Unmodified Primary Amine Organocatalysts for Asymmetric Michael Reactions in Aqueous Media

Article abstract of DOI:10.1002/ejoc.201500913

The organocatalytic asymmetric Michael addition of aldehydes to a nitro olefin in aqueous organic solvents catalysed by a broad range of simple primary amines and amino alcohols is reported. In particular, the use of (S,S)-diphenylethylenediamine, which is the chiral backbone of various organocatalysts, gave addition products in good yields and with good to high enantioselectivities (45-96% ee). Remarkably high enantioselectivities were observed for the demanding conjugate addition of α,α-disubstituted aldehydes to nitrostyrene (96-98% ee) in aqueous organic solvent mixtures.

Full text of DOI:10.1002/ejoc.201500913

FULL PAPER
DOI: 10.1002/ejoc.201500913
Unmodified Primary Amine Organocatalysts for Asymmetric Michael
Reactions in Aqueous Media
[a]
[a,b]
´
Maria Rogozinska-Szymczak and Jacek Mlynarski*
Keywords: Organocatalysis / Asymmetric synthesis / Green chemistry / Michael addition / Amines
The organocatalytic asymmetric Michael addition of alde-
hydes to a nitro olefin in aqueous organic solvents catalysed
by a broad range of simple primary amines and amino
alcohols is reported. In particular, the use of (S,S)-diphenyl-
with good to high enantioselectivities (45–96% ee). Remark-
ably high enantioselectivities were observed for the de-
manding conjugate addition of α,α-disubstituted aldehydes
to nitrostyrene (96–98% ee) in aqueous organic solvent mix-
ethylenediamine, which is the chiral backbone of various or- tures.
ganocatalysts, gave addition products in good yields and
attached to the proline core.[8] Later, Headley and Ni devel-
Introduction
oped two examples of water-soluble prolinol silyl ethers,
which could be used to promote highly efficient asymmetric
Michael addition reactions of aldehydes to nitro olefins.[9]
Interesting results were also obtained with primary
amine catalysts, particularly a bifunctional sulfonamide–
primary-amine catalyst developed from diaminocyclohex-
ane,[10] and three different primary-thiourea-based catalysts
based on diphenylethylenediamine.[11,12] In these cases,
however, organic solvents were used; water was used in only
a small amount (15–500 mol-%), although its presence re-
sulted in significant improvements.
Interestingly, most of the previously published reports
have described the use of complex organocatalysts, and the
direct application of the primary amines used as the precur-
sors of these complex organocatalysts was not exhaustively
tested. For this reason, we propose that there is a need to
study water-compatible organocatalysts, in particular read-
ily available simple amines. In 2006, Chin demonstrated that
the use of (R,R)-diphenylethylenediamine (10 mol-%) in
THF resulted in the selective formation of (R)-warfarin
from 4-hydroxycoumarin and trans-4-phenyl-3-buten-2-one
(94% yield, ca. 80% ee).[13] In this case, however, dry or-
ganic solvents were used as the reaction medium. Neverthe-
less, this result encouraged us to undertake broader studies
on the possible application of unmodified low-molecular-
weight diamines as efficient and “greener” organocatalysts
for the asymmetric Michael additions of nitroalkenes to al-
dehydes in aqueous solvents.[14]
Of the various organocatalytic C–C bond-forming reac-
tions,[1] organocatalytic asymmetric Michael additions play
a significant role.[2] In particular, the conjugate addition re-
actions of nitroalkenes to carbonyl compounds result in the
formation of γ-nitro carbonyl compounds, which are valu-
able building blocks in organic synthesis.[3]
Recently, research into the development of efficient or-
ganocatalytic reactions has also focussed on economic and
ecological aspects.[4] Thus, additional efforts have been
made to develop efficient organocatalysts for asymmetric
reactions in water or in aqueous solvent mixtures.[5] The
design of small-molecule organocatalysts with significant
activity and selectivity within the principles of “green chem-
istry” is a crucial scientific challenge. Aqueous reactions
promoted by small, commercially available catalysts are
recognized as “green” processes because they have advan-
tages from the points of view of environmental concerns,
safety, and cost.[6]
A few examples of organocatalytic Michael reactions in
aqueous media have recently been reported in the literature.
In the very first example, Barbas et al. reported a highly
enantioselective (up to 97% ee) direct Michael addition of
aldehydes and ketones to nitro olefins catalysed by a pro-
line-based diamine/TFA (trifluoroacetic acid) organo-
catalyst.[7] For this and most of the other reported cases,
the organocatalysts were designed to be less water soluble,
or even water insoluble, with a large hydrophobic group
[a] Institute of Organic Chemistry, Polish Academy of Sciences,
Kasprzaka 44/52, 01-224 Warsaw, Poland
Results and Discussion
[b] Faculty of Chemistry, Jagiellonian University,
Ingardena 3, 30-060 Krakow, Poland
E-mail: jacek.mlynarski@gmail.com
http://www.jacekmlynarski.pl/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500913.
We first tested a broad range of cheap and readily avail-
able unmodified amines as organocatalysts in the aqueous
Michael reaction between nitrostyrene and 2-propanal
Eur. J. Org. Chem. 2015, 6047–6051
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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M. Rogozin´ska-Szymczak, J. Mlynarski
FULL PAPER
(Scheme 1). We turned our attention to this demanding al- deed, at the initial screening stage, we observed the best
dehyde substrate as only a small number of reports have results when an acid additive was used. To explore this ef-
addressed α,α-disubstituted aldehydes as potential nucleo- fect, diamine 11 was chosen for further evaluation, and was
philic partners in combination with nitroalkenes.[7,12] The tested as a catalyst for the same reaction with and without
model reaction between nitrostyrene (1) and aldehyde 2 was acid additives. The results are summarized in Table 2. When
initially carried out in a homogeneous DMF/water (9:1) benzoic acid was used, the reaction yield and the enantio-
solution in the presence of 20 mol-% of catalysts 4–11. The selectivity both increased significantly (Table 2, entry 1 vs.
screening results are shown in Table 1. The yield of Michael 2). Some of the other Brønsted acids tested (acetic, formic,
adduct 3a was rather disappointing for most of the struc- and salicylic acids) gave worse results. Interestingly, the use
tures tested, reaching 50–60% for only two examples of stronger acids (HCl) resulted in a decrease of the reac-
(Table 1, entries 2 and 3). For these amino alcohols, how- tion yield. The use of trifluoroacetic acid, which is usually
ever, the observed enantioselectivity was poor. Only in the beneficial for organocatalytic Michael addition reactions,[8a]
cases of amino alcohol 10 and diamine 11 did the enantio- resulted in the formation of only a trace of 3a (Table 2,
selectivity meet our expectations. In spite of the lower yields entry 6).
observed for these organocatalysts, we decided to use these
amines for further optimization because of the observed
Table 2. Screening of acid additives.[a]
Entry
Additive
Yield [%][b]
ee [%][c]
higher stereoselectivity compared to the other examples. In
particular, the use of readily available (S,S)-diphenylethyl-
enediamine seemed exciting in terms of yield and enantio-
selectivity (91%). Diaminocyclohexane 9 (Table 1, entry 6)
did not give promising results, unfortunately.
1
2
3
4
5
6
7
8
9
–
14
42
35
21
20
Ͻ5
22
22
16
84
91
90
92
93
n.d.
98
76
PhCO2H
AcOH
HCO2H
HCl
CF3CO2H
Salicylic acid
3-Nitrophenol
PhOH
79
[a] The reaction was carried out using
1
(0.50 mmol), 2a
(1.00 mmol), (S,S)-catalyst 11 (20 mol-%), acid additive (40 mol-
%), and DMF/H2O (9:1) as solvent (1 mL) at room temp. for 3 d.
[b] Isolated yield after silica gel chromatography. [c] ee’s were deter-
mined by HPLC analysis on a chiral phase (Daicel OD-H column).
Further studies revealed that the catalyst loading could
not be decreased, but that the reaction time could be short-
ened from 5 to 3 d without influence on the reaction yield.
These conditions were used for a screening of solvents to
test the reaction efficiency. The results are collected in
Table 3. Interestingly, in all cases (DMF, THF, MeOH,
Table 3. Solvent screening.[a]
Scheme 1. Model Michael reaction of (E)-nitrostyrene and 2-meth-
ylpropanal promoted by primary amine-based organocatalysts.
Entry
Solvent
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
DMF
26
40
48
30
50
52
55
58
59
54
67
65
54
36
28
82
88
93
97
97
96
75
88
89
76
91
90
86[d]
84
72
Table 1. Initial catalyst screening.[a]
DMF/H2O (9:1)
DMF/H2O (1:1)
THF
THF/H2O (9:1)
THF/H2O (1:1)
MeOH
MeOH/H2O (9:1)
MeOH/H2O (1:1)
EtOH
EtOH/H2O (9:1)
EtOH/H2O (1:1)
EtOH/H2O (1:1)
H2O
Entry
Catalyst
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
4
5
20
62
57
45
36
22
28
42
22 (R)
16 (S)
20 (S)
48 (R)
11 (S)
30 (R)
93 (S)
91 (S)[d]
6
7
8
9
9
10
11
12
13
14
15
10
11
[a] The reaction was carried out using
1
(0.50 mmol), 2a
(1.00 mmol), catalyst 4–11 (20 mol-%), PhCO2H (20 mol-%) as ad-
ditive, and DMF/H2O (9:1) as solvent (1 mL) at room temp. for
5 d. [b] Isolated yield after silica gel chromatography. [c] ee’s were
determined by HPLC analysis on a chiral phase (Daicel OD-H
column). [d] 40 mol-% of PhCO2H was used.
Neat
[a] The reaction was carried out using
1
(0.50 mmol), 2a
(1.00 mmol), (S,S)-catalyst 11 (20 mol-%), PhCO2H (40 mol-%) as
additive, and solvent (1 mL) at room temp. for 3 d. [b] Isolated
yield after silica gel chromatography. [c] ee’s were determined by
HPLC analysis on a chiral phase (Daicel OD-H column). [d] The
reaction was carried out using (S,S)-catalyst 11 (10 mol-%) and
It was reported[2,7] that the addition of a Brønsted acid
to an amine-promoted Michael reaction can enhance the
formation of the enamine, thereby improving the yield. In- PhCO2H (20 mol-%).
6048
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 6047–6051

Unmodified Primary Amine Organocatalysts
EtOH), the presence of a large amount of water did not
These results confirm that chiral 1,2-diphenylethylenedi-
adversely affect the reaction yields or the enantioselectivity. amines could have broad applications as efficient organoca-
On the contrary, the addition of water seems to be advan- talysts for aqueous Michael reactions between α,α-disubsti-
tageous. Two aqueous solvent mixtures: THF/water (1:1) tuted aldehydes and nitrostyrene. This particularly difficult
and EtOH/water (1:1) delivered the best results in terms of reaction proceeds efficiently in the case of a diaminocyclo-
yields. By using a green chemistry protocol with pure water hexane (DACH)-based thiourea organocatalyst,[11] but it
as the solvent, the reaction gave a good enantioselectivity seems reasonable to replace it by commercially available op-
but with a lower yield (Table 3, entry 14).
tically pure diphenylethylenediamine (DPEDA) 11.
On the basis of the results summarized in Table 3, the
reaction conditions of entries 6 and 12 were chosen to study
the scope of the Michael reactions using a series of alde-
hydes 2a–2f, and the results are summarized in Scheme 2.
First, combinations of α,α-disubstituted aldehydes and
nitrostyrene were surveyed to determine the efficiency of
tested diamine catalyst 11. To our delight, excellent enantio-
selectivity was maintained with aldehydes 2a, 2b, and 2c in
homogeneous THF/water and EtOH/water solutions. In all
cases, the observed enantioselectivity for the formation of
adducts 3a–3c reached the same high level as was observed
using the thiourea organocatalysts presented by Jacobsen[12]
for similar substrates.
Conclusions
We have shown that chiral (S,S)-diphenylethylenedi-
amine (11) can efficiently promote the highly enantioselec-
tive Michael addition of aldehydes to nitro olefins in aque-
ous organic solvents. This cheap and commercially available
chiral primary amine, which is the chiral backbone of vari-
ous organocatalysts, gives the addition products in good
yields and with good to high enantioselectivities (45–96%
ee). It is noteworthy that high enantioselectivities were ob-
served for the more demanding conjugate addition of α,α-
disubstituted aldehydes to nitrostyrene (96–98% ee) in
THF/water or EtOH/water solvents. These remarkably
enantioselective examples of the application of unmodified
amines represents a promising foundation for further
screening, not only for laboratory-scale work, but also for
industrial applications of small and readily available cata-
lysts without any modification of their structures.
Experimental Section
General Remarks: Unless otherwise stated, all reagents were pur-
chased from commercial sources and used as received. Infrared
(IR) spectra were recorded with a Fourier-transform infrared
(FTIR) spectrometer. 1H NMR spectra were measured at 400 MHz
in CDCl3. Data are reported as follows: chemical shifts in parts per
million (ppm), calibrated using the residual solvent as an internal
standard, multiplicity (s = singlet, d = doublet, t = triplet, q =
quartet, dd = doublet of doublets, m = multiplet, br = broad),
coupling constants (in Hz), integration. 13C NMR spectra were
measured at 100 MHz with complete proton decoupling. Chemical
shifts are reported in ppm, calibrated using the residual solvent as
an internal standard. High-resolution mass spectra (HRMS) were
measured with an electron ionization (EI) mass spectrometer. Op-
tical rotations were measured with a digital polarimeter at room
temperature. Reactions were monitored using TLC on silica [alu-
minium-backed plates (0.2 mm)]. All reagents and solvents were
purified and dried according to common methods. All organic
solutions were dried with anhydrous magnesium sulfate. Reaction
products were purified by flash chromatography using silica gel 60
(240–400 mesh). HPLC analysis was carried out with an HPLC
system equipped with chiral stationary-phase columns.
Scheme 2. Extension of the developed procedure to a wide range
of substrates. Conditions: the reaction was carried out using 1
(0.50 mmol), 2a–2g (1.00 mmol), (S,S)-catalyst 11 (20 mol-%),
PhCO2H (40 mol-%) as additive, and THF/H2O (1:1; 1 mL) as a
solvent at room temp. for 2 d. Isolated yield after silica gel
chromatography. ee and dr were determined by HPLC analysis on
a chiral phase. [a] The reaction was carried out in EtOH/H2O (1:1;
1 mL) as a solvent at room temp. for 3 d.
General Procedure for the Organocatalytic Michael Reaction of Al-
dehydes with Nitro Olefins: β-Nitrostyrene (1; 75.0 mg, 0.5 mmol),
(S,S)-1,2-diphenylethylene-1,2-diamine (11; 0.1 mmol, 20 mol-%),
and the carboxylic acid (0.2 mmol, 40 mol-%) were dissolved in an
appropriate solvent, and aldehyde 2a–2f (1.0 mmol) was added.
The mixture was stirred at room temperature for 2 or 3 d, de-
pending on the solvent. The organic solvent was then removed. The
mixture was partitioned between EtOAc and water, and then the
At the other extreme, only modest enantio- and dia-
stereoselectivities were for observed for adducts 3d–3f ob-
tained from pentanal, decanal, and phenylethanal, respec-
tively. The absolute stereochemistry of major product 3a
was determined to be (3S) by comparing its optical rotation
with literature data.[7b,12]
Eur. J. Org. Chem. 2015, 6047–6051
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6049

M. Rogozin´ska-Szymczak, J. Mlynarski
FULL PAPER
crude product was purified by column chromatography on silica
gel (hexane/ethyl acetate) to give the pure product. The enantio-
meric excess of the products was determined by HPLC using a
chiral stationary phase.
(t, JH,H = 7.3 Hz, 1.2 H), 0.81 (t, JH,H = 7.1 Hz, 1.8 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 203.3, 203.1, 136.8, 136.2, 129.1,
129.1, 128.2, 128.2, 128.1, 128.0, 78.4, 77.9, 53.8, 53.3, 44.5, 43.2,
29.6, 29.5, 20.3, 19.8, 13.9, 13.9 ppm. MS (EI): m/z (%) = 235 (2)
[M]+, 145 (77), 131 (15), 117 (49), 104 (86), 91 (100), 78 (26), 55
(21), 41 (27). HRMS (EI): calcd. for C13H17NO3 [M]+ 235.1208;
found 235.1208.
2,2-Dimethyl-4-nitro-3-phenylbutanal (3a):[12] The compound was
isolated as a colourless to pale yellow liquid. The enantiomeric ex-
cess was determined by HPLC analysis of the purified product with
a Daicel OD-H column [hexane/iPrOH (4:1), 1.0 mLmin–1, λ =
220 nm]: tR = 13.7 min (minor), tR = 20.2 min (major). Data for
sample with ee = 90% (S): [α]2D6 = –4.7 (c = 1.1, CHCl3) [ref.[7b]
2-(2-Nitro-1-phenylethyl)decanal (3e): The compound was isolated
as a pale oil. The enantiomeric excess was determined by HPLC
analysis of the purified product with a Daicel OD-H column [hex-
ane/iPrOH (4:1), 0.2 mLmin–1, λ = 254 nm]: tR = 47.5 min (major,
syn), tR = 50.5 min (major, anti), tR = 58.9 min (minor, syn) and tR
[α]2D6 = –4.9 (c = 1.0, CHCl ), ee = 98% (S)]. IR (film, CH Cl ): ν
˜
3
2
2
= 2962, 2919, 2849, 1724, 1553, 1378, 881, 704 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 9.53 (s, 1 H), 7.35–7.27 (m, 3 H), 7.20–
7.18 (m, 2 H), 4.85 (dd, JH,H = 13.1, 11.2 Hz, 1 H), 4.69 (dd, JH,H
= 13.1, 4.2 Hz, 1 H), 3.78 (dd, JH,H = 11.2, 4.2 Hz, 1 H), 1.13 (s,
3 H), 1.01 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 204.2,
135.4, 129.1, 128.7, 128.1, 76.3, 48.5, 48.2, 21.7, 18.9 ppm. MS (EI):
m/z (%) = 221 (0.5) [M]+, 145 (25), 131 (11), 117 (12), 104 (100),
91 (60), 77 (16), 72 (22), 43 (23). HRMS (EI): calcd. for C12H15NO3
[M]+ 221.1052; found 221.1048.
= 79.7 min (minor, anti). IR (film, CH Cl ): ν = 2953, 2926, 2855,
˜
2
2
1
1724, 1555, 1455, 1379, 701 cm–1. H NMR (400 MHz, CDCl3): δ
= 9.71 (d, JH,H = 2.8 Hz, 0.6 H), 9.48 (d, JH,H = 3.0 Hz, 0.4 H),
7.38–7.27 (m, 3 H), 7.17 (dd, JH,H = 8.1, 1.2 Hz, 2 H), 4.86–4.59
(m, 2 H), 3.84–3.73 (m, 1 H), 2.74–2.57 (m, 1 H), 1.74–1.42 (m, 2
H), 1.35–1.07 (m, 12 H), 0.87 (dt, JH,H = 8.5, 6.9 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 203.3, 203.2, 136.8, 136.3, 129.1,
129.1, 128.2, 128.2, 128.1, 128.0, 78.4, 77.9, 53.9, 53.5, 44.5, 43.2,
31.8, 31.7, 29.5, 29.4, 29.2, 29.1, 29.1, 29.0, 27.5, 27.3, 27.0, 26.4,
22.6, 22.6, 14.0, 14.0 ppm. MS (EI): m/z (%) = 305 (2) [M]+, 258
(8), 162 (27), 145 (95), 131 (41), 117 (57), 104 (100), 91 (93), 78
(18), 69 (23), 55 (34), 41 (43). HRMS (EI): calcd. for C18H27NO3
[M]+ 305.1991; found 305.1982.
2,2-Diethyl-4-nitro-3-phenylbutanal (3b): The compound was iso-
lated as a colourless oil. The enantiomeric excess was determined
by HPLC analysis of the purified product with a Daicel OD-H
column [hexane/iPrOH (97:3), 0.5 mLmin–1, λ = 220 nm]: tR
=
32.1 min (minor), tR = 34.6 min (major). Data for sample with ee
= 94% (S): [α]2D4 = +7.7 (c = 1.0, CHCl ). IR (film, CH Cl ): ν =
4-Nitro-2,3-diphenylbutanal (3f):[15,16] The compound was isolated
as a white solid. The enantiomeric excess was determined by HPLC
analysis of the purified product with a Daicel OD-H column [hex-
ane/iPrOH (98:2), 0.8 mLmin–1, λ = 208 nm]: tR = 27.3 min (major,
anti), tR = 30.3 min (minor, syn), tR = 33.9 min (major, syn) and tR
˜
3
2
2
2969, 2942, 2882, 1719, 1556, 1455, 1379, 704 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 9.58 (s, 1 H), 7.40–7.27 (m, 3 H), 7.15–
7.12 (m, 2 H), 4.88–4.78 (m, 2 H), 3.70 (dd, JH,H = 9.8, 5.8 Hz, 1
H), 1.79–1.49 (m, 4 H), 0.92 (t, JH,H = 7.5 Hz, 3 H), 0.89 (t, JH,H
= 7.5 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 207.6,
135.6, 129.1, 128.7, 128.1, 76.9, 53.3, 48.1, 23.5, 22.7, 7.9, 7.5 ppm.
MS (EI): m/z (%) = 249 (3) [M]+, 173 (20), 150 (15), 131 (33), 117
(26), 104 (100), 100 (80), 91 (73), 85 (13), 77 (20), 71 (26), 57 (30),
43 (52). HRMS (EI): calcd. for C14H19NO3 [M]+ 249.1365; found
249.1374.
= 36.5 min (minor, anti). IR (KBr): ν = 3406 (br), 3026, 2861, 1712,
˜
1
1546, 1382, 758, 702, 559 cm–1. H NMR (400 MHz, CDCl3): δ =
9.56 (d, JH,H = 2.1 Hz, 1 H), 7.46–7.25 (m, 10 H), 4.49 (dd, JH,H
= 12.8, 10.2 Hz, 1 H), 4.40 (dd, JH,H = 12.8, 4.4 Hz, 1 H), 4.30 (dt,
JH,H = 10.2, 4.4 Hz, 1 H), 4.07 (dd, JH,H = 10.2, 2.1 Hz, 1 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 196.7, 137.0, 132.4, 129.8, 129.4,
129.1, 128.9, 128.2, 128.1, 78.4, 61.7, 44.4 ppm. MS (EI): m/z (%)
= 269 (13) [M]+, 193 (23), 178 (15), 120 (100), 115 (30), 104 (97),
91 (86), 78 (17), 65 (16). HRMS (EI): calcd. for C16H15NO3 [M]+
269.1052; found 269.1054.
2-Methyl-2-(2-nitro-1-phenylethyl)pentanal (3c):[7b] The compound
was isolated as a colourless oil. The enantiomeric excess was deter-
mined by HPLC analysis of the purified product with a Daicel OJ-
H column [hexane/iPrOH (9:1), 0.8 mLmin–1, λ = 254 nm]: tR
=
29.4 min (major, syn), tR = 32.7 min (minor, anti), tR = 38.3 min
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra of reaction products.
(major, anti) and tR = 46.7 min (minor, syn). IR (film, CH Cl ): ν =
˜
2
1
2
2963, 2935, 2873, 1723, 1555, 1456, 1379, 751, 705 cm–1. H NMR
(400 MHz, CDCl3): δ = 9.54 (s, 0.8 H), 9.52 (s, 0.2 H), 7.37–7.27
Acknowledgments
(m, 3 H), 7.22–7.15 (m, 2 H), 4.90–4.71 (m, 1 H), 4.63 (dd, JH,H
=
13.0, 3.9 Hz, 1 H), 3.80–3.75 (m, 1 H), 1.56–1.41 (m, 1 H), 1.29–
1.16 (m, 3 H), 1.11 (s, 2.4 H), 1.10 (s, 0.6 H), 0.92–0.82 (m, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 205.3, 135.4, 129.2, 128.7,
128.1, 77.2, 51.6, 47.7, 37.6, 17.0, 15.9, 14.5 ppm. MS (EI): m/z (%)
= 249 (0.4) [M]+, 203 (7), 173 (11), 159 (13), 150 (14), 131 (34), 104
(100), 100 (74), 91 (69), 77 (13), 71 (32), 43 (38). HRMS (EI): calcd.
for C14H19NO3 [M]+ 249.1365; found 249.1369.
This project was operated with funding from the Polish National
Science Centre (grant number NCN 2011/03/B/ST5/03126). Finan-
cial support from the European Social Fund cofinanced with the
European Union funds is gratefully acknowledged.
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by HPLC analysis of the purified product with a Daicel OD-H
column [hexane/iPrOH (9:1), 0.8 mLmin–1, λ = 208 nm]: tR
=
23.4 min (major, syn), tR = 25.5 min (major, anti), tR = 28.3 min
(minor, syn) and tR = 38.9 min (minor, anti). IR (film, CH Cl ): ν =
˜
2
2
2961, 2933, 2873, 1721, 1554, 1380, 702 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 9.71 (d, JH,H = 2.8 Hz, 0.6 H), 9.48 (d, JH,H = 3.0 Hz,
0.4 H), 7.37–7.28 (m, 3 H), 7.21–7.12 (m, 2 H), 4.83–4.62 (m, 2 H),
3.81–3.75 (m, 1 H), 2.74–2.60 (m, 1 H), 1.75–1.11 (m, 4 H), 0.93
6050
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Received: July 9, 2015
Published Online: August 7, 2015
Eur. J. Org. Chem. 2015, 6047–6051
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6051