Bioinspired intramolecular diels-alder reaction: A rapid access to the highly-strained cyclopropane-fused polycyclic skeleton

Article abstract of DOI:10.1002/chem.201304839

A bioinsipred gold-catalyzed tandem Diels-Alder/Diels-Alder reaction of an enynal and a 1,3-diene, forming the highly-strained benzotricyclo[3.2.1.0 ^2,7]octane skeleton, was reported. In contrast, a Diels-Alder/Friedel-Crafts tandem reaction occurred instead when silver salts were used as the catalyst. Although both reactions experienced the similar Diels-Alder reaction of a pyrylium intermediate with a 1,3-diene, they have different reaction mechanisms. The former proceeded with a stepwise Diels-Alder reaction, while the latter one with a concerted one. Mother nature knows best! A gold-catalyzed reaction of enynals and 1,3-dienes, giving rapid access to the highly strained benzotricyclo[3.2.1.0^2,7]octane skeleton, is reported (see scheme; QMD=quinodimethane). Owing to the mild reaction conditions, excellent substrate scope, and high functional-group tolerance, this system holds potential for the construction of complex molecules with the tricyclo[3.2.1.0^2,7]octane skeleton. Copyright

Full text of DOI:10.1002/chem.201304839

DOI: 10.1002/chem.201304839
Communication
&
Synthetic Methods
Bioinspired Intramolecular Diels–Alder Reaction: A Rapid Access
to the Highly-Strained Cyclopropane-Fused Polycyclic Skeleton
Shifa Zhu,* Zhengjiang Guo, Zhipeng Huang, and Huanfeng Jiang[a]
Abstract: A bioinsipred gold-catalyzed tandem Diels–
Alder/Diels–Alder reaction of an enynal and a 1,3-diene,
forming the highly-strained benzotricyclo[3.2.1.02,7]octane
skeleton, was reported. In contrast, a Diels–Alder/Friedel–
Crafts tandem reaction occurred instead when silver salts
were used as the catalyst. Although both reactions experi-
enced the similar Diels–Alder reaction of a pyrylium inter-
mediate with a 1,3-diene, they have different reaction
mechanisms. The former proceeded with a stepwise
Diels–Alder reaction, while the latter one with a concerted
one.
Scheme 1. Naturally occurring compounds containing tricyclo[3,2,1.02,7]-
octane.
Architecturally complex natural or unnatural molecules contin-
ue to serve as a testing ground for state-of-the-art synthetic
organic chemistry and as a powerful avenue for the invention
of novel synthetic technologies and strategies.[1] One of the
most challenging issues in synthesizing these complex mole-
cules is how to efficiently and selectively construct the highly
strained polycyclic skeleton.[2] Cyclopropane is the smallest all-
carbon cyclic molecule with the highest ring-strain in cycloal-
kanes.[3] The cyclopropane-fused polycyclic structure represents
Scheme 2. Proposed biosynthesis of salvileucalin B.
an even higher-strained motif. Construction of such an unusual
system still remains highly challenging despite extensive re-
search in the area of metal-catalyzed cyclopropanation.[3,4]
semble these tough skeletons. For instance, salvileucalin B has
Cyclopropane-fused tricyclo[3.2.1.02,7]octane consists of
fused three-, five-, and six-membered rings. It is the core struc-
ture of many naturally occurring and biologically active sub-
stances, such as cycloseychellene,[5] ishwarane/ishwarone,[6]
ent-trachyloban-3b-ol,[7] and salvileucalin B[8] (Scheme 1). For
example, salvileucalin B, obtained from the plant Salvia leucan-
tha, was found to exhibit cytotoxic activity against A549
(human lung adenocarcinoma) and HT-29 (human colon ade-
nocarcinoma) cells.[8]
been hypothesized to originate biosynthetically from salvileu-
calin A by a tandem enzymatic oxidation and intramolecular
Diels–Alder reaction (Scheme 2).[8b,9]
Such a highly efficient molecular architecture strategy in
nature has sparked strong interest from synthetic chemists. For
example, Chen and co-workers reported an elegant modular
synthetic strategy to construct the key tricyclo[3.2.1.02,7]octane
fragment B of salvileucalin B from cyclohexadiene A through
the intramolecular Diels–Alder reaction (Scheme 3).[8b] However,
the reaction was limited by its harsh conditions: iterative mi-
crowave heating and high temperature (2508C). Such harsh re-
action conditions may be attributed to the high strain of the
fully substituted cyclopropane and the abnormal electron-
Although many of these molecules were found to exhibit ex-
cellent biological activities, the construction of the cyclopro-
pane-based polycyclic structures typically required a multi-step
procedure or harsh reaction conditions.[4] Nature has endowed
the chemical world with an elegant and magic power to as-
[a] Prof. Dr. S. Zhu, Z. Guo, Z. Huang, Prof. Dr. H. Jiang
School of Chemistry and Chemical Engineering
South China University of Technology
Guangzhou 510640 (P. R. China)
E-mail: zhusf@scut.edu.cn
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201304839.
Scheme 3. Biomimetic synthesis of the core structure of salvileucalin B.
Chem. Eur. J. 2014, 20, 2425 – 2430
2425
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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
www.chemeurj.org
2426
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
Table 2. Substrate scopes of enynal/enynone with 1,3-diene.[a]
Table 2. (Continued)
[a] Unless specified, the reactions were carried out under N2 with a molar
ratio of 1/2=1:5. [1]=0.05m. The yield refers to isolated yield.
in addition to phenyl 1,3-butadiene 2a, various 1,3-butadiene
derivatives could be effectively reacted with enynal 1a as well
(Table 2, 3a–s). The reaction proceeded particularly smoothly
for different aryl-substituted 1,3-butadiene derivatives, with
the yields typically higher than 60% (3a–l). The reactions were
not sensitive to the electron properties of aryl 1,3-butadienes.
Both the electron-rich and -poor aryl 1,3-butadienes could give
satisfactory yields (electron-rich dienes: 3a–d; electron-poor
dienes: 3g–l). Notably, the reaction could proceed smoothly
even for the extremely electron-deficient pentafluoro-phenyl-
substituted 1,3-butadiene with the yield up to 85% (3l). Bulky
1,3-butadienes typically gave a little bit lower yields (3e, 3 f).
In addition to the aryl 1,3-butadienes, 1,3,5-hexatriene could
be used as the substrate as well, giving the desired product
3m in 52% yield. Furyl 1,3-butadiene, a heteroaryl substrate,
was also successfully converted into the desired product 3n in
26% yield. Furthermore, the reaction could smoothly occur
even for the 1,3-butadiene with a free hydroxyl group, albeit in
lower yield (3o, 30%). The alkyl-substituted 1,3-butadienes
provided the corresponding products in moderate yields (3p,
3q). It is worth noting that an ester functional group was in-
troduced in the cases of 3r and 3s when 4-methyl- or 4-
phenyl-substituted 1-carboalkoxy-1,3-butadienes were used as
the substrates. The yields of 3r and 3s were 63 and 55%, re-
spectively. Compared with the 1,3-butadienes 2, the reaction
was more sensitive to the properties of enynals 1 (3t–ae). For
example, the enynals substituted with electron-donating
groups furnished the desired products in higher yields than
those with electron-withdrawing groups (3t–x). The reaction
was depressed completely when a pyridine was introduced
into the enynal (3y). Presumably, the strong coordinating ca-
pability of the pyridine poisoned the catalyst. For enynals bear-
ing the alkyl alkynes, the reactions proceed smoothly as well
(3z–ab), with the yields ranging from 72–85%. Importantly,
the enynal with a terminal alkyne could be applied as the sub-
strate as well, furnishing the product 3ac (30%) with an alde-
hyde functional group. The reaction functioned particularly ef-
ficiently for the enynones, which gave the products 3ad and
3ae in 84 and 91% yields, respectively. Once again, only
a single isomer was found for all the cases in Table 2 when
Chem. Eur. J. 2014, 20, 2425 – 2430
www.chemeurj.org
2427
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
mixtures of cis- and trans-dienes 2 were applied as the starting
materials.
teresting bridged compound 4, which was observed as a side
product during the course of optimization of reaction condi-
tions (Table 1). It could be obtained as the sole product when
silver salt was used as the catalyst (Table 1, entry 1). As shown
by its X-ray structure (see the Supporting Information), 4 con-
tains a benzocycloheptene, in which the C=C double bond
takes cis-configuration. Therefore, retrosynthetically, the prod-
uct 4 may be generated only from cis-1,3-butadiene 2. The
control reactions were carried out as well to clarify the silver-
catalyzed reaction pathway. As shown in Scheme 8, 4a could
Based on the above results, a possible reaction mechanism
was then proposed (Scheme 6). The coordination of the triple
bond of enynal 1 to [Au] enhances the electrophilicity of the
Scheme 8. Control Reactions: 1/2=1:1; [1]=0.05m; isolated yield.
be obtained only in 34% yield when 1,3-diene 2a (cis/trans
ꢀ50:50) was used. The yield almost doubled to 62% when the
cis/trans ratio was increased to> 90:10. All of trans-2a (cis/
trans<1:99) failed to give the desired product. Obviously, this
indicated that only cis-1,3-diene 2 can result in the desired
product 4.
Scheme 6. Proposed gold-catalyzed reaction mechanism.
Based on the control reactions above, the scope and gener-
ality of this silver-catalyzed transformation was then investigat-
ed further (Table 3). With the cis-dominant 1,3-butadiene 2a
(cis/trans>9:1) as the substrate, different enynals were then
tested for this process. The aryl–enynals (1a–b) produced the
desired products 4a and 4b in 62 and 51% yields, respectively.
However, alkyl–enyal 1c gave the desired bridged product 4c
only in 20% yield. Actually, another unexpected product dihy-
dronaphthalene 5c was isolated as the dominant product in
49% yield (entry 3). Similarly, enynal 1d also gave the mixture
of 4d and 5d, with the yields being 41 and 48% respectively.
The bridged compound 4e was isolated as the sole product in
46% when the enynal with a terminal alkyne 1e was applied.
Furthermore, the reaction proceeded smoothly as well when
naphthalene-substituted cis-1,3-diene was used as the sub-
strate, giving the desired product 4 f in 59% yield.
alkyne, and the subsequent nucleophilic attack of the carbonyl
oxygen to the electron-deficient alkyne would form the inter-
mediate pyrylium E. A stepwise Diels–Alder reaction between
1,3-diene 2 (cis+trans) and pyrylium E can then be then fol-
lowed to furnish the intermediate G. In this course, an allyl
cation F was formed initially. Then elimination of the catalyst
[Au] led to the key intermediate C, vinyl-substituted cyclic-o-
QDM. Finally, an intramolecular Diels–Alder reaction then
occurs to furnish the desired product 3.
To clarify the reaction pathway, a set of control reactions
were then carried out. As shown in Scheme 7, three different
cis/trans ratios of 2a were used as the starting materials. The
As for the silver-catalyzed transformation, a tentative mecha-
nism was also depicted in Scheme 9 to account for its different
product formation with the gold-catalyzed system. Initially,
silver catalyzed the intramolecular reaction of enynal to form
the pyrylium H. Different from the gold-catalyzed version,
a concerted Diels–Alder reaction was proposed between 1,3-
diene 2 and pyrylium H to form the intermediate K. In this pro-
cess, the diene’s configuration remained unchanged in this
course. For example, cis-diene 2 would result in only cis-K in-
termediate. Finally, a Friedel–Crafts reaction or b-H elimination
then occurred to furnish the products 4 and 5, respectively.
In conclusion, we have developed an efficient method to
rapidly construct the highly-strained benzotricyclo[3.2.1.02,7]-
octane skeleton through the gold-catalyzed reactions of eny-
nals 1 and 1,3-butadienes 2. The reaction was proposed to
Scheme 7. Control reactions: 1/2=1:5; [1]=0.05m; isolated yield.
yields of 3a remained almost unchanged regardless the cis/
trans ratios of 1,3-diene 2a. These observations clearly sup-
ported the ionic stepwise Diels–Alder reaction mechanism.
Having established the gold-catalyzed reaction of enynals
and 1,3-butadienes as a reliable and efficient synthetic process
to construct the benzotricyclo[3.2.1.02,7]octane structure, we
then turned our attention to another minor, but structurally in-
Chem. Eur. J. 2014, 20, 2425 – 2430
www.chemeurj.org
2428
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
functional-group tolerance, this system holds considerable po-
tential in the construction of complex molecules with a tricy-
clo[3.2.1.02,7]octane skeleton. Moreover, another structurally in-
teresting bridged compound 4 could be formed instead when
the catalyst was changed into silver salt. The control reactions
revealed that only cis-isomers of 1,3-butadienes 2 could be
converted into the desired product 4. The asymmetric version,
a detailed reaction mechanism, and additional applications of
these transformations are underway in our laboratory.
Table 3. Substrate scope of enynal with 1,3-diene.[a]
Entry
1
4
5
Experimental Section
General experimental procedure
1
2
1a (X=H)
1b (X=Me)
62% (4a)
51% (4b)
trace (5a)
trace (5b)
Enynals/enynones (0.1 mmol) and 1,3-dienes (0.5 mmol) were
added to a solution of the corresponding catalyst combination of
[AuCl(SIMes)] (2.7 mg, 0.005 mmol) and Selectfluor (5.31 mg,
0.015 mmol) in DCE (2 mL, 0.05m). The reaction mixture was stirred
under nitrogen atmosphere at 808C for 14 h. After the reaction
was finished, the mixture was filtered by short silica, then the sol-
vent was evaporated under reduced pressure and the residue was
purified by flash chromatography on silica gel to afford the desired
product 3.
3
4
5
1c (R=cyclopropyl) 20% (4c)
1d (R=tert-butyl)
1e (R=H)
49% (5c)
48% (5d)
trace (5e)
41% (4d)
46% (4e)
Acknowledgements
We are grateful to the NNSFC (21172077, 21372086), the Pro-
gram for New Century Excellent Talents in University (NCET-10–
0403), The National Basic Research Program of China (973)
(2011CB808600), the Changjiang Scholars and Innovation Team
Project of the Ministry of Education, SRF for ROCS, State Educa-
tion Ministry, Guangdong NSF (10351064101000000), and the
Fundamental Research Funds for the Central Universities.
6
1a
<59% (4 f)
trace (5 f)
[a] Unless specified, the reactions were carried out under N2 with a molar
ratio of 1/2=1:1. [1]=0.05m. The yield refers to isolated yield.
Keywords: catalysis · cyclopropanes · Diels–Alder reaction ·
gold · tandem reactions
[1] a) K. C. Nicolaou, E. J. Sorensen, Classics in Total Synthesis: Targets, Strat-
egies, Methods, Wiley-VCH, Weinheim, 1996; b) K. C. Nicolaou, S. A.
Snyder, Classics in Total Synthesis II: More Targets, Strategies, Methods,
Wiley-VCH, Weinheim, 2003; c) K. C. Nicolaou, J. S. Chen, Classics in
Total Synthesis III: Further Targets, Strategies, Methods, Wiley-VCH, Wein-
heim, 2011.
[2] a) K. Tanino, M. Takahashi, Y. Tomata, H. Tokura, T. Uehara, T. Narabu, M.
Miyashita, Nat. Chem. 2011, 3, 484; b) K. Watanabe, Y. Suzuki, K. Aoki, A.
Sakakura, K. Suenaga, H. Kigoshi, J. Org. Chem. 2004, 69, 7802; c) K.
Tanino, K. Onuki, K. Asano, M. Miyashita, T. Nakamura, Y. Takahashi, I. Ku-
wajima, J. Am. Chem. Soc. 2003, 125, 1498; d) E. J. Corey, M. Kang, M. C.
Desai, A. K. Ghosh, J. N. Houpis, J. Am. Chem. Soc. 1988, 110, 649.
[3] a) D. Y.-K. Chen, R. H. Pouwerb, J.-A. Richard, Chem. Soc. Rev. 2012, 41,
4631; b) H. Lebel, J. F. Marcoux, C. Molinaro, A. B. Charette, Chem. Rev.
2003, 103, 977; c) H. M. L. Davies, B. D. Doan, J. Org. Chem. 1999, 64,
8501; d) S. F. Zhu, X. Xu, J. A. Perman, X. P. Zhang, J. Am. Chem. Soc.
2010, 132, 12796; e) S. F. Zhu, J. A. Perman, X. P. Zhang, Angew. Chem.
2008, 120, 8588; Angew. Chem. Int. Ed. 2008, 47, 8460; f) S. F. Zhu, J. V.
Ruppel, H. Lu, L. Wojtas, X. P. Zhang, J. Am. Chem. Soc. 2008, 130, 5042.
[4] a) M. P. Doyle, D. C. Forbes, Chem. Rev. 1998, 98, 911; b) G. Yue, L. Yang,
C. Yuan, X. Jiang, B. Liu, Org. Lett. 2011, 13, 5406; c) Y.-S. Lu, X.-S. Peng,
Org. Lett. 2011, 13, 2940; d) R. P. L. Bell, J. B. P. A. Wijnberg, A. de Groot,
J. Org. Chem. 2001, 66, 2350; e) F. R. Petronijevic, P. Wipf, J. Am. Chem.
Soc. 2011, 133, 7704; f) A. Fꢁrstner, P. Hannen, Chem. Eur. J. 2006, 12,
3006; g) C. Fehr, J. Galindo, Angew. Chem. 2006, 118, 2967; Angew.
Scheme 9. Proposed silver-catalyzed reaction mechanism.
proceed through the intramolecular Diels–Alder reaction of an
in situ-generated vinyl-substituted cyclic-o-QDM. Owing to the
mild reaction conditions, excellent substrate scope and high
Chem. Eur. J. 2014, 20, 2425 – 2430
www.chemeurj.org
2429
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
Chem. Int. Ed. 2006, 45, 2901; h) C. Fehr, B. Winter, I. Magpantay, Chem.
Eur. J. 2009, 15, 9773; i) V. Mamane, T. Gress, H. Krause, A. Furstner, J.
Am. Chem. Soc. 2004, 126, 8654; j) A. Fꢁrstner, P. Hannen, Chem.
Commun. 2004, 2546.
12650; b) N. Asao, T. Nogami, S. Lee, Y. Yamamoto, J. Am. Chem. Soc.
2003, 125, 10921; c) N. Asao, T. Nogami, K. Takahashi, Y. Yamamoto, J.
Am. Chem. Soc. 2002, 124, 764; d) N. Asao, H. Aikawa, Y. Yamamoto, J.
Am. Chem. Soc. 2003, 125, 7458; e) N. Asao, T. Kasahara, Y. Yamamoto,
Angew. Chem. 2003, 115, 3628; Angew. Chem. Int. Ed. 2003, 42, 3504;
f) Q. Ding, J. Wu, Org. Lett. 2007, 9, 4959; g) G. Dyker, D. Hildebrandt, J.
Liu, K. Merz, Angew. Chem. 2003, 115, 4536; Angew. Chem. Int. Ed. 2003,
42, 4399; h) S. Bhunia, K.-C. Wang, R.-S. Liu, Angew. Chem. 2008, 120,
5141; Angew. Chem. Int. Ed. 2008, 47, 5063; i) R.-Y. Tang, J.-H. Li, Chem.
Eur. J. 2010, 16, 4733; j) D. Yue, N. D. Ca, R. C. Larock, J. Org. Chem.
2006, 71, 3381; k) S.-Y. Yu, H. Zhang, Y. Gao, L. Mo, S. Wang, Z.-J. Yao, J.
Am. Chem. Soc. 2013, 135, 11402; l) H. Kusama, H. Funami, J. Takaya, N.
Iwasawa, Org. Lett. 2004, 6, 605.
[5] S. C. Welch, J. M. Gruber, P. A. Morrison, J. Org. Chem. 1985, 50, 2676.
[6] a) R. B. Kelly, J. Zamecnik, B. A. Beckett, J. Chem. Soc. D 1971, 479;
b) R. B. Kelly, J. Zamecnik, B. A. Beckett, Can. J. Chem. 1972, 50, 3455.
[7] a) X. Wu, C.-H. Lu, Y.-M. Shen, Helv. Chim. Acta 2009, 92, 2783; b) S.
Block, C. Stevigny, M.-C. De Pauw-Gillet, E. de Hoffmann, G. Llabres, V.
Adjakidje, J. Quetin-Leclercq, Planta Med. 2002, 68, 647.
[8] a) S. Levin, R. R. Nani, S. E. Reisman, J. Am. Chem. Soc. 2011, 133, 774;
b) C.-C. Tseng, H. Ding, A. Li, Y. Guan, D. Y.-K. Chen, Org. Lett. 2011, 13,
4410.
[9] a) Y. Aoyagi, A. Yamazaki, C. Nakatsugawa, H. Fukaya, K. Takeya, S. Ka-
wauchi, H. Izumi, Org. Lett. 2008, 10, 4429; b) D. J. Tantillo, Org. Lett.
2010, 12, 1164.
[10] For general reviews on o-QDMs: a) J. L. Segura, N. Martin, Chem. Rev.
1999, 99, 3199; b) N. Martin, C. Seoane, M. Hanack, Org. Prep. Proced.
Int. 1991, 23, 237.
[13] a) A. D. Melhado, W. E. Brenzovich, Jr., A. D. Lackner, F. D. Toste, J. Am.
Chem. Soc. 2010, 132, 8885; b) W. E. Brenzovich Jr., D. Benitez, A. D.
Lackner, H. P. Shunatona, E. Tkatchouk, W. A. Goddard III, F. D. Toste,
Angew. Chem. 2010, 122, 5651; Angew. Chem. Int. Ed. 2010, 49, 5519;
c) G. Zhang, L. Cui, Y. Wang, L. Zhang, J. Am. Chem. Soc. 2010, 132,
1474; d) S. F. Zhu, L. Ye, W. Wu, H. Jiang, Tetrahedron 2013, 69, 10375.
[11] a) S. F. Zhu, R. X. Liang, H. F. Jiang, W. Q. Wu, Angew. Chem. 2012, 124,
11019; Angew. Chem. Int. Ed. 2012, 51, 10861; b) S. F. Zhu, Z. Zhang, X.
Huang, H. Jiang, Z. Guo, Chem. Eur. J. 2013, 19, 4695; c) S. F. Zhu, Y.
Xiao, Z. Guo, H. Jiang, Org. Lett. 2013, 15, 898.
Received: December 10, 2013
[12] Representative examples of the benzopyrilium ion: a) N. Asao, K. Taka-
hashi, S. Lee, T. Kasahara, Y. Yamamoto, J. Am. Chem. Soc. 2002, 124,
Published online on February 5, 2014
Chem. Eur. J. 2014, 20, 2425 – 2430
www.chemeurj.org
2430
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim