Acceptor/acceptor-substituted diazo reagents for carbene transfers: Cobalt-catalyzed asymmetric Z-cyclopropanation of alkenes with a-nitrodiazoacetates

Article abstract of DOI:10.1002/anie.200803857

(Chemical Equation Presented) Surprisingly cis-tematic! The cobalt(II) complex of a D₂-symmetric chiral porphyrin is an effective catalyst for asymmetric cyclopropanation with α-nitrodiazoacetates (see scheme). The catalytic system is general and suitable for electron-sufficient, -neutral, and -deficient alkenes, forming the corresponding cyclopropane nitroesters in high yields. In addition to high diastereo- and enantioselectivity, the catalytic process exhibits atypical Z selectivity.

Full text of DOI:10.1002/anie.200803857

Communications
DOI: 10.1002/anie.200803857
Asymmetric Cyclopropanation
Acceptor/Acceptor-Substituted Diazo Reagents for Carbene Transfers:
Cobalt-Catalyzed Asymmetric Z-Cyclopropanation of Alkenes with
a-Nitrodiazoacetates**
Shifa Zhu, Jason A. Perman, and X. Peter Zhang*
Cyclopropanes are an important class of compounds that have
numerous fundamental and practical applications.[1] One of
the most general approaches for the stereoselective construc-
tion of cyclopropanes, which are the smallest all-carbon cyclic
molecules, is the metal-catalyzed asymmetric cyclopropana-
tion of alkenes with diazo reagents.[2] Among the three classes
of common diazo reagents,[3] acceptor-substituted diazo
reagents, such as diazoesters, are well established as the
most effective carbene sources for metal-catalyzed stereose-
lective cyclopropanation.[4] There has been great progress in
metal-catalyzed selective carbene transfers with donor/
acceptor-substituted diazo reagents such as vinyldiazoesters
and aryldiazoesters.[3,5] However, asymmetric cyclopropana-
tion with acceptor/acceptor-substituted diazo reagents
remains a major challenge in the field because of their
inherent low reactivity and perceived poor enantioselectiv-
ity.[2,3] Therefore, more reactive and enantiodiscriminating
catalysts need to be developed to meet this challenge.[2,3]
A family of cobalt(II) D2-symmetric chiral porphyrins
[Co(Por)] with tunable electronic, steric, and chiral environ-
ments (Figure 1), has emerged as a new class of effective
catalysts for various asymmetric cyclopropanation reactions,
including that of electron-deficient olefins with diazosul-
fones.[6,7] Having recognized their distinct catalytic proper-
ties,[6–8] we initiated a project to examine the potential of CoII-
based catalysts for asymmetric cyclopropanation with
acceptor/acceptor-substituted diazo reagents. Our first
target was a-nitrodiazoacetates (NDAs),[9] as the resulting
cyclopropanes have been demonstrated to be valuable
precursors for a number of useful compounds, including the
synthetically and biologically important cyclopropane a-
amino acids and aminocyclopropanes (Scheme 1).[10] Among
Figure 1. Structures of D2-symmetric chiral cobalt(II) porphyrins.
several previous efforts towards metal-catalyzed cyclopropa-
nation with NDA,[10–13] it is notable that Charette et al.
conducted a systematic evaluation of the reaction by employ-
ing various Rh- and Cu-based chiral catalysts.[12] While the
[*] Dr. S. Zhu, J. A. Perman, Prof. Dr. X. P. Zhang
Department of Chemistry, University of South Florida
Tampa, FL 33620-5250 (USA)
Fax: (+1)813-974-1733
Scheme 1. Synthesis and further reactions of cyclopropane nitroesters.
E-mail: pzhang@cas.usf.edu
Homepage: http://chemistry.usf.edu/faculty/zhang/
desired cyclopropanes were obtained predominantly as
E isomers in good yields, the best enantioselectivity, which
was achieved by using a Cu-based catalyst in the presence of
ethyl diazoacetate (20%) as additive, was 72% ee.[12,14] We
report herein a CoII-based catalytic system for highly
[**] We are grateful to USF (Startup Funds), ACS-PRF (AC Grant), NSF
(CAREER Award), and NSF (CHE-0443611, Mass Facility) for
financial support of this work.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200803857.
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Chemie
Table 2: [Co(P1)]-catalyzed diastereo- and enantioselective cyclopropa-
nation of different alkenes with a-nitrodiazoacetates.[a]
diastereo- and enantioselective cyclopropanation of various
alkenes with NDA.[15] Furthermore, the catalytic process
produced the atypical Z isomers as the dominant products.
Initial efforts were focused on the systematic evaluation of
various catalytic conditions for the cyclopropanation of
styrene with ethyl a-nitrodiazoacetates (ENDAs) by different
[Co(Por)] (Table 1 and Table S1 in the Supporting Informa-
Entry Cyclopropane
R
Yield
[%][b]
Z/E[c]
ee [%][d] [a][e]
1
Et
Et
87
93
92:08
92:08
>99:1
>99:1
93:07
89
92
91
94
90
92
(ꢀ)
(ꢀ)
(ꢀ)
(ꢀ)
(ꢀ)
(ꢀ)
2[g,h]
3
tBu 91
tBu 97
Et
4[g,h]
5[g,h]
6[h]
86[k]
Table 1: Asymmetric Z-cyclopropanation of styrene with ethyl a-nitro-
diazoacetate by D2-symmetric chiral cobalt(II) porphyrins.[a]
tBu 90
>99:1
7[g,h]
8[g,h]
Et
91
96:04
92:08
91
91
(ꢀ)
Et
Et
82
83
(ꢀ)
Entry
[Co(Por)][b]
Solvent
Yield
[%][c]
Z/E[d]
ee
9[g,h]
10[h]
92:08
>99:1
90
92
(ꢀ)
(ꢀ)
[%][e]
tBu 87
1
2
3
4
5
6
7
8
[Co(tpp)]
[Co(P1)]
[Co(P2)]
[Co(P3)]
[Co(P4)]
[Co(P5)]
[Co(P6)]
[Co(P1)]
[Co(P1)]
[Co(P1)]
[Co(P1)]
[Co(P1)]
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
C2H4Cl2
C2H4Cl2
C2H4Cl2
C6H5Cl
n-C6H14
15[f]
99
99
20
69
58:42
91:09
91:09
67:33
81:19
66:34
85:15
93:07
92:08
92:08
88:12
92:08
–
81
58
33
11[g,h]
12[g,h]
13[g,h]
Et
Et
84
82
91:09
91:09
91:09
90
90
90
(ꢀ)
(ꢀ)
(ꢀ)
47
31
ꢀ23
n.d.[g]
86
90
92
<5[f]
91
Et
Et
87
88
9[h]
10[i]
11
12
90
98
99
87
14[g,h]
15[h]
92:08
96:04
90
88
(ꢀ)
(ꢀ)
tBu 98
82
89
16
Et
Et
90
81
91:09
93:07
94
95
(ꢀ)[f]
17[g,h]
(ꢀ)[f]
[a] Performed at RT for 24 h using 1 mol% [Co(Por)] under N2 with
1.0 equiv of styrene (0.25m) and 1.2 equiv of ENDA. [b] See Figure 1 for
structures. [c] Isolated yields. [d] Determined by NMR. [e] ee of Z isomer
determined by HPLC using a chiral stationary phase. [f] Estimated by
NMR. [g] Not determined. [h] 08C; 2 mol% [Co(Por)]. [i] ꢀ208C; 5 mol%
[Co(Por)].
18[h,l]
Et
Et
51
90:10
94:06
82
83
(ꢀ)
(ꢀ)
19
70[k]
tion). While the ineffectiveness of [Co(tpp)] (tpp = tetraphe-
nylporphyrin) for the reaction might be expected (Table 1,
entry 1), it was a disappointing revelation that [Co(P6)],
which was previously shown to be the best catalyst for
asymmetric cyclopropanation with diazosulfones,[6e] gave an
even poorer result (Table 1, entry 7). However, in contrast to
previous systems,[10–14] it was noted that the Z-cyclopropane
was the major product. Subsequent experiments with other
D2-symmetric chiral porphyrins with varied environments
revealed a dramatic ligand effect (Table 1, entries 2–7).
Among them, [Co(P1)] proved to be the optimal catalyst,
producing the Z-dominant cyclopropane a-nitroester (Z/E =
91:09) in 99% yield and 81% ee (Table 1, entry 2). The
[Co(P1)]-based catalytic system was further improved by
optimizing other reaction conditions (Table 1, entries 8–12
and Table S1 in the Supporting Information).
20[h,m]
21[h,m]
tBu 45
tBu 43
92:08 ꢁ80[n]
92:08 ꢁ86[n]
(ꢀ)
(+)
22[h,j]
23[h,j]
Et
Et
42
62
53:47
56:44
88
88
(ꢀ)
(ꢀ)
24[h,j]
Et
92
63:37
75
(ꢀ)
[a] Performed in n-hexane at RT for 24 h under N2 using [Co(P1)] 1 mol%
with 1.0 equiv of alkene 0.25m and 1.2 equiv of NDA. [b] Isolated yields.
[c] Determined by NMR. [d] ee of Z isomer determined by HPLC using a
chiral stationary phase. [e] Sign of optical rotation. [f] [1S,2S] absolute
configuration determined by X-ray crystal structural analysis and optical
rotation. [g] 08C!RT. [h] 5 mol%. [j] In C2H4Cl2. [k] Determined by NMR.
[l] Alkene/NDA=5:1; 48 h. [m] No solvent; 48 h. [n] ee of Z isomer
determined by chiral HPLC after derivatization.
The effectiveness of [Co(P1)] could perhaps be rational-
ꢀ
ized as a consequence of two potential N H···O hydrogen-
bonding interactions between two of the chiral amide N-H
=
moieties on the P1 ligand with both the N O (-NO2 group)
=
and the C O (-CO2Et group) units of the carbene moiety,
respectively. These interactions occur in a postulated metal-
locarbene intermediate[16] and would promote the carbene
formation from the less reactive diazo reagent and rigidify the
intermediate towards its subsequent reaction with the olefin
substrate, which would lead to an more effective and selective
catalytic process. While similar interactions would also exist
in the [Co(P2)]-catalyzed reaction, the intercomponent
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Communications
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(Table 2 and Table S2 in the Supporting Information).
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[9] As reported in Ref. [11], a-nitrodiazoacetates were synthesized
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Received: August 5, 2008
Published online: September 29, 2008
Keywords: asymmetric catalysis · carbenes · cobalt ·
.
cyclopropanation · nitroesters · porphyrinoids
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Angewandte
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