, CHCl3); HPLC of diol 7b: 94% ee
D
Benzyl (2E)-5-[(tert-Butoxycarbonyl)amino]pent-2-enoate (8).
To a magnetically stirred suspension of PCC (3.068 g, 14.2
mmol) and NaOAc (1.167 g, 14.2 mmol) in anhyd CH2Cl2
(40 mL) was added tert-butyl (3-hydroxypropyl)carbamate
(10) (1.556 g, 8.89 mmol) in anhyd CH2Cl2 (5 mL), followed
by the addition of (benzyloxycarbonylmethylene) triphenylpho-
sphorane (4.014 g, 9.78 mmol) in one portion. The mixture was
stirred at rt for 7 h. Et2O (50 mL) was added and the supernatant
solution was decanted from the black granular solid. The
combined organic solutions were filtered through a short bed
of Celite and the filtrate obtained was evaporated to give a
residue that was purified by column chromatography on silica
gel (hexanes:EtOAc=7:3) to give pure benzyl (2E)-5-[(tert-bu-
toxycarbonyl)amino]pent-2-enoate (8) (1.955, 72%) as a color-
less viscous liquid. IR (neat) 3373, 1712, 1693 cm-1. 1H NMR
(300 MHz, CDCl3) δ 1.45 (s, 9H), 2.42 (q, J=6.6 Hz, 2H), 3.28
(q, J=6.0 Hz, 2H), 4.62 (br s, 1H), 5.20 (s, 2H), 5.95 (d, J=15.6
Hz, 1H), 6.96 (ddd, J=6.9, 7.2, 15.6 Hz, 1H), 7.35-7.38 (m, 5H).
13C NMR (75 MHz, CDCl3) δ 28.3, 32.9, 39.0, 66.2, 79.6, 123.0,
128.3, 128.5, 128.6, 136.0, 146.1, 155.8, 166.0. HRMS m/z
[M þ Na]þ calcd for C17H23NO4Na 328.1525, found 328.1518.
Benzyl 5-[(tert-Butoxycarbonyl)amino]-2,3-dihydroxypentan-
oate (7). To a stirred solution of 8 (0.736 g, 2.41 mmol) in
acetone-water 8:1 (v/v) (18 mL) was added NMO (0.566 g, 4.83
mmol) and aq 1% OsO4 (2 mL). The mixture was stirred at rt for
8 h. Na2SO3 (3.2 g) in 5 mL of water was added and the mixture
was further stirred for 1 h, then concentrated on a vacuum pump
to remove acetone. EtOAc (30 mL) was added and the aq layer
was extracted with EtOAc (3ꢀ20 mL). The combined organic
layer was dried over anhyd Na2SO4, concentrated, and purified
by column chromatography on silica gel (hexanes:EtOAc=6:4)
to give the diol 7 (0.679 g, 83%) as a white semisolid. IR (KBr)
(Rt=11.8 min for the major enantiomer, Rt=17.2 min for the
minor one; column: Chiralpak AD, UV detector, 254 nm, 20%
2-propanol in n-hexane; flow rate: 0.7 mL/min).
General Procedure for Monotosylation of Diol 7 (7a and 7b).
To a one-necked round-bottomed flask were added the
2,3-dihydroxy ester 7 (0.600 g, 1.77 mmol), CH2Cl2 (15 mL,
0.2 M solution in 2, 3-dihydroxy ester 7), and Et3N (0.268 g,
2.85 mmol). The flask was placed in an ice-water bath and the
reaction mixture was allowed to equilibrate for 20 min and then
p-toluenesulfonyl chloride (0.371 g, 1.94 mmol) was added in
one portion. The flask was fitted with septum and placed in a
refrigerator (5 °C) for 72 h. The mixture was then concentrated
to afford a paste that was dissolved in CHCl3 (40 mL). The
organic phase was washed with 1 N HCl (3 ꢀ15 mL), sat.
NaHCO3 (1 ꢀ 20 mL), and brine (2 ꢀ 15 mL), dried over anhyd
Na2SO4, and concentrated to afford the crude mixture, which
was purified by column chromatography on silica gel (hexanes:
EtOAc=6:4) to give the rac-monotosylate 6 as a white solid
(0.575 g, 66%), mp 88-89 °C. IR (KBr) 3621-3140, 1764, 1685
cm-1. 1H NMR (300 MHz, CDCl3) δ 1.42 (s, 9H), 1.64 (m, 2H),
2.44 (s, 3H), 3.16 (m, 1H), 3.42 (m, 2H), 4.13-4.17 (m, 1H), 4.75
(br s, 1H), 4.95 (d, J=3.3 Hz, 1H), 5.13 (s, 2H), 7.26-7.36 (m,
7H), 7.80 (d, J=8.4 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 21.7,
28.3, 33.5, 36.7, 67.5, 68.7, 79.8, 79.9, 128.2, 128.3, 128.4, 128.5,
128.7, 132.9, 134.8, 145.1, 157.1, 167.0. HRMS m/z [M þ Na]þ
calcd for C24H31NO8SNa 516.1668, found 516.1658.
Benzyl (2R,3S)-5-[(tert-Butoxycarbonyl)amino]-2-tosyl-3-hy-
droxypentanoate, 6a. Product 6a (0.609 g, 65%) was obtained
from 7a (0.645 g) as a white solid: mp 89-90 °C; [R]31D -13.33
(c 0.150, CHCl3); HPLC of monotosylate 6a: 91% ee (Rt=28.1
min for the major enantiomer, Rt=26.1 min for the minor one;
column: Chiralpak AD, UV detector, 254 nm, 10% 2-propanol
in n-hexane; flow rate: 1.0 mL/min).
1
3602-3041, 1749, 1680 cm-1. H NMR (300 MHz, CDCl3) δ
1.43 (s, 9H), 1.64-1.69 and 1.81-1.91 (2m, 2H), 2.84 (br s, 2H),
3.15-3.20 and 3.38-3.48 (2m, 2H), 4.0-4.03 (m, 1H), 4.13
(d, J=2.4 Hz, 1H), 5.26 (br s, 3H), 7.37 (s, 5H). 13C NMR (75
MHz, CDCl3) δ 28.3, 34.1, 37.2, 67.6, 69.7, 73.8, 79.8, 128.3,
128.5, 128.6, 135.1, 157.0, 173.1. HRMS m/z [M þ Na]þ calcd
for C17H25NO6Na 362.1580, found 362.1579.
Benzyl (2S,3R)-5-[(tert-Butoxycarbonyl)amino]-2-tosyl-3-hy-
droxypentanoate, 6b. Product 6b (0.437 g, 65%) was obtained
from 7b (0.460 g) as a white solid: mp 88-89 °C; [R]31D þ13.42
(c 0.149, CHCl3); HPLC of monotosylate 6b: 94% ee (Rt=27.5
min for the major enantiomer, Rt=30.1 min for the minor one;
column: Chiralpak AD, UV detector, 254 nm, 10% 2-propanol
in n-hexane; flow rate: 1.0 mL/min). IR and 1H and13CNMRdata
for 6a and 6b were identical with those of rac- 6 described
above.
General Procedure for Dihydroxylation of Alkene 8 with a
Chiral Catalyst. A mixture of K3Fe(CN)6 (2.731 g, 8.36 mmol),
K2CO3 (1.142 g, 8.36 mmol), and either (DHQ)2PHAL (0.108 g,
0.139 mmol, AD-mix R) or (DHQD)2PHAL (5 mol %, AD-
mix β) were stirred in t-BuOH (10 mL) and H2O (10 mL), after
which OsO4 (0.7 mL, 1% aq OsO4 soln.) was added with further
General Procedure for the Preparation of Tedanalactam (1).
To a stirred solution of monotosylate 6 (0.501 g, 1.02 mmol) in
CH2Cl2 (12 mL) was added TFA (3 mL) at 0 °C. The mixture
6380 J. Org. Chem. Vol. 74, No. 16, 2009

Majik et al.
JOCNote
was stirred at rt for 2 h and then concentrated under vacuum. Aq
NH3 (6 mL) was added to the resulting residue in CH2Cl2 (10
mL) at 0 °C and the solution was stirred for 2 h at rt. The mixture
was diluted with EtOAc (20 mL), washed with aq NH4Cl
(2ꢀ15 mL), and brine (1ꢀ15 mL), dried over anhyd Na2SO4,
concentrated, and purified by column chromatography on silica
gel (MeOH:CHCl3=1:19) to give the tedanalactam 1 (0.084 g,
74%) as a pale yellow oil. IR (neat) 3268, 1680 cm-1. 1H NMR
(300 MHz, CDCl3) δ 2.05 (ddd, J=6.0, 6.6, 12.3 Hz, 1H), 2.34-
2.90 (m, 1H), 3.06 (ddd, J=6.0, 6.6, 12.3 Hz, 1H), 3.34 (dd, J=4.2,
(3R,4R)-Epoxy-2-piperidone [(þ)-Tedanalactam] (1b). Pro-
duct 1b (0.031 g, 72% yield) was obtained from 6b (0.189 g) as
a yellow oil: [R]30 þ8.47 (c 0.118, MeOH); HPLC of tedana-
D
lactam 1b: 94% ee (Rt=10.9 min for the major enantiomer, Rt=
12.6 min for the minor one; column: Chiralpak AD, UV
detector, 206 nm, 10% 2-propanol in n-hexane; flow rate: 1.0
1
mL/min). IR and H and 13C NMR data for 1a and 1b were
identical with those of rac-1 described above.
Acknowledgment. We thank IISc, Bangalore, for the
HRMS facility and DST, CSIR New Delhi, for the financial
support. M.S.M. is thankful to CSIR for the award of the
Senior Research Fellowship.
12.3 Hz, 1H), 3.42 (m, 1H), 3.63 (br s, 1H), 6.18 (br s, 1H). 13
C
NMR (75 MHz, CDCl3) δ 23.5, 35.2, 50.6, 53.1, 169.1. HRMS: m/
z [M þ Na]þ calcd for C5H7NO2Na 136.0351, found 136.0374.
(3S,4S)-Epoxy-2-piperidone [(-)-Tedanalactam] (1a). Product
1a (0.092 g, 77% yield) was obtained from 6a (0.521 g) as a yellow
Supporting Information Available: Copies of 1H NMR, 13
C
oil: [R]30 -7.60 (c 0.130, MeOH); HPLC of tedanalactam 1a:
D
NMR, and DEPT spectra of all the compounds and the HPLC
chromatograph of 7, 6, and 1. This material is available free of
charge via the Internet at http://pubs.acs.org.
91% ee (Rt=14.5 min for the major enantiomer, Rt=12.7 min for
the minor one; column: Chiralpak AD, UV detector, 206 nm,
10% 2-propanol in n-hexane; flow rate: 1.0 mL/min).
J. Org. Chem. Vol. 74, No. 16, 2009 6381