Kamijo et al.
TABLE 4. Optimization of Reaction Conditions for the
Isomerization from 1k to 5k
as a catalyst. The reactions in polar solvents such as 1,4-
dioxane, CH3CN, and 2-propanol did not consume all of
the starting material even after 24 h at 120 °C and gave
the lower yields of 5k with a recovery of 1k (entries 12-
14), whereas 1k was consumed completely in 2 h when
the reaction was carried out in toluene and the isomer-
ized product 5k was obtained in high yield (entry 1). With
the desired vinyltriazole 5k in hand, we examined
removal of the vinyl group on a nitrogen atom in the
triazole ring. The standard acidic treatments in an
alcoholic solvent, used for common vinylamines and
vinylamides, did not work at all, and the starting
material 5k was recovered.25 To our surprise, oxidative
cleavage of the vinyl group in 5k using O3 produced the
N-unsubstituted triazole 2k in a high yield without
forming the corresponding formamide.26
We then examined the scope and limitation of the
present stepwise protocol for deallylation of allylated
azoles. The results of the reaction using 1-allyltriazoles
1c, 1d, and 1l are summarized in Table 5. The reaction
of 4-phenyl-1-allyl-1,2,3-triazole 1c with a catalytic amount
of HRuCl(CO)(PPh3)3 (5 mol %) in toluene at 120 °C was
completed in 2 h to give 4-phenyl-1-(1-propenyl)-1,2,3-
triazole 5c in 92% yield as an 85:15 mixture of trans and
cis isomers (entry 1). Subsequently ozonolysis of the
vinyltriazole 5c was carried out in CH2Cl2/MeOH (3/2,
0.1 M) at -78 °C, and the reaction mixture was then
treated with Me2S. The corresponding N-unsubstituted
triazole 2c was obtained in 93% yield. The allyltriazole
1d afforded the corresponding vinyltriazole 5d in 85%
yield, and ozonolysis gave 2d in an excellent yield (entry
2). The reaction of the diallyltriazole 1l required a higher
loading of the catalyst and a longer time and gave 1,5-
di(1-propenyl)-4-phenyl-1,2,3-triazole 5l′ in 81% yield as
a mixture of possible four stereoisomers (entry 3). The
treatment of 5l′ with O3 took place to produce 4-formyl-
5-phenyl-1,2,3-triazole 2l′ as the final product in a
moderate yield.
entry
catalyst
solvent
toluene
toluene
toluene
toluene
NMR yield of 5k,a %
1
2
3
4
5
6
7
8
HRuCl(CO)(PPh3)3
H2Ru(CO)(PPh3)3
H2Ru(PPh3)4
RuCl2(PPh3)3
Cl2(Cy3P)2Ru(dCHPh) toluene
Ru3(CO)12
RuCl3‚nH2O
HRh(CO)(PPh3)3
83b
tracec
tracec
0c
0c
toluene
toluene
CH3CN/H2O
toluene
toluene
toluene
dioxane
CH3CN
2-propanol
0c
0c
8.5c
0c
9d RhCl(PPh3)3
10e IrCl(CO)(PPh3)2
11 PdCl2(PPh3)2
0c
0c
12 HRuCl(CO)(PPh3)3
13 HRuCl(CO)(PPh3)3
14 HRuCl(CO)(PPh3)3
59c
15c
54c
a NMR yield otherwise noted. b Isolated yield. c The recovery of
1k was observed. d The reaction was carried out at 100 °C for 10
h. e The reaction was carried out for 24 h.
thenium-catalyzed isomerization of N-allylazoles 1 and
3 to N-vinylazoles 5 and 6 and oxidative cleavage of the
intermediates 5 and 6 to the corresponding N-unsubsti-
tuted azoles 2 and 4 by a treatment with O3 (Scheme 2b).
We first screened various transition-metal catalysts for
the isomerization of the allyltriazole 1k to the corre-
sponding vinyltriazole 5k. The representative results are
summarized in Table 4.23 We found that the transforma-
tion from 1k to 5k was efficiently catalyzed by the
HRuCl(CO)(PPh3)3 complex in toluene at 120 °C for 2 h
(entry 1).24 The hydridoruthenium catalysts such as H2-
Ru(CO)(PPh3)3 and H2Ru(PPh3)4 afforded a trace amount
of the desired product 5k (entries 2 and 3), whereas the
rest of the ruthenium catalysts did not promote the
isomerization at all (entries 4-7). The hydridorhodium
catalyst, HRh(CO)(PPh3)3, gave a low yield of 5k (entry
8), although no reaction took place with Wilkinson’s
catalyst, RhCl(PPh3)3, Vaska’s catalyst, IrCl(CO)(PPh3)2,
and PdCl2(PPh3)2, and a quantitative recovery of the
starting material 1k was observed (entries 9-11). We
also examined solvent effects using HRuCl(CO)(PPh3)3
The results of the stepwise deallylation of 2-allyltri-
azoles 1m, 1k, and 1i are summarized in Table 6. The
phenyl-substituted 2-allyltriazole 1m gave the desired
2-vinyltriazole 5m with the Ru catalyst, and ozonolysis
furnished the corresponding product 2c in a high yield
(entry 1). The product obtained in entry 1 was exactly
identical with the compound derived from the corre-
sponding 1-allyltriazole 1c. The allyltriazoles 1k and 1i
bearing electron-withdrawing groups afforded the isomer-
ized vinyltriazoles 5k and 5i, and the following ozonolysis
gave the N-unsubstituted triazoles 2k and 2i in high
yields, respectively (entries 2 and 3). On the basis of the
analysis of its spectroscopic data, the compound 2i is
found to be 4,5-di(methoxycarbonyl)-2H-1,2,3-triazole.27
(23) For representative transition metals used for isomerization of
allylamines and/or allylamides, see: (a) Stille, J. K.; Becker, Y. J. Org.
Chem. 1980, 45, 2139-2145 (Ru, Fe). (b) Tani, K.; Yamagata, T.;
Akutagawa, S.; Kumobayashi, H.; Taketomi, T.; Yakaya, H.; Miyashita,
A.; Noyori, R.; Otsuka, S. J. Am. Chem. Soc. 1984, 106, 5208-5217 (c)
Tani, K. Pure. Appl. Chem. 1985, 57, 1845-1854 (Rh). (d) Sonesson,
C.; Hallberg, A. Tetrahedron Lett. 1995, 36, 4505-4506 (Pd). (e)
Neugnot, B.; Cintrat, J.-C.; Rousseau, B. Tetrahedron Lett. 2004, 60,
3575-3579 (Ir). (f) Alcaide, B.; Almendros, P.; Alonso, J. M.; Aly, M.
F. Org. Lett. 2001, 3, 3781-3784 (Ru). (g) Sergeyev, S.; Hesse, M.
Synlett 2002, 1313-1317 (Fe). (h) Moreau, B.; Lavielle, S.; Marquet,
A. Tetrahedron Lett. 1977, 30, 2591-2594 (Rh, Pt, Pd). (i) Alcaide, B.;
Almendros, P.; Alonso, J. M. Chem. Eur. J. 2003, 9, 5793-5799 (Ru).
(j) Alcaide, B.; Almendros, P.; Alonso, J. M. Tetrahedron Lett. 2003,
44, 8693-8695 (Ru).
(24) (a) Wakamatsu, H.; Nishida, M.; Adachi, N.; Mori, M. J. Org.
Chem. 2000, 65, 3966-3970. (b) Dom´ıngues, G.; Casarrubios, L.;
Rodr´ıguez-Noriega, J.; Pe´rez-Castells, J. Helv. Chim. Acta 2002, 85,
2856-2861. (c) Krompiec, S.; Pigulla, M.; Szczepankiewicz, W.; Bieg,
T.; Kuznik, N.; Leszczynska-Sejda, K.; Kubicki, M.; Borowiak, T.
Tetrahedron Lett. 2001, 42, 7095-7098.
We next investigated the deallylation of N-allyltetra-
zoles 3b, 3d, and 3e by utilizing the same stepwise
(25) In ref 10a, pp 574-576 and references therein.
(26) Protecting groups for nitrogen-containing heteroaromatics,
see: (a) Theodoridis, G. Tetrahedron Lett. 1998, 39, 9365-6368
(triazolinone). (b) Hartley, D. J.; Iddon, B. Tetrahedron Lett. 1997, 38,
4647-4650 (imidazole). (c) Montgomery, J. A.; Thomas, H. J. J. Org.
Chem. 1965, 30, 3235-3236 (purine). (d) Kimbonguila, A. M.; Boucida,
S.; Guibe´, F.; Loffet, A. Tetrahedron 1997, 53, 12525-12538 (imida-
zole).
(27) Due to the symmetrical structure of 2i, the position of a proton
attached to nitrogen atom was easily determined; see the Supporting
Information for details.
6394 J. Org. Chem., Vol. 70, No. 16, 2005