Nitroalkanes in Aqueous Medium as an Efficient and Eco-Friendly Source for the One-Pot Synthesis of 1,4-Diketones, 1,4-Diols, δ-Nitroalkanols, and Hydroxytetrahydrofurans

Article abstract of DOI:10.1021/jo0351163

The Michael addition of primary aliphatic nitro compounds to α,β-unsaturated enones, performed in aqueous media, provides the one-pot synthesis of 1,4-diketones, 1,4-diols, δ-nitroalkanols, and hydroxytetrahydrofurans, respectively, by the appropriate cho

Full text of DOI:10.1021/jo0351163

Nitr oa lk a n es in Aqu eou s Med iu m a s a n
Efficien t a n d Eco-F r ien d ly Sou r ce for th e
On e-P ot Syn th esis of 1,4-Dik eton es,
SCHEME 1
1
,4-Diols, δ-Nitr oa lk a n ols, a n d
Hyd r oxytetr a h yd r ofu r a n s
Roberto Ballini,* Luciano Barboni, and Guido Giarlo
Dipartimento di Scienze Chimiche dell’Universit a` di
Camerino, Via S. Agostino 1, 62032 Camerino, Italy
roberto.ballini@unicam.it
Received J uly 30, 2003
With the aim to develop more efficient synthetic
processes, reduce the number of separate reaction steps,
and minimize byproducts, and in continuation with our
studies devoted to the chemistry of nitro compounds, we
have now found an interesting synergy between nitroal-
kanes and aqueous medium4 for the one-pot synthesis
Abstr a ct: The Michael addition of primary aliphatic nitro
compounds to R,â-unsaturated enones, performed in aqueous
media, provides the one-pot synthesis of 1,4-diketones, 1,4-
diols, δ-nitroalkanols, and hydroxytetrahydrofurans, respec-
tively, by the appropriate choice of the reaction conditions.
(Scheme 1) of the following compounds: (i) δ-nitroal-
kanols 3, which have proven to be the key building blocks
for the synthesis of tetrahydrofurans and spiroacetals;
Aliphatic nitro compounds have proven to be valuable
intermediates, and the chemical literature continuously
reports progress in their utilization for the synthesis of
a variety of target molecules. Moreover, these compounds
are very powerful synthetic tools because they facilitate
the carbon-carbon bond-forming processes and they can
5
(
ii) hydroxytetrahydrofurans (lactols) 4, intermediates in
6
7
the synthesis of cyclic ethers, dihydrofurans, zoapatanol
derivatives (the menses and labor-inducing principle of
the Mexican plant Montonoa tormentosa), and nonactic
8
1
9
be easily converted into many other functionalities.
acid, a component of the macrolide antibiotic nonactin;
The synthesis of complex molecules is traditionally
performed by a chain of separate reaction steps, each step
requiring its own conditions, reagents, solvent, catalyst,
and purification step. Now, environmental and economic
pressure are forcing the chemical community to search
for more efficient ways of performing chemical transfor-
mations, and in this context, a goal in present organic
synthesis is to perform more synthetic steps by “one-pot”
methods.2
Recently, there has been increasing recognition that
organic reactions carried out in water may offer advan-
tages over those occurring in organic solvents because
water is cheap and safe, it allows a precise control of the
pH, and the reactivity and/or the selectivity of the
the hydroxytetrahydrofuran unit is also present in
natural products such as seco-furoeremophilane deriva-
tives, which are characteristic constituents of the plants
10
of genus Euryops; (iii) 1,4-diketones 5, which are
important intermediates in the synthesis of cyclopenten-
11-16
ones, furans, pyrroles, thiophenes, and pyridazines;
and (iv) 1,4-diols 6, widely used molecules for the
preparation of important heterocycles such as γ-lactones,
pyrroles, and tetrahydrofurans,7
,17
(4) (a) Lubineau, A.; Aug e´ , J . Tetrahedron Lett. 1992, 33, 8073-
8
1
074. (b) Da Silva, F. M.; Gomes, A. K.; J ones, J ., J r. Can. J . Chem.
999, 77, 624-627. (c) Ballini, R.; Barboni, L.; Bosica, G.; Filippone,
P.; Peretti, S. Tetrahedron 2000, 56, 4095-4099.
reaction can be dramatically influenced when carried out
(5) (a) Ballini, R.; Fiorini, D.; Gil, M. V.; Palmieri, A.; Rom a´ n, E.;
Serrano, J . A. Tetrahedron Lett. 2003, 44, 2795-2797. (b) Occhiato,
E. G.; Guarna, A.; De Sarlo, F.; Scarpi, D. Tetrahedron: Asymmetry
in water.3
1
995, 6, 2971-2976.
*
Corresponding author.
(6) Yoda, H.; Mizutani, M.; Takabe, K. Heterocycles 1998, 48, 679-
(1) (a) Seebach, D.; Colvin, E. W.; Lehr, F.; Weller, T. Chimia 1979,
686.
3
3, 1-18. (b) Rosini, G.; Ballini, R. Synthesis 1988, 833-847. (c) Ballini,
(7) (a) Corey, E. J .; Cheng, X.-M. The Logic of Chemical Synthesis;
R. In Studies in Natural Products Chemistry; Atta-ur-Rahman, Ed.;
Elsevier: Amsterdam, 1997; Vol. 19, p 117. (d) Ballini, R. Synlett 1999,
J ohn Wiley and Sons: New York, 1989. (b) Lindberg, T. Strategies and
Tactics in Organic Synthesis; Academic Press: San Diego, 1994; Vol.
1. (c) Ho, T. L. Tactics of Organic Synthesis; J ohn Wiley and Sons:
New York 1994.
1
009-1018. (e) Ono, N. The Nitro Group in Organic Synthesis; J ohn
Wiley: New York, 2001.
2) (a) Hall, N. Science 1994, 266, 32. (b) Anastas, P. T.; Williamson,
(
(8) Hajois, Z. G.; Wachter, M. P.; Werblood, H. M.; Adams, R. E. J .
Org. Chem. 1984, 49, 2600-2608.
T. C. Green Chemistry. Frontiers in Benign Chemical Synthesis and
Processes; Oxford University Press: Oxford, 1998. (c) Riiter, S. K. Sci.
Technol. 2002, 19-23. (d) Tietze, L. F.; Haunert, F. In Stimulating
Concepts in Chemistry; Shibasaki, M., Stoddart, J . F., V o¨ gtle, F., Eds.;
Wiley-VCH: Weinheim, 2000; pp 39-64. (e) Filippini, M. H.; Rod-
riguez, J . Chem. Rev. 1999, 99, 27-76. (f) Drews, J . Science 2000, 287,
(9) Lee, J . Y.; Kim, B. H. Tetrahedron 1996, 52, 571-588.
(10) Gonser, P.; J akupovic, J .; Mungai, G. M. Phytochemistry 1991,
30, 899-904.
(11) Eicher, T.; Hauptmann, S. The Chemistry of Heterocycles; Georg
Thieme Verlag Stuttgart: New York 1995.
1
960-1964.
(12) Dean, F. M. Adv. Heterocycl. Chem. 1982, 30, 172.
(13) Sundberg, R. J . In Compehensive Heterocyclic Chemistry; Vol.
4; Katritsky, A. R., Rees, C. W., Eds.; Pergamon: Oxford, 1984; p 329.
(14) Hellison, R. A. Synthesis 1973, 397-412.
(15) Ho, T. L. Synth. Commun. 1974, 4, 265-287.
(16) Stetter, H.; Kuhlmann, H. Org. React. 1991, 40, 407-496.
(17) Comprehensive Organic Functional Group Transformations;
Katrinsky, A. R., Meth-Cohn, O., Rees, C. V., Eds.; Pergamon Press:
Oxford, 1995; Vol. 6.
(3) (a) Grieco, P. A. Organic Synthesis in Water; Blackie Academic
and Professional: London, 1998. (b) Li, C. J .; Chan, T. H. Organic
Reactions in Aqueous Media; J ohn Wiley and Sons: New York, 1997;
p 159. (c) Lubineau, A. Chem. Ind. 1996, 123. (d) Fringuelli, F.;
Piermatti, O.; Pizzo, F. In Target in Heterocyclic Systems, Chemistry
and Properties; Attanasi, O., Spinelli, D., Eds.; Italian Society of
Chemistry: Rome, 1997; Vol. 1, p 57. (e) Li, C. J . Chem. Rev. 1993, 93,
2
023-2035.
1
0.1021/jo0351163 CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/24/2003
J . Org. Chem. 2003, 68, 9173-9176
9173

TABLE 1. δ-Nitr oa lk a n ols 3 P r ep a r ed
SCHEME 4
3
R
R1
yield (%)
3
R
R1
yield (%)
a
b
c
d
Me
Et
Pr
Me
Me
Me
Et
82
86
83
94
e
f
g
Et
Pr
Ph
Et
Et
Et
82
78
79
Me
SCHEME 2
SCHEME 5
SCHEME 3
mixture using the modified Nef reaction showed they
were the cis and trans diastereoisomers in a 3:1 ratio (see
compound 4′a ). On the basis of the NOESY spectrum,
the configuration of the carbon bearing the nitro group
could not be assigned.
In the past, numerous methods have been reported for
the synthesis of the compounds 3, 4, 5, and 6;
1
8
19
20
21
however, they need a multistep sequence and most of
them suffer from drawbacks such as the use of harsh
conditions, employment of expensive chemical, and/or
tedious, toxic procedures. Furthermore, no method is
general for the synthesis of all these classes of molecules,
so that other efficient, eco-friendly sources for their
preparation are welcomed.
We have now found that the two- and three-step
sequences needed for the preparation of compounds 3-6
could be reduced in a one-pot procedure by employing
the aqueous medium and starting from nitroalkanes and
R,â-unsaturated ketone, using K CO and the appropriate
2 3
combination of oxidative/reductive conditions.
P r ep a r a tion of δ-Nitr oa lk a n ols (3). The preparation
of δ-nitroalkanols 3 was achieved in good yields (78-94%,
Table 1) by reaction between the nitroalkanes 1 and the
unsaturated ketones 2, followed by in situ reduction with
P r ep a r a tion of Hyd r oxytetr a h yd r ofu r a n s (La c-
tols) (4). Hydroxytetrahydrofurans 4 were obtained by
in situ Nef reaction of the corresponding δ-nitroalkanols
obtained as reported above, using a 30% water solution
of H
2 2
O (Scheme 4). The conversion of a nitro group into
a carbonyl can be accomplished by several alternative
methods22 although the use of H
O /K CO in a modified
2 2 2 3
Nef reaction23 appeared to us to be the most compatible
with our effort to develop environmentally friendly
processes.
The expected γ-hydroxyketones could not be isolated.
They spontaneously cyclized to the corresponding lactols
4
, which were isolated as diatereomeric mixtures and
1
3
identified on the basis of their C NMR spectra (signals
at about 110-115 ppm corresponding to the hemiketal-
C).
When cyclohexenone was used as a Michael acceptor
the cyclization could not happen and the expected γ-hy-
droxyketones 4′ were obtained (Scheme 5) in satisfactory
yields. In the case of compound 4′a ,24 the cis and trans
diastereoisomers were isolated in a 3:1 ratio and their
configuration was assigned on the basis of the NOESY
experiment. For compound 4′b, only the cis diastereo-
NaBH
it can be used in water and because it does not reduce
the nitro group. Another advantage of NaBH is the
4
(Scheme 2). The latter was chosen both because
4
absence of environmental effects of the byproducts (see
the safety data sheet of sodium borate at http://msds.
ehs.cornell.edu/msdsdoddata.asp).
The nitroalkanols were obtained as a 1:1 diastereo-
isomeric mixture. In the case of compound 3h (Scheme
(
22) Pinnick, H. W. Org. React. 1990, 38, 655-792.
(23) (a) Olah, G. A.; Arvanghi, M.; Vankar, Y. D.; Prakash, G. K. S.
3
, 86% yield), two of the four possible diastereomers were
Synthesis 1980, 662-663. (b) Ballini, R.; Marcantoni, E.; Petrini, M.;
isolated. Further transformation of the diatereoisomeric
Rosini, G. Synthesis 1988, 915-918.
(24) Ceccherelli, P.; Curini, M.; Marcotullio, M. C.; Epifano, F.;
Rosati, O. Synth. Commun. 1998, 28, 3057-3064.
(25) (a) Ballini, R.; Petrini, M.; Marcantoni, E.; Rosini, G. Synthesis
1988, 231-233. (b) Yasuda, M.; Oh-hata, T.; Shibata, I.; Baba, A.;
Matsuda, H. J . Chem. Soc., Perkin Trans. 1 1993, 859-866.
(26) Larcheveque, M.; Valette, G.; Cuvigny, T.; Normant, H. Syn-
thesis 1975, 256-259.
(27) Bach, J .; Berenguer, R.; Garcia, J .; Lopez, M.; Manzanal, J .;
Vilarrasa, J . Tetrahedron 1998, 54, 14947-14962.
(28) Yasuda, M.; Nishio, M.; Shibata, I.; Baba, A.; Matsuda, H. J .
Org. Chem. 1994, 59, 486-487.
(
18) (a) Shechter, H.; Ley, D. E.; Zeldin, L. J . Am. Chem. Soc. 1952,
7
4, 3664-3668. (b) Stanchev, S.; Milenkov, B.; Hesse, M. Tetrahedron
Lett. 1993, 34, 6107-6108. (c) (d) Reetz, M. T.; W u¨ nsch, T. J . Chem.
Soc., Chem. Commun. 1990, 1562-1564. (d) Forsyth, A. C.; Gould, R.
O.; Paton, R. M.; Salder, I. H.; Watt, I. J . Chem. Soc., Perkin Trans. 1
1
993, 2737-2741.
(
19) (a) Lali c´ , G.; Petrovski, Zˇ .; Galoni c´ , D.; Matovi c´ , R.; Sai cˇ i c´ , R.
N. Tetrahedron 2001, 57, 583-591. (b) Nakano, T.; Terada, T.; Ishii,
Y.; Ogawa, M. Synthesis 1986, 774-776.
(20) (a) Brown, H. C.; Racherla, U. S.; Singh, S. M. Synthesis 1984,
(29) Ikeda, H.; Sato, E.; Sugai, T.; Ohta, H. Tetrahedron 1996, 52,
8113-8122.
9
22-924. (b) Vankar, P. S.; Rathore, R.; Chandrasekaran, S. Synth.
Commun. 1987, 17, 195-201. (c) Baciocchi, E.; Casu, A.; Ruzziconi,
(30) Burk, M. J .; Feaster, J . E.; Harlow, R. L. Tetrahedron: Asym-
metry 1991, 2, 569-592.
R. Tetrahedron Lett. 1989, 30, 3707-3710.
(21) (a) Utimoto, K.; Uchida, K.; Yamaya, M.; Nozaki, H. Tetrahe-
(31) (a) Foubelo, F.; Gutierrez, A.; Yus, M. Synthesis 1999, 503-
514. (b) Nakamura, K.; Kitayama, T.; Inoue, Y.; Ohno, A. Bull. Chem.
Soc. J pn. 1990, 63, 91-96.
dron 1977, 33, 1945-1948. (b) Ballini, R.; Bosica, G.; Damiani, M.;
Righi, P. Tetrahedron 1999, 55, 13451-13456.
9
174 J . Org. Chem., Vol. 68, No. 23, 2003

SCHEME 6
ecologically friendly conditions with evident environmen-
tal advantages for widespread industrial use. Moreover,
by the obtained results it is evident that water shows a
great versatility in order to assembly different method-
ologies for the one-pot transformations of the starting
nitroalkanes and the conjugated enones into the title
targets. Thus, our report clearly demonstrates the im-
proved versatility of the nitroalkanes in aqueous media
and enhances the importance of both nitroalkanes and
aqueous media in current organic synthesis.
TABLE 2. 1,4-Dik eton es 5 P r ep a r ed
Exp er im en ta l Section
5
R
R1
yield (%)
5
R
R1
yield (%)
Gen er a l P r oced u r e for th e P r ep a r a tion of th e δ-Ni-
tr oa lk a n ols (3). A 2 mL water solution of the nitroalkane 1
(1.5 mmol) and K CO (3 mmol) was stirred at room temperature
2 3
for 5 min, and then the conjugated enone 2 (1.5 mmol) was
added. After the mixture was stirred at room temperature for 3
a a
27
28
Me
Me
Et
Me
Et
Et
73
68
72
f
i
Pr
Ph
Et
Me
70
69
2
5
d
e
2
6
a
Compound commercially available.
h, NaBH
stirred at rt for 3 h and then extracted with AcOEt. The organic
layer was dried over Na SO , filtered, and evaporated. The crude
4
(1,5 mmol) was added, and the reaction mixture was
2
4
SCHEME 7
product 3 was purified by column chromatography (silica gel,
cyclohexane/AcOEt ) 4:1).
1
Com p ou n d 3a (Dia ster eom er ic Mixtu r e). Yellow oil. H
NMR (200 MHz, CDCl
H), 1.54 (d, J ) 6.6 Hz, 3H), 1.98 (m, 2H), 3.82 (m, 1H), 4.60
m, 1H). 13C NMR (75 MHz, CDCl
): δ 19.4, 19.6, 23.8, 23.87,
1.4, 31.8, 34.9, 35.2, 67.1, 67.5, 83.6, 84.0. IR (neat): 3392, 2970,
930, 1560, 1547, 1391, 1361. GC-MS (EI): m/z 132 (M - CH ),
: C, 48.95; H, 8.91;
3
): δ 1.21 (d, J ) 6.6 Hz, 3H), 1.48 (m,
2
(
3
2
3
TABLE 3. 1,4-Diols 6 P r ep a r ed
3
R1
R1
83, 55, 45 (100). Anal. Calcd for C
N, 9.52. Found: C, 49.02; H, 8.89; N, 9.53.
Com p ou n d 3b (Dia ster eom er ic Mixtu r e). Yellow oil. H
NMR (200 MHz, CDCl ): δ 0.97 (t, J ) 7.0 Hz, 3H), 1.20 (d, J )
.8 Hz, 3H), 1.43 (m, 2H), 1.92 (m, 4H), 3.80 (m, 1H), 4.44 (m,
H). 13C NMR (75 MHz, CDCl
): δ 10.4, 10.5, 23.9, 24.1, 27.5,
7.6, 29.7, 30.3, 35.0, 35.4, 67.1, 67.8, 90.3, 90.9. IR (neat): 3391,
6 3
H13NO
6
R
yield (%)
6
R
yield (%)
2
9
31
a
e
f
Me Me
60
64
61
i
l
Ph
Bu
Me
Me
72
60
1
2
6,30
21a
Et
Pr
Et
Et
3
5
1
2
3
isomer could be isolated. Of great interest is the possibil-
ity of preserving the hydroxyl group under our oxidative
conditions.
P r ep a r a tion of 1,4-Dik eton es (5). Due to the good
results obtained for the synthesis of γ-hydroxyketones,
2973, 2933, 1560, 1548, 1372, 1334. GC-MS (EI): m/z 146 (M
- CH ), 97, 55 (100), 45. Anal. Calcd for C : C, 52.13;
H, 9.38; N, 8.69. Found: C, 52.22; H, 9.36; N, 8.68.
Com p ou n d 3c (Dia ster eom er ic Mixtu r e). Yellow oil. 1H
NMR (200 MHz, CDCl ): δ 0.94 (t, J ) 7.0 Hz, 3H), 1.20 (d, J )
3
7 3
H15NO
3
1
3
5
.9 Hz, 3H), 1.23-2.20 (m, 8H), 3.81 (m, 1H), 4.52 (m, 1H).
C
2 2
we successfully investigated the use of H O for the one-
3
NMR (75 MHz, CDCl ): δ 13.6 (2C), 19.26, 19.28, 23.9, 24.0,
30.0, 30.6, 34.9, 35.4, 36.1, 36.2, 67.1, 67.7, 88.6, 89.2. IR
(neat): 3400, 2965, 2933, 1558, 1551, 1377. GC-MS (EI): m/z
pot preparation of 1,4-diketones. Thus, after reaction
between the nitroalkanes (1) and the unsaturated ke-
tones (2), the mixture was treated with a 30% water
1
5
60 (M - CH
3
), 131, 69 (100), 55. Anal. Calcd for C
4.81; H, 9.78; N, 8.00. Found: C, 54.69; H, 9.80; N, 7.99.
8
H
17NO
3
: C,
solution of H
Scheme 6) in good yields (Table 2).
In the case of compounds 5a and 5e, an acidic workup
2 2
O , giving the corresponding diketone 5
1
Com p ou n d 3d (Dia ster eom er ic Mixtu r e). Yellow oil. H
(
NMR (200 MHz, CDCl ): δ 0.93 (t, J ) 7.3 Hz, 3H), 1.32-1.60
3
(
m, 4H), 1.55 (d, J ) 6.6 Hz, 3H), 1.73-2.28 (m, 2H), 3.54 (m,
1
3
of the reaction gave a mixture of the expected diketones
and the corresponding 2,5-dihydroxytetrahydrofuran ana-
logues 5′. The cis/trans configuration of compounds 5′ was
assigned on the basis of the -OH chemical shift, consid-
ering the higher downfield shift of the -OH protons due
to the intramolecular hydrogen bonding in the case of
the cis stereoisomer. For the product 5a only the trans
diastereoisomer was isolated, whereas for 5e both dias-
tereoisomers were isolated in a 1:1 ratio.
P r ep a r a tion of 1,4-Diols (6). 1,4-Diols were prepared
by in situ reduction of the 1,4-diketones obtained as
4
reported above, using an excess of NaBH as reducing
agent (Scheme 7). For all the diols, the yields reported
in Table 3 refer to the 1:1 diastereomeric inseparable
mixture.
With our procedure, a variety of different building
blocks can be easily prepared in one-pot starting from a
common intermediate. Moreover, the method provides
satisfactory to good overall yields using inexpensive and
1H), 4.61 (m, 1H). C NMR (75 MHz, CDCl ): δ 9.9, 10.0, 19.35,
19.44, 30.3, 30.4, 31.4, 31.7, 32.5, 32.9, 72.2, 72.6, 83.6, 84.1. IR
3
(
neat): 3400, 2965, 2936, 1560, 1538, 1390, 1358. GC-MS (EI):
m/z 132 (M - CH CH ), 97, 85, 55 (100). Anal. Calcd for C
NO : C, 52.13; H, 9.38; N, 8.69. Found: C, 52.21; H, 9.40; N,
.68.
Com p ou n d 3e (Dia ster eom er ic Mixtu r e). Yellow oil. H
2
3
7 15
H -
3
8
1
NMR (200 MHz, CDCl ): δ 0.91 (t, J ) 7.6 Hz, 3H), 0.95 (t, J )
3
7.6 Hz, 3H), 1.29-1.60 (m, 4H), 1.71-2.18 (m, 4H), 3.52 (m, 1H),
4
2
.43 (m, 1H). 13C NMR (75 MHz, CDCl
7.4, 27.5, 29.6, 30.3, 30.5, 30.6, 32.6, 33.1, 72.2, 72.9, 90.3, 90.9.
3
): δ 9.9, 10.0, 10.4 (2C),
IR (neat): 3400, 2971, 2936, 1545, 1538, 1375. GC-MS (EI): m/z
46 (M - CH CH ), 117, 99, 69 (100). Anal. Calcd for C
NO : C, 54.81; H, 9.78; N, 8.00. Found: C, 54.73; H, 9.80; N,
7.98.
Com p ou n d 3f (Dia ster eom er ic Mixtu r e). Yellow oil. 1
NMR (200 MHz, CDCl ): δ 0.93 (t, J ) 7.6 Hz, 3H), 0.94 (t, J )
.9 Hz, 3H), 1.24-1.57 (m, 6H), 1.58-2.24 (m, 4H), 3.54 (m, 1H),
.53 (m, 1H). 13C NMR (75 MHz, CDCl
): δ 9.96, 10.05, 13.7
1
2
3
8 17
H -
3
H
3
6
4
3
(
7
2C), 19.3, 19.3, 29.9, 30.6, 30.7 (2C), 32.7, 33.2, 36.2, 36.3, 72.3,
3.0, 88.7, 89.3. IR (neat): 3391, 2964, 2935, 1548, 1538, 1379.
GC-MS (EI) m/z 160 (M - CH CH ), 95, 69, 55, 41 (100). Anal.
2
3
J . Org. Chem, Vol. 68, No. 23, 2003 9175

Calcd for C
7.18; H, 10.14; N, 7.41.
Com p ou n d 3g (Dia ster eom er ic Mixtu r e). Yellow oil. H
NMR (200 MHz, CDCl ): δ 1.22 (bd, J ) 5.9 Hz, 3H), 1.46 (m,
H), 2.22 (m, 1H), 2.59 (m, 1H), 3.87 (m, 1H), 5.51 (m, 1H), 7.44
9
H
19NO
3
: C, 57.10; H, 10.12; N, 7.40. Found: C,
2.13 (s, 3H), 2.41 (m, 1H), 3.61 (m, 1H). 13C NMR (75 MHz,
CDCl ): δ 23.4, 27.6, 28.2, 35.1, 37.0, 50.0, 69.9, 211.3. IR
5
3
1
(neat): 3394, 2933, 2858, 1702. GC-MS (EI): m/z 142 (M), 124,
3
81, 67, 43 (100). Anal. Calcd for C
Found: C, 59.79; H, 10.06.
Com p ou n d cis-4′b. Yellow oil. H NMR (200 MHz, CDCl
8 16 3
H O : C, 59.96; H, 10.07.
2
1
3
(
3
(
1
(
6
m, 5H). C NMR (75 MHz, CDCl
5.2, 35.4, 67.3, 67.5, 91.4, 91.7, 127.8 (2C), 127.9 (2C), 129.2
4C), 130.0 (2C), 134.7 (2C). IR (neat): 3391, 3092, 2969, 2930,
560, 1547, 1538, 1364, 1304, 717, 696. GC-MS (EI): m/z 163
M - NO ), 145 (100), 117, 91. Anal. Calcd for C11 : C,
3.13; H, 7.23; N, 6.70. Found: C, 63.30; H, 7.25; N, 6.68.
3
): δ 23.8, 23.9, 30.3, 30.6,
1
3
):
δ 1.05 (t, J ) 7.3 Hz, 3H), 1.13-1.45 (m, 4H), 1.87 (m, 4H), 2.09
13
(
m, 1H), 2.45 (m, 1H), 2.48 (q, J ) 7.3 Hz, 2H), 3.64 (m, 1H).
C
NMR (75 MHz, CDCl ): δ 8.0, 23.5, 27.8, 34.0, 35.3, 37.2, 49.1,
3
2
H15NO
3
7
1
6
0.1, 213.6. IR (neat): 3402, 2936, 2859, 1708. GC-MS (EI): m/z
56 (M), 138, 127, 109, 81 (100). Anal. Calcd for C
9.18; H, 10.33. Found: C, 69.31; H, 10.35.
9 16 2
H O : C,
1
Com p ou n d cis-3h . Yellow oil. H NMR (200 MHz, CDCl
3
):
δ 0.83-1.39 (m, 4H), 1.52 (d, J ) 6.6 Hz, 3H), 1.67 (m, 2H), 1.94
Gen er a l P r oced u r e for th e P r ep a r a tion of th e 1,4-
Dik eton es (5). A 2 mL water solution of the nitroalkane 1 (1.5
mmol) and K CO (3 mmol) was stirred at room temperature
1
3
(
m, 3H), 3.61 (m, 1H), 4.42 (m, 1H). C NMR (75 MHz, CDCl
δ 16.5, 23.5, 27.2, 35.2, 38.7, 40.9, 70.1, 88.0. IR (neat): 3390,
975, 2930, 1560, 1547, 1370, 1334. GC-MS (EI): m/z 126 (M
HNO ), 109 (100), 67, 55. Anal. Calcd for C : C, 55.46;
H, 8.73; N, 8.09. Found: C, 55.41; H, 8.71; N, 8.11.
3
):
2
3
2
-
for 5 min, and then the conjugated enone 2 (1.5 mmol) was
added. After the mixture was stirred at room temperature for 3
h, 4 mL of a 30% aqueous solution of H O was added and the
2 2
reaction mixture was stirred overnight at rt. The mixture was
then extracted with AcOEt, and the organic layer was dried over
2
8 3
H15NO
1
Com p ou n d tr a n s-3h . Yellow oil.
CDCl ): δ 0.88-1.36 (m, 4H), 1.52 (d, J ) 6.6 Hz, 3H), 1.64 (m,
H), 1.92 (m, 3H), 3.63 (m, 1H), 4.41 (m, 1H). C NMR (75 MHz,
CDCl ): δ 16.5, 23.3, 28.6, 35.4, 37.3, 40.9, 70.3, 88.2. IR (neat):
390, 2976, 2930, 1561, 1548, 1370, 1334. GC-MS (EI): m/z 126
M - HNO ) 109 (100), 67, 55. Anal. Calcd for C : C,
5.46; H, 8.73; N, 8.09. Found: C, 55.45; H, 8.70; N, 8.10.
Gen er a l P r oced u r e for th e P r ep a r a tion of th e γ-Hy-
d r oxyk eton es a n d Hyd r oxytetr a h yd r ofu r a n s (4). A 2 mL
water solution of the nitroalkane 1 (1.5 mmol) and K CO (3
H NMR (200 MHz,
3
1
3
2
2 4
Na SO , filtered, and evaporated. The crude product 5 was
purified by column chromatography (silica gel, cyclohexane/
3
3
(
5
AcOEt ) 4:1).
2
8 3
H15NO
Com p ou n d 5′a . Amorphous solid. 1H NMR (200 MHz,
CDCl
3
): δ 1.49 (s, 6H), 1.64 (m, 2H), 1.88 (m, 2H), 8.34 (bs, 2H).
1
3
C NMR (75 MHz, CDCl ): δ 19.3, 26.6, 108.3. IR (neat): 3338,
3
2
4
5
997, 1378, 1120. GC-MS (EI): m/z 115 (M - OH), 99, 88, 71,
2
3
3 (100). Anal. Calcd for C
4.46; H, 9.15.
6
H
12
O
3
: C, 54.51; H, 9.16. Found: C,
mmol) was stirred at room temperature for 5 min, and then the
conjugated enone 2 (1.5 mmol) was added. After the mixture
1
Com p ou n d cis-5′e. Yellow oil. H NMR (200 MHz, CDCl
δ 0.94 (t, J ) 7.3 Hz, 6H),1.64-2.20 (m, 8H), 9.09 (bs, 2H).
3
NMR (75 MHz, CDCl ): δ 8.6, 28.2, 31.6, 116.8. IR (neat): 3340,
3
):
C
was stirred at room temperature for 3 h, NaBH
added, and the resulting mixture was stirred at rt for 3 h. A
0% aqueous solution of H (4 mL) was then added, and the
4
(1,5 mmol) was
1
3
3
2 2
O
2
5
6
995, 1375, 1124. GC-MS (EI): m/z 142 (M - H
7, 29. Anal. Calcd for C
0.08; H, 10.08.
2
O), 113 (100),
reaction mixture was stirred overnight at rt and then acidified
with 6 N HCl and extracted with AcOEt. The organic layer was
8 16 3
H O : C, 59.96; H, 10.07. Found: C,
dried over Na
2
SO
4
, filtered, and evaporated. The crude product
4
was purified by column chromatography (silica gel, cyclohex-
Com p ou n d tr a n s-5′e. Yellow oil. 1H NMR (200 MHz,
CDCl ): δ 0.98 (t, J ) 7.3 Hz, 6H),1.78 (m, 2H), 2.10 (m, 6H),
7.98 (s, 2H). C NMR (75 MHz, CDCl
IR (neat): 3338, 2994, 1378, 1120. GC-MS (EI): m/z 142 (M -
O), 113 (100), 57, 29. Anal. Calcd for C : C, 59.96; H,
10.07. Found: C, 59.91; H, 10.05.
ane/AcOEt ) 4:1).
3
1
13
Com p ou n d 4a (Dia ster eom er ic Mixtu r e). Yellow oil. H
3
): δ 8.8, 28.9, 32.2, 116.8.
NMR (200 MHz, CDCl
)
4
3
3
4
3
): δ 1.28 (d, J ) 5.9 Hz, 3H), 1.35 (d, J
5.9 Hz, 3H), 1.52 (s, 3H), 1.56 (s, 3H), 1.40-2.20 (m, 10H),
H
2
8 16 3
H O
1
3
3
.30 (m, 2H). C NMR (75 MHz, CDCl ): δ 20.9, 21.0, 22.7, 23.4,
2.88, 32.93, 35.75, 35.83, 75.7, 76.3, 112.1, 113.2. IR (neat):
Gen er a l P r oced u r e for th e P r ep a r a tion of th e 1,4-Diols
326, 2973, 1540, 1375, 1159. GC-MS (EI): m/z 99 (M - OH),
(6). A 2 mL water solution of the nitroalkane 1 (1.5 mmol) and
3 (100). Anal. Calcd for C
6
H
12
O
2
: C, 62.02; H, 10.42. Found:
2 3
K CO (3 mmol) was stirred at room temperature for 5 min, and
then the conjugated enone 2 (1.5 mmol) was added. After the
mixture was stirred at room temperature for 3 h, 4 mL of a 30%
C, 62.15; H, 10.40.
1
Com p ou n d 4b (Dia ster eom er ic Mixtu r e). Yellow oil. H
NMR (200 MHz, CDCl
7
1
δ 8.8, 8.9, 20.7, 22.3, 28.0, 28.2, 32.4, 32.7, 32.8, 33.6, 76.2, 77.9,
1
3
): δ 0.94 (t, J ) 7.3 Hz, 3H), 0.95 (t, J )
.3 Hz, 3H), 1.27 (d, J ) 6.6 Hz, 3H), 1.35 (d, J ) 6.6 Hz, 3H),
.30-2.20 (m, 14H), 4.31 (m, 2H). 13C NMR (75 MHz, CDCl
):
aqueous solution of H
was stirred overnight at rt. The mixture was then treated with
an excess of NaBH (180 mg), stirred at rt for 2 h, and then
extracted with AcOEt. The organic layer was dried over Na
SO , filtered, and evaporated. The crude product 6 was purified
2 2
O was added and the reaction mixture
3
4
2
-
15.6, 115.8. IR (neat): 3342, 2973, 1560, 1380, 1154. GC-MS
4
(
6
EI) m/z 113 (M - OH), 57 (100). Anal. Calcd for C : C,
7 14 2
H O
by column chromatography (silica gel, cyclohexane/AcOEt ) 7:3).
0.97; H, 11.95. Found: C, 60.83; H, 11.97.
1
Com p ou n d 6f (Dia ster eom er ic Mixtu r e). Yellow oil.
NMR (200 MHz, CDCl
.3 Hz, 3H), 1.33-1.78 (m, 10H), 2.35 (bs, 2H), 3.61 (m, 2H).
H
Com p ou n d 4c (Dia ster eom er ic Mixtu r e). Yellow oil. 1
): δ 0.93 (m, 12H), 1.21-2.20 (m, 22H),
.51 (m, 2H). C NMR (75 MHz, CDCl
H
3
): δ 0.94 (t, J ) 6.9 Hz, 3H), 0.95 (t, J )
NMR (300 MHz, CDCl
3
7
1
3
4
1
1
3
): δ 9.9, 10.0, 13.7, 14.5,
13
C NMR (50 MHz, CDCl
0.3, 30.7, 32.8, 33.4, 33.8, 34.3, 39.8, 40.1, 71.7, 72.2, 73.4, 73.9.
IR (neat): 3306, 2928, 1456. GC-MS (EI): m/z 131 (M - CH
CH ), 113, 95, 55, 43 (100), 29. Anal. Calcd for C : C, 67.44;
H, 12.59. Found: C, 67.32; H, 12.60.
3
): δ 10.2 (2C), 14.3 (2C), 19.1 (2C),
9.3, 19.3, 29.9, 30.4, 32.6, 32.7, 36.1, 36,3, 37.5, 38.2, 72.5, 73.2,
3
10.2, 110.6. IR (neat): 3342, 2975, 1558, 1380, 1156. GC-MS
2
-
(
6
9 18 2
EI) m/z 141 (M - OH), 71 (100). Anal. Calcd for C H O : C,
3
9 20 2
H O
8.30; H, 11.47. Found: C, 68.17; H, 11.50.
1
Com p ou n d tr a n s-4′a . Yellow oil.
H NMR (200 MHz,
CDCl ): δ 1.20-1.97 (m, 8H), 2.16 (s, 3H), 2.83 (m, 1H), 4.15
3
1
3
Ack n ow led gm en t. This work was supported by the
University of Camerino-Italy and by MIUR-Italy (Project
“Il Mezzo Acquoso nelle Applicazioni Sintetiche dei
Nitrocomposti Alifatici”).
(
m, 1H). C NMR (75 MHz, CDCl
3
): δ 19.9, 27.8, 28.2, 32.8,
3
4.7, 45.8, 66.0, 212.5. IR (neat): 3400, 2935, 2860, 1708. GC-
MS (EI) m/z 142 (M), 124, 81, 67, 43 (100). Anal. Calcd for
: C, 67.56; H, 9.93. Found: C, 67.70; H, 9.91.
8 14 2
C H O
1
Com p ou n d cis-4′a . Yellow oil. H NMR (200 MHz, CDCl
3
):
δ 1.12-1.40 (m, 4H), 1.82 (m, 2H), 1.93 (m, 1H), 2.10 (m, 1H),
J O0351163
9
176 J . Org. Chem., Vol. 68, No. 23, 2003