PtCl2-catalyzed tandem enyne cyclization/1,2 ester migration reaction controlled by substituent effects of all-carbon 1,6-enynyl esters

Full text of DOI:10.1002/asia.201300018

COMMUNICATION
DOI: 10.1002/asia.201300018
PtCl2-Catalyzed Tandem Enyne Cyclization/1,2 Ester Migration Reaction
Controlled by Substituent Effects of All-Carbon 1,6-Enynyl Esters
Xing Huo,[a] Changgui Zhao,[a] Gaoyuan Zhao,[a] Shouchu Tang,[a] Huilin Li,[a]
Xingang Xie,[a] and Xuegong She*[a, b]
Cyclopentenes are important structural motifs in many
natural products of significant bioactivity such as Roseophi-
lin,[1] Scabronine G[2], and Przewalskin B (Figure 1).[3] In the
past two decades, numerous methods to prepare cyclopen-
tenes based on simple acyclic building blocks have been de-
In all cases, however, no enyne cycloisomerization products
were obtained.[11c,12]
Recently, our group reported a PtCl2-catalyzed cascade
1,2-acyloxy migration/intramolecular [3+2]-1,3-dipolar cy-
cloaddition reaction of oxygen-tethered 1,7-enynyl esters 1.
A series of useful substituted hexahydropyrans were ob-
tained based on this transformation (Scheme 1).[13] This re-
Figure 1. Natural products with cyclopentene motifs.
veloped.[4] Among them, transition metal-catalyzed (espe-
cially Pt, Au, and Ru) 1,6-enyne cycloisomerization reac-
tions play an extremely important role considering their
atom-economy and synthetic efficiency.[5–10]
Propargylic esters, which are well known for their transi-
tion metal-catalyzed 1,2- and 1,3-acyloxy migrations reac-
tions, are a specific class of alkynes that have been studied
by many groups.[11] Among them, the 1,n-enyne esters are
most widely used. However, in most studies, an acetate
group was required to be located between the alkyne and
the alkene group. Recently, several groups reported exam-
ples of 1,n-enyne esters in which an acyloxy group was locat-
ed on the far side of the triple bond away from the alkene.
Scheme 1. PtCl2-catalyzed tandem reaction of 1,n-enyne ester.
action was subsequently expanded successfully to its nitro-
gen series using [AuClACTHNUTRGNEUNG
(PPh3)] as catalyst.[12b] When the reac-
tion conditions were applied to the simple all-carbon 1,6-
enynyl ester 3, the expected cyclopentane 4 was obtained in
54% yield as a major product. However, when all-carbon
1,6-enynyl ester 5a with a isopropyl substituent at C6 was
tested under the standard conditions, to our surprise, the
enol ester 6a was obtained in 76% yield. Obviously, the for-
mation of 6a was attributed to the effect of the isopropyl
substituent, and it could be rationalized as the result of
a tandem enyne cyclization/1,2-ester migration reaction of
precursor 5a. To our knowledge, a substituent-controlled
enyne cyclization reaction has not been reported previously.
This inspired us to investigate the effects of substituents on
the reaction in detail. Herein, we report a new PtCl2-cata-
lyzed tandem 1,6-enyne cyclization/1,2-acyloxy migration re-
action controlled by substituent effects.
[a] X. Huo,+ C. Zhao,+ G. Zhao, S. Tang, H. Li, Dr. X. Xie,
Prof. Dr. X. She
State Key Laboratory of Applied Organic Chemistry
Department of Chemistry, Lanzhou University
222 South Tianshui Road, Lanzhou, 730000 (P. R. China)
Fax : (+86)931-8912582
E-mail: shexg@lzu.edu.cn
[b] Prof. Dr. X. She
State Key Laboratory of Oxo Synthesis and Selective Oxidation
Lanzhou Institute of Chemical Physics
Chinese Academy of Sciences
Lanzhou, Gansu, 730000 (P. R. China)
[+] These authors contributed equally to this work.
To determine the factors that control the chemoselectivity
and to examine the scope of the tandem enyne cyclization
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201300018.
Chem. Asian J. 2013, 8, 892 – 895
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Xuegong She et al.
Table 1. Platinum-catalyzed tandem enyne cyclization/1,2-ester migration reaction.[a]
Enynyl esters with two substituents attached
were also tested (Table 1, entries 8–11). Those with
C5,C6 disubstitution in trans (5h, 5i) could generate
cyclopentene enol esters 6h and 6h in yields of
90% and 68%, respectively (Table 1, entries 8 and
9), of which the latter contains the core of Roseo-
philin. It is worth mentioning here that the 5,6-spiro
bicyclic skeleton that is present in many natural
products could also be prepared by this method
from enynyl ester 5j (Table 1, entry 10).[3,14] Surpris-
ingly, the C4,C5-disubstituted ester 5k gave the [3-
1-0]-fused ring product 6k (Table 1, entry 11),
which indicated that a cyclopropyl intermediate
exists in this tandem process. The substrate with
a substituent at C7 was also tolerated (Table 1,
entry 12).
Entry Substrate
R
Products
Yield [%][b]
1
2
iPr=5a
Ph=5b
76
48
3
–
50
4
5
6
iPr=5d
Ph=5e
Cy=5 f
94
92
79
7
90
On the basis of the above observations, this Pt-
catalyzed cascade transformation should involve
one of two possible pathways (Scheme 2, path a or
b). In path a, Pt-promoted 1,2-ester migration of
the propargylic ester 4 occurs first and leads to the
formation of the Pt carbene intermediate I, fol-
lowed by cyclopropanation with the terminal
alkene to give the bicyclic [3-1-0] intermediate A.
Skeleton rearrangement of this fused bicyclic inter-
mediate A produces the product 6.[15] Alternatively,
in path b, in which enyne cyclization occurs first,
the cyclopropyl metal carbenoid II is formed. If 1,2-
ester migration reaction of II occurs subsequently,
the same bicyclic [3-1-0] intermediate A will be gen-
erated. On the other hand, skeleton rearrangement
of carbenoid II will deliver a new carbenoid III. For
cabenoid III, 1,2-ester migration reaction will gen-
erate the final product 6,[16] and 1,2-H migration
will produce the conjugated cyclopentene ester 7.
Both of the two mechanisms seem plausible
based on the formation of the bicyclic [3-1-0] prod-
uct 6k (Table 1, entry 11) mentioned above. To
obtain more conclusive evidence concerning the
mechanism in this tandem reaction, additional
enynyl esters 5m–o with different esters were used
8[c]
–
90
9[c]
–
–
68
32
10[d]
11
12
–
–
66
66
[a] Reaction conditions: enynyl ester (0.1m in toluene), 10 mol% PtCl2, CO (1 atm),
608C, 1 h. Piv=pivaloyl, Cy=cyclohexyl. [b] Isolated yields. [c] Relative configura-
tion. [d] Reaction time of 8 h; the starting material was recovered in 40% yield.
reaction, a series of 1,6-enynyl esters with different substitu-
ents were prepared and tested under the standard conditions
(Table 1). First, substrates with a single alkyl or phenyl sub-
stituent were tested (Table 1, entries 1–7). When the sub-
stituent was located at C6 of 1,6-enynyl esters (Table 1, en-
tries 1 and 2), it could be seen that the tandem enyne cycli-
zation was favored in case of a more bulky substituent. For
enynyl ester 5c, which has a substituent at C4 (Table 1,
entry 3), only the [3+2] cycloaddition product 6c was ob-
tained, thus indicating that the substituent at this position
inhibited completely the enyne cycloisomerization reaction.
For enynyl esters with C5 substituents (Table 1, entries 4–7),
the substituents had no effect on the conversion and the cor-
responding cyclopentene enol esters were obtained in high
yields.
under our standard conditions. The corresponding cyclopen-
tene enol esters 6m–o were obtained in 69, 56 and 22%
yield, respectively, along with the corresponding conjugated
dienes 7m–o (Table 2, entries 1–3). The formation of conju-
gated dienes 7 indicates that cabinoid III exists as an inter-
mediate in this tandem process, thus supporting the exis-
tence of the proposed path b. Furthermore, the ratio of
products 6 and 7 in these three examples also indicated that
the electronegativity at the ester carbonyl has a great influ-
ence on the reaction rate of the 1,2-H migration step.
In conclusion, a new PtCl2-catalyzed tandem enyne cycli-
zation/1,2-ester migration reaction of all-carbon 1,6-enynyl
esters, which was controlled by substitution, was developed.
By using this reaction, cyclopentene enol esters with various
alkyl substituents can be efficiently synthesized starting
from the corresponding 1,6-enyne ester. Further modifica-
Chem. Asian J. 2013, 8, 892 – 895
893
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Xuegong She et al.
Keywords: catalysis · enyne cyclization · ester migration ·
platinum · synthesis
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Entry
Substrate
6, yield [%]
7, yield [%]
1
2
5m, R=Ph
5n, R=Me
5o, R=
6m, 69
6n, 56
7m, 25
7n, 40
3
6o, 22
7o, 64
tion of this reaction and its application to synthesize Roseo-
philin is currently in progress and will be reported in due
course.
Experimental Section
General experimental procedure: A suspension of the propargylic ester 5
(0.15 mmol) and PtCl2 (0.015 mmol) in toluene (1.5 mL) under CO
(1 atm) was stirred for 1 h at 608C. After cooling to room temperature,
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PE/EtOAc 100:1 afforded the desired products (see the Supporting Infor-
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Acknowledgements
We are grateful for the generous financial support by the MOST
(2010CB833200), PCSIRT: IRT1138, the NSFC (21202068, 21102064),
the Fundamental Research Funds for the Central Universities (lzujbky-
2012-76), and program 111.
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Received: January 5, 2013
Published online: February 20, 2013
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