New chiral CuII complexes and their catalytic activity in enantioselective Henry reaction

Article abstract of DOI:10.1007/s11172-016-1318-y

New chiral polydentante ligands capable of complexation of Cu²⁺ ions were synthesized using readily available derivatives of (S)-proline, d-glyceraldehyde, and imidazole as the starting materials. The synthesized complexes are efficient catalys

Full text of DOI:10.1007/s11172-016-1318-y

440
Russian Chemical Bulletin, International Edition, Vol. 65, No. 2, pp. 440—444, February, 2016
II
New chiral Cu complexes and their catalytic activity
in enantioselective Henry reaction
V. V. Veselovsky and M. V. Zlokazov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
4
7 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 ( 499) 135 5328. Eꢀmail: ves@ioc.ac.ru
New chiral polydentante ligands capable of complexation of Cu2+ ions were synthesized
using readily available derivatives of (S)ꢀproline, Dꢀglyceraldehyde, and imidazole as the startꢀ
ing materials. The synthesized complexes are efficient catalysts for enantioselective nitroaldol
condensation (the Henry reaction).
Key words: CuII chiral complexes, enantioselective synthesis, nitroaldol condensation.
Design of novel catalytic systems based on the copper
reaction affords hitherto unknown compounds 4—6 bearꢀ
ing additional nucleophilic centers. It should be emphaꢀ
sized that due to the presence of a free amino group in
imidazole 5, we succeeded in immobilization of this polyꢀ
dentate ligand on a surface of the modified polystyrene to
obtain modified resin 7.
Isopropylidene derivative of Dꢀglyceraldehyde 8 was
chosen as an alternative source of primary chirality. Conꢀ
densation of 8 with lithium derivative of 2ꢀmethylimidꢀ
azole 9 stereoselectively affords a mixture of stereoisomers
10 (10a : 10b ≈ 7 : 2), which can be easily resolved by chroꢀ
matography (Scheme 2). Acidic protolysis of the major
isomer 10a results in triol 11 possessing, apparently, enꢀ
hanced chelating ability due to the presence of three hyꢀ
droxy groups in addition to the imidazole moiety.
complexes with the various chiral ligands is one of the
actual trends in the development of modern homogeneous
enantioselective catalysis. This is due to the capability of
such copper complexes to catalyze aldol condensation,
the Michael addition, cycloadditions, and carbonylꢀene
reactions (see, for example, Ref. 1) widely used in the
2
synthesis of natural compounds. Earlier, starting from
(
S)ꢀ1,1ꢀdiphenylprolinol 1 we have synthesized two chiral
II
ligands, whose complexes with Cu was found to effiꢀ
ciently catalyze nitroaldol condensation (the Henry reacꢀ
tion). We report herein new results from our ongoing studꢀ
ies. In the present work, amino alcohol 1 was used as a
chiral component in the reductive amination involving
the known aldehydes 2 and 3 (Scheme 1). The studied
Scheme 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 0440—0444, February, 2016.
066ꢀ5285/16/6502ꢀ0440 © 2016 Springer Science+Business Media, Inc.
1

Chiral copper complexes
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 2, February, 2016
441
Scheme 2
Structures of compounds 4—7, 10, and 11 were conꢀ
firmed by spectral data and elemental analysis. The relaꢀ
tive (absolute) configurations of stereoisomers 10 were deꢀ
termined by Xꢀray diffraction analysis (Table 1). Taking
into account the crystallographic data and the known
and its product of proteolytic deprotection 11 was assigned
as (S) (Fig. 1). Consequently, the same center of the miꢀ
nor isomer 10b has (R)ꢀconfiguration.
The ability of compounds 4—6 and 10—11 to bind the
Cu2+ is indicated by the formation of dark blue solutions
after short sonication (10 min) of these substances with a
(
R)ꢀconfiguration of the isopropylidene moiety, the conꢀ
i
figuration of secondary hydroxy group of diastereomer 10a
small excess of Cu(OAc) •2H O in anhydrous Pr OH.
2
2
During this treatment, Cu(OAc) •2H O completely disꢀ
2
2
solves.* When modified polystyrene 7 is used, crystals
of copper acetate dissolve and the polymer particles change
their color to blue. Adding 4ꢀnitrobenzaldehyde 12
Table 1. Crystallographic characteristics, Xꢀray data collection,
and structure refinement statistics Rꢀ0458F7 for compound 10a
(
~10 mmol equiv.) and nitromethane (~100 mmol equiv.)
Parameter
Value
into these solutions (or suspension in the case of polymer
7) would induce nitroaldol condensation of the compoꢀ
nent to give nonꢀracemic nitroalcohol 13 (Scheme 3).
The yields and enantiomeric excesses of the reaction prodꢀ
ucts are summarized in Table 2.
Molecular formula
Molecular weight
T/K
Crystal system
Space group
Z (Z´)
a/Å
b/Å
c/Å
α/deg
C29H30N O3
2
379.48
110
Triclinic
–
P1
4 (2)
10.5470(11)
11.0226(12)
12.1351(13)
114.678(2)
106.106(2)
92.025(2)
1213.0(2)
1.269
Scheme 3
β/deg
γ/deg
V/Å3
dcalc/g cm
–
3
–
3
μ/cm
F(000)
θmax/deg
0.83
808
58
2
i
i. 4—6, 10, 11, Cu(OAc) •2H O, MeNO , Pr OH, ~20 °C.
2
2
2
Number of reflections
measured
independent (Rint
with I > 2σ(I)
Number of refined parameters
R1
wR2
GOOF
13869
11984 (0.0459)
10703
In summary, the obtained results (see Table 2) indiꢀ
cate that the more bulky chiral diphenylprolinol residue
(
effect than the more conformationally mobile chiral
moieties of ligands 10 and 11. The size of the substituents
more remote from the chiral centers affects the enantiꢀ
)
L, 4—6) exerts greater pronounced stereodifferentiation
634
0.0532
0.1232
1.048
Residual electron density,
0.339/–0.508
*
In the absence of compounds 4—6, 10 and 11,
–
3
e Å (dmax/dmin
)
i
Cu(OAc) •2H O is virtually insoluble in Pr OH.
2
2

4
42
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 2, February, 2016
Veselovsky and Zlokazov
C(4A)
N(3A)
C(5A)
N(1A)
C(18A)
C(19A)
O(1A)
C(2A)
C(14A)
C(31A)
C(17A)
C(6A)
C(13A)
C(21A)
C(16A)
C(7A)
C(10A)
C(15A)
C(26A)
C(8A)
C(27A)
C(22A)
O(3A)
C(20A)
O(2A)
C(23A)
C(29A)
C(9A)
C(28A)
C(11A)
C(25A)
C(24A)
C(12A)
Fig. 1. Geometry of one of the independent molecules of compound 10a. Nonhydrogen atoms are depicted at the 50% probability level.
Table 2. A comparison of nitroaldol condensation of
positive ion mode (the mass range 500—3000 Da), rate of the
nebulizer gas (nitrogen) flow was 4 L min– (180 °C). Optical
rotation was measured on a Jasco DIP polarimeter. Xꢀray difꢀ
fraction study of compound 10a were performed with a Bruker
SMART APEX2 diffractometer (MoꢀKα irradiation, graphite
monochromator, ω scan mode). The structure was solved by
direct method and refined anisotropically by full matrix least
squares on F2hkl. Hydrogen atoms of the hydroxy groups and
solvate water molecule were localized by a difference Fourier
synthesis, all other hydrogen atoms were placed in calculated
positions and refined using a riding model. Main crystallographꢀ
ic data and refinement parameters are given in Table 1. All
calculations were performed with a SHELXTL PLUS program
1
nitromethane and 4ꢀnitrobenzaldehyde in the
II
presence of complexes Cu •L
La
τ/hb
Y13 (%)c
ee (%)d
Entry
1
2
3
4
5
6
7
4
5
6
8
91
90
87
99
70
71
85
72 (R)
64 (R)
57 (R)
29 (R)
4 (R)
~0
24
20
8
90
90
60
7
10a
10b
11
2 (S)
3
package .
a
L is ligand.
τ is the reaction time.
Y is the yield of nitro alcohol 13.
Column chromatography was performed on Silica gel 60
b
c
(
40—60 μm, Fluka) if not stated otherwise. The R values were
f
measured using the precoated plates Silufol (Chemapol) and
Kieselgel F254 (Fluka). Products of nitroaldol condensation were
analyzed by HPLC (UV detection at 250 nm, elution with
d
Enantiomeric excess; the configuration of the major
isomer is given in the parenthesis.
i
–1
1
0 vol.% of Pr OH in hexane, flow rate of 1 mL min ) with
Kromasil 3 CelluCoat chiral stationary phase (a 4.6×150 mm
column). The retention times for (R)ꢀ13 and (S)ꢀ13 are ~12 and
oselectivity of the reaction in lesser extent (cf. entries 1
and 2).
~
15 min, respectively (cf. Ref. 2). Sonication was performed
with an ultrasonic bath UZVꢀ1/100ꢀTN. The solvents including
petroleum ether (b.p. 40—70 °C) were purified and dried followꢀ
ing the standard procedures.
Experimental
Melting points were measured on a Kofler apparatus.
IR spectra were recorded with a Bruker ALPHAꢀT spectrophoꢀ
tometer. H and C NMR spectra were run on Bruker ACꢀ200
Commercially
available
(Acros
Organics) 95%
NaBH(OAc) , 2ꢀmethylimidazole, and Merrifield resin (1.0—
3
1
13
–1
1.1 (mmol of Cl) g , 200—400 mesh) were used. (S)ꢀ1,1ꢀDipheꢀ
and Bruker AMꢀ300 instruments at 298 K in CDCl (if not indiꢀ
nylprolinol
1
(see Ref. 4), (1ꢀtritylꢀ1Hꢀimidazolꢀ2ꢀ
3
cated otherwise); the chemical shifts are given in the δ scale
relative to the residual solvent signal (δH 7.27 and δC 77.0). High
resolution electrospray ionization (ESI) mass spectra were reꢀ
corded with a Bruker micrOTOF II mass spectrometer at capilꢀ
lary voltage of 4.5 kV using direct inlet (via a syringe pump) with
MeOH as a solvent (a flow rate of 3 μL min–1) operating on a
yl)acetaldehyde 2 (see Ref. 5), (2S)ꢀ1ꢀbenzylpirrolidineꢀ2ꢀcarbꢀ
aldehyde 3 (see Ref. 6), and (4R)ꢀ2,2ꢀdimethylꢀ1,3ꢀdioxolaneꢀ
4ꢀcarbaldehyde 8 (see Ref. 7) were synthesized by the known
procedures. 2ꢀMethylꢀ1ꢀtritylꢀ1Hꢀimidazole 9 was synthesized
similarly to 4ꢀmethyl derivative following the earlier described
procedure.8

Chiral copper complexes
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 2, February, 2016
443
Diphenyl{(2S)ꢀ1ꢀ[2ꢀ(1ꢀtritylꢀ1Hꢀimidazolꢀ2ꢀyl)ꢀ
ethyl]pyrrolidinꢀ2ꢀyl}methanol (4). To a stirred solution of amiꢀ
no alcohol 1 (1.1 g, 4.34 mmol) and aldehyde 2 (1.8 g, 5.11 mmol)
in ClCH CH Cl (20 mL), 95% NaBH(OAc) (1.5 g, 6.72 mmol)
62.5, 62.6 (2 CHN); 71.8 (CHO); 125.4, 125.9, 126.0, 126.2,
126.8, 127.9, 128.1, 128.9, 147.99 (C ).
Ar
Modified polymer (7). A suspension of Merrifield resin (1.02 g,
1.02 equiv.), compound 5 (63 mg, 1.8 mmoL), and NaI (10 mg,
0.07 mmol) in MeCN (6 mL) was stirred at 80 °C for 60 h under
argon. The resin was collected by filtration and successively
2
2
3
was added at 20 °C under argon. The reaction mixture was stirred
at 20 °C for 5 h, treated with 1 M NaOH (30 mL), and extracted
t
with Bu OMe. The organic layer was washed with brine, dried
washed with MeCN (10 mL), MeCN—Et N (9 : 1, 2×10 mL),
3
with Na SO , and solvent was removed in vacuo. Recrystallizaꢀ
EtOH—Et N (9 : 1, 2×10 mL), EtOH (2×10 mL), and CH Cl
2
4
3
2
2
tion from MeOH afforded compound 4 in the yield of 1.87 g
(2×10 mL). Drying the resin at 80 °C under vacuum (2 Torr)
afforded polymer 7 in the yield of 1.32 g (96%). Found (%):
N, 3.71. Calculated (%): 4.20. IR (KBr), ν/cm– : 744, 906, 1027,
1066, 1154, 1180, 1267, 1363, 1448, 1491, 1601, 2852, 2922,
3024, 3082, 3423.
2
5
(
73%), coloress crystals, m.p. 183—185 °C, [α]D +2.4 (c 1.00,
1
CH Cl ). Found (%): C, 83.45; H, 6.67; N, 7.28. C H N O.
2
2
41 39
3
–
1
Calculated (%): C, 83.50; H, 6.67; N, 7.12. IR (CHCl ), ν/cm
:
3
6
2
1
67, 703, 782, 1002, 1034, 1128, 1209, 1448, 1493, 2807, 2874,
967, 3011, 3063, 3190, 3602, 3672. H NMR (300.13 MHz), δ:
1
(1S)ꢀ1ꢀ[(4R)ꢀ2,2ꢀDimethylꢀ1,3ꢀdioxolanꢀ4ꢀyl]ꢀ2ꢀ(1ꢀtritylꢀ
1Hꢀimidazolꢀ2ꢀyl)ethanol (10a) and (1R)ꢀ1ꢀ[(4R)ꢀ2,2ꢀdimethylꢀ
1,3ꢀdioxolanꢀ4ꢀyl]ꢀ2ꢀ(1ꢀtritylꢀ1Hꢀimidazolꢀ2ꢀyl)ethanol (10b).
To a stirred solution of 2ꢀmethylimidazole derivative 9 (5.3 g,
13.3 mmol) in THF (100 mL) chilled to –65 °C, 1.75 M BuLi in
hexane (10 mL, 17.5 mmol) was added dropwise over 10 min
under argon. The brown solution was stirred at –65 °C for
30 min, when a solution of aldehyde 8 (2.4 g, 18.3 mmol) in THF
(10 mL) was added within 5 min. After warming up to –30 °C, the
reaction mixture was neutralized by adding 5% aqueous citric
acid (50 mL). The aqueous layer was separated, extracted with
.12—1.86 (m, 6 H, 3 CH ); 1.94, 2.31, 2.59, 2.76 (all m, 1 H
2
each, 2 CH N); 3.71 (m, 1 H, HCN); 6.87 (br.s, 1 H, OH); 6.70,
2
6
.96 (both br.s, 1 H each, HC=); 7.03—7.60 (m, 25 H, H ).
Ar
{
(2S)ꢀ1ꢀ[2ꢀ(1HꢀImidazolꢀ2ꢀyl)ethyl]pyrrolidinꢀ2ꢀyl}ꢀ
diphenyl)methanol (5). A solution of compound 4 (200 mg,
.34 mmol) in 1 M HCl (5 mL) was heated at 80 °C for 4 h. The
(
0
precipitate (80 mg) was filtered off and washed with water.
The filtrate was concentrated in vacuo (2 Torr, 45 °C). The
residue was dried under vacuum (40 °C, 2 Torr) for 1 h and
dissolved in MeOH (3 mL). The solution was treated with K CO3
2
t
(
200 mg, 1.45 mmol) and the mixture was stirred for 2 h. The
Bu OMe, the organic phase was washed with brine, dried with
reaction mixture was diluted with AcOEt (5 mL), filtered through
a short SiO layer, and the SiO pad was washed with AcOEt—
Na SO , and the solvent was removed in vacuo. After column
2
4
chromatography on SiO (70 g) using gradient elution from peꢀ
2
2
2
MeOH, 1 : 1. Removal of the solvent afforded compound 5 in
the yield of 95 mg (81%), colorless crystals, m.p. 204—205 °C
(
troleum ether to EtOAc, the following compounds were isolatꢀ
ed, in order of elution: isomer 10a (2.12 g, 35%) and isomer 10b
(0.6 g, 10%).
AcOEt—MeOH), Rf 0.68 (AcOEt—MeOH, 2 : 1), [α]D22
+
100.5 (c 1.00, MeOH). MS (ESI), m/z: found 348.2072 and
Alcohol 10a. R 0.89 (EtOAc), colorless crystals, m.p. 133—
f
+
25
3
70.1887. Calculated for C H N O, [M + H] , 348.2070;
135 °C (diethyl ether—hexane), [α]D +4.34 (c 1.00, CH Cl ).
2
9
34
2
2
2
+
–1
[
M + Na] 370.1890. IR (KBr), ν/cm : 703, 752, 767, 873,
MS (ESI), m/z: found 477.2145. Calculated for C H N O ,
29 30 2 3
+
–1
1
2
2
032, 1130, 1164, 1303, 1360, 1447, 1589, 2681, 2812, 2894,
961, 3030, 3061, 3377, 3443. H NMR (300.13 MHz), δ: 1.59—
.02 (m, 4 H, 2 CH ); 2.28—2.80, 3.26 (m, 6 H, 2 CH N,
[M + Na] , 477.2149. IR (KBr), ν/cm : 640, 703, 747, 758,
1
858, 1059, 1134, 1171, 1209, 1267, 1367, 1406, 1447, 1492, 2820,
1
2873, 2901, 2934, 2983, 3056, 3205, 3301, 3321, 3503. H NMR
2
2
CH C=); 3.94 (dd, 1 H, HCN, J = 9.0 Hz, J = 4.1 Hz); 5.34 (br.s,
(200.13 MHz), δ: 1.14, 1.22 (both s, 3 H each, 2 Me); 1.96 (dd,
1 H, HCC=, J = 16.4 Hz, J = 9.2 Hz); 2.19 (dd, 1 H, HCC=, J =
= 16.4 Hz, J = 2.5 Hz); 3.45 (ddd, 1 H, HCOH, J = 9.2 Hz, J =
= 6.5 Hz, J = 2.5 Hz); 3.67 (dd, 1 H, HCCO, J = 7.8 Hz, J = 5.1 Hz);
3.79 (m, 1 H, HCO); 3.80 (dd, 1 H, H´CCO, J = 7.8 Hz, J = 6.1 Hz);
6.75 (d, 1 H, HC=, J = 1.5 Hz); 6.93 (d, 1 H, HC=, J = 1.5 Hz);
2
1
H, OH); 6.87 (br.s, 2 H, 2 HC=); 7.07—7.81 (m, 15 H, HAr).
(2S)ꢀ1ꢀ{[(2S)ꢀ1ꢀBenzylpyrrolidinꢀ2ꢀyl]methyl}pyrrolidinꢀ2ꢀ
yl)(diphenyl)methanol (6). To a stirred solution of amino alcohol
(253 mg, 1.03 mmol) and aldehyde 3 (230 mg, 1.22 mmol) in
ClCH CH Cl (4 mL), 95% NaBH(OAc) (0.35 g, 1.57 mmol)
(
1
2
2
3
was added at 20 °C under argon. The reaction mixture was stirred
at 20 °C for 3 h, poured into 1 M NaOH (10 mL), and extracted
with Bu OMe. The organic layer was separated, washed with
7.13 (m, 5 H, H ); 7.34 (m, 10 H, HAr).
Ar
Alcohol 10b. R 0.73 (EtOAc), colorless crystals, m.p. 177—
f
t
25
179 °C (diethyl ether—hexane), [α]D –2.96 (c 1.00, CH Cl ).
2
2
brine, dried with Na SO , and the solvent was removed in vacuo.
MS (ESI), m/z: found 477.2150. Calculated for C H N O ,
29 30 2 3
[M + H] , 477.2145. IR (KBr), ν/cm : 640, 704, 752, 859, 880,
2
4
+
–1
Column chromatography on Al O (5/40 μm, L, neutral, from
2
3
t
CHEMAPOL) using elution with petroleum ether—Bu OMe
9 : 1) afforded compound 6 in the yield of 290 mg (68%), oil,
R 0.75 (petroleum ether—Bu OMe 2 : 1, Aluminumoxide 60 Typ
E, Merck), [α]D –92.1 (c 1.00, CH Cl ). MS (ESI), m/z: found
27.2742. Calculated for C H N O, [M + H] , 427.2744.
29 34 2
1074, 1133, 1231, 1378, 1458, 1492, 2871, 2907, 2934, 3058,
1
(
3280. H NMR (200.13 MHz), δ: 1.19, 1.25 (both s, 3 H each,
t
2 Me); 1.95 (m, 2 H, H CC=); 3.22 (dd, 1 H, HCO, J = 8.0 Hz,
f
2
2
5
J = 7.0 Hz); 3.48 (dd, 1 H, HCCO, J = 12.2 Hz, J = 6.0 Hz);
3.60 (m, 1 H, HCO); 3.82 (dd, 1 H, H´CCO, J = 12.2 Hz, J =
= 6.1 Hz); 4.97 (br.s, 1 H, OH); 6.75 (d, 1 H, HC=, J = 1.3 Hz);
2
2
+
4
–
1
IR (KBr), ν/cm : 699, 704, 746, 1032, 1117, 1372, 1450, 1493,
598, 2800, 2871, 2921, 2963, 3027, 3060, 3330. H NMR (300.13
1
1
6.95 (d, 1 H, H´C=, J = 1.3 Hz); 7.13 (m, 5 H, H ); 7.35 (m,
Ar
MHz), δ: 1.18—1.91 (m, 8 H, 4 CH ); 2.00, 2.13 (both m, 1 H
10 H, HAr).
2
each, CH N); 2.30 (m, 4 H, 2 CH N); 2.52, 2.70 (both m, 1 H
(2R,3S)ꢀ4ꢀ(1HꢀImidazolꢀ2ꢀyl)butaneꢀ1,2,3ꢀtriol (11). A soꢀ
lution of compound 10a (2.78 g, 6.14 mmol) in 1 M HCl (50 mL)
was heated at 80 °C for 4 h. After cooling to 20 °C, the precipiꢀ
tate was filtered off and washed with water. The filtrate was
concentrated in vacuo (2 Torr, 50 °C). The residue was dried
in vacuo (2 Torr, 40 °C, 1 h), dissolved in MeOH (30 mL) folꢀ
2
2
each, CH N); 3.19 (m, 1 H, HCN); 3.37 (d, 1 H, H´CPh, J =
2
=
13.1 Hz); 3.77 (d, 1 H, HCPh, J = 13.1 Hz); 3.88 (dd, 1 H,
NCH—CO, J = 8.7 Hz, J = 4.2 Hz); 4.88 (br.s, 1 H, OH); 7.15,
1
3
7
2
.26, 7.54, 7.56 (all m, 15 H, HAr). C NMR (75.03 MHz), δ:
2.8, 24.5, 28.9, 29.3 (4 CH ); 54.3, 55.9, 59.5, 61.8 (4 CH N);
2
2

4
44
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 2, February, 2016
Veselovsky and Zlokazov
lowed by addition of K CO (2.49 g, 18 mmol). The reaction
mixture was stirred at 20 °C for 1 h, diluted with AcOEt (30 mL),
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 13ꢀ03ꢀ00197).
2
3
and filtered through a short SiO layer (elution with AcOEt—
2
MeOH (1 : 1)). Removal of the solvent in vacuo and silica gel
column chromatography of the residue (gradient elution from
References
CHCl —EtOH (1 : 1) to EtOH) afforded triol 11 in the yield of
3
0
.7 g (66%), resinous substance, R 0.68 (EtOAc—MeOH, 2 : 1),
1. (a) J. S. Johnson, D. A. Evans, Acc. Chem. Res., 2000, 33, 325;
(b) B. L. Feringa, R. Naasz, R. Imbos, L. A. Arnold, in Modꢀ
ern Organocopper Chemistry, Ed. N. Krause, WileyꢀVCH, Ltd,
Weinheim, 2002, 224—258; (c) A. S. E. Karlström, J.ꢀE. Bäckꢀ
vall, ibid. 259—288; (c) G. Evano, N. Blanchard, M. Toumi,
Chem. Rev., 2008, 108, 3054; (d) Tetrahedron Symposiumꢀinꢀ
Print Number 157, New Trends in Enantioselective Catalysis
with Copper (I), Ed. O. Riant, Tetrahedron, 2012, 68, 3385.
2. V. V. Veselovsky, A. V. Stepanov, Russ. Chem. Bull. (Int. Ed.),
2014, 63, 422 [Izv. Akad. Nauk, Ser. Khim., 2014, 422].
3. G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr.,
2008, 64, 112.
f
2
2
[
α]D –23.65 (c 1.00, MeOH). MS (ESI), m/z: found 173.0923,
+
1
calculated for C H N O , [M + H] , 173.0921. H NMR
7
12
2
3
(
200.13 MHz), δ: 2.65 (dd, 1 H, HCC=, J = 15.0 Hz, J = 8.6
Hz); 2.95 (dd, 1 H, H´CC=, J = 15.0 Hz, J = 3.5 Hz); 3.24—
.81 (m, 4 H, HCO); 6.39 (br.s, 1 H, OH); 6.90 (br.d, 2 H,
3
HC=, J = 1.5 Hz).
Nitroaldol condensation. A. A mixture of a ligand (0.10 mmol),
i
Cu(OAc) •2H O (21 mg, 0.11 mmol), and anhydrous Pr OH
2
2
(
1.5 mL) was sonicated for 10 min to give dark blue solution.
Then 4ꢀnitrobenzaldehyde 12 (152 mg, 1.0 mmol) and MeNO2
610 mg, 10 mmol) were added. The reaction mixture was mainꢀ
(
tained at 20 °C for the time specified in Table 2 until complete
consumption of aldehyde 12 (TLC monitoring), then the solvent
was removed in vacuo. Silica gel column chromatography of the
4. K. Nakano, K. Nozaki, T. Hiyama, J. Am. Chem. Soc., 2003,
125, 5501.
5. J. A. MartinezꢀPerez, M. A. Pickel, E. Caroff, W.ꢀD. Wogꢀ
gon, Synlett, 1999, 1875.
residue (elution with CHCl ) afforded compound 13.
3
B. A mixture of polymer 7 (129 mg, ~0.1 equiv., ~10 mol.%),
6. C. J. Deur, M. W. Miller, L. S. Hegedus, J. Org. Chem., 1996,
61, 2871.
i
Cu(OAc) •2H O (22 mg, 0.11 mmol), and Pr OH (1.5 mL) was
2
2
sonicated for 10 min and the resulting colored suspension was
7. C. H. Sugisaki, Y. Ruland, M. Baltas, Eur. J. Org. Chem.,
2003, 672.
treated with MeNO (610 mg, 10 mmol, 0.54 mL) and 4ꢀniꢀ
2
trobenzaldehyde (151 mg, 1 mmol). The reaction mixture was
stirred for 8 h until complete consumption of the starting aldeꢀ
hyde (TLC monitoring). The resin was filtered off, washed with
8. D. P. Davis, K. L. Kirk, L. A. Cohen, J. Heterocyclic Chem.,
1982, 19, 253.
CHCl , and the solvent was removed in vacuo. Silica gel column
3
chromatography of the residue (elution with CHCl ) afforded
Received October 8, 2015;
3
nitroalcohol 13 in the yield of 210 mg (85%).
in revised form November 2, 2015