Enantioselective Michael reaction of anthrone catalyzed by chiral tetraoxacalix[2]arene[2]triazine derivatives

Article abstract of DOI:10.1039/c9ra03029h

A highly enantioselective Michael addition reaction of anthrone with nitroalkenes by chiral tetraoxacalix[2]arene[2]triazine catalysts was investigated as a novel topic. The stereoselective conversion progressed smoothly by employing 10 mol% of the catalyst and afforded the corresponding Michael adducts with acceptable to high enantioselectivities (up to 97% ee) and very high yields (up to 96%).

Full text of DOI:10.1039/c9ra03029h

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Enantioselective Michael reaction of anthrone
catalyzed by chiral tetraoxacalix[2]arene[2]triazine
derivatives†
Cite this: RSC Adv., 2019, 9, 21063
*
Hayriye Nevin Genc
A
highly enantioselective Michael addition reaction of anthrone with nitroalkenes by chiral
Received 23rd April 2019
Accepted 23rd May 2019
tetraoxacalix[2]arene[2]triazine catalysts was investigated as a novel topic. The stereoselective
conversion progressed smoothly by employing 10 mol% of the catalyst and afforded the
corresponding Michael adducts with acceptable to high enantioselectivities (up to 97% ee) and very
high yields (up to 96%).
DOI: 10.1039/c9ra03029h
rsc.li/rsc-advances
eld of study, similar to the case of a Michael donor, various
carbon-centered nucleophiles such as aldehydes and
ketones,15–19 malonate esters,20–22 ketoesters,23 and 1,3-dike-
tones24–26 have been comprehensively studied; in contrast, not
much development has taken place in the improvement of the
usage of anthrone as a nucleophile for the Michael addition
reaction.27–33
1. Introduction
The chemical properties of anthrone and compounds con-
taining the anthrone skeleton are signicant in organic
chemistry. Anthrones and their enol tautomers, i.e., 9-
anthrols form a vital part of anthracenes since the oxidation
of the central rings yields 9,10-anthraquinones, while their
reduction affords anthracenes, which are useful intermedi-
ates.1,2 However, naturally occurring compounds bearing
the anthrone platform are isolated either as O- or C-
glycosides or in a free form from a broad diversity of
plants and shrubs such as rhubarb, cassia, and cascara
sagrada.3,4 Several such substances have noteworthy bio-
logical characteristics and are utilized as antimicrobial,
emetic, antipsoriatic or androgen receptors and telomerase
blockers.5,6 Recent studies have demonstrated that some
anthrone- or anthraquinone-based naturally occurring
compounds show strong and distinctive antitumor
behaviours.7–11
The Michael reaction of carbon-centered nucleophiles with
different Michael acceptors provides a straightforward and
robust technique for the formation of C–C bonds and has
received prevalent preference in the production of organic
materials. As a result, substantial works have been carried out
for the development of the enantioselective forms of this
conversion.12–14 Although remarkable developments have
emerged in the catalytic asymmetric Michael reaction, devel-
oping a new Michael reaction for the effective production of
different novel materials remains a signicant target for studies
conducted in both academic and industrial contexts. In this
Calixarenes and macromolecules bearing one or more cal-
ixarene platforms are known as efficient supramolecular
materials. Heteroatom-bridged calixaromatics, also called
heteroaromatic calixarenes, are a novel group of macrocyclic
host compounds in supramolecular chemistry.34,35 Despite
their exceptional physical and bonding characteristics that
come from the electronic and steric inuences of heteroatom
bridges, heteroaromatic calixarenes are far rarer in usage.36,37
The self-tuning and ne-tuning cavities of their electronic
characteristics make heteroaromatic calixarenes strong
macrocyclic hosts regarding their interactions with neutral
organic guests38,39 and with positively40 and negatively charged
compounds.41–43 Oxygen- and nitrogen-bridged calix[2]arene[2]
triazines are noteworthy heterocalixaromatics.44–47 Based on
the characteristics of the heteroatoms in the bridging units,
calix[2]arene[2]triazines use adaptable conformational
constructs and may provide a diverse set of cavity sizes. Not
limited to interactions of inclusion,48 these materials may also
show p–p interactions of aromatic rings and hydrogen
bonding interactions on the triazine nitrogen atoms as chiral
host compounds.
In the past decade, we have reported the synthesis and
applications of lower-rim-substituted calix[4]arene-based
macromolecules with different functional groups as multiple
H-bond donor chiral catalysts for stereoselective conver-
sions.49–51 Likewise, we have recently reported substituted
tetraoxacalix[2]arene[2]triazine derivatives with different
purposes as chiral catalysts in the stereoselective Michael
additions of isobutyraldehyde using different substituted and
Department of Science Education, A. K. Education Faculty, Necmettin Erbakan
University, Konya 42090, Turkey. E-mail: hngenc@erbakan.edu.tr; Fax: +90 332
3238225; Tel: +90 332 3238220/5534
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c9ra03029h
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unsubstituted aromatic trans-b-nitrostyrenes.52 Here, we 16H), 2.60–2.75 (m, 10H), 2.85–2.90 (m, 8H), 4.13 (q, J ¼ 2.7 Hz,
described an efficient one-pot process to synthesize optically 2H), 7.01–7.15 (m, 20H), 7.20 (t, J ¼ 8.4, 0.5 Hz, 2H), 7.25–7.30
active tetraoxacalix[2]arene[2]triazine derivatives and their (m, 4H), 7.37–7.42 (m, 2H), NH-signals not found; 13C NMR (100
possible applications as organic catalysts in the Michael MHz, CDCl3): d ¼ 14.16, 21.03, 27.51, 32.04, 32.50, 34.14, 57.00,
addition of anthrone to b-nitroolens under mild conditions. 60.47, 62.33, 102.86, 116.90, 128.41, 128.90, 128.96, 130.28,
As far as we know, this study is the rst implementation of 140.40, 157.07, 158.21, 166.00; anal. calcd. for C66H74N10O4
tetraoxacalix[2]arene[2]triazine catalysts in the enantiose- (1071.35): C, 73.99; H, 6.96; N, 13.07%; found: C, 74.15; H,
lective reactions of anthrone.
7.12; N, 12.98%.
2.1.2. Procedure for Michael reaction. A solution of
nitroalkenes 6a–k (0.4 mmol) and the chiral catalyst (0.04
mmol) in toluene (4 mL) was stirred and then, anthrone 5
(0.48 mmol) was added. Aer being stirred for 36–72 h at
room temperature, the reaction mixture was subjected
directly to ash column chromatography on silica gel
(hexane/EtOAc ¼ 5 : 1) to furnish the corresponding prod-
ucts. The ee% values of the Michael reaction products were
determined by chiral HPLC analysis using Daicel Chiralpak
OD-H or AS-H columns. The HPLC conditions for products
7a–7k are shown in Table 1; the 1H NMR, 13C NMR and FTIR
spectroscopy values of products 7a–7k are shown in Table 2.
2. Experimental
2.1. Synthesis
2.1.1. Procedure for the synthesis of compounds 4a-4b.
Tetraoxa-bridged calix[2]arene[2]triazine was prepared following
a procedure described by Wang et al.53,54 A mixture of (R)-2-amino-
1-((S)-2-benzhydrylpyrrolidin-1-yl)-2-phenylethanone 1 or (1S,2S)–
N,N-bis(3-phenylpropyl)cyclohexane-1,2-diamine 2 (1.1 mmol)
and DIPEA (2.2 mmol) in THF (20 mL) was added to a solution of
tetraoxa-bridged calix[2]arene[2]triazine 3 (0.5 mmol) in THF (20
mL) at room temperature. The mixture was reuxed for 48–56 h,
aer which the solvent was evaporated under vacuum, giving off
a solid residue. The crude mixture was puried by column
chromatography on silica gel using hexane/EtOAc (10 : 1, v/v) to
3. Results and discussion
afford the desired products as crystalline solids. The products The chiral tetraoxacalix[2]arene[2]triazine derivatives 4a and 4b,
were characterized by a combination of 1H NMR, 13C NMR, which were chosen as chiral catalysts in the model asymmetric
FTIR,55,56 and elemental analysis.
Michael reaction, were synthesized in four steps starting from
Compound 4a. Crystalline solid; 75% yield; a2D5 ¼ ꢀ205.00 (R)-phenylglycine and (1S,2S)-(+)-1,2-diaminocyclohexane,
(c 1, CHCl3); mp 220–222 ꢁC; IR (cmꢀ1): 1358, 1479, 1563, respectively. The chiral subunits (R)-2-amino-1-((S)-2-
1708, 3261; 1H NMR (400 MHz, CDCl3): d ¼ 1.21–1.40 (m, benzhydrylpyrrolidin-1-yl)-2-phenylethanone 1 and (1S,2S)–N,N-
8H), 2.98–3.17 (m, 4H), 4.72 (d, 2H, J ¼ 6.7 Hz), 5.04 (d, J ¼ bis(3-phenylpropyl) cyclohexane-1,2-diamine 2, which were
6.8 Hz, 2H), 6.18 (s, 2H), 7.16–7.38 (m, 32H), 7.82–7.87 (m, synthesized in three steps, were prepared according to previ-
6H), NH-signals not found; 13C NMR (100 MHz, CDCl3): d ¼ ously reported procedures,57,58 as illustrated in Scheme 1.
23.34, 29.47, 46.29, 51.17, 58.64, 65.80, 124.74, 127.33, Subsequently, the chiral tetraoxacalix[2]arene[2]triazines 4a and
127.63, 128.00, 128.23, 128.43, 128.60, 128.73, 129.05, 4b were synthesized from 1 and 2, respectively, in overall good
129.68, 130.00, 138.20, 140.53, 140.68, 158.20, 162.20, yields (up to 75–78%), as illustrated in Scheme 2.
166.00, 169.10; anal. calcd. for C68H58N10O6 (1111.25): C,
In the rst review of the conditions, having selected the
73.49; H, 5.26; N, 12.60%; found: C, 73.51; H, 5.31; N, Michael addition of anthrone 5 and trans-b-nitrostyrene 6a as
12.48%.
the enantioselective reaction, we found that the tetraoxacalix[2]
Compound 4b. Crystalline solid; 78% yield; a2D5 ¼ +218.00 (c 1, arene[2]triazine catalysts catalyzed the process effectively,
CHCl3); mp 326–328 ꢁC; IR (cmꢀ1): 1365, 1483, 1569, 1705, 3281; affording the expected adduct 7a in an optically active form. The
1H NMR (400 MHz, CDCl3): d ¼ 1.19–1.35 (m, 8H), 1.82–2.12 (m, reaction progressed successfully in nonpolar solvents including
Table 1 HPLC conditions of products 7a–7k
Product
Column
Hexane/2-propanol
Flow rate
tR (minor)
tR (major)
7a
7b
7c
7d
7e
7f
7g
7h
7i
AS-H
OD-H
OD-H
AS-H
OD-H
AS-H
AS-H
AS-H
OD-H
AS-H
AS-H
90 : 10
80 : 20
80 : 20
80 : 20
70 : 30
80 : 20
80 : 20
90 : 10
80 : 20
90 : 10
70 : 30
0.7 mL minꢀ1
1.0 mL minꢀ1
1.0 mL minꢀ1
1.0 mL minꢀ1
1.0 mL minꢀ1
1.0 mL minꢀ1
1.0 mL minꢀ1
1.0 mL minꢀ1
1.0 mL minꢀ1
1.0 mL minꢀ1
1.0 mL minꢀ1
25.96 min
15.94 min
11.82 min
12.85 min
18.14 min
13.25 min
17.43 min
18.19 min
19.62 min
26.11 min
12.35 min
23.25 min
12.85 min
10.06 min
10.15 min
15.32 min
10.42 min
14.65 min
16.02 min
26.21 min
21.93 min
10.19 min
7j
7k
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Table 2 1H NMR, 13C NMR, and FTIR spectroscopy values of products 7a–7k
7a
Mp
147–148 ꢁ
928, 1310, 1548, 1600, 1671
4.03–4.06 (m, 1H), 4.53 (d, J ¼ 3.7 Hz, 1H), 4.60 (dd, J ¼ 13.3, 7.0 Hz,
1H), 4.88–4.91 (dd, J ¼ 13.3, 9.1 Hz, 1H), 6.07 (d, J ¼ 7.6 Hz, 2H), 6.91
(t, J ¼ 7.8 Hz, 2H), 7.14–7.17 (m, 1H), 7.39–7.43 (m, 2H), 7.50 (d, J ¼
8.5 Hz, 2H), 7.60–7.68 (m, 2H), 7.94 (d, J ¼ 7.8 Hz, 1H), 8.01 (d, J ¼
8.0 Hz, 1H)
C
IR (cmꢀ1
)
1H NMR (400 MHz, CDCl3)
13C NMR (100 MHz, CDCl3)
Mp
45.9, 52.8, 76.4, 126.1, 126.9, 127.8, 128.0, 128.1, 128.2, 128.3, 128.7,
131.9, 132.2, 132.9, 133.4, 134.6, 139.8, 142.3, 183.1
7b
65–67 ꢁ
C
929, 1317, 1552, 1598, 1671
IR (cmꢀ1
)
1H NMR (400 MHz, CDCl3)
13C NMR (100 MHz, CDCl3)
Mp
4.31–4.39 (m, 2H), 4.59–4.69 (m, 2H), 6.18 (d, J ¼ 8.5 Hz, 1H), 6.80 (d,
J ¼ 6.7 Hz, 1H), 7.00 (d, J ¼ 7.1 Hz, 1H), 7.40–7.61 (m, 4H), 7.63 (s,
2H), 8.13 (t, J ¼ 7.8 Hz, 2H)
45.0, 48.0, 74.0, 126.3, 127.1, 127.3, 127.9, 128.3, 128.5, 128.6, 129.8,
130.3, 131.7, 132.5, 133.0, 133.3, 133.6, 134.9, 136.0, 138.9, 140.2,
183.4
7c
141–143 ꢁC
935, 1322, 1551, 1600, 1671
IR (cmꢀ1
)
1H NMR (400 MHz, CDCl3)
4.18–4.24 (m, 1H), 4.37 (dd, J ¼ 13.3, 8.4 Hz, 1H), 4.50 (dd, J ¼ 13.6,
6.9 Hz, 1H), 4.68 (d, J ¼ 3.6 Hz, 1H), 5.57 (d, J ¼ 3.3 Hz, 1H), 6.20–6.22
(m, 1H), 7.00 (d, J ¼ 7.5 Hz, 1H), 7.19 (d, J ¼ 1.1 Hz, 1H), 7.49–7.54 (m,
4H), 7.60–7.63 (m, 1H), 8.20 (t, J ¼ 6.1 Hz, 2H)
44.8, 46.9, 73.9, 109.3, 110.1, 126.0, 127.3, 127.8, 128.2, 128.3, 128.5,
133.0, 133.2, 133.5, 133.7, 139.9, 140.5, 142.7, 148.4, 183.2
13C NMR (100 MHz, CDCl3)
Mp
7d
7e
63–65 ꢁ
C
938, 1320, 1555, 1601, 1659
IR (cmꢀ1
)
1H NMR (400 MHz, CDCl3)
4.00–4.03 (m, 1H), 4.81 (d, J ¼ 5.4 Hz, 1H), 4.89–5.01 (m, 1H), 5.12
(dd, J ¼ 13.9, 5.5 Hz, 1H), 6.60–6.62 (m, 1H), 7.10–7.13 (m, 2H), 7.29–
7.36 (m, 2H), 7.51–7.65 (m, 5H), 7.96 (d, J ¼ 7.6 Hz, 1H)
45.0, 49.9, 77.1, 126.0, 126.1, 126.9, 127.8, 128.2, 129.0, 129.4, 130.0,
131.9, 132.2, 132.4, 133.1, 135.0, 139.8, 140.3, 181.3
13C NMR (100 MHz, CDCl3)
Mp
69–72 ꢁ
C
IR (cmꢀ1
)
936, 1313, 1529, 1551, 1604, 1670
1H NMR (400 MHz, CDCl3)
13C NMR (100 MHz, CDCl3)
Mp
4.69–4.74 (m, 1H), 4.83 (d, J ¼ 5.2 Hz, 1H), 5.09 (dd, J ¼ 13.6, 10.3 Hz,
1H), 5.30 (dd, J ¼ 13.9, 5.5 Hz, 1H), 6.69–6.72 (m, 1H), 7.29–7.38 (m,
3H), 7.48–7.62 (m, 6H), 7.90 (dd, J ¼ 13.9, 7.6 Hz, 2H)
44.9, 45.5, 76.8, 123.9, 125.8, 126.1, 127.6, 127.8, 128,2, 128.9, 129.1,
129.2, 129.5, 131.9, 132.0, 132.5, 132.9, 134.0, 140.0, 140.9, 150.0,
183.1
7f
129–131 ꢁ
C
IR (cmꢀ1
)
929, 1320, 1509, 1555, 1600, 1661
1H NMR (400 MHz, CDCl3)
3.19 (s, 1H), 4.39–4.43 (m, 1H), 4.69 (d, J ¼ 3.9 Hz, 1H), 4.79 (dd, J ¼
13.1, 10.1 Hz, 1H), 5.09 (dd, J ¼ 13.4, 5.9 Hz, 1H), 6.03 (d, J ¼ 6.5 Hz,
1H), 6.50 (t, J ¼ 7.4 Hz, 1H), 6.70 (d, J ¼ 8.0 Hz, 1H), 7.10 (t, J ¼ 7.3 Hz,
1H), 7.39–7.50 (m, 4H), 7.59–7.62 (t, J ¼ 7.4 Hz, 2H), 7.82 (d, J ¼
7.4 Hz, 1H), 7.89 (m, J ¼ 7.9 Hz, 1H)
13C NMR (100 MHz, CDCl3)
Mp
44.9, 45.0, 54.8, 76.7, 109.9, 120.4, 121.3, 124.6, 125.8, 126.2, 127.5,
128.0, 128.4, 129.0, 129.4, 131.9, 132.9, 141.0, 142.6, 156.9, 183.0
7g
115–117 ꢁ
C
934, 1313, 1549, 1600, 1661
IR (cmꢀ1
)
1H NMR (400 MHz, CDCl3)
4.01–4.06 (m, 1H), 4.56–4.62 (m, 2H), 4.89 (dd, J ¼ 13.3, 8.8 Hz, 1H),
5.99 (d, J ¼ 7.3 Hz, 1H), 6.17 (s, 1H), 6.86 (t, J ¼ 7.9 Hz, 1H), 7.32 (d, J
¼ 9.1 Hz, 1H), 7.42–7.59 (m, 4H), 7.65–7.71 (m, 2H), 8.05 (d, J ¼
7.6 Hz, 1H), 8.15 (d, J ¼ 7.7 Hz, 1H)
13C NMR (100 MHz, CDCl3)
Mp
45.9, 53.0, 76.1, 121.9, 126.6, 127.2, 127.6, 128.3, 128.4, 128.5, 128.7,
129.6, 131.6, 131.9, 132.7, 133.0, 133.5, 134.6, 135.7, 139.0, 141.6,
183.0
7h
156–158 ꢁ
C
929, 1315, 1548, 1600, 1659
IR (cmꢀ1
)
1H NMR (400 MHz, CDCl3)
2.09 (s, 3H), 4.00–4.04 (m, 1H), 4.49 (d, J ¼ 3.5 Hz, 1H), 4.54 (dd, J ¼
13.1, 7.1 Hz, 1H), 4.82 (dd, J ¼ 13.1, 8.9 Hz, 1H), 5.99 (d, J ¼ 8.0 Hz,
2H), 6.74 (d, J ¼ 7.7 Hz, 2H), 7.35–7.45 (m, 2H), 7.49 (d, J ¼ 7.4 Hz,
2H), 7.56–7.61 (m, 2H), 8.03 (d, J ¼ 7.7 Hz, 1H), 8.10 (d, J ¼ 7.3 Hz,
1H)
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Table 2 (Contd.)
13C NMR (100 MHz, CDCl3)
Mp
20.9, 45.9, 53.1, 75.8, 126.4, 126.9, 127.4, 127.9, 128.3, 128.5, 128.6,
129.9, 132.4, 132.8, 133.4, 134.3, 138.1, 139.3, 142.0, 182.9
7i
7j
119–121 ꢁ
C
IR (cmꢀ1
)
929, 1312, 1511, 1548, 1599, 1671
1H NMR (400 MHz, CDCl3)
3.71 (s, 3H), 3.99–4.01 (m, 1H), 4.49 (d, J ¼ 3.8 Hz, 1H), 4.57 (dd, J ¼
13.3, 7.4 Hz, 1H), 4.82 (dd, J ¼ 13.3, 9.1 Hz, 1H), 6.00 (d, J ¼ 8.8 Hz,
2H), 6.50 (d, J ¼ 8.8 Hz, 2H), 7.40–7.54 (m, 4H), 7.60–7.67 (m, 2H),
8.02 (d, J ¼ 7.9 Hz, 1H), 8.10 (d, J ¼ 7.3 Hz, 1H)
13C NMR (100 MHz, CDCl3)
Mp
45.9, 52.4, 54.9, 76.9, 113.2, 125.0, 127.1, 127.5, 127.8, 128.0, 128.2,
128.3, 129.4, 132.6, 132.8, 133.9, 134.8, 139.0, 141.9, 160.0, 182.9
168–171 ꢁ
C
IR (cmꢀ1
)
929, 1321, 1549, 1600, 1659
1H NMR (400 MHz, CDCl3)
4.01–4.04 (m, 1H), 4.49 (d, J ¼ 3.4 Hz, 1H), 4.60 (dd, J ¼ 13.3, 7.6 Hz,
1H), 4.87 (dd, J ¼ 13.3, 8.5 Hz, 1H), 5.99 (d, J ¼ 8.5 Hz, 2H), 6.92 (d, J ¼
8.5 Hz, 2H), 7.40–7.55 (m, 4H), 7.61–7.67 (m, 2H), 8.03 (d, J ¼ 7.9 Hz,
1H), 8.09 (d, J ¼ 7.6 Hz, 1H)
13C NMR (100 MHz, CDCl3)
Mp
45.8, 52.5, 76.4, 126.8, 127.0, 127.2, 127.6, 127.9, 128.1, 128.2, 128.4,
130.0, 131.9, 132.2, 132.9, 133.1, 134.0, 134.5, 138.9, 141.7, 182.9
7k
171–172 ꢁ
C
IR (cmꢀ1
)
929, 1323, 1511, 1548, 1605, 1658
1H NMR (400 MHz, CDCl3)
4.01–4.06 (m, 1H), 4.55 (d, J ¼ 3.7 Hz, 1H), 4.60 (dd, J ¼ 13.3, 7.3 Hz,
1H), 4.90 (dd, J ¼ 13.3, 9.1 Hz, 1H), 5.99 (dd, J ¼ 8.8, 5.2 Hz, 2H), 6.67
(t, J ¼ 8.8 Hz, 2H), 7.45–7.58 (m, 4H), 7.64–7.68 (m, 2H), 7.98 (d, J ¼
7.3 Hz, 1H), 8.07 (d, J ¼ 7.9 Hz, 1H)
13C NMR (100 MHz, CDCl3)
46.3, 52.8, 76.6, 114.8, 115.2, 127.1, 127.6, 127.9, 128.0, 128.2, 128.5,
128.9, 129.5, 130.8, 131.9, 132.8, 133.6, 134.5, 138.9, 142.1, 161.9,
182.9
hexane, CHCl3, CH2Cl2 or toluene (Table 3, entries 1–8);
Other aspects of this reaction such as temperature, use of
however, when we used a polar solvent, such as ethyl acetate, the recycled catalyst, and catalyst loading were investigated
diethyl ether or acetone, signicant decrease was observed in (Table 4). When the same reaction was performed at 0 ꢁC with
chemical yield and enantioselectivity (Table 3, entries 15–20). 10 mol% of 4a and 4b as catalysts, the desired adduct 7a was
This may be due to the fact that the polar solvents interacted obtained with low to 88–89% ee in 83–85% yield, with further
with the organocatalysts through hydrogen bonding to weaken extension of the reaction time (72 h, Table 4, entries 3 and 4).
the activation ability of 4a and 4b towards the reaction. As In addition, similar to the reaction conducted at 0 ꢁC, the
projected by our tentative hypothesis, the best yield (96%) and reaction carried out at ꢀ20 ꢁC showed less desired yields and
enantioselectivity (97% ee) were obtained using the less polar enantioselectivities than the reaction at room temperature
solvent, i.e., toluene.
(Table 4, entries 1 and 2). Additionally, we conducted recy-
cling analysis of the chiral catalysts 4a and 4b in the Michael
Scheme 1 The synthetic routes for starting materials 1 and 2.
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Scheme 2 The synthetic route for tetraoxa-bridged calix[2]arene[2]triazine derivatives 4a/4b.
reaction of 5 and 6a. Thus, the compounds 4a and 4b could adducts. However, by prolonging the reaction time, low
be easily recycled by ash chromatography alongside Michael enantioselectivity and yield values were found at room
temperature, as seen in Table 4 (entries 7 and 8). In the
presence of 10 mol% catalysts, 4a and 4b showed similar
Table 3 Michael addition between anthrone 5 and trans-b-nitro- enantioselectivities, but 4b showed slightly higher catalytic
styrene 6a catalysed by 4a–4b in various solvents
activity than 4a (Table 4, entries 5 and 6). When the loading
of the catalysts 4a and 4b went up to 15 mol%, trans-b-
nitrostyrene gave Michael products in low yields with 93–95%
and 93–95% enantiomeric excess, respectively (Table 4,
entries 9 and 10). These results were better than that for the
use of 5 mol% of catalyst, in which case the yields of the
Michael products were 88% for catalyst 4a and 90% for
catalyst 4b and the enantiomeric excesses of the Michael
products were 89% for catalyst 4a and 90% for catalyst 4b
(Table 4, entries 11 and 12). These ndings led us to choose
the reaction conditions using toluene as a solvent at room
temperature in the presence of 10 mol% of 4b to probe the
scope of nitroolens.
As we enhanced the reaction details for the Michael
addition of anthrone 5 to trans-b-nitrostyrene 6a (catalyst 4b
10 mol% in toluene at room temperature), a set of different
nitrostyrenes with various substituent groups were analyzed,
and the results are summarized in Table 5. These nitro-
styrenes reacted with anthrone to afford the corresponding
adducts 7a–7k in moderate to excellent yields with excellent
enantioselectivities (Table 5, entries 1–11). As demonstrated
in Table 5, anthrone reacts smoothly with a wide range of
ortho-, meta- or para-substituted nitrostyrenes with electron-
releasing or electron-withdrawing groups and the corre-
sponding Michael adducts in good to excellent yields (86–
96%) and enantioselectivities (81–97%) are obtained. To our
satisfaction, trans-b-nitrostyrene and 4-Me-nitrostyrene as
Michael acceptors gave good yields and enantioselectivities
(Table 5, entries 1 and 8).
Entrya
Catalyst
Solvent
Time (h)
Yieldb (%)
eec,d (%)
1
2
3
4
5
6
7
8
4a
4b
4a
4b
4a
4b
4a
4b
4a
4b
4a
4b
4a
4b
4a
4b
4a
4b
4a
4b
Hexane
Hexane
CHCl3
CHCl3
CH2Cl2
CH2Cl2
Toluene
Toluene
CH3CN
CH3CN
Xylene
Xylene
THF
72
72
48
48
48
48
48
48
72
72
72
72
72
72
48
48
72
72
48
48
88
90
85
89
81
83
95
96
92
95
87
90
82
85
87
91
83
86
85
88
93
95
90
91
92
93
96
97
80
81
91
95
84
87
80
85
88
89
82
85
9
10
11
12
13
14
15
16
17
18
19
20
THF
EtOAc
EtOAc
Et2O
Et2O
Acetone
Acetone
a
Conditions: anthrone (0.48 mmol), trans-b-nitrostyrene (0.40 mmol)
b
and 4a/4b (10 mol%) in solvents (4.0 mL). Isolated yield aer ash
chromatograpy. Determined by HPLC. Determined by comparing
reported data.
c
d
In conclusion, we developed highly efficient asymmetric
Michael addition of anthrone to nitroalkenes catalyzed by
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based chiral polyesters,59 and Ar-BINMOLs60 catalysts for the
reaction of anthrone to a series of nitroalkenes. The steric
bulkiness and carbonyl groups were crucial in this reaction to
give the corresponding adducts in lower ee than that for the
catalyst without carbonyl groups. Efforts to elucidate the
mechanistic details of this catalytic system and to further
extend the scope and limitations of these kinds of organo-
catalysts are currently in progress.
Table 4 Screening of various reaction conditions
Temp.
4. Conclusions
Entrya
Catalyst
(ꢁC)
Time (h)
Yieldb (%)
eec,d (%)
In conclusion, in this work, a new class of chiral tetraoxa-
bridged calix[2]arene[2]triazine derivatives described as effec-
tive organocatalysts for the Michael reaction of anthrone to
various nitrostyrenes was reported for the rst time. The addi-
tion reactions were carried out smoothly in toluene at room
temperature by utilizing 10 mol% of 4a and 4b to give Michael
products with high yields (up to 96%) and ee values (up to 97%).
1
2
3
4
5
6
4a
4b
4a
4b
4a
4b
4a
4b
4a
4b
4a
4b
ꢀ20
ꢀ20
0
72
72
72
72
48
48
72
72
48
48
48
48
80
81
83
85
95
96
75
78
93
95
88
90
85
86
88
89
96
97
86
90
93
95
89
90
0
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
7e
8e
9f
10f
11g
12g
Conflicts of interest
There are no conicts to declare.
a
Conditions: anthrone (0.48 mmol), trans-b-nitrostyrene (0.40 mmol),
b
and 4a/4b (10 mol%) in toluene (4.0 mL).
Isolated yield.
c
e
d
Notes and references
Determined by HPLC. Determined by comparing reported data.
f
Reaction was performed with recycled catalyst. 15 mol% of catalyst
g
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a
Conditions: anthrone (0.48 mmol), trans-b-nitrostyrene (0.40 mmol),
b
and 4b (10 mol%) in toluene (4.0 mL). Isolated yield aer ash
chromatograpy. Determined by HPLC. The congurations were
determined by comparing reported data.
c
d
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