Polydentate chiral heteroorganic ligands/catalysts - Impact of particular functional groups on their activity in selected reactions of asymmetric synthesis

Article abstract of DOI:10.1016/j.tetasy.2013.08.012

The influence of each functional group in enantiomerically pure ligands 1, bearing a hydroxy moiety, a stereogenic sulfinyl group and an enantiomeric amine moiety, on ligand catalytic efficiency in enantioselective nitroaldol (Henry) reactions was investi

Full text of DOI:10.1016/j.tetasy.2013.08.012

Tetrahedron: Asymmetry 24 (2013) 1417–1420
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Polydentate chiral heteroorganic ligands/catalysts—impact
of particular functional groups on their activity in selected
reactions of asymmetric synthesis
a,
⇑
b
a
b
Piotr Kiełbasi n´ ski , Michał Rachwalski , Sylwia Kaczmarczyk , Stanisław Le s´ niak
a
Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Heteroorganic Chemistry, Sienkiewicza 112, 90-363 Łód ´z , Poland
University of Łód ´z , Faculty of Chemistry, Department of Organic and Applied Chemistry, Tamka 12, 91-403 Łód ´z , Poland
b
a r t i c l e i n f o
a b s t r a c t
Article history:
The influence of each functional group in enantiomerically pure ligands 1, bearing a hydroxy moiety, a
stereogenic sulfinyl group and an enantiomeric amine moiety, on ligand catalytic efficiency in enantiose-
lective nitroaldol (Henry) reactions was investigated by subsequent transformation and/or protection of
these groups. It was found that, although the absolute configuration of the amine moiety exerted a deci-
sive influence on the stereochemical outcome of the reaction, the presence of the sulfinyl group was cru-
cial. The hydroxy group could be replaced by a second enantiomeric amine moiety, but in order to achieve
high catalytic activity of the ligand, it was necessary to retain the sulfinyl moiety in its molecule. This
clearly indicated that the simultaneous presence of three coordinating centres was essential for the effi-
ciency of the catalysts and allowed us to conclude that the original ligands 1 demonstrated a tridentate
character.
Received 1 August 2013
Accepted 27 August 2013
Available online 27 September 2013
Ó 2013 Elsevier Ltd. All rights reserved.
1
. Introduction
Over the course of our studies, we have developed a strategy for
HO
B
O
the synthesis of chiral polydentate catalysts/ligands 1 with three
functional groups: a stereogenic sulfinyl group, a hydroxy group
and an amino group bearing an additional stereogenic centre on
a carbon atom (Fig. 1).1 The strategy comprised of an initial
enzyme-promoted desymmetrization of a prochiral bis-hydroxy
sulfoxide, followed by subsequent introduction of a chiral amine
moiety. These ligands/catalysts were found to very efficiently
catalyse various enantioselective reactions of asymmetric
carbon–carbon bond formation. Thus, the catalysts with chiral
S
1
B:
H3C
H
C
NH
H
H3C NH
C
H
H3C
CH3
NH
acyclic amine moieties (ꢀ)-(S)- and (+)-(R)-1-phenylethylamine
a: (-)-(S)
b: (+)-(R)
c: (-)-(S)
e
0
d: (+)-(R)
1
a,b, (ꢀ)-(S)- and (+)-(R)-1-(1 -naphthyl)-ethylamine 1c,d turned
out to be particularly useful in the stereoselective nitroaldol
Henry), aza-Henry, aldol4 and Mannich5 reactions, while those
2
3
Pri
H
Me
H
(
bearing chiral enantiomeric aziridinyl substituents 1f–h were
H
Pri
N
N
N
useful for the enantioselective diethylzinc and phenylethynylzinc
additions to aldehydes6 and enantioselective conjugate Michael
,7
g
h
additions of diethylzinc to enones.8
f
Since there has always been some uncertainty about the real
contribution of particular functional groups to the activity of the
catalysts, we decided to study this matter in detail. Some initial at-
tempts were made during the investigations of the application of
Figure 1.
our catalysts in stereoselective Mannich reactions and clearly indi-
cated the importance of each moiety for the stereochemical effi-
5
ciency of this transformation. In order to gain
a better
understanding into the problem, we extended our studies into
another carbon–carbon bond forming reaction, the stereoselective
⇑
Corresponding author. Tel.: +48 42 6815832; fax: +48 42 6803261.
E-mail address: piokiel@cbmm.lodz.pl (P. Kiełbasi n´ ski).
0
957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.08.012

1
418
P. Kiełbasi n´ ski et al. / Tetrahedron: Asymmetry 24 (2013) 1417–1420
nitroaldol (Henry) reaction. Herein we report our results and com-
pare them with those obtained for the Mannich reaction.
were synthesized, in which the functional groups were subse-
quently transformed and/or protected. As this basis, ligand 1d
0
bearing a (+)-(R)-1-(1 -naphthyl)ethylamine moiety was used. All
of the ligands are shown in Figure 2. In the first row, the hydroxy
2
. Results and discussion
In one of our previous papers, we described the results of the
group was either acetylated to give 4, or replaced with the next
2
0
(
+)-(R)-1-(1 -naphthyl)ethylamine group to give 5. The second
row represents the analogues in which the sulfinyl moiety was
reduced to the sulfenyl group and the hydroxy group in the parent
compound 6 thus formed was treated as above to give the acety-
lated analogue 7 and the diamino derivative 8. Finally, the last
row shows the analogues, in which the sulfinyl moiety was
oxidized to the sulfonyl group and the hydroxy group was treated
as above, to give compounds 9, 10 and 11, respectively. It should be
noted that derivatives 6–11 are deprived of the stereogenic centre
at the sulfur atom and in compound 5 the sulfinyl moiety is not a
stereogenic centre anymore due to the presence of two identical
amine substituents.
application of a series of catalysts 1 in asymmetric Henry reactions.
In this context it should be mentioned that this reaction has
recently attracted a great deal of attention from researchers, diffi-
9
cult to summarize in one publication, which stems from the fact
that the reaction products, enantiomerically pure (or at least
enriched) 2-nitroalcohols can be easily transformed into valuable
chiral building blocks via appropriate transformations of both the
hydroxy and nitro groups. The asymmetric Henry reaction relies
upon the aldol-type addition of a nitroalkane to an aldehyde,
performed in the presence of metal complexes with chiral ligands.
Among the ligands, a variety of chiral amine derivatives have
been applied, including diamides10 and those based on chiral
All of the ligands were applied as catalysts in the asymmetric
Henry reaction, in which benzaldehyde was used as a model
reagent. The results are shown in Table 1.
1
1
12
diamines, trans-1,2-diaminocyclohexane, bis-oxazolines, oxaz-
1
3a
13b
14
olidines,
imidazolidines,
aziridines and chiral biaryl-based
1
5
Inspection of Table 1 indicates that the modification of the
catalysts had a considerable impact on the outcome of the reaction.
Thus, protection of the hydroxy group or removal of the stereogen-
ic centre at the sulfur atom significantly lowered both the yield and
enantiomeric excess of the product (entries 2 and 4–9). This may
be taken as proof that the combination of the free hydroxy group
and the stereogenic sulfinyl moiety constitutes as an essential
condition for the catalytic efficiency of the ligands in spite of the
fact that the main stereocontrol is exerted by the stereogenic
centre located on the amine moiety (cf. Scheme 1). Interestingly,
replacement of the hydroxy group by the chiral amine moiety, to
produce the diamino derivative 5, caused an enhancement in the
chemical yield and the stereoselectivity of the chiral Henry product
bis(thiourea). Although the use of copper diacetate as the metal
component seems to be most common, other metal salts have also
1
6
been applied.
Recently, sterically modified salenchromium
complexes have been successfully applied as catalysts to give
2
-nitroalcohols with ee’s of up to 94%.17
In our case, the best results were obtained when ligands bearing
the 1-(1’-naphthyl)ethylamine moiety, 1c and 1d, were used. The
absolute configuration at the amine moiety had a decisive impact
on the absolute configuration of the product (Scheme 1).
ligand, Cu(OAc)2
EtOH, rt
OH
C
O
H
R
C
+
MeNO2
R
CH2NO2
H
(
entry 3). Since the absolute configuration of both amino moieties
2
3
in 5 is the same, the sulfinyl group is no longer a stereogenic
centre, which again proves the decisive role played by the
stereogenic centre located in the amine part of the catalyst. This
led us to conclude that the diamine catalyst is more efficient than
amino alcohols in the asymmetric Henry reaction. However,
Scheme 1.
In order to check the influence of each functional group present
in the ligands on their catalytic efficiency, a series of analogues
Me
Np
Me
Np
Np
Me
Me
Np
HO
NH
AcO
NH
HN
NH
O
O
O
S
S
S
1
d
4
5
Me
Np
Me
Np
Np
Me
Me
Np
HO
NH
AcO
NH
HN
NH
S
S
S
6
7
8
Me
Np
Me
Np
Me
Np
Me
Np
HO
NH
AcO
NH
HN
NH
O
O
S
O
S
S
O
O
O
9
10
11
Figure 2.

P. Kiełbasi n´ ski et al. / Tetrahedron: Asymmetry 24 (2013) 1417–1420
1419
Table 1
Nitroaldol (Henry) reaction with benzaldehyde 2 (R = Ph) using various catalysts
600 MHz and 151 MHz, respectively, with CDCl
as the solvent
3
and relative to TMS as the internal standard. Data are reported as
s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet,
b = broad. Optical rotations were measured on a Perkin-Elmer
Entry
Ligand
Product 3
ee (%)
rt
D
Yield (%)
½aꢁ
Absol. conf.
2
1
41 MC polarimeter with a sodium lamp at room temperature (c
). Column chromatography was carried out using Merck 60 silica
1
2
3
4
5
6
7
8
9
1d2
4
5
6
7
8
9
10
11
87
62
95
71
58
74
59
43
62
ꢀ22.0
ꢀ13.3
ꢀ22.0
ꢀ14.6
ꢀ11.5
ꢀ15.6
ꢀ11.7
ꢀ9.2
98
59
98
65
51
70
52
41
58
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
gel. TLC was performed on Merck 60 F254 silica gel plates. Visuali-
zation was accomplished with UV light (254 nm). The enantio-
meric excess (ee) values were determined by chiral HPLC
(
Knauer, Chiralcel OD).
4
.2. Synthesis of catalysts 1d, 4, 5, 6 and 9
ꢀ13.1
Chiral enantiopure catalysts 1d, 4, 5, 6 and 9 were synthesized
according to the procedures described previously.
ligands 8 and 11, which bear two identical amino substituents but
are deprived of the sulfinyl moiety, turned out to be inefficient as
catalysts (entries 6 and 9). This is most probably due to the partic-
ular coordinating ability of the sulfinyl group. These results al-
lowed us to assume that the original catalysts 1 have a tridentate
character since all three coordinating centres must simultaneously
be present to make them efficient. These findings are in full agree-
ment with our previous investigations concerning the influence of
the coordinating centres on the efficiency of the catalysts in the
asymmetric Mannich reaction.5
Nevertheless, since catalyst 5 exhibited the highest efficiency in
terms of chemical yield and the enantiomeric excess of the prod-
ucts of the Henry reaction, we decided to determine the scope of
its applicability to other aldehydes. The results are collected in
Table 2. As can be seen, the diamino ligand 5 turned out to be a ver-
satile catalyst in the reaction discussed and proved to be efficient
in the stereoselective transformation of both aryl and alkyl
aldehydes.
1,5
4
.3. Synthesis of catalysts 7 and 8
Catalysts 7 and 8 were synthesized starting from compounds 4
and 5, respectively, using a procedure described by Drabowicz and
18
Oae. A round-bottomed flask was charged with acetone (3 mL),
catalyst
.16 mmol). The flask was immersed in an ice bath (0 °C) and an
acetone solution of trifluoroacetic anhydride (264 mg, 1.25 mmol,
.175 mL) was slowly added with stirring. After 0.5 h, TLC showed
4 or 5 (0.48 mmol) and sodium iodide (174 mg,
1
0
the completion of the reduction of sulfoxide. After acetone was
evaporated, water was added and the mixture was extracted with
diethyl ether (7 mL). The ether extract was washed with sodium
thiosulfate solution and water. Upon evaporation of the ether from
the dried extract, virtually pure sulfides 7 and 8 were obtained.
Final purification was accomplished by filtration through a short
silica gel column with hexane as eluent to yield 7 (0.137 g, 65%)
and 8 (0.183 g, 69%) as yellow oils.
Table 2
Nitroaldol (Henry) reaction with various aldehydes using catalyst 5
4
.4. Catalyst 7
Entry
Aldehyde 2
R
Product 3
ee (%)
rt
D
); 1H NMR (CDCl
): d = 1.38 (d,
3 3
rt
D
Yield (%)
½
aꢁ
Absol. conf.
½
a
ꢁ
¼ ꢀ17:4 (c 1, CHCl
J = 6.2 Hz, 3H), 1,68 (br s, 1H), 1.87 (s, 3H), 3.75 (s, 2H), 4.52 (s,
2H), 4.60 (q, J = 6.2 Hz, 1H), 6.80–6.86 (m, 2H), 7.20–7.30 (m,
1
2
3
4
5
6
C
6
H
5
95
92
94
91
84
90
ꢀ22.0
ꢀ46.5
98
97
93
92
90
94
(R)
(R)
(R)
(R)
(R)
(R)
o-MeOC
o-NO
o-ClC
CH
6 4
H
2
C
H
6 4
+235.7
ꢀ53.4
+15.0
ꢀ9.3
6H), 7.33–7.45 (m, 10H), 7.65–7.72 (m, 2H), 7.82–7.88 (m, 2H);
6
H
4
13
C NMR (CDCl
3
3 3
): d = 22.8 (CH ), 27.2 (CH ), 46.2 (CH), 51.2
C
6
H
4
2 2
CH
(CH
2
N), 59.7 (CH
2
O), 122.3 (Car), 124.5 (Car), 125.2 (Car), 125.7
n-Bu
(C
ar), 126.1 (Car), 126.5 (Car), 127.1 (Car), 127.8 (Car), 128.6 (Car),
1
29.1 (Car), 129.6 (Car), 130.3 (Car), 130.8 (Car), 133.4 (Car), 133.8
3
. Conclusion
Modification of chiral ligands containing a hydroxy moiety and
(
(
(
C
C
ar), 134.7 (Car), 136.3 (Car), 140.1 (C
q ar), 141.2 (Cq ar), 141.9 (Cq ar), 170.1 (C@O); MS (CI): m/z 442
M + H); HRMS (CI): calcd for C28 27NO S: 441.1267; found
q q
ar), 140.4 (C ar), 140.9
H
2
two stereogenic centres, one located on the sulfinyl sulfur atom,
and the other on the carbon atom in the enantiomeric amine moi-
ety, led us to the conclusion that the simultaneous presence of
these three coordinating centres is essential for their efficiency as
catalysts for enantioselective nitroaldol (Henry) reactions. The ste-
reogenic centres located in the amine moieties were found to have
a decisive influence on the absolute configuration of the products.
Replacement of the hydroxy moiety with a second enantiomeric
amine gave ligands, which exhibited the highest catalytic effi-
ciency provided that the sulfinyl group was retained in the
molecule.
4
41.1258.
4
.5. Catalyst 8
rt
D
); 1H NMR (CDCl
): d = 1.46 (d,
3 3
½
a
ꢁ
¼ ꢀ55:1 (c 1, CHCl
J = 6.5 Hz, 6H), 1.75 (br s, 2H), 3.87 (AB, J = 13.4 Hz, 4H), 4.64 (q,
J = 6.5 Hz, 2H), 6.84–6.86 (m, 2H), 7.24–7.32 (m, 6H), 7.38–7.49
1
3
(
m, 10H), 7.70–7.76 (m, 2H), 7.88–7.89 (m, 2H); C NMR (CDCl
3
):
d = 23.6 (2CH ), 50.2 (2CH), 53.2 (2CH N), 122.9 (2Car), 123.0 (2Car),
3
2
1
1
1
25.2 (2Car), 125.6 (2Car), 127.2 (2Car), 128.4 (2Car), 128.8 (2Car),
29.4 (2Car), 130.6 (2Car), 131.3 (2Car), 131.5 (2Car), 132.3 (2Car),
33.2 (2Car), 133.9 (2Car), 134.0 (2Car), 134.8 (2Car), 135.6 (4Cq ar),
4
4
. Experimental
.1. General
140.8 (2C
q
ar), 142.1 (2C
q
ar), 143.6 (2C
q
ar); MS (CI): m/z 553
(
M+H); HRMS (CI): calcd for C38H N
36 2
S: 552.1389; found 552.1387.
4
.6. Synthesis of the catalysts 10 and 11
Unless otherwise specified, all reagents were purchased from
1
commercial suppliers and used without further purification.
H
Catalysts 10 and 11 were synthesized starting from the com-
pounds 4 and 5, respectively. Catalyst 4 or 5 (0.24 mmol) was dis-
1
3
and C NMR spectra were recorded on a Bruker instrument at

1
420
P. Kiełbasi n´ ski et al. / Tetrahedron: Asymmetry 24 (2013) 1417–1420
solved in dry dichloromethane (10 mL) after which MCPBA (0.17 g,
.98 mmol) was added and the solution was stirred for 24 h at
room temperature. After this time, the reaction mixture was
washed with 5% aqueous Na CO , extracted with dichloromethane
and dried over anhydrous MgSO . After evaporation of the solvent
nents were evaporated and the crude product was purified by col-
umn chromatography (chloroform). All spectroscopic data of the
Henry adducts were in good agreement with those reported
0
2
2
3
earlier.
4
the crude mixture was purified via column chromatography on sil-
ica gel using a mixture of ethyl acetate with hexane (in gradient) to
afford the corresponding sulfones 10 (0.097 g, 85%) and 11
Acknowledgments
Financial support by the Polish Ministry of Science and Higher
Education, Grant no. N N204 131140 for P.K., is gratefully
acknowledged.
(
0.110 g, 78%) as colourless oils.
4
.7. Catalyst 10
References
rt
D
1
½
a
ꢁ
¼ ꢀ6:1 (c 1, CHCl
3 3
); H NMR (CDCl ): d = 1.97 (s, 3H), 1.98
1.
Rachwalski, M.; Kwiatkowska, M.; Drabowicz, J.; Kłos, M.; Wieczorek, W. M.;
Szyrej, M.; Siero n´ , L.; Kiełbasi n´ ski, P. Tetrahedron: Asymmetry 2008, 19, 2096–
(
(
d, J = 6.9 Hz, 3H), 5.21 (q, J = 6.9 Hz, 1H), 5.33 (s, 4H), 7.44–8.13
m, 15H); C NMR (CDCl
1
3
3
): d = 23.5 (CH
3 3
), 28.6 (CH ), 47.4 (CH),
2101.
5
1
2.8 (CH
2
N), 60.6 (CH
2
O), 122.8 (Car), 125.2 (Car), 125.9 (Car),
2. Rachwalski, M.; Le s´ niak, S.; Sznajder, E.; Kiełbasi n´ ski, P. Tetrahedron:
Asymmetry 2009, 20, 1547–1549.
26.1 (Car), 126.9 (Car), 127.1 (Car), 127.8 (Car), 128.2 (Car), 129.2
ar), 129.8 (Car), 130.5 (Car), 131.1 (Car), 131.9 (Car), 134.3 (Car),
34.9 (Car), 135.7 (Car), 136.9 (Car), 140.9 (C
41.9 (Cq ar), 142.6 (C q ar), 143.2 (Cq ar), 170.8 (C@O); MS (CI): m/
27NO S: 473.1398; found
3.
Rachwalski, M.; Le s´ niak, S.; Kiełbasi n´ ski, P. Tetrahedron: Asymmetry 2011, 22,
087–1089.
4. Rachwalski, M.; Le s´ niak, S.; Kiełbasi n´ ski, P. Tetrahedron: Asymmetry 2011, 22,
325–1327.
(C
1
1
1
q q
ar), 141.1 (C ar),
1
5.
Rachwalski, M.; Leenders, T.; Kaczmarczyk, S.; Kiełbasi n´ ski, P.; Le s´ niak, S.;
z 474 (M+H); HRMS (CI): calcd for C28
H
4
Rutjes, F. P. J. T. Org. Biomol. Chem. 2013, 11, 4207–4213.
4
73.1386.
6. Le s´ niak, S.; Rachwalski, M.; Sznajder, E.; Kiełbasi n´ ski, P. Tetrahedron:
Asymmetry 2009, 20, 2311–2314.
7
8
9
.
.
.
Rachwalski, M.; Le s´ niak, S.; Kiełbasi n´ ski, P. Tetrahedron: Asymmetry 2010, 21,
687–2689.
Rachwalski, M.; Le s´ niak, S.; Kiełbasi n´ ski, P. Tetrahedron: Asymmetry 2010, 21,
4
.8. Catalyst 11
2
rt
D
); 1H NMR (CDCl
): d = 1.64 (d,
3 3
½
a
ꢁ
¼ ꢀ36:1 (c 1, CHCl
1890–1892.
For reviews see (a) Palomo, C.; Oiarbide, M.; Laso, A. Eur. J. Org. Chem. 2007,
J = 6.7 Hz, 6H), 1.78 (br s, 2H), 4.09–4.18 (m, J = 13.4 Hz, 4H), 5.68
2561–2574; (b) Boruwa, J.; Gogoi, N.; Saikia, P. P.; Barua, N. C. Tetrahedron:
(
(
(
(
(
(
q, J = 6.7 Hz, 2H), 6.85–8.05 (m, 22H); 13C NMR (CDCl
2CH ), 50.8 (2CH), 54.1 (2CH N), 123.7 (2Car), 124.1 (2Car), 125.9
2Car), 126.3 (2Car), 127.8 (2Car), 128.9 (2Car), 129.4 (2Car), 130.1
2Car), 130.9 (2Car), 131.8 (2Car), 132.6 (2Car), 133.4 (2Car), 133.9
2Car), 134.5 (2Car), 135.2 (2Car), 135.9 (2Car), 136.8 (4Cq ar), 141.4
3
): d = 24.3
Asymmetry 2006, 17, 3315–3326. for selected recent publications see; (c)
Thorat, P. B.; Goswami, S. V.; Jadhav, W. N.; Bhusare, S. R. Aust. J. Chem. 2013, 66,
3
2
6
61–666; (d) Bania, K. K.; Karunakar, G. V.; Goutham, K.; Deka, R. C. Inorg.
Chem. 2013, 52, 8017–8029; (e) Lang, K.; Park, J.; Hong, S. Angew. Chem., Int. Ed.
012, 51, 1620–1624.
10. Nitabaru, T.; Kumagai, N.; Shibasaki, M. Tetrahedron Lett. 2008, 49, 272–276.
2
1
1. Kowalczyk, R.; Sidorowicz, Ł.; Skar z_ ewski, J. Tetrahedron: Asymmetry 2008, 19,
310–2315. and references therein.
2C
q
ar), 142.8 (2C
q
ar), 144.4 (2C
q
ar); MS (CI): m/z 585 (M + H);
2
36 2 2
HRMS (CI): calcd for C38H N O
S: 584.1376; found 584.1379.
1
2. (a) Evans, D. A.; Seidel, D.; Rueping, M.; Lam, H. W.; Shaw, J. T.; Downey, C. W. J.
Am. Chem. Soc. 2003, 125, 12692–12693; (b) Mao, J.; Nie, X.; Wang, M.; Wang,
Q.; Zheng, B.; Bian, Q.; Zhong, J. Tetrahedron: Asymmetry 2012, 23, 965–971.
3. (a) Liu, S.; Wolf, C. Org. Lett. 2008, 10, 1831–1834; (b) Drabina, P.; Karel, S.;
Panov, I.; Sedlak, M. Tetrahedron: Asymmetry 2013, 24, 334–339.
4
.9. Copper acetate-catalysed Henry reaction of nitromethane
1
1
with aldehydes; general procedure
4. Bulut, A.; Aslan, A.; Dogan, O. J. Org. Chem. 2008, 73, 7373–7375.
The ligand (0.055 mmol) and Cu(OAc)
2
monohydrate (10 mg,
15. Nakayama, Y.; Hidaka, Y.; Ito, K. Synlett 2013, 24, 883–885.
1
1
1
6. Arai, T.; Takashita, R.; Endo, Y.; Watanabe, M.; Yanagisawa, A. J. Org. Chem.
008, 73, 4903–4906. and references therein.
7. Kowalczyk, R.; Kwiatkowski, P.; Skarzewski, J.; Jurczak, J. J. Org. Chem. 2009, 74,
753–756.
0
(
.05 mmol) were placed in a round-bottomed flask. Ethanol
1.5 mL) was then added and the mixture was stirred for 1 h. Next,
nitromethane (0.54 mL, 10 mmol) and the corresponding aldehyde
1 mmol) were added. After stirring for 48 h the volatile compo-
2
_
8. Drabowicz, J.; Oae, S. Synthesis 1977, 404–405.
(