Gold-Catalyzed Enantioselective Intramolecular Annulation of Ene-Yne-Carbonyls via Benzopyrylium-Type Intermediates

Article abstract of DOI:10.1002/ejoc.201801537

It has been established that a cationic gold(I)/(R)-H₈-binap complex catalyzes the enantioselective intramolecular [4+2] annulation of benzene-linked ene-yne-carbonyls via benzopyrylium-type intermediates at room temperature to give chiral tric

Full text of DOI:10.1002/ejoc.201801537

A Journal of
Accepted Article
Title: Gold-Catalyzed Enantioselective Intramolecular Annulation of
Ene-Yne-Carbonyls via Benzopyrylium-Type Intermediates
Authors: Takumi Koshikawa, Masakazu Satoh, Koji Masutomi, Yu
Shibata, and Ken Tanaka
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801537
Link to VoR: http://dx.doi.org/10.1002/ejoc.201801537
Supported by

10.1002/ejoc.201801537
European Journal of Organic Chemistry
COMMUNICATION
Gold-Catalyzed Enantioselective Intramolecular Annulation of
Ene-Yne-Carbonyls via Benzopyrylium-Type Intermediates
Takumi Koshikawa,[a] Masakazu Satoh,[a] Koji Masutomi,[a] Yu Shibata,[a] and Ken Tanaka*[a]
Dedication ((optional))
Abstract: It has been established that a cationic gold(I)/(R)-H8-binap
complex catalyzes the enantioselective intramolecular [4+2]
annulation of benzene-linked ene-yne-carbonyls via benzopyrylium-
type intermediates at room temperature to give chiral tricyclic
compounds, bearing two stereogenic centers, as single
diastereomers with moderate ee values. Interestingly, the reactions
of sterically demanding naphthalene-linked ene-yne-carbonyls with
the same gold(I) catalyst gave not only [4+2] annulation products but
also [3+2] annulation products as minor products with good ee
values.
should be used.[8] In this paper, we disclose the cationic
gold(I)/(R)-H8-binap complex-catalyzed enantioselective
intramolecular [4+2] annulation of benzene-linked ene-yne-
carbonyls, possessing the 1,1-disubstituted alkene moieties,
leading to chiral non-aromatizable tricyclic compounds (Scheme
1, bottom).[9,10] Importantly, the thus constructed chiral
oxygenated tricyclic core is found in some bioactive natural
products as shown in Figure 1.[11]
precedents (Asao and Yamamoto in 2005)
H
O
O
H
2 mol % Cu(OTf)2
Introduction
H
nBu
Lewis or Brønsted acid-catalyzed [4+2] annulations of 2-
alkynylbenzoyl compounds with alkynes and alkenes are useful
methods for the synthesis of substituted naphthalenes and 1,2-
dihydronaphthalenes.[1] These annulations are initiated by
electrophilic activation of the alkyne moiety of the 2-
alkynylbenzoyl compounds to form benzopyrylium-type
intermediates.[1] In 2002, Asao, Yamamoto, and co-workers
reported that highly π-electrophilic Lewis acids, AuX3 (X = Cl, Br),
catalyze the intermolecular [4+2] annulation of 2-alkynylbenzoyl
compounds with alkynes.[2,3] Subsequently, in 2003, the same
research group reported that Cu(OTf)2 catalyzes the
intermolecular [4+2] annulation of 2-alkynylbenzoyl compounds
with alkenes.[4,5] It was envisioned that intramolecular variants of
these annulations would afford the corresponding polycyclic
products. Indeed, in 2005, Asao, Yamamoto, and co-workers
Me
nBu
85–87% yield
O
[Cu]
nBu
A
this work
R1
O
H
O
chiral AuI+ catalyst
Z
Z
R2
R1
R2
R2 ≠ H
Scheme 1. Transition-metal-catalyzed intramolecular annulations of ene-yne-
reported the AuX3 (X
= Cl, Br) or Cu(OTf)2-catalyzed
carbonyls.
intramolecular [4+2] annulation of benzene-linked diyne-
carbonyls leading to tricyclic naphthalenes.[6] In this report, they
also reported the Cu(OTf)2-catalyzed intramolecular [4+2]
annulation of benzene-linked ene-yne-carbonyls leading to a
tricyclic 1,2-dihydronaphthalene, possessing two stereogenic
centers, via benzopyrylium-type intermediate A (Scheme 1,
top).[6] However, two stereogenic centers of the thus generated
1,2,3,10a-tetrahydrophenanthren-4(4aH)-one skeleton readily
disappear as a result of easy aromatization under air.[7] In order
to develop an asymmetric variant of this reaction, ene-yne-
carbonyl substrates that afford non-aromatizable products
Cl
O
OMe
NH
O
O
O
O
O
HO
Me
OH
HN
Me
O
H
Me
Xantholipin (ref 11a)
Tubingensin A (ref 11b)
O
Me
Me
O
OH
Me
HO
HO
O
H
[a]
T. Koshikawa, M. Satoh, Dr. K. Masutomi, Dr. Y. Shibata, Prof. Dr.
K. Tanaka
HO
Department of Chemical Science and Engineering
Tokyo Institute of Technology
O-okayama, Meguro-ku, Tokyo 152-8550 (Japan)
E-mail: ktanaka@apc.titech.ac.jp
Me
HO
Andirobicin B glucoside (ref 11c)
Homepage: http://www.apc.titech.ac.jp/~ktanaka/
Figure 1. Structures of bioactive natural products with a chiral oxygenated
tricyclic core.
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801537
European Journal of Organic Chemistry
COMMUNICATION
Results and Discussion
4
5
AgNTf2
AgSbF6
Cu(OTf)2
Cu(OTf)2
82
85
86
85
13 (+)
16 (+)
28 (+)
26 (+)
Our research group has been reported a number of cationic
rhodium(I)/axially chiral biaryl bisphosphine complex-catalyzed
[2+2+2] cycloadditions of 1,6-enynes with unsaturated
compounds.[12] In the course of this study, we synthesized
benzene-linked ene-yne-carbonyl 1a and unexpectedly found
the formation of intramolecular [4+2] annulation product 2a as a
by-product. Therefore, the reaction of 1a with a cationic
rhodium(I)/(S)-binap complex was examined in the absence of
cycloaddition partners. Although the desired product 2a was
obtained at the elevated temperature (95 °C) as a single
diastereomer, the yield of 2a was low and 2a was obtained as a
racemate (Scheme 2).
6
7[c]
[a] (R)-binap-(AuCl)2 (0.010 mmol), AgX (0.020 mmol), 1a (0.10 mmol), and
(CH2Cl)2 (2.0 mL) were used. [b] Isolated yield. [c] (R)-binap (0.012 mmol),
AuCl(SMe2) (0.010 mmol), Cu(OTf)2 (0.010 mmol), 1a (0.10 mmol), and
(CH2Cl)2 (2.0 mL) were used.
The results of the screening of chiral phosphine ligands
(Figure 2) are shown in Table 2. Increasing a dihedral angle of
an axially chiral biaryl bisphosphine ligand increased the ee
value of 2a [dihedral angle:[14] segphos (entry 2) < binap (entry
1) < H8-binap (entry 3), ee value: entry 2 < entry 1 < entry 3].
However, increasing the steric bulk on the phosphorus atom
decreased both the yield and ee value of 2a (entries 4 and 5).
Non-biaryl bis- and monophosphine ligands and an axially chiral
biaryl monophosphine ligand were also tested, but the observed
ee values did not exceed that using (R)-H8-binap (entries 6–9 vs.
entry 3). Thus, (R)-H8-binap was selected as the best ligand.
Interestingly, decreasing the catalyst loading to 5 mol %
improved both the product yield and ee value (entry 10),
although the precise reason is not clear at the present stage.[15]
Me
10 mol %
O
[Rh(cod)2]BF4/
O
BnO2C
H
(S)-binap
BnO2C
BnO2C
BnO2C
C3H6Cl2, 95 °C
12 h
Me
Me
Me
1a
2a (single diastereomer)
19% (90% conv), <1% ee
Table 2. Screening of ligands for gold-catalyzed enantioselective
intramolecular [4+2] annulation of 1a.[a]
Scheme 2. Rhodium-catalyzed intramolecular [4+2] annulation of ene-yne-
carbonyl 1a leading to tricyclic compound 2a.
10 mol %
AuCl(SMe)2
12 mol %
Ligand
20 mol %
Cu(OTf)2
Me
O
H
As π-electrophilicity of the cationic rhodium(I)/(S)-binap
complex may not be sufficiently high, highly π-electrophilic
gold(I) complexes were applied to this [4+2] annulation. Firstly,
an isolated cationic gold(I)/(R)-binap complex (10 mol %) was
tested, while no reaction was observed (Table 1, entry 1). In
order to increase Lewis acidity of the gold(I) complex, a
cationic gold(I)/(R)-binap complex, generated by the addition of
AgBF4 (20 mol %), was tested. Pleasingly, the desired reaction
proceeded at room temperature to give 2a in good yield as a
single diastereomer, although the ee value was low (entry 2).
O
BnO2C
BnO2C
BnO2C
BnO2C
(CH2Cl)2, RT
1 h
Me
Me
Me
1a
2a (single diastereomer)
Entry
Ligand
Yield (%)[b]
ee (%)
26 (+)
7 (+)
1
2
(R)-binap
85
85
82
76
82
87
86
84
79
94
(R)-segphos
(R)-H8-binap
Screening of silver(I) and copper(II) additives (entries 2–6)
3
31 (+)
16 (–)
5 (–)
[13]
revealed that the use of Cu(OTf)2
affords 2a in high yield
4
(S)-xyl-H8-binap
(R)-dtbm-segphos
(S,S)-diop
with the highest ee value (entry 6). The use of a non-isolated
and in-situ generated cationic gold(I)/(R)-binap complex, which
allows simple operation, afforded 2a with almost the same yield
and ee value (entry 7).
5
6
1 (+)
7
(R,R)-Me-duphos
(R)-MeO-mop
phosphoramidite
(R)-H8-binap
14 (–)
19 (+)
6 (–)
8
Table 1. Optimization of reaction conditions for gold-catalyzed
enantioselective intramolecular [4+2] annulation of 1a.[a]
9
10[c]
41 (+)
Me
10 mol %
(R)-binap-(AuCl)2
20 mol % MX
O
H
O
BnO2C
BnO2C
[a] Ligand (0.012 mmol), AuCl(SMe2) (0.010 mmol), Cu(OTf)2 (0.020 mmol),
1a (0.10 mmol), and (CH2Cl)2 (2.0 mL) were used. [b] Isolated yield. [c]
Ligand (0.0060 mmol), AuCl(SMe2) (0.0050 mmol), Cu(OTf)2 (1.010 mmol),
1a (0.10 mmol), and (CH2Cl)2 (2.0 mL) were used.
BnO2C
BnO2C
(CH2Cl)2, RT
1 h
Me
Me
Me
1a
2a (single diastereomer)
Entry
MX
–
Yield (%)[b]
ee (%)
–
1
2
3
0
AgBF4
AgOTf
70
90
16 (+)
15 (+)
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801537
European Journal of Organic Chemistry
COMMUNICATION
O
O
annulation product 2k, but both the product yield and ee value
were low (entry 11). In this case, a significant amount of [3+2]
annulation product 3k was generated as a minor product with
good ee value (entry 11).
PPh2
PPh2
PAr2
PAr2
PPh2
PPh2
O
O
(R)-binap
(R)-segphos
(Ar = Ph)
(R)-H8-binap
Entry (Time)
Substrate
O
Product
(R)-dtbm-segphos
(Ar = 3,5-tBu2-4-MeOC6H2)
Me
O
H
Me
RO2C
RO2C
P
Me
O
O
Me
Me
RO2C
RO2C
PAr2
PAr2
PPh2
PPh2
Me
Me
P
Me
Me
Me
1 (1 h)
2 (1 h)
1a (R = Bn)
1b (R = Me)
(+)-2a / 94% yield, 41% ee
(+)-2b / 92% yield, 38% ee
(S)-xyl-H8-binap
(Ar = 3,5-Me2C6H3)
(S,S)-diop
(R,R)-Me-duphos
R
O
H
O
BnO2C
BnO2C
Ph
BnO2C
BnO2C
Me
Me
O
OMe
PPh2
P N
Ph
Me
O
R
Me
(+)-2c / 80% yield, 35% ee
(+)-2d / 88% yield, 31% ee
(+)-2e / 88% yield, 32% ee
(+)-2f / 65% yield, 34% ee
3 (23 h)
4 (23 h)
5 (23 h)
6 (23 h)
1c (R = H)
1d (R = iPr)
1e (R = Ph)
(R)-MeO-mop
phosphoramidite
1f (R = 2-naphthyl)
Figure 2. Structures of chiral phosphine ligands.
Ph
O
O
BnO2C
BnO2C
H
With the optimized conditions in hand, we examined the
substrate scope of the gold-catalyzed enantioselective
intramolecular [4+2] annulation of benzene-linked ene-yne-
carbonyls as shown in Figure 3. The reactions of dibenzyl and
dimethyl malonates derived ene-yne-carbonyls 1a and 1b
afforded the corresponding tricyclic dihydronaphthalenes 2a and
2b in high yields with moderate ee values (entries 1 and 2). The
relative configuration of [4+2] annulation product (±)-2b was
unambiguously determined by an X-ray crystallographic analysis
(Figure 4).[16] With respect to substituents on the carbonyl group,
not only methyl (1a, entry 1) but also hydrogen (1c, entry 3),
isopropyl (1d, entry 4), phenyl (1e, entry 5), and 2-naphthyl (1f,
entry 6) substituted carbonyl compounds could be employed.
Ethyl-substituted alkene substrate 1g (entry 7) and tosylamide-
linked substrate 1h (entry 8) could also be employed, although
the product ee values decreased, especially for 2h. The reaction
of sterically demanding naphthalene-linked ene-yne-carbonyl 1i
was also tested, which afforded the corresponding [4+2]
annulation product 2i with higher ee value than 2a, although the
yield of 2i was lower than that of 2a (entry 9 vs. entry 1).
Unexpectedly, not only [4+2] annulation product 2i but also [3+2]
annulation[17] product 3i was generated as a minor product with
excellent ee value (entry 9). Naphthyl phenyl ketone derivative
2j was found to be less reactive, and so the reaction was
conducted by using a high catalyst loading of 20 mol % Au. The
corresponding [4+2] annulation product 2j was obtained with the
highest ee value of 53%, while the yield was low and the
corresponding [3+2] annulation product 3j was not generated
(entry 10). The reactivity of naphthaldehyde derivative 1k was
even lower than naphthyl phenyl ketone derivative 1j, and no
reaction was observed at room temperature. Pleasingly, the
reaction proceeded at 80 °C to give the corresponding [4+2]
BnO2C
BnO2C
Et
Ph
Et
1g
(+)-2g / 88% yield, 25% ee
7 (23 h)
Ph
O
O
H
TsN
TsN
Me
Ph
Me
8 (23 h)
1h
(–)-2h / 62% yield, 4% ee
R
O
O
BnO2C
BnO2C
H
BnO2C
BnO2C
Me
R
Me
9 (1 h)[a]
10 (23 h)[a]
11 (1 h)[a,b]
1i (R = Me)
1j (R = Ph)
1k (R = H)
(+)-2i / 50% yield, 49% ee
(+)-2j / 20% yield, 53% ee
(+)-2k / 38% yield, 23% ee
R
Me
BnO2C
BnO2C
H
O
(+)-3i / 5% yield, 93% ee
(+)-3j / 0% yield
(–)-3k / 19% yield, 78% ee
Figure 3. Gold-catalyzed enantioselective intramolecular [4+2] and [3+2]
annulations of ene-yne-carbonyls 1. The reactions were conducted using (R)-
H8-binap (0.0060 mmol), AuCl(SMe2) (0.0050 mmol), Cu(OTf)2 (0.010 mmol),
1 (0.10 mmol), and (CH2Cl)2 (2.0 mL) at RT. The cited yields were of isolated
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801537
European Journal of Organic Chemistry
COMMUNICATION
products. [a] (R)-H8-binap (0.0120 mmol), AuCl(SMe2) (0.010 mmol), Cu(OTf)2
(0.020 mmol), 1 (0.10 mmol), and (CH2Cl)2 (2.0 mL) were used [b] At 80 °C.
subsequent deprotonation gives neutral gold(I) intermediate F,
which can be drawn as intermediate F’. Finally,
protodemetalation gives chiral tricyclic product 2. On the other
hand, when using sterically demanding naphthalene-linked ene-
yne-carbonyls 1i–k, the intramolecular [3+2] cycloaddition of the
benzopyrylium moiety and the alkene moiety in intermediate G
proceeds to generate gold(I) carbenoid H. Addition of H2O into
gold(I) carbenoid H gives alcohol I. Demetalation gives enol J
and its tautomerization gives ketone K. Finally, dehydration
gives chiral tetracyclic product 3.
Conclusions
In conclusion, we have established that a cationic gold(I)/(R)-H8-
binap complex catalyzes the enantioselective intramolecular
[4+2] annulation of benzene-linked ene-yne-carbonyls via
benzopyrylium-type intermediates at room temperature to give
chiral tricyclic compounds, bearing two stereogenic centers, as
single diastereomers with moderate ee values. Interestingly, the
reactions of sterically demanding naphthalene-linked ene-yne-
carbonyls with the same gold(I) catalyst gave not only [4+2]
annulation products but also [3+2] annulation products as minor
products with good ee values. Future works will include further
development of transition-metal-catalyzed asymmetric reactions
involving the benzopyrylium-type intermediates.
Figure 4. X-ray crystallographic analysis of (±)-2b with ellipsoids at 50%
probability.
A possible mechanism for the formation of 2 and 3 is shown
in Scheme 3.[1–6] The cationic gold(I) complex coordinates the
alkyne moiety of ene-yne-carbonyl 1 to form intermediate B.
Oxycyclization gives benzopyrylium-type intermediate C. The
intramolecular [4+2] cycloaddition of the benzopyrylium moiety
and the alkene moiety gives intermediate D. Regeneration of the
carbonyl group gives carbocation intermediate
E
and
O
R1
R1
R1
Me
H
Z
O
O
Z
–H+
R2
[Au]
Z
–[Au+]
[Au]
OH
E
R2
I
1
O
R1
R1
Z
Me
Z
OH
[Au+]
R1
H2O
R1
R2
[Au]
F
OH
Me
J
O
O
R1
O
Z
Z
Z
R2
[Au]
O
[Au]
[Au]
R1
[Au]
R2
Me
Z
OH
H
D
Z
B
[4+2]
[3+2]
R2
H
R1
H+
O
F'
K
R1
O
–[Au+]
R1
O
–H2O
[Au]
[Au]
Z
R1
Z
O
R2
Me
Me
H
G
C
Z
Z
H
R2
O
R1
3
2
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801537
European Journal of Organic Chemistry
COMMUNICATION
Scheme 3. Plausible mechanisms for gold-catalyzed intramolecular [4+2] and [3+2] annulations of ene-yne-carbonyls 1.
[9]
For reviews of the gold-catalyzed enantioselective annulation, see: a) Y.
Li, W. Li, J. Zhang, Chem. Eur. J. 2017, 23, 467; b) W. Zi, D. Toste,
Chem. Soc. Rev. 2016, 45, 4567; c) F. Lopez, J. L. Mascarenas,
Beilstein J. Org. Chem. 2013, 9, 2250.
Acknowledgments
This work was supported partly by ACT-C (No.
JPMJCR1122YR) from the Japan Science and Technology
Agency (JST), Japan and a Grant-in-Aid for Scientific Research
on Innovative Areas "π-System Figuration: Control of Electron
[10] For selected recent examples of the gold-catalyzed enantioselective
annulation, see: a) Q. Du, J.-M. Neudörfl, H.-G. Schmalz, Chem. Eur. J.
2018, 24, 2379; b) H. Kim, S. Y. Choi, S. Shin, Angew. Chem. Int. Ed.
2018, 57, 13130; Angew. Chem. 2018, 130, 13314; c) Z. Wang, C.
Nicolini, C. Hervieu, Y.-F. Wong, G. Zanoni, L. Zhang, J. Am. Chem.
Soc. 2017. 139. 16064; d) H. Hu, Y. Wang, D. Qian, Z.-M. Zhang, L. Liu,
J. Zhang, Org. Chem. Front. 2016, 3, 759; e) Y. Wang, P. Zhang, D.
Qian, J. Zhang, Angew. Chem. Int. Ed. 2015, 54, 14849; Angew. Chem.
2015, 127, 15062; f) Y. Wang. P. Zhang, Y. Liu, F. Xia, J. Zhang, Chem.
Sci. 2015, 6, 5564.
and Structural Dynamism for Innovative Functions" (No.
JP26102004) from the Japan Society for the Promotion of
Science (JSPS), Japan. We thank Prof. Keiichi Noguchi (Tokyo
University of Agriculture and Technology) for the X-ray
crystallographic analysis, Takasago International Corporation for
the gift of (R)-segphos, (R)-H8-binap, and (S)-xyl-H8-binap, and
Umicore for generous support in supplying the rhodium and
palladium complexes.
[11] a) Y. Terui, C. Yiwen, L. Junying, T. Ando, H. Yamamoto, Y. Kawamura,
Y. Tomishima, S. Uchida, T. Okazaki, E. Munetomo, T. Seki, K.
Yamamoto, S. Murakami, A. Kawashima, Tetrahedron Lett. 2003, 44,
5427; b) M. R. TePaske, J. B. Gloer, D. T. Wicklow, P. F. Dowd, J. Org.
Chem. 1989, 54, 4743; c) L. M. Valente, A. A. L. Gunatilaka, T. E.Glass,
D. G. I. Kingston, A. C. Pinto, J. Nat. Prod. 1993, 56, 1772.
Keywords: Annulations • Asymmetric Catalysis • Ene-Yne-
[12] a) H. Ueda, K. Masutomi, Y. Shibata, K. Tanaka, Org. Lett. 2017, 19,
2913; b) K. Masutomi, H. Sugiyama, H. Uekusa, Y. Shibata, K. Tanaka,
Angew. Chem. Int. Ed. 2016, 55, 15373; Angew. Chem. 2016, 128,
15599; c) S. Yoshizaki, Y. Nakamura, K. Masutomi, T. Yoshida, K.
Noguchi, Y. Shibata, K. Tanaka, Org. Lett. 2016, 18, 388; d) K.
Masutomi, K. Noguchi, K. Tanaka, J. Am. Chem. Soc. 2014, 136, 7627;
e) K. Masutomi, N. Sakiyama, K. Noguchi, K. Tanaka, Angew. Chem.
Int. Ed. 2012, 51, 13031；Angew. Chem. 2012, 124, 13208.
Carbonyls • Gold • Benzopyrylium-Type Intermediates
[1]
For reviews of the Lewis or Brønsted acid-catalyzed [4+2] annulation of
2-alkynylbenzoyl compounds with alkynes and alkenes via
benzopyrylium-type intermediates, see: a) L. Chen, K. Chen, S. Zhu.
Chem. 2018, 4, 1208; b) N. Asao, Y. Ishikawa, in Transition-Metal-
Mediated Aromatic Ring Construction, ed. by K. Tanaka, Wiley,
Hoboken, 2013, Chap. 15; c) B. F. Straub, Chem. Commun. 2004,
1726.
[13] a) A. Guérinot, W. Fang, M. Sircoglou, C. Bour, S. B. Lafollee. V.
Gandon, Angew. Chem. Int. Ed. 2013, 52, 5848; Angew. Chem. 2013,
125, 5960; b) W. Fang, M. Presset, A. Guerinot, C. Bour, S. B. Lafollee,
V. Gandon, Org. Chem. Front. 2014, 1, 608.
[2]
[3]
N. Asao, K. Takahashi, S. Lee, T. Kasahara, Y. Yamamoto, J. Am.
Chem. Soc. 2002, 124, 12650.
For other examples of the Lewis or Brønsted acid-catalyzed
intermolecular [4+2] annulation of 2-alkynylbenzoyl compounds with
alkynes via benzopyrylium-type intermediates, see: a) J. Barluenga, H.
V. Villa, A. Ballesteros, J. M. Gonzalez, Org. Lett. 2003, 5, 4121; b) N.
Asao, T. Nogami, S. Lee, Y. Yamamoto, J. Am. Chem. Soc. 2003, 125,
10921; c) Y. Isogai, Menggenbateer, F. N. Khan, N. Asao, Tetrahedron
2009, 65, 9575; d) R. Umeda, K. Kaiba, S. Morishita, Y. Nishiyama,
ChemCatChem. 2011, 3, 1743.
[14] H. Shimizu, I. Nagasaki, T. Saito, Tetrahedron 2005, 61, 5405.
[15] Further decreasing the catalyst loading (2 mol %) did not improve both
the product yield and ee value.
[16] CCDC 1868715 [(±)-2b] contains the supplementary crystallographic
data for this paper. This data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ,
UK; fax: (+44) 1223-336-033; or deposit@ccdc.cam.ac.uk).
[4]
[5]
N. Asao, T. Kasahara, Y. Yamamoto, Angew. Chem. Int. Ed. 2003, 42,
3504; Angew. Chem. 2003, 42, 3504.
[17] a) C. H. Oh, S. M. Lee, C. S. Hong, Org. Lett. 2010, 12, 1308; b) C. H.
Oh, S. Y. Tak, J. H. Lee, L. Piao, Bull. Korean Chem. Soc. 2011, 32,
2978.
For other examples of the Lewis or Brønsted acid-catalyzed
intermolecular [4+2] annulation with alkenes via benzopyrylium-type
intermediates, see: a) N. Asao, H. Aikawa, J. Org. Chem. 2006, 71,
5249; b) D. Yue, N. D. Ca, R. C. Larock, J. Org. Chem. 2006, 71, 3381;
c) Z. L. Hu, W. J. Qian, Sheng. Wang, Shaozhong. Wang, Z. J. Yao, J,
Org, Chem. 2009, 74, 8787; d) Y.-C. Hsu, C.-M. Ting, R.-S. Liu, J. Am.
Chem. Soc. 2009, 131, 2090; e) T.-M. Teng, R.-S. Liu, J. Am. Chem.
Soc. 2010, 132, 9298; f) T.-M. Teng, A. Das, D. B. Huple, R.-S. Liu J.
Am. Chem. Soc. 2010, 132, 12565.
[6]
[7]
N. Asao, K. Sato, Meggenbateer, Y. Yamamoto, J. Org. Chem. 2005,
70, 3682.
For an example of aromatization of 1,2,3,10a-tetrahydrophenanthren-
4(4aH)-one derivatives under air, see: Z . L. Hu, W. J. Qian, S. Wang,
S.-Z. Wang, Z. J. Yao, Org. Lett. 2009, 11, 4676.
[8]
The enantioselective [4+2] annulation of 2-alkynylbenzoyl compounds
with 2-hydroxystyrenes via benzopyrylium-type intermediates catalyzed
by Pd(OAc)2 and a chiral phosphoric acid has been reported. See: a)
S.-Y. Yu, H. Zhang, Y. Gao, L. Mo, S. Wang, Z.-J. Yao, J. Am. Chem.
Soc. 2013, 135, 11402; b) H. Zhang, L. Zhu, S. Wang, Z.-J. Yao, J. Org.
Chem. 2014, 79, 7063.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801537
European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
COMMUNICATION
Gold Catalysis
R1
R1
5 mol % AuCl(SMe)2
3 mol % (R)-H8-binap
5 mol % Cu(OTf)2
Me
H
O
H
O
BnO2
C
C
Takumi Koshikawa, Yu Shibata,
Masakazu Satoh, Koji Masutomi, and
Ken Tanaka*
Z
BnO2
(CH2Cl)2, RT
Z
O
R2
R1
R2
up to 94% yield
up to 53% ee
minor products
5–19% yield
78–93% ee
(RT–80 °C)
PPh2
PPh2
Page No. – Page No.
(R)-H8-binap
It has been established that a cationic gold(I)/(R)-H8-binap complex catalyzes the
enantioselective [4+2] annulation of benzene-linked ene-yne-carbonyls to give
chiral tricyclic compounds with moderate ee values. Interestingly, the reactions of
naphthalene-linked ene-yne-carbonyls with the same gold(I) catalyst gave not only
[4+2] annulation products but also [3+2] annulation products as minor products with
good ee values.
Gold-Catalyzed Enantioselective
Intramolecular Annulation of Ene-
Yne-Carbonyls via Benzopyrylium-
Type Intermediates
This article is protected by copyright. All rights reserved.