Chromatography-free synthesis of Corey's intermediate for Tamiflu

Article abstract of DOI:10.1016/j.tet.2014.09.081

Column chromatography-free stereoselective synthesis of Corey's intermediate for Tamiflu (oseltamivir phosphate) was achieved, starting from l-glutamic acid γ-ethyl ester. The reagents and solvents used in the reaction scheme are industrially tractable, r

Full text of DOI:10.1016/j.tet.2014.09.081

Tetrahedron 70 (2014) 9113e9117
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Chromatography-free synthesis of Corey’s intermediate for Tamiflu
Makoto Furutachi, Naoya Kumagai, Takumi Watanabe , Masakatsu Shibasaki *
*
Institute of Microbial Chemistry (BIKAKEN), Tokyo, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 26 August 2014
Received in revised form 25 September 2014
Accepted 26 September 2014
Available online 2 October 2014
Column chromatography-free stereoselective synthesis of Corey’s intermediate for Tamiflu (oseltamivir
phosphate) was achieved, starting from L-glutamic acid g-ethyl ester. The reagents and solvents used in
the reaction scheme are industrially tractable, rendering the synthesis a potential starting point for
process research.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Tamiflu
Stereoselective synthesis
Chromatography-free synthesis
Corey’s intermediate
1. Introduction
Seasonal influenza virus infection in humans threatens the
quality of life and negatively impacts the economy. Vaccination is
the most effective method of preventing pathogenic spread, but it
can be rendered ineffective by genetic mutation of the virus. Fur-
ther, highly virulent mutants could cause a pandemic and high
mortality, as exemplified by three historical influenza pandemics,
the Spanish flu in 1918, the Asian flu in 1957, and the Hong Kong flu
in 1968.
The use of anti-influenza drugs is another powerful option to
combat these pathogens, and several medicines of this class are
available in the market. Among anti-influenza drugs, only Tamiflu
(
1, Scheme 1), an inhibitor of influenza viral neuraminidase de-
1
2
veloped by Gilead Science and Roche, can be orally administered,
and, due to the ease of usage, it is the most commonly prescribed
anti-influenza drug in clinical use. Although the process route is
carefully established and unarguably efficient, alternative synthetic
routes toward Tamiflu have been reported by many research
groups3 in response to concerns regarding the supply of shikimic
acid, the starting material of the current manufactured synthesis of
Tamiflu.
Scheme 1. Formal total synthesis of Tamiflu: glutamate route.
,4
opening of meso-aziridine and the DielseAlder reaction.5 More
recently, we completed a formal total synthesis of Tamiflu by tar-
We previously reported syntheses of Tamiflu using several ap-
proaches, taking advantage of a variety of catalytic asymmetric
reactions to address key stereochemical issues: nucleophilic
6
geting ‘Corey’s intermediate’ (3) as the synthetic goal. In the
present study, we used a Dieckmann condensation reaction to
construct a six-membered ring core (5), for which the acyclic
substrate 4 was prepared in a stereo-controlled manner according
to two different strategies:
component reaction; and use of
a chiral starting material (>99% ee). While the catalytic asymmetric
three-component reaction produced modest level of
a
catalytic asymmetric three-
*
Corresponding authors. Tel.: þ81 3 3441 4173; fax: þ81 3 3441 7589 (T.W.); tel.:
L-glutamic acid -ethyl ester 2 as
g
þ81 3 3447 7779; fax: þ81 3 3441 7589 (M.S.); e-mail addresses: twatanabe@bi-
kaken.or.jp (T. Watanabe), mshibasa@bikaken.or.jp, mshibasa@mol.f.u-tokyo.ac.jp
(
M. Shibasaki).
a
http://dx.doi.org/10.1016/j.tet.2014.09.081
040-4020/Ó 2014 Elsevier Ltd. All rights reserved.
0

9114
M. Furutachi et al. / Tetrahedron 70 (2014) 9113e9117
ꢁ
C
enantioselectivity, up to 76% ee, the use of
ester 2 as a chiral starting material to retain its enantiopurity
during the entire process to give Corey’s intermediate in 13 steps.
L
-glutamic acid
g
-ethyl
a byproduct, and the HWE olefination was performed at ꢀ78
(entry 5e1), which is too low to be practical at an industrial scale.
The oxidation problem was resolved by changing the conditions to
a copper-catalyzed TEMPO-promoted methodology, which was
recently reported by Stahl. Although the catalyst loading had to be
increased to 20 mol %, clean conversion to 10 was observed in 1.5 h
(entries 4e2 and 3). After thorough optimization, the succeeding
7
The results indicated that ‘the glutamate route’ was a good starting
point for further elaboration to an industrial-scale synthesis, and
prompted us to optimize the scheme toward this end (Scheme 1).
Although the chemical yield of each step in the synthesis should be
better than moderate, most of the steps required silica gel column
chromatography, which is not practical for industrial-scale syn-
thesis. In addition, this route includes reagents and conditions that
are unacceptable for industrial processes, including volatile and
11
ꢁ
HWE process was effective at ꢀ40 C, at the slight expense of Z-
selectivity (Z/E¼7/1), which essentially had no detrimental effects
in the subsequent reactions (entry 5e2). Purification by silica gel
chromatography, performed in the previous report, was not
necessary.
corrosive reagent (HCO
2
H), an explosive reagent (HClO
4
), extremely
ꢁ
low reaction temperature (ꢀ78 C), long reaction time (2 days), and
reactions that emit an unpleasant odor (DoeringeParikh oxidation).
Herein, we report a column chromatography-free synthesis of
A key reaction of this synthetic route, Dieckmann condensation
of the crude material of diester 4, was conducted with lithium
diisopropylamide (LDA) as a base (entry 6e2) instead of lithium
hexamethyl disilazide (LHMDS; entry 6e1), providing the same
efficiency to give a cyclohexenone derivative 5. A 1,2-reduction of
the crude material from each condition resulted in the same
chemical yield over two steps (62%, entries 6e1 and 2).
Exchange of the protecting group of the resultant cyclohexenol
12 from diallyl to Boc exhibited efficient conversion, but it was the
most difficult process to avoid silica gel column chromatography
purification (Scheme 3). Subsequent elimination of the secondary
hydroxyl group gave many byproducts, thereby affording a low
yield of Corey’s intermediate (3), which definitely required silica gel
column chromatography purification. It was particularly difficult to
eliminate the stoichiometric amount of diallyl barbiturate during
‘Corey’s intermediate’ for the synthesis of Tamiflu by thorough
optimization of the previously reported glutamate route, which
relies on liquideliquid partition and recrystallization as purification
methods to avoid the use of silica gel column chromatography. In
the present synthesis, many of the problematic steps for process
research were updated to more preferable conditions for process
development.
2
. Results and discussion
The glutamate route commences with
a-esterification of
L
-glutamic acid
esterification with AcOt-Bu (Scheme 2). In the original procedure,
HClO (entry 1e1), an explosive and strong oxidant, was used as an
g-ethyl ester 2 by acid-promoted trans-
8
2
the deallylation work-up, as well as to remove superfluous Boc O
4
after reprotection of the primary amine. Through extensive in-
vestigation of the deprotection, a tactic liquid-liquid partition
afforded the substrate for Boc-protection with satisfactory purity:
the free amine product was treated with 1 M HCl to form the cor-
responding salt 15 to be dissolved in water, and the barbiturate
derivative 14 was washed away with extraction by organic solvent.
The aqueous solution of the salt could be directly used for in-
troduction of the Boc group under biphasic conditions. The
acidic promoter. While the usual esterification conditions com-
prising an alcoholic solution with a more conventional protic acid
suffered from low conversion (data not shown), HClO
replaced with H SO to afford the corresponding tert-butyl ester 6
entry 1e4). The reaction time was shortened to 18 h, and AcOEt
could be used instead of Et O for extraction of the product upon
4
was
2
4
(
2
work-up, without a substantial loss of chemical yield.
In the next diallylation of the primary amino group, three
equimolar amounts of allyl bromide (1.5-fold of the theoretically
required amount, entry 2e3) showed satisfactory conversion to 7,
which enabled complete removal of the reagent and byproducts
during simple work-up with filtration and evaporation. When allyl
bromide was further decreased to 2.5 equimolar amounts, the re-
action did not complete within 20 h (entry 2e4). The thus-
optimized reaction conditions produced a relatively clean crude
mixture, making silica gel chromatography unnecessary at this
stage.
remaining Boc
the resulting -hydroxy ester 13 as a solid in a pure form. Although
the yield was modest after purification by recrystallization (33% in
two steps), these modifications would be key to realizing a col-
umn-free reaction sequence.
Final elimination of the hydroxyl group via a mesylate was un-
eventful, even while using THF, which was replaced the originally
2 2
used volatile toxic solvent, CH Cl , to provide Corey’s intermediate
2
O was dissolved in n-hexane and discarded to give
b
12
(3) in quantitative yield (total yield of 4%). The thus-obtained
samples showed satisfactory purity without silica gel chromatog-
raphy even after the last step, as shown in Supplementary data.
In the original protocol, the subsequent acid-mediated depro-
tection of tert-butyl ester to the corresponding carboxylic acid 8
required a large excess of volatile and corrosive HCO
2
H (also used
3. Summary
as the solvent, entry 3e1). Although H SO as an acidic component
2
4
was not effective (entries 3e2 and 3), the desired carboxylic acid 8
Column chromatography-free synthesis of Corey’s intermediate
for the synthesis of Tamiflu was completed. The newly refined
synthetic scheme used reagents and reaction conditions more
suitable for applying to process research in the next stage of de-
velopment. Further optimization of this route to improve the yield
of each step, and to increase the cost-effectiveness and benignity of
all of the conditions is ongoing.
was obtained in 97% yield using 4 M solution of HCl in 1,4-dioxane
ꢁ
with gentle warming at 50 C for 12 h (entry 3e4). Chemoselective
reduction of the carboxyl group to the primary alcohol 9 via mixed
9
anhydride was then achieved according to the previously reported
conditions, and no chromatography was needed to attain the purity
required for the subsequent steps.
With the primary alcohol 9 in hand, the two-step procedure to
access a substrate for Dieckmann condensation to furnish a skeletal
six-membered ring of Tamiflu was applied: originally, Doer-
4. Experimental
4.1. General
ingeParikh oxidation (SO
3 3
$pyridine, Et N, DMSO, entry 4e1) was
followed by the Z-selective HornereWadswortheEmmons (HWE)
1
0
reaction with phosphonate 11, reported by Still and Gennari. Al-
though the reaction sequence effectively afforded the desired olefin
4
All reactions were performed in round-bottom flasks with
a Teflon-coated magnetic stirring bar under air unless otherwise
noted. All work-up and purification procedures were performed
with reagent grade solvents under ambient atmosphere. Infrared
in 88% yield in a highly Z-selective manner (Z/E¼15/1), the
DoeringeParikh oxidation inevitably outputs foul-smelling Me S as
2

M. Furutachi et al. / Tetrahedron 70 (2014) 9113e9117
9115
Scheme 2. Chromatography-free synthesis of Corey’s intermediate for the synthesis of Tamiflu.
(
IR) spectra were recorded on a JASCO FT/IR 4100 Fourier-transform
a JASCO HPLC system equipped with Daicel chiral-stationary-phase
columns ( CN, and CH Cl were purified
by passing through a solvent purification system (Glass Contour).
IR spectrophotometer. NMR was recorded on a JEOL ECS-400
4
f
0.46 cmꢂ25 cm). THF, CH
3
2
2
1
00 MHz spectrometer. For H NMR (400 MHz), chemical shifts
of protons are reported in parts per million downfield from tetra-
methylsilane and are referenced to residual protium in the NMR
4.2. Synthesis of Corey’s intermediate
13
solvent (CDCl
are reported in a scale relative to the NMR solvent (CDCl
77.0 ppm) as an internal reference. The NMR data are reported as
3
, d 7.24 ppm). For C NMR (100 MHz), chemical shifts
3
,
4.2.1. (S)-1-tert-Butyl 5-ethyl 2-aminopentanedioate (6). A solution
ꢁ
d
of 95% H
2
SO
4
(5.077 mL, 90.00 mmol) at 4 C was added to a solu-
follows: chemical shifts, multiplicity (s: singlet, d: doublet, dd:
doublet of doublets, t: triplet, q: quartet, m: multiplet), coupling
constant (Hertz), and integration. Optical rotation was measured
using a 2-mL cell with a 1.0-dm path length on a polarimeter. High-
resolution mass spectra (ESI-Orbitrap) were measured on a Thermo
Fisher Scientific LTQ Orbitrap XL. HPLC analysis was conducted on
tion of -glutamic acid
L
g
-ethyl ester 2 (8.760 g, 50.00 mmol) in
AcOt-Bu (217.4 mL). The resulting solution was warmed to room
temperature and stirred for 18 h, then 0.1 M aqueous HCl
(350.0 mL) and AcOEt were sequentially added to the mixture. The
aqueous phase was separated from the organic phase, and adjusted
to pH¼9 with saturated aqueous Na
2 3
CO . The aqueous phase was

9116
M. Furutachi et al. / Tetrahedron 70 (2014) 9113e9117
THF (93.33 mL) was slowly added to a solution of 10 (20.00 mmol)
ꢁ
in THF (106.7 mL) over 45 min at ꢀ40 C. After the addition was
completed, the mixture was stirred at the same temperature for an
additional 15 min. Then, the reaction mixture was quenched with
cold water. After the mixture was warmed to room temperature,
the product was extracted with AcOEt. The combined organic layers
were washed with brine, dried over Na
under reduced pressure to afford a crude material containing 4
estimated to be 93% yield, Z/E¼7/1), which was used directly in the
next step without purification.
2 4
SO , and concentrated
(
4
.2.6. (5S)-Ethyl 5-(diallylamino)-2-hydroxycyclohex-3-
enecarboxylate (12). A 1.13 M THF solution of LDA (22.94 mL,
2
5.92 mmol) was slowly added to a stirred solution of 4
ꢁ
(8.640 mmol) in THF (20.26 mL) at ꢀ40 C, and the mixture was
Scheme 3. Protocol for the synthesis of 13 from 12.
stirred at the same temperature for 30 min. The reaction mixture
was then quenched with saturated aqueous NH Cl, warmed to
4
extracted with AcOEt, and the organic layers were combined,
washed with brine, dried over Na SO , and concentrated to afford
room temperature, and the product was extracted with AcOEt. The
combined organic layers were washed with brine, dried over
2
4
the desired ester 6 as a pale yellow oil (7.190 g, 62%). The crude
product was NMR pure and was used directly in the next step
without purification.
Na
2 4
SO , filtered, and concentrated to give crude 5 (ketoeenol
mixture), which was used for the next reaction without further
purification. NaBH
4
(653.7 mg, 17.28 mmol) was added to a stirred
ꢁ
solution of crude 5 (8.640 mmol) in MeOH (43.20 mL) at ꢀ20 C,
4.2.2. (S)-1-tert-Butyl5-ethyl-2-(diallylamino)pentanedioate(7). Diester
and the mixture was stirred for 30 min at the same temperature.
6
(4.626 g, 20.00 mmol) was dissolved in EtOH (100.0 mL), and pow-
4
After adding saturated aqueous NH Cl, the reaction mixture was
dered NaHCO
3
(6.721 g, 80.00 mmol) and allyl bromide (5.186 mL,
warmed to room temperature, and MeOH was removed under re-
duced pressure. AcOEt was added, and the resulting aqueous layer
was extracted with AcOEt. The combined organic layers were
washed with brine, dried over Na SO , filtered, and concentrated to
2 4
give crude 12 (estimated to be 62% yield over two steps), which was
used for the next reaction without further purification.
60.00 mmol) were added at room temperature. The mixture was stir-
red under reflux for 20 h, then cooled to room temperature, concen-
trated under reduced pressure, filtered through a Celite pad using
AcOEt, and concentrated to give crude material containing 7 (estimated
to be 80% yield), which was used directly in the next step without
purification.
4
. 2 . 7. ( 5S )- Et hyl 5- ((ter t- bu to xyca r bo nyl) a mi no ) -2 -
4.2.3. (S)-Ethyl 4-(diallylamino)-5-hydroxypentanoate (9). Diester 7
hydroxycyclohex-3-enecarboxylate (13). Pd(PPh (619.3 mg,
3 4
)
(
20.00 mmol) was dissolved in 4 M HCl in 1,4-dioxane (400.0 mL)
0.5357 mmol, 10 mol %) and N,N-dimethylbarbituric acid (5.017 g,
32.14 mmol) were successively added to a stirred solution of crude
ꢁ
and stirred at 50 C for 12 h. The reaction mixture was cooled to
room temperature and concentrated under reduced pressure to
afford the crude mixture containing 8. Et N (13.86 mL,100.0 mmol),
3
12 (5.357 mmol) in CH
mixture was stirred for 1 h. Then, 1.0 M aqueous HCl was added and
washed with AcOEt. Na CO (5.678 g, 53.57 mmol) and a 1.0 M
solution of Boc O in AcOEt (26.79 mL, 26.79 mmol) were succes-
2 2
Cl (26.79 mL) at room temperature, and the
followed by ethyl chloroformate (5.711 mL, 60.00 mmol), was
2
3
ꢁ
added to the resultant residue in toluene (400.0 mL) at ꢀ20 C.
2
After 45 min, NaBH
4
(3.026 g, 80.00 mmol) was added in one
sively added to the aqueous phase at room temperature, and the
mixture was stirred for 2 h at room temperature. After the addition
portion. MeOH (133.3 mL) was then added dropwise to the mixture
ꢁ
over 30 min at ꢀ20 C. The solution was stirred for an additional
3
of saturated aqueous NaHCO , the aqueous layer was extracted
ꢁ
1
5 min at ꢀ20 C and then quenched with cold water. After the
with AcOEt. The combined organic layers were dried over Na SO4,
2
mixture was warmed to room temperature, the organic solvents
were evaporated under reduced pressure, and the product was
extracted with AcOEt, washed with brine, dried over Na SO , and
2 4
concentrated under reduced pressure to afford crude material
containing 9 (estimated to be 74% yield over two steps), which was
used directly in the next step without purification.
n-hexane was added (AcOEten-hexane¼1:1), filtered through thin-
layered silica gel, and concentrated to give a crude mixture, which
was purified by recrystallization by n-hexane/AcOEt to afford 13
(234.7 mg, 0.8226 mmol, diastereomeric mixture, 3% yield over
thirteen steps) as a pale yellow solid.
4
.2.8. (S)-Ethyl 5-((tert-butoxycarbonyl)amino)cyclohexa-1,3-
dienecarboxylate (3). MsCl (17.04 L, 0.2200 mmol) and Et
(55.45 L, 0.4000 mmol) were successively added to a stirred so-
4
.2.4. (S)-Ethyl 4-(diallylamino)-5-oxopentanoate (10). [Cu(MeCN)
4
]
m
3
N
ꢀ
0
BF
4
(1.258 g, 4.000 mmol), 2,2 -bipyridyl (624.8 mg, 4.000 mmol),
L,
.000 mmol) were successively added to a solution of alcohol 9
20.00 mmol) in CH CN (100.0 mL) at room temperature. The so-
m
ꢁ
TEMPO (625.2 mg, 4.000 mmol), and 1-methylimidazole (631.5
m
lution of 13 (57.06 mg, 0.2000 mmol) in THF (1.000 mL) at 4 C, and
8
(
the mixture was stirred for 10 min at the same temperature. DBU
(89.53 mL, 0.6000 mmol) was added to the mixture, and the mixture
3
lution was stirred for 1.5 h at the same temperature and then
quenched with water. The product was extracted with AcOEt,
was stirred further for 1 h at room temperature. After the addition
of 1 M aqueous HCl, the aqueous layer was extracted with AcOEt.
2 4
washed with brine, dried over Na SO , and concentrated under
The combined organic layers were dried over Na
2
SO
4
, filtered, and
reduced pressure to afford crude material containing 10 (estimated
to be 91% yield), which was used directly in the next step without
purification.
concentrated to give Corey’s intermediate
3
(55.77 mg,
0.2086 mmol, quantitative yield) as a pale yellow oil. The crude
product was NMR pure. Physicochemical data were identical to
6
1
those previously reported, as follows. H NMR (CDCl
7.03 (d, J¼3.9 Hz, 1H), 6.18e6.09 (m, 2H), 4.61 (m, 1H), 4.42 (m,
1H), 4.20 (q, J¼7.1 Hz, 2H), 2.76e2.61 (m, 2H), 1.42 (s, 9H), 1.29 (t,
3
, 400 MHz)
4
.2.5. (S)-Diethyl 4-(diallylamino)-(Z)-hept-2-enedioate (4). A so-
lution of NaI (4.497 g, 30.00 mmol), DBU (4.178 mL, 28.00 mmol),
and (CF CH O) P(]O)CH CO Et (11) (6.002 mL, 28.00 mmol) in
d
13
3
2
2
2
2
J¼7.1 Hz, 3H); C NMR (CDCl
3
, 100 MHz) d 166.8, 154.9, 132.7, 131.7,

M. Furutachi et al. / Tetrahedron 70 (2014) 9113e9117
9117
1
27.0, 124.8, 79.5, 60.6, 43.5, 28.8, 28.4, 14.3; IR (neat, cmꢀ1) 3352,
Shie, J.-J.; Fang, J.-M.; Wong, C.-H. Angew. Chem., Int. Ed. 2008, 47, 5788; (j)
Matveenko, M.; Willis, A. C.; Banwell, M. G. Tetrahedron Lett. 2008, 49, 7018; (k)
Ishikawa, H.; Suzuki, T.; Hayashi, Y. Angew. Chem., Int. Ed. 2009, 48, 1304; (l)
Ishikawa, H.; Suzuki, T.; Orita, H.; Uchimaru, T.; Hayashi, Y. Chem.dEur. J. 2010,
16, 12616; (m) Ishikawa, H.; Bondzic, B. P.; Hayashi, Y. Eur. J. Org. Chem. 2011,
þ
2
978, 1705; ESI-HRMS calcd for C14
H
21NO
4
Na [MþNa] 290.1363,
2
5
25
found 290.1361; [
a]
D
ꢀ205.5 (98.9% ee, c 1.1, CHCl
3
), lit. [
a]
D
ꢀ217
6
(
>99% ee, c 1.1, CHCl
ALPAK AD-H, 1.0 mL/min, 254 nm) t
major).
3
); HPLC (n-hexane/2-propanol¼50/1, CHIR-
6020; (n) Mukaiyama, T.; Ishikawa, H.; Koshino, H.; Hayashi, Y. Chem.dEur. J.
2013, 19, 17789; (o) Zhu, S.; Yu, S.; Wang, Y.; Ma, D. Angew. Chem., Int. Ed. 2010,
49, 4656; (p) Sullivan, B.; Carrera, I.; Drouin, M.; Hudlicky, T. Angew. Chem., Int.
R
¼16.4 min (minor), 19.3 min
(
Ed. 2009, 48, 4229; (q) Werner, L.; Machara, A.; Hudlicky, T. Adv. Synth. Catal.
010, 352, 195; (r) Mandai, T.; Oshitari, T. Synthesis 2009, 783; (s) Oshitari, T.;
Mandai, T. Synlett 2009, 787; (t) Sun, H.; Lin, Y.-J.; Wu, Y.-L.; Wu, Y. Synlett 2009,
473; (u) Osato, H.; Jones, I. L.; Chen, A.; Chai, C. L. L. Org. Lett. 2010, 12, 60; (v)
Wichienukul, P.; Akkarasamiyo, S.; Kongkathip, N.; Kongkathip, B. Tetrahedron
Lett. 2010, 51, 3208; (w) Ma, J.; Zhao, Y.; Ng, S.; Zhang, J.; Zeng, J.; Than, A.; Chen,
P.; Liu, X.-W. Chem.dEur. J. 2010, 16, 4533; (x) Weng, J.; Li, Y.-B.; Wang, R.-B.; Li,
F.-Q.; Liu, C.; Chan, A. S. C.; Lu, G. J. Org. Chem. 2010, 75, 3125; (y) Kamimura, A.;
Nakano, T. J. Org. Chem. 2010, 75, 3133; (z) Ko, J. S.; Keum, J. E.; Ko, S. Y. J. Org.
Chem. 2010, 75, 7006; (aa) Trost, B. M.; Zhang, T. Chem.dEur. J. 2011, 17, 3630;
2
Acknowledgements
2
M.S and M.F. are grateful to Adaptable and Seamless Technology
Transfer Program through Target-driven R&D, JST for financial
support. The authors appreciate Dr. Shinjiro Sumi, Mr. Hiroyuki
Yamaguchi, Mr. Tadashi Ishiyama, and Mr. Shinya Ikeda (Meiji Seika
Pharma Co., Ltd.) for their valuable suggestions. The authors thank
Ms. Chiharu Sakashita (BIKAKEN) for her technical assistance. The
authors are thankful to Dr. Ryuichi Sawa, Ms. Yumiko Kubota, and
Ms. Yuko Takahashi (BIKAKEN) for spectroscopic analysis.
(
(
ab) Trajkovic, M.; Ferjancic, Z.; Saicic, R. N. Org. Biomol. Chem. 2011, 9, 6927;
ac) Trajkovic, M.; Ferjancic, Z.; Saicic, R. N. Synthesis 2013, 45, 389; (ad) Werner,
L.; Machara, A.; Sullivan, B.; Carrera, I.; Moser, M.; Adams, D. R.; Hudlicky, T.;
Andraos, J. J. Org. Chem. 2011, 76, 10050; (ae) Oh, H.-S.; Kang, H.-Y. J. Org. Chem.
2012, 77, 8792; (af) Rehak, J.; Hut’ka, M.; Latika, A.; Brath, H.; Almassy, A.;
Hajzer, V.; Durmis, J.; Toma, S.; Sebesta, R. Synthesis 2012, 44, 2424; (ag) Cha-
van, S. P.; Chavan, P. N.; Khairnar, L. B. RSC Adv. 2014, 4, 11417 For alternative
approaches using (ꢀ)-shikimic acid as starting materials, see: (ah) Karpf, M.;
Trussardi, R. Angew. Chem., Int. Ed. 2009, 48, 5760; (ai) Nie, L.-D.; Shi, X.-X.
Tetrahedron: Asymmetry 2009, 20, 124; (aj) Nie, L.-D.; Shi, X.-X.; Ko, K. H.; Lu,
W.-D. J. Org. Chem. 2009, 74, 3970; (ak) Nie, L.-D.; Wang, F.-F.; Ding, W.; Shi, X.-
X.; Lu, X. Tetrahedron: Asymmetry 2013, 24, 638.
. For reviews, see: (a) Shibasaki, M.; Kanai, M. Eur. J. Org. Chem. 2008, 1839; (b)
Farina, V.; Brown, J. D. Angew. Chem., Int. Ed. 2006, 45, 7330; (c) Magano, J.
Chem. Rev. 2009, 109, 4398; (d) Andraos, J. Org. Process Res. Dev. 2009, 13, 161;
Supplementary data
1H and 13C NMR spectra, and HPLC data for 3. Supplementary
data related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2014.09.081.
4
References and notes
(
e) Magano, J. Tetrahedron 2011, 67, 7875.
1
. Kim, C. U.; Lew, W.; Williams, M. A.; Liu, H. T.; Zhang, L. J.; Swaminathan, S.;
Bischofberger, N.; Chen, M. S.; Mendel, D. B.; Tai, C. Y.; Laver, W. G.; Stevens, R. C.
J. Am. Chem. Soc. 1997, 119, 681.
5. (a) Fukuta, Y.; Mita, T.; Fukuda, N.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc.
2006, 128, 6312; (b) Mita, T.; Fukuda, N.; Roca, F. X.; Kanai, M.; Shibasaki, M.
Org. Lett. 2007, 9, 259; (c) Yamatsugu, K.; Kamijo, S.; Suto, Y.; Kanai, M.; Shi-
basaki, M. Tetrahedron Lett. 2007, 46, 1403; (d) Yamatsugu, K.; Yin, L.; Kamijo, S.;
Kimura, Y.; Kanai, M.; Shibasaki, M. Angew. Chem., Int. Ed. 2009, 48, 1070; (e)
Yamatsugu, K.; Kanai, M.; Shibasaki, M. Tetrahedron 2009, 65, 6017.
6. Yeung, Y.-Y.; Hong, S.; Corey, E. J. J. Am. Chem. Soc. 2006, 128, 6310.
7. Alagiri, K.; Furutachi, M.; Yamatsugu, K.; Kumagai, N.; Watanabe, T.; Shibasaki,
M. J. Org. Chem. 2013, 78, 4019.
8. Hu, J.; Miller, M. J. J. Am. Chem. Soc. 1997, 119, 3462.
9. Ishizumi, K.; Koga, K.; Yamada, S.-I. Chem. Pharm. Bull. 1968, 16, 492.
10. Still, W. C.; Gennari, C. Tetrahedron Lett. 1983, 24, 4405.
11. (a) Hoover, J. M.; Stahl, S. S. J. Am. Chem. Soc. 2011, 133, 16901; (b) Hoover, J. M.;
Ryland, B. L.; Stahl, S. S. J. Am. Chem. Soc. 2013, 135, 2357.
12. When the product was purified by silica gel column chromatography in a pre-
2
. (a) Karpf, M.; Trussardi, R. J. Org. Chem. 2001, 66, 2044; (b) Rohloff, J. C.; Kent, K.
M.; Postich, M. J.; Becker, M. W.; Chapman, H. H.; Kelly, D. E.; Lew, W.; Louie, M.
S.; McGee, L. R.; Prisbe, E. J.; Schultze, L. M.; Yu, R. H.; Zhang, L. J. J. Org. Chem.
1998, 63, 4545; (c) Abrecht, S.; Harrington, P.; Iding, H.; Karpf, M.; Trussardi, R.;
Wirz, B.; Zutter, U. Chimia 2004, 58, 621.
3
. (a) Bromfield, K. M.; Graden, H.; Hagberg, D. P.; Olsson, T.; Kann, N. Chem.
Commun. 2007, 3183; (b) Satoh, N.; Akiba, T.; Yokoshima, S.; Fukuyama, T.
Angew. Chem., Int. Ed. 2007, 46, 5734; (c) Satoh, N.; Akiba, T.; Yokoshima, S.;
Fukuyama, T. Tetrahedron 2009, 65, 3239; (d) Shie, J.-J.; Fang, J.-M.; Wang, S.-Y.;
Tsai, K.-C.; Cheng, Y.-S. E.; Yang, A.-S.; Hsiao, S.-C.; Su, C.-Y.; Wong, C.-H. J. Am.
Chem. Soc. 2007, 129, 11892; (e) Chen, C.-A.; Fang, J.-M. Org. Biomol. Chem. 2013,
1
1, 7687; (f) Kipassa, N. T.; Okamura, H.; Kina, K.; Hamada, T.; Iwagawa, T. Org.
Lett. 2008, 10, 815; (g) Trost, B. M.; Zhang, T. Angew. Chem., Int. Ed. 2008, 47,
759; (h) Zutter, U.; Iding, H.; Spurr, P.; Wirz, B. J. Org. Chem. 2008, 73, 4895; (i)
vious attempt, the isolated yield was 87%
3