.
Angewandte
Communications
beyond CDA and NDA. Considering the aforesaid challenges
in the area, we embarked on a specific project to investigate
the use of dicarbonyl diazo reagents such as KDA for
Table 1: Asymmetric cyclopropanation of styrene with ADA by the
metalloradical catalyst [Co(P1)].
[
a]
II
asymmetric intermolecular cyclopropanation by Co MRC.
II
In view of the radical nature of Co -based metalloradical
[
15]
[b]
[c]
cyclopropanation, it was unclear at the onset of this project
Entry CO
2
R
Catalyst
Solvent Yield [%]
E/Z ee [%]
if [Co(D -Por*)] could allow achievement of high control of
2
1
2
3
4
5
6
CO Me [Rh (Oct) ] CH Cl
62
99
86
81
71
88
22:78
79:21
>99:1
>99:1
96:4
–
63
90
92
82
94
2
2
4
2
2
2
2
enantio- and diastereoselectivity by discriminating between
two similar carbonyl groups of a common KDA. As the result
of this investigation, we herein report the first catalytic system
for asymmetric cyclopropanation with simple a-acetodiazo-
acetates (ADA) and it is effective for different kinds of
olefins, thus leading to high-yielding synthesis of 1,1-cyclo-
propaneketoesters as E diastereoisomers in high enantiomer-
ic purity. In addition to using olefins as limiting substrates, this
highly asymmetric catalytic system can be run at room
temperature without the need for slow addition of the diazo
reagents. Furthermore, we describe an unprecedented epi-
merization process promoted by NaI and it allows conversion
of the resulting E-1,1-cyclopropaneketoesters into their
Z isomers with complete retention of the enantiopurity.
CO Me [Co(P1)]
CH Cl
2
2
CO tBu [Co(P1)]
CH Cl
2
2
CO
tBu [Co(P1)]
PhCl
2
CO tBu [Co(P1)]
hexanes
toluene
2
[
d]
CO tBu [Co(P1)]
96:4
2
[a] Reactions were carried out in a one-time protocol using 5 mol%
Co(P1)] under N at RT for 36 h with [olefin]=0.20m. [b]Yields of
[
2
isolated products. [c] Enantiomeric excess of the major E diastereo-
isomer was determined by HPLC analysis using a chiral stationary phase.
d] [1R,2S] Absolute configuration determined by X-ray diffraction
[
measurement on single crystal.
in near quantitative yield (entry 2). In addition to the
excellent yield, it is important to note that the E diastereo-
selectivity exhibited by the Co -based system is the opposite
of that previously reported for [Rh ]-based catalytic systems
II
The cobalt(II) complex of the D -symmetric chiral
2
t
porphyrin 3,5-Di Bu-ChenPhyrin, [Co(P1)] (Figure 1a), was
2
[
4b,5d,16]
shown to be an effective catalyst for asymmetric cyclopropa-
(entry 1).
Furthermore, the E selectivity allowed us to
[6d]
[6b]
nation with NDA and CDA. Its catalytic effectiveness
improve the diastereoselectivity of the catalytic system
significantly by employing the bulkier tert-butyl acetodiazo-
acetate (t-BADA) while increasing its enantioselectivity at
the same time (entry 3). Among the solvents screened,
toluene was found to be the solvent of choice, thus producing
the 1,1-cyclopropaneketoester 2a in 88% yield with 92% de
and 94% ee (entries 3–6). The relative and absolute config-
urations of 2a were established as E and (1R,2S), respectively,
by anomalous-dispersion effects in X-ray diffraction mea-
surement of its single crystal (see Figure S1 in the Supporting
Information).
The [Co(P1)]-catalyzed asymmetric cyclopropanation
could be successfully applied to a wide range of olefins
under similar reaction conditions (Table 2). For example,
styrene derivatives, regardless of the position and electronic
property of the substituent (including electron-donating Me
and MeO as well as electron-withdrawing Br, CF , and NO
II
Figure 1. Structures of D -symmetric chiral Co porphyrins. * For
2
clarity, 3,5-di-tert-butylphenyl unit in the back of the ligand is omitted.
3
2
toward these two acceptor/acceptor-substituted diazo
reagents was attributed to the double hydrogen-bonding
interactions between the amide NH donors on the P1 ligand
and two acceptors on the carbene moiety in the postulated
groups), could be reliably cyclopropanated with t-BADA,
thus generating the corresponding cyclopropaneketoesters
2a–f in high yields with both high diastereoselectivity and
enantioselectivity. As a further highlight of the unique
[6b,d]
II
metallocarbene radical intermediate.
Since the C=O unit
catalytic property of the Co MRC, cyclopropanation of
of ketone groups is also known as a suitable hydrogen-bond
acceptor, we hypothesized the potential existence of similar
double hydrogen-bonding interactions in the resulting cobalt–
carbene radical intermediate from the reaction with KDA
even the extremely electron-deficient pentafluorostyrene
could be positively performed to form the desired cyclo-
propane 2g with complete control of stereoselectivity, albeit
in a lower yield. The use of a-methylstyrene allowed the
stereoselective construction of the cyclopropane 2h having
two contiguous all-carbon quaternary stereogenic centers.
(
Figure 1b). This hypothesis prompted us to systematically
examine the asymmetric cyclopropanation with the common
a-acetodiazoacetates using styrene (1a) as a model substrate
II
Furthermore, the Co -based asymmetric cyclopropanation
(
Table 1). We were pleased to observe that the simple methyl
acetodiazoacetate (MADA) could be effectively activated by
Co(P1)] to cyclopropanate styrene under mild reaction
could be effectively applied to styrenes containing sensitive
functionalities such as an aldehyde group (2i) and olefins
derived from heteroarenes such as indole (2j) without
complications arising from potential ylide-mediated reac-
tions. When conjugated alkenes were used as substrates,
regioselective cyclopropanation of the terminal double bonds
[
conditions using a practical protocol (at room temperature
with the alkene as the limiting reagent without slow addition
of the diazo reagent), thus affording the desired cyclopropane
1
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 11857 –11861