A new, one pot synthesis of alkylated methyl tri- and tetracarboxylate derivatives by nitrolkanes

Article abstract of DOI:10.1055/s-2004-815948

The reaction of nitroalkanes with trimethyl trans-aconitate in acetonitrile, in the presence of DBU as base, allows the one pot formation of alkylated methyl tri- and tetralkanoate derivatives via base induced nitrous acid elimination. The title compounds can also be obtained, in one flask, starting with the reaction of methyl nitroacetate with dimethyl maleate, followed by the addition, in the same flask of the nitroalkane.

Full text of DOI:10.1055/s-2004-815948

PAPER
605
A New, One Pot Synthesis of Alkylated Methyl Tri- and Tetracarboxylate
Derivatives by Nitrolkanes
Synthesis of
A
lky
o
lated Methy
b
l
Tri- and Te
e
tracarboxyl
r
ate
D
eri
t
vatives
o
by Nitrolkanes Ballini,* Giovanna Bosica, Dennis Fiorini, Maria Victoria Gil, Alessandro Palmieri
Dipartimento di Scienze Chimiche , Università di Camerino, Via S. Agostino 1, 62032 Camerino, Italy
Fax +39(0737)402297; E-mail: roberto.ballini@unicam.it
Received 22 December 2003; revised 5 January 2004
COOMe
COOMe
Abstract: The reaction of nitroalkanes with trimethyl trans-aconi-
+
R
NO2
MeOOC
tate in acetonitrile, in the presence of DBU as base, allows the one
pot formation of alkylated methyl tri- and tetralkanoate derivatives
via base induced nitrous acid elimination. The title compounds can
also be obtained, in one flask, starting with the reaction of methyl
nitroacetate with dimethyl maleate, followed by the addition, in the
same flask of the nitroalkane.
1a-l
2
DBU
MeCN, r.t.,
20-25 h
Key words: nitroalkanes, dimethyl maleate, methyl trialkanoate,
methyl tetraalkanoate, triols
NO2
COOMe
COOMe
- HNO2
R
COOMe
COOMe
R
MeOOC
H
MeOOC
Alkylated methyl tri- and tetralkanoate derivatives are
very important polyfunctionalized structures because they
serve as useful building blocks in organic synthesis1–7 and
4a-l
3a-l
are included as the main features in substances of biolog- Scheme 1
ical interest.8,9 The synthesis of complex molecules is tra-
ditionally performed by a sequence of separate reaction
Table 1 Synthesis of Methyl Tri- and Tetraesters 4a–l, from 2
steps, each step requiring its own conditions, reagents,
solvent, and catalyst. After each reaction is completed, the
solvent and the waste products are removed and discard-
ed, and the intermediate product is separated and purified.
Now environmental and economical pressures are forcing
the chemical community to search for more efficient
transformations.10 These issues can be addressed by de-
velopment of new synthetic methods that, bringing to-
gether small and simple components, generating complex
structures in one pot, much the same way as nature does.11
Com-
R
Yield (%)a Time (h)
dr of 4 (E/Z)
pound 4
of 4
a
b
c
81
90
74
23
20
25
88:12
95:5
94:6
O
(CH2)2
O
MeO
(CH2)2
O
MeO
(CH2)4
Over the last number of years aliphatic nitro compounds
were demonstrated as a valuable source for the one pot
preparation of alkylated complex molecules.12–20 In con-
tinuation of our studies we wish to report here a general,
one pot synthesis of the title compounds using nitro-
alkanes and an appropriate electrophilic alkene as com-
mon starting materials. Thus, conjugate addition of the
nitronate (Scheme 1) derived from the nitro compounds 1,
to trimethyl trans-aconitate 2 in acetonitrile with DBU as
base allows the one pot formation (66–90% yields,
Table 1) of the products 4, via base induced nitrous acid
elimination from the intermediate 3.
d
e
f
Ph
68
79
83
82
83
81
24
22
20
21
20
24
100:0
88:12
90:10
90:10
92:8
CH3CH2
CH3(CH2)2
CH3(CH2)3
CH3(CH2)4
O
g
h
i
100:0
EtO
(CH2)4
j
76
24
100:0
CH2
O
The reaction shows good diastereoselectivity since the E-
isomers in the title compounds are clearly predominant
(see Table 1). Compounds 4 represent a new class of
alkylated tri- or tetraesters (4b,c,i) with the presence of
k
l
HO(CH2)4
66
70
23
22
87:13
85/15
O
(CH2)2
a Yield of pure products.
SYNTHESIS 2004, No. 4, pp 0605–0609
x
x
.
x
x
.2
0
0
4
Advanced online publication: 03.02.2004
DOI: 10.1055/s-2004-815948; Art ID: Z18303SS.pdf
© Georg Thieme Verlag Stuttgart · New York

606
R. Ballini et al.
PAPER
other functionalities introduced through the nitroalkanes,
such as ketone (4a,l), hydroxyl (4k), furan (4j), that could
be further elaborated.
Table 2 One-Pot Synthesis of Compounds 4a–l from Dimethyl
Maleate 6
Compound
Yield (%)
Compound
Yield (%)
If the starting nitro compound is a -nitroalkanol (1n,
Scheme 2), the reaction produces the methyl tricarboxy-
late 5 (75% yield) in which the tetrahydrofuran moiety is
produced by the intramolecular conjugate addition of the
hydroxyl to the electrophilic alkene of the intermediate
4m. The ring closure is poorly stereoselective; indeed 5 is
obtained as a diatereomeric mixture.
4a
4b
4c
4d
4e
4f
60
63
59
62
55
61
4g
4h
4i
58
62
57
64
61
56
4j
4k
4l
OH
COOMe
+
MeOOC
COOMe
NO2
tios of E/Z diasteromers were similar to those obtained in
1m
2
the Scheme 1.
DBU
MeCN, r.t., 24 h
The presence of a C,C double bond in compounds 4 re-
sults in an , -unsaturated, a , -unsaturated and a , -
unsaturated ester moiety being present within the one
molecule. All these classes of esters are of great impor-
tance in organic synthesis and can be further manipulated
for the synthesis of an interesting class of triols 7, by their
reduction with LiAlH4 in Et2O (Scheme 4).
O
HO
COOMe
COOMe
75%
COOMe
COOMe
MeOOC
MeOOC
4m
5
COOMe
LiAlH4, 6 equiv.
R
R
OH
OH
Scheme 2
MeOOC
COOMe
Et2O, 8 h, 65-74%
HO
In Scheme 3, the straightforward synthesis of 2 (68%
yield) starting from dimethyl maleate 6 and methyl ni-
troacetate 1o is reported, following the same approach and
conditions as for the preparation of 4.
4e-h
7e-h
Scheme 4
The trialkanols 7 are directly obtained in 65–72% yields,
from 4, and it is important to point out that in the same
molecule, three different hydroxyl groups are present: an
allylic one, an homoallylic one and a bis-homoallylic one.
In Table 3, yield and diastereomeric ratio (E/Z) of the ob-
tained triols are reported.
O
COOMe
COOMe
DBU
MeOOC
MeO
+
MeCN, 60 °C, 5 h
68%
NO2
COOMe
COOMe
1n
2
6
1) DBU (1 equiv.),
MeCN, 60 °C, 5 h
Table 3 Synthesis of Methyl Trialcohols 7e–h
Compound 7 R
Yield (%)a of 7 dr of 7 (E/Z)
NO2
2)
, DBU (1 equiv.),
60 °C, 2.5 h
e
f
CH3CH2
65
70
74
72
80:20
74:26
78:22
75:25
R
1a-l
CH3(CH2)2
CH3(CH2)3
CH3(CH2)4
COOMe
COOMe
R
g
h
MeOOC
4a-l
a Yield of pure products.
Scheme 3
In conclusion, our procedure allows the one pot synthesis
of a new class of both tri- and tetralkanoate derivatives
starting from nitroalkanes and dimethyl maleate or trime-
thyl trans-aconitate.
The above result led to the idea of developing a one flask
synthesis of the title compound 4 starting from 6, in fact
when the methyl nitroacetate 1n reacted with dimethyl
maleate 6, giving 2, we added in the same flask the nitroal-
kane 1a–l and one more equivalent of DBU, heated the so-
lution at 60 °C and, after 3 hours the target compounds 4
were obtained in 55–62% overall yields (Table 2). The ra-
Moreover, the easy preparation of triols having simulta-
neously, allylic, homoallylic and bis-homoallylic hydrox-
yls, is reported.
Synthesis 2004, No. 4, 605–609 © Thieme Stuttgart · New York

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Synthesis of Alkylated Methyl Tri- and Tetracarboxylate Derivatives by Nitrolkanes
607
Table 4 Spectroscopic Data of 4a–l
1
No. IR (KBr) (cm–1) H NMR (200 MHz, CDCl3) , J (Hz)
13C NMR (50 MHz, CDCl3) , J (Hz) EI-MS (70 eV) m/z
4a 1652, 1738
2.15 (s, 3 H), 2.42–2.63 (m, 4 H), 3.20 (dd, 2 H, J = 7.3, 23.0, 29.8, 30.1, 35.2, 36.3, 39.1, 42.0, 301, 268, 236, 208,
18.8 Hz), 3.66 (s, 3 H), 3.69 (s, 3 H), 3.72 (s, 3 H), 4.12 52.0, 52.1, 52.2, 52.3, 52.5, 52.6,
(t, 1 H, J = 7.0 Hz), 6.16 (t, 0.12 H, J = 7.0 Hz), 6.85 (t, 129.7, 130.3, 144.7, 145.6, 166.6,
165, 137, 79, 59, 43
(100)
0.88 H, J = 7.0 Hz)
172.2, 172.5, 172.6, 172.8, 200.6,
206.9
4b 1653, 1736,
2.43–2.69 (m, 5 H), 3.21 (dd, 1 H, J = 7.3, 16.8 Hz), 3.65 24.3, 32.8, 35.2, 39.7, 52.1, 52.2, 52.6, 284, 252, 224, 192,
1755
(s, 3 H), 3.67 (s, 3 H), 3.69 (s, 3 H), 3.71 (s, 3 H), 4.13 (t, 130.7, 144.1, 166.2, 172.4, 172.6,
1 H, J = 6.6 Hz), 6.17 (t, 0.05 H, J = 7.0 Hz), 6.89 (t, 0.95 172.8
H, J = 7.0 Hz)
164, 137, 79, 59
(100)
4c 1214, 1648,
1.41–1.78 (m, 4 H), 2.22–2.58 (m, 5 H), 3.21 (dd, 1 H,
24.8, 28.2, 28.6, 34.2, 39.6, 52.0, 52.1, 345, 312, 252, 220
1736
J = 7.3, 16.5 Hz), 3.66 (s, 3 H), 3.67, (s, 3 H), 3.69 (s, 3 52.4, 52.5, 60.5, 129.6, 129.8, 146.1,
(100), 188, 160, 79,
59
H), 3.72 (s, 3 H), 4.10 (t, 1 H, J = 7.1 Hz), 6.12 (t, 0.06
H, J = 7.5 Hz), 6.92 (t, 0.94 H, J = 7.5 Hz)
147.3, 166.7, 172.3, 172.6, 173.5
4d 1640, 1760,
2.48 (dd, 1 H, J = 5.1, 16.5 Hz), 3.25 (dd, 1 H, J = 8.4,
16.1 Hz), 3.62 (s, 3 H), 3.68, (s, 3 H), 3.82 (s, 3 H), 4.48 128.1, 128.3, 128.5, 136.1, 139.0,
(dd, 1 H, J = 5.1, 8.4 Hz), 7.35–7.50 (m, 5 H), 7.90 (s, 1 167.1, 171.2, 172.3
34.8, 50.2, 51.3, 51.6, 58.2, 124.5,
306, 274, 242, 214,
183, 155, 143, 128
(100), 115, 79, 77
1736, 3061
H)
4e 1654, 1738
4f 1654, 1740
4g 1653, 1741
4h 1655, 1740
1.03 (t, 0.36 H, J = 7.7 Hz), 1.09 (t, 2.64 H, J = 7.7 Hz), 10.5, 10.6, 30.7, 35.4, 50.4, 50.5, 50.8, 226, 194, 166, 134
2.22–2.36 (m, 2 H), 2.45 (dd, 1 H, J = 6.6, 16.8 Hz), 3.19 51.2, 130.1, 137.2, 166.7, 172.4,
(100), 137, 121, 79,
59, 41
(dd, 1 H, J = 7.7, 16.5 Hz), 3.63 (s, 3 H), 3.69 (s, 3 H),
3.72 (s, 3 H), 4.13 (t, 1 H, J = 7.0 Hz), 6.12 (t, 0.12 H,
J = 7.6 Hz), 6.89 (t, 0.88 H, J = 7.5 Hz)
172.5, 173.1
0.93 (t, 3 H, J = 7.3 Hz), 1.40–1.58 (m, 2 H), 2.21–2.34 13.9, 14.1, 22.0, 22.5, 30.9, 31.8, 35.3, 240, 208, 180, 152,
(m, 2 H), 2.44 (dd, 1 H, J = 6.2, 16.8 Hz), 3.20 (dd, 1 H, 36.3, 39.7, 51.7, 52.0, 52.3, 52.5,
J = 7.7, 16.8 Hz), 3.65 (s, 3 H), 3.71 (s, 3 H), 3.73 (s, 3 128.8, 129.6, 146.7, 147.8, 166.8,
148, 93 (100), 79,
59, 41
H), 4.12 (t, 1 H, J = 7.0 Hz), 6.25 (t, 0.10 H, J = 7.4 Hz), 172.3, 172.6, 172.7, 173.0
6.94 (t, 0.90 H, J = 7.5 Hz)
0.95 (t, 3 H, J = 7.3 Hz), 1.39–1.58 (m, 2 H), 2.20–2.56 13.8, 14.0, 22.0, 22.5, 30.8, 31.7, 35.4, 254, 222, 194, 162
(m, 3 H), 3.20 (dd, 1 H, J = 7.7, 16.5 Hz), 3.64, (s, 3 H), 36.3, 39.6, 51.7, 51.9, 52.3, 52.5,
3.67 (s, 3 H), 3.71 (s, 3 H), 4.12 (t, 1 H, J = 6.6 Hz), 6.12 128.8, 129.6, 138.1, 138.8, 146.6,
(100), 137, 121, 93,
79, 59, 41
(t, 0.13 H, J = 7.3 Hz), 6.95 (t, 0.87 H, J = 7.3 Hz)
147.8, 166.7, 172.3, 172.6, 172.7,
173.0
0.82–0.93 (m, 3 H), 1.22–1.57 (m, 6 H), 2.20–2.59 (m, 3 14.0, 14.1, 22.5, 22.7, 30.1, 30.2, 31.3, 268, 236, 208, 176
H), 3.22 (dd, 1 H, J = 7.7, 16.5 Hz), 3.67 (s, 3 H), 3.70 (s, 32.6, 35.5, 36.6, 39.3, 51.5, 51.9, 52.2, (100), 152, 137, 93,
3 H), 3.73 (s, 3 H), 4.14 (t, 1 H, J = 7.0 Hz), 6.18 (t, 0.27 52.5, 128.7, 129.4, 146.5, 147.9,
H, J = 7.4 Hz), 6.96 (t, 0.73 H, J = 7.5 Hz) 166.9, 172.0, 172.5, 172.9, 173.1
79, 59, 41
4i 1435, 1682,
1.25 (t, 3 H, J = 7.3 Hz), 1.38–1.77 (m, 5 H), 2.21–2.39 14.0, 24.6, 28.4, 28.7, 34.3, 39.4, 51.9, 359, 326, 266, 248,
1732, 1748
(m, 4 H), 2.47 (dd, 1 H, J = 6.6, 16.8 Hz), 3.22 (dd, 1 H, 52.2, 52.4, 52.6, 60.7, 130.0, 146.8,
J = 7.3, 16.7 Hz), 3.66 (s, 3 H), 3.68, (s, 3 H), 3.74 (s, 3 166,5, 172.4, 172.6, 173.6
H), 4.15 (q, 2 H, J = 7.3 Hz), 6.94 (t, 1 H, J = 7.7 Hz)
220 (100), 188, 160,
91, 79, 59
4j 1456, 1732,
2.50 (dd, 1 H, J = 6.7, 16.7 Hz), 2.80 (dd, 1 H, J = 7.4,
33.6, 33.9, 43.3, 44.0, 50.6, 50.7, 52.1, 310, 278, 250, 218
1766
16.8 Hz), 3.35–3.60 (m, 3 H), 3.65 (s, 3 H), 3.70 (s, 3 H), 52.2, 52.3, 52.5, 52.6, 108.9, 109.1,
3.75 (s, 3 H), 6.0 (dd, 1 H, J = 9.9, 15.6 Hz), 6.23–6.42 111.5, 111.6, 122.0, 122.1, 123.0,
(100), 191, 177,
159, 131, 105, 91,
77, 59
(m, 2 H), 7.35 (d, 1 H, J = 1.8 Hz)
123.6, 142.5, 142.6, 151.7, 151.9,
172.0, 172.1, 172.7, 173.3
4k 1654, 1732,
1.36–1.67 (m, 5 H), 2.21–2.37 (m, 2 H), 2.43 (dd, 1 H,
25.5, 25.6, 28.4, 28.8, 32.5, 35.3, 39.6, 284, 253, 206, 192,
1740, 3568
J = 6.7, 16.8 Hz), 3.20 (dd, 1 H, J = 7.3, 16.5 Hz), 3.61 52.0, 52.4, 52.5, 62.8, 62.9, 124.2,
(s, 3 H), 3.64 (s, 3 H), 3.67 (s, 3 H), 3.54–3.70 (m, 2 H), 124.3, 129.6, 136.3, 137.0, 146.5,
4.10 (t, 0.90 H, J = 7.0 Hz), 4.40 ( t, 0.10 H, J = 6.9 Hz), 147.8, 166.7, 172.7
6.16 (t, 0.10 H, J = 7.5 Hz), 6.93 (t, 0.90 H, J = 7.4 Hz)
164, 137, 119, 105,
91, 79, 59 (100), 41,
31
4l 1655, 1732,
1.07 (t, 3 H, J = 7.3 Hz), 2.40–2.62 (m, 7 H), 3.22 (dd, 1 7.8, 7.9, 23.0, 35.2, 36.1, 39.6, 40.6,
H, J = 7.3, 16.5 Hz), 3.67 (s, 3 H), 3.69 (s, 3 H), 3.71 (s, 52.0, 52.1, 52.3, 52.4, 52.6, 130.2,
282, 222, 193, 165,
137, 79, 57 (100)
1740
3 H), 4.13 (t, 1 H, J = 7.3 Hz), 6.98 (t, 1 H, J = 7.4 Hz)
132.3, 141.1, 142.3, 144.9, 166.6,
172.5, 172.6, 209.7
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R. Ballini et al.
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Table 5 Spectroscopic Data of Alcohols 7e–h
No. IR (KBr) (cm-1) 1H NMR (200 MHz, CDCl3) , J (Hz)
13C NMR (50 MHz, CDCl3) ,
Elemental Analysis
J (Hz)
7e 3305, 1734,
0.94–1.01 (m, 2 H), 1.60–1.92 (m, 3 H), 2.02–2.20 (m, 2 14.3, 14.8, 21.1, 21.2, 32.6, 32.7, Anal. calcd for C9H18O3:
H), 2.42–2.57 (m, 0.20 H), 2.82–2.97 (m, 0.80 H), 3.16 39.2, 61.3, 61.4, 65.4, 65.8, 129.0, C, 62.04; H, 10.41.
1651
(br s, 3 H), 3.43–3.78 (m, 4 H), 3.91–4.22 (m, 2 H), 5.42 129.1, 133.8, 135.6, 138.1
Found: C, 61.89; H, 10.58
(t, 0.20 H, J = 7.0 Hz), 5.60 (t, 0.80 H, J = 7.0 Hz)
7f 3310, 1735,
0.83–1.00 (m, 3 H), 1.30–1.44 (m, 2 H), 1.56–1.87 (m, 3 13.9, 14.1, 23.0, 23.3, 29.9, 30.5, Anal. calcd for C10H20O3:
H), 1.96–2.14 (m, 2 H), 2.41–2.54 (m, 0.26 H), 2.79–2.90 32.6, 33.8, 39.1, 60.9, 61.3, 65.3, C, 63.80; H, 10.71.
1648
(m, 0.74 H), 3.42–3.74 (m, 6 H), 3.86–4.20 (m, 2 H), 5.40 65.7, 66.8, 127.0, 127.3, 131.7,
(t, 0.26 H, J = 7.6 Hz), 5.58 (t, 0.74 H, J = 7.6 Hz) 133.6, 138.7
Found: C, 63.97; H, 10
7g 3306, 1734,
0.83–0.94 (m, 3 H), 1.21–1.38 (m, 4 H), 1.50–1.87 (m, 3 13.8, 14.2, 22.5, 22.6, 22.7, 27.5, Anal. calcd for C11H22O3:
H), 1.92–2.15 (m, 2 H), 2.41–2.50 (m, 0.22 H), 2.76–2.88 27.6, 32.0, 32.3, 32.6, 39.0, 60.7, C, 65.31; H, 10.96.
1650
(m, 0.78 H), 3.56–3.72 (m, 4 H), 4.00–4.26 (m, 4 H), 5.38 61.3, 65.3, 65.7, 128.1, 128.3,
(t, 0.22 H, J = 7.3 Hz), 5.57 (t, 0.78 H, J = 7.3 Hz) 131.8, 133.6, 138.5
Found: C, 65.48; H, 11.19
7h 3320, 1738,
0.82–0.93 (m, 3 H), 1.22–1.41 (m, 6 H), 1.52–1.91 (m, 3 14.0, 14.2, 22.5, 22.6, 22.8, 22.9, Anal. calcd for C12H24O3:
H), 2.01–2.20 (m, 2 H), 2.43–2.57 (m, 0.25 H), 2.81–2.93 23.0, 27.5, 27.7, 32.1, 32.5, 32.6, C, 66.63; H, 11.18.
(m, 0.75 H), 3.45–3.78 (m, 6 H), 3.89–4.18 (m, 2 H), 5.42 39.2, 60.8, 61.5, 65.5, 65.7, 128.2, Found: C, 66.86; H, 9.98
1652
(t, 0.25 H, J = 7.3 Hz), 5.59 (t, 0.75 H, J = 7.3 Hz)
128.3, 131.7, 133.7, 138.2
1H and 13C NMR were recorded in CDCl3 at 200 MHz and 50MHz,
respectively, on Varian Gemini 200. Chemical shift are expressed
in ppm downfield from TMS. Mass spectra were recorded with a
nonpolar capillary column, utilizing electron impact (EI) at an ion-
izing energy of 70 eV. Element analyses were performed using a C,
H Analyzer Model 185 from Hewlett-Packard. All the reactions
were monitored by TLC and/or gas chromatography analysis, per-
formed on Hewlett-Packard 5890 series II using a capillary column
(0.32 mm × 25 m).
IR (KBr): 1676, 1739, 1736 cm–1.
1H NMR (200 MHz, CDCl3): = 1.10–1.21 (m, 3 H), 1.38–1.75 (m,
2 H), 1.90–2.12 (m, 2 H), 2.49–2.98 (m, 4 H), 3.63 (s, 3 H), 3.65 (s,
3 H), 3.69 (s, 3 H), 3.85–4.40 (m, 2 H).
EI-MS (70 eV): m/z = 271, 239, 157, 125, 85 (100), 79, 67, 59, 41.
Anal. calcd for C14H22O7: C, 55.62; H, 7.33. Found: C, 55.77; H,
7.51.
Synthesis of Compounds 4a–m from 2; General Procedure
To a stirred solution of 2 (0.216 g, 1 mmol) in CH3CN (10 mL),
DBU (0.149 mL, 1 mmol) and the nitro compound 1 (1 mmol) were
added. The resulting mixture was stirred at r.t. for the appropiate
time (Table 1), than the solvent was removed under vacuum and the
crude pruduct was purified by flash cromatography (cyclohexane–
EtOAc).
Acknowledgment
This work was supported by the University of Camerino, by
MURST (Project ‘Il Mezzo Acquoso nelle Applicazioni Sintetiche
dei Nitrocomposti Alifatici’). M.V.G. also thanks the Spanish Mi-
nistero de Education, Cultura y Deporte for a postdoctoral fel-
lowship.
Synthesis of Compounda 4a–m from 6; General Procedure
To a stirred solution of dimethyl maleate 6 (0.125 mL, 1mmol) and
methyl nitroacetate 1n (0.092 mL, 1 mmol) in CH3CN (10 mL),
DBU (0.149 mL, 1 mmol) was added. The resulted mixture was
warm to 60 °C and stirred for 5 h at this temperature, than, after
cooling to r.t., the nitro compound 1 (1 mmol) and DBU (0.149 mL,
1 mmol) were added. After stirring for a further 2.5 h at 60 °C the
mixture was cooled and the solvent was removed under vacuum. Fi-
nally, the crude product was purified by flash chromatography (cy-
clohexane–EtOAc). Analytical data are given in Table 4.
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To a stirred suspension of LiAlH4 (0.228, 6 mmol) in anhyd Et2O
(10 mL) under nitrogen, a solution of triester 4e–h (1 mmol) in an-
hyd Et2O (10 mL) was added dropwise. The mixture was stirred at
r.t. for 8 h, then diluted with water, acidified with 2 N HCl to pH 2–
3, and extracted with EtOAc. The organic layer was dried (MgSO4),
the solvent removed by distillation, and the crude product was puri-
fied by flash chromatography (EtOH–EtOAc–cyclohexane,
10:30:60). Analytical data are given in Table 5.
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Compound 5
Following the above procedure, mixing 2 (0.216g, 1 mmol) and 4-
hydroxynitropentane (1m; 0.133 g, 1 mmol) the pure tetrahydrofur-
an derivative 5 was obtained in 75% yield (0.226 g).
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Synthesis 2004, No. 4, 605–609 © Thieme Stuttgart · New York