A. I. Siriwardana et al. / Tetrahedron Letters 44 (2003) 4547–4550
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80°C with water to afford 2a, 2b and 2f in 86, 87 and
92% yields, respectively (entries 1, 2 and 6). Likewise,
the addition of water to the unsymmetrical MCPs,
(1-phenyl-3,4-dimethylbenzylidene)cyclopropane 1c, (1-
phenyl-m-toludene)cyclopropane 1d, (1-phenylnaph-
thyledene)cyclopropane 1e and [(1-phenyl)-4-chloro-
benzylidene]cyclopropane 1g, proceeded smoothly to
afford 2c, 2d, 2e and 2g as E/Z isomers, respectively.
We attempted to determine the ratio and stereochem-
istry of the stereoisomers, but all the isomers were
unseparable.
We investigated the effect of the amount of water on
the chemical yield of 2a in the reaction of 1a using 10
mol% Cu(OTf)2. As shown in Table 1, the use of 2
equiv. of H2O gave the highest chemical yield. Lower
chemical yields were obtained when one or three equiv-
alents of water were used. Interestingly, the yield
dropped dramatically upon the use of a larger amount
of water (entry 4). This is perhaps a reason why Min
Shi and Bo Xu obtained only 25% yield when they
carried out the reaction of 1a with water in the presence
of 10 mol% of Sn(OTf)2.
The reaction of 1f bearing an electron-donating group
gave 2f in 92% yield (entry 6). On the other hand, the
reaction of 1g bearing an electron-withdrawing group
gave the corresponding homoallylic alcohol 2g in a
moderate yield (entry 7).
The reaction was sensitive to air and should be per-
formed under an inert-gas atmosphere; if the reaction
was carried out under air, the chemical yield
decreased.10 In entries 1–2, 4, and 6–7, when a mixture
of the MCPs (0.5 mmol) and water (1 mmol) was
heated at 80°C, if the MCPs became liquid although
they were solid at room temperature or even at 60°C. If
an MCP became liquid at 80°C, we obtained the corre-
sponding homoallylic alcohol in excellent or good yield.
However, in entries 3 and 5, 1c and 1e did not became
liquid at 80°C and the mixture of the MCPs and water
consisted of solid and liquid.11 In these cases, addition
of very small amounts (0.1–0.15 ml) of benzene
changed the solid MCPs into liquids, and the desired 2c
and 2e could be obtained in high chemical yields.
Except for entries 3 and 5, no organic solvents were
used in the other entries; if THF, 1,4-dioxane, CH3CN,
or DMSO were used as the solvent in the reaction of
1a, 2a was not obtained at all. If small amounts (0.1–
0.15 ml) of benzene were used as the solvent, 2a was
produced in 69% yield (cf. entry 1). The use of cyclo-
hexane and hexane gave a similar result as benzene.
Accordingly, the reaction of 1 with water was very
sensitive to reaction conditions: (1) the use of a sealed
pressure vial under an inert gas atmosphere: (2) 2 equiv.
of H2O; (3) 80°C without organic solvents (very small
amounts of benzene or hydrocarbon solvent are accept-
able if needed). In the absence of Lewis acid catalysts,
no reaction occurred. Among the Lewis acids exam-
ined, Cu(OTf)2 gave the best result. Sn(OTf)2 was less
reactive than Cu(OTf)2, and no reaction occurred in the
presence of Yb(OTf)3, Sc(OTf)3 and Zn(OTf)3. It
should be mentioned that the protic acid, TfOH (10
mol%), can catalyze the addition of water to 1a under
similar conditions, but the yield of 2a (46%) was lower
than that of the Cu(OTf)2 catalyzed reaction. Increas-
ing the mol% of TfOH did not change the yield of the
desired homoallylic alcohol and decreasing the mol%
TfOH gave 2a in much lower yield.
We are now in a position to synthesize symmetrical and
unsymmetrical gem-diaryl substituted homoallylic alco-
hols in good to high yields. The starting materials,
diarylidenecyclopropanes, are readily available, and the
other substrates are 2 equiv. of water and catalytic
amounts of Cu(OTf)2. Accordingly, this new procedure
seems to provide a useful protocol for the synthesis of
homoallylic alcohols, although at the present stage the
reaction is limited to diarylsubstituted MCPs. The
related reaction of di- or mono-alkylsubstituted MCPs
is under active investigation in our laboratories.
The preparation of 3-bromopropyltriphenylphosphonium
bromide.12 A mixture of an equimolar amount of
trimethylene bromide and triphenylphosphine was
heated in xylene at 130°C for 16 h. Repeated recrystal-
lization of the crude product using ethanol gave the
desired product in 90% yield.
The preparation of 1a as a representative procedure for
the synthesis of MCPs.13 To a suspension of 3-bromo-
propyltriphenylphosphonium bromide (10.212 g, 22
mmol) in THF (100 ml) were added three portions of
t-BuOK (4.937 g, 44 mmol) at intervals of 15 min at
room temperature under an Ar atmosphere. After
refluxing for 2 h, benzophenone (3.699 g, 20.3 mmol)
was added into the yellow–brown suspension at 65°C.
The reaction was monitored by TLC. After 2 h, the
reaction mixture was cooled to ambient temperature
and 100 ml of water was added. The mixture was
extracted with hexane twice. The combined organic
layer was washed with brine and dried over sodium
sulphate. The solvent was evaporated and the residue
was filtered through a plug of Celite. Purification by
silica gel column chromatography using hexane as elu-
ent gave 1a in 75% yield.
At higher temperatures (100–140°C) decomposition of
MCPs competed with formation of homoallylic alco-
hols and the desired products were obtained in lower
yields. At a lower temperature (60°C) the reaction did
not proceed well even after 4–5 days because MCPs
were solid at this temperature. The symmetrical MCPs,
(1-phenylbenzylidene)cyclopropane 1a, [1-(4-methyl-
benzyl)-p-toludene]cyclopropane 1b and [1-(4-methoxy-
phenyl)-4-methoxybenzylidene]cyclopropane 1f, under-
went facile ring opening of the cyclopropane ring at
The preparation of 2a as a representative procedure for
the synthesis of homoallylic alcohols. To 1a (103.1 mg,
0.5 mmol) in a pressure vial under an Ar atmosphere
was added water (18 ml, 1.0 mmol) and the mixture was
stirred at 80°C for 3 days. After completion of the
reaction, which was monitored by GC, the mixture was
then filtered through a short silica column with ethyl