diazocompounds11 in the Rh(II)-catalyzed chemoselective
reaction with terminal alkynes to produce indolizines 2 or
3-(2-pyridyl)cyclopropenes 3, depending upon catalyst source
(eq 3).10 The presence of the halogen substituent in 1 was
crucial, as no reaction occurred with triazoles possessing H
or alkyl groups at C-7.10 Although the direct Rh(II) perfluo-
robutyrate-catalyzed transannulation of triazoles provided a
rapid and convenient approach toward indolizines,10 it was
not without limitations. Thus, only triazoles that possessed
strong electron-withdrawing group at C-3 (R2 ) CO2R) were
efficient in this transannulation reaction. We hypothesized
that, potentially, the rearrangement of 3-(2-pyridyl)cyclo-
propenes 3 could provide alternative routes to indolizines 2
as shown in eq 2.
Table 1. Rh2(S-DOSP)4-Catalyzed Cyclopropenation of
Pyridotriazoles with Alkynes
no. R1
R2
R3
yield,a %
1
2
3
4
5
6
7
8
9
Cl Ph
1a Ph
3a
3b
3c
3d
3e
3f
81
79
65
88b
67
45
68
93
93c
67
72
87
69
86d
68
Cl Ph
Cl Ph
Br Ph
Cl p-OMeC6H4 1c Ph
Cl p-OMeC6H4 1c o-tolyl
Cl p-CF3C6H4
Cl p-CF3C6H4
Cl CO2Me
1a p-OMeC6H4
1a p-CO2MeC6H4
1b Ph
1d Ph
1d 1-cyclohexenyl 3h
1e p-tolyl
1e p-OMeC6H4
1e p-CO2MeC6H4
1e m-CO2MeC6H4 3l
1b n-butyl
1e Ph
3g
3i
3j
3k
10 Cl CO2Me
11 Cl CO2Me
12 Cl CO2Me
13 Br Ph
14 Cl CO2Me
15 Cl Ph
3m
3n
3o
1a (CH2)3Cl
a Isolated yield. b 8% ee. c 86% ee. d 84% ee.
To this end, we tested the generality of the Rh2(S-DOSP)2-
catalyzed cyclopropenation of triazoles with alkynes. To our
delight, we found that a variety of pyridyl-containing
cyclopropenes can easily be synthesized in good yields via
this method (Table 1).12 Thus, triazoles 1a-d possessing both
electron-rich and electron-deficient aryl substituents at C-3
reacted smoothly with various alkyl-, aryl-, and alkenyl-
containing alkynes to afford corresponding cyclopropenes 3
chemoselectively (Table 1). Cyclopropenation of 3-car-
bomethoxytriazole 1e proceeded uneventfully, producing
corresponding cyclopropenes 3 in good to excellent yields
(entries 9-12, 14).
pothesis on the cyclopropene into N-fused pyrrole transfor-
mation (eq 2). To this end, we tested rearrangement of
cyclopropene 3a into indolizines 2a and 4a in the presence
of a series of transition-metal catalysts (Table 2). The
Table 2. Metal-Catalyzed Rearrangement of Cyclopropene 3a
Naturally, having in hand this convenient method for the
synthesis of 3-iminocyclopropenes, we evaluated our hy-
(6) (a) Padwa, A.; Blacklock, T.; Loza, R. J. Am. Chem. Soc. 1981, 103,
2404. (b) Padwa, A.; Blackbock, T. J.; Loza, R. J. Org. Chem. 1982, 47,
3712. (c) Mu¨ller, P.; Pautex, N.; Doyle, M. P.; Baheri, V. HelV. Chim.
Acta 1990, 73, 1233. (d) Cho, S. H.; Liebeskind, L. S. J. Org. Chem. 1987,
52, 2631. (e) Padwa, A.; Kassir, J. M.; Xu, S. L. J. Org. Chem. 1997, 62,
1642. (f) Mu¨ller, P.; Gra¨nicher, C. HelV. Chim. Acta 1993, 76, 521. (g)
Mu¨ller, P.; Gra¨nicher, C. HelV. Chim. Acta 1995, 78, 129.
(7) (a) Tomilov, Y. V.; Shapiro, E. A.; Protopopova, M. N.; Ioffe, A. I.;
Dolgii, I. E.; Nefedov, O. M. IzV. Akad. Nauk SSSR, Ser. Khim. 1985, 631.
(b) Davies, H. M. L.; Romines, K. R. Tetrahedron 1988, 44, 3343. (c)
Padwa, A.; Kassir, J. M.; Xu, S. L. J. Org. Chem. 1991, 56, 6971. (d) Ma,
S.; Zhang, J. J. Am. Chem. Soc. 2003, 125, 12386.
no.
catalyst
T (°C)
2a:4a ratioa
yield,b %
1
2
3
4
5
6
7
8
9
PdCl2
PtCl2
rt
rt
2:1
4:1
5:1
23
38
86
0c
32
49
92
31
0c
0c
78
Pt(PPh3)4
NiCl2
60
60
60
60
rt
rtd
60
60d
rt
RuCl2(PPh3)3
[Ir(cod)py(PCy3)]PF6
RhCl(PPh3)3
Rh2(pfb)4
AgSbF6
8:1
>99:1
>99:1
<1:99
(8) For photochemical isomerization, see: Zimmerman, H. E.; Wright,
C. W. J. Am. Chem. Soc. 1992, 114, 6603.
(9) For selected examples on biological activity of indolizines, see: (a)
Hagishita, S.; Yamada, M.; Shirahase, K.; Okada, T.; Murakami, Y.; Ito,
Y.; Matsuura, T.; Wada, M.; Kato, T.; Ueno, M.; Chikazawa, Y.; Yamada,
K.; Ono, T.; Teshirogi, I.; Ohtani, M. J. Med. Chem. 1996, 39, 3636. (b)
Gundersen, L.-L.; Malterud, K. E.; Negussie, A. H.; Rise, F.; Teklu, S.;
Østby, O. B. Bioorg. Med. Chem. 2003, 11, 5409.
10
11
AuCl3
CuI
<1:99
a NMR ratio. b Combined NMR yield of both isomers. c A mixture of
unidentified products formed. d Dichloroethane used as solvent.
(10) Chuprakov, S.; Hwang, F. W.; Gevorgyan, V. Angew. Chem., Int.
Ed. 2007, 46, 4757.
(11) For cyclopropanation with 2-pyridyl diazo compounds, see: Davies,
H. M. L.; Townsend, R. J. J. Org. Chem. 2001, 66, 6595.
(12) Despite the efficiency of Rh2(S-DOSP)4 in enantioselective cyclo-
propenations,13 we observed very low levels of enantioselectivity in synthesis
of 3-aryl-substituted cyclopropenes. However, selected examples indicate
highly enantioselective cyclopropenation in a case of 3-carbomethoxy
derivatives (see Table 1).
employment of Pd(II) and Pt(II) chlorides in DMF at room
temperature resulted in low yields and moderate regioselec-
tivity of rearrangement (entries 1 and 2). The yield was
improved upon switching to Pt(0) complex (entry 3);
however, the selectivity remained unsatisfactory. Gratify-
4464
Org. Lett., Vol. 9, No. 22, 2007