Xiong et al.
SCHEME 1. The Lewis Acid Mediated Reactions of
â-Hydroxymethylcyclopropanylamides 1
Results and Discussion
In our initial studies, the 1-(1-hydroxyethyl)-N-(2-methoxy-
phenyl)cyclopropanecarboxamide (5), prepared by reducing
1-acetyl-N-(2-methoxyphenyl)cyclopropanecarboxamide6 with
sodium borohydride,16 was selected as the substrate (Scheme
2). Unfortunately, it was found that no reaction occurred upon
treatment of 5 with Lewis acids, such as SnCl4‚5H2O, TiCl4,
and BF3‚OEt2 in acetonitrile. However, the SnCl4‚5H2O medi-
ated reaction of (E)-1-(1-hydroxy-3-phenylallyl)-N-(2-methoxy-
phenyl)cyclopropanecarboxamide (1a) (obtained by the sodium
borohydride reduction of 1-cinnamoyl-N-(2-methoxyphenyl)-
cyclopropanecarboxamide,16 which was prepared by the con-
densation of 1-acetyl-N-(2-methoxyphenyl)cyclopropanecar-
boxamide with benzaldehyde)17 provided a ring-opened product
6 in 43% yield, an intramolecular Friedel-Crafts alkylation
product dihydroquinolin-2-one 3a in 41% yield, and a ring-
opened/recylization product γ-iminolactone18 2a in 6% yield,
respectively, in acetonitrile for 0.5 h (Scheme 2). With the aim
to improve the yield of 2a (according to our previous work
regarding the O-annulation of 2-(2-chloroethyl)-N-(2-methoxy-
phenyl)-3-oxobutanamide),6a 2.0 equiv of NaI19 was added to
the SnCl4‚5H2O mediated reaction of 1a in acetonitrile for 1 h,
then NEt3 (3.0 equiv) was added and reacted for another 1 h.
To our delight, 2a was obtained in 78% isolated yield (Table
1, entry 1). In addition, our experiments showed that a small
amount of SnCl4‚5H2O (for example, 0.5 equiv) was not efficient
(Table 1, entry 2). Other Lewis acids, including TiCl4, FeCl3,
and AlCl3, gave 2a in relatively lower yields (Table 1, entries
3-5). The reaction could be carried out in DMF, THF, xylene,
and dichloroethane but with lower yields of 2a (Table 1, entries
7-10). Interestingly, 3a was obtained as the major product (in
yield of 52%) for the BF3‚OEt2 mediated reaction of 1a (Table
1, entry 6). Therefore, selecting BF3‚OEt2 as the Lewis acid,
we tried to improve the yield of 3a by changing the solvent
system and reaction temperature without the activation of NaI
(Table 1, entries 11 and 12). Mediated by BF3‚OEt2, the reaction
of 1a exclusively afforded 3a in 70% isolated yield within 15
min with dicholormethane as the solvent at room temperature
(Table 1, entry 12). It is noteworthy that both γ-iminolactone
2a and dihydroquinolin-2-one 3a could be obtained in high
yields from the same substrate 1a (Table 1, entries 1 and 12).
In fact, selective synthesis has been a formidable challenge in
organic synthesis, especially controlled highly selective synthesis
cyclobutyl cation7 or ring cleavage to give a homoallyl cation8
to relieve ring strain. Recently, the ring-cleavage pathway of
cyclopropyl carbinol through stabilization of the homoallyl
cation by a silylmethyl function was efficiently utilized for the
synthesis of multiply substituted tetrahydropyran rings.9 Lewis
acids have been used as catalysts for an enormous variety of
organic reactions, for example, alkene alkylation and dimer-
ization,10 formation and hydrolysis of acetals,11 Friedel-Crafts
reactions,12 aldol and related reactions,13 and electrocyclic
reactions.14 Recent reports show that Lewis acid-mediated
halogenative ring-opening of cyclopropyl carbinol substrates
offered a practical, useful, and versatile method for the stereo-
selective synthesis of substituted olefins.15 In our recent research,
the cyclopropyl carbinol substrates, â-hydroxymethylcyclopro-
panylamides 1, showed divergent behavior with respect to the
Lewis acid catalyst. As a result, in the presence of SnCl4, TiCl4,
and BF3‚OEt2, a series of ring-opening/N- or O-annulation and
Friedel-Crafts alkylation products were obtained in high to
excellent yields, respectively, as described in Scheme 1.
(7) (a) Kanemoto, S.; Shimizu, M.; Yoshioka, H. Tetrahedron Lett. 1987,
28, 6313-6316. (b) Hardouin, C.; Taran, F.; Doris, E. J. Org. Chem. 2001,
66, 4450-4452. (c) Bernard, A. M.; Frongia, A.; Secci, F.; Piras, P. P.
Chem. Commun. 2005, 3853-3855.
(8) (a) Sarel, S.; Yovell, J.; Sarel-Imber, M. Angew. Chem., Int. Ed. Engl.
1968, 7, 577-588. (b) Wong, H. N. C.; Hon, M. Y.; Tse, C. W.; Yip, Y.
C.; Tanko, J.; Huldicky, T. Chem. ReV. 1989, 89, 165-198.
(9) Yadav, V. K.; Kumar, N. V. J. Am. Chem. Soc. 2004, 126, 8652-
8653.
(10) (a) Buchmann, W.; Desmazieres, B.; Morizur, J.-P.; Nguyen, H.
A.; Cheradame, H. Macromolecules 2001, 34, 2783-2791. (b) Angle, S.
R.; Frutos, R. P. J. Chem. Soc., Chem. Commun. 1993, 171-172. (c) Keller,
A. J. Mol. Catal. 1991, 64, 171-178.
(11) (a) Chang, J.-W.; Jang, D.-P.; Uang, B.-J.; Liao, F.-L.; Wang, S.-
L. Org. Lett. 1999, 1, 2061-2063. (b) Du, Y.; Kong, F. J. Carbohydr.
Chem. 1995, 14, 341-352. (c) Thompson, J. E. J. Org. Chem. 1967, 32,
3947-3950.
(12) (a) Uto, K.; Sakamoto, T.; Matsumoto, K.; Kikugawa, Y. Hetero-
cycles 1996, 43, 633-640. (b) Tashiro, M. Synthesis 1979, 921-936. (c)
Park, B.-D.; Lee, H.-I.; Ryoo, S.-J.; Lee, Y.-S. Tetrahedron Lett. 1997, 38,
591-594.
(16) For details for the preparation of 1-(1-hydroxyethyl)-N-(2-methoxy-
phenyl)cyclopropanecarboxamide (5) and â-hydroxymethylcyclopropanyl-
amides 1, please see the Supporting Information and also see: (a) Liu, J.;
Liang, F.; Liu, Q.; Li, B. Synlett 2007, 156-160. (b) Liu, J.; Wang, M.;
Li, B.; Liu, Q.; Zhao, Y. J. Org. Chem. 2007, 72, 4401-4405.
(17) For the preparation of condensation adducts of 1-acetyl-N-arylcy-
clopropanecarboxamides with aromatic aldehydes, please see: (a) Bi, X.;
Dong, D.; Liu, Q.; Pan, W.; Zhao, L.; Li, B. J. Am. Chem. Soc. 2005, 127,
4578-4579. (b) Bi, X.; Liu, Q.; Sun, S.; Liu, J.; Pan, W.; Zhao, L.; Dong,
D. Synlett 2005, 49-54.
(18) For selected examples for the synthesis of γ-iminolactones, see:
(a) Nair, V.; Rajesh, C.; Vinod, A. U.; Bindu, S.; Sreekanth, A. R.; Mathen,
J. S.; Balagopal, L. Acc. Chem. Res. 2003, 36, 899-907. (b) Ma, S.; Gu,
Z.; Yu, Z. J. Org. Chem. 2005, 70, 6291-6294. (c) Tang, Y.; Li, C.-Z.
Tetrahedron Lett. 2006, 47, 3823-3825. (d) Ma, S.; Xie, H. J. Org. Chem.
2002, 67, 6575-6578.
(13) (a) Mukaiyama, T.; Narasaka, K. Org. Synth. 1987, 65, 6-10. (b)
Walker, M. A.; Heathcock, C. H. J. Org. Chem. 1991, 56, 5747-5750. (c)
Uno, H.; Baldwin, J. E.; Churcher, I.; Russell, A. T. Synlett 1997, 390-
393. (d) Maeda, K.; Shinokubo, H.; Oshima, K. J. Org. Chem. 1997, 62,
6429-6431. (e) Paterson, I. Tetrahedron 1988, 44, 4207-4219.
(14) (a) Haynes, R. K.; King, G. R.; Vonwiller, S. C. J. Org. Chem.
1994, 59, 4743-4748. (b) Mandal, A. B.; Gomez, A.; Trujillo, G.; Mendez,
F.; Jimenez, H. A.; de Rosales, M.; Martinez, R.; Delgado, F.; Tamariz, J.
J. Org. Chem. 1997, 62, 4105-4115. (c) Liu, H. J.; Han, Y. Tetrahedron
Lett. 1993, 34, 423-426. (d) Engler, T. A.; Gfesser, G. A.; Draney, B. W.
J. Org. Chem. 1995, 60, 3700-3706. (e) Hojo, M.; Tomita, K.; Hirohara,
Y.; Hosomi, A. Tetrahedron Lett. 1993, 34, 8123-8126. (f) Conde, S.;
Corral, C.; Madronero, R. Synthesis 1974, 28-29.
(19) (a) Bartoli, G.; Bellucci, M. C.; Petrini, M.; Marcantoni, E.; Sambri,
L.; Torregiani, E. Org. Lett. 2000, 2, 1791-1793. (b) Kamal, A.; Prasad,
B. R.; Ramana, A. V.; Babu, A. H.; Reddy, K. S. Tetrahedron Lett. 2004,
45, 3507-3509. (c) Node, M.; Kajimoto, T.; Nishide, K.; Fujita, E.; Fuji,
K. Tetrahedron Lett. 1984, 25, 219-222.
(15) (a) Li, W.-D. Z.; Yang, J.-H. Org. Lett. 2004, 6, 1849-1852. (b)
Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C. Chem. ReV. 1989,
89, 165-198. (c) Li, W.-D. Z.; Peng, Y. Org. Lett. 2005, 7, 3069-3072.
(d) Ranu, B. C.; Banerjee, S. Eur. J. Org. Chem. 2006, 3012-3015.
8006 J. Org. Chem., Vol. 72, No. 21, 2007