Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

Article abstract of DOI:10.3762/BJOC.16.155

To develop new efficient stereoselective catalysts for Biginelli-like reactions, a chiral phosphoric acid bearing two hydroxy groups derived from L-tartaric acid was successfully synthesized via highly regioselective transformations of enantiopure 1,1,4,4

Full text of DOI:10.3762/BJOC.16.155

Stereoselective Biginelli-like reaction catalyzed by a chiral
phosphoric acid bearing two hydroxy groups
Xiaoyun Hu*1, Jianxin Guo1, Cui Wang1, Rui Zhang1 and Victor Borovkov*2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2020, 16, 1875–1880.
1College of Chemistry and Materials South-Central University for
Nationalities, Wuhan, China and 2Department of Chemistry and
Biotechnology, Tallinn University of Technology, Akadeemia tee 15,
Tallinn 12618, Estonia
doi:10.3762/bjoc.16.155
Received: 05 June 2020
Accepted: 19 July 2020
Published: 31 July 2020
Email:
Xiaoyun Hu* - xyhu@mail.scuec.edu.cn; Victor Borovkov* -
victor.borovkov@taltech.ee
Associate Editor: M. Rueping
© 2020 Hu et al.; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
asymmetric Biginelli-like reaction; chiral
1,1,4,4-tetraphenylbutanetetraol; chiral phosphoric acid
Abstract
To develop new efficient stereoselective catalysts for Biginelli-like reactions, a chiral phosphoric acid bearing two hydroxy groups
derived from ʟ-tartaric acid was successfully synthesized via highly regioselective transformations of enantiopure 1,1,4,4-
tetraphenylbutanetetraol. The obtained catalyst effectively catalyzed Biginelli-like reactions with moderate to good enantioselectivi-
ties. Control experiments indicated that the presence of the two hydroxy groups were indispensable for achieving a high enantiose-
lectivity.
Introduction
Dihydropyrimidinethiones (DHPMs) are an important class of logical activity of DMPMs came to light, the development of an
heterocyclic compounds featuring in a large number of natural efficient and reliable asymmetric synthesis of enantiopure
and artificial compounds possessing various biological activi- DHPMs becomes an urgent and paramount task.
ties, and serving as key intermediates for the synthesis of
medical drugs [1-4]. In the last decade, chiral DHPMs showed In connection with this, multicomponent Biginelli and Biginelli-
valuable pharmacological properties such as antiviral, anti- like reactions of aldehydes, urea/thiourea, and enolizable
tumor, antibacterial, anti-inflammatory, and antihypertensive carbonyls revealed as very efficient tools to prepare DHPMs
effects [5,6]. However, the individual enantiomers of DHPMs [3]. Although the Biginelli reaction was firstly discovered over
were found to exhibit different or even opposite pharmaceutical a century ago [10], little attention was given to asymmetric
activities [7,8]. For example, (S)-monastrol is 15-fold more pathways. Only in 2003, Juaristi and Muñoz-Muñiz have re-
effective in the inhibition of Eg 5 ATPase than its enantiomer, ported the reaction of benzaldehyde, urea, and methyl aceto-
(R)-monastrol [9]. As more reports on the enantiospecific bio- acetate using a chiral amide with CeCl3 for the first time. How-
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ever, only 40% enantiomeric excess (ee) was obtained [11]. tained from enantiopure tartaric acids. The hydroxy group com-
Then, Zhu described the efficient asymmetric Biginelli reaction position of 1 ensures its diverse reactivity. In 2010, our group
with a chiral ytterbium catalyst to provide excellent enantiose- established a convenient access [18] to 1 via a direct alkylation
lectivities up to >99% ee [12]. Later, Gong reported the first of diethyl tartrates by using PhMgBr followed by further modi-
organocatalytic Biginelli reaction using 1,1'-bi-2-naphthol fications involving highly regioselective 1,4-cycloetherization
(BINOL) derived chiral phosphoric acids as catalysts, [19], 2,3-spiroboration [20], 2,3-sulfitation [21], and 2,3-meth-
furnishing the DHPMs with up to 97% ee [13,14].
ylation [22] of 1. Therefore, the strategy for the catalyst’s prep-
aration was based on the established regioselective 2,3-sulfita-
Though the BINOL-derived chiral phosphoric acids were suc- tion reaction of 1 and ready hydrolysis of the corresponding
cessfully applied in the Biginelli reactions, the costs are essen- sulfite ester 2 in NaOH solution to yield the chiral phosphoric
tially high because of complex preparative procedures, espe- acid 3 bearing two free hydroxy groups at the 2 and 3- posi-
cially for the introduction of a substituent at the 3,3'-position of tions, respectively, as shown in Scheme 1.
BINOL [15]. Besides BINOL, 2,2-dimethyltetraphenyl-1,3-
dioxolane-4,5-dimethanol (TADDOL) was also widely used as Our previous work indicated that the phosphoric acid deriva-
a C2 chiral diol. However, TADDOL-derived phosphoric acids tive 3 was able to catalyze the asymmetric Biginelli reaction of
were not comprehensively investigated as catalysts in Biginelli unsubstituted and electron-rich aromatic aldehydes [17]. To
and Biginelli-like reactions yet. The first example of their suc- further expand the application of this type of chiral phosphoric
cessful application was reported in 2005 by the Akiyama’s acids, the asymmetric Biginelli-like catalytic reaction was ex-
group [16]. This work clearly demonstrated the potential of amined. Firstly, coupling of benzaldehyde (4a), cyclohexanone,
these catalysts in enantioselective transformations. An addition- and N-benzylthiourea was set as a model reaction (Table 1).
al important point of this work was the use of enantiopure Screening of solvents indicated that chiral phosphoric acid 3
tartaric acid as a precursor for the catalyst preparation being a stereoselectively promoted this reaction in aprotic solvents
conventional natural compound making its application highly (Table 1, entries 1–6), while in protic solvent, such as ethanol,
attractive from the viewpoint of sustainability and green chem- the racemic product was obtained (Table 1, entry 7). To our
istry. Recently, our group reported an asymmetric Biginelli pleasure, the solvent screening showed that the target product
reaction catalyzed by a new chiral phosphoric acid derived from could be obtained in 95% ee catalyzed by 3 in CHCl3 (Table 1,
natural tartaric acid, that yielded a high enantioselectivity (up to entry 4). However, acidic and basic additives [23,24] resulted in
99% ee) [17]. This new chiral phosphoric acid featured a facile a decrease of the enantioselectivity (Table 1, entries 10–12), or
preparation and low cost. In order to further develop this new even to racemization in the case of TFA (Table 1, entry 13).
chiral phosphoric acid as an asymmetric catalyst, herein its cata- The role of the reaction temperature was also investigated
lytic efficacy in the Biginelli-like reactions of aldehydes, (Table 1, entries 8 and 9) and it was found that decreasing or
benzylthiourea, and cyclohexanone was explored, and moder- raising the temperature was unfavorable for both the yield and
ate to good enantioselectivities (up to 95% ee) were obtained. enantioselectivity. Based on these results, the optimal condi-
Furthermore, a control experiment was designed to disclose the tions were selected as follows: 10 mol % 3 as the catalyst,
indispensability of the two hydroxy groups for achieving high CHCl3 as the reaction solvent at 50 °C for 6 days.
enantioselectivities of the Biginelli-like reaction.
With the optimal conditions in hand, the scope of aromatic alde-
Results and Discussion hydes 4 was explored. As shown in Table 2, a range of aromat-
Enantiomerically pure 1,1,4,4-tetrasubstituted butanetetraol 1 is ic aldehydes gave the target products in high yields with moder-
a parent compound of TADDOLs, which conventionally are ob- ate to good enantioselectivities in general. However, it should
Scheme 1: Synthesis of chiral phosphoric acid 3.
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Beilstein J. Org. Chem. 2020, 16, 1875–1880.
Table 1: Optimization of reaction conditionsa.
entry
solvent
additive
T [°C]
yield [%]b
ee [%]c
1
toluene
THF
–
50
50
50
50
50
50
50
30
70
50
50
50
50
76
43
56
85
75
43
82
60
50
32
30
87
91
89
51
44
95
76
32
0
2
–
3
acetone
CHCl3
CH2Cl2
CH3CN
EtOH
–
4
–
5
–
6
–
7
–
8
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
–
33
47
16
12
44
0
9
–
10
11
12
13
Py
NaHCO3
PhCOOH
CF3COOH
aReaction was carried out on a 0.2 mmol scale, the ratio of 4a/N-benzylthiourea/cyclohexanone was 1.5:1.0:5.0 and 10 mol % of 3. bIsolated yields.
cThe ee was determined by HPLC.
Table 2: Results of the Biginelli-like reaction with various aromatic aldehydes catalyzed by 3aa.
entry
R
product
yield [%]b
ee [%]c
1
H
5a
5b
5c
5d
5e
5f
85
86
83
90
88
85
89
79
76
72
73
95
77
91
87
80
83
73
42
23
53
20
2
2-Br
3
3-Br
4
4-Br
5
4-Me
4-OMe
4-F
6
7
5g
5h
5i
8
4-NO2
2-NO2
2-Cl
9
10
11
5j
4-t-Bu
5k
aReaction was carried out on a 0.2 mmol scale, the ratio of 4/N-benzylthiourea/cyclohexanone was 1.5:1.0:5.0 and 10 mol % of 3. bIsolated yields.
cThe ee was determined by HPLC.
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Beilstein J. Org. Chem. 2020, 16, 1875–1880.
be noted that the enantiomer self-disproportionation effect may amined and the corresponding product 5a was obtained in 60%
take place during the purification by column chromatography yield and 7% ee (Scheme 3). Compared to the dihydroxy com-
especially in the case of products having strongly electronega- pound 3, both the yield and enantioselectivity of the reaction
tive groups [25-29].
dropped dramatically, hence confirming our initial proposal that
the free hydroxy groups in the chiral phosphoric acid 3 played
In particular, benzaldehyde (4a) and 3-bromobenzaldehyde (4c) an important role in this enantioselective transformation.
gave products 5a and 5c with 95% and 91% ee, respectively
(Table 2, entries 1 and 3). As further can be seen from Table 2, Based on these results, a plausible transition-state structure was
the position of substituents had a dramatic influence on the en- proposed. As shown in Figure 1, the chiral phosphoric acid 3
antioselectivity (Table 2, entries 2–4). This may be attributable activated the imine derivative, which in turn was formed by the
to the different inductive effects induced by the o-, p-, and condensation of benzaldehyde with N-benzylthiourea. The two
m-bromo substituent in the aromatic aldehydes 4b–d and steric hydroxy groups formed five-numbered intramolecular (blue
hindrance. Both the electron-donating and electron-with- dotted line) and seven-numbered intermolecular (red dotted
drawing groups in the 2-position were unfavorable for the enan- lines) H bondings with the enolizable ketone, respectively. This
tioselectivity (Table 2, entries 2, 9, and 10). The presence of rigid chiral transition-state structure favored the stereoselective
electron-donating groups in the 4-position was more favorable attack of the enol on the imine. Once the two hydroxy groups
for the enantioselectivity (Table 2, entries 4–6, and 8) except for were etherified, the loss of the rigid structure would lead to low
the sterically demanding tert-butyl group (Table 2, entry 12). enantioselectivity. Additionally, this explains that more polar or
Obviously, steric effects in the aromatic aldehydes played a key protic solvents and strong acidic additives also destroyed the
role for the enantioselectivity of the reaction.
To further confirm the importance of two secondary free
hydroxy groups in 3 for this reaction, the methylated derivative
7 was synthesized (Scheme 2). As shown in Scheme 2, first
(2R,3R)-1 was subjected to highly regioselective 2,3-dimethyla-
tion [23] with NaH/MeI to give product (2R,3R)-6. Then the
corresponding dimethylated chiral phosphoric acid 7 was syn-
thesized in a similar manner as described in [17].
Figure 1: A plausible chiral transition-state structure in the Biginelli-like
reaction catalyzed by phosphoric acid 3.
Next, the model reaction of 4a, cyclohexanone, and N-benzyl-
thiourea catalyzed by 7 under the optimized conditions was ex-
Scheme 2: Synthesis of methylated chiral phosphoric acid 7.
Scheme 3: Control experiment with catalyst 7.
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Beilstein J. Org. Chem. 2020, 16, 1875–1880.
H-bondings resulting in decreased enantioselectivities or even (0.105 g, 4.2 mmol), and dried THF (16 mL). The mixture was
racemization (Table 1, entries 7 and 13).
stirred at rt for 2 h, and then methyl iodide (0.61 g, 4.3 mmol)
was added and the mixture stirred at rt for 6 h. Then, distilled
water (12 mL) and diethyl ether (15 mL) were added, the
Conclusion
In summary, a new phosphoric acid bearing two free hydroxy organic phase was separated, dried, and concentrated. The
groups was synthesized based on a highly regioselective trans- residue was recrystallized from ethanol to afford 0.776 g
formation of chiral 1,1,4,4-tetraphenylbutanetetraol obtained (2R,3R)-6. Yield 90%; mp 124–125 °C; [α]D25 −151 (c 0.8,
from natural tartaric acid. The chiral phosphoric acid was suc- CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.63–7.55 (m, 8H,
cessfully applied as asymmetric catalyst in the Biginelli-like Ph-H), 7.43 (t, J = 7.5 Hz, 4H, Ph-H), 7.32–7.12 (m, 8H, Ph-H),
reaction affording the products in good yields and enantioselec- 4.91 (s, 2H, O-H), 4.43 (s, 2H, C-H), 2.53 (s, 6H, 2CH3);
tivities of up to 95%. A control experiment indicated that the 13C NMR (75 MHz, CDCl3) δ 145.9, 145.0, 128.7, 128.2,
two free hydroxy groups in phosphoric acid 3 played a pivotal 127.5, 127.0, 126.3, 126.2, 126.1, 85.62, 85.57, 80.19, 61.35,
role in improving the stereoselectivity. A plausible activation 61.26.
model and reaction pathways of the stereogenic step in the
phosphoric acid 3-catalyzed Biginelli-like reaction was pro- Preparation of 7: In a similar manner as described in [17],
posed. This promising result prompted us to expand the applica- under Ar, a dried three-necked round-bottomed 250 mL flask
bility of this kind of catalysts to other types of asymmetric reac- equipped with a magnetic stirring bar, reflux condenser with oil
tions, which is underway in our laboratory.
seal, and a 100 mL pressure-equalizing dropping funnel was
charged with 10 mL of dry THF and 3.2 mL of NEt3
(22 mmol). The flask was placed in an ice-bath and PCl3 (1 mL)
Experimental
Materials and general methods: 1H and 13C NMR spectra added, and the resulting mixture was stirred at 0 °C for 20 min.
were performed on a Varian Mercury VS 300 or Bruker Avance Then, the dropping funnel was charged with a THF solution of
III 400. Optical rotations were measured on a PE-341 Mc (2R,3R)-6 (6.1 g, 13 mmol) and added dropwise to the mixture.
polarimeter. Melting points were determined on a VEB After the addition, the mixture was stirred at 0 °C for 1 h,
Wägetechnik Rapio PHMK05 instrument, and are uncorrected. warmed to rt, and stirred for an additional 0.5 h. Then, 1.5 mL
Enantiomeric excess (ee) values were analyzed by a Thermo of H2O were added, followed by 10.9 g of I2, and 7.1 mL of
UltiMate 3000 HPLC and SHIMADZU LC-20 AR at room pyridine and the mixture stirred for another 1 h. Afterwards, the
temperature with n-hexane/isopropanol as eluent. Diethyl mixture was poured into a saturated NaHSO3 solution and
ʟ-tartrate was prepared from ʟ-tartaric acid and ethanol. THF stirred to remove the excess I2. Finally, 2 M HCl was added to
was freshly distilled after refluxing with Na, while SOCl2, pyri- adjust the pH to 2–3. The solution was extracted with Et2O
dine, PCl3, and I2 were purchased and used directly. Commer- (20 mL × 3), dried and concentrated. Recrystallization from
cially available starting materials were used without further ethanol furnished 4.2 g of (5R,6R)-2-hydroxy-5,6-dimethoxy-
purification if not specified otherwise. Chiral phosphoric acid 3 4,4,7,7-tetraphenyl-1,3,2-dioxaphosphepane 2-oxide (7). Yield
was prepared according to a previous method [18].
62%; mp 188–190 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.57
(d, J = 7.5 Hz, 4H, Ar-H), 7.34 (t, J = 7.4 Hz, 4H, Ar-H), 7.23
Preparation of 1 [18]: A THF solution of ʟ-diethyl tartrate (d, J = 6.7 Hz, 6H, Ar-H), 7.16–7.03 (m, 6H, Ar-H), 4.53 (s,
(6.2 g, 30 mmol) was slowly added dropwise into a freshly pre- 2H, CH), 3.41 (d, J = 27.2 Hz, 6H, CH3); 13C NMR (101 MHz,
pared PhMgBr solution. After the addition, the mixture was DMSO-d6) δ 146.7, 144.3, 128.5, 127.6, 127.5, 127.3, 126.7,
heated to reflux for 2 h. Then, 100 mL of saturated aqueous 126.3, 87.7, 86.3, 58.7; Anal. calcd for C30H29O6P: C, 69.76;
NH4Cl were added into the mixture after cooling to rt. The re- H, 5.66; found: C, 69.67; H, 5.59.
sulting solution was extracted with EA (20 mL × 3), dried, and
concentrated. The residue was recrystallized from 80% ethanol Typical procedure for asymmetric catalyzed Biginelli-like
(ethanol/H2O 4:1, v/v) to give 7.2 g of (2R,3R)-1. Yield 56%; reactions: In a similar manner as described in [17], after a solu-
mp 149–151 °C; [α]D25 +153.9 (c 0.5, CHCl3); 1H NMR tion of an aromatic aldehyde 4 (0.3 mmol, 1.5 equiv), N-benzyl-
(CDCl3, 400 MHz) δ 7.31–7.16 (m, 20H, Ar-H), 4.66 (d, J = thiourea (0.2 mmol), and chiral phosphoric acid 3 (0.02 mmol)
7.3 Hz, 2H, OH), 4.42 (d, J = 4.8 Hz, 2H, CH), 3.78 (d, J = in CHCl3 (1.5 mL) was stirred at 25 °C for 2 h, cyclohexanone
5.4 Hz, 2H, OH); 13C NMR (CDCl3, 75 MHz) δ 144.1, 143.9, (1 mmol) was added. The resulting mixture was warmed to
128.7, 128.5, 127.4, 127.3, 126.1, 125.0, 81.8, 71.2.
50 °C, stirred for 6 days, and then silica gel was added.
After removal of the solvent, the residue was purified by
Preparation of 6 [22]: A dried round-bottomed flask was column chromatography using petroleum ether/ethyl acetate
charged with (2R,3R)-1 (0.916 g, 2.0 mmol), sodium hydride 6:1–3:1.
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Beilstein J. Org. Chem. 2020, 16, 1875–1880.
15.Rueping, M.; Sugiono, E.; Azap, C.; Theissmann, T. Metal-Free
Reduction of Imines: Enantioselective Brønsted Acid-Catalysed
Transfer Hydrogenation using Chiral BINOL-Phosphates as Catalysts.
In Catalysts for Fine Chemical Synthesis; Roberts, S. M.; Whittall, J.,
Eds.; John Wiley & Sons: Chichester, UK, 2007; Vol. 5, pp 161–170.
The synthesis has been described as part of the synthesis of the
corresponding phosphoric acid derivative.
Supporting Information
Supporting Information File 1
Experimental data and copies of 1H NMR and 13C NMR
spectra.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-16-155-S1.pdf]
16.Akiyama, T.; Saitoh, Y.; Morita, H.; Fuchibe, K. Adv. Synth. Catal.
2005, 347, 1523–1526. doi:10.1002/adsc.200505167
17.Hu, X.; Zhang, R.; Xie, J.; Zhou, Z.; Shan, Z. Tetrahedron: Asymmetry
2017, 28, 69–74. doi:10.1016/j.tetasy.2016.11.014
18.Shan, Z.; Hu, X.; Zhou, Y.; Peng, X.; Li, Z. Helv. Chim. Acta 2010, 93,
497–503. doi:10.1002/hlca.200900274
Funding
19.Hu, X.; Shan, Z.; Peng, X.; Li, Z. Tetrahedron: Asymmetry 2009, 20,
2474–2478. doi:10.1016/j.tetasy.2009.10.005
The National Nature Science Foundation of China
(No.21302233), the Nature Science Foundation of Hubei
Province of China (No. 2012FFB07410) and the Fundamental
Research Funds for the Central Universities, South-Central
University for Nationalities (CZY20016) are acknowledged for
financial support.
20.Hu, X.; Shan, Z.; Song, S. Tetrahedron: Asymmetry 2014, 25,
503–506. doi:10.1016/j.tetasy.2014.01.018
21.Hu, X.; Shan, Z.; Soloshonok, V. A. Cryst. Growth Des. 2012, 12,
33–36. doi:10.1021/cg201219g
22.Hu, X. Y.; Yin, Z. Y.; Tang, Y. L.; Wu, L. M.
J. South-Cent. Univ. Natl., Nat. Sci. Ed. 2019, 38, 22–26.
23.Li, S.; Lü, J.; Luo, S. Acta Chim. Sin. (Chin. Ed.) 2018, 76, 869–873.
doi:10.6023/a18060227
ORCID® iDs
Xiaoyun Hu - https://orcid.org/0000-0002-5251-2521
24.Győrffy, N.; Tungler, A. J. Mol. Catal. A: Chem. 2011, 336, 72–77.
doi:10.1016/j.molcata.2011.01.001
Victor Borovkov - https://orcid.org/0000-0001-7898-0457
25.Han, J.; Soloshonok, V. A.; Klika, K. D.; Drabowicz, J.; Wzorek, A.
Chem. Soc. Rev. 2018, 47, 1307–1350. doi:10.1039/c6cs00703a
26.Han, J.; Kitagawa, O.; Wzorek, A.; Klika, K. D.; Soloshonok, V. A.
Chem. Sci. 2018, 9, 1718–1739. doi:10.1039/c7sc05138g
27.Soloshonok, V. A.; Wzorek, A.; Klika, K. D. Tetrahedron: Asymmetry
2017, 28, 1430–1434. doi:10.1016/j.tetasy.2017.08.020
28.Hosaka, T.; Imai, T.; Wzorek, A.; Marcinkowska, M.; Kolbus, A.;
Kitagawa, O.; Soloshonok, V. A.; Klika, K. D. Amino Acids 2019, 51,
283–294. doi:10.1007/s00726-018-2664-x
References
1. Matos, L. H. S.; Masson, F. T.; Simeoni, L. A.; Homem-de-Mello, M.
Eur. J. Med. Chem. 2018, 143, 1779–1789.
doi:10.1016/j.ejmech.2017.10.073
2. Kaur, R.; Chaudhary, S.; Kumar, K.; Gupta, M. K.; Rawal, R. K.
Eur. J. Med. Chem. 2017, 132, 108–134.
doi:10.1016/j.ejmech.2017.03.025
3. Nagarajaiah, H.; Mukhopadhyay, A.; Moorthy, J. N. Tetrahedron Lett.
2016, 57, 5135–5149. doi:10.1016/j.tetlet.2016.09.047
4. Cho, H. Heterocycles 2013, 87, 1441–1479. doi:10.3987/rev-13-771
5. Kappe, C. O.; Stadler, A. Org. React. 2004, 63, 1–116.
doi:10.1002/0471264180.or063.01
29.Han, J.; Wzorek, A.; Kwiatkowska, M.; Soloshonok, V. A.; Klika, K. D.
Amino Acids 2019, 51, 865–889. doi:10.1007/s00726-019-02729-y
6. Kappe, C. O. Eur. J. Med. Chem. 2000, 35, 1043–1052.
doi:10.1016/s0223-5234(00)01189-2
License and Terms
7. Gong, L.-Z.; Chen, X.-H.; Xu, X.-Y. Chem. – Eur. J. 2007, 13,
8920–8926. doi:10.1002/chem.200700840
This is an Open Access article under the terms of the
Creative Commons Attribution License
8. Kappe, C. O. The Biginelli reaction. In Multicomponent Reactions;
Zhu, J.; Bienayme, H., Eds.; Wiley-VCH: Weinheim, Germany, 2005;
pp 95–120. doi:10.1002/3527605118.ch4
(http://creativecommons.org/licenses/by/4.0). Please note
that the reuse, redistribution and reproduction in particular
requires that the authors and source are credited.
9. DeBonis, S.; Simorre, J.-P.; Crevel, I.; Lebeau, L.; Skoufias, D. A.;
Blangy, A.; Ebel, C.; Gans, P.; Cross, R.; Hackney, D. D.; Wade, R. H.;
Kozielski, F. Biochemistry 2003, 42, 338–349. doi:10.1021/bi026716j
10.Biginelli, P. Gazz. Chim. Ital. 1893, 23, 360–413.
11.Munoz-Muniz, O.; Juaristi, E. ARKIVOC 2003, No. xi, 16–26.
12.Huang, Y.; Yang, F.; Zhu, C. J. Am. Chem. Soc. 2005, 127,
16386–16387. doi:10.1021/ja056092f
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(https://www.beilstein-journals.org/bjoc)
13.Chen, X.-H.; Xu, X.-Y.; Liu, H.; Cun, L.-F.; Gong, L.-Z.
J. Am. Chem. Soc. 2006, 128, 14802–14803. doi:10.1021/ja065267y
14.Li, N.; Chen, X.-H.; Song, J.; Luo, S.-W.; Fan, W.; Gong, L.-Z.
J. Am. Chem. Soc. 2009, 131, 15301–15310. doi:10.1021/ja905320q
The definitive version of this article is the electronic one
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doi:10.3762/bjoc.16.155
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