Enhancement of cyclopropanation chemistry in the silver-catalyzed reactions of aryldiazoacetates

Article abstract of DOI:10.1021/ja069314y

AgSbF₆ is an effective catalyst for the reactions of donor/acceptor substituted carbenoids and shows a very different reactivity profile from the traditional rhodium-catalyzed reactions. Most notably, cyclopropanation of sterically hindered alk

Full text of DOI:10.1021/ja069314y

Published on Web 04/19/2007
Enhancement of Cyclopropanation Chemistry in the Silver-Catalyzed
Reactions of Aryldiazoacetates
Janelle L. Thompson and Huw M. L. Davies*
Department of Chemistry, UniVersity at Buffalo, The State UniVersity of New York, Buffalo, New York 14260
Received December 27, 2006; E-mail: hdavies@buffalo.edu
The transition-metal catalyst has a crucial effect on modulating
the decomposition chemistry of diazo compounds.1 Dirhodium
catalysts have supplanted the traditional copper catalysts because
in general they give much cleaner transformations for many
reactions, such as cyclopropanation, C-H insertion, and ylide
formation.1 The silver-catalyzed decomposition of diazo ketones
is a component of the venerable Arndt-Eistert homologation.1,2 The
resulting highly reactive silver carbenoids undergo a Wolff rear-
rangement instead of the typical reaction seen with dirhodium
catalysis. Effective intermolecular reactions in silver carbenoid
chemistry with ethyl diazoacetate have been limited to reactions
catalyzed by silver scorpionate catalysts.3-5
clopropanation and C-H insertion would be highly beneficial, and
silver catalysis was found to have a profound influence on this
selectivity.
A comparison between AgSbF6- and rhodium(II) acetate-
catalyzed reactions was conducted with a range of substrates. Silver
catalysis strongly favors cyclopropanation as can be seen in the
reaction between cyclohexene and methyl phenyldiazoacetate (1)
(eq 2). The cyclopropane 3 was produced in high yield (88%) and
diastereoselectivity (>94% de), while the rhodium acetate-catalyzed
reaction gave a mixture of 3 and the C-H insertion product 4 in a
1:2.2 ratio.
The profound effect of the carbenoid structure on carbenoid
reactivity has become widely recognized.1,6 The traditional car-
benoids functionalized with one or two electron acceptor groups
(ester, ketone, phosphonate, etc.) are highly electrophilic.1 We have
found that carbenoids with a donor (aryl, vinyl, or alkynyl) and an
acceptor group are much more chemoselective than the traditional
carbenoids.6 This has led to a number of highly stereoselective
synthetic methods such as cyclopropanation,7 [4 + 3] cycloaddi-
tion,8 [3 + 2] cycloaddition,9 and intermolecular C-H insertion.3a,10
In this paper, we demonstrate that the silver hexafluoroantimonate
(AgSbF6)-catalyzed reactions of donor/acceptor-substituted car-
benoids offer new synthetic opportunities, which cannot be achieved
with dirhodium catalysis.
The first stage of this project was to screen the commonly
available silver salts in the cyclopropanation of styrene with methyl
phenyldiazoacetate 1 (eq 1). AgSbF6 gave the highest yield (96%)
in this reaction, generating the cyclopropane 2 with very high
diastereoselectivity (>94% de). The catalytic activity of the silver
salt seems to be dependent upon the counterion, as more tightly
bound counterions (e.g., AgO2CCF3, AgOAc, Ag2SO4) gave poor
yields or no reaction at all.11
Further investigation into a more highly substituted system, trans-
â-methylstyrene, gave even more contrasting results. The AgSbF6-
catalyzed reaction yielded the cyclopropane 5 in excellent yield
(80%) and diastereoselectivity (>94% de), retaining the trans
orientation between the phenyl and methyl groups in the final
product (eq 3). The same reaction catalyzed by rhodium acetate
gave only a 4% yield of the C-H insertion product 6; carbene
dimerization was the dominant product despite the presence of the
substrate in large excess. This result confirms that the rhodium-
catalyzed reactions of donor/acceptor-substituted carbenoids are
especially inefficient at mediating the cyclopropanation reaction
of trans-1,2-disubstituted alkenes, but the silver-catalyzed reactions
have a very different reactivity profile.
Having demonstrated that the silver carbenoid is capable of
intermolecular cyclopropanation, a comparative study of the
reactivity profile of silver- versus dirhodium-catalyzed reactions
was performed. In rhodium-catalyzed reactions of donor/acceptor
carbenoids, monosubstituted alkenes and 1,2-disubstituted alkenes
efficiently undergo cyclopropanation.7 Cis-1,2-disubstituted alkenes
are less favorable substrates for cyclopropanation and intermolecular
C-H insertion becomes a competing process. Trans-1,2-disubsti-
tuted or more highly substituted alkenes are sterically protected
and very few examples of their cyclopropanation by donor/acceptor
carbenoids are known.7d Controlling the selectivity between cy-
The results of the AgSbF6-catalyzed cyclopropanation of a range
of alkenes are summarized in Table 1. Only the reaction with 1,1-
diphenylethylene (entry 5) can be effectively achieved under
rhodium catalysis. In entries 1-3 the cyclopropanation of cyclic
cis alkenes is very effective with AgSbF6, but allylic C-H insertion
9
6090
J. AM. CHEM. SOC. 2007, 129, 6090-6091
10.1021/ja069314y CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Silver-Catalyzed Cyclopropanation with 1
no cyclopropanation products. The cyclopropanations are all highly
diastereoselective, as is characteristic for the donor/acceptor car-
benoids.7
entry
R1
R2
R3
yield, %
1
2
H
H
-(CH2)4-
-(CH)CHCH2CH2)-
88
79
3
H
80
4
5
6
7
8
9
H
H
Ph
H
Me
H
Ph
Ph
H
Ph
Ph
Ph
Ph
96
82
80
86
84
54
Ph
Me
H
Ph
H
In conclusion, these studies show that AgSbF6 is an effective
catalyst for the reactions of donor/acceptor substituted carbenoids
and shows a different reactivity profile from the traditional rhodium-
catalyzed reactions. Most notably, sterically hindered alkenes, which
are unreactive under rhodium(II) acetate-catalyzed conditions, can
be effectively cyclopropanated under silver-catalyzed conditions.
Table 2. Silver-Catalyzed Cyclopropanation with 7
Acknowledgment. This research was supported by the National
Science Foundation (Grant CHE-0350536).
Supporting Information Available: Full experimental procedures
for the rhodium acetate-catalyzed reactions and the characterization of
new compounds are detailed. This material is available free of charge
via the Internet at http://pubs.acs.org.
entry
R1
R2
R3
yield, %
1
2
H
H
-(CH2)4-
43
-(CH)CHCH2CH2)-
67a
References
(1) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds; Wiley-Interscience: New York,
1998.
(2) (a) Gill, G. B. In ComprehensiVe Organic Synthesis; Trost, B. M.;
Flemming, I., Eds.; John Wiley: New York, 1991; Vol. 3, pp 887. (b)
Ye, T.; McKervey, A. Chem. ReV. 1994, 94, 1091. (c) Bachmann, W. E.;
Struve, W. S. Org. React. 1946, 1, 38.
(3) (a) Dias, H. V. R.; Browning, R. G.; Polach, S. A.; Diyabalanage, H. V.
K.; Lovely, C. J. J. Am. Chem. Soc. 2003, 125, 9270. (b) Dias, H. V. R.;
Browning, R. G.; Richey, S. A.; Lovely, C. J. Organometallics 2004, 23,
1200. (c) Lovely, C. J.; Browning, R. G.; Badarinarayana, V.; Dias, H.
V. R. Tetrahedron Lett. 2005, 46, 2453. (d) Urbano, J.; Belderrain, T. R.;
Nicasio, M. C.; Trofimenko, S.; Diaz-Requejo, M. M.; Perez, P. J.
Organometallics 2005, 24, 1528.
(4) For a recent example describing ineffective cyclopropanation by ethyl
diazoacetate catalyzed by silver triflate, see: Lee, H. M.; Bianchini, C.;
Jia, G.; Barbaro, P. Organometallics 1999, 18, 1961.
3
H
57
4
5
6
7
H
H
Ph
H
Ph
H
Ph
Ph
82
56b
65
34
Ph
Me
Ph
H
a Includes 15% of insertion product. b Reaction conducted at room
temperature.
is a major competing reaction in rhodium-catalyzed reactions.12
AgSbF6-catalyzed cyclopropanation of more hindered substrates can
also be achieved (entries 6-10), despite the fact that these substrates
give virtually no cyclopropanation when the reaction is catalyzed
by rhodium(II) acetate. In every case the cyclopropanation is highly
diastereoselective, and no second diastereomer was evident by
NMR.
Silver catalysis also has a major effect on the chemistry of
vinyldiazoacetates as illustrated in eq 4. AgSbF6-catalyzed reaction
of the vinyldiazoacetate 7 with 1,3-cyclohexadiene resulted in
primarily a tandem cyclopropanation/Cope rearrangement6 to form
the formal [4 + 3] cycloadduct 8 in 52% yield (eq 4). In contrast,
the rhodium acetate-catalyzed reaction gave a 1.4:1 ratio of the
cycloadduct 8 and the C-H functionalization product 9 derived
from a combined C-H activation/Cope rearrangement.13 Table 2
summarizes the AgSbF6-catalyzed cyclopropanation of a range of
alkenes by vinyldiazoacetate 7. Only the reactions with styrene
(entry 4) and 1,1-diphenylethylene (entry 5) can be effectively
achieved under rhodium catalysis.12 For the other substrates, the
rhodium(II) acetate-catalyzed reactions gave either a mixture or
(5) For an example of an intramolecular C-H insertion of donor/acceptor-
substituted carbenoids catalyzed by silver salts, see: Burgess, K.; Lim,
H.-J.; Porte, A. M.; Sulikowski, G. A. Angew. Chem., Int. Ed. 1996, 35,
220.
(6) (a) Davies, H. M. L.; Walji, A. M. In Modern Rhodium-Catalyzed Organic
Reactions; Evans, P. A., Ed.; Wiley-VCH: Stamford, CT, 2005; pp 301-
340. (b) Davies, H. M. L.; Loe, Ø. Synthesis 2004, 2595.
(7) (a) Davies, H. M. L.; Townsend, R. J. J. Org. Chem. 2001, 66, 6595. (b)
Davies, H. M. L.; Antoulinakis, E. G. Org. React. 2001, 57, 1. (c) Davies,
H. M. L.; Bruzinski, P.; Hutcheson, D. K.; Kong, N.; Fall, M. J. J. Am.
Chem. Soc. 1996, 118, 6897. (d) Davies, H. M. L.; Ren, P. J. Am. Chem.
Soc. 2001, 123, 2070.
(8) Davies, H. M. L. In AdVances in Cycloaddition; Harmata, M., Ed.; JAI
Press: Weinheim, 1998; Vol. 5, pp 119-164.
(9) Davies, H. M. L.; Xiang, B.; Kong, N.; Stafford, D. G. J. Am. Chem.
Soc. 2001, 123, 7461.
(10) Davies, H. M. L.; Beckwith, R. E. J. Chem. ReV. 2003, 103, 2861.
(11) See Table 3 in the Supporting Information for a description of the effect
of other silver salts on this reaction.
(12) See the Supporting Information for a detailed description of the corre-
sponding rhodium-catalyzed reactions.
(13) (a) Davies, H. M. L.; Stafford, D. G.; Hansen, T. Org. Lett. 1999, 1, 233.
(b) Davies, H. M. L.; Jin, Q. J. Am. Chem. Soc. 2004, 126, 10862.
JA069314Y
9
J. AM. CHEM. SOC. VOL. 129, NO. 19, 2007 6091