Каскадні реакції альдольного приєднання та циклізації на основі хірального комплексу Ni(II) основи Шифа гліцину
Using platform of a new type of chiral Ni(II) complex of glycine Schiff base we designed addition-cyclization reaction cascade to explore aspects of kinetic/thermodynamic formation of the corresponding (S)(2S,3S)/(S)(2S,3R) diastereomers. It was found that the final lactone products reflect the the...
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V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine
2021
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| author | Zou, Yupiao Yin, Zizhen Mei, Haibo Konno, Hiroyuki Moriwaki, Hiroki Soloshonok, Vadim A. Han, Jianlin |
| author_facet | Zou, Yupiao Yin, Zizhen Mei, Haibo Konno, Hiroyuki Moriwaki, Hiroki Soloshonok, Vadim A. Han, Jianlin |
| author_institution_txt_mv | [
{
"author": "Yupiao Zou",
"institution": "College of Chemical Engineering, Nanjing Forestry University, 159 Lonpan Road, Nanjing, 210037, China"
},
{
"author": "Zizhen Yin",
"institution": "College of Chemical Engineering, Nanjing Forestry University, 159 Lonpan Road, Nanjing, 210037, China"
},
{
"author": "Haibo Mei",
"institution": "College of Chemical Engineering, Nanjing Forestry University, 159 Lonpan Road, Nanjing, 210037, China"
},
{
"author": "Hiroyuki Konno",
"institution": "Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan"
},
{
"author": "Hiroki Moriwaki",
"institution": "Hamari Chemicals Ltd., 1-19-40, Nankokita, Suminoe-ku, Osaka, 559-0034, Japan"
},
{
"author": "Vadim A. Soloshonok",
"institution": "Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV\/EHU, Paseo Manuel Lardizábal 3, 20018 San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Maria Diaz de Haro 3, 48013 Bilbao, Spain"
},
{
"author": "Jianlin Han",
"institution": "College of Chemical Engineering, Nanjing Forestry University, 159 Lonpan Road, Nanjing, 210037, China"
}
] |
| author_sort | Zou, Yupiao |
| baseUrl_str | https://bioorganica.com.ua/index.php/journal/oai |
| collection | OJS |
| datestamp_date | 2026-07-19T14:56:53Z |
| description |
Using platform of a new type of chiral Ni(II) complex of glycine Schiff base we designed addition-cyclization reaction cascade to explore aspects of kinetic/thermodynamic formation of the corresponding (S)(2S,3S)/(S)(2S,3R) diastereomers. It was found that the final lactone products reflect the thermodynamic stereocontrol due to much greater rates of the reversible aldol addition vs. subsequent cyclization step. The observed 4/1 (S)(2S,3S)/(S)(2S,3R) diastereoselectivity in the reactions of new type of (S)-Ni(II) complexes constitute an improvement over the previously reported 1.7/1 ratio. |
| doi_str_mv | 10.15407/bioorganica2021.01.003 |
| first_indexed | 2025-07-17T12:19:43Z |
| format | Article |
| fulltext |
ISSN 1814-9758. Ukr. Bioorg. Acta, 2021, Vol. 16, N 1
UDC 544.122.3 : 547.466.22 : 546.742
DOI: https://doi.org/10.15407/bioorganica2021.01.003
3
RESEARCH ARTICLE
Aldol addition-cyclization reaction cascade on a platform of
chiral Ni(II) complex of glycine schiff base
Yupiao Zou1, Zizhen Yin1, Haibo Mei1, Hiroyuki Konno2, Hiroki Moriwaki3, Vadim A. Soloshonok4,5*
and Jianlin Han1*
1 College of Chemical Engineering, Nanjing Forestry University, 159 Lonpan Road, Nanjing, 210037, China
2 Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan
3 Hamari Chemicals Ltd., 1-19-40, Nankokita, Suminoe-ku, Osaka, 559-0034, Japan
4 Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizábal 3, 20018
San Sebastián, Spain
5 IKERBASQUE, Basque Foundation for Science, Maria Diaz de Haro 3, 48013 Bilbao, Spain
Abstract: Using platform of a new type of chiral Ni(II) complex of glycine Schiff base we designed addition-cyclization reaction cascade
to explore aspects of kinetic/thermodynamic formation of the corresponding (S)(2S,3S)/(S)(2S,3R) diastereomers. It was found that the
final lactone products reflect the thermodynamic stereocontrol due to much greater rates of the reversible aldol addition vs. subsequent
cyclization step. The observed 4/1 (S)(2S,3S)/(S)(2S,3R) diastereoselectivity in the reactions of new type of (S)-Ni(II) complexes constitute
an improvement over the previously reported 1.7/1 ratio.
Keywords: asymmetric synthesis; aldol additions; tailor-made amino acids; Ni(II) complexes; Schiff bases; cascade/domino/tandem
reaction.
Introduction
Tailor-made amino acids (AAs) [1] are in high demand
in modern pharmaceutical industry. Along with fluorine [2],
AAs’ residues can be found in a growing number of
marketed drugs and medicinal formulations [3]. The
growing acceptance of peptides and modified peptides as
drugs [4], strongly suggest that the pivotal role of tailor-
made AAs in the design of pharmaceuticals will continue to
increase [5]. Asymmetric synthesis of AAs is a mature
science offering a plethora of various approaches [6]. Over
the last decade, preparation of tailor-made AAs via Ni(II)
Received:
Revised:
Accepted:
Published online:
10.05.2021
24.05.2021
27.05.2021
30.06.2021
Corresponding author. Tel.: +34-94-301-5177;
e-mail: vadym.soloshonok@ehu.es (V. A. Soloshonok);
hanjl@njfu.edu.cn (J. Han)
ORCID: 0000-0003-0681-4526 (V. A. Soloshonok);
0000-0002-3817-0764 (J. Han)
complex intermediates (Scheme 1) has emerged as the most
frequently used, methodologically dominant approach [7-8].
In this approach, chiral tridentate ligands 1 can
be directly used in the reactions with racemic α- and
β-AAs offering highly efficient deracemization, as well as
(S)-to-(R) interconversion protocols [9-10]. In a more
general version, chiral ligands 1 are transformed to Ni(II)
complexes of glycine Schiff bases 2 by the reaction with
glycine and source of Ni(II) ions. Compounds 2 are widely
used as chiral nucleophilic glycine equivalents in the alkyl
halide alkylations [11], Michael [12], Mannich [13], aldol
[14] addition reactions, as well as various multi-step
transformations [15]. Products 3 can be conveniently
disassembled to release target AAs 4 along with the
recovery and reuse of chiral ligands 1. The overall process
is economically and operationally attractive for large-scale
asymmetric synthesis of tailor-made AAs [16]. Among the
above-mentioned major pathways for homologation of the
glycine moiety in complexes 2, aldol addition, due to its
inherent reversibility, is the most challenging approach
(Scheme 2) [7b]. In this methodological work, using a new
© Zou Yu. et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original author and source are credited.
Ukrainica Bioorganica Acta
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ISSN 1814-9758. Ukr. Bioorg. Acta, 2021, Vol. 16, N 1
4
type of chiral ligands, we designed an aldol-cyclization
reaction cascade in attempt to investigate the effect of the
formation of irreversible final products on the overall
stereochemical outcome of this reaction sequence. The
results reported here expand our knowledge of Ni(II)
complexes aldol reactivity and highlight noticeably greater
stereocontrolling properties of new type of chiral tridentate
ligands.
Scheme 1. Asymmetric synthesis of tailor-made amino acids via
homologation of chiral glycine (S)-1 Schiff base.
Scheme 2. General aspects of aldol addition reactions of Ni(II)
complexes 5; formation of reversible syn-8 and anti-9, followed by
cyclization to afford irreversible products 10.
From the standpoint of mechanism and stereochemical
outcome, aldol addition reactions of Ni(II) complexes of
glycine Schiff bases have two distinct patterns (Scheme 2)
depending on the reaction conditions. The first type of
reactivity is observed in the presence of strong bases, such
as alkoxides [17] or DBU [18]. In this case the reactions
Scheme 3. Aldol addition-cyclization reaction cascade; major (S)(2S,3S)-14 and minor (S)(2S,3R)-15 products and crystallographic
structure of major diastereomer (S)(2S,3S)-14.
Yu. Zou, Z. Yin, H. Mei et al.
5
proceed with very high diastereoselectivity (> 90% de) and
are virtually irreversible due to the in situ formation of
hydroxy group-coordinated species 6. Upon acidification of
the reaction mixture, during work-up procedure, compounds
6 rearrange to a normal, carboxy group-coordinated
complexes 7. In the second option, under weakly basic
conditions, such as catalyzed by triethylamine, aldol
addition reactions are distinctively reversible with the
equilibrium strongly favoring the starting compounds [19].
Consequently, the reactions usually require over 10-fold
of the corresponding aldehyde to achieve a meaningful
conversion of starting Ni(II) complexes 5. Furthermore,
under these reaction conditions the thermodynamically
controlled diastereoselectivity (syn-8 and anti-9) is quite
low, ranging from 0 to 35% de. Considering these
challenging inherent synthetic limitations, we were
interested to know whether or not the stereochemical
outcome can be improved when the aldol addition is
followed by a transformation of reversible products syn-8
and anti-9 to irreversible derivatives 10.
Results and Discussion
We posited that such process can be realized in addition-
cyclization reaction cascade with in situ esterification of the
key hydroxy group critical for the reverse aldol addition. As
presented in Scheme 2, we selected methyl 2-formyl-
benzoate, possessing well-positioned aldehyde and ester
functionalities for the desired addition-cyclization cascade.
As for the starting glycine Schiff base Ni(II) complex, we
selected recently developed compound (S)-11, derived from
strategically chloro-substituted ligand [20]. Complex (S)-11
has never been used in the aldol additions but showed
superior stereocontrolling properties in the alkyl halide
alkylation [21] and deracemization of unprotected α- [22]
and β-AAs [10].
After a series of preliminary experiments, we established
that 6 equivalents of triethylamine, as a base, and 2
equivalents of methyl 2-formylbenzoate can be suitably
used as the starting point in the investigation. As presented
in Table 1, screening the reaction solvents, such as
dichloromethane (entry1), acetone (entry 2), acetonitrile
(entry 3) and methanol (entry 4) at ambient temperature
gave more or less similar results in term of
diastereoselectivity affording (S)(2S,3S)-complex 14 as the
major reaction product. Diastereomers (S)(2S,3S)-14 and
(S)(2S,3R)-15 were separated by column chromatography
and fully characterized. Absolute configuration of major
(S)(2S,3S)-14 was established by single crystal X-ray
analysis (Scheme 3 and SI). Absolute configuration of
minor product (S)(2S,3R)-15 was inferred based on its
optical rotation ([α]D = +1811.8), suggesting the (2S)
stereochemistry and the (3R) by the deduction. No products
with the (2R) absolute configuration, showing negative sign
[19] of optical rotation, were found in the reaction mixture.
Considering entries 1-4, we concluded that the reaction
solvent has virtually no effect on the diastereoselectivity of
this aldol additions providing products (S)(2S,3S)-14 and
Table 1. Optimization of reaction conditionsa.
Entry Temp
(oC)
Solvent Ester
(equiv)
Yield
(%)
Drc
1 rt CH2Cl2 2.0 21 32:68
2 rt aceton 2.0 16 28:72
3 rt MeCN 2.0 12 34:66
4 rt MeOH 2.0 53 37:63
5 -20 MeOH 2.0 66 64:36
6 0 MeOH 2.0 76 54:46
7 40 MeOH 2.0 58 25:75
8 60 MeOH 2.0 50 22:78
9 80 MeOH 2.0 45 19:81
10 40 MeOH 3.0 77 13:87
11 40 MeOH 5.0 93 20:80
12 40 MeOH 10.0 93 26:74
13d 40 MeOH 5.0 89 21:79
14d 40 MeOH 2.0 79 22:78
a Reaction conditions: S-CBPB 11 (0.1 mmol), methyl 2-formyl-
benzoate, triethylamine (6 eq.), solvent (2.5 mL), 12 h;
b Isolated yield;
c Dr was determined by 1H NMR;
d Ethyl 2-formylbenzoate was used.
(S)(2S,3R)-15 in ratios between 28:72 and 37:63. By
contrast, the chemical yields ranged much more
prominently depending the reaction solvent (entry 3 vs. 4),
suggesting methanol as an optimal choice (entry 4). Thus
using menthol as a solvent, we explored the effect of the
reaction temperature on the diastereoselectivity. Quite
unexpectedly, the reaction of glycine Schiff base Ni(II)
complex (S)-2 with methyl 2-formylbenzoate conducted at
-20 oC gave rise to the reverse diastereomeric preferences
affording (S)(2S,3R)-15 as a major product (entry 5). The
same trend of the diastereoselectivity was still observed in
the reaction conducted at 0 oC, albeit the preference for
diastereomer (S)(2S,3R)-15 was significantly reduced (entry
6). In sharp contrast the aldol addition performed at
elevated temperature (40 oC, entry 7). Further increase of
the reaction temperature to 60 oC (entry 8) and 80 oC (entry
9) led to gradual increase in (2S,3S) diastereoselectivity
recording the diastereomeric ratios of 22:78 and 19:81,
respectively. On the other hand, the chemical yield followed
the opposite trend gradually decreasing from 76% (entry 6)
to 45% (entry 9).
Based on these results, we concluded that the optimal
temperature for these aldol reactions should be 40 oC (entry
7). It should be noted that the reactions were quite sluggish
and the starting materials were never fully converted to
products (S)(2S,3S)-14 and (S)(2S,3R)-15 within the
standard 12 hours of the reaction time. Accordingly, we
conducted series of reactions using greater than 2
equivalents excess of methyl 2-formylbenzoate. As
presented in entries 10-12 the increase in the aldehyde
stoichiometry allowed for noticeable improvement of the
chemical yield to a respected 93% (entries 11, 12),
suggesting 5 equivalents of the aldehyde as the optimal
condition. Similar results were observed with application of
ISSN 1814-9758. Ukr. Bioorg. Acta, 2021, Vol. 16, N 1
6
ethyl 2-formylbenzoate in the place of methyl 2-formyl-
benzoate (entries 13, 14).
Conclusions
In conclusion, in this methodological work we explored
the triethylamine-catalyzed addition-cyclization reaction
cascade between a new type of chiral Ni(II) complex of
glycine Schiff and methyl/ethyl 2-formylbenzoates. The
results obtained point to the thermodynamically controlled
diastereoselectivity due to the much greater reaction rates of
the reversible aldol additions vs. irreversible cyclizations.
Nevertheless, the observed temperature-dependent
oscillation of the stereochemical preferences, giving
preference for (2S,3R) at low and (2S,3S) at elevated
temperatures, was quite unexpected. Furthermore, the
achieved 4/1 level of diastereoselectivity with over 90%
chemical yields suggest synthetic potential of these
reactions clearly deserving more comprehensive and
focused investigation.
Experimental section
All the commercial reagents including solvents were
used directly without further purification. All the
experiments were monitored by thin layer chromatography
(TLC) with UV light. The TLC employed 0.25 mm silica
gel coated on glass plates. Column chromatography was
performed with silica gel 60 (300-400 mesh). NMR spectra
were recorded on Bruker 600 MHz spectrometers. Mass
spectra (MS) were measured on Shimadzu LCMS-2020
with an etrospray ionization (ESI) probe operating in
positive mode. Values of optical rotation were measured on
Automatic Polarimeter SGW-531.
General procedures for the reaction between methyl
2-formylbenzoate and (S)-11
Into a 10 mL vial were taken (S)-11 (0.1 mmol), methyl
2-formylbenzoate (5 equiv), triethylamine (6 equiv),
methanol (2.5 mL). The mixture was stirred at 40 oC for
12 h. Then the reaction was concentrated in vacuo. The
residue was purified by column chromatography using
DCM/EtOAc (1:1, v/v) as eluent to afford the desired
product.
Compound (S)(2S3S)-14: red solid, mp 168-169 oC;
[α]D
25 +2514.4 (c 0.09, MeOH). 1H NMR (600 MHz,
CDCl3) δ 8.99 (d, J 2.04 Hz, 1H), 8.14 (d, J 9.24 Hz, 1H),
7.88-7.86 (m, 1H), 7.80-7.79 (m, 1H), 7.77-7.74 (m, 1H),
7.72-7.69 (m, 1H), 7.60-7.57 (m, 1H), 7.54-7.48 (m, 2H),
7.45-7.43 (m, 1H), 7.41 (d, J 8.16 Hz, 1H), 7.19-7.17 (m,
1H), 7.10-7.08 (m, 1H), 6.73 (d, J 2.58 Hz, 1H), 6.40-6.39
(m, 1H), 5.29 (s, 1H), 4.51 (d, J 1.74 Hz, 1H), 4.27 (d,
J 12.66 Hz, 1H), 4.19-4.11 (m, 1H), 3.61-3.58 (m, 1H),
3.41-3.38 (m, 1H), 3.21 (d, J 12.72 Hz, 1H), 2.94-2.88 (m,
1H), 2.68-2.60 (m, 1H), 2.31-2.27 (m, 1H), 2.12-2.06 (m,
1H). 13C{1H} NMR (150 MHz, CDCl3) δ 180.5, 172.3,
171.4, 169.3, 145.2, 141.5, 135.2, 134.3, 133.8, 133.4,
133.2, 133.1, 132.9, 132.1, 131.0, 130.7, 130.1, 129.9,
129.8, 127.4, 127.1, 127.0, 125.9, 125.7, 125.5, 124.7,
121.6, 81.6, 72.8, 71.7, 63.0, 58.9, 31.3, 29.9, 23.2.
MS (ESI) m/z Calcd. for C35H27Cl3N3NiO5
+ [M+H]+ 732.0.
Found 732.0.
Compound (S)(2S3R)-15: red solid, mp 142-144 oC;
[α]D
25 +1811.8 (c 0.06, MeOH). 1H NMR (600 MHz,
CDCl3) δ 9.00 (d, J 2.04 Hz, 1H), 8.18 (d, J 9.36 Hz, 1H),
7.82-7.80 (m, 1H), 7.75-7.73 (m, 1H), 7.50-7.42 (m, 4H),
7.32 (d, J 8.22 Hz, 1H), 7.27-7.25 (m, 1H), 7.15-7.12 (m,
1H), 7.07-7.05 (m, 1H), 6.92-6.91 (m, 1H), 6.41 (d, J 2.58
Hz, 1H), 6.06 (d, J 3.84 Hz, 1H), 6.00-5.98 (m, 1H), 4.50
(d, J 3.9 Hz, 1H), 4.29 (d, J 12.6 Hz, 1H), 4.11-4.05 (m,
1H), 3.58-3.56 (m, 1H), 3.40-3.37 (m, 1H), 3.18-3.14 (m,
2H), 2.73-2.66 (m, 1H), 2.29-2.22 (m, 1H), 2.16-2.11 (m,
1H). 13C{1H} NMR (150 MHz, CDCl3) δ 179.8, 175.4,
172.4, 168.6, 144.9, 141.7, 135.2, 134.5, 133.6, 133.4,
133.3, 132.9, 132.8, 132.3, 131.1, 130.2, 129.8, 129.7,
129.6, 129.2, 128.8, 127.2, 127.1, 125.9, 125.8, 125.4,
123.5, 123.4, 80.5, 72.1, 71.8, 63.3, 58.9, 30.6, 29.7, 23.3.
MS (ESI) m/z Calcd. for C35H27Cl3N3NiO5
+ [M+H]+ 732.0.
Found 732.7.
Notes
Acknowledgments and finances. This research was
funded by the National Natural Science Foundation of
China (No. 21761132021) and IKERBASQUE, Basque
Foundation for Science (for Soloshonok).
The authors declare no conflict of interest.
Author contributions. Yupiao Zou, Zizhen Yin:
Synthesis of compounds, Investigation, Formal analysis,
writing experimental section. Haibo Mei, Hiroyuki
Konno: Investigation, Formal analysis, writing most of the
manuscript. Hiroki Moriwaki, Vadim A. Soloshonok and
Jianlin Han: Conceptualization, Supervision, Writing -
review & editing. Zizhen Yin: X-ray analysis.
Supporting information
The characterization data, NMR spectra and single
crystal for 14.
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Yu. Zou, Z. Yin, H. Mei et al.
9
Каскадні реакції альдольного приєднання та циклізації на основі хірального
комплексу Ni(II) основи Шифа гліцину
Ю. Чжоу1, Ц. Їнь1, Х. Мей1, Х. Конно2, Х. Морівакі3, В. А. Солошонок4,5*, Ц. Хань1*
1 Нанкінський лісотехнічний університет, вул. Лонпан роуд, 159, Нанкін, 210037, КНР
2 Вища школа науки і технології, Ямагатський університет, Йонезава, Ямагата, 992-8510, Японія
3 Гамарі Кемікалс Лтд., 1-19-40, Нанкокіта, Суміное-ку, Осака, 559-0034, Японія
4 Університет Країни Басків, вул. Пасео Мануель Лардізабаля, 3, Сан-Себастьян, 20018, Іспанія
5 ІКЕРБАСК, Баскський фонд науки, вул. Марії Діас де Аро, Більбао, 48013, Іспанія
Резюме: На базі хірального комплексу Ni(II) основи Шифа гліцину нового типу було розроблено каскадні реакції приєднання-циклізації з метою
вивчення аспектів кінетичного/термодинамічного утворення відповідних (S)(2S,3S)/(S)(2S,3R) діастереомерів. Було знайдено, що утворені
лактони в значній мірі є продуктами термодинамічно контрольованої діастереоселективності завдяки значному внеску зворотньої реакції
альдольного приєднання порівняно із подальшою циклізацією. Досить несподіваним виявився факт температурної залежності стереохімічних
співвідношень продуктів реакції: при низькій температурі утворювався переважно (2S,3R) діастереомер, у той час як при підвіщеній – (2S,3S).
Спостережувана діастереоселективність становила 4/1 (S)(2S,3S)/(S)(2S,3R), що є значно кращим показником порівняно із попередніми даними
(1.7/1). Подібний рівень діастереоселективності, а також сумарний вихід продуктів реакції (більш ніж 90%), свідчать про великий синтетичний
потенціал даного методу, що однозначно заслуговує на всебічне та цілеспрямоване дослідження.
Ключові слова: асиметричний синтез; альдольне приєднання; специфічні неприродні амінокислоти; Ni(II) комплекси; основи Шифа;
каскадні/доміно/тандемні реакції.
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| id | oai:ojs2.bioorganica.com.ua:article-42 |
| institution | Ukrainica Bioorganica Acta |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-20T01:00:59Z |
| publishDate | 2021 |
| publisher | V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine |
| record_format | ojs |
| resource_txt_mv | bioorganicacomua/98/9eb6d1c25b01d581199d1de3d0c2ef98.pdf |
| spelling | oai:ojs2.bioorganica.com.ua:article-422026-07-19T14:56:53Z Aldol addition-cyclization reaction cascade on a platform of chiral Ni(II) complex of glycine schiff base Каскадні реакції альдольного приєднання та циклізації на основі хірального комплексу Ni(II) основи Шифа гліцину Zou, Yupiao Yin, Zizhen Mei, Haibo Konno, Hiroyuki Moriwaki, Hiroki Soloshonok, Vadim A. Han, Jianlin asymmetric synthesis aldol additions tailor-made amino acids; Ni(II) complexes Schiff bases cascade/domino/tandem reaction асиметричний синтез альдольне приєднання специфічні неприродні амінокислоти Ni(II) комплекси основи Шифа каскадні/доміно/тандемні реакції Using platform of a new type of chiral Ni(II) complex of glycine Schiff base we designed addition-cyclization reaction cascade to explore aspects of kinetic/thermodynamic formation of the corresponding (S)(2S,3S)/(S)(2S,3R) diastereomers. It was found that the final lactone products reflect the thermodynamic stereocontrol due to much greater rates of the reversible aldol addition vs. subsequent cyclization step. The observed 4/1 (S)(2S,3S)/(S)(2S,3R) diastereoselectivity in the reactions of new type of (S)-Ni(II) complexes constitute an improvement over the previously reported 1.7/1 ratio. На базі хірального комплексу Ni(II) основи Шифа гліцину нового типу було розроблено каскадні реакції приєднання-циклізації з метою вивчення аспектів кінетичного/термодинамічного утворення відповідних (S)(2S,3S)/(S)(2S,3R) діастереомерів. Було знайдено, що утворені лактони в значній мірі є продуктами термодинамічно контрольованої діастереоселективності завдяки значному внеску зворотньої реакції альдольного приєднання порівняно із подальшою циклізацією. Досить несподіваним виявився факт температурної залежності стереохімічних співвідношень продуктів реакції: при низькій температурі утворювався переважно (2S,3R) діастереомер, у той час як при підвіщеній – (2S,3S). Спостережувана діастереоселективність становила 4/1 (S)(2S,3S)/(S)(2S,3R), що є значно кращим показником порівняно із попередніми даними (1.7/1). Подібний рівень діастереоселективності, а також сумарний вихід продуктів реакції (більш ніж 90%), свідчать про великий синтетичний потенціал даного методу, що однозначно заслуговує на всебічне та цілеспрямоване дослідження. V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2021-06-30 Article Article application/pdf application/pdf https://bioorganica.com.ua/index.php/journal/article/view/42 10.15407/bioorganica2021.01.003 Ukrainica Bioorganica Acta; Vol. 16 No. 1 (2021): Ukrainica Bioorganica Acta; 3-9 Ukrainica Bioorganica Acta; Том 16 № 1 (2021): Ukrainica Bioorganica Acta; 3-9 1814-9766 1814-9758 10.15407/bioorganica2021.01 en https://bioorganica.com.ua/index.php/journal/article/view/42/41 https://bioorganica.com.ua/index.php/journal/article/view/42/42 Copyright (c) 2021 Yupiao Zou, Zizhen Yin, Haibo Mei, Hiroyuki Konno, Hiroki Moriwaki, Vadim A. Soloshonok, Jianlin Han https://creativecommons.org/licenses/by/4.0 |
| spellingShingle | асиметричний синтез альдольне приєднання специфічні неприродні амінокислоти Ni(II) комплекси основи Шифа каскадні/доміно/тандемні реакції Zou, Yupiao Yin, Zizhen Mei, Haibo Konno, Hiroyuki Moriwaki, Hiroki Soloshonok, Vadim A. Han, Jianlin Каскадні реакції альдольного приєднання та циклізації на основі хірального комплексу Ni(II) основи Шифа гліцину |
| title | Каскадні реакції альдольного приєднання та циклізації на основі хірального комплексу Ni(II) основи Шифа гліцину |
| title_alt | Aldol addition-cyclization reaction cascade on a platform of chiral Ni(II) complex of glycine schiff base |
| title_full | Каскадні реакції альдольного приєднання та циклізації на основі хірального комплексу Ni(II) основи Шифа гліцину |
| title_fullStr | Каскадні реакції альдольного приєднання та циклізації на основі хірального комплексу Ni(II) основи Шифа гліцину |
| title_full_unstemmed | Каскадні реакції альдольного приєднання та циклізації на основі хірального комплексу Ni(II) основи Шифа гліцину |
| title_short | Каскадні реакції альдольного приєднання та циклізації на основі хірального комплексу Ni(II) основи Шифа гліцину |
| title_sort | каскадні реакції альдольного приєднання та циклізації на основі хірального комплексу ni(ii) основи шифа гліцину |
| topic | асиметричний синтез альдольне приєднання специфічні неприродні амінокислоти Ni(II) комплекси основи Шифа каскадні/доміно/тандемні реакції |
| topic_facet | asymmetric synthesis aldol additions tailor-made amino acids Ni(II) complexes Schiff bases cascade/domino/tandem reaction асиметричний синтез альдольне приєднання специфічні неприродні амінокислоти Ni(II) комплекси основи Шифа каскадні/доміно/тандемні реакції |
| url | https://bioorganica.com.ua/index.php/journal/article/view/42 |
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