Amberlyst A-27, an efficient heterogeneous catalyst for the Michael reaction of nitroalkanes with β-substituted alkene acceptors

Full text of DOI:10.1021/jo9520553

J . Org. Chem. 1996, 61, 3209-3211
3209
methods have important limitations. At first, KF was
applied, under an inert atmosphere,22 but a large excess
of nitroalkane (20 times) was necessary. Then, a weakly
basic macroreticular resin24 and various sorts of alu-
mina23,28 were used as heterogeneous bases. However,
these bases have been shown to be effective only with a
restricted class of electrophilic olefins such as R,â-
unsaturated esters24 or conjugated enones.23,28 Adsorbing
KF on neutral alumina25 greatly enhances the activity
of this basic catalyst, but the yields were low to moderate
and an excess of nitroalkane (4-8 times) was required.
Aliquat 336 provides27 a useful catalyst for the title
reaction with unsaturated esters, but again, an excess
(3-15 times) of nitro compound and the use of ultrasound
irradiations were required. Recently, layered zirconium
hydrogen phosphate has been reported as a new hetero-
geneous catalyst,26 but only one example was described.
The requirement for a large excess of nitroalkane in
many of the above-reported methods is a serious draw-
back, expecially when valuable nitro derivatives are
employed.
With the aim to avoid all these limitations, we explored
several catalysts, and now, we report a significant
improvement on this reaction by using commercial Am-
berlyst A-27, a macroreticular anionic resin with the
[-N(CH3)3+] as functional group.
The reaction was performed by adding 8-12 g of
Amberlyst A-27 to a mixture of 0.05 mol of nitroalkane
1 and 0.05 mol of alkene 2 at 0 °C, without solvent, and
then leaving the reaction at room temperature (see Table
1), followed by extraction with diethyl ether, filtration,
evaporation, and purification by flash chromatography,
affording the pure adduct 3 in high yield.
Under these conditions both primary and secondary
nitroalkanes easily react with a variety of electrophilic
alkenes, even those substituted in the â-position (entries
l, m , and q, Table 1). The yields of products vary from
good to excellent, and the reaction was found to be
substantially independent of catalyst:starting material
ratio.
The results reported in Table 1 refer to the solvent-
free reaction; however, different solvents such as THF
and Et2O can be used without a significant change of the
yield.
Of special interest is the conjugate addition of nitroal-
kanes to the 5,6-dihydro-2H-pyran-2-one (entry q, Table
1), because the nitro group facilitates a variety of carbon-
carbon bond-forming processes and offers a wide range
of efficient methods for its transformation into other
functionalities.3,4 Thus, further elaborations of the ob-
tained lactone derivative are possible.
Compared with other heterogeneous methods, our
procedure offers better yields with a large variety of
substrates without the need for an excess of nitroalkane.
Am ber lyst A-27, a n Efficien t
Heter ogen eou s Ca ta lyst for th e Mich a el
Rea ction of Nitr oa lk a n es w ith
â-Su bstitu ted Alk en e Accep tor s
Roberto Ballini,* Paola Marziali, and
Andrea Mozzicafreddo
Dipartimento di Scienze Chimiche dell’Universita`, Via S.
Agostino no. 1, 62032 Camerino, Italy
Received November 21, 1995
The Michael addition of nitroalkanes to electrophilic
double bonds provides a convenient method1,2 for the
preparation of a number of useful synthetic intermedi-
ates3,4 since the nitro group can be transformed into
various functionalities.3
Different organic bases such as tetramethylguanidine,5-8
potassium fluoride/18-crown-6,9,10 sodium hydride/18-
crown-6,11 diisopropylamine,6,12 potassium tert-butox-
ide,6,11 tri-n-butylphosphine,15 triphenyphosphine,11,16 1,8-
diazobicyclo[5.4.0]undec-7-ene,17 and tetrabutylammonium
fluoride11 have been used in homogeneous solutions.
Under these conditions, multiple Michael adducts are
often formed in significant amounts. This problem is
most acute in the case of vinylcarbonyl derivatives.
In recent years there has been a tremendous upsurge
of interest in various chemical transformations mediated
by heterogeneous catalysts, and the associated literature
is extensive.18-21 Innumerable chemical bonds are bro-
ken and new chemical bonds are formed during these
catalytic processes, and such events frequently occur
without a significant change of the catalyst. Moreover,
under heterogeneous catalyst, chemical transformations
can occur with better efficiencies, higher purity of the
products, and an easier workup.
Different heterogeneous catalysts22-28 have been em-
ployed for the Michael reaction of nitroalkanes, but these
(1) Padeken, H. G. In Houben-Weyl, 4th ed.; Thieme: Stuttgart,
1971; Vol. x/1, p 9.
(2) Bergmann, E. D.; Ginsburg, D.; Pappo, R. Org. React. 1959, 10,
179.
(3) Seebach, D.; Colvin, E. W.; Leher, F.; Weller, T. Chimia 1979,
33, 1.
(4) Rosini, G.; Ballini, R. Synthesis 1988, 833.
(5) Pollini, G. P.; Barco, A.; De Giuli, G. Synthesis 1972, 44.
(6) Bakuzis, P.; Bakuzis, M. L. F.; Weingartner, T. F. Tetrahedron
Lett. 1978, 2371.
(7) Miller, D. D.; Moorthy, K. B.; Hamada, A. Tetrahedron Lett. 1983,
24, 555.
(8) Stevens, R. V.; Lee, A. W. M. J . Chem. Soc., Chem. Commun.
1982, 102.
(9) Clark, J . H.; Cork, D. G. Chem. Lett. 1983, 1145.
(10) Clark, J . H.; Cork, D. G. J . Chem. Soc., Chem. Commun. 1982,
635.
(11) Nakashita, Y.; Hesse, M. Helv. Chim. Acta 1983, 66, 845.
(12) McMurry, J . E.; Melton, J . J . Org. Chem. 1973, 38, 4367.
(13) Miyakoshi, T.; Saito, S. Yukagaku 1982, 31, 35; Chem. Abstr.
1982, 96, 142217.
(14) Miyakoshi, T.; Saito, S. Yukagaku 1982, 31, 231; Chem. Abstr.
1982, 97, 38526.
(15) Miyakoshi, T.; Saito, S. Yukagaku 1982, 31, 143; Chem. Abstr.
1982, 97, 6536.
(16) Ono, N.; Miyake, H.; Kaji, A. J . Chem. Soc., Chem. Commun.
1983, 875.
Exp er im en ta l Section
Gen er a l. All 1H NMR spectra were recorded in CDCl3 at 300
MHz. Chemical shifts are expressed in ppm downfield from
TMS as internal standard. All the reactions were monitored
(17) Ono, N.; Kamimura, A.; Kaji, A. Synthesis 1984, 226.
(18) Posner, G. H. Angew. Chem., Int. Ed. Engl. 1978, 17, 487.
(19) Bailey, D. C.; Langer, S. H. Chem. Rev. 1981, 81, 109.
(20) Laszlo, P. Acc. Chem. Res. 1986, 19, 121.
(21) (a) Schwarz, J . A. Chem. Rev. 1995, 95, 477. (b) Gates, B. C.
Ibid. 511. (c) Goodman, D. W. Ibid. 523. (d) Hattori, H. Ibid. 537. (e)
Boudart, M. Ibid. 661.
(23) Rosini, G.; Marotta, E.; Ballini, R.; Petrini, M. Synthesis 1986,
237.
(24) Ballini, R.; Petrini, M.; Rosini, G. Synthesis 1987, 711.
(25) Bergbreiter, D. E.; Lalonde, J . J . J . Org. Chem. 1987, 52, 1601.
(26) Costantino, U.; Marmottini, F.; Curini, M.; Rosati, O. Chem.
Lett. 1993, 22, 333.
(22) Clark, J . H.; Cork, D. G.; Gibbs, H. W. J . Chem. Soc., Perkin
Trans. 1 1983, 2253.
(27) J ouglet, B.; Blanco, L.; Rousseau, G. Synlett 1991, 907.
(28) Ranu, B. C.; Bhar, S. Tetrahedron 1992, 48, 1327.
S0022-3263(95)02055-X CCC: $12.00 © 1996 American Chemical Society

3210 J . Org. Chem., Vol. 61, No. 9, 1996
Ta ble 1. Mich a el Rea ction of Nitr oa lk a n es Ca ta lyzed by Am ber lyst A-27
Notes
by TLC or GC performed on a Carlo Erba Fractovap 4160 using
a capillary column of Duran Glass, stationary phase OV1. The
products 3 were purified by flash chromatography29 on Merck
silica gel (0.040-0.063 mm). Amberlyst A-27 was purchased
from Carlo Erba Reagenti (also easily available from Fluka and
Aldrich).
Gen er a l P r oced u r e for th e Mich a el Ad d ition of Nitr oa l-
k a n es to Electr op h ilic Alk en es. A 100 mL two-necked flask
equipped with a mechanical stirrer was charged with the nitro
compound 1 (0.05 mol) and cooled with an ice-water bath. After
5 min the alkene 2 (0.05 mol) was added, and the mixture was
stirred for 10 min. Amberlyst A-27 (8-10 g) was added, and
after being stirred for 15 min, the mixture was left at room
temperature for the appropriate time (see Table 1). The Am-
berlyst was washed with Et2O (4 × 40 mL), the filtered extract
was evaporated, and the crude nitroderivative 3 was purified
by flash chromatography (cyclohexane/EtOAc 8:2).
6H), 4.4 (t, 1H, J ) 6.0 Hz). Anal. Calcd for C7H13NO3: C,
52.82; H, 8.23; N, 8.8. Found: C, 53.04; H, 8.41; N, 8.56.
5-Meth yl-5-n itr oh exa n -2-on e (en tr y c): IR (film) 1715,
1540 cm-1; 1H NMR δ 1.60 (s, 6H), 2.00-2.60 (m + s, 7H). Anal.
Calcd for C7H13NO3: C, 52.82; H, 8.23; N, 8.8. Found: C, 52.63;
H, 8.42; N, 9.01.
6-Nitr oocta n -3-on e (en tr y d ): IR (film) 1710, 1545 cm-1
;
1H NMR δ 0.95 (t, 3H, J ) 7.4 Hz), 1.05 (t, 3H, J ) 7.4 Hz),
1.7-2.18 (m, 4H), 2.38-2.5 (m, 4H), 4.35-4.5 (m, 1H). Anal.
Calcd for C8H15NO3: C, 55.47; H, 8.73; N, 8.09. Found: C, 55.70;
H, 8.51; N, 7.95.
6-Nitr od eca n -3-on e (en tr y e): IR (film) 1710, 1540 cm-1
;
1H NMR δ 0.88 (t, 3H, J ) 7.2 Hz), 1.05 (t, 3H, J ) 7.3 Hz),
1.2-1.45 (m, 4H), 1.85-2.15 (m, 4H), 2.38-2.51 (m, 4H), 4.4-
4.58 (m, 1H). Anal. Calcd for C10H19NO3: C, 59.68; H, 9.52; N,
6.96. Found: C, 59.88; H, 9.75; N, 6.73.
5-Nitr od eca n e-2,8-d ion e (en tr y f): IR (film) 1700, 1535
cm-1; 1H NMR δ 1.05 (t, 3H, J ) 7.5 Hz), 2.0-2.18 (m, 4H), 2.32-
2.6 (m + s, 9H), 4.4-4.6 (m, 1H). Anal. Calcd for C10H17NO4:
C, 55.8; H, 7.96; N, 6.51. Found: C, 56.1; H, 8.13; N, 6.32.
6-Meth yl-6-n itr oh ep ta n -3-on e (en tr y g): IR (film) 1710,
5-Nitr oh exa n -2-on e (en tr y a ): IR (film) 1715, 1545 cm-1
;
1H NMR δ 1.56 (d, 3H, J ) 6.3 Hz), 1.88-2.32 (t + s, 5H, J )
6.5 Hz), 2.4-2.72 (m, 2H), 4.4-4.92 (m, 1H, J ) 6.3 Hz). Anal.
Calcd for C6H11NO3: C, 49.65; H, 7.64; N, 9.65. Found: C, 49.82;
H, 7.78; N, 9.38.
1535 cm-1 1H NMR δ 1.05 (t, 3H, J ) 7.3 Hz), 1.58 (s, 6H),
;
2.12-2.25 (m, 2H), 2.38-2.52 (m, 4H). Anal. Calcd for C8H15
-
5-Nitr oh ep ta n -2-on e (en tr y b): IR (film) 1710, 1545 cm-1
;
NO3: C, 55.47; H, 8.73; N, 8.09. Found: C, 55.70; H, 8.59; N,
8.22.
1H NMR δ 0.96 (t, 3H, J ) 7.0 Hz), 2.2 (s, 3H), 1.6-2.85 (m,
1-(1-Nitr ocycloh exyl)p en ta n -3-on e (en tr y h ): IR (film)
(29) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
1710, 1520 cm-1; 1H NMR δ 1.05 (t, 3H, J ) 7.3 Hz), 1.25-1.75

Notes
J . Org. Chem., Vol. 61, No. 9, 1996 3211
(m, 10H), 2.05-2.2 (m, 2H), 2.31-2.5 (m, 4H). Anal. Calcd for
Anal. Calcd for C9H15NO6: C, 46.35; H, 6.48; N, 6.01. Found:
C, 46.51; H, 6.32; N, 6.2.
C
11H19NO3: C, 61.95; H, 8.98; N, 6.57. Found: C, 62.2; H, 9.12;
N, 6.44.
4-(1-Nitr oeth yl)tetr a h yd r op yr a n on e (en tr y q): IR (film)
7-Nitr on on a n -4-on e (en tr y i): IR (film) 1700, 1535 cm-1
;
1705, 1535 cm-1 1H NMR δ 1.58 (d, 3H, J ) 6.8 Hz), 1.6-2.4
;
1H NMR δ 0.91 (t, 3H, J ) 7.2 Hz), 0.95 (t, 3H, J ) 7.3 Hz),
1.5-2.18 (m, 6H), 2.32-2.48 (m, 4H), 4.35-4.5 (m, 1H). Anal.
Calcd for C9H17NO3: C, 57.73; H, 9.15; N, 7.48. Found: C, 57.89;
H, 9.00; N, 7.31.
(m, 3H), 2.5-2.8 (m, 2H), 4.2-4.35 (m, 1H), 4.4-4.6 (m, 2H).
Anal. Calcd for C7H11NO4: C, 48.55; H, 6.4; N, 8.09. Found:
C, 48.66; H, 6.58; N, 7.91.
1-(P h en ylsu lfon yl)-3-n itr oh ep ta n e (en tr y r ): IR (film)
1540, 1360, 1135 cm-1; 1H NMR δ 0.88 (t, 3H, J ) 7.4 Hz), 1.2-
1.45 (m, 4H), 1.65-2.1 (m, 2H), 2.2-2.4 (m, 2H), 3.1 (t, 2H, J )
7.3 Hz), 4.52-4.7 (m, 1H), 7.55-7.78 (m, 3H), 7.88-7.95 (m, 2H).
Anal. Calcd for C13H19NO4S: C, 54.72; H, 6.71; N, 4.91; S, 11.23.
Found: C, 54.90; H, 6.54; N, 5.02; S, 11.0.
7-Nitr od eca n -4-on e (en tr y j): IR (film) 1700, 1535 cm-1
;
1H NMR δ 0.85-1.0 (m, 6H), 1.23-1.43 (m, 2H), 1.5-1.75 (m,
2H), 1.85-2.15 (m, 4H), 2.3-2.5 (m, 4H), 4.45-4.6 (m, 1H). Anal.
Calcd for C11H19NO3: C, 59.68; H, 9.52; N, 6.51. Found: C,
59.55; H, 9.35; N, 6.38.
7-Meth yl-7-n itr oocta n -4-on e (en tr y k ): IR (film) 1700,
1535 cm-1 1H NMR δ 0.85 (t, 3H, J ) 7.4 Hz), 1.57 (s, 6H),
;
1-(P h en ylsu lfon yl)-3-m eth yl-3-n itr obu ta n e (en tr y s): IR
(film) 1535, 1380, 1165 cm-1; 1H NMR δ 1.6 (s, 6H), 2.3-2.4 (m,
2H), 3.08-3.19 (m, 2H), 7.58-7.73 (m, 3H), 7.58-7.9 (m, 2H).
Anal. Calcd for C11H15NO4S: C, 50.56; H, 7.33; N, 5.36; S, 12.27.
Found: C, 50.73; H, 7.49; N, 5.2; S, 12.07.
2.11-2.21 (m, 4H), 2.32-2.44 (m, 4H). Anal. Calcd for C9H17
-
NO3: C, 57.73; H, 9.15; N, 7.48. Found: C, 57.98; H, 9.32; N,
7.33.
5-Meth yl-6-n itr oh ep ta n -3-on e (en tr y l): IR (film) 1710,
1540 cm-1; 1H NMR δ 0.9-1.1 (m, 6H), 1.5 (dd, 3H, J ) 2.9, 6.7
1-(P h en ylsu lfon yl)-2-(1-n it r ocycloh exyl)et h a n e (en t r y
t): IR (film) 1540, 1380, 1160 cm-1; 1H NMR δ 1.5-1.7 (m, 10H),
2.18-2.47 (m, 2H), 3.0-3.1 (m, 2H), 7.52-7.75 (m, 3H), 7.86-
7.96 (m, 2H). Anal. Calcd for C14H19NO4S: C, 56.55; H, 6.44;
N, 4.71; S, 10.78. Found: C, 56.38; H, 6.59; N, 4.80; S, 10.90.
Hz), 2.3-2.7 (m, 4H), 4.5-4.7 (m, 1H). Anal. Calcd for C8H15
-
NO3: C, 55.47; H, 8.73; N, 8.09. Found C, 55.65; H, 8.54; N,
7.95.
3-(1-Nitr oeth yl)cycloh exa n on e (en tr y m ): IR (film) 1710,
1545 cm-1 1H NMR δ 1.32-2.6 (m, 9H), 1.6 (d, 3H, J ) 6.65
;
4-Nitr oocta n en itr ile (en tr y u ): IR (film) 2240, 1535 cm-1
;
Hz), 4.36-4.80 (m, 1H). Anal. Calcd for C8H13NO3: C, 56.13;
H, 7.65; N, 8.18. Found: C, 55.97; H, 7.84; N, 7.98.
Meth yl 4-n itr oocta n oa te (en tr y n ): IR (film) 1730, 1545
cm-1; 1H NMR δ 0.9 (t, 3H, J ) 7.3 Hz), 1.3-1.4 (m, 4H), 1.89-
2.44 (m, 6H), 3.69 (s, 3H), 4.47-4.63 (m, 1H). Anal. Calcd for
C9H17NO4: C, 53.19; H, 8.43; N, 6.89. Found: C, 52.97; H, 8.60;
N, 7.04.
1H NMR δ 0.91 (t, 3H, J ) 6.7 Hz), 1.2-1.45 (m, 4H), 1.7-2.55
(m, 6H), 4.5-4.7 (m, 1H). Anal. Calcd for C8H14N2O2: C, 56.45;
H, 8.29; N, 16.46. Found: C, 56.24; H, 8.44; N, 10.32.
4-Meth yl-4-n itr op en ta n en itr ile (en tr y v): IR (film) 2220,
1540 cm-1 1H NMR δ 1.64 (s, 6H), 2.26-2.46 (m, 4H). Anal.
;
Calcd for C6H10N2O2: C, 50.69; H, 7.09; N, 19.71. Found: C,
50.90; H, 6.91; N, 19.9.
Meth yl 4-m eth yl-4-n itr op en ta n oa te (en tr y o): IR (film)
1715, 1535 cm-1 1H NMR δ 1.58 (s, 6H), 2.16-2.39 (m, 4H),
;
3.69 (s, 3H). Anal. Calcd for C7H13NO4: C, 40.19; N, 7.23; N,
6.7. Found: C, 39.88; H, 7.45; N, 6.55.
Ack n ow led gm en t. We thank the University of
Camerino, Italy, and CNR-Italy for financial support.
Dim eth yl 4-n itr op im eloa te (en tr y p ): IR (film) 1720, 1535
cm-1; 1H NMR δ 2.0-2.45 (m, 8H), 3.7 (s, 6H), 4.6-4.7 (m, 1H).
J O9520553