Preparation of (+)-biotin: Process development and scale-up

Article abstract of DOI:10.3987/COM-15-13379

A practical asymmetric total synthesis of (+)-biotin based upon the chiral bifunctional sulfamide 8-promoted enantioselective anhydride desymmetrization has been achieved via the key chiral intermediacy of (3aS, 6aR)-1,3-bis(4-methoxybenzyl)tetrahydro-4H-thieno[3,4-d]imidazole-2,4(1H)-dione (4). In addition, the installation of the 4-carboxybutyl side chain at C-4 position of 4 was efficiently introduced by an improved C4+C1 strategy.

Full text of DOI:10.3987/COM-15-13379

HETEROCYCLES, Vol. 92, No. 3, 2016, pp. -. © 2016 The Japan Institute of Heterocyclic Chemistry
Received, 21st November, 2015, Accepted, 22nd January, 2016, Published online, 28th January, 2016
DOI: 10.3987/COM-15-13379
PREPARATION OF (+)-BIOTIN: PROCESS DEVELOPMENT AND
SCALE-UP
Fei Xiong,1,2,3,* Jin Li,2 Gen Li,2 Bo Song,2 Yu-Xiao Zhou,2 Fen-Er Chen,3 and
Dan Li3
1 Hubei Key Laboratory of Drug Synthesis and Optimization, JingChu University
of Technology, Jingmen 448000, P. R. China
2 Department of Chemistry, University of Shanghai for Science and Technology,
Shanghai 200093, P. R. China
3 Department of Chemistry, Fudan University, Shanghai 200043, P. R. China;
e-mail: feixiong09@fudan.edu.cn or fxiong@usst.edu.cn
Abstract – A practical asymmetric total synthesis of (+)-biotin based upon the
chiral bifunctional sulfamide 8-promoted enantioselective anhydride desymmetri-
zation has been achieved via the key chiral intermediacy of (3aS,6aR)-1,3-bis(4-
methoxybenzyl)tetrahydro-4H-thieno[3,4-d]imidazole-2,4(1H)-dione (4). In addi-
tion, the installation of the 4-carboxybutyl side chain at C-4 position of 4 was
efficiently introduced by an improved C4+C1 strategy.
The Roche lactone-thiolactone strategy for the synthesis of (+)-biotin originally described by Goldberg
and Sternbach in 19511-3 has proven to be the most efficient method so far.4-7 It is thus not surprising that
over the past decades, the major interest has been focused on developing commercially viable approach to
prepare the optically pure Roche lactone, which has been obtained by various methods involving optical
resolution4-7 and more recently, via asymmetric synthesis.8-17 Despite the progress made since the report
of the original patent description, there are very few reports that relate to the deprotection (debenzylation)
of N-benzylated imidazolido-thiophanes by reaction with hydrobromic acid13 or a mixture of sulfuric and
glacial acetic acid10,18 in the final step of the total synthesis. Even then, many of these procedures suffer
from one or more disadvantages such as prolonged reaction time, poor yields, and use of environmentally
unfriendly reagents. Therefore, the design of an efficient and convenient method for the cleavage of the
protective group (usually benzyl) of N,N-diprotected (as dibenzyl) biotin to (+)-biotin or the use of an
alternate and more readily removable protecting group instead of the classical benzyl group is still a

desirable target for the preparation of (+)-biotin on a large scale.
A complete literature search (Chemical Abstracts) revealed that removal of the N-(p-methoxybenzyl)
group could be readily accomplished by treatment with potassium persulfate19 or ceric ammonium
nitrate.20 In connection with our sustained interest in the synthesis of (+)-biotin, we recently reported the
preparation of cis-1,3-bis(4-methoxybenzyl)tetrahydro-2H-furo[3,4-d]imidazole-2,4,6-trione (1).21 On the
basis of the previously reported success of the cleavage of N-(p-methoxybenzyl) groups,19,20 it was
anticipated that the use p-methoxybenzyl groups (and presumably their facile removal) in N,N-bis-(p-
methoxybenzyl)biotin to (+)-biotin might constitute an improved procedure. We now report the success-
ful execution of this new procedure to (+)-biotin, albeit removal of the p-methoxybenzyl group did not
occur as anticipated from the literature reports.
O
O
PMBN
H
NPMB
H
CO2H
PMBN
H
NPMB
H
1) KBH4, CaCl2
2) 10% Na2CO3 aq.
3) 5% HCl
trans-cinnamyl alcohol, 8
25 oC
PhCH=CHCH2O2C
O
O
O
2
1
CF3
O
O
O
O
S
PMBN
H
NPMB
H
PMBN
H
NPMB
H
MeCOSK
DMF
HN
CF3
OTr
O
O
O
S
NMe2
4
3
O2N
catalyst 8
Scheme 1
Our improved process started with the generation of chiral building block (4S,5R)-hemiester 2, the direct
precursor to (3aS,6aR)-lactone 3, via the asymmetric alcoholysis of cis-1,3-bis-(p-methoxy-
benzyl)tetrahydro-2H-furo[3,4-d]imidazole-2,4,6-trione (1) (Scheme 1). The use of the chiral amines
(Cinchona alkaloids)-based sulfonamide12 as the organocatalyst to mediate the nucleophilic ring-opening
of the prochiral cyclic anhydride facilitated the highly enantioselective desymmetrization of 1 with
cinnamyl alcohol compared to existing methods9-13,15-18 in terms of enantioselectivity, rapid reaction times
and the practicality on large-scale production. Inspired by this potential approach and our continued
interest to discover other chiral amine scaffolds, we first investigated the nucleophilic opening of 1 in the
presence of alkamine-derived bifunctional sulfamide 8 (110 mol%), which was synthesized from a novel
chiral source (1S,2S)-2-amino-1-(p-nitrophenyl)propane-1,3-diol,22 a by-product in the industrial
production of chloramphenicol. As expected, the asymmetric desymmetrization reaction proceeded

readily in methyl tert-butyl ether (MTBE) at room temperature to afford the desired (4S,5R)-hemiester 2
in nearly quantitative yield in 80% ee after 5 min (Table 1, entry 1). Encouraged by these promising
results, a range of various reaction conditions (solvent, catalyst loading and concentration) were then
screened in the presence of this chiral sulfamide catalyst 8, and the results are illustrated in Table 1.
Table 1. Optimization of the reaction conditions in the asymmetric desymmetrization of 1 with cinnamyl
alcohol using chiral bifunctional sulfamide catalyst 8.
Entry
Catalyst loading
(mol%)
solvent
T
Concn.a
(M)
ee
(%)
80
(oC)
25
1
2
3
4
5
6
7
8
9
110
MTBE
Et2O
0.1
110
110
110
100
80
25
25
25
25
25
25
25
25
0.1
0.1
78
91
64
82
64
91
90
91
dioxane
toluene
dioxane
dioxane
dioxane
dioxane
dioxane
0.1
0.1
0.1
120
110
110
0.1
0.15
0.05
a Refers to the concentration of 1 in the solvent.
A number of solvents were examined (Table 1, entries 1-4), the optimum solvent with high level of
enantiocontrol was aprotic, H-bonding accepting solvent dioxane. Furthermore, it was found that decrease
the catalyst loading had a significant negative influence on the enantioselectivity (Table 1, entries 3, 5-7).
In contrast to the remarkable catalyst loading effect, the change of the reaction concentration of 1 in the
dioxane (from 0.15 to 0.05 M) led only to subtle variation in the enantioselectivities (Table 1, entries 3,
8-9). It is also noteworthy that chiral bifunctional sulfamide catalyst 8 was easily recovered quantitatively
by a simple 2M HCl extraction followed by basification of its aqueous hydrochloride salt solution and it
could be reused without purification.
Reduction of the crude 2 to the sodium salt of the corresponding (4S,5R)-hydroxy acid (after alkaline
saponification with 10% aqueous sodium carbonate) followed by lactonization using 5% hydrochloric
acid gave 3 in 99% yield and 91% ee. The enantiomeric purity of 3 was easily improved to 98% by one
recrystallization from ethanol. Subsequently (3aS,6aR)-lactone 3 was subjected to thiolactonization by
treatment with potassium thioacetate in refluxing dimethylformamide for 40 min under argon atmosphere
to provide the desired intermediate (3aS,6aR)-thiolactone 4 in 87% yield. It was also rewarding that
cinnamyl alcohol was easily recovered quantitatively by evaporation of the separated organic phase at the

stage of alkaline treatment with 10% aqueous sodium carbonate.
Although our earlier procedure involving the generation of the di-Grignard from 1,4-dibromobutane and
carboxylation with carbon dioxide18 to install the Z-carboxybutyl side-chain at the C-4 position of the
chiral thiolactone 4, under these reaction conditions, only a 75% conversion to the hydroxy acid was
observed possibly because of the low solubility of Grignard reagent in THF at the cryogenic temperature
(-25 oC). A significant improvement in the conversion 4 to the hydroxyl acid (100%) was achieved when
toluene was added as a co-solvent to the reaction mixture. Dehydration of the hydroxy acid was
performed using 30% H2SO4 in THF at reflux to afford pentanoic acid 5, which upon catalytic
hydrogenation over 10% Pd/C in 2-propanol at 120 oC and 60 atm (882 psi), gave
N,N-bis(p-methoxybenzyl)biotin (6). Surprisingly, attempts to deprotect 6 with potassium persulfate or
ceric ammonium nitrate under the reported conditions19,20 gave none of the expected (+)-biotin (7).
Fortunately, the target molecule [(+)-biotin (7)] was obtained via a one-pot simultaneous deprotection and
ring-opening of 6 using 47% aqueous HBr followed by in situ treatment of the resulting dihydrobromide
salt of diamine with triphosgene in 83% yield after recrystallization from deionized water. The NMR and
mass spectra for 7 were in agreement with those of authentic (+)-biotin.18
O
O
PMBN
H
NPMB
H
PMBN
H
NPMB
H
1) BrMg(CH2)4MgBr
2) CO2
H2
10% Pd/C
3) 30% H2SO4
O
CO2H
S
S
5
4
O
O
S
PMBN
H
NPMB
HN
H
NH
1) 47% HBr
2) triphosgene
H
H
H
H
CO2H
CO2H
S
(+)-biotin 7
6
Scheme 2
In summary, we have developed an improved and commercially scalable process for the stereocontrolled
total synthesis of (+)-biotin from the known cis-1,3-bis(p-methoxybenzyl)tetrahydro-2H-furo[3,4-d]-
imidazole-2,4,6-trione (1) in high purity and satisfactory overall yield (54%) from 1. Although we have
successfully carried out this sequence on a kilogram scale (e. g. starting with 1.39 kg of 1), this article
describes only the laboratory scale preparation of (+)-biotin starting with about 10 g of 1.

EXPERIMENTAL
Melting points were determined with a WRS-1B digital melting point apparatus and are uncorrected.
NMR spectra were recorded on a Bruker Avance 400 spectrometer using TMS as an internal standard.
Chemical shifts (δ) are expressed in ppm. Optical rotations were measured with a JASCO P1020 digital
automatic polarimeter. HPLC analysis conditions: mobile phase A: 85% H3PO4 (0.85 mL) and K2HPO4
(2.7 g) dissolved in 1000 mL H2O; mobile phase B: acetonitrile; gradient elution. Unless otherwise noted,
all the reagents were obtained from commercial sources and used as received.
(3aS,6aR)-1,3-bis(4-Methoxybenzyl)tetrahydro-4H-furo[3,4-d]imidazole-2,4(1H)-dione
(3).
trans-Cinnamyl alcohol (17.0 g, 16.2 mL, 126.5 mmol) was added dropwise to a suspension of 1 (10.0 g,
25.3 mmol) and chiral bifunctional sulfonamide catalyst 8 (21.0 g, 27.8 mmol) in dioxane (253 mL) under
o
nitrogen atmosphere at 25 C, and the mixture was stirred at this temperature for 5 min. Removal of the
solvent in vacuo gave a residue which was dissolved in EtOAc (100 mL) and washed with 2M HCl (3 ×
50 mL). The separated organic phase was washed with brine, dried over MgSO4 and evaporated to give
the crude (4S,5R)-hemiester 2, which was used in the next step without purification.
To recover the chiral bifunctional sulfonamide catalyst 8, the collected acidic aqueous phase was basified
with 2 M NaOH and extracted with CH2Cl2 (3 × 50 mL). The combined organic layers were dried over
MgSO4 and evaporated to give the organocatalyst in quantitative yield, which could be reused directly
without purification.
To a solution of 2 (13.4 g, 25.3 mmol) and anhydrous powdered CaCl2 (2.8 g, 25.3 mmol) in EtOH (130
o
mL) was added KBH4 (4.1 g, 75.9 mmol) in three portions at 0 C and the reaction mixture was then
o
allowed to warm up to 25 C. After stirring for 18 h, the resulting mixture was concentrated and the
residue was dissolved in EtOAc (80 mL). The solution was then extracted with 10% aqueous Na2CO3 (3
o
× 50 mL) and the combined aqueous layers were treated with 5% HCl (106 mL) at 60 C for 30 min.
After cooling, the mixture was extracted with CH2Cl2 (3 × 80 mL). The combined organic layers were
washed with H2O (80 mL), dried over MgSO4, and the solvent was evaporated to give the crude product
which was then purified by recrystallization from EtOH to afford the pure 3 (8.91 g, 92%) as a white solid
in 99% purity, mp 110-111 oC (lit.21 mp 110.6-110.9 oC).
1H NMR (CDCl3): δ 7.346-7.368 (d, 2H, J = 8.8 Hz), 7.207-7.209 (d, 2H, J = 8.8 Hz), 6.907-6.928 (d, 4H,
J = 8.4 Hz), 5.002-5.038 (d, 1H, J = 14.4 Hz), 4.574-4.612 (d, 1H, J = 15.2 Hz), 4.323-4.360 (d, 2H, J =
13
14.8 Hz), 4.116-4.193 (m, 3H), 3.926-3.948 (d, 1H, J = 8.8 Hz), 3.847 (s, 3H), 3.844 (s, 3H). C NMR
(CDCl3): δ 172.401, 158.907, 129.195, 127.469, 113.697, 76.603, 76.282, 69.897, 45.987, 44.264. IR
(KBr): 3525, 2954, 2832, 1770, 1699, 1687, 1513, 1237, 1253, 1030, 818 cm-1. MS (ESI): m/z = 405.0
(M+Na+).
To recover the trans-cinnamyl alcohol, the collected EtOAc layer was dried over MgSO4 and evaporated

to give the trans-cinnamyl alcohol in quantitative yield.
(3aS,6aR)-1,3-bis(4-Methoxybenzyl)tetrahydro-4H-thieno[3,4-d]imidazole-2,4(1H)-dione
(4).
(3aS,6aR)-Lactone 3 (8.91 g, 23.3 mmol), potassium thioacetate (3.1 g, 26.8 mmol) were added to DMF
o
o
(10 mL) at 25 C under a nitrogen atmosphere. The reaction mixture heated to 150 C and stirred for 45
min. After completion of the reaction as monitored by TLC, the resulting mixture was poured into H2O
(250 mL) and extracted with CH2Cl2 (3 × 70 mL). The combined organic layers were then washed with
H2O (200 mL), dried over MgSO4, and concentrated under reduced pressure to give the crude product,
which was purified by recrystallization from 2-propanol to afford product 4 (8.07 g, 87%) as an off-white
crystalline powder, mp 126-127 oC (lit.21 mp 125-126 oC).
1H NMR (CDCl3): δ 7.308-7.330 (d, 2H, J = 8.8 Hz), 7.247-7.269 (d, 2H, J = 8.8 Hz), 6.906-6.928 (d, 2H,
J = 8.4 Hz), 6.890-6.912 (d, 2H, J = 8.8 Hz), 4.989-5.025 (d, 1H, J = 14.4 Hz), 4.649-4.686 (d, 1H, J =
14.8 Hz), 4.294-4.349 (m, 2H), 4.118-4.157 (m, 1H), 3.819-3.849 (m, 1H), 3.849 (s, 3H), 3.839 (s, 3H),
3.308-3.430 (m, 2H). 13C NMR (CDCl3): δ 203.145, 157.804, 127.779, 113.610, 76.280, 61.635, 54.861,
44.263, 32.747. IR (KBr): 3361, 2932, 2832, 1692, 1510, 1448, 1245, 1213, 1029, 824 cm-1.
MS (ESI): m/z = 421.1 (M+Na+).
(3aS,6aR)-[1,3-bis(4-Methoxybenzyl)tetrahydro-2(3H)-oxo-1H-thieno[3,4-d]imidazol-4-yl]pentanoic
Acid (5). Under the atmosphere of argon, 1,4-dibromobutane (0.4 mL, 3.5 mmol) was added into the
suspension of magnesium (5.6 g, 232.7 mmol) in anhydrous THF (48 mL) at 35 oC. After the reaction had
started, the remaining 1,4-dibromobutane (13.0 mL, 110.0 mmol) in THF (60 mL) was added dropwise
over a period of 1 h and stirred at reflux for another 2 h. The solution of 4 (8.07 g, 20.3 mmol) in
anhydrous THF (25 mL) and toluene (50 mL) was then added dropwise into the freshly prepared
o
di-Grignard reagent at -25 C within 30 min followed by stirring at this temperature for 3 h. Then dry
o
gaseous carbon dioxide was bubbled into the resulting mixture for 3 h at -25 C. After being allowed to
warm up to room temperature, the mixture was quenched with saturated aqueous NH4Cl (150 mL) and the
mixture was extracted with toluene (3 × 100 mL). The combined organic extracts were washed with brine
(80 mL) and concentrated in vacuo to afford a yellow oily residue, which was subjected to dehydration by
treatment with 30% H2SO4 (40 mL) in refluxing THF (20 mL). After being stirred under reflux for 0.5 h,
the reaction mixture was extracted with EtOAc (80 mL) and the separated organic layer was concentrated
under reduced pressure. The residue was neutralized with 10% aqueous Na2CO3 (80 mL) and extracted
with EtOAc (3 × 80 mL). The pH of the aqueous phase to 5.5 by addition of 2 M HCl then extracted with
EtOAc (3 × 80 mL). The combined organic extracts were washed successively with brine (50 mL) and
H2O (50 mL), dried over MgSO4, and concentrated in vacuo to afford 5 (7.93 g, 81%, 99% pure by
HPLC) as a yellow oil.
Anal. Calcd for C26H30N2O5S: C, 64.71; H, 6.27; N, 5.80; S, 6.64. Found: C, 64.67; H, 6.34; N, 5.74; S,

6.63. 1H NMR (CDCl3): δ 7.264-7.286 (d, 2H, J = 8.8 Hz), 7.200-7.222 (d, 2H, J = 8.8 Hz), 6.905-6.927
(d, 2H, J = 8.8 Hz), 6.901-6.923 (d, 2H, J = 8.8 Hz), 5.468-5.503 (t, 1H, J = 7.2 Hz), 4.921-4.959 (d, 1H,
J = 15.2 Hz), 4.746-4.784 (d, 1H, J = 15.2 Hz), 4.188-4.297 (m, 2H), 4.059-4.101 (m, 1H), 3.977-4.016
(d, 1H, J = 15.6 Hz), 3.849 (s, 3H), 3.843 (s, 3H), 2.950-3.033 (m, 2H), 2.353-2.391 (t, 2H, J = 7.6 Hz),
2.111-2.228 (m, 2H), 1.721-1.793 (m, 2H). 13C NMR (CDCl3): δ 177.502, 158.485, 137.828, 128.566,
124.840, 113.650, 76.279, 64.038, 58.454, 54.860, 45.499, 43.857, 36.670, 32.788, 30.588, 23.577. IR
(KBr): 3433, 2938, 1717, 1652, 1515, 1477, 1258, 1240, 1172 cm-1. MS (ESI): m/z = 505.1 (M+Na+).
(+)-Biotin.- A suspension of 10% Pd/C (1.2 g), 5 (7.93 g, 16.5 mmol), and H2O (7 mL) in 2-propanol (38
mL) was stirred at 120 oC under hydrogen pressure of 60 atm (882 psi) for 20 h then filtered. The filtrate
was concentrated under reduced pressure to give the product 6, which was subjected to next step without
further purification.
A mixture of 6 (7.99 g, 16.5 mmol) and 47% HBr (53 mL) was heated to reflux for 36 h then extracted
with toluene (3 × 10 mL). The aqueous phase was concentrated under reduced pressure. After dissolution
of the residue in water (26 mL), a solution of triphosgene (14.7 g, 49.5 mmol) in anisole (100 mL) was
o
added dropwise at 35 C over a period of 2 h. The pH of the reaction mixture was maintained at 10 by
simultaneous addition of 40% aqueous KOH. After 12 h at this temperature, the separated aqueous phase
o
was acidified to pH1 with conc. HCl and cooled to 0 C. The precipitated crystals were collected and
recrystallized from deionized water to give pure (+)-biotin (3.35 g, 83%) as colorless crystals, mp
232-233 oC ([α]D22.1 +91.2 (c 1.0, 0.1 N NaOH); lit.18 mp 230-232 oC, [α]D22 +91.1 (c 1.0, 0.1 N NaOH)).
Anal. Calcd for C10H16N2O3S: C, 49.16; H, 6.60; N, 11.47; S, 13.12. Found: C, 49.01; H, 6.55; N, 11.55;
1
S, 13.20. H NMR (CDCl3): δ 11.9 (s, 1H), 6.40 (s, 1H), 6.33 (s, 1H), 4.30 (dd, 1H, J = 7.6, 5.2 Hz),
4.11-4.15 (m, 1H), 3.07-3.12 (m, 1H), 2.82 (dd, 1H, J = 12.4, 5.2 Hz), 2.57 (d, 1H, J = 12.4 Hz), 2.20 (t,
13
2H, J = 7.6 Hz), 1.41-1.62 (m, 4H), 1.30-1.37 (m, 2H). C NMR (CDCl3): δ 174.8, 163.1, 61.5, 59.6,
55.8, 40.0, 33.9, 28.57, 28.52, 25.0. IR (KBr): 3359, 3308, 2961, 2469, 1941, 1707, 1480, 1318, 1270,
1154, 1015, 842, 753, 651 cm-1. MS (ESI): m/z = 283.2 (M+K+).
ACKNOWLEDGEMENTS
The authors gratefully acknowledge the financial support of the Shanghai Municipal Education
Commission (No. SLG14033); the research project of teachers’ teaching development of University of
Shanghai for Science and Technology for the year of 2016 and the open project program of Hubei Key
Laboratory of Drug Synthesis and Optimization, JingChu University of Technology (No.
OPP2014ZD01).

REFERENCES
1. M. W. Goldberg and L. H. Sternbach, US Pat 2489232, 1949 (Chem. Abstr., 1951, 45, 184).
2. M. W. Goldberg and L. H. Sternbach, US Pat 2489235, 1949 (Chem. Abstr., 1951, 45, 186s).
3. M. W. Goldberg and L. H. Sternbach, US Pat 2489235, 1949 (Chem. Abstr., 1951, 45, 186g).
4. P. J. De Clercq, Chem. Rev., 1997, 97, 1755.
5. M. Seki, Med. Res. Rev., 2006, 26, 434.
6. B. Xie and F. E. Chen, Chin. J. Med. Chem., 2008, 18, 468 (Chem. Abstr., 2009, 153, 313361).
7. Z. Zhong, X. F. Wu, and F. E. Chen, Chin. J. Org. Chem., 2012, 32, 1792 (Chem. Abstr., 2012, 158,
272707).
8. C. Choi, S. K. Tian, and L. Deng, Synthesis, 2001, 1737.
9. J. Huang, F. Xiong, and F. E. Chen, Tetrahedron: Asymmetry, 2008, 19, 1436.
10. H. F. Dai, W. X. Chen, L. Zhao, F. Xiong, H. Sheng, and F. E. Chen, Adv. Synth. Catal., 2008, 350,
1635.
11. S. X. Wang and F. E. Chen, Adv. Synth. Catal., 2009, 351, 547.
12. F. Xiong, X. X. Chen, and F. E. Chen, Tetrahedron: Asymmetry, 2010, 21, 665.
13. X. X. Chen, F. Xiong, H. Fu, Z. Q. Liu, and F. E. Chen, Chem. Pharm. Bull., 2011, 59, 488.
14. M. Yoshimura, K. Tsuda, H. Nakatsuka, and T. Yamamura, Tetrahedron, 2011, 67, 10006.
15. F. Xiong, F. J. Xiong, W. X. Chen, H. Q. Jia, and F. E. Chen, J. Heterocycl. Chem., 2013, 50, 1078.
16. F. Xiong, X. K. Li, M. Xu, S. P. Zhang, F. E. Chen, B. Liao, H. J. Hua, and J. H. He, Asian J. Chem.,
2014, 26, 3659.
17. F. Xiong, Z. Y. Shen, X. K. Li, Y. N. Peng, H. Y. Zhu, S. P. Zhang, Y. Y. Song, and J. L. Du, Org.
Prep. Proced. Int., 2015, 47, 242.
18. F. E. Chen, H. F. Dai, Y. Y. Kuang, and H. Q. Jia, Tetrahedron: Asymmetry, 2003, 14, 3667.
19. G. Gerona-Navarro, M. A. Bonache, R. Herranz, M. T. Garcia-Lopez, and R. Gonzalez-Muniz, J.
Org. Chem., 2001, 66, 3538.
20. H. Ishibashi, C. Kameoka, H. Iriyama, K. Kodama, T. Sato, and M. Ikeda, J. Org. Chem., 1995, 60,
1276.
21. D. Li, F. J. Xiong, F. Xiong, and F. E. Chen, Chin. J. Pharm., 2014, 45, 919 (Chem. Abstr., 2015,
180854).
22. H. J. Yang, F. J. Xiong, J. Li, and F. E. Chen, Chin. Chem. Lett., 2013, 24, 553.