Construction of an aryliridium-salen complex for highly cis- and enantioselective cyclopropanations

Article abstract of DOI:10.1002/anie.200604385

(Chemical Equation Presented) Ringing the changes: Iridium(lll)-salen complexes 1 bearing a σ-coordinated aryl ligand (L = CH₃C ₆H₄, C₆H₅) at the apical position are found to efficiently catalyze the cis- and enantioselective cyclopropanation of mono- and disubstituted olefins (see scheme).

Full text of DOI:10.1002/anie.200604385

Angewandte
Chemie
DOI: 10.1002/anie.200604385
Cyclopropanation
Construction of an Aryliridium–Salen Complex for Highly cis- and
Enantioselective Cyclopropanations**
Shigefumi Kanchiku, Hidehiro Suematsu, Kazuhiro Matsumoto, Tatsuya Uchida, and
Tsutomu Katsuki*
Optically active cyclopropane moieties are frequently found
in natural products and bioactive compounds, and the metal-
catalyzed asymmetric cyclopropanation of olefins is a potent
[
1]
method for their synthesis. There are two stereochemical
issues that need to be considered in asymmetric cyclopropa-
nation, namely enantioselectivity and diastereoselectivity
(
cis/trans selectivity). Since the seminal report on metal-
[
2]
mediated asymmetric cyclopropanation by Nozaki et al.,
significant effort has been devoted to the development of
transition-metal-catalyzed enantioselective cyclopropanation
reactions. However, most of these methods are trans-selec-
[
3]
[4,5]
tive; cis-selective methods are very limited in number.
Recently, we achieved the highly cis- and enantioselective
cyclopropanation of simple olefins with ruthenium–salen or
[
6,7]
cobalt–salen complexes as the catalyst.
subsequently reported a Ru(PNNP) complex (PNNP =
1S,2S)-N,N’-bis[2-(diphenylphosphino)benzylidene]cyclo-
hexane-1,2-diamine) that catalyzes cyclopropanation with a
Mezzetti et al.
(
[
8]
high cis- and good enantioselectivity, although the scope of
these reactions is narrow.
Among complexes of the Group 9 metals, chiral cobalt
and rhodium complexes have been shown to be useful as
[
9,10]
asymmetric carbene-transfer catalysts.
To the best of our
knowledge, however, there is no report of both an asymmetric
carbene-transfer reaction using an iridium complex and the
[
11]
synthesis of a stable Ir–salen complex.
Thus, we were
intrigued by our synthesis of a new chiral Ir–salen complex
and the subsequent discovery that such complexes bearing an
aryl ligand at the apical position are stable and can be handled
in air at room temperature. Herein, we describe the synthesis
of a new class of Ir –salen complexes and their application as
asymmetric cyclopropanation catalysts.
Scheme 1. Synthesis of Ir–salen complexes.
(cod)(toluene)]PF (2), was washed sequentially with toluene
6
III
and water, and dried; 2) treatment of complex 2 with the salen
ligand in toluene at reflux under nitrogen for 10 h gave
complex 3; 3) filtration of the solution and concentration on a
The Ir–salen complex 1 was synthesized by the sequence
[
12]
III
depicted in Scheme 1: 1) a mixture of [{Ir(cod)Cl} ] (cod =
rotary evaporator in air led to the Ir complex 4; 4) heating 4
2
III
1
3
,5-cyclooctadiene) and AgPF6 in toluene was stirred for
0 min at room temperature and then filtered through celite.
in toluene under nitrogen gave the (aR,R)-Ir –salen complex
1, which contains a tolyl group. High-resolution fast-atom
After concentration of the filtrate, the resultant solid, [Ir-
bombardment (FAB) mass spectrometry suggested that the
[
13]
tolyl group is s-coordinated to the iridium ion.
This s-
[*] S. Kanchiku, H. Suematsu, K. Matsumoto, Dr. T. Uchida,
coordination of the tolyl group is probably determined by an
Prof. T. Katsuki
S Ar mechanism in the final step as no involvement of a
E
I
Department of Chemistry, Faculty of Science
Graduate School, Kyushu University
Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan)
Fax: ( +81)92-642-2607
toluene component is observed until the Ir complex 3 is
[14]
III
exposed to air. The diastereomeric (aR,S)-Ir –salen com-
plex 5 was synthesized in the same manner. Complex 6 was
also synthesized from 2 following the same procedure but
with benzene as the solvent.
E-mail: katsuscc@mbox.nc.kyushu-u.ac.jp
[
**] Financial support for this work was provided by Specially Promoted
Research (18002011). K.M. is grateful for a JSPS Research Fellow-
ship for Young Scientists
III
To explore the properties of Ir –salen complexes in
asymmetric catalysis, we initially examined the cyclopropa-
nation of styrene with tert-butyl a-diazoacetate as the carbene
source and complexes 1, 4, and 5 as the catalysts (Table 1).
Supporting Information for this article is available on the WWW
under http://www.angewandte.org or from the author.
[
15]
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Communications
Table 1: Asymmetric cyclopropanation of styrene and its derivatives with
tert-butyl a-diazoacetate.
entries 5–7): the reaction proceeded even at À788C and
gave the cis isomer exclusively, in quantitative yield, with
[
a]
9
9% ee. These results suggest that more than one active
species might participate in this cyclopropanation and that the
ratio of the species depends on the reaction conditions. The
formation of the diesters was almost completely suppressed at
À788C. The reaction with 1 mol% of 1 proceeded with the
same stereoselectivity and yield (Table 1, entry 8), and the
reaction with complex 6 also led to identical stereochemical
outcome (Table 1, entry 9).
The cyclopropanation of substituted styrenes also pro-
ceeded with excellent stereoselectivity, irrespective of the
nature and the position of the substituents (Table 1,
entries 10–15). Although we carried out the reactions on a
0.1-mmol scale, they can just as easily be carried out on a 1-
mmol scale (see Table 1, entry 16 and the Experimental
Section). It is noteworthy that high enantio- and excellent
diastereoselectivity were also achieved in the reaction of
styrene with commercial ethyl a-diazoacetate (Table 1,
entry 17).
[
c]
Entry
Ar
T
Yield
[%]
cis/trans
eecis
[%]
ee
[%]
trans
[
b]
[d]
[d]
[8C]
[
e]
[f]
[f]
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
RT
RT
RT
RT
40
87
43
36
87
40:60
55:45
58:42
66:34
87:13
96:4
>99:1
>99:1
>99:1
97:3
>99:1
>99:1
99:1
>99:1
>99:1
>99:1
>99:1
76
96
96
70
18
96
93
92
–
–
–
–
–
[f]
[f]
[f]
[f]
[f]
[f]
[f]
84
À37
64
93
96
99
99
98
99
97
97
98
98
98
99
97
[
[
g]
h]
[f]
[f]
[
[
[
f]
f]
f]
À20
À40
À78
À78
À78
À78
À78
À50
À78
À78
À78
À78
À78
85
>99
>99
>99
90
88
>99
90
91
>99
90
[
[
[
[
[
[
[
[
[
[
i]
[f]
[f]
[k]
[k]
[k]
[k]
[k]
[k]
[k]
[f]
j]
j]
1
1
1
1
1
1
1
1
o-MeOC H4
m-MeOC H4
6
j]
6
j]
p-MeOC H4
o-ClC H4
m-ClC H4
p-ClC H4
Ph
Ph
6
j,l]
j]
–
–
–
–
6
6
j]
6
i,m]
i,o]
[n]
The cyclopropanation of indene and benzofuran also
proceeded with high enantio- and cis selectivity, albeit with
>99
–
[
16]
only moderate yield (Scheme 2).
To the best of our
[
1
[
a] Reactions were carried out in THF for 24 h on a 0.1-mmol scale with a
/diazo ester/olefin molar ratio of 0.05:1:10, unless otherwise noted.
b] Yields are based on the amount of diazo acetate used. Total yields of
knowledge, this is the first selective approach to optically
active cyclopropanes of this type.
1
the cis and trans cyclopropanes were determined by H NMR spectros-
copy (400 MHz) using 1-bromonaphthalene as an internal standard.
1
[
c] Determined by H NMR spectroscopy (400 MHz). [d] Determined by
HPLC analysis on a chiral column (Daicel Chiralcel OD-H). [e] 1 equiv of
styrene was used. [f] The absolute configurations of the cis and trans
isomers were determined to be 1R,2S and 1R,2R, respectively, by
comparing their elution order in the HPLC analysis with that of authentic
samples. [g] Complex 5 was used as the catalyst. [h] Complex 4 was used
as the catalyst. [i] 1 mol% of 1 was used as the catalyst. [j] Complex 6 was
used as the catalyst. [k] The absolute configuration was not determined.
Scheme 2. Asymmetric cyclopropanation of cyclic olefins.
[l] The reaction was carried out for 48 h. [m] The reaction was carried out
on a 1-mmol scale. [n] Yield of isolated product. [o] Ethyl a-diazoacetate
was used instead of tert-butyl a-diazoacetate.
A single crystal of the phenyliridium–salen complex 6 was
obtained by crystallization from dichloromethane and meth-
anol and examined by X-ray crystallography, which clearly
demonstrated that the phenyl group is s-coordinated to the
The reaction proceeded rapidly with good enantioselectivity
at room temperature, although the diastereoselectivity was
low and the yield of the desired product was unsatisfactory
because of the competitive production of fumaric and maleic
esters (Table 1, entry 1). We therefore decided to carry out
the reaction in the presence of an excess of styrene to suppress
this undesired diazo coupling (Table 1, entry 2). As expected,
the formation of the diesters was suppressed and the yield of
the desired products improved considerably. In addition, the
diastereoselectivity shifted from trans to cis products and the
enantiomeric excess of the cis isomer increased. The reaction
with 5 gave a similar level of diastereoselectivity but its
enantioselectivity was inferior to that with 1 (Table 1,
entry 3). The reaction with 4 also gave only moderate
enantioselectivity (Table 1, entry 4).
[
17]
iridium ion at the apical position.
This analysis also
disclosed that two complexes with different conformations
are present in each unit cell. The salen ligand in each
conformer adopts an umbrella-shaped or planar conforma-
tion and the conformation of the apical phenyl substituent in
each conformer is also different (Figure 1).
We next examined the reactions with 1 at lower temper-
atures and found that both the cis selectivity and the
enantiomeric excess of the cis isomer improved as the
reaction temperature decreased, while the enantiomeric
excess of the trans isomer diminished slightly (Table 1,
Figure 1. X-ray structure of 6. Hydrogen atoms and solvent molecules
are omitted for clarity. Ir small gray, C black, N blue, O red.
3
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Angew. Chem. Int. Ed. 2007, 46, 3889 –3891

Angewandte
Chemie
III
In conclusion, we have synthesized stable chiral Ir –salen
782; c) F. Estevan, J. Lloret, M. Sanaffl, M. A. Úbeda, Organo-
metallics 2006, 25, 4977 – 4984.
6] a) T. Uchida, R. Irie, T. Katsuki, Synlett 1999, 1163 – 1165; b) T.
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7] a) T. Niimi, T. Uchida, R. Irie, T. Katsuki, Tetrahedron Lett. 2000,
complexes that contain a s-coordinated aryl ligand. Prelimi-
nary results show that complex 1 is a unique and potent
catalyst for asymmetric cyclopropanation. Application of
[
[
[
[
III
these new Ir –salen complexes to other asymmetric reactions
is now in progress.
41, 3647 – 3651; b) T. Niimi, T. Uchida, R. Irie, T. Katsuki, Adv.
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2001, 20, 2102 – 2108.
Cyclopropanation of styrene with 1: tert-Butyl a-diazoacetate
0.14 mL, 1 mmol) and styrene (1.4 g, 10 mmol) were dissolved in
anhydrous THF (2.4 mL) under N and the solution was cooled to
À788C and stirred for 10 min. Complex 1 (11 mg, 10 mmol) was added
and the mixture was stirred for one day at this temperature. The
mixture was then allowed to warm to room temperature and
concentrated on a rotary evaporator. The residue was chromato-
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(
2
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968 – 9978.
graphed on silica gel (neat hexane to hexane/iPr O 10:1) to give the
2
9
cis product (197 mg, 90%) as a colorless oil.
1
[11] a) For an example of a non-enantioselective carbene-transfer
reaction, namely aziridination of imines, catalyzed by an Ir
complex, in which the complex serves as a Lewis acid to activate
the imines, see: T. Kubo, S. Sakaguchi, Y. Ishii, Chem. Commun.
The trans product could not be detected by H NMR (400 MHz)
spectroscopic analysis of the crude reaction mixture. The enantio-
meric excess of the cis product was determined by HPLC analysis
(
Daicel Chiralcel OD-H; 99% ee).
2000, 625 – 626; b) an Ir–salen complex prepared in situ and
incorporated into a zeolite has been used as a catalyst for
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Hölderich, Catal. Lett. 2001, 74, 69 – 75.
Received: October 26, 2006
Revised: December 14, 2006
Published online: April 12, 2007
[
[
12] The reaction was monitored by ESI mass spectrometry using
methanol as the matrix. The structure of complex 4 might be
Keywords: asymmetric catalysis · cyclopropanation · iridium ·
III
either a dimeric m-oxo Ir –salen complex or a monomeric
.
III
N,O ligands · salen
cationic Ir –salen complex.
13] 1 (red solid): Elementary analysis (%) calcd for
C H IrN O ·CH C H ·2H O: C 70.32, H 4.84, N 2.45; found:
6
0
44
2
2
3
6
4
2
C 70.11, H 4.85, N 2.54. HR FAB MS: m/z calcd. for
[
1] a) G. Maas, Chem. Soc. Rev. 2004, 33, 183 – 190; b) P. Müller,
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Catalysis, Vol. 2, Springer, Berlin, 1999, pp. 513 – 603.
C H IrN O ·CH C H : 1108.3580; found: 1108.3577. FAB
6
0
44
2
2
3
6
4
MS: m/z calcd. for C H IrN O ·CH C H ): 1108.37 (100%),
6
0
44
2
2
3
6
4
1109.37 (68.1%), 1106.36 (50.9%), 1107.37 (38.4%); found:
1108.36 (100%), 1109.36 (68.6%), 1106.36 (50.8%), 1107.36
(38.6%).
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E
III
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2
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Angew. Chem. Int. Ed. 2007, 46, 3889 –3891
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3891