A R T I C L E S
Yamauchi et al.
Table 1. Ruthenium-Catalyzed Reaction of
to be necessary for obtaining the corresponding conjugated (E)-
enynes (3) effectively (Table 2, runs 1-4).6 The use of 10 equiv
of aniline to 1 increased the yield of 3 in all cases. The use of
the 2-thienyl moiety in place of the benzene group in propargylic
alcohol decreased the product yield (Table 2, run 5). On the
other hand, reaction of 1-cyclopropyl-1-phenylmethanol with
aniline in the presence of a catalytic amount of 2a did not give
any ring-opening products, and only the benzylic substituted
product was obtained (eq 1). Also, reaction of propargylic
1-Cyclopropyl-1-phenyl-2-propyn-1-ol (1a) with Aniline in the
Presence of Thiolate-Bridged Diruthenium Complex (2a)a
reaction conditions
time
(h)
yield of 3a
run
temp
(%)b
1
60 °C
room temp
60 °C
1
2
1
1
89
77
78
32
2
3c
4d
60 °C
a All reactions of 1a (0.25 mmol) with aniline (2.50 mmol; 10 equiv to
1a) were carried out in the presence of 2a (0.0075 mmol) in ClCH2CH2Cl
(2.5 mL). b Isolated yield. c Aniline (0.50 mmol; 2 equiv to 1a) was used.
d 2b (0.0125 mmol) was used together with NH4BF4 (0.025 mmol) in place
of 2a.
alcohol bearing an internal alkyne moiety with aniline did not
proceed smoothly, the corresponding enyne being obtained in
<10% yield even for a longer reaction time (eq 2).8 These results
Table 2. Ruthenium-Catalyzed Reactions of
1-Cyclopropyl-2-propyn-1-ols (1) with Anilines in the Presence
of 2aa
propargylic
yield of 3,
(%)b
run
alcohol 1 (Ar)
aniline
indicate that a terminal alkyne moiety in the propargylic alcohol
works as a trigger to promote the carbon-carbon bond
cleaVage of a cyclopropane ring.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1b, p-MeC6H4
1c, p-MeOC6H4
1d, p-FC6H4
1e, p-ClC6H4
1f, 2-thienyl
1a, Ph
1a, Ph
1a, Ph
1a, Ph
1a, Ph
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
p-MeC6H4NH2
3,5-Me2C6H3NH2
p-FC6H4NH2
p-ClC6H4NH2
p-MeOC(O)C6H4NH2
o-MeOC(O)C6H4NH2
p-CF3C6H4NH2
PhNHMe
3b, 73c (83)
3c, (65)
3d, 63 (80)
3e, 66 (83)
3f, (45c)
Next, reactions with other nucleophiles were carried out under
the same reaction conditions. A variety of anilines were revealed
to be available as nucleophiles to give the corresponding 1,3-
enynes in good to high yields (Table 2, runs 6-12). In contrast,
reactions of N-substituted anilines such as N-methylaniline and
N,N-diphenylamine were sluggish (Table 2, runs 13 and 14).
Unfortunately, the use of alkylamines and amides such as
benzylamine, butylamine, acetamide, and benzenesulfonamide
was in vain although amides were known to work as nucleo-
philes in the propargylic substitution reactions catalyzed by 2.3a
Reactions of some propargylic alcohols in water also pro-
ceeded smoothly to give the corresponding conjugated (E)-
enynes in good to high yields. Typical results are shown in Table
3. It was clearly confirmed that water works as a nucleophile
when H218O was used as solvent (Table 3, run 2). Thus, we
have newly found that water can be used as a nucleophile in
the reactions accompanied by ring opening. This is the first
successful example of catalytic reactions with water, where
allenylidene complexes are considered to be important inter-
mediates.
3g, (75)
3h, (67d)
3i, 68 (80)
3j, 68 (78)
3k, 69 (78)
3l, (71)
3m, 66 (82)
3n, 75e (82e)
3o, 39e (52e)
1a, Ph
1a, Ph
1a, Ph
1a, Ph
Ph2NH
a All reactions of 1 (0.25 mmol) with aniline (0.50 mmol; 2 equiv to 1)
were carried out in the presence of 2a (0.0075 mmol) in ClCH2CH2Cl (2.5
mL) at 60 °C for 1 h. b Isolated yield. The value in parentheses is the isolated
yield of the reaction with aniline (2.50 mmol; 10 equiv to 1). c For 3 h.
d For 6 h. e 2a (0.0125 mmol; 5 mol % to 1) was used and for 24 h.
(µ2-SMe)2RuCp*(OH2)]OTf4 (Cp* ) η5-C5Me5; OTf ) OSO2-
CF3; 2a) (3 mol %) in ClCH2CH2Cl at 60 °C for 1 h afforded
the (E)-1,3-enynes (3a, E only) in 89% isolated yield with a
complete selectivity (Scheme 1; Table 1, run 1). No stereoiso-
mers were detected by 1H NMR. The reaction proceeded
smoothly even at room temperature only with a slight decrease
in the product yield (Table 1, run 2). Even the use of 2 equiv
of aniline to 1a worked well with only a slight decrease of 3a
(Table 1, run 3). This catalytic reaction also proceeded smoothly
when the corresponding neutral diruthenium complex [Cp*RuCl-
(µ2-SMe)]24 (2b) was used as a catalyst together with NH4BF4
(Table 1, run 4). Interestingly, the reaction did not proceed at
all in the presence of a catalytic amount of other transition metal
salts and Brønsted acid such as AuCl3, FeCl3, and p-toluene-
sulfonic acid.5
In order to obtain some information about the reaction
pathway, the following stoichiometric and catalytic reactions
were investigated. Treatment of 2a with a stoichiometric amount
of 1a in tetrahydrofuran (THF) at room temperature for 30 min
gave the corresponding allenylidene complex bearing a cyclo-
(5) Some metal salts and Brønsted acid were reported to work as catalysts for
the propargylic substitution reactions; see: (a) Georgy, M.; Boucard, V.;
Campagne, J.-M. J. Am. Chem. Soc. 2005, 127, 14180. (b) Zhan, Z.; Yu,
J.; Liu, H.; Cui, Y.; Yang, R.; Yang, W.; Li, J. J. Org. Chem. 2006, 71,
8298. (c) Sanz, R.; Mart´ınez, A.; AÄ ivarez-Gutie´rrez, J. M.; Rodr´ıguez, F.
Eur. J. Org. Chem. 2006, 1383. (d) Qin, H.; Yamagiwa, N.; Matsunaga,
S.; Shibasaki, M. Angew. Chem., Int. Ed. 2007, 46, 409.
(6) The stereochemistry of some enyne products was determined by X-ray
analysis. See the Supporting Information for experimental details.
(7) See the Supporting Information for experimental details.
(8) (a) For a review of cyclopropylmethyl cations, see: Richey, H. G., Jr. In
Carbonium Ions; Olah, G. A., Schleyer, P. V. R., Eds.; Wiley-Inter-
science: New York, 1972; Vol. III, Chapter 25. (b) Childs, R. F.; Kostyk,
M. D.; Lock, C. J. L.; Mahendran, M. J. Am. Chem. Soc. 1990, 112, 8912.
Catalytic reactions of other propargylic alcohols (1) with
aniline were investigated by using 2a as a catalyst. Typical
results are shown in Table 2. The presence of an aryl moiety at
the propargylic position of propargylic alcohols was revealed
(4) Nishibayashi, Y.; Imajima, H.; Onodera, G.; Inada, Y.; Hidai, M.; Uemura,
S. Organometallics 2004, 23, 5100 and references therein.
9
5176 J. AM. CHEM. SOC. VOL. 129, NO. 16, 2007