Gold(I)-catalyzed reactions of propargyl esters with vinyl derivatives

Article abstract of DOI:10.1002/ejoc.201100291

A gold-catalyzed olefin cyclopropanation reaction of propargyl esters with vinyl ester or vinyl sulfonamide derivatives was investigated for the synthesis of highly substituted cyclopropane derivatives in good diastereoselectivity. By varying the vinyl sp

Full text of DOI:10.1002/ejoc.201100291

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201100291
Gold(I)-Catalyzed Reactions of Propargyl Esters with Vinyl Derivatives
[a]
[a]
[a]
Christian A. Sperger, Jørn E. Tungen, and Anne Fiksdahl*
Keywords: Alkynes / Carbenoids / Cyclopropanation / Diastereoselectivity / Gold
A gold-catalyzed olefin cyclopropanation reaction of propar-
gyl esters with vinyl ester or vinyl sulfonamide derivatives
was investigated for the synthesis of highly substituted cyclo-
propane derivatives in good diastereoselectivity. By varying
the vinyl species, trans-cyclopentenyl esters were selectively
formed by a formal [3+2] cycloaddition.
Introduction
toluene was suitable in the same way as DCM, whereas ni-
tromethane or acetonitrile hampered the reaction. It is
known that aryl propargyl esters can undergo intramolecu-
lar cyclization reactions via an allene or a gold carbenoid
The cyclopropane unit can be found in many naturally
occurring products with interesting biological properties.
[
1]
They have further been used as versatile substrates for a
number of useful chemical transformations.[ In recent
years, gold catalysts have been shown to catalyze cycloisom-
erization reactions of different 1,n-enynes to provide com-
plex molecular structures.[ For these types of transforma-
tions, gold carbenoid species were proposed as reactive in-
termediates. In recent years, easily accessible propargylic es-
ters have been investigated as precursors for the formation
of gold vinyl carbenoids in a variety of reactions.[ On the
basis of the gold-catalyzed 1,2-acyl migration of terminal
propargyl esters (Scheme 3), Toste et al. have performed a
stereoselective intermolecular olefin cyclopropanation reac-
[7]
intermediate to provide indenes.
2]
1
We were pleased to see that, according to H NMR spec-
troscopy, only minor amounts (approx. 10%) of the indene
22 byproduct was formed (Scheme 1).
3]
Changing the substrate from propargyl acetate 1 to piva-
loate 2 led to a slight decrease in yield but had no effect on
the cis/trans selectivity of product 12 (Table 1, entry 2).
When the reaction was performed with propargyl acetate 3
or pivaloate 4, bearing two methyl groups in the propargylic
position, no influence on the yields or the stereoselectivity
of cyclopropanes 13 and 14 was observed (Table 1, entries
4]
3
and 4). Increasing the steric bulk of vinyl derivative 5 by
[
5]
tion. Recently they published an enantioselective intramo-
replacing the methyl group by a phenyl group in 6 had a
dramatic effect on the cis/trans ratio with 34:66 and 21:79
in favour of the trans isomers of product 15 and 16 (Table 1,
entries 5 and 6). The reaction of 2 with the unsubstituted,
less sterically hindered vinyl acetate 7 highly favoured the
formation of cis-17 with approximately 87% (Table 1, entry
[
6]
lecular version to provide chiral cyclopropane derivatives.
In contrast to previous studies, our aim was to trap dif-
ferent propargyl esters with olefins directly connected to a
heteroatom, such as vinyl acetates and vinyl sulfonamides,
to provide highly substituted cyclopropanes. These products
may further be used as versatile building blocks for the for-
mation of cyclopropyl alcohols or amines. Herein we fur-
ther report a gold-catalyzed formal [3+2] cycloaddition re-
action, which was observed during our investigation.
7
). The cyclopropanation of cyclic vinyl acetate 8 with piva-
loate 2 provided the two diastereomers cis- and trans-18 in
6% yield and a ratio of 77:23 in favour of the cis isomer
6
(Table 1, entry 8).
We then turned our attention on the cyclopropanation
reaction with different vinyl sulfonamides 19–21 (Table 1,
entries 9–11). Treatment of propargyl ester 4 with unsubsti-
tuted olefin substrate 9 provided the two diastereomers in
a 69:31 ratio in favour of cis-19 (Table 1, entry 9). When
vinyl amide 9 was replaced by the more sterically hindered
alkene 10 by introducing a phenyl group, we were pleased
to find that cis-20 was formed as the only diastereomer
Results and Discussion
In a first attempt, we treated propargyl acetate 1 with
vinyl acetate 5 in DCM with 5 mol-% of the gold phos-
phane catalyst and observed cyclopropane derivative 11 in
75% yield as a 53:47 mixture of cis/trans isomers (Table 1,
entry 1). Screening for other possible solvents revealed that
(
Table 1, entry 10). Isomer cis-21 was also exclusively
[
a] Department of Chemistry, Norwegian University of Science
formed in 48% yield when the reaction was performed with
pivaloate 2 (Table 1, entry 11).
The observed diastereoselectivity can be explained by a
stereochemical model also used by Toste et al. (Scheme 2).[
On the basis of that model, the steric interactions between
and Technology
Sem Særlands vei 8, 7491 Trondheim, Norway
Fax: +47-73550877
E-mail: anne.fiksdahl@chem.ntnu.no
5]
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100291.
Eur. J. Org. Chem. 2011, 3719–3722
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3719

C. A. Sperger, J. E. Tungen, A. Fiksdahl
SHORT COMMUNICATION
Table 1. Cyclopropanation reactions.[a]
[
(
a] The reactions were performed with 4 equiv. of vinyl ester 5–8 or 2 equiv. of vinyl amides 9 and 10 in DCM or toluene [c = 100 mm]
1
based on propargyl ester) and 5 mol-% of the gold catalyst at room temp. [b] The cis/trans ratios were determined by H NMR spec-
troscopy of the crude reaction mixture. [c] Isolated yield of cis and trans isomer. Most of the diastereomers were separated to enable
characterization of the single diastereomers (see Supporting Information). [d] The double bond was determined to be cis. [e] Ratio
1
determined by GC analysis of the crude reaction mixture because of overlapping signals in the H NMR spectrum. [f] According to GC
of the crude reaction mixture 16% of cyclopentenyl pivaloate was formed.
Scheme 1. Intramolecular cyclization of propargyl ester 1.
Scheme 2. Model for the observed stereochemistry.
the gold ligand (L) and the substituents on the vinyl moiety
4
5
(
R and R ) in the transition state play a crucial role for
Our results confirm the previously reported diastereo-
selectivity in similar gold-catalyzed olefin cyclopropan-
the observed stereoselectivity.
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Eur. J. Org. Chem. 2011, 3719–3722

Gold(I)-Catalyzed Reactions of Propargyl Esters
ation[5] but are contradictory to those recently reported for ate, performed in an NMR experiment in either CD Cl2
2
[
8]
gold-catalyzed cyclopropanations from α-diazoacetates.
(reflux) or [D ]tetrachloroethane at 80 °C, achieved no con-
2
An unexpected result was obtained when phenylprop- version. In contrast to Nevado’s observation,[11] these re-
argyl ester 2 was treated with unsubstituted vinyl amide 9, sults indicate that the direct cycloaddition pathway, involv-
providing selectively a trans-cyclopentene derivative 24 as ing intermediate 26b (Scheme 4), is more likely than a sub-
the only product in 73% yield (Scheme 3). The same reac- sequent ring expansion of cyclopropane 19.
tion occurred when the sterically hindered silylenol ether 23
was used as the vinyl substrate to give product 25
1
(
Scheme 3). According to H NMR spectroscopy, small
Conclusions
amounts (approx. 16% on the basis of GC analysis) of a
cyclopentenyl pivaloate were observed in the reaction of
propargyl ester 4 and vinyl amide 9 (Table 1, entry 9).
We performed a number of gold-catalyzed cyclopropan-
ation reactions of vinyl esters and vinyl sulfonamides with
different propargyl esters. We demonstrated that the dia-
stereoselectivity is controlled by the sterically more de-
manding olefin substituent and obtained up to 99% dia-
stereoselectivity. Moreover, we observed a formal [3+2] cy-
cloaddition reaction between propargyl pivaloate 2 and vin-
yl amide 9 or silylenol ether 23, providing stereoselectively
trans-cyclopentenyl pivaloates 24 and 25. In contrast to a
possible ring expansion of cyclopropylvinyl esters,[ we
propose a direct [3+2] cycloaddition pathway involving in-
termediate 26b. These observations may contribute to the
ongoing discussion on the “true nature” of gold carbenoid
11]
Scheme 3. Formation of cyclopentenyl esters.
As the reaction of alkenyl gold carbenoid intermediates
with olefins generally results in the formation of cyclo-
propane derivatives,[ [3+2] cycloadditions of α-carbonyl-
carbenoids with alkenes have been reported.[ Among dif-
ferent cycloadditions involving gold carbenoids[ Nevado
[
12]
intermediates.
5,6]
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details and spectroscopic data.
9]
10]
recently reported a phosphate-gold-catalyzed cyclopentaan-
nulation of olefins with propargyl esters.[ They demon- Acknowledgments
11]
strated that in a cascade reaction, the initially formed cy-
clopropylvinyl esters undergo a subsequent gold-catalyzed We thank the Norwegian Research Council for financial support.
ring expansion at elevated temperatures to provide trans-
cyclopentenyl esters.
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C. A. Sperger, J. E. Tungen, A. Fiksdahl
SHORT COMMUNICATION
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Received: March 2, 2011
Published Online: May 3, 2011
12599.
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Eur. J. Org. Chem. 2011, 3719–3722