Silver triflate-catalyzed cyclopropenation of internal alkynes with donor-/acceptor-substituted diazo compounds

Article abstract of DOI:10.1021/ol201503j

Silver triflate was found to be an efficient catalyst for the cyclopropenation of internal alkynes using donor-/acceptor-substituted diazo compounds as carbenoid precursors. Highly substituted cyclopropenes, which cannot be synthesized directly via rhodium(II)-catalyzed carbenoid chemistry, can now be readily accessed.

Full text of DOI:10.1021/ol201503j

ORGANIC
LETTERS
2011
Vol. 13, No. 15
3984–3987
Silver Triflate-Catalyzed
Cyclopropenation of Internal
Alkynes with Donor-/Acceptor-
Substituted Diazo Compounds
John F. Briones and Huw M. L. Davies*
Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia
30322, United States
hmdavie@emory.edu
Received June 3, 2011
ABSTRACT
Silver triflate was found to be an efficient catalyst for the cyclopropenation of internal alkynes using donor-/acceptor-substituted diazo
compounds as carbenoid precursors. Highly substituted cyclopropenes, which cannot be synthesized directly via rhodium(II)-catalyzed
carbenoid chemistry, can now be readily accessed.
Cyclopropenes continue to attract attention from
the synthetic community because of their versatility as
building blocks for an array of interesting reactions.1
Scheme 1
These carbocycles are highly strained, which causes
them to undergo useful transformations that are
thermodynamically unfavorable for typical olefins.2 One
of the most general approaches for the synthesis of
cyclopropenes 4 involves the reaction of alkynes 3 with
metal carbenoids 2 generated from diazo compounds 1
(Scheme 1).3
Three major classes of carbenoids have been used in
cyclopropenation reactions; acceptor carbenoids, accep-
tor/acceptor carbenoids, and donor/acceptor carbenoids.3
The outcome of the reaction is dependent on whether the
(1) For reviews on cyclopropenes, see: (a) Padwa, A. Acc. Chem. Res.
1979, 12, 310. (b) Baird, M. S. Chem. Rev. 2003, 103, 1271. (c) Walsh, R.
Chem. Soc. Rev. 2005, 34, 714. (d) Marek, I.; Simaan, S.; Masarwa, A.
Angew. Chem., Int. Ed. 2007, 46, 7364. (e) Rubin, M.; Rubina, M.;
alkyne is a terminal alkyne or a disubstituted alkyne.
Acceptor carbenoids, such as those derived from ethyl
diazoacetate, are very reactive and will cyclopropenate
both terminal and disubstituted alkynes. The early studies
with ethyl diazoacetate used copper(I) salts at elevated
Gevorgyan, V. Chem. Rev. 2007, 107, 3117.
(2) (a) Fox, J. M.; Yan, N. Curr. Org. Chem. 2005, 9, 719. (b)
Nakamura, M.; Isobe, H.; Nakamura, E. Chem. Rev. 2003, 103, 1295.
(c) Trost, B. M. Angew. Chem. 1986, 98, 1. (d) Ito, K.; Saito, K. Recent
Res. Dev. Pure Appl. Chem. 2000, 4, 81. (e) Methods of Organic
Chemistry (Houben-Weyl), Vol. E17; de Meijere, A., Ed.; Thieme:
Stuggart, 1996. (f) Baird, M. S. Top. Curr. Chem. 1988, 144, 139. (g)
Rubina, M.; Rubin, M.; Gevorgyan, V. J. Am. Chem. Soc. 2003, 125,
7198. (h) Diev, V.; Kostikov, R.; Gleiter, R.; Molchanov, A. P. J. Org.
Chem. 2006, 71, 4006. (i) Tarwade, V.; Liu, X.; Fox, J. M. J. Am. Chem.
Soc. 2009, 131, 5382. (j) Padwa, A.; Fryxell, G. E. Cyclization Reactions
of Cyclopropenes. In Advances in Strain in Organic Chemistry, Vol. 1;
Halton, B., Ed.; Jai Press: Greenwich, CT, 1991.
(4) Protopova, M. N.; Shapiro, E. A. Russ. Chem. Rev. 1989, 58, 667.
(5) For recent Cu-catalyzed cyclopropenation, see: (a) Diaz-Requejo,
M. M.; Mairena, M. A.; Beldarrain, T. R.; Nicasio, M. C.; Trofimenko,
S.; Perez, P. J. Chem. Commun. 2001, 1804. (b) Rodriguez, P.; Caballero,
A.; Diaz-Requejo, M. M.; Nicasio, M. C.; Perez, P. J. Org. Lett. 2006, 8,
557. (c) Park, E. J.; Kim, S. H.; Chang, S. J. Am. Chem. Soc. 2008, 130,
17268.
(3) (a) Davies, H. M. L.; Antoulinakis, E. G. Org. React. 2001, 57, 1.
(b) Rubin, M.; Rubina, M.; Gevorgyan, V. Synthesis 2006, 1221.
r
10.1021/ol201503j
Published on Web 06/27/2011
2011 American Chemical Society

temperatures (90À140 °C),4,5 but the copper catalysts have
been largely supplanted by dirhodium catalysts, which
form the cyclopropenes under very mild conditions.6,7 In
recent years, several chiral dirhodium catalysts have been
developed for asymmetric cyclopropenation with acceptor
carbenoids.8
Effective cyclopropenation with acceptor/acceptor car-
benoids and donor/acceptor carbenoids is a more recent
development compared to the reactions with acceptor
carbenoids.9,10 Highly enantioselective cyclopropenation
of terminal alkynes has been achieved with cobalt,9a
iridium,9b and rhodium10aÀc catalysts, but the reactions
fail with disubstituted alkynes.10a Computational studies
of dirhodium catalysts indicate that the alkyne has close to
an end-on approach to the carbenoid with a deviation of
18.2° that would cause a steric clash for a disubstituted
alkyne. Furthermore the terminal hydrogen of the alkyne
interacts with the carboxylate ligands in the transition state
for cyclopropenation with donor/acceptor carbenoids.
This may explain why donor/acceptor carbenoids do not
cyclopropenate internal alkynes.10c
A potential way to overcome this limitation would be to
use more reactive types of donor/acceptor carbenoids.
Studies have shown that silver catalysts result in effective
reactions with donor/acceptor carbenoids.11 These silver
carbenoids do not undergoWolff rearrangements, which is
a common outcome for the silver catalyzed reactions of
acceptor carbenoids.12,13 Moreover, silver catalysts will
induce cyclopropanation by donor/acceptor carbenoids of
highly substituted olefins which were unreactive under
rhodium-catalyzed conditions.11a In this paper, we de-
scribe that silver catalysis is an excellent approach for the
cyclopropenation of internal alkynes with donor/acceptor
carbenoids.
yields using 10 mol % of silver(I) salts having loosely
bound counterions with silver triflate providing the highest
yield of 97% (Scheme 2). Only trace amounts of cyclopro-
pene product were obtained when silver(I) salts of moÀre
CO32À, PhCO2À, SO42À) were used as a catalyst. These
results were consistent with the trend observedin the silver-
catalyzed cyclopropanation of styrene with 5.11a
tightly bound counterions (i.e., NO3À, PO43À, CF3CO2
,
Scheme 2
Acceptor- and acceptor-/acceptor-substituted diazo
compounds were also utilized as carbenoid precursors to
determine the effect of the carbenoid structure on the
silver-catalyzed reactions (Scheme 3). Ethyl diazoacetate
7 failed to undergo cyclopropenation with 3a. Instead
CÀCl insertion occurred into the solvent dichloro-
methane to produce the dichloro derivative 8 in 85% yield.
Similar reactivity has been reported for silver scorpionate
catalysts.14 Diazomalonate also did not afford the desired
cyclopropene products. The 1H NMR analysis of the crude
reaction mixture showed that the diazo compounds remained
unchanged. Silver complexes are known to be capable of
forming thermally stable complexes with diazo compounds
We commenced the study by investigating the use of
various readily available silver salts in the cyclopropena-
tion of 1-phenyl-1-propyne 3a with methyl phenyldiazoa-
cetate 5. Indeed, cyclopropene 4a was obtained in excellent
Scheme 3
(6) Petiniot, N.; Anciaux, A. J.; Noels, A. F.; Hubert, A. J.; Teyssie,
Ph. Tetrahedron Lett. 1978, 1239.
(7) For reviews, see: (a) Doyle, M. P. Russ. Chem. Bull. 1994, 43,
1770. (b) Doyle, M. P. Pure Appl. Chem. 1998, 70, 1123. (c) Doyle, M. P.
Enantiomer 1999, 4, 621. (d) Doyle, M. P.; Hu, W. Synlett 2001, 43, 5997.
(8) (a) Doyle, M. P.; Winchester, W. P.; Hoorn, J. A.; Lynch, V.;
Simonsen, S. H.; Ghosh, R. J. Am. Chem. Soc. 1993, 115, 9968. (b)
Doyle, M. P.; Protopova, M.; Muller, P.; Ene, D.; Shapiro, E. A. J. Am.
Chem. Soc. 1994, 116, 8492. (c) Lou, Y.; Horikawa, M.; Kloster, R. A.;
Hawryluk, N. A.; Corey, E. J. J. Am. Chem. Soc. 2004, 60, 1803.
(9) For cyclopropenation with acceptor-/acceptor-substituted diazo
compounds, see: (a) Cui, X.; Xu, X.; Lu, H.; Zhu, S.; Wojtas, L.; Zhang,
P. X. J. Am. Chem. Soc. 2011, 133, 3304. (b) Uehara, M.; Suematsu, H.;
Yasutomi, Y.; Katsuki, T. J. Am. Chem. Soc. 2011, 133, 170.
(10) For cyclopropenation with donor-/acceptor-substituted diazo
compounds, see: (a) Lee, G. H.; Davies, H. M. L. Org. Lett. 2004, 6,
1233. (b) Briones, J. F.; Hansen, J.; Hardcastle, K. I.; Autschbach, J.;
Davies, H. M. L. J. Am. Chem. Soc. 2010, 132, 17211. (c) Briones, J. F.;
Davies, H. M. L. Tetrahedron 2011, 67, 4313.
(11) (a) Thompson, J.; Davies, H. M. L. J. Am. Chem. Soc. 2007, 129,
6090. (b) Hansen, J. H.; Davies, H. M. L. Chem. Sci. 2011, 2, 457. (c)
Yue, Y.; Wang, Y.; Hu, W. Tetrahedron Lett. 2007, 48, 3975.
(12) For a review on Wolff rearrangement involving silver salts, see:
Kirmse, W. Eur. J. Org. Chem. 2002, 2193.
(13) For recent examples on silver-catalyzed Wolff rearrangement,
see: (a) Seki, H.; Georg, G. I. J. Am. Chem. Soc. 2010, 132, 15512. (b)
Seki, H.; Georg, G. I. Org. Lett. 2011, 13, 2147.
containing two electron-withdrawing groups,15,16 and this
may explain the lack of reactivity with these systems.
Ethyl-2-diazopropanoate 10 was converted to ethyl
(14) Dias, H. V. R.; Browning, R. G.; Polach, S. A.; Diyabalanage,
H. V. K.; Lovely, C. J. J. Am. Chem. Soc. 2003, 125, 9270.
(15) Julian, R. R.; May, J. A.; Stoltz, B. M.; Beauchamp, J. L. J. Am.
Chem. Soc. 2003, 125, 4478.
(16) Dias, H. V. R.; Polach, S. A. Inorg. Chem. 2000, 39, 4676.
Org. Lett., Vol. 13, No. 15, 2011
3985

acrylate 11, the product of a β-hydride elimination in 69%
yield, although, under rhodium catalysis, effective cyclo-
propenation can be achieved with 10.17 These results are
consistent with the hypothesis that silver carbenoids be-
have as more reactive intermediates than the rhodium
carbenoids,11a and it is only in the case of donor/acceptor
carbenoids that the carbenoid is sufficiently stabilized for
effective cyclopropenation to occur.
Table 1. Silver-Catalyzed Cyclopropenation of Various Alkynes
with Methyl Phenyldiazoacetate 5a
The generality of the silver-catalyzed cyclopropenation
was investigated with a range of disubstituted alkynes, and
the cyclopropene products were obtained in good to
excellent yields (Table 1). The structure of cyclopropene
4b was confirmed by X-ray crystallography.18 1,2-Diaryl
alkynes (entries 12À15) were effectively cyclopropenated
(64À98%). Cyclopropenation of alkyne with a boronic
ester functionality was achieved, as in the case of entry 14.
Monocyclopropenation of 1,3-diyne was also a viable
process affording the alkynyl cyclopropene 4p. It is also
interesting to note that the cyclopropenation reaction is
very chemoselective as CÀH insertion at the benzylic site
(entries 7, 9À11) as well as the methylene site next to siloxy
groups (entries 8 and 17) was not observed. Terminal
alkynes such as phenylacetylene and 1-TMS-phenylacety-
lene (entries 18 and 19) did not afford the desired cyclo-
propenes. The reactions with these substrates resulted in
the formation of precipitates. It is well-known that term-
inal alkynes react with silver salts to form insoluble silver
acetylides,19 and this may be the reason for unproductive
cyclopropenation of the terminal alkyne.
Several substrates were tested to further determine the
chemoselectivity of the AgOTf-catalyzed reaction in more
functionalized systems (Table 2). Substrates that contain
both alkyne and alkene moieties were tested to determine
whether cyclopropenation would be more favored over
cyclopropanation. In the case of entry 1, only the cyclopro-
panation product 13 was obtained as a single diastereomer.
The relative configuration of 13 was assigned based on NOE
analysis. Interestingly, when the olefin is more highly sub-
stituted, the reaction favors the formation of the cyclopro-
pene 15 in 85% yield. In the case of entry 3, cyclopropene 17
was isolated in excellent yield (86%). Only a trace amount of
the product from the cyclopropanation of the electronically
neutral and unsubstituted olefin was observed.
The scope of the AgOTf-catalyzed cyclopropenation
was further examined by utilizing various donor-/accep-
tor-substituted diazo compounds with 1-phenyl-1-pro-
pyne 3a as the representative alkyne trap (Table 3).
Excellent yields of the cyclopropene were obtained using
both electron-poor and relatively electron-rich aryldiazoa-
cetates. However, cyclopropenation was not observed in
the case of p-methoxyphenyl diazoacetate (entry 12) reflect-
ing the low reactivity of the p-methoxyphenyl carbenoid
(17) Panne, P.; Fox, J. M. J. Am. Chem. Soc. 2007, 129, 22.
(18) The crystal structure of 4b have been deposited at the Cambridge
Crystallographic Data Centre, and the deposition numbers CDCC
827875 have been allocated.
(19) (a) Letinois-Halbes, U.; Pale, P.; Berger, S. J. Org. Chem. 2005,
70, 9185. (b) Viterisi, A.; Orsini, A.; Weibel, J. M.; Pale, P. Tetrahedron
Lett. 2006, 47, 2779. (c) Bruce, M. I.; Humphrey, M. G.; Matisons, J. G.;
Roy, S. K.; Swincer, A. G. Aust. J. Chem. 1984, 37, 1955.
a Reaction conditions: 1 mmol of 3 used in 10 mL of solvent, 0.5
mmol of 5 used. b Isolated yield. c p-Br phenyldiazoacetate used.
3986
Org. Lett., Vol. 13, No. 15, 2011

Table 2. Chemoselectivity Studies: Cyclopropenation vs Cyclo-
propanationa
Table 3. AgOTf-Catalyzed Cyclopropenation of 3a and Various
Diazoacetatesa
a Reaction conditions: 1 mmol of substrate and 0.5 mmol of 5 used in
10 mL of solvent. b Isolated yield. c Product 13 formed with >20:1% dr.
even at refluxing conditions. Reaction with sterically de-
manding diazo compound such as in the case of entry 4 with
the substituted ortho positions was also a viable process.
Varying the electron-withdrawing group on the carbenoid
was also possible as the trifluoromethyl-, phosphonate-, and
cyano-substituted cyclopropenes were formed in excellent
yields (84À98%, entries 9À11). Although methyl styryldia-
zoacetate has been shown to be an effective carbenoid pre-
cursor for Ag(I)-catalyzed cyclopropanation reactions,11a it
failed to afford the desired cyclopropene product (entry 13).
This failure is probably due to product instability.9a,b
In summary, we have demonstrated that silver triflate is an
effective catalyst for cyclopropenation of disubstituted al-
kynes using donor-/acceptor-substituted diazo compounds.
Highly substituted cyclopropenes that have not been synthe-
sized before are now readily accessible. These studies demon-
strate that silver catalysis has advantages in certain cases over
rhodium catalysis. Further studies are ongoing to develop
suitable chiral silver catalysts, in order to achieve enantiose-
lective variants of the cyclopropenation reactions.
a Reaction conditions: 1 mmol of 3a used in 10 mL of solvent, 0.5
mmol of aryldiazo used. b Isolated yield. c 1H NMR analysis of the crude
reaction mixture showed formation of carbene dimers.
Supporting Information Available. Detailed experimen-
tal procedures and full characterization including 1H and
13C spectra for all new compounds. This material is
available free of charge via the Internet at http://pubs.
acs.org.
Acknowledgment. Financial support of this work by the
National Science Foundation is greatly acknowledged. We
thank Dr. Kenneth I. Hardcastle for the X-ray crystal
structure determination.
Org. Lett., Vol. 13, No. 15, 2011
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