Synthesis of stable acyclic aminals derived from L-(+)-aspartic acid and their application in asymmetric Henry reactions

Article abstract of DOI:10.5560/ZNB.2013-2228

A series of stable acyclic aminals derived from L-(+)-aspartic acid were synthesized in excellent yields (up to 96%) and characterized by spectroscopic methods. They were applied as enantioselective catalysts in Henry reactions of nitromethane with various aldehydes in the presence of Cu(II) ions, affording the corresponding adducts in high yields (up to 90%) and enantioselectivities (up to 92% ee).

Full text of DOI:10.5560/ZNB.2013-2228

Synthesis of Stable Acyclic Aminals Derived from L-(+)-Aspartic Acid
and Their Application in Asymmetric Henry Reactions
Gamze Koz, Demet Astley and Stephen T. Astley
Department of Chemistry, Faculty of Science, Ege University, 35100, Izmir, Turkey
Reprint requests to Dr. G. Koz. E-mail: gamzedoganer@yahoo.com
Z. Naturforsch. 2013, 68b, 57 – 63 / DOI: 10.5560/ZNB.2013-2228
Received August 21, 2012
A series of stable acyclic aminals derived from L-(+)-aspartic acid were synthesized in excellent
yields (up to 96%) and characterized by spectroscopic methods. They were applied as enantioselec-
tive catalysts in Henry reactions of nitromethane with various aldehydes in the presence of Cu(II)
ions, affording the corresponding adducts in high yields (up to 90%) and enantioselectivities (up to
92% ee).
Key words: Acyclic Aminals, L-(+)-Aspartic Acid, Enantioselective Henry Reaction
Introduction
The catalytic asymmetric Henry (nitroaldol) reac-
Results and Discussion
Recently, we prepared (S)-2-amino-1,1,4,4-tetra-
tion is an ideal, atom-economical and powerful method phenyl-1,4-butanediol from L-(+)-aspartic acid via es-
for stereoselective carbon-carbon bond formation. The terification and Grignard addition reactions, and this
resulting chiral adducts, β-nitro alcohols, can be con- compound was converted into the chiral tridentate
veniently converted into β-amino alcohols, α-hydroxy ONO Schiff base ligand L (Fig. 1). The Lewis-acidic
carboxylic acids, aziridines, and other complex target catalyst system obtained from L and Cu(II) ions was
molecules that are highly versatile building blocks for observed to catalyze the Henry reaction in high yields
the synthesis of bioactive natural products and pharma- (up to 96%) and enantioselectivities (up to 92%) [24].
ceutical agents [1 – 6]. Since the pioneering work initi-
We were keen to extend this chemistry in order to
ated by Shibasaki and co-workers in 1992 [7], interest exploit the high enantioselectivity offered by this type
in asymmetric Henry reactions has grown, and vari- of ligand, and so we attempted to prepare additional
ous catalysts [8 – 19] have been developed over the last Schiff bases from (S)-2-amino-1,1,4,4-tetraphenyl-1,4-
two decades. Although significant progress has been butanediol using a variety of 2-hydroxybenzaldehydes.
made, many of the current catalytic systems still share However, instead of the expected Schiff base lig-
a number of disadvantages such as low substrate gen- ands, we obtained a series of stable acyclic aminals
erality, high cost of catalysts, and harsh reaction con- (Scheme 1).
ditions. Therefore, the exploitation of mild, efficient,
cheap, and readily available catalysts is still desirable.
Chiral cyclic aminals are one of the ligands that are
used extensively in catalytic asymmetric reactions such
as α-bromination of cyclic ketones [20], the Diels-
Alder reaction [21] and the addition of aldehydes to
substrates such as diethyl azodicarboxylate [22] or
vinyl sulfones [23]. However no attention has been fo-
cused upon catalytic application of cyclic or acyclic
aminals in Henry reactions.
Fig. 1. The structure of the ONO Schiff base ligand L.
© 2013 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com

58
G. Koz et al. · Stable Acyclic Aminals Derived from L-(+)-Aspartic Acid
Scheme 1. Synthesis of the acyclic aminals.
The number of known stable acyclic aminals is istic singlet signal at δ = 5.5 ppm for the methylene
quite limited, and those that are known have gener- group was observed in the 1H NMR spectra of all the
ally been shown to be stabilized by hydrogen bond- products.
ing. In particular, a series of stable acyclic aminals ob-
Our initial experiment was performed to screen the
tained from pyridine carboxaldehydes and amines such effect of the ligand structure on the Henry reaction
as 8-aminoquinoline [25] and 2-aminopyridine [26] by using 2-chlorobenzaldehyde as a model substrate
have been reported. Therefore, it can be expected that with nitromethane in the presence of a catalyst (10
such an effect of multiple hydrogen bond stabiliza- mol-%) which was generated in situ from the aminal
tion is also present in the aminals prepared from the and Cu(OAc)2 · nH2O. The results are summarized in
L-(+)-aspartic acid-derived amino alcohol (Fig. 2). At Table 1.
this point, it is interesting to consider that when 2-
It was apparent that the flexibility of the C–C bond
hydroxynaphtaldehyde was used as the substrate, in associated with the amino and hydroxyl groups in the
place of the aminal the originally expected Schiff base ligand had a strong influence on the coordination with
was obtained. In this case, it seems reasonable to as- Cu(OAc)2 · nH2O, and consequently on the enantios-
sume that the naphtaldehyde ring system in some way electivity of the reaction. Ligands 1a, b were clearly
manages to affect the hydrogen bond stabilization.
superior to 1c–e in terms of ee values, among which
The aminal structure of the products was clearly as- 1a distinguished itself as the best ligand.
signed by IR and NMR spectroscopy and by elemen-
tal analysis. In particular, the presence of a character-
Table 1. Ligand Screening.
Entry
Ligand
R
Yield (%)a
ee (%)b
1
2
3
4
5
1a
1b
1c
1d
1e
3-OCH3
5-Br
H
3-OH
5-t-Bu
90
60
82
51
61
92
90
88
82
36
a
b
Isolated yields after column chromatography; determined by
HPLC analysis using a Chiralcel OD-H column; the absolute con-
figuration of the major product was assigned as S by comparison to
the literature values [27 – 29].
Fig. 2. Multiple hydrogen bonding in stable acyclic aminals.

G. Koz et al. · Stable Acyclic Aminals Derived from L-(+)-Aspartic Acid
Table 2. Optimization of the reaction conditions.
59
Finally, we examined the substrate tolerance of the
reaction by carrying out reactions using a variety of
aromatic aldehydes (Table 3). All of the substrates used
in this study, regardless of whether the aromatic ring
contained electron-withdrawing or electron-donating
groups at the ortho, meta or para positions, gave
the corresponding S-enriched products in moderate
to good yield (61% – 90%) of isolated products with
good enantioselectivities (66% – 92%) in most cases.
Entry
Solvent
Temp. (◦C) Yielda (%)
eeb,c (%)
1
2
3
4
5
6
7
8d
9e
10f
11g
Ethanol
Methanol
2-Propanol
tert-Butanol
Tetrahydrofuran
Diethyl ether
Hexane
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
r. t.
50
90
79
90
93
68
56
47
86
89
94
22
92
78
81
80
82
66
54
80
74
70
86
Conclusion
We have successfully synthesized five stable acyclic
aminals containing a chiral L-(+)-aspartic acid skele-
ton and applied these aminals as enantioselective cata-
lysts in asymmetric Henry reactions for the first time.
The mild reaction conditions, tolerance of air and
moisture, lack of additives, high efficiency and enan-
tioselectivity makes this catalytic system useful for the
synthesis of many valuable compounds.
Ethanol
Ethanol
Ethanol
Ethanol
0
a
b
Isolated yields after column chromatography; determined by
HPLC analysis using a Chiralcel OD-H column; c the absolute con-
figuration of the major product was assigned as S by comparison to
d
e
literature values [27 – 29]; 5 mol-% catalyst loading; 20 mol-%
catalyst loading; f the reaction was completed within 12 h; g the re-
action was completed within 5 d.
Experimental Section
Materials and physical measurements
In subsequent studies, the reaction parameters, in-
cluding solvents, catalyst loadings and reaction tem-
peratures, were optimized. From the data listed in Ta-
ble 2, we noted that the reaction was highly sensitive to
the nature of solvent employed; ethanol was found to
be the superior solvent in terms of yield (90%) and ee
value (92%) (Table 2, entry 1). Catalyst loadings (Ta-
ble 2, entry 1, 8, 9) also had a significant effect on the
enantioselectivities; 10 mol-% loading of catalyst gave
the highest ee value (92%, Table 2, entry 1).
All chemicals were purchased from Merck, Sigma-
Aldrich, Alfa Aesar, or Fluka and used without any further
purification. Solvents were used as received from commer-
cial suppliers. Silica gel F254 (Merck 5554) precoated plates
were used for thin layer chromatography. For column chro-
matography silica gel 60 (Merck 7743) was used. IR spec-
tra were recorded using a Mattson FTIR 1000 spectrome-
1
ter. H NMR and 13C NMR spectra were carried out using
a 400 MHz Varian NMR spectrometer at ambient temper-
ature. Melting points were recorded with an electrothermal
Table 3. Substrate scope.
Entry
ArCHO
Time (h)
Yield (%)a
ee (%)b
Config.c
1
2
3
4
5
6
7
8
2-Nitrobenzaldehyde
3-Nitrobenzaldehyde
4-Nitrobenzaldehyde
2-Chlorobenzaldehyde
4-Methoxybenzaldehyde
4-Methylbenzaldehyde
4-Ethylbenzaldehyde
Benzaldehyde
18
12
12
71
66
76
90
61
79
82
69
84
74
66
92
72
73
90
72
S
S
S
S
S
S
n. d.
S
48
120
120
120
120
a Isolated yields after column chromatography; b determined by HPLC analysis using a Chiralcel
c
OD-H column; the absolute configuration of the major product was assigned by comparison
to literature values [27 – 29]; n. d. = not determined.

60
G. Koz et al. · Stable Acyclic Aminals Derived from L-(+)-Aspartic Acid
digital melting point apparatus. Optical rotations were deter- products were crystallized using dichloromethane-hexane
mined using a Rudolph Research Analytical Autopol I au- solvent systems.
tomatic polarimeter. HPLC analyses were performed using
(2S,20S)-2,20-(((2-Hydroxy-3-methoxyphenyl)methylene)-
a Chiralcel OD-H column.
bis(azanediyl))bis(1,1,4,4-tetraphenylbutane-1,4-diol) (1a)
Preparation of (S)-dimethyl-2-aminosuccinate
79% yield; m. p. 103 – 104 ◦C. – IR (NaCl): ν = 3504,
SOCl2 (12 mL) was added dropwise to a suspension of L- 3276, 3058, 2936, 2938, 1628, 1598, 1492, 1463, 1448,
(+)-aspartic acid (354 mg, 2.66 mmol) in 60 mL of methanol 1266, 1169, 1060, 1031, 736, 700 cm−1. – 1H NMR
at 0 ◦C. The resulting colorless solution was refluxed until (400 MHz, CDCl3): δ = 7.46 – 7.09 (m, 43H, Ar-H), 5.56
all L-(+)-aspartic acid had been consumed. Methanol was (s, 1H), 4.31 (dd, J = 5.6, 3.2 Hz, 1H), 4.22 (dd, J = 11.2,
evaporated in vacuo, and water (5 mL) was added. Saturated 1.6 Hz, 1H), 3.84 (s, 2H), 3.82 (s, 3H), 2.87 (bs, 1H), 2.65
aqueous NaHCO3 was then added dropwise (pH = 8), and (bs, 1H), 2.38 (m, 2H), 2.00 (dd, J = 14.4, 12 Hz, 1H). –
the mixture was extracted with ethyl acetate. The organic 13C NMR (400 MHz, CDCl3): δ = 167.14, 148.13, 147.98,
phase was dried with Na2SO4 and filtered. Ethyl acetate was 147.92, 147.11, 145.31, 144.88, 144.28, 144.03, 142.02,
evaporated to give the title compound as a yellow oil (82% 129.02, 128.69, 128.46, 128.21, 128.16, 128.10, 128.04,
yield). – IR (NaCl): ν = 3385, 2956, 2851, 1738, 1438, 1366, 127.93, 127.49, 127.37, 127.13, 127.07, 127.02, 126.92,
1203 cm−1. – 1H NMR (400 MHz, CDCl3): δ = 3.84 (dd, 126.70, 126.66, 126.56, 126.49, 126.17, 126.00, 125.88,
J = 4.8, 7.6 Hz, 1H), 3.76 (s, 3H, CH3), 3.71 (s, 3H, CH3), 125.59, 125.47, 125.38, 124.89, 124.82, 123.26, 118.98,
2.82 (dd, J = 4.8, 16.4 Hz, 1H), 2.71 (dd, J = 7.6, 16.4 Hz, 118.35, 118.09, 117.37, 113.75, 111.81, 81.17, 81.08, 80.66,
1H), 1.88 (bs, 2H, -NH2). – 13C NMR (400 MHz, CDCl3): 79.09, 77.41, 72.65, 56.85, 55.91, 55.85, 53.35, 42.90, 35.24.
δ = 174.7, 171.8, 52.5, 52.0, 38.9. – C6H11O4N (161.2): – C64H60N2O6 (953.2): calc. C 80.65, H 6.34, N 2.94; found
calcd. C 44.72, H 6.88, N 8.69; found C 43.86, H 6.04, N C 79.98, H 6.28, N 2.69. – [α]2D5 = +5.60 (c = 2.5, CH2Cl2).
9.01.
(2S,20S)-2,20-(((5-Bromo-2-hydroxyphenyl)methylene)-
Preparation of (S)-2-amino-1,1,4,4-tetraphenylbutane-
1,4-diol
bis(azanediyl))bis(1,1,4,4-tetraphenylbutane-1,4-diol) (1b)
90% yield; m. p. 201 – 203 ◦C. – IR (NaCl): ν = 3460,
To a solution of L-(+)-aspartic acid dimethyl ester 3271, 3059, 3027, 2926, 1632, 1493, 1476, 1448, 1374,
(1 mmol) in dry ethyl ether was added an excess of a freshly 1274, 1173, 1061, 1031, 738, 700 cm−1. – 1H NMR
prepared 1 M PhMgBr solution in 10 mL of dry ether. (400 MHz, CDCl3): δ = 7.83 (dd, J = 2.4, 0.8 Hz, 1H),
The resulting solution was refluxed until all L-(+)-aspartic 7.49 – 7.13 (m, 41H, Ar-H), 6.64 (d, J = 8.8 Hz, 1H), 5.43
acid dimethyl ester had been consumed. The reaction was (s, 1H), 4.36 (dd, J = 6.8, 2 Hz, 1H), 4.17 (d, J = 11.6 Hz,
quenched with saturated NH4Cl solution. The product was 1H), 2.80 (m, 1H), 2.50 (s, 1H), 2.43 (dd, J = 14, 2 Hz, 1H),
extracted with ether-water, and the organic phase was dried 1.99 (dd, J = 14, 11.6, 1H). – 13C NMR (400 MHz, CDCl3):
with Na2SO4 and filtered. Then the ether fraction was evap- δ = 165.91, 159.86, 154.76, 147.59, 147.11, 145.27, 144.30,
orated in vacuo. The crude product was purified with col- 144.09, 144.00, 143.81, 141.68, 134.87, 133.68, 132.47,
umn chromatography (1 : 3 ethyl acetate-hexane) to give 129.23, 128.77, 128.74, 128.35, 128.27, 128.25, 128.08,
the title compound as colorless crystals (78% yield); m. p. 127.79, 127.52, 127.24, 127.23, 127.12, 127.00, 126.97,
145.9 – 149.5 ◦C. – IR (NaCl): ν = 3376, 1491, 1596, 1447 126.88, 126.49, 126.17, 126.03, 125.95, 125.57, 125.25,
1
700 cm−1. – H NMR (400 MHz, CDCl3): δ = 7.12 – 7.41 124.93, 119.76, 118.76, 118.52, 111.49, 109.62, 81.53,
(m, 20H, Ar-H), 3.65 (dd, J = 10.8, 1.2 Hz, 1H), 2.60 (bs, 81.06, 80.07, 79.44, 77.45, 72.68, 57.12, 42.52, 35.52. –
-OH), 2.44 (dd, J = 1.2, 14.4, Hz, 1H), 2.05 (dd, J = C63H52BrN2O5 (1002.0): calc. C 75.51, H 5.73, N 2.80;
10.8, 14 Hz, 1H). – 13C NMR (400 MHz, CDCl3): δ = found C 74.96, H 5.6, N 2.70. – [α]2D5 = +14.8 (c = 1.08,
128.8, 128.6, 128.2, 128.1, 127.4, 127.2, 126.9, 126.8, CH2Cl2).
126.7, 125.96, 125.91, 125.8, 81.4, 78.2, 55.2, 40.1. –
(2S,20S)-2,20-(((2-Hydroxyphenyl)methylene)bis-
C28H27O2N(409,5): calc. C 82.12, H 6.65, N 3.42; found C
(azanediyl))bis(1,1,4,4-tetraphenylbutane-1,4-diol) (1c)
81.11, H 6.61, N 3.61.
87% yield; m. p. 204 – 205 ◦C. – IR (NaCl): ν = 3555,
3449, 3275, 3058, 3027, 1628, 1583, 1492, 1448, 1389,
General procedure for the synthesis of aminals
The solution of aldehyde (1 mmol) and (S)-2-amino- 1347, 1266, 1153, 1108, 1032, 893, 755, 699 cm−1. – 1H
1,1,4,4-tetraphenylbutane-1,4-diol (2 mmol) in 20 mL NMR (400 MHz, CDCl3): δ = 7.74 (d, J = 7.6 Hz, 1H),
ethanol was refluxed until all of the starting materials 7.46 – 7.07 (m, 38H, Ar-H), 6.97 – 6.89 (m, 2H), 6.78 – 6.67
were consumed. Ethanol was evaporated in vacuo, and the (m, 3H), 5.48 (s, 1H), 4.32 (dd, J = 8, 2 Hz, 1H), 4.16 (dd,

G. Koz et al. · Stable Acyclic Aminals Derived from L-(+)-Aspartic Acid
61
J = 11.6, 1.6 Hz, 1H), 2.90 – 2.78 (m, 2H), 2.65 (bs, 1H), 31.23, 31.07, 22.49, 15.01, 13.99. – C67H66N2O5 (979.3):
2.43 (dd, J = 14.4, 2 Hz, 1H), 1.99 (dd, J = 14, 11.6 Hz, 1H). calc. C 82.18, H 6.90, N 2.46; found C 81.98, H 6.88, N
–
13C NMR (400 MHz, CDCl3): δ = 160.68, 155.60, 147.93, 2.49. – [α]2D5 = +18.2 (c = 0.88, CH2Cl2).
147.15, 145.46, 144.42, 144.21, 144.15, 144.01, 142.02,
132.28, 131.71, 129.68, 129.11, 128.65, 128.63, 128.26,
128.17, 128.15, 128.13, 127.97, 127.61, 127.43, 127.36,
127.09, 127.06, 126.98, 126.78, 126.74, 126.63, 126.54,
126.19, 126.09, 126.06, 125.68, 125.32, 124.87, 124.09,
119.33, 118.39, 118.25, 116.69, 116.66, 81.18, 81.08, 80.71,
79.41, 77.48, 72.78, 57.11, 42.71, 35.39. – C63H58N2O5
(923,1): calc. C 81.97, H 6.33, N 3.03; found C 81.96, H
6.30, N 3.00. – [α]2D5 = +21.4 (c = 0.56, CH2Cl2).
General procedure for the Henry reaction
The dark-green solution of Cu(OAc)2 · nH2O (0.1 mmol)
and the aminal ligand (0.05 mmol) in 2 mL of solvent
was stirred at r. t. for 2 h. Then the appropriate aldehyde
(0.5 mmol) and nitromethane (2.5 mmol) were added. The
reaction mixture was stirred at r. t. until most of the aldehyde
had been consumed. The solvent was evaporated in vacuo,
and the crude product was purified by column chromato-
graphy.
(2S,20S)-2,20-(((2,3-Dihydroxyphenyl)methylene)-
bis(azanediyl))bis(1,1,4,4-tetraphenylbutane-1,4-diol) (1d)
(S)-1-(2-Chlorophenyl)-2-nitroethanol
96% yield; m. p. 198 ◦C. – IR (NaCl): ν = 3426, 3059,
3027, 1639, 1599, 1545, 1493, 1465, 1448, 1391, 1359,
1266, 1241, 1166, 1066, 1031, 894, 738, 699 cm−1. – 1H
NMR (400 MHz, CDCl3): δ = 7.47 – 6.77 (m, 41H, Ar-H),
6.38 (t, J = 8 Hz, 1H), 6.25 (dd, J = 8, 1.2 Hz, 1H), 5.51
(s, 1H), 4.35 (dd, J = 8.2, 6.8 Hz, 1H), 4.19 (dd, J = 11.6,
2 Hz, 1H), 2.88 (m, 3H), 2.42 (dd, J = 14, 2 Hz, 1H), 2.03
(dd, J = 14, 11.6 Hz, 1H). – 13C NMR (400 MHz, CDCl3):
δ = 166.05, 147.92, 147.02, 146.36, 145.93, 145.06, 144.31,
144.08, 143.84, 143.49, 142.46, 141.98, 129.16, 128.71,
128.67, 128.55, 128.35, 128.32, 128.16, 128.14, 127.66,
127.41, 127.39, 127.19, 127.15, 127.03, 126.83, 126.66,
126.18, 126.14, 125.97, 125.75, 125.27, 124.91, 124.27,
122.66, 119.55, 116.92, 116.06, 115.41, 114.86, 114.78,
81.23, 81.08, 80.74, 79.56, 77.37, 68.93, 57.13, 42.07, 35.48,
31.57, 22.63, 14.09. – C63H58N2O6 (939.1): calc. C 80.57, H
6.22, N 2.98; found C 80.56, H 6.31, N 2.97. – [α]2D5 = +44.3
(c = 0.63, CH2Cl2).
Colorless oil, 95% yield. – 1H NMR (400 MHz, CDCl3):
δ = 7.56 (dd, J = 2, 7.6 Hz, 1H, Ar-H), 7.24 (m, 3H, Ar-
H), 5.75 (m, 1H), 4.57 (dd, J = 2.4, 13.6 Hz, 1H), 4.36
(dd, J = 9.6, 13.6 Hz, 1H). – HPLC conditions: 93 : 7 hex-
ane : i-PrOH, 0.8 mL min−1, 267 nm, tminor = 14.4 min (R),
tmajor = 15.3 min (S), 90% ee. – [α]2D5 = +44.0 (c = 0.55,
CH2Cl2).
(S)-1-(2-Nitrophenyl)-2-nitroethanol
Brown crystals, 81% yield. – 1H NMR (400 MHz,
CDCl3): δ = 8.06 (dd, J = 1.2, 8 Hz, 1H, Ar-H), 7.95 (d,
J = 8 Hz, 1H, Ar-H), 7.75 (td, J = 0.8, 7.6 Hz, 1H, Ar-H),
7.55 (td, J = 1.6, 8.4 Hz, 1H, Ar-H), 6.03 (d, J = 8 Hz, 1H),
4.85 (dd, J = 2.4, 14 Hz, 1H), 4.56 (dd, J = 9.2, 13.6 Hz,
1H), 3.35 (bs, 1H, -OH). – HPLC conditions: 90 : 10 he-
xane : i-PrOH, 1 mL min−1, 267 nm, tminor = 15.9 min (R),
tmajor = 18.3 min (S), 88% ee. – [α]2D5 = +23.5 (c = 0.89,
CH2Cl2).
(2S,20S)-2,20-(((5-(tert-Butyl)-2-hydroxyphenyl)methylene)-
bis(azanediyl))bis(1,1,4,4-tetraphenylbutane-1,4-diol) (1e)
(S)-1-(3-Nitrophenyl)-2-nitroethanol
Yellow oil, 90% yield. – 1H NMR (400 MHz, CDCl3):
δ = 8.30 (m, 1H, Ar-H), 8.19 (m, 1H, Ar-H), 7.78 (m, 1H,
Ar-H), 7.61 (t, J = 7.6 Hz, 1H, Ar-H), 5.61 (dd, J = 4.4,
7.6 Hz, 1H), 4.63 (m, 2H), 3.51 (bs, 1H, -OH). – HPLC
conditions: 90 : 10 hexane : i-PrOH, 1 mL min−1, 267 nm,
tminor = 25.9 min (R), tmajor = 28.6 min (S), 70% ee. –
[α]2D5 = +28.8 (c = 1.04, CH2Cl2).
91% yield, liquid at r. t. – IR (NaCl): ν = 3450, 3058,
2962, 1633, 1594, 1493, 1448, 1363, 1265, 1031, 831,
748, 700 cm−1. – 1H NMR (400 MHz, CDCl3): δ = 7.75
(d, J = 2.4 Hz, 1H), 7.48 – 7.09 (m, 40H, Ar-H), 6.91 (t,
J = 7.2 Hz, 1H), 6.71 (m, 2H), 5.48 (s, 1H), 4.38 (dd, J = 6.4,
2 Hz, 1H), 4.18 (dd, J = 11.6, 2 Hz, 1H), 2.83 (m, 2H), 2.44
(dd, J = 14.4, 2 Hz, 1H), 2.00 (dd, J = 14.4, 11.6 Hz, 1H),
1.27 (s, 9H). – 13CNMR (400 MHz, CDCl3): δ = 167.36,
158.87, 152.96, 148.06, 147.23, 145.57, 144.39, 144.31,
144.27, 142.15, 141.72, 140.44, 129.59, 128.93, 128.35,
128.29, 128.13, 128.01, 127.94, 127.89, 127.80, 127.39,
127.01, 126.98, 126.82, 126.76, 126.62, 126.50, 126.34,
126.20, 125.99, 125.78, 125.32, 124.59, 123.34, 122.52,
117.48, 116.34, 116.06, 80.92, 80.84, 80.76, 79.13, 77.24,
(S)-1-(4-Nitrophenyl)-2-nitroethanol
Colorless crystals, 71% yield. – 1H NMR (400 MHz,
CDCl3): δ = 8.26 (m, 2H, Ar-H), 7.63 (m, 2H, Ar-H), 5.61
(m, 1H), 4.60 (d, J = 6 Hz, 1H), 4.58 (d, J = 2 Hz, 1H),
3.17 (bs, 1H, -OH). – HPLC conditions: 90 : 10 hexane : i-
PrOH, 1 mL min−1, 267 nm, tminor= 28.7 min (R), tmajor
=
72.40, 65.54, 57.08, 42.73, 35.12, 33.99, 33.63, 31.52, 31.42, 35.40 min (S), 76% ee. – [α]2D5 = +29.3 (c = 0.75, CH2Cl2).

62
G. Koz et al. · Stable Acyclic Aminals Derived from L-(+)-Aspartic Acid
(S)-1-Phenyl-2-nitroethanol
1H), 4.50 (dd, J = 9.6, 13.2 Hz, 1H), 4.48 (dd, J = 3.2,
13.2 Hz, 1H), 2.86 (d, J = 3.6 Hz, 1H), 2.65 (q, J = 7.6 Hz,
Yellow oil, 96% yield. – 1H NMR (400 MHz, CDCl3):
δ = 7.38 (m, 5H, Ar-H), 5.43 (dd, J = 2.8, 9.6 Hz, 1H), 4.59
(dd, J = 9.6, 13.6 Hz, 1H), 4.49 (dd, J = 2.8, 13.2 Hz, 1H),
3.08 (bs, 1H, -OH). – HPLC conditions: 90 : 10 hexane : i-
2H, -CH2), 1.23 (t, J = 7.6 Hz, 3H, CH3). – HPLC condi-
tions: 90 : 10 hexane : i-PrOH, 1 mL min−1, 267 nm, tminor
=
12.2 min (R), tmajor = 15.7 min (S), 76% ee. – [α]2D5 = +32.0
(c = 0.75, CH2Cl2).
PrOH, 1 mL min−1, 267 nm, tminor = 13.8 min (R), tmajor
=
15.0 min (S), 78% ee. – [α]2D5 = +35.3 (c = 1.36, CH2Cl2).
(S)-1-(4-Methoxyphenyl)-2-nitroethanol
Yellow oil, 68% yield. – 1H NMR (400 MHz, CDCl3):
δ = 7.30 (d, J = 8.8 Hz, 2H, Ar-H), 6.91 (d, J = 8.8 Hz,
2H, Ar-H), 5.39 (m, 1H), 4.59 (dd, J = 9.6, 13.2 Hz, 1H),
4.46 (dd, J = 2.8, 12.8 Hz, 1H), 3.81 (s, 3H, -OCH3), 2.84
(bs, 1H, -OH). – HPLC conditions: 90 : 10 hexane : i-
(S)-1-(4-Methylphenyl)-2-nitroethanol
Yellow crystals, 88% yield. – 1H NMR (400 MHz,
CDCl3): δ = 7.26 (m, 4H, Ar-H), 5.42 (d, J = 9.2 Hz, 1H),
4.60 (dd, J = 10.4, 13.6 Hz, 1H), 4.48 (dd, J = 2.8, 13.2 Hz,
1H), 2.74 (bs, 1H, -OH), 2.36 (s, 3H, CH3). – HPLC con-
ditions: 85 : 15 hexane : i-PrOH, 0.5 mL min−1, 267 nm,
tminor = 19.8 min (R), tmajor = 24.5 min (S), 74% ee. –
[α]2D5 = +17.3 (c = 0.81, CH2Cl2).
PrOH, 1 mL min−1, 267 nm, tminor = 20.4 min (R), tmajor
=
25.5 min (S), 70% ee. – [α]2D5 = +28.0 (c = 0.50, CH2Cl2).
Acknowledgement
We are grateful to The Scientific and Technological Re-
search Council of Turkey (TUBITAK) for their financial sup-
(S)-1-(4-Ethylphenyl)-2-nitroethanol
Yellow oil, 60% yield. – 1H NMR (400 MHz, CDCl3): port (210T147). G. K. thanks TUBITAK for a postdoctoral
δ = 7.29 (m, 2H, Ar-H), 7.22 (m, 2H, Ar-H), 5.42 (m, fellowship.
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