Olefin cyclopropanation with aryl diazocompounds upon catalysis by a dirhodium(II) complex

Article abstract of DOI:10.1016/j.tetlet.2011.01.002

A dirhodium(II) complex with N-perfluorooctylsulfonylprolinate ligands is found to catalyze the cyclopropanation of olefins with simple aryl diazomethanes. In contrast to previously reported dirhodium(II) catalysts, the present complex works well not only with very electron-rich olefins such as enol ethers, but also with styrenes. Consequently, the present catalyst allows to prepare functionalized diarylcyclopropanes in moderate yields with good diastereoselectivity for the cis product, whereas the enantioselectivity of the reaction appears negligible.

Full text of DOI:10.1016/j.tetlet.2011.01.002

Tetrahedron Letters 52 (2011) 1136–1139
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Olefin cyclopropanation with aryl diazocompounds upon catalysis
by a dirhodium(II) complex
⇑
Mirella Verdecchia, Cristina Tubaro, Andrea Biffis
Dipartimento di Scienze Chimiche, Università di Padova, via Marzolo 1, 35131 Padova, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
A dirhodium(II) complex with N-perfluorooctylsulfonylprolinate ligands is found to catalyze the cyclo-
propanation of olefins with simple aryl diazomethanes. In contrast to previously reported dirhodium(II)
catalysts, the present complex works well not only with very electron-rich olefins such as enol ethers, but
also with styrenes. Consequently, the present catalyst allows to prepare functionalized diarylcyclopro-
panes in moderate yields with good diastereoselectivity for the cis product, whereas the enantioselectiv-
ity of the reaction appears negligible.
Received 19 October 2010
Revised 24 December 2010
Accepted 5 January 2011
Available online 15 January 2011
Keywords:
Rhodium
Ó 2011 Elsevier Ltd. All rights reserved.
Cyclopropanation
Phenyldiazomethane
Asymmetric catalysis
Transition metal-catalyzed olefin cyclopropanation with diazo-
compounds is one of the best known reactions involving organo-
metallic catalysis1 and has been extensively employed for the
preparation of structurally diverse cyclopropanes, which are
widely used building blocks or intermediates for organic synthesis.
In fact, the cyclopropane unit is present in various agrochemicals
and pharmaceuticals; furthermore, it can be cleaved in a variety
of ways to yield molecules with increased complexity.2,3 However,
cyclopropanation with diazocompounds also presents some limita-
tions: for example, only diazocompounds bearing at least one elec-
tron-withdrawing group can be efficiently employed as reagents.
In most other cases (with the only notable exception of simple
diazomethane) the diazo reagent is either not sufficiently stable
and/or inefficiently transferred to the olefin by the metal catalyst,
which instead promotes the formation of coupling products of the
diazocompound itself.
Direct cyclopropanations with simple aryl diazocompounds not
substituted by an electron-withdrawing group at the carbon atom,
like the parent compound phenyl diazomethane, have been occa-
sionally reported in the past, mainly using group 8 metal centers
as reaction promoters or catalysts.4,5 In particular, certain iron4c
and ruthenium5a porphyrin catalysts display a synthetically useful
reactivity, yielding with model olefin acceptors such as styrene
mainly the trans cyclopropane product. In contrast, the catalytic
efficiency exhibited by dirhodium(II) complexes, which rank
among the best cyclopropanation catalysts known to date, proved
scarce, with the parent dirhodium(II) acetate being active mainly
with very electron rich olefin acceptors such as enol ethers.4c,6
A few years ago, we reported that the perfluoroalkylated com-
plex I (Scheme 1), closely related to the highly successful N-aryl-
sulfonylprolinate complexes originally proposed by McKervey7
and extensively developed by Davies,1b,8 is an efficient and easily
recoverable and recyclable catalyst for asymmetric carbene trans-
fer reactions (cyclopropanations, insertions into C–H bonds).9 In
this contribution, we show that the same compound can be em-
ployed as catalyst for the cyclopropanation of styrenes and other
olefins with simple aryl diazocompounds, yielding the cyclopropa-
nation product in moderate yields with good cis stereoselectivity.
tetrakis-Dirhodium(II)-N-(4-t-butylphenyl)sulfonylprolinate
was already tested several years ago by Davies as the catalyst for
the cyclopropanation of styrene with phenyl diazomethane
(Scheme 2) and found to produce only trace yields of cyclopropa-
nation products.10 Consequently, we were quite surprised to record
O
O
Rh
Rh
C
N
S
O
O
(CF2)7CF3
4
I
⇑
Corresponding author.
E-mail address: andrea.biffis@unipd.it (A. Biffis).
Scheme 1.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.01.002

M. Verdecchia et al. / Tetrahedron Letters 52 (2011) 1136–1139
1137
H
R'
R
N2
I
+
R
R'
Scheme 2.
Table 1
Synthesis of cyclopropanes from olefins and diazocompounds
Entry
Olefin
Diazocompound
Olefin/diazo
10
Ia (mol %)
Yieldb (%)
56
drc
N2
1
1
88:12
75:25
71:29
H
N2
H
2
3
10
20
2
1
56
76
N2
H
N2
H
4
5
10
10
1
1
20
54
80:20
87:13
N2
H
Cl
F
N2
H
6
7
10
10
1
1
57
17
84:16
88:12
N2
H
NC
N2
H
8
10
1
14d
84:16d
NO2
N2
H
9
10
10
1
1
50
6
80:20
83:17
85:15
MeO
N2
H
10
MeO
N2
H
11
12
10
10
1
1
48
0
Cl
N2
—
CH3
(continued on next page)

1138
M. Verdecchia et al. / Tetrahedron Letters 52 (2011) 1136–1139
Table 1 (continued)
Entry
Olefin
Diazocompound
Olefin/diazo
10
Ia (mol %)
Yieldb (%)
drc
—
N2
13
14
15
1
0
H
O
N2
H
O
10
10
1
1
6
80:20
83:17
N2
H
O
96
Reaction conditions: see Ref. 11.
a
I (mol %) with respect to the limiting reagent (the aryl diazomethane).
Isolated yields.
Diastereomeric ratio (cis:trans).
b
c
d
Yields after 48 h reaction time.
in the same reaction with our closely related catalyst I an isolated
cyclopropanation yield of 56%, under conventional reaction condi-
tions (1 equiv diazocompound, 10 equiv styrene, 1 mol % catalyst,
controlled diazocompound addition over 5 h, toluene, 14 h),11
other products being coupling or decomposition products of the
diazocompound. In accordance with previous findings, the ob-
served stereoselectivity was found to be opposite to that exhibited
by iron and ruthenium porphyrins, which are known to yield pref-
erentially the trans cyclopropanation product.4c,5a
We have briefly examined the effect of changing the reaction
conditions on the yield of the reaction (Table 1, entries 1–3).
Increasing the amount of catalyst from 1 to 2 mol % had no signif-
icant effect on the overall yield in cyclopropanation products
whereas the selectivity for the cis product was lowered. On the
contrary, working with a greater excess of olefin acceptor (20 equiv
instead of 10) significantly improved the cyclopropanation yields
but also decreased the diastereoselectivity. Consequently, in our
further investigations we decided to keep on working with
10 equiv olefin and 1 mol % catalyst.
The scope and limitations of the reaction have been examined,
particularly with reference to the effect of the nature of the substit-
uents on the aromatic ring of the olefin and/or of the diazocom-
pound.12 As expected, cyclopropanation is favored by electron-
donating substituents at the olefin and by electron-withdrawing
substituents at the aryldiazocompound. The former raises the
HOMO energy of the olefin and consequently its tendency to add
the intermediate carbene (Table 1, entries 4–9), the latter stabilizes
the diazocompound as well as the intermediate metal carbene
against decomposition, thereby favoring its effective transfer (Ta-
ble 1, entries 10 and 11). It is important to remark that this oppo-
site effect of the nature of the substituents on the olefin and on the
diazocompound potentially allows the preparation of diarylcyclo-
propanes bearing a wide range of substituents at the aryl groups,
since electron-donating substituents can be conveniently incorpo-
rated in the alkene whereas electron-withdrawing substituents can
be placed on the aryldiazomethane. On the other hand, the pres-
ence of additional electron-donating substituents on the carbene
carbon of the aryldiazocompound is not tolerated: in fact, no cyclo-
propanation product is observed with methyl phenyl diazometh-
ane (Table 1, entry 12).
pound reagent,12 which is, however, not isolated: instead, the as-
synthesized diazocompound solution can be directly employed as
the reagent for the cyclopropanation reaction.11
We have also performed a preliminary evaluation of the scope of
the reaction with respect to the olefin substrate. For example, a 1,2-
disubstituted olefin such as cis-propenylbenzene did not add the
carbene (Table 1, entry 13), in contrast to a less sterically encum-
bered 1,1-disubstituted olefin such as
a-methylstyrene, which is
known to be much more prone to give cyclopropanation products.4,5
Incidentally, the group of Che also reported much lower yields for a
1,2 disubstituted olefin (trans-propenylbenzene) compared to an
analogous 1,1-disubstituted one
(a-methylstyrene) using a
ruthenium porphyrin catalyst.5a Vinyl acetate also gave poor yields
(Table 1, entry 14), as previously reported using simple dirho-
dium(II) acetate as the catalyst.4c,6 On the contrary, a more
electron-rich olefin substrate such as butyl vinyl ether gave as
expected a high yield (96%) in cyclopropanation products (Table 1,
entry 15), again similarly to what has been previously reported with
simple dirhodium(II) acetate.6 The diastereoselectivity for the cis
product remained good in all cases. Finally, we investigated on the
enantioselectivity of the reaction by subjecting the isolated products
to chiral HPLC analysis following an analytical protocol previously
described by Berkessel et al. for diphenylcyclopropanes.5b Unfortu-
nately, the enantioselectivity of the reaction proved in all cases
negligible for both diastereomeric cyclopropane products.
In conclusion, we have demonstrated that in contrast to previ-
ous reports a tetrakis-dirhodium(II) prolinate complex such as I is
an efficient catalyst for cyclopropanations of olefins with aryl dia-
zomethanes. This catalyst promotes the reaction not only with
very electron-rich olefins such as enol ethers, but also with
styrenes, which opens the way to the synthesis of substituted
diarylcyclopropanes. The reaction is featured by negligible enanti-
oselectivity but by good diastereoselectivity for the cis diarylcyclo-
propane product.
Acknowledgments
M.V. wishes to thank the University of Padova (Assegni di ric-
erca 2008) for a scholarship. We wish to thank Dr. Cristiano Zonta,
University of Padova, for skillful assistance in chiral HPLC analysis.
In this way, an isolated yield of 50–60% in diarylcyclopropane
products can be reached, with a diastereomeric ratio which is
apparently almost independent of the nature of the substituents
on the reagents, ranging from 80:20 to 88:12 and always favoring
the cis isomer. It needs to be remarked that the employed synthetic
procedure involves the preliminary preparation of the diazocom-
References and notes
1. (a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds; Wiley: New York, 1998; (b) Davies, H. M. L.;
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C.; Charette, A. B. Chem. Rev. 2003, 103, 977.

M. Verdecchia et al. / Tetrahedron Letters 52 (2011) 1136–1139
1139
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11. General procedure for the catalytic tests. Complex I (15
l
mol or 30
l
mol) and
olefin (15 mmol or 30 mmol) were dissolved in 20 mL 1:1 toluene/
tetrahydrofuran under an inert argon atmosphere. To this solution, the
diazocompound solution (1.5 mmol), freshly prepared as described in Ref. 12,
was added over a 5 h period using a syringe pump. The reaction mixture was
left under stirring overnight at room temperature, after which it was
evaporated to dryness under reduced pressure. The resulting oil was then
purified by column chromatography over silica gel (petroleum ether/ethyl
acetate, 98:2 v:v) to afford the cyclopropanation products. The configuration of
the various diastereoisomers was attributed by comparing their NMR spectra
with those of the pure diastereoisomers previously reported in the literature.
12. General procedure for the synthesis of the aryl diazocompounds. Commercial
benzaldehyde tosylhydrazone, or p-substituted benzaldehyde tosylhydrazone
prepared according to Ref. 13, (1.5 mmol) was dissolved in 10 mL toluene and
slowly added to a solution of 0.041 g benzyltriethylammonim chloride in
4.1 mL aqueous NaOH (14% w/w) under an inert argon atmosphere. The
reaction mixture was heated to 70 °C and maintained at that temperature with
stirring for 2 h. A progressive red coloration of the solution was observed. After
cooling to room temperature, the organic phase was quickly separated from
the aqueous phase, washed twice with 5 mL water, dried with Na2SO4 for
30 min, filtered, and immediately employed as the reagent for the
cyclopropanation reaction.
13. Creary, X. Org. Synth. 1986, 64, 207.