Communication
matching between the diene and dienophine (both are elec-
tron rich).
Table 1. Optimization of reaction conditions.[a]
o-Quinodimethane (o-QDM) is a transient short-lived and
highly reactive species.[10] A cis-diene, o-QDM is much more re-
active than the related classical diene (such as butadiene and
cyclopentadiene) in Diels–Alder reactions. Inspired by the
above biosynthetic proposal of salvileucalin B, also as part of
our continuing efforts to develop o-QDM chemistry,[11] we envi-
sioned that benzotricyclo[3.2.1.02,7]octane D could be readily
available from the vinyl-substituted cyclic-o-QDM C through an
intramolecular Diels–Alder reaction (Scheme 4).
Entry
Catalyst
Additive
Yield 3a [%]
Yield 4a [%]
1
2
3
AgSbF6
FeCl3
ZnCl2
–
–
–
n.d.
3
9
34
7
13
4
5
6
7
8
9
CuCl2·2H2O
KAuCl4·2H2O
[AuCl(IMes)]
[AuCl(IMes)]
[AuCl(SIMes)]
[AuCl(IPr)]
[AuCl(SIPr)]
[AuCl(SIMes)]
[AuCl(SIMes)]
–
–
–
–
10
20
n.d.
41
51
32
43
78
5
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
Selectfluor
10
11[b]
12[b,c]
13
Scheme 4. Proposed bioinspired synthesis of tricyclo[3.2.1.02,7]octane D from
vinyl cyclic-o-QDM C.
96[d]
n.d.
[a] Unless otherwise noted, the reactions were performed in DCE at 808C
for 14 h using 5 mol% catalyst and 10 mol% additive under N2, 1a/2a=
1:1. [1a]=0.05m. The yield was determined by 1H NMR spectroscopy
with MeNO2 as the internal standard. IMes: 1,3-dimesitylimidazol-2-yli-
dene; SIMes: 1,3-dimesitylimidazolin-2-ylidene; IPr: 1,3-bis(2,6-diisopropyl-
phenyl)imidazol-2-ylidene; SIPr: 1,3-bis(2,6-diisopropylphenyl)imidazolin-
2-ylidene. [b] 1a/2a=1:5. [c] 15 mol% Selectfluor. [d] Isolated yield.
Herein, we would like to report the realization of such a hy-
pothesis to rapid access to the benzotricyclo[3.2.1.02,7]octane
skeleton through the gold-catalyzed generation and trapping
of the cyclic-o-QDM from the reaction of enynals and 1,3-buta-
dienes. The reaction proceeded through the well-known pyryi-
lium intermediate[12] (Scheme 5).
dant in generating NHC–AuIII+ in situ through the reaction of
NHC–AuI and Selectfluor.[11b,13] Inspired by these facts, we tried
to produce the NHC–AuIII+ complex through the reaction of
NHC–AuI and Selectfluor. Interestingly, a significant positive
effect was observed when the combination of [AuCl(IMes)]/Se-
lectfluor (1:2) was applied. The yield of 3a was improved to
41% (entry 7). Among four different [AuCl(NHC)] complexes
being tested, [AuCl(SIMes)] functioned better than the other
three (entries 7–10). The yield of 3a was enhanced to 51% for
the combination of [AuCl(SIMes)]/Selectfluor. Increasing the
amount of diene (2a) or Selectfluor could improve the yields
further (entries 11–12). For example, the yield of 3a was 78%
when five equivalents of 2a were applied (entry 11). The best
result was obtained when the reaction was conducted in DCE
at 808C for 14 h by using 5 mol% [AuCl(SIMes)] as the catalyst
and 15 mol% Selectfluor as additive under N2, and the molar
ratio of 1a/2a=1:5 (entry 12). Under the optimized reaction
conditions, the yield of 3a climbed to 96% (entry 12). The re-
action did not occur without the gold catalyst (entry 13, see
the Supporting Information for detailed condition screening).
The structures of 3a and 4a were confirmed by their X-ray dif-
fraction analysis (see the Supporting Information). It’s interest-
ing to find that only one isomer of 3a was found for all cases
in Table 1, although the mixture of cis- and trans-diene 2a was
used as the starting material.
Scheme 5. Rapid synthesis of the highly strained polycyclic structure.
Initial efforts were made to systematically investigate various
catalytic reaction conditions for the reaction of enynal and 1,3-
diene. Heating equimolar amounts of enynal (1a) and phenyl
1,3-butadiene (2a) in 1,2-dichloroethane (DCE) with a catalytic
amount of AgSbF6 did not furnish the desired product 3a,
however, an unexpected Friedel–Crafts product 4a was ob-
tained in 34% instead (Table 1, entry 1). Gratifyingly, the de-
sired product 3a could be obtained in low yields when FeCl3,
ZnCl2, and CuCl2·2H2O were used as catalysts (entries 2–4). In
these cases, 4a was also observed as a side product. Further
screening of the catalysts and additives revealed that AuIII can
catalyze this reaction leading to 3a as the sole product (en-
tries 5–12). For example, 3a could be obtained in 20% yield
when KAuCl4·2H2O was used as the catalyst. N-heterocyclic car-
bene (NHC)-supported gold(I) complex ([AuCl(IMes)]) alone
was inefficient for this transformation (entry 6). With the fact
that AuIII was a better catalyst to promote this transformation,
we then focused our attention to find other AuIII sources. Re-
cently, Selectfluor was extensively used as a mild organic oxi-
With the optimized reaction conditions (Table 1, entry 12) in
hand, the substrate scope was then examined. As summarized
in Table 2, the catalytic process could be successfully applied
to a variety of enynals/enynones 1 and dienes 2. For example,
Chem. Eur. J. 2014, 20, 2425 – 2430
2426
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