Gold-Catalyzed Ring Expansion of Enyne-Lactone: Generation and Transformation of 2-Oxoninonium

Article abstract of DOI:10.1021/acs.orglett.7b02834

An efficient gold-catalyzed ring-expansion reaction of enyne-lactones to form 2-oxoninonium intermediates is reported. The 2-oxoninonium generated in this work could undergo further 6π electrocyclization and aromatization reaction to produce different aromatic compounds.

Full text of DOI:10.1021/acs.orglett.7b02834

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX-XXX
Gold-Catalyzed Ring Expansion of Enyne-Lactone: Generation and
Transformation of 2‑Oxoninonium
Kui Luo,† Tongxiang Cao,† Huanfeng Jiang,† Lianfen Chen,*,† and Shifa Zhu*,†,‡
†Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering,
South China University of Technology, Guangzhou 510640, P. R. China
‡State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. China
S
* Supporting Information
ABSTRACT: An efficient gold-catalyzed ring-expansion reaction
of enyne-lactones to form 2-oxoninonium intermediates is
reported. The 2-oxoninonium generated in this work could
undergo further 6π electrocyclization and aromatization reaction
to produce different aromatic compounds.
Scheme 2. Reaction of 1a with Phenol
cyloxycarbocations are highly reactive species and
Aimportant intermediates in organic synthesis (Scheme
1).1 Among them, the acyclic acyloxycarbocation2 and five-
membered-ring 2-oxofuranium3 are well-known and extensively
used in organic synthesis. The higher ordered analogues 2-oxo-
oxepinium (seven-membered ring) and 2-oxo-oxoninium (nine-
membered ring) have been rarely investigated owing to difficult
access. As part of our continuing efforts to develop highly
efficient tandem reactions based on alkyne chemistry,4 we
expected that upon transition-metal activation enyne-lactone
would undergo a tandem cyclization/ring-expansion reaction to
rapidly generate the nine-membered ring 2-oxo-oxoninium
intermediate (Scheme 1). For the ease of substrate preparation
and to avoid the E- and Z-isomerization of the CC double
bond, a benzo-fused enyne-lactone 1 was initially chosen as the
substrate, which could be readily available from the reaction of
enynal and dimethyl acetylenedicarboxylate (DMAD) in one
step (Scheme 1).5
On the basis of previous reports,6 the acyloxycarbocation
intermediates were generally not stable enough to be separated.
Nevertheless, it could be trapped by phenol. We therefore began
the investigations by using phenol to trap the proposed 2-oxo-
oxoninium intermediate with enyne-lactone 1a as the model
substrate. As shown in Scheme 2, three metal salts (AgBF4,
Ph3PAuCl/AgBF4, and PtCl2), which were typically good
catalysts to promote the reaction of alkynes,7 failed to give the
desired phenol-trapped product 2a. When Ph3PAuCl/AgBF4 was
applied as the catalyst, an unexpected naphthalene product 3a
was obtained in 36% yield instead, which might come from the
6π-electrocyclization/aromatization of 2-oxo-oxoninium.
Scheme 1. Generation of 2-Oxoninonium from Ring
Expansion of Enyne-Lactone
With these preliminary results in hand, we then systematically
investigated different Lewis acids and reaction conditions to
improve the yield of 3a in the absence of phenol. As shown in
Table 1, four different silver salts were initially used as the
halogen scavenger to test the catalytic performance of Ph3PAuCl.
When AgNTf2 was tested, only trace amount of 3a was detected
(Table 1, entry 1). The yield could be improved to 34% and 40%,
respectively, when it came to AgOTf and AgBF4 (Table 1, entries
2 and 3). The yield of 3a could be further improved to 58% when
AgSbF6 was utilized as the additive (Table 1, entry 4). When 1.0
equiv of H2O was used as additional additive, the yield could be
enhanced to 74%. On the contrary, the reaction did not occur
when 4 Å MS was added to remove the adventitious water
Received: September 11, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b02834
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Optimization of Reaction Conditions
Scheme 4. Reaction Scope for the Formation of 4
b
entry
cat.
additive
solvent
temp (°C)
3a (%)
1
2
3
4
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
Ph3PAuCl
AgNTf2
AgOTf
AgBF4
DCE
80
80
80
80
80
80
80
80
80
80
40
60
100
80
80
trace
34
DCE
DCE
40
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
DCE
58
d
c
5
DCE
DCE
74
e
6
trace
55
Scheme 5. Possible Mechanism for the Formation of 6
d
7
CH2Cl2
THF
d
8
<5
nd
<5
47
d
9
CH3CN
toluene
DCE
d
10
d
11
d
12
DCE
63
d
13
DCE
46
d
14
DCE
<10
nr
d
15
DCE
a
Unless otherwise noted, the reaction was performed with 1a (0.2
b
mmol) in DCE (2 mL), 12 h, under N2. The yield was determined by
1H NMR using 1-methyl-4-nitrobenzene as an internal standard.
c
d
e
Isolated yield. 1.0 equiv of H2O. 100 mg of 4 Å MS.
Scheme 6. Formation of 7 from 3a and Further
Transformations
a
Scheme 3. Reaction Scope for the Formation of 3
With the optimized reaction conditions (Table 1, entry 4) in
hand, the substrate scope was then explored. As shown in
Scheme 3, this catalytic system could be successfully applied to a
variety of enyne-lactones 1 substituted with different groups at
the distal alkyne or fused with different aryl rings. For example, in
addition to 1a, various derivatives of enyne-lactones 1 with aryl
groups of R1 could be effectively transformed, obtaining the
desired products 3b−p in 51−67% yields, and the reaction
seemed insensitive to the electron properties of R1 group on the
substrates. It is noted that the enyne-lactone with a 3-thienyl
group of R1 could serve as effective substrate as well, giving the
desired product 3p in 63% yield. No reaction occurred with
enyne-lactone containing a 2-pyridyl terminal group under the
same conditions (see 3q), probably due to the strong
coordination of pyridyl moiety to the cationic Au center, which
would inhibit the catalyst turnover. The enyne-lactones with an
alkylalkyne or terminal alkyne group were inactive for this
transformation as well (see 3r and 3s). Furthermore, the
substrates bearing different aryl rings were also tested, and both
a
Conditions: 1 (0.20 mmol), Ph3PAuCl (5 mol %) and AgSbF6 (5 mol
%), 1.0 equiv of H2O in DCE (2 mL) at 80 °C under N2 for 12 h,
b
isolated yield. 1a (3 mmol, 1.04 g).
introduced by solvent and catalyst, with a negligible amount of
product detected (entry 6). These results indicated that the
reaction was mediated with water. The variations of solvent or
reaction temperature could not further improve the reaction
yield (Table 1, entries 7−13). AgSbF6 alone gave the product 3a
in less than 10% yield (Table 1, entry 14). Furthermore, the
reaction did not take place at all in the absence of catalyst and
additive (Table 1, entry 15; see the Supporting Information for
more details of reaction condition screening).
B
DOI: 10.1021/acs.orglett.7b02834
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 7. Proposed Mechanisms for the Formation of 3 and 4
To determine whether the enyne-lactone without substituents
at the lactone moiety could be used as an effective substrate for
this transformation, enyne-lactone 5 was then prepared and
subjected to the standard reaction conditions. As shown in
Scheme 5, a new naphthalene product 6 was furnished in 21%
yield, in which the lactone structure was preserved. It is proposed
that the reaction may be initiated by the move of CC double
bond of the lactone to conjugate with the benzene ring in the
presence of transition metal, which was followed by a sequential
6-endo-dig cycloisomerization and aromatization reaction. This
hypothesis was further supported by the successful trans-
formation of 5′ to 6 in 23% yield under the same reaction
conditions.
Scheme 8. Reaction of 1a with MeOH
With the naphthyl ester products 3 in hand, several further
chemical transformations were also carried out to demonstrate
the potential applications of these molecules (Scheme 6). Taking
3a as an example, the ester group could be hydrolyzed into the
carboxylic acid 7 in quantitative yield under alkaline conditions,
which could be easily transferred into fluorenone 8 in 97% yield
through a Friedel−Crafts reaction.8 In addition, it could be
converted into amide 9 (81%), cyanide compound 10 (69%),
and lactone 11 (75%) through the well-established methods.9−11
Possible reaction pathways for the generation of products 3
and 4 under the gold-catalyzed conditions were proposed in
Scheme 7. For the generation of 3, the triple bond of benzo-fused
enyne-lactone substrate 1 was initially activated by the gold salt
to give the intermediate A, followed by a 6-endo-dig cyclization to
form the oxonium intermediate B. The ring fragmentation of
intermediate B led to the nine-membered ring intermediate 2-
oxo-oxoninium C, which could isomerize to the intermediate C′.
As for the more stable intermediate C, a 6π electrocyclization and
aromatization then occurred to deliver the product 3,
accompanied by the release of monomethyl oxalate, which
could be detected by NMR spectrum. For the generation of 4, a
similar process gave the nine-membered ring intermediate 2-oxo-
oxoninium H, which could isomerized to a more stable
intermediate H′, followed by a similar 6π electrocyclization
and aromatization to form the phenyl ketone 4.
the electron-withdrawing and electron-donating substituents had
little effects on the transformation (3t−x, 63−70%). However,
only a trace amount of product 3y could be detected when the
methoxyl group was present on the phenylene ring. The
structure of the 4-fluoro-substituted product 3u was confirmed
by X-ray diffraction analysis (see the SI). In addition to the
phenylene-fused enyne-lactones, the heteroaryl ring-fused ones
were examined for this reaction as well. The thienyl-fused
substrate gave the desired product 3z in 30% yield, accompanied
by another unexpected product 3z′ in 37% yield. In accordance
with the result of 3q, pyridyl-fused enyne-lactone could not be
used as an effective substrate either (3aa) owing to its potential
coordination to the cationic Au center. What’s more, the reaction
could be conducted on a gram scale and gave the product 3a in
75% yield.
To further explore the substrate scope, the enyne-lactones 1
containing a simple CC double bond were also prepared and
tested under the standard reaction conditions. Surprisingly,
instead of the naphthalene products 3, ketones 4 bearing two
ester groups were produced, whether in the presence of H2O or
not. As shown in Scheme 4, for enyne-lactones with an
unsubstituted CC double bond, the reaction proceeded
smoothly and gave the products 4a and 4b in 65% and 69%
yields, respectively. The structure of compound 4a was also
verified by X-ray crystallography (see the SI). The reaction
functioned equally well when the CC double bond was
substituted with a phenyl group (4c, 67%). Moreover, the
reaction was compatible with methoxy group (4d, 70%).
Furthermore, the corresponding ketone 4e could be obtained
in 54% yield when the cyclohexene-fused enyne-lactone was
applied as the substrate.
As illustrated in Scheme 2, the attempts to trap the nine-
membered ring intermediate 2-oxo-oxoninium C or C′ using
phenol were frustrating. It is supposed that the phenol is too
weak a nucleophile to attack the proposed 2-oxo-oxoninium, as
the oxonium moiety was conjugated with three CC double
bonds. For this reason, some more stronger nucleophiles, such as
N,N-dimethylaniline, 1,4-dimethoxybenzene, and 1,3,5-trime-
C
DOI: 10.1021/acs.orglett.7b02834
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(2) (a) Ghosh, A. K.; Keyes, C.; Veitschegger, A. M. Tetrahedron Lett.
2014, 55, 4251. (b) Thomas, J. D.; Sloan, K. B. Int. J. Pharm. 2009, 371,
25. (c) Folkmann, M.; Lund, F. J. Synthesis 1990, 1990, 1159. (d) Creary,
X.; Mehrsheikh-Mohammadi, M. E.; Eggers, M. D. J. Am. Chem. Soc.
1987, 109, 2435. (e) Yoshida, H.; Nakajima, M.; Ogata, T.; Matsumoto,
K. Bull. Chem. Soc. Jpn. 1982, 55, 1973. (f) Ho, T.; Olah, G. A. Synthesis
1977, 1977, 418. (g) Luk’yanov, S. M.; Etmetchenko, L. N.; Koblik, A.
V.; Rakina, O. A.; Dorofeenko, G. N. Zh. Org. Khim. 1977, 13, 287.
(h) Cleve, N. J.; Euranto, E. K. Acta Chem. Scand. 1973, 27, 1841.
(i) Euranto, E. K. Acta Chem. Scand. 1967, 21, 721.
(3) (a) Shcherbinin, V. A.; Shpuntov, P. M.; Konshin, V. V.; Butin, A.
V. Tetrahedron Lett. 2016, 57, 1473. (b) Niedek, D.; Schuler, S. M. M.;
Eschmann, C.; Wende, R. C.; Seitz, A.; Keul, F.; Schreiner, P. R. Synthesis
2016, 49, 371. (c) Ghosh, A. K.; Kulkarni, S.; Xu, C.; Shurrush, K.
Tetrahedron: Asymmetry 2008, 19, 1020. (d) Ghosh, A. K.; Swanson, L. J.
Org. Chem. 2003, 68, 9823. (e) Bhatt, M. V.; Ashry, S. H. El. Indian J.
Chem. B, Org. Incl. Med. 1980, 19, 487. (f) Bhatt, M. V.; Ashry, S. H.; El.
Somayaji, V. Proc. Indian Acad. Sci. (Chem. Sci.) 1980, 89, 7.
(4) (a) Qiu, S.; Chen, L.; Jiang, H.; Zhu, S. Org. Lett. 2017, 19, 4540.
(b) Zhang, J.; Jiang, H.; Zhu, S. Adv. Synth. Catal. 2017, 359, 2924.
(c) Zhang, C.; Jiang, H.; Zhu, S. Chem. Commun. 2017, 53, 2677.
(d) Chen, K.; Zhu, S. Synlett 2017, 28, 640. (e) Luo, H.; Chen, K.; Jiang,
H.; Zhu, S. Org. Lett. 2016, 18, 5208. (f) Zhang, J.; Xiao, Y.; Chen, K.;
Wu, W.; Jiang, H.; Zhu, S. Adv. Synth. Catal. 2016, 358, 2684. (g) Zhu,
D.; Ma, J.; Luo, K.; Fu, H.; Zhang, L.; Zhu, S. Angew. Chem., Int. Ed.
2016, 55, 8452. (h) Ma, J.; Chen, K.; Fu, H.; Zhang, L.; Wu, W.; Jiang,
H.; Zhu, S. Org. Lett. 2016, 18, 1322. (i) Ma, J.; Zhang, L.; Zhu, S. Curr.
Org. Chem. 2015, 20, 102. (j) Zhu, S.; Zhang, Q.; Chen, K.; Jiang, H.
Angew. Chem., Int. Ed. 2015, 54, 9414. (k) Liang, R.; Jiang, H.; Zhu, S.
Chem. Commun. 2015, 51, 5530. (l) Zhu, S.; Huang, X.; Zhao, T.; Ma, T.;
Jiang, H. Org. Biomol. Chem. 2015, 13, 1225. (m) Liang, R.; Ma, T.; Zhu,
S. Org. Lett. 2014, 16, 4412. (n) Ma, J.; Jiang, H.; Zhu, S. Org. Lett. 2014,
16, 4472. (o) Zhu, S.; Huang, H.; Zhang, Z.; Ma, T.; Jiang, H. J. Org.
Chem. 2014, 79, 6113. (p) Zhu, S.; Hu, L.; Jiang, H. Org. Biomol. Chem.
2014, 12, 4104. (q) Zhu, S.; Guo, Z.; Huang, Z.; Jiang, H. Chem. - Eur. J.
2014, 20, 2425.
thoxybenzene, were then used to trap the 2-oxo-oxoninium.
However, they all failed to give the desired product. What’s more,
we also tried to use different reductants to trap the possible
intermediates, such as Hantzsch ester and triethylsilane.
Regrettably, there was no reduction product detected. When
1.0 equiv of MeOH was applied as the nucleophile, an
unexpected product 12 was obtained in 65% yield instead,
accompanied by the release of methyl benzoate, which could be
detected by GC−MS and NMR. The formation of 12 may
proceed through the nucleophilic trap of 2-oxo-oxoninium C′
with MeOH (Scheme 8).
In conclusion, we have developed an efficient gold-catalyzed
ring-expansion reaction of enyne-lactone to form the 2-
oxoninonium intermediate, which is an unknown intermediate
and has not been studied before. It was found that the 2-
oxoninonium generated in this work could undergo an
interesting 6π electrocyclization and aromatization reaction to
produce different aromatic compounds. We hope that this work
will not only help in understanding 2-oxo-oxoninium but also
promote the development and application of other cyclic
acyloxycarbocations.
ASSOCIATED CONTENT
* Supporting Information
■
S
Typical experimental procedure and characterization for all
products. Crystallographic data for 1e, 3u, and 4a(CIF) The
Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.orglett.7b02834.
Typical experimental procedure and characterization for
all products (PDF)
Crystallographic data for 1e (CIF)
Crystallographic data for 3u (CIF)
Crystallographic data for 4a (CIF)
(5) The structure of 1e was confirmed by X-ray diffraction analysis (see
the SI). (a) Deng, J.; Chan, F.; Kuo, C.; Cheng, C.; Huang, C.; Chuang,
S. Eur. J. Org. Chem. 2012, 2012, 5738. (b) Bayat, M.; Imanieh, H.;
Hassanzadeh, F. Tetrahedron Lett. 2010, 51, 1873. (c) Li, C.; Shi, M. Org.
Lett. 2003, 5, 4273.
(6) (a) McGowan, J.; Thiele, N.; Sloan, K. B. Tetrahedron Lett. 2015,
56, 5441. (b) Thomas, J. D.; Sloan, K. B. Synthesis 2008, 2008, 272.
(c) Thomas, J. D.; Sloan, K. B. Tetrahedron Lett. 2007, 48, 109.
(d) Thomas, J. D.; Sloan, K. B. Tetrahedron Lett. 2006, 47, 8785.
(e) Sloan, K. B.; Koch, S. A. M. J. Org. Chem. 1983, 48, 3777. (f) Bodor,
N.; Sloan, K. B.; Kaminski, J. J.; Shih, C.; Pogany, S. J. Org. Chem. 1983,
48, 5280.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: zhusf@scut.edu.cn.
*E-mail: chenlf@scut.edu.cn.
ORCID
Huanfeng Jiang: 0000-0002-4355-0294
Shifa Zhu: 0000-0001-5172-7152
Notes
(7) (a) Zheng, Z.; Wang, Z.; Wang, Y.; Zhang, L. Chem. Soc. Rev. 2016,
45, 4448. (b) Zhang, L. Acc. Chem. Res. 2014, 47, 877. (c) Pflasterer, D.;
̈
The authors declare no competing financial interest.
Hashmi, A. S. K. Chem. Soc. Rev. 2016, 45, 1331. (d) Hashmi, A. S. K. Acc.
Chem. Res. 2014, 47, 864. (e) Wang, Y. M. A.; Lackner, D.; Toste, F. D.
Acc. Chem. Res. 2014, 47, 889. (f) Liu, L.; Zhang, J. Chem. Soc. Rev. 2016,
45, 506. (g) Qian, D.; Zhang, J. Chem. Soc. Rev. 2015, 44, 677. (h) Dorel,
R.; Echavarren, A. M. Chem. Rev. 2015, 115, 9028. (i) Obradors, C.;
ACKNOWLEDGMENTS
■
We are grateful to Ministry of Science and Technology of the
People’s Republic of China (2016YFA0602900), the NSFC
(21372086, 21422204, and 21672071), Guangdong NSF
(2014A030313229, 2016A030310433), the Science and Tech-
nology Program of Guangzhou (201707010316), and the
Fundamental Research Funds for the Central Universities,
SCUT.
Echavarren, A. M. Acc. Chem. Res. 2014, 47, 902. (j) Jimen
́
ez-Nunez, E.;
́
̃
Echavarren, A. M. Chem. Rev. 2008, 108, 3326. (k) Furstner, A. Acc.
̈
Chem. Res. 2014, 47, 925. (l) Huple, D. B.; Ghorpade, S.; Liu, R.-S. Adv.
Synth. Catal. 2016, 358, 1348.
(8) Sun, D.; Li, B.; Lan, J.; Huang, Q.; You, J. Chem. Commun. 2016, 52,
3635.
(9) Lauwagie, S.; Millet, R.; Pommery, J.; Depreux, P.; Hen
́
ichart, J.
Heterocycles 2006, 68, 1149.
REFERENCES
■
(10) Li, D.; Yuan, T.; Wang, G. J. Org. Chem. 2012, 77, 3341.
(11) Li, Y.; Ding, Y.; Wang, J.; Su, Y.; Wang, X. Org. Lett. 2013, 15,
2574.
(1) (a) Luk’yanov, S. M.; Koblik, A. V. Russ. Chem. Rev. 1996, 65, 1.
(b) Neuenschwander, M.; Bigler, P.; Christen, K.; Iseli, R.; Kyburz, R.;
Muhle, H. Helv. Chim. Acta 1978, 61, 2047. (c) Schmidt, R. R. Angew.
̈
Chem., Int. Ed. Engl. 1973, 12, 212. (d) Kochetkov, N. K.; Nifant’ev, E. E.
Russ. Chem. Rev. 1961, 30, 15. (e) Wagner, A.; Rall, U. Angew. Chem.
1959, 71, 193.
D
DOI: 10.1021/acs.orglett.7b02834
Org. Lett. XXXX, XXX, XXX−XXX