4894
S. Ghosh et al. / Tetrahedron Letters 50 (2009) 4892–4895
Table 2 (continued)
Entry
R1
X
Amine
E:Z
Time (min)
20
Yielda (%)
88
Ref.
13
14
15
16
17
a
4-OMe
CN
00:100
N
H
Ph
H
CO2Me
CO2Me
CO2Me
CN
100:00
100:00
100:00
00:100
30
90
90
75
70
75
70
80
4a
4a
NH
2
NH
2
H
NH
2
H
Br
NH
2
4-OMe
MeO
Yields refer to those of pure isolated products characterized by spectroscopic data (IR,1H, 13C NMR, and HR-MS).
1220; (c) Gardner, B.; Nakanishi, H.; Kahn, M. Tetrahedron 1993, 49, 3433–3448;
(d) Chen, A.; Nelson, A.; Tanikkul, N.; Thomas, E. J. Tetrahedron Lett. 2001, 42,
1251–1254; (e) Lee, C. G.; Gowrisankar, S.; Kim, J. N. Bull. Korean Chem. Soc.
2005, 26, 481–484.
20 min at room temperature. The reactions of anilines (Table 2, en-
tries 15–17) were carried out at 80 °C. Interestingly, the reactions
of BH adducts bearing –CN moiety were rarely addressed in the lit-
erature.4j,k In a recent Letter by Yadav et al.4k only
a
-addition prod-
ucts were obtained using DABCO and Kim et al.4j reported only one
reaction giving Z-isomer of -product for this type of aza-Michael
reaction. Nevertheless, our procedure addressed a variety of BH
adducts containing CN moiety giving Z-isomer of -products with
4. (a) Paira, M.; Mandal, S. K.; Roy, S. C. Tetrahedron Lett. 2008, 49, 2432–2434; (b)
Shafig, Z.; Liu, L.; Liu, Z.; Wang, D.; Chen, Y.-J. Org. Lett. 2007, 9, 2525–2528; (c)
Singh, V.; Pathak, R.; Kanojiya, S.; Batra, S. Synlett 2005, 2465–2468; (d) Pathak,
R.; Roy, A. K.; Batra, S. Synlett 2005, 848–850; (e) Rajesh, S.; Banerji, B.; Iqbal, J. J.
c
Org.
Chem. 2002, 67, 7852–7857; (f) Lee, C. G.; Lee, K. Y.; Gowrisankar, S.; Kim, J.
N. Tetrahedron Lett. 2004, 45, 7409–7413; (g) Basavaiah, D.; Satyanarayana, T.
Tetrahedron Lett. 2002, 43, 4301–4303; (h) Azizi, N.; Saidi, M. R. Tetrahedron Lett.
2002, 43, 4305–4308; (i) Kim, J. N.; Chung, Y. M.; Im, Y. J. Tetrahedron Lett. 2002,
43, 6209–6211; (j) Kim, J. N.; Kim, H. S.; Gong, J. H.; Chung, Y. M. Tetrahedron
Lett. 2001, 42, 8341–8344; (k) Yadav, L. D. S.; Srivastava, V. P.; Patel, R.
Tetrahedron Lett. 2009, 50, 1423–1426.
c
a clear distinction from others. Without water, the neat reactions
at room temperature were very sluggish and inconsistent. Thus,
water plays an important role in this reaction. It is likely that water
promotes the reaction through hydrogen bond formation with the
carbonyl oxygen atoms of acetate and carboxylic ester moieties
increasing the electrophilic character at the b-carbon and this facil-
itates the nucleophilic attack by amine followed by elimination of
acetate group.
5. (a) Li, C. J.; Chang, T. H. In Organic Reactions in Aqueous Media; Wiley: New York,
1997; (b)Organic Synthesis in Water; Grieco, P. A., Ed.; Blackie Academic and
Professional: London, 1998; (c) Chanda, A.; Fokin, V. V. Chem. Rev. 2009, 109,
725–748.
6. (a) Azizi, N.; Saidi, M. R. Org. Lett. 2005, 7, 3649–3651; (b) Azizi, N.; Aryanasab,
F.; Torkiyan, L.; Ziyaei, A.; Saidi, M. R. J. Org. Chem. 2006, 71, 3634–3635; (c)
Khatik, G. L.; Kumar, R.; Chakraborti, A. K. Org. Lett. 2006, 8, 2433–2436; (d)
Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb, H. C.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2005, 44, 3275–3279.
7. (a) Ranu, B. C.; Banerjee, S. Tetrahedron Lett. 2007, 48, 141–143; (b) Ranu, B. C.;
Mandal, T. Synlett 2007, 925–928; (c) Ranu, B. C.; Chattopadhyay, K.; Adak, L.
Org. Lett. 2007, 9, 4595–4598; (d) Ranu, B. C.; Dey, R.; Chattopadhyay, K.
Tetrahedron Lett. 2008, 49, 3430–3432; (e) Bhadra, S.; Saha, A.; Ranu, B. C. Green
Chem. 2008, 10, 1224–1230; (f) Saha, D.; Chattopadhyay, K.; Ranu, B. C.
In conclusion, we have developed a mild and efficient method
for the synthesis of
a-dehydro-b-amino esters and nitriles by the
reaction of amines and acetates of Baylis–Hillman adducts in water
at room temperature without using any basic, acidic, or metal cat-
alyst. The reactions provided only c-addition products. The addi-
tions are also highly stereoselective providing (E)-isomers in case
of BH adducts bearing carboxylic ester moiety and (Z)-isomers
for adducts containing CN functionality. Certainly, the simple oper-
ation, high yields, fast reaction, excellent regio- and stereoselectiv-
ity of products, applicability to a variety of amines and BH adducts
and green reaction conditions using water without any catalyst in
aerobic atmosphere make this procedure more attractive for aca-
demia as well as industries.
Tetrahedron
Lett. 2009, 50, 1003–1006; (g) Saha, A.; Saha, D.; Ranu, B. C. Org.
Biomol. Chem. 2009, 7, 1652–1657.
8. Representative experimental procedure for the aza-Michael addition of amine to
Baylis–Hillman acetate adduct (Table 2, entry 1): A mixture of pyrrolidine
(106 mg, 1.5 mmol) and Baylis–Hillman acetate, 2-(acetoxy-phenyl-methyl)-
acrylic acid methyl ester (202 mg, 1 mmol) in water (2 mL) was stirred at room
temperature in aerobic atmosphere for 10 min (TLC). The reaction mixture was
extracted with ethyl acetate (2 Â 10 mL) and the combined extract was washed
with brine, dried (Na2SO4), and evaporated to leave the crude product which
was purified by column chromatography over silica gel to provide a viscous
liquid (190 mg, 90%), which was identified as 3-phenyl-2-pyrrolidine-1-yl-
methyl-acrylic acid methyl ester by comparison of its 1H NMR and 13C NMR
spectroscopic data with the reported values.4h
Acknowledgments
This procedure is followed for all the reactions listed in Table 2. The known
products were easily identified by comparison of their spectroscopic data with
those reported (see Table 1). The unknown compounds were characterized by
their IR, 1H NMR, 13C NMR, and HR-MS spectroscopic data. These were provided
below in order of their entries in Table 1.
The financial support from DST, New Delhi under the J. C. Bose
National Fellowship to B. C. Ranu (SR/S2/JCB-11/2008) is gratefully
acknowledged. S.G., R.D., and K.C. thank CSIR, New Delhi for their
fellowships.
3-Phenyl-2-pyrrolidin-1-ylmethyl-acrylonitrile (Table 1, entry 2): Yellow liquid; IR
(neat) 2962, 2212, 1608, 1512, 1348, 1126, 758 cmÀ1 1H NMR (300 MHz, CDCl3)
;
References and notes
d 1.80–1.86 (m, 4H), 2.61–2.65 (m, 4H), 3.39 (s, 2H), 7.12 (s, 1H), 7.38–7.40 (m,
3H), 7.74–7.77 (m, 2H); 13C NMR (75 MHz, CDCl3) d 23.6 (2C), 53.7 (2C), 60.0,
109.4, 118.8, 127.0, 128.8 (2C), 129.0 (2C), 133.4, 144.7; HR-MS Calcd for
C14H16N2 [M+H]+: 213.139; found: 213.131.
1. (a) Basavaiah, D.; Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811–891; (b)
Basavaiah, D.; Reddy, K. R.; Kumaragurubaran, N. Nat. Protocols 2007, 2, 2665–
2676; (c) Basavaiah, D.; Roy, S. Org. Lett. 2008, 10, 1819–1822; (d) Aggarawal, V.
K.; Patin, A.; Tisserand, S. Org. Lett. 2005, 7, 2555–2557; (e) Wasnaire, P.; Wiaux,
M.; Touillaux, R.; Marko, I. E. Tetrahedron Lett. 2006, 47, 985–989; (f) Clive, D. L.
J.; Li, Z.; Yu, M. J. Org. Chem. 2007, 72, 5608–5617.
2. (a) Kabalka, G. W.; Venkataiah, B.; Dong, G. Org. Lett. 2003, 5, 3803–3805; (b)
Basavaiah, D.; Satyanarayana, T. Org. Lett. 2001, 3, 3619–3622; (c) Lee, K. Y.;
Gowrisankar, S.; Lee, Y. J.; Kim, J. N. Tetrahedron 2006, 62, 8798–8804.
3. (a) Baldwin, J. E.; Moloney, M. G.; North, M. J. Chem. Soc.; Perkin Trans. 1 1989,
833–834; (b) Buchholz, R.; Hoffman, H. M. R. Helv. Chim. Acta 1991, 74, 1213–
3-(4-Chloro-phenyl)-2-pyrrolidin-1-ylmethyl-acrylonitrile (Table 2, entry 4):
Yellow liquid; IR (neat) 2882, 2218, 1615, 1240, 700 cmÀ1 1H NMR (300 MHz,
;
CDCl3) d 1.77–1.81 (m, 4H), 2.50–2.58 (m, 4H), 3.36 (s, 2H), 7.06 (s, 1H), 7.34 (d,
J = 8.3 Hz, 2H), 7.67 (d, J = 8.3 Hz, 2H); 13C NMR (75 MHz, CDCl3) 23.6 (2C), 53.8
(2C), 59.9, 110.1, 118.5, 129.6 (2C), 130.1 (2C), 131.9, 136.0, 143.2; HR-MS Calcd
for C14H15N2Cl [M+H]+: 247.10; found: 247.09.
3-(3-Chloro-phenyl)-2-morpholin-4-ylmethyl-acrylic acid methyl ester (Table 2,
entry 5): Yellow liquid; IR (neat) 3016, 2820, 1710, 1553, 1240, 710 cmÀ1 1H
;
NMR (300 MHz, CDCl3) d 2.40 (t, J = 4.2 Hz, 4H), 3.26 (s, 2H), 3.60 (t, J = 4.2 Hz,