One-pot synthesis of α,β-epoxy ketones through domino reaction between alkenes and aldehydes catalyzed by proline based chiral organocatalysts

Article abstract of DOI:10.1039/c7ob00031f

Proline based metal free organocatalysts were developed by using a new approach for the synthesis of epoxide derivatives through a domino reaction. This domino reaction (oxidative coupling) allows a direct access to epoxides from various alkenes and aldehydes through C-H functionalization and C-C/C-O bond formation. The catalytic efficiencies of the newly synthesized organocatalysts were also determined by domino reaction in the presence of various functional groups containing aldehyde and alkene derivatives with very good yields (up to 95%) and ee's (up to 99%).

Full text of DOI:10.1039/c7ob00031f

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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One-pot synthesis of ɑ,β-epoxy ketones through domino reaction
between alkenes and aldehydes catalyzed by proline based chiral
organocatalysts
Received 00th January 20xx,
Accepted 00th January 20xx
Veeramanoharan Ashokkumar and Ayyanar Siva*
DOI: 10.1039/x0xx00000x
www.rsc.org/
Abstract: A proline based metal free organocatalysts developed by new approach for the synthesis of epoxide derivatives
through domino reaction. This domino reaction (oxidative coupling) allows the direct access to epoxides from various
alkene and aldehyde through C–H functionalization and C–C/C–O bond formation. The catalytic efficiencies of the newly
synthesized organocatalysts were also determined by domino reaction in presence of various functional groups containing
aldehyde and alkene derivatives with very good yield (up to 95 %) and ee’s (up to 99 %).
the chemical transformations easily.14 However, bifunctionalization
of alkenes to different functional group such as aldehyde, alcohol,
1. Introduction
α,-Epoxy ketones are important intermediates and precursors
in modern synthetic organic chemistry.1 Further, they can be
reliably functionalized to provide numerous products (e.g.
pharmaceuticals, natural products, agricultural chemicals,
fragrances, and inhibitors of cytosolic epoxide hydrolases) including
α- and -carbonyls, α,-epoxy alcohols, 1,3-diols, etc.2 In general,
α,-epoxy ketones can be prepared either by the Darzens reaction
of α-halocarbonyl compounds with aldehydes under strong basic
conditions3 or epoxidation of α,-unsaturated ketones, with
various oxidants, catalyzed by different catalytic systems such as
Lewis acids or phase-transfer catalysts.4-10 An alternative method of
oxidative coupling of aldehydes with styrenes catalyzed by base,
with TBHP as an oxidant, has also been reported for its synthesis.11
However, these methods were required either prefunctionalized
starting materials, expensive metal catalysts, or often employ a
large excess of aldehydes and oxidants (TBHP, H2O2) at high
temperatures, thus resulting in low chemical yield and low atom
economy of the process.12
amine and peroxide is still a distinct challenge.15,16 The catalyst
design is important for enhancing enantiomeric excess, a C3-
symmetric proline catalyst has been found to be an excellent
catalyst for domino reaction with higher reactivity and better
asymmetric induction than the C1-and C2-symmetric catalyst.
Herein, we wish to disclose a novel proline based organocatalyzed,
metal-free and base free domino reaction (oxidative coupling) in
presence of alkenes, aldehydes, and hydroperoxide to afford α,-
epoxy ketones with higher yield and excellent ee’s under mild
reaction conditions (Scheme 1). Our chiral organocatalysts itself act
as a base as well as catalyst.
2. Results and discussion
Organocatalyzed reactions represented an attractive alternative
method to metal-catalyzed processes, because of their low cost and
benign environmental impact in comparison to organometallic
catalysis. As organocatalysts, proline catalyst has a wide range of
C−C, C−O, and C−N bond-forming reactions.13 In addition, proline is
an abundant chiral molecule that is inexpensive and bifunctional
compound, such as carboxylic acid and amine portion. These two
functional groups can act as an acid or base and can also facilitate
Scheme 1 Proline based organocatalytic domino reaction (oxidative
coupling) of alkenes with aldehydes.
The scaffold 7 and 10, obtained from the modified procedure
(Scheme 2).17 Further, the proline based chiral C3-symmetric
organocatalysts (12a and 12b) synthesized by using compound 7
and 10 with chiral precursor proline, as depicted in (Scheme 2). The
initial attempt an optimization of domino reaction, we carried out
this reaction in different solvent condition, the product yields and
ee’s decreases gradually from polar to non-polar solvents (Table 1,
entries 1-14).
a.Supramolecular and Organometallic Chemistry Lab, School of Chemistry, Madurai
Kamaraj University, Madurai-625 021, Tamil Nadu, India. E.mail.
drasiva@gmail.com
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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DOI: 10.1039/C7OB00031F
Scheme 2 Synthesis of proline based organocatalysts 12a and 12b.
Table 1 Effect of various solvents on domino reaction (oxidative the lack of hydrogen bonding in the solvent and the nucleophile is
coupling) between benzaldehyde and styrene.
relatively “free” in solution, making them more reactive.
Table 2 Optimization of oxidants and bases for domino reaction
(oxidative coupling) between benzaldehyde and styrene.
Ent. Solvents
Cat.
Time (h)a Yield (%)b
ee (%)c
Ent. Oxidant Base
Time (h)a Yield (%)b
ee (%)c
1
2
3
Ethanol
Ethanol
1-butanol
12a
12b
12a
15
15
15
60
65
43
47
59
31
1
2
3
H2O2
H2O2
H2O2
BQ
Kt-OBu
TEA
-
17
17
17
24
24
36
36
48
48
10
10
10
10
10
-
20
31
-
31
47
-
-
-
-
-
-
-
4
5
6
1-butanol
Acetonitrile 12a
Acetonitrile 12b
12b
15
10
10
10
10
10
10
24
24
24
24
51
90
95
85
90
78
85
Trace
Trace
n.re
n.re
41
95
99
89
92
79
86
-
4
TEA
n.re
Trace
n.re
Trace
n.re
Trace
-
5
BQ
-
7
8
9
DMSO
DMSO
THF
12a
12b
12a
12b
12a
12b
12a
12b
6
7
APS
APS
TEA
-
8
9
PMS
PMS
TBHP
TBHP
TBHP
TBHP
TBHP
TEA
-
10
11
12
13
14
THF
Toluene
Toluene
Xylene
Xylene
10
11
12
13
14
NaOH
Kt-OBu
TEA
Pyridine
-
-
-
-
-
76
57
95
-
62
41
99
a
The domino reaction was carried out between the
benzaldehyde (1 mmol), styrene (1 mmol), TBHP (2 equiv.) and
solvents (2 mL) at room temperature with different time.
Isolated yield of purified material.
determined by HPLC analysis of epoxide product using a chiral
column (Chiralcel OD-H) with hexane: IPA as an eluent.
a
The domino reaction was carried out between the benzaldehyde
(1 mmol), styrene (1 mmol), oxidants (2 equiv.) and acetonitrile
(2 mL) at room temperature with different time. b Isolated yield of
purified material. c Enantiopurity was determined by HPLC analysis
of epoxide product using a chiral column (Chiralcel OD-H) with
b
c
Enantiopurity was
d
d
Absolute configuration (2R,3S) was determined by comparison
hexane: IPA as an eluent. Absolute configuration (2R,3S) was
of the HPLC retention time using known literature data.4-10
determined by comparison of the HPLC retention time using known
e
e
literature data.4-10 no reaction. BQ = 1,4-benzoquinone, APS =
TBHP= tert-butyl hydrogen peroxide (70 % in water),
no
reaction
ammonium peroxysulphate, PMS
monosulphate.
=
potassium peroxy
The protic polar solvents such as ethanol and 1-butanol gave
lower yields and ee’s, due to hydrogen bonding solvents tending to
decrease the reactivity of nucleophile (Table 1, entries 1-4). On the
other hand, the aprotic polar solvents gave higher yields and ee’s
with lower reaction time (Table 1, entries 5-10). This may be due to
Furthermore, these solvents do not participate in the
reaction; they serve only as the reaction medium. Finally, in the
presence of the non-polar solvents does not give any considerable
effect in the reaction, even increased the reaction time to 24 hrs
2 | J. Name., 2012, 00, 1-3
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(Table 1, entries 11-14), this may be due to the non-polar solvents the oxidative coupling reaction. Further, we selecteVdiewTBAHrtiPcleaOsnlainne
DOI: 10.1039/C7OB00031F
have low dielectric constants (< 5) and hence reduce the binding oxidant and triethylamine as a base, we got better yield and poor
ability of the organocatalysts. But, the enantiomeric excess as well enantioselectivity (Table 2, entry 12). Remarkably, without adding
as an excellent chemical yield was observed when the reaction was any base, we got a very good yield and ee’s. This may be due to the
performed in acetonitrile as a solvent (Table 1, entry 5 and 6). presence of amine portion in the proline moiety of our
Henceforth, we have chosen an acetonitrile as a suitable solvent for organocatalysts which may act as a base to abstract the active
further investigations.
hydrogen from the intermediate 19 (Scheme 3) to afford desired
Table 3 Effect of temperature and concentration of catalyst on product. Hence, we conclude that, our organocatalyst itself acting
domino reaction (oxidative coupling) between benzaldehyde and as a base as well as catalyst.
styrene.
From the obtained results (Table 3, entries 1-12), which shows
that the concentration of the catalyst and temperature was
affected the chemical yields and ee’s of the desired product, it can
be noted from the Table 3, the 2 mol % of the catalyst gave a higher
chemical yields and excellent ee’s when compared to others. This
Ent.
Tempe-
rature
65 °C
65 °C
65 °C
30 °C
30 °C
30 °C
0 °C
0 °C
0 °C
−10 °C
−10 °C
−10 °C
mol % of
cat.
Time
(h)a
10
10
10
10
10
10
20
20
20
24
24
Yield
(%)b
90
86
40
95
90
48
17
ee
(%)c
92
89
67
99
95
80
47
31
-
may be due to the catalyst poison may take place in this reaction
irrespective of the organocatalyst 12b. Furthermore, the
temperature of the reaction medium strongly affected the product
yields and ee’s. From the observed results, higher chemical yields
and ee’s were obtained at room temperature, when compared to
other temperature conditions, i.e. 65 °C, 0 °C and -10 °C (Table 3,
entries 1–12). In summary, from these investigations, the optimized
reaction conditions are: concentration of organocatalysts (2 mol
%), acetonitrile as a solvent, TBHP (2 equiv.) as an oxidant and room
temperature. Furthermore, we carried out the oxidative coupling
reaction between benzaldehyde and styrene by using C1-, C2-and
C3-symmetric proline based organocatalysts. From the observed
results, we found that C3-symmetric proline catalysts (12a and 12b)
is more efficient catalyst than the C1- and C2-symmetric catalysts
(Table S1, entries 1-4, See ESI). This may be due to the presence of
multiactive sites in C3-symmetric proline catalysts compared to
others.
1
2
3
4
5
6
7
8
9
2
5
15
2
5
15
2
5
15
2
5
15
Trace
Trace
Trace
Trace
10
11
12
-
-
-
15
24
a
The domino reaction was carried out between the benzaldehyde
(1 mmol), styrene (1 mmol), TBHP (2 equiv.) and acetonitrile (2 mL)
b
at various temperature with different time. Isolated yield of
purified material. c Enantiopurity was determined by HPLC analysis
of epoxide product using a chiral column (Chiralcel OD-H) with
d
hexane: IPA as an eluent. Absolute configuration (2R,3S) was
determined by comparison of the HPLC retention time using known
literature data.4-10
The scope of both alkenes and aldehydes was investigated at
above mentioned optimized reaction conditions in the presence of
organocatalysts 12a and 12b (Table 4 and Table 5). The results in
Table
4
show that the oxidative coupling reaction of
Further, we carried out the optimization of oxidants for the
oxidative coupling of benzaldehyde and styrene by using 2 mol % of
the organocatalyst 12a or 12b along with different oxidants in
acetonitrile at room temperature. The reaction was carried out in
the presence of H2O2 as an oxidant, we got our expected product
with very low yield and ee’s, obtained from more than 10 hrs (Table
2, entries 1-3). When using 1,4- benzoquinone, APS and PMS as
oxidants in combination with the organocatalysts 12b in acetonitrile
produced only a trace amount of desired product (Table 2, entries
4-9). In the presence of TBHP, the oxidative coupling reaction
occured to give the corresponding product phenyl(3-phenyloxiran-
2-yl)methanone with very good yields and ee’s without adding any
base (Table 2, entry 14). In addition to that, we investigated various
inorganic and organic bases in the oxidative coupling reaction
between the styrene and benzaldehyde. The α,-epoxy ketones are
not formed in the presence of strong bases like NaOH and KtOBu
(Table 2, entries1-14). This may be due to the formation of
secondary product (i.e. cleavage of epoxide to diol formation) to
4‐methylbenzaldehyde successfully proceeded with either
electron‐withdrawing or electron‐donating substituents on the
styrene ring. The addition of an electron‐withdrawing group at any
position on the styrene ring allows the coupling reaction with
4‐methylbenzaldehyde to form the desired product in high yields
and ee’s (Table 4, entries 1–7). The above results also show that the
appropriate product is obtained with higher yield when styrene was
used as a reactant (Table 4, entry 8). It is interesting to note that
the use of a substrate having an electron‐donating group such as
methyl and methoxy group on the styrene ring resulted in a
moderate yields and good ee’s (Table 4, entries 9 and 10).
From the observed results of Table 5, it is evident that
benzaldehyde with various substituents (such as -Cl, -Br, -CH3,
-OCH3, -CH2CH3 and -CF3) at the para position can react with styrene
to form the desired products in high yields and ee’s (Table 5, entries
1–4 and 7-9). Using 2‐ or 3‐methoxyl benzaldehyde as reactants, the
product yields obtained 43 % and 64 % respectively, and moderate
ee’s (Table 5, entries 5 and 6).
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Table 4 Scope of styrene compounds.
Entry
Substratea
Substrate
code
Product
Product
Catalyst
Yield (%)b
ee (%)c
code
12a
12b
85
90
88
94
1
2
3
1a
1b
1c
3a
12a
12b
83
92
87
95
3b
3c
12a
12b
12a
80
86
90
80
90
91
4
5
6
7
1d
1e
1f
3d
3e
3f
12b
12a
94
80
97
83
12b
12a
12b
12a
12b
87
81
89
84
93
93
85
92
90
98
1g
3g
12b
12a
90
95
87
95
8
9
1h
1i
3h
3i
12b
62
84
12a
12b
73
60
91
86
10
1j
3j
12a
72
91
a
The domino reaction was carried out between the 4-methylbenzaldehyde (1 mmol), various styrene (1 mmol), TBHP (2 equiv.) and
acetonitrile (2 mL) at room temperature. b Isolated yield of purified material. c Enantiopurity was determined by HPLC analysis of epoxide
d
product using a chiral column (Chiralcel OD-H) with hexane: IPA as an eluent. Absolute configuration (2R,3S) was determined by
comparison of the HPLC retention time using known literature data.4-10
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Table 5 Scope of aldehyde compounds.
Entry
1
Substratea
Substrate
code
Product
Product
code
Catalyst
Yield (%)b
ee (%)c
12a
12b
90
95
95
99
2a
2b
2c
2d
4a
4b
4c
4d
4e
4f
12a
12b
89
94
92
98
2
3
4
5
6
12a
12b
12a
12b
87
93
85
90
92
97
86
92
12a
12b
14a
12b
43
53
52
64
67
75
60
73
2e
2f
12a
60
87
7
8
2g
2h
4g
4h
12b
12a
12b
72
87
91
95
82
93
12a
12b
12a
14b
85
90
37
44
88
97
65
71
9
2i
2j
4i
4j
10
a The domino reaction was carried out between various aldehydes (1 mmol), styrene (1 mmol), TBHP (2 equiv.) and Acetonitrile (2 mL) at
room temperature.b Isolated yield of purified material. c Enantiopurity was determined by HPLC analysis of epoxide product using a chiral
d
column (Chiralcel OD-H) with hexane: IPA as an eluent. Absolute configuration was (2R,3S) determined by comparison of the HPLC
retention time using known literature data.4-10
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Compared to various aldehyde, the alkyl aldehyde (caproaldehyde) methodology are: 1) metal and base-free synthesis, 2) milder
is less reactive, than the aryl aldehyde, due to generate a poor acyl reaction conditions, and 3) functional-group tolerance and excellent
radical which can reduce the product yields and ee’s (Table 5, entry enantioselectivity. This work demonstrates a facile method for the
10). Further, the results demonstrate that changing the para
position of the aryl substituents of the aldehyde has an obvious
influence on this oxidative coupling reaction. Among the newly
synthesized organocatalysts 12b gave better yields and ee’s than
12a. This may be due to the electron rich nitrogen present in the
central core moiety of the chiral organocatalyst 12b. This is in very
good agreement with the observed results. Therefore, this
metal‐free organocatalytic synthetic procedure can be successfully
extended to a variety of styrene‐ and aldehyde‐based substrates.
The plausible mechanism of domino reaction followed by a radical
mechanism (Scheme 3).11 The butoxide radical (VI) abstract the
proton from the aldehyde to form the acyl radical (I), then it is
coupled with alkene (II) to form the intermediate (III) and (V)
respectively. In this stage our chiral organocatalyst play a crucial
role (acting as a base as well as catalyst), that is amine part of the
proline moiety abstract the proton from the intermediate (V) to
form the desired α,-epoxy ketone and eliminate the butoxide
radical (VI) which is used for another cycle.
synthesis of α,‐epoxy ketones and further investigation of this
reaction is underway in our laboratory.
4. Experimental section
Materials and methods
All the chemicals and reagents used in this work were of
analytical grade. 4-Methylacetophenone, 4-Methylbenzonitrile,
trifluoroacetic acid, n-Bromosuccinamide, benzoyl peroxide,
1,4-Benzoquinone, Ammonium peroxysulphate, Potassium peroxy
monosulphate were purchased from Alfe Aesar. L-Proline, tert-butyl
hydroperoxide, 4-Fluorostyrene, 4-Chlorostyrene, 4-Bromostyrene,
3-Bromostyrene, 2-Bromostyrene, 4-Nitrostyrene, 4-Methylstyrene,
Benzaldehyde, 4-Chlorobenzaldehyde, 4-bromobenzaldehyde,
2-Chlorobenzaldehyde,
4-Methoxybenzaldehyde,
Styrene,
3-Methoxybenzaldehyde,
4-Methylbenzaldehyde,
2-Methoxybenzaldehyde,
4-Ethylbenzaldehyde,
4-(trifluoromethyl)benzaldehyde
and
Caproaldehyde
were
purchased from Sigma Aldrich. Potassium carbonate was purchased
from Merck and all the solvents were obtained from laboratory
grade. The 1H and 13C NMR spectra were recorded on a Bruker
(Avance) 300 MHz and 400 MHz NMR instrument using TMS as an
internal standard and CDCl3 as a solvent. Standard Bruker software
was used throughout. Chemical shifts were given in parts per
million (δ-scale) and the coupling constants are given in Hertz. Silica
gel-G plates (Merck) were used for TLC analysis with a mixture of n-
hexane and ethyl acetate as an eluent. Column chromatography
was carried out in silica gel (60-120 mesh) using n-hexane and ethyl
acetate as an eluent. The HPLC was recorded in SHIMADZU LC-6AD
with Chiral column (Chiralcell OD-H), using HPLC grade n-hexane
and isopropanol as mobile phase solvents. High Resolutin mass
spectroscopic (HRMS) data were obtained using Bruker Apex IV
RTMS. Optical rotations were measured on Rudolph Research
Analytical AUTOPOL-II (readability
(readability ± 0.001°) automatic polarimeters.
± 0.01°) and AUTOPOL-IV
Scheme 3 Probable catalytic cycle for domino reaction (oxidative
coupling) of aldehydes with alkenes (styrenes)
Preparation of 1,3,5-tris(methylphenyl)benzene (6).
4-methylacetophenone 5 (2 g, 14.90 mmol) was added to
trifluoromethane sulfonic acid (6 mL) in small portions at 0 C. After
3. Conclusions
°
In conclusion, first time we designed and synthesized a novel
proline based organocatalysts, the catalytic efficiencies were
successfully applied to one‐pot synthetic procedure for the domino
reaction (oxidative coupling) of alkenes with aldehydes, thus
leading to a synthesis of the α, -epoxy ketones in moderate to
good yields with excellent ee’s. The salient features of the
the addition, the mixture was warmed to room temperature and
stirred for about 24 h. After completion of reaction, the reaction
mixture was quenched with a saturated NH4OH aqueous solution,
extracted with EtOAc, and dried with anhydrous Na2SO4. The crude
product was purified by silica gel column chromatography
(hexane/EtOAc) to get pure orange colour solid product 6 (4.25 g,
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yield 83 %). 1H NMR (300 MHz, CDCl3) δ 7.74 (s, 3H), 7.61 (d, J = 7.9 Synthesis of proline based triazine containing C3-symmetric
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DOI: 10.1039/C7OB00031F
Hz, 6H), 7.30 (d, J = 8.0 Hz, 6H), 2.43 (s, 9H); 13C NMR (75 MHz, organocatalysts (12b).
CDCl3) δC 142.10, 138.34, 137.19, 129.48, 127.13, 124.51, 21.09.
Preparation of 1,3,5-tris(p-bromomethylphenyl)benzene (7).
A mixture of 2,4,6-tris-(4-bromomethyl-phenyl)-[1,3,5]triazine
10 (0.5 g, 10 mmol), L-proline 11 (0.29 g, 30 mmol) was dissolved in
A mixture of 1,3,5-tris(methylphenyl)benzene 6 (3 g, 8.60 1: 1 ratio of DMF: ACN solvent mixture and heated to reflux for
mmol), NBS (4.6 g, 25.84 mmol) and benzoyl peroxide (50 mg) was overnight. The reaction mass was poured into cold water the white
refluxed in chloroform (70 mL) for about 24 h. After completion of solid was filtered, washed with diethylether and dried it, to get pure
the reaction, the solvent was evaporated under reduced pressure chiral C3-symmetric organocatalyst 12b (1.02 g, yield 87 %). IR (KBr)
1
and then ethyl acetate and H2O was added. The organic layer was cm-1: 3396, 3320, 3012, 2140, 1725, 1695, 1585, 1340, 1150; H
extracted and washed with brine solution (3 x 75 mL), dried over NMR (400 MHz, CDCl3) δH12.38 (br, 3H), 8.06 (d, J = 11.3 Hz, 6H),
sodium sulphate, and concentrated in vacuum, compound 7 was 7.46 (d, J = 9.4 Hz, 6H), 3.57 (s, 6H), 3.21 (t, J = 8.0 Hz, 3H), 2.41-2.30
obtained as a yellow solid (4.10 g, yield 81 %).1H NMR (300 MHz, (m, 6H), 1.96-1.71 (m, 6H), 1.64-1.54 (m, 6H); 13C NMR (100 MHz,
CDCl3) δH 7.70 (s, 3H), 7.55 (d, J = 7.9 Hz, 6H), 7.25 (d, J = 8.0 Hz, CDCl3) δC 174.61, 171.58, 138.65, 133.43, 129.34, 125.51, 73.64,
6H), 4.56 (s, 6H); 13C NMR (75 MHz, CDCl3) δC 142.29, 138.52, 62.08, 57.68, 29.70, 22.03; HRMS calculated for C39H42N6O6:
137.38, 129.67, 127.31, 124.69, 33.37.
690.3166, found: 687.3167.
Preparation of p-cyanobenzylbromide (9).
Synthesis of proline based triazine containing C2-symmetric
A mixture of p-toluonitrile 8 (5 g, 42.68 mmol), NBS (7.6 g, 42.70 organocatalysts (12c).
mmol) and benzoyl peroxide (50 mg) was refluxed in chloroform
A mixture of 2,4,6-tris-(4-bromomethyl-phenyl)-[1,3,5]triazine
(100 mL) for about 24 h. After completion of the reaction, the 10 (0.5 g, 10 mmol), L-proline 11 (0.19 g, 20 mmol) was dissolved in
solvent was evaporated under reduced pressure and then ethyl 1: 1 ratio of DMF: ACN solvent mixture and heated to reflux for
acetate and H2O was added. The organic layer was extracted and overnight. The reaction mass was poured into cold water the white
washed with brine solution (3 x 75 ml), dried over sodium sulphate, solid was filtered, washed with diethylether and dried it, to get pure
1
and concentrated in vacuum, compound 9 was obtained as a white chiral C2-symmetric organocatalyst 12c with 84 %. Yield. H NMR
solid (7.7 g, yield 92 %). This product was used for the next step (300 MHz, CDCl3) δH12.32 (br, 2H), 8.58 (d, J = 7.8 Hz, 6H), 7.43 (d, J
1
without any further purification. H NMR (300 MHz, CDCl3) δH 7.64 = 8.01 Hz, 6H), 4.56 (s, 2H), 3.62 (s, 4H), 3.21 (t, J = 6.3 Hz, 2H), 2.40-
(d, J = 8.2 Hz, 2H), 7.50 (d, J = 8.2 Hz, 2H), 4.47 (s, 2H); 13C NMR (75 2.30 (m, 4H), 1.95-1.70 (m, 4H), 1.64-1.56 (m, 4H); 13C NMR (100
MHz, CDCl3) δC 142.86, 132.61, 129.74, 118.38, 112.21, 31.49.
Preparation of 2, 4, 6-Tris-(4-bromomethyl-phenyl)-[1, 3, 5]triazine 132.13, 129.54, 129.33, 126.14, 125.44, 73.74, 62.17, 57.27, 33.32,
(10). 29.22, 22.01.
MHz, CDCl3) δC 174.22, 172.16, 171.04, 138.66, 138.11, 134.01,
p-Cyanobenzylbromide 9 (2.50 g, 12.8 mmol) was added to Synthesis of proline based triazine containing C1-symmetric
°
trifluoromethane sulfonic acid (3 mL) in small portions at 0 C. After organocatalysts (12d).
the addition, the mixture was warmed to room temperature and
A mixture of 2,4,6-tris-(4-bromomethyl-phenyl)-[1,3,5]triazine
stirred for about 24 h, and then the reaction mixture was poured 10 (0.5 g, 10 mmol), L-proline 11 (0.09 g, 10 mmol) was dissolved in
into ice, neutralized by ammonium hydroxide. The solid phase was 1: 1 ratio of DMF: ACN solvent mixture and heated to reflux for
collected by filtration. The white powder product was used for the overnight. The reaction mass was poured into cold water the white
next step without any further purification. (1.80 g, yield 72 %). 1H solid was filtered, washed with diethylether and dried it, to get pure
1
NMR (300 MHz, CDCl3) δH 8.72 (d, J = 8.3 Hz, 6H), 7.60 (d, J = 8.2 Hz, chiral C1-symmetric organocatalyst 12d with 85 %. Yield. H NMR
6H), 4.59 (s, 6H); 13C NMR (100 MHz, CDCl3) δC 142.86, 132.61, (300 MHz, CDCl3) δH12.30 (br, 1H), 8.59 (d, J = 7.4 Hz, 6H), 7.46 (d, J
129.74, 118.38, 112.21, 31.49.
Synthesis of proline based C3-symmetric organocatalysts (12a).
= 6.4 Hz, 6H), 4.56 (s, 4H), 3.61 (s, 2H), 3.21 (t, J = 4.4 Hz, 1H), 2.40-
2.31 (m, 2H), 1.96-1.71 (m, 2H), 1.64-1.57 (m, 2H); 13C NMR (100
A mixture of 1,3,5-tris(p-bromomethylphenyl)benzene 7 (0.5 g, MHz, CDCl3) δC 173.24, 172.19, 171.06, 138.71, 138.20, 134.18,
10 mmol), L-proline 11 (0.29 g, 30 mmol) was dissolved in 1: 1 ratio 132.13, 129.54, 129.38, 126.16, 125.53, 74.64, 62.40, 57.34, 33.48,
of DMF: ACN solvent mixture and heated to reflux for overnight. 29.45, 22.14.
The reaction mass was poured into cold water the white solid was General procedure for domino reaction (oxidative coupling
filtered, washed with diethylether and dried it, to get pure chiral reaction).
multifunctional organocatalyst 12a (1.0 g, yield 85 %). IR (KBr) cm-1:
The proline based organocatalyst 12a or 12b (0.1 mmol),
3415, 3340, 3020, 2604, 1705, 1585, 1356, 1210, 1162; 1H NMR acetonitrile (2 mL), TBHP (70 % in water, 2 equiv.), benzaldehyde
(400 MHz, CDCl3) δH 12.36 (br, 3H), 8.05 (s, 3H), 7.46 (d, J = 8.1 Hz, (1 mmol) were taken into the round bottom flask. Further, a slow
6H), 7.41 (d, J = 7.5 Hz, 6H), 3.69 (s, 6H), 3.21 (t, J = 6.9 Hz, 3H), addition of styrene (1 mmol) is added to the reaction mixture. The
2.40-2.30 (m, 6H), 1.91-1.77 (m, 6H), 1.64-1.54 (m, 6H); 13C NMR mixture was stirred at room temperature for about 10 h. After that
(100 MHz, CDCl3) δC 174.60, 139.50, 137.48, 129.50, 127.22, 126.11, H2O (5 mL) and CH2Cl2 (5 mL) were added, the phases were
73.29, 62.18, 57.61, 29.11, 21.99; HRMS calculated for C42H45N3O6: separated and the organic layer was washed with water (2 x 5 mL).
687.3308, found: 687.3309.
The organic phase was subsequently evaporated under reduced
pressure to give the crude product. The product was purified by
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column chromatography on silica gel using petroleum ether/ethyl 130.32, 129.61, 128.57, 124.57,123.03, 60.77, 58.3V2ie,w2A1rt.i7cl9e.OnTlhinee
DOI: 10.1039/C7OB00031F
acetate as an eluent.
Characterization of ɑ,β-epoxy ketones.
enantiomeric excess was determined by HPLC, Chiralcel (OD-H), 254
nm, hexane: IPA 95: 5, flow rate: 1 mL min−1, retention time: 17.90
(3-(4-Fluorophenyl)oxiran-2-yl)(p-tolyl)methanone (3a). Yield 90 % min (major) and 40.93 min (minor). The absolute stereochemistry of
; ee 94 % ; [α] 25D = +17.4 (c= 0.19, CHCl3); 1H NMR (300 MHz, CDCl3) the ɑ,β-epoxy ketone was assigned as (2R, 3S) by comparison of the
δH 7.91 (d, J = 5.0 Hz, 2H), 7.38 – 7.32 (m, 2H), 7.29 (d, J = 5.0 Hz, optical data with a known literature reported value. 4-10
2H), 7.10 (t, J = 8.1 Hz, 2H), 4.24 (d, J = 1.1 Hz, 1H), 4.06 (d, J = 1.2 (3-(2-Bromophenyl)oxiran-2-yl)(p-tolyl)methanone (3f). Yield 89 %
Hz, 1H), 2.43 (s, 3H); 13C NMR (75 MHz, CDCl3) δC 192.58, 164.26, ; ee 92 % ; [α] 25D = +29.4 (c= 0.20, CHCl3); 1H NMR (300 MHz, CDCl3)
145.23, 133.84, 131.23, 129.42, 128.55, 127.41, 115.70, 115.42, δH 7.97 (d, J = 7.0 Hz, 2H), 7.56 (dd, J = 9.3, 1.0 Hz, 1H), 7.36 (dd, J =
60.77, 58.69, 21.58. The enantiomeric excess was determined by 9.4, 2.0 Hz, 2H), 7.28 (d, J = 8.7 Hz, 2H), 7.26 (s, 1H), 4.34 (d, J = 1.4
HPLC, Chiralcel (OD-H), 254 nm, hexane: IPA 95: 5, flow rate: 1 mL Hz, 1H), 4.15 (d, J = 1.4 Hz, 1H), 2.45 (s, 3H); 13C NMR (75 MHz,
min−1, retention time: 20.16 min (major) and 46.15 min (minor). The CDCl3) δC 192.15, 145.17, 135.57, 132.71, 130.00, 129.57, 128.58,
absolute stereochemistry of the ɑ,β-epoxy ketone was assigned as 128.03, 127.84, 126.52, 122.54, 60.05, 59.35, 21.85. The
(2R, 3S) by comparison of the optical data with a known literatures enantiomeric excess was determined by HPLC, Chiralcel (OD-H), 254
reported value.4-10
nm, hexane: IPA 95: 5, flow rate: 1 mL min−1, retention time: 14.97
(3-(4-Chlorophenyl)oxiran-2-yl)(p-tolyl)methanone (3b). Yield 92 % min (major) and 37.86 min (minor). The absolute stereochemistry of
; ee 95 % ; [α] 25D = +19.2 (c= 0.21, CHCl3); 1H NMR (300 MHz, CDCl3) the α,β-epoxy ketone was assigned as (2R, 3S) by comparison of the
δH 7.82 (d, J = 6.8 Hz, 2H), 7.30 (d, J = 6.5 Hz, 2H), 7.23 (dd, J = 7.0, optical data with a known literature reported value. 4-10
3.1 Hz, 4H), 4.16 (d, J = 1.3 Hz, 1H), 3.98 (d, J = 1.2 Hz, 1H), 2.37 (s, (3-(4-Nitrophenyl)oxiran-2-yl)(p-tolyl)methanone (3g). Yield 93 % ;
3H); 13C NMR (75 MHz, CDCl3) δC 192.13, 145.32, 134.92, 134.34, ee 98 % ; [α] 25D = +34.1 (c= 0.15, CHCl3); 1H NMR (300 MHz, CDCl3)
132.92, 129.57, 129.25, 128.73, 127.14, 60.80, 58.54, 21.84. The δH 8.17 (d, J = 5.4 Hz, 2H), 7.59-7.45 (m, 4H), 6.75 (d, J = 6.6 Hz, 2H),
enantiomeric excess was determined by HPLC, Chiralcel (OD-H), 254 4.42 (d, J = 1.2 Hz, 1H), 4.35 (d, J = 1.3 Hz, 1H), 2.39 (s, 3H); 13C NMR
nm, hexane: IPA 95: 5, flow rate: 1 mL min−1, retention time: 16.89 (75 MHz, CDCl3) δC 192.59, 147.43, 142.66, 137.61, 129.30, 128.95,
min (major) and 44.97 min (minor). The absolute stereochemistry of 128.73, 126.13, 123.83, 60.96, 59.42, 21.32. The enantiomeric
the ɑ,β-epoxy ketone was assigned as (2R, 3S) by comparison of the excess was determined by HPLC, Chiralcel (OD-H), 254 nm, hexane:
optical data with a known literature reported value. 4-10
IPA 95: 5, flow rate: 1 mL min−1, retention time: 26.71 min (major)
(3-(2-Chlorophenyl)oxiran-2-yl)(p-tolyl)methanone (3c). Yield 86 % and 34.93 min (minor). The absolute stereochemistry of the ɑ,β-
; ee 90 % ; [α] 25D = +24.1 (c= 0.12, CHCl3); 1H NMR (300 MHz, CDCl3) epoxy ketone was assigned as (2R, 3S) by comparison of the optical
δH 7.96 (d, J = 6.2 Hz, 2H), 7.41 – 7.37 (m, 2H), 7.35 – 7.27 (m, 4H), data with a known literature reported value. 4-10
4.40 (d, J = 1.2 Hz, 1H), 4.15 (d, J = 1.3 Hz, 1H), 2.44 (s, 3H); 13C NMR (3-Phenyloxiran-2-yl)(p-tolyl)methanone (3h). Yield 95 % ; ee 95 %
25
1
(75 MHz, CDCl3)
δC 192.27, 145.34, 133.96, 133.39, 132.97, ; [α] D = +23.2 (c= 0.17, CHCl3); H NMR (300 MHz, CDCl3) δH 7.84
129.61, 129.37, 128.51, 127.28, 126.19, 60.01, 57.05, 21.78. The (d, J = 6.4 Hz, 2H), 7.36 – 7.27 (m, 5H), 7.20 (d, J = 6.2 Hz, 2H), 4.21
enantiomeric excess was determined by HPLC, Chiralcel (OD-H), 254 (d, J = 1.7 Hz, 1H), 3.99 (d, J = 1.9 Hz, 1H), 2.34 (s, 3H); 13C NMR (75
nm, hexane: IPA 95: 5, flow rate: 1 mL min−1, retention time: 15.98 MHz, CDCl3) δC 192.59, 147.43, 142.66, 137.61, 129.29, 128.95,
min (major) and 34.27 min (minor). The absolute stereochemistry of 128.73, 126.13, 123.83, 60.96, 59.42, 21.32. The enantiomeric
the ɑ,β-epoxy ketone was assigned as (2R, 3S) by comparison of the excess was determined by HPLC, Chiralcel (OD-H), 254 nm, hexane:
optical data with a known literature reported value. 4-10
IPA 95: 5, flow rate: 1 mL min−1, retention time: 10.69 min (major)
(3-(4-Bromophenyl)oxiran-2-yl)(p-tolyl)methanone (3d). Yield 94 % and 31.72 min (minor). The stereochemistry of the ɑ,β-epoxy
; ee 97 % ; [α] 25D = +19.4 (c= 0.17, CHCl3); 1H NMR (300 MHz, CDCl3) ketone was assigned as (2R, 3S) by comparison of the optical data
δH 7.91 (d, J = 6.9 Hz, 2H), 7.54 (d, J = 6.0 Hz, 2H), 7.30 (d, J = 5.4 Hz, with a known literature reported value. 4-10
2H), 7.23 (d, J = 5.4 Hz, 2H), 4.22 (d, J = 1.3 Hz, 1H), 4.04 (d, J = 1.2 (3-(4-Methoxyphenyl)oxiran-2-yl)(p-tolyl)methanone (3i). Yield 73
25
D
1
Hz, 1H), 2.43 (s, 3H); 13C NMR (75 MHz, CDCl3) δC 192.34, 145.35, % ; ee 91 % ; [α]
= +21.4 (c= 0.12, CHCl3); H NMR (300 MHz,
134.53, 133.03, 131.96, 129.63, 128.49, 127.42, 123.10, 60.84, CDCl3) δH 7.41 (d, J = 6.0 Hz, 2H), 7.28 (d, J = 6.7 Hz, 2H), 6.89 (d, J =
58.66, 21.76. The enantiomeric excess was determined by HPLC, 6.9 Hz, 2H), 6.75 (d, J = 6.6 Hz, 2H), 4.42 (d, J = 1.8 Hz, 1H), 4.35 (d, J
Chiralcel (OD-H), 254 nm, hexane: IPA 95: 5, flow rate: 1 mL min−1, = 1.6 Hz, 1H), 3.82 (s, 3H), 2.42 (s, 3H); 13C NMR (75 MHz, CDCl3) δC
retention time: 11.98 min (major) and 20.20 min (minor). The 192.19, 160.14, 142.84, 129.23, 128.91, 128.73, 127.85, 125.15,
absolute stereochemistry of the ɑ,β-epoxy ketone was assigned as 114.18, 61.71, 59.43, 55.81, 21.30. The enantiomeric excess was
(2R, 3S) by comparison of the optical data with a known literature determined by HPLC, Chiralcel (OD-H), 254 nm, hexane: IPA 95: 5,
reported value. 4-10
flow rate: 1 mL min−1, retention time: 15.13 min (major) and 48.04
(3-(3-Bromophenyl)oxiran-2-yl)(p-tolyl)methanone (3e). Yield 84 % min (minor). The absolute stereochemistry of the ɑ,β-epoxy ketone
; ee 93 % ; [α] 25D = +27.1 (c= 0.24, CHCl3); 1H NMR (300 MHz, CDCl3) was assigned as (2R, 3S) by comparison of the optical data with a
δH 7.91 (d, J = 5.0 Hz, 2H), 7.49 (dd, J = 6.9, 2.6 Hz, 2H), 7.34 – 7.27 known literature reported value. 4-10
(m, 4H), 4.24 (d, J = 1.6 Hz, 1H), 4.04 (d, J = 1.4 Hz, 1H), 2.43 (s, 3H); p-Tolyl(3-p-tolyloxiran-2-yl)methanone (3j). Yield 72 % ; ee 91 % ;
13C NMR (75 MHz, CDCl3) δC 192.12, 145.40, 138.09, 132.96, 132.07, [α] 25D = +20.3 (c= 0.16, CHCl3); 1H NMR (300 MHz, CDCl3) δH 7.91 (d,
8 | J. Name., 2012, 00, 1-3
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J = 7.8 Hz, 2H), 7.30 – 7.27 (m, 4H), 7.22 (d, J = 7.0 Hz, 2H), 4.28 (d, J (3-Methoxyphenyl)(3-phenyloxiran-2-yl)methanone (4e). Yield 64
View Article Online
DOI: 10.1039/C7OB00031F
= +41.4 (c= 0.20, CHCl3); H NMR (300 MHz,
25
D
1
= 1.4 Hz, 1H), 4.04 (d, J = 1.3 Hz, 1H), 2.42 (s, 3H), 2.39 (s, 3H); 13
C
% ; ee 75 % ; [α]
NMR (75 MHz, CDCl3) δC 192.65, 151.13, 135.67, 133.28, 128.92, CDCl3) δH 7.58 (d, J = 6.1 Hz, 1H), 7.53 (t, J = 4.8 Hz, 1H), 7.43 – 7.35
128.75, 128.63, 128.40, 125.80, 61.05, 59.27, 21.78, 21.27. The (m, 6H), 7.15 (dd, J = 5.4, 2.4 Hz, 1H), 4.28 (d, J = 1.4 Hz, 1H), 4.07
enantiomeric excess was determined by HPLC, Chiralcel (OD-H), 254 (d, J = 1.1 Hz, 1H), 3.84 (s, 3H); 13C NMR (75 MHz, CDCl3) δC 192.93,
nm, hexane: IPA 95: 5, flow rate: 1 mL min−1, retention time: 25.21 160.04, 136.83, 135.55, 129.85, 129.03, 128.76, 125.81, 121.00,
min (major) and 42.85 min (minor). The stereochemistry of the ɑ,β- 120.57, 61.05, 59.42, 55.46. The enantiomeric excess was
epoxy ketone was assigned as (2R, 3S) by comparison of the optical determined by HPLC, Chiralcel (OD-H), 254 nm, hexane: IPA 95: 5,
data with a known literature reported value. 4-10
flow rate: 1 mL min−1, retention time: 16.06 min (major) and 34.89
Phenyl(3-phenyloxiran-2-yl)methanone (4a). Yield 95 % ; ee 99 % ; min (minor). The absolute stereochemistry of the ɑ,β-epoxy ketone
[α] 25D = +31.4 (c= 0.17, CHCl3); 1H NMR (300 MHz, CDCl3) δH 8.01 (d, was assigned as (2R, 3S) by comparison of the optical data with a
J = 4.0 Hz, 2H), 7.62 (t, J = 6.5 Hz, 1H), 7.49 (t, J = 8.5 Hz, 2H), 7.42 – known literature reported value. 4-10
7.36 (m, 5H), 4.30 (d, J = 1.8 Hz, 1H), 4.08 (d, J = 1.6 Hz, 1H); 13C (2-Methoxyphenyl)(3-phenyloxiran-2-yl)methanone (4f). Yield 52
25
D
1
NMR (75 MHz, CDCl3) δC 193.11, 135.56, 133.96, 129.05, 128.89, % ; ee 73 % ; [α]
= +47.2 (c= 0.23, CHCl3); H NMR (300 MHz,
128.78, 128.39, 125.81, 61.01, 59.36. The enantiomeric excess was CDCl3) δH 7.85 (dd, J = 5.4, 1.4 Hz, 1H), 7.57 – 7.49 (m, 1H), 7.44 –
determined by HPLC, Chiralcel (OD-H), 254 nm, hexane: IPA 95: 5, 7.33 (m, 5H), 7.05 (t, J = 4.0 Hz, 1H), 6.93 (d, J = 6.1 Hz, 1H), 4.31 (d,
flow rate: 1 mL min−1, retention time: 20.45 min (major) and 40.33 J = 1.0 Hz, 1H), 4.00 (d,
J = 1.0 Hz, 1H), 3.57 (s, 3H); 13C NMR (75
min (minor). The stereochemistry of the ɑ,β-epoxy ketone was MHz, CDCl3) δC 194.88, 159.54, 136.55, 134.86, 130.76, 128.61,
assigned as (2R, 3S) by comparison of the optical data with a known 128.52, 126.08, 125.83, 121.08, 111.56, 64.46, 59.76, 55.59. The
literature reported value. 4-10
enantiomeric excess was determined by HPLC, Chiralcel (OD-H), 254
(4-Chlorophenyl)(3-phenyloxiran-2-yl)methanone (4b). Yield 94 % ; nm, hexane: IPA 95: 5, flow rate: 1 mL min−1, retention time: 22.86
25
1
ee 98 % ; [α] D = +34.2 (c= 0.19, CHCl3); H NMR (300 MHz, CDCl3) min (major) and 42.40 min (minor). The absolute stereochemistry of
δH 7.97 (d, J = 7.0 Hz, 2H), 7.47 (d, J = 7.5 Hz, 2H), 7.40 – 7.33 (m, the ɑ,β-epoxy ketone was assigned as (2R, 3S) by comparison of the
5H), 4.23 (d, J = 1.1 Hz, 1H), 4.08 (d, J = 1.3 Hz, 1H); 13C NMR (75 optical data with a known literature reported value. 4-10
MHz, CDCl3) δC 192.06, 104.65, 135.26, 133.70, 129.83, 129.27, (3-Phenyloxiran-2-yl)(p-tolyl)methanone (4g). Yield 95 % ; ee 95 % ;
25
1
129.16, 128.80, 125.74, 61.06, 59.39. The enantiomeric excess was [α] D = +23.2 (c= 0.17, CHCl3); H NMR (300 MHz, CDCl3) δH 7.84
determined by HPLC, Chiralcel (OD-H), 254 nm, hexane: IPA 95: 5, (d, J = 6.4 Hz, 2H), 7.36 – 7.27 (m, 5H), 7.20 (d, J = 6.2 Hz, 2H), 4.21
flow rate: 1 mL min−1, retention time: 12.10 min (major) and 32.64 (d, J = 1.7 Hz, 1H), 3.99 (d, J = 1.9 Hz, 1H), 2.34 (s, 3H); 13C NMR (75
min (minor). The absolute stereochemistry of the ɑ,β-epoxy ketone MHz, CDCl3) δC 192.59, 147.43, 142.66, 137.61, 129.29, 128.95,
was assigned as (2R, 3S) by comparison of the optical data with a 128.73, 126.13, 123.83, 60.96, 59.42, 21.32. The enantiomeric
known literature reported value. 4-10
(4-Bromophenyl)(3-phenyloxiran-2-yl)methanone (4c). Yield 93 % ; IPA 95: 5, flow rate: 1 mL min−1, retention time: 10.69 min (major)
excess was determined by HPLC, Chiralcel (OD-H), 254 nm, hexane:
25
1
ee 97 % ; [α] D = +39.1 (c= 0.21, CHCl3); H NMR (300 MHz, CDCl3) and 31.72 min (minor). The stereochemistry of the ɑ,β-epoxy
δH 7.90 (d, J = 6.7 Hz, 2H), 7.65 (d, J = 6.4 Hz, 2H), 7.44 – 7.38 (m, ketone was assigned as (2R, 3S) by comparison of the optical data
3H), 7.34 (dt, J = 4.6, 2.1 Hz, 2H), 4.23 (d, J = 1.4 Hz, 1H), 4.07 (d, J = with a known literature reported value. 4-10
1.1 Hz, 1H);
13C NMR (75 MHz, CDCl3) δC 192.42, 135.23, 134.13, (3-Phenyloxiran-2-yl)(4-(trifluoromethyl)phenyl)methanone (4h).
25
1
132.28, 129.86, 129.46, 129.21, 128.86, 125.79, 61.07, 59.42. The Yield 91 % ; ee 93 % ; [α] D = +47.2 (c= 0.19, CHCl3); H NMR (300
enantiomeric excess was determined by HPLC, Chiralcel (OD-H), 254 MHz, CDCl3) δH 8.12 (d, J = 7.2 Hz, 2H), 7.76 (d, J = 7.2 Hz, 2H), 7.41
nm, hexane: IPA 95: 5, flow rate: 1 mL min−1, retention time: 25.13 (d, J = 6.9 Hz, 3H), 7.39 – 7.34 (m, 2H), 4.26 (d, J = 1.3 Hz, 1H), 4.09
min (major) and 49.28 min (minor). The absolute stereochemistry of (d, J = 1.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) δC 192.59, 137.93,
the ɑ,β-epoxy ketone was assigned as (2R, 3S) by comparison of the 135.07, 129.32, 129.26, 128.91, 128.83, 125.80, 61.46, 59.65. The
optical data with a known literature reported value. 4-10
enantiomeric excess was determined by HPLC, Chiralcel (OD-H), 254
(4-Methoxyphenyl)(3-phenyloxiran-2-yl)methanone (4d). Yield 90 nm, hexane: IPA 95: 5, flow rate: 1 mL min−1, retention time: 13.93
25
D
1
% ; ee 92 % ; [α]
= +33.2 (c= 0.15, CHCl3); H NMR (300 MHz, min (major) and 44.10 min (minor). The absolute stereochemistry of
CDCl3) δH 8.02 (d, J = 4.3 Hz, 2H), 7.44 – 7.33 (m, 5H), 6.95 (d, J = 6.3 the ɑ,β-epoxy ketone was assigned as (2R, 3S) by comparison of the
Hz, 2H), 4.25 (d, J = 1.8 Hz, 1H), 4.07 (d, J = 1.9 Hz, 1H), 3.88 (s, 3H); optical data with a known literature reported value. 4-10
13C NMR (75 MHz, CDCl3) δC 191.36, 164.34, 135.79, 130.76, 128.93, (4-Ethylphenyl)(3-phenyloxiran-2-yl)methanone (4i). Yield 90 % ;
25
1
128.73, 128.65, 125.80, 114.24, 60.88, 59.11, 55.54. The ee 97 % ; [α] D = +44.3 (c= 0.21, CHCl3); H NMR (300 MHz, CDCl3)
enantiomeric excess was determined by HPLC, Chiralcel (OD-H), 254 δH 7.94 (d, J = 6.0 Hz, 2H), 7.45 – 7.34 (m, 5H), 7.31 (d, J = 6.1 Hz,
nm, hexane: IPA 95: 5, flow rate: 1 mL min−1, retention time: 15.11 2H), 4.28 (d, J = 1.4 Hz, 1H), 4.07 (d, J = 1.2 Hz, 1H), 2.72 (q, J = 8.6
min (major) and 36.83 min (minor). The absolute stereochemistry of Hz, 2H), 1.26 (t, J = 8.1 Hz, 3H); 13C NMR (75 MHz, CDCl3) δC 192.55,
the ɑ,β-epoxy ketone was assigned as (2R, 3S) by comparison of the 151.42, 135.65, 133.26, 128.99, 128.72, 128.61, 128.41, 125.84,
optical data with a known literature reported value. 4-10
61.05, 59.24, 29.07, 15.06. The enantiomeric excess was
determined by HPLC, Chiralcel (OD-H), 254 nm, hexane: IPA 95: 5,
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flow rate: 1 mL min−1, retention time: 21.98 min (major) and 33.29
Rev., 2007, 107, 5656. (f) G. D. Faveri, G. IlVyiaewshAertnickleoO,nlMine.
DOI: 10.1039/C7OB00031F
Watkinson, Chem. Soc. Rev., 2011, 40, 1722.
min (minor). The absolute stereochemistry of the ɑ,β-epoxy ketone
was assigned as (2R, 3S) by comparison of the optical data with a 6 (a) X. Wang, L. Yin, T. Yang, Y. Wang, Tetrahedron Asymmetry,
known literature reported value. 4-10
2007, 18, 108; (b) K. Hori, M. Tamura, K. Tani, N. Nishiwaki, M.
Ariga, Y. Tohda, Tetrahedron Lett., 2006, 47, 3115; (c) M. J.
Portera, J. Skidmore, J. Chem. Commun., 2000, 1215; (d) J. Ye,
Y. Wang, R. Liu, G. Zhang, Q. Zhang, J. Chen, X. Liang, Chem.
Commun., 2003, 2714.
1-(3-Phenyloxiran-2-yl)hexan-1-one (4j). Yield 44 % ; ee 71 % ; [α]
25
D
1
= +61.4 (c= 0.24, CHCl3); H NMR (300 MHz, CDCl3) δH 7.36 (s,
3H), 7.28 (d, J = 7.0 Hz, 2H), 3.97 (d, J = 1.0 Hz, 1H), 3.51 (d, J = 1.0
Hz, 1H), 2.61 – 2.39 (m, 2H), 1.69 – 1.60 (m, 2H), 1.31 (d, J = 2.7 Hz,
4H), 0.91 (t, J = 7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) δC 206.15, 7 (a) Y. Liu, B. A. Provencher, B. J. Bartelson, L. Deng, Chem.
136.26, 128.88, 128.68, 128.62, 125.75, 63.14, 58.07, 37.79, 31.33,
22.84, 22.45, 13.95. The enantiomeric excess was determined by
HPLC, Chiralcel (OD-H), 254 nm, hexane: IPA 95: 5, flow rate: 1 mL
min−1, retention time: 20.63 min (major) and 40.76 min (minor). The
absolute stereochemistry of the ɑ,β-epoxy ketone was assigned as
(2R, 3S) by comparison of the optical data with a known literature
reported value. 4-10
Sci.,2011, 2, 1301; (b) O. Cusso, I. G. Bosch, X. Ribas, J. L. Fillol,
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VA acknowledges the financial support of CSIR-HRDG, New Delhi,
India (122279/2K15/1) for providing SRF and also Department of
Science and Technology, Extramural Research Project
EMR/2015/000969, Department of Science and Technology. New
Delhi, India (Grant No. SR/F/1584/2012-13).
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