Communication
in relatively low yield (entry 4, Table 2). In addition, diene 4d
was obtained as major product (44%, Supporting Information,
Table 2). Thus, the electronic nature of the aryl function has
a subtle control on the reaction pathway. Not unexpectedly,
no reaction was observed when the enyne was equipped with
an electron-poor aryl group that is, p-nitrophenyl to form
allene 3j (entry 10, Table 2). Introduction of an electron-rich
indole moiety yielded indole-substituted exocyclic allenes 3k–
l in moderate yields.
Table 1. Synthesis of exocyclic allene 3a from 1,7-enyne 1a.
Entry
Catalyst
Solvent
t [h]
T [8C]
Yield 3a [%][a]
1
2
3
4
I/AgSbF6
II
III/AgSbF6
III/AgSbF6
DCE
DCE
DCE
DCE
48
48
48
4
RT
RT
RT
40
–
–
13
17
–
In addition to variation of the styryl moiety, substitution of
the acetylene was tolerated and led to formation of the corre-
sponding allenes in very viable yields (3a, 3e–i, 3l–n). Further-
more, the diethylmalanoate tether could successfully be re-
placed with a bis(phenylsulfonyl) group to provide exocyclic al-
lenes 3m–p in good yields (entries 13–16, Table 2). These re-
sults are significant since the bis(phenylsulfonyl) tether could
not be employed in rearrangement reactions of 1,6-enynes.[3]
However, with an ether tether, the expected allene 3q was not
obtained under the optimized conditions (entry 17, Table 2).
The preferred formation of diene 4d over allene 3d during
rearrangement of (3,4-dimethyl)phenyl substituted enyne 1d
(Table 2) indicates the strong influence of the electronic nature
of the aryl ring on the enyne rearrangement. Likewise, enyne
1r with a phenyl-substituted olefin yielded only diene 4r
under the optimized reaction conditions. In the presence of
a m-methoxyphenyl group the transformation was much
slower and yielded again the diene product (4s, Scheme 2a).
We envisioned that nucleophilic addition of the aryl ring to the
gold carbene (2, pathway iii, Scheme 2a) might indeed
become relevant if the appropriate electronic and possibly
steric parameters would be matched.[3a] However, the reaction
of the corresponding enyne equipped with a more nucleophil-
ic 4-OMe-phenyl group had yielded exclusively the allene (3b,
Scheme 2a). Based on these observations, a mechanistic ra-
tionale for formation of the different products is depicted in
Scheme 2a. Allene formation is triggered by the generation of
[b]
5
IV/AgSbF6
DCE
4
40
6
7
8
9
10
11
V
V
V
V
V
V
DCE
DCE
DCM
toluene
THF
48
1.5
2
2
2
RT
13
77
63
28
19
–
80/MW
80/MW
80/MW
80/MW
80/MW
MeCN
2
[a] Conversion determined by means of gas chromatography. [b] When
the reaction time was extended to 3 days allene 3a was formed in 19%
yield (see the Supporting Information). DCE=dichloroethane; DCM=di-
chloromethane; THF=tetrahydrofuran;“–” no reaction observed.
varren et al. for a [4+2] cycloaddition reaction of 1,6-eny-
nes.[38,p] While treatment of 1,7-enyne 1a with this catalyst
(entry 5, Table 1) was uneventful, cationic gold(I) complex (V)
bearing a bulky biaryl-phosphine at room temperature (48 h)
yielded the novel exocyclic allene 3a in low yield (entry 6).
Heating the reaction mixture under microwave (MW) condi-
tions at 808C in the presence of this catalyst not only en-
hanced the yield to 77% but also reduced the reaction time to
1.5 h. While using DCM, toluene or THF as solvent reduced the
yield (entries 8–10), no reaction was observed in acetnonitrile
as solvent (entry 11). Thus, for the synthesis of exocyclic allene
3a, the best results were obtained by treatment of the DCE so-
lution of 1,7-enyne 1a with 5 mol% of catalyst V under micro-
wave irradiation and heating to 808C for 1.5 h. Although, al-
lenes themselves in principle are subject to gold activation
and thereby to further transformations, the novel exocyclic
allene 3a was stable and inert to gold catalysis.[7]
a
delocalized and stable benzylic carbocation 5 (path i,
Scheme 2a) which may undergo a 1,5-hydride shift leading to
tertiary carbocation 6. Deauration of the gold complex com-
pletes the catalytic cycle and affords the allene 3. A sufficient
nucleophilic character of the aryl group that facilitates forma-
tion of stable benzylic carbocation is a prerequisite for the in-
termediate 2 to follow this route to generate allene 3 (path i,
Scheme 2a). Alternatively, in the absence of carbocation-stabi-
lizing phenyl groups gold carbene 2 prefers to react to a terti-
ary carbocation 7 (path ii, Scheme 2a). Ring opening of the cy-
clobutane then yields the diene 4 (Scheme 2a).
Exposure of differently substituted 1,7-enynes 1 to the opti-
mized reaction conditions afforded exocyclic allenes 3 (Table 2)
in preparatively viable yields, demonstrating that the enyne re-
arrangement has substantial scope. Variation of the aryl moiety
on the styryl part of the enynes indicated that electron-rich
aryl groups are required for this transformation of enynes 1.
Enynes with mono-, di- and trimethoxyphenyl groups on the
olefin yielded the desired allenes in acceptable to high yields
(Table 2). The corresponding enyne with a less electron donat-
ing dimethylphenyl substituent yielded the expected allene 3d
The proximity of aryl and gold carbene moieties in cyclo-
propyl gold carbene intermediate 2 suggests that steric effects
might also influence the enyne skeletal rearrangement. In par-
ticular, in anti-2 carbene intermediate, a sterically relatively de-
manding substitution on the alkyne group might disfavor
a direct attack of the nucleophilic aryl groups on the gold car-
bene intermediate (2, Scheme 2b). In order to investigate
whether reduction of the possible steric hindrance between
the aryl group and the acetylenic substituent in 2 would open
up a different reaction channel, enyne 1t embodying a methyl
Chem. Eur. J. 2015, 21, 13526 – 13530
13527
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Mei?, Rebecca
