One-Pot Tandem Michael Addition/Enantioselective Conia-Ene Cyclization Mediated by Chiral Iron(III)/Silver(I) Cooperative Catalysis

Article abstract of DOI:10.1002/anie.202007180

The first one-pot tandem Michael addition/enantioselective Conia-ene cyclization of N-protected prop-2-yn-1-amines with 2-methylene-3-oxoalkanoates promoted by chiral iron(III)/silver(I) cooperative catalysts has been developed. Alkyl 4-methylenepyrrolidine-3-acyl-3-carboxylates, which can be transformed into β-proline derivatives, are obtained in high yield with high enantioselectivity.

Full text of DOI:10.1002/anie.202007180

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
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Accepted Article
Title: One-Pot Michael Addition-Enantioselective Conia-Ene Cyclization
Tandem Reaction Induced through Chiral Iron(III)-Silver(I)
Cooperative Catalysis
Authors: takahiro Horibe, Masato Sakakibara, Rin Hiramatsu, Kazuki
Takeda, and Kazuaki Ishihara
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202007180
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10.1002/anie.202007180
Angewandte Chemie International Edition
COMMUNICATION
One-Pot Michael Addition–Enantioselective Conia-Ene
Cyclization Tandem Reaction Induced through Chiral Iron(III)–
Silver(I) Cooperative Catalysis
Takahiro Horibe, Masato Sakakibara, Rin Hiramatsu, Kazuki Takeda, and Kazuaki Ishihara*
Dedication ((optional))
[*]
Dr. T. Horibe, M. Sakakibara, R. Hiramatsu, K. Takeda, Prof. Dr. K. Ishihara*
Graduate School of Engineering, Nagoya University
B2-3(611), Furo-cho, Chikusa, Nagoya 464-8603 (Japan)
E-mail: ishihara@cc.nagoya-u.ac.jp
Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://
Abstract: The first one-pot Michael addition–enantioselective Conia-
ene cyclization tandem reaction of N-protected prop-2-yn-1-amines
with 2-methylene-3-oxoalkanoates promoted by chiral iron(III)–
silver(I) cooperative catalysts has been developed. Thus, alkyl 4-
Michael reaction. Here we describe the first one-pot Michael
addition–enantioselective Conia-ene cyclization tandem reaction
induced through chiral iron(III)–silver(I) cooperative catalysis.[6]
The effectiveness of chiral iron(III) salt catalysts for activation of
β-ketoesters has already been reported by White et al.[5e] and
methylenepyrrolidine-3-acyl-3-carboxylates,
which
can
be
transformed to β-proline derivatives, are obtained in high yield with
Pappo et al.[7c,d]
Chiral salan,[7a,b] chiral salen,[5e] chiral
high enantioselectivity.
phosphate,[7c,d] and chiral bis(phosphine oxide)[7e] complexes
have been known as representative asymmetric iron(III)
catalysts.
Optically active nitrogen-containing five-membered azacycles
such as pyrrolidines, including α- and β-prolines, are important
core structures in organic chemistry because of their presence in
many natural products and their biological activity. For this
reason, mild and efficient processes for the one-step
construction of functionalized pyrrolidines are highly desirable.
In 1997, Dulcère reported the first tandem Michael addition–
Conia-ene cyclization[1] reaction of prop-2-yn-1-amines 2 with
nitroalkenes 1 to give 3-methylene-pyrrolidines 4.[2a] After this
report, Balme,[2b–e] Yamazaki,[2f] and Kerr[2g] independently
developed one-pot methods for the synthesis of various
pyrrolidines (Scheme 1a).[3,4] However, there have been no
examples of catalytic enantioselective tandem Michael addition–
Conia-ene cyclization reactions of propargylamines with Michael
acceptors. In contrast, a catalytic enantioselective Conia-ene
reaction of alkynyl β-ketoesters 5 to give cyclopentanes 6 has
been developed by Toste,[5a] Dixon,[5b] Shibasaki–Kumagai,[5c]
Shibata,[5d] White,[5e] Enders,[5f] and Wasa[5g] based on the
strategy of catalytic dual activation of the ketone moiety and the
alkyne moiety in 5 (Scheme 1b).
Initially, we explored the Conia-ene reaction of Michael adduct
3aa which was prepared from ethyl 2-benzoylacrylate 1a and 4-
methoxy-N-(prop-2-yn-1-yl)benzenesulfonamide 2a in the
presence of 10 mol% of iron(III) triflate at 0 °C in 94% yield
(a) This work: Catalytic 1,4-addition–enantioselective Conia–ene
tandem reactions
Ew1 Ew2
catalysts
Ew1 Ew2
+
PG
N
1,4-addition
N
H
PG
1
2
3
Ew = electron-withdrawing group
PG = protective group
Ew1 Ew2
*
CO2H
*
Conia–ene
N
HN
PG
4
β-proline derivatives
(b) Catalytic Conia-ene reaction
O
O
O
catalysts
CO2R2
R1
OR2
R1
*
We were interested in the catalytic Michael addition of N-
5
6
protected prop-2-yn-1-amines
2
to alkyl 2-methylene-3-
Hard and soft Lewis acid catalysts (Mh/Ms)
Single catalyst (M)
oxoalkanoates 1 (Ew1 = COR1, Ew2 = CO2R2) and subsequent
enantioselective Conia-ene reaction to produce alkyl 4-
methylenepyrrolidine-3-acyl-3-carboxylates 4 (Ew1 = COR1, Ew2
= CO2R2) which can be transformed to β-proline derivatives
(Scheme 1a). Michael adducts 3 are isolable but unstable due
Mh
Base
L*
L*
M
L*
Mh
NH
O
O
H
R1
OR2
R1
O
O
O
O
OR2
R1
OR2
R1
to the retro-Michael reaction.
reaction gives certain amount of 1, which polymerize under
acidic condition. Therefore, Conia-ene reaction of intermediate
3 should be fast for quick consumption of 1.
synthesis of 4 has been accomplished by a catalytic one-pot
process.[1]
Nevertheless, there have been no asymmetric
catalysis because Conia-ene reaction is slower than retro-
Besides, the retro-Michael
Dixon 2009[5b]
White 2014[5e]
Ms
Enders 2017[5f] Wasa 2019[5g]
Ms
Ms
Toste 2005[5a]
Thus far, the
Shibasaki–Kumagai 2011[5c]
Shibata 2012[5d]
Mh: hard Lewis acid
Ms: soft Lewis acid
Scheme 1. Conia-ene reaction.
1
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10.1002/anie.202007180
Angewandte Chemie International Edition
COMMUNICATION
towards the development of
a
one-pot Michael addition–
situ-generated
Fe(OTf)3,
the
chemical
yield
and
enantioselective Conia-ene cyclization tandem reaction as
shown in Table 1. We chose iron(III) triflate as a hard Lewis
acid to activate the ketone of 3aa and silver(I) triflate as a soft
Lewis acid to activate the alkyne of 3aa. After screening of
various chiral bis(phosphine oxide) ligands for iron(III) triflate,[7e]
chiral 1,1’-binaphthol-derived (9,9-dimethyl-9H-xanthene-4,5-
diyl)bis(phosphonate)s L were selected as chiral ligands of
iron(III) triflate. This Conia-ene reaction proceeded well in the
presence of 10 mol% of iron(III) chloride•L1 complex and 40
mol% of silver(I) triflate, and desired product 4aa was obtained
in 94% yield with 75% ee (entry 1). Precipitated silver(I) chloride
was removed before the addition of 3aa. We expected that 10
mol% of iron(III) triflate•L1 complex and 10 mol% of silver(I)
enantioselectivity of 4aa were increased to >98% and 84% ee,
respectively (entry 2). In situ-generated of palladium(II) triflate
was also effective as a soft Lewis acid (entry 3). To enhance
the enantioselectivity, the steric effect of the 6,6’-substituents of
L were examined under the same conditions as in entry 2
(entries 4–6).
When bulkier ligand L4 was used, the
enantioselectivity was increased up to 92% ee (entries 6 and 7).
Moreover, freshly in situ-generated of iron(III) triflate was better
than the use of commercially available one (entry 7 versus entry
8). It is noteworthy that when either in situ-generated or
commercially available iron(III) triflate or silver(I) triflate was
used with L4, the Conia-ene reaction was much slow and
seriously competed with the retro-Michael addition (entry 9, 10
triflate might be generated in situ under the conditions for entry 1. or 11). It was also confirmed that AgCl and TfOH were inactive
Surprisingly, when 5 mol% of L1 was used for 10 mol% of the in
as catalysts for the present reaction (entries 12 and 13). These
results suggest that the Conia-ene reaction proceeded by chiral
iron(III)–silver(I) cooperative catalysis (entries 6~13).[8]
Table 1: Optimization of ligand and conditions[a]
L, FeCl3,
Table 2: Substrate Scope[a]
O
O
O
O
O
Fe(OTf)3
(10 mol%)
AgOTf
MXn
CO2Et
Ph
OEt
Ph
OEt
Ph
+
L4 (5 mol%)
HN
MBS
2a
CH2Cl2
rt, time
CH2Cl2
0 °C, 1 h
in situ-generated Fe(OTf)3
N
N
O
(10 mol%)
AgOTf (10 mol%)
O
O
MBS
CO2R2
MBS
1a
3aa
4aa
R1
+
94% yield
R1
OR2
CH2Cl2
rt, 3~24 h
NHSO2R
O
N
RO2S
1a ~ 1q
2a ~ 2e
4aa ~ 4ae
4ba ~ 4qa
S
OMe
O
O
O
P
O
P
O
O
MBS
O
N
O
O
4aa (R = 4-MeOC6H4)
4ab (R = 4-t−BuC6H4)
4ac (R = 4-MeC6H4)
4ad (R = Me)
3 h, 98% yield, 91% ee
4 h, 97% yield, 86% ee
4.5 h, 98% yield, 91% ee
4.5 h, 98% yield, 88% ee
4.5 h, 98% yield, 87% ee
R
R
CO2Et
L1 (R = H)
L2 (R = i-Pr)
L3 (R = CHPh2)
L4 (R = CH(C6H4-Me-p)2)
4ae (R = 4-NO2C6H4)
RSO2
O
O
O
R
R
4aa
Yield
[%]
CO2Me
CO2i-Pr
CO2Et
En
-try
FeCl3
[mol%]
AgOTf
[mol%]
MXn
[mol%]
L
Time
[h]
4aa
Ee
[%]
[mol%]
N
N
N
MBS
MBS
MBS
4ba
4ca
4da
24 h,b 94% yield, 94% ee 3.5 h, 98% yield, 91% ee
6 h, 80% yield, 81% ee
1
2
10
10
10
10
10
10
10
0
40
40
50
40
40
40
40
10
30
0
–
–
L1, 10
L1, 5
L1, 5
L2, 5
L3, 5
L4, 5
L4, 5
L4, 5
L4, 5
L4, 5
L4, 5
L4, 5
L4, 5
4
3
3
3
6
2
1
1
3
3
3
3
3
94
>98
>98
>98
>98
>98
88
75
84
82
85
90
92
92
85
77
–
O
4ea (R = MeO)
4fa (R = t-Bu)
4ga (R = F)
4ha (R = Cl)
4ia (R = Br)
3.5 h, 98% yield, 86% ee
24 h,[b] 76% yield, 86% ee
3 h, 95% yield, 92% ee
3 h, 84% yield, 90% ee
3.5 h,79% yield, 89% ee
CO2Et
R
N
3
PdCl2, 10
MBS
O
O
4
–
CO2Et
CO2Et
5
–
N
N
MBS
MBS
4ja
4ka
6
–
24 h,[b] 94% yield, 73% ee
24 h,[b] <5% yield, –
O
O
O
7
–
Fe(OTf)3,[b] 10
–
CO2Et
CO2Et
CO2Et
8
60
S
S
N
MBS
N
N
MBS
MBS
4la
4ma
4na
9
10
0
7
5 h, 95% yield, 93% ee
3 h, 90% yield, 93% ee 24 h,[b] 60% yield, 80% ee
Fe(OTf)3,[b] 10
–
0[c]
53
O
O
O
10
11
12
13
CO2Et
CO2Et
CO2Et
t-Bu
0
10
0
0
N
N
N
MBS
MBS
MBS
0
AgCl, 10
TfOH, 10
0
–
4oa
4pa
4qa
3 h, 95% yield, 81% ee
4 h, 44% yield, 44% ee 24 h,[b] 38% yield, 60% ee
0
0
0
–
[a] Fe(OTf)3 was prepared from FeCl3 (10 mol%) and AgOTf (30 mol%) in situ
and precipitated AgCl was removed by filtration. The absolute configuration of
products 4 shown in Table 2 was assigned by analogy with product 4aa. [b]
The reaction was performed at 0 °C.
[a] Fe(OTf)3 was prepared from FeCl3 (10 mol%) and AgOTf (30 mol%) in situ
and precipitated AgCl was removed by filtration. [b] Commercially available
Fe(OTf)3 (Aldrich, Alfa Aesar) was used in place of FeCl3. [c] The conversion
of 3aa was 30~40%. Retro-Michael adducts 1a and 2a were reproduced in
5~15% and 10~20% yields, respectively.
2
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10.1002/anie.202007180
Angewandte Chemie International Edition
COMMUNICATION
Next, one-pot Michael addition–enantioselective Conia-ene
cyclization tandem reaction of 1a with 2a was examined under
the optimal conditions (entry 6 in Table 1). As expected, 4aa
was obtained in 98% yield with 91% ee (Table 2). The substrate
Fe(OTf)3•••[OTf]–.[10] When excess amounts of ethyl 3-oxo-3-
phenylpropanoate were added to the above solution, a different
M+ peak (Found: 1266.1639), which corresponded to a 1:1:1
complex 10+ of [Fe(OTf)]2+, L1 and the enolate anion, was
detected by ESI-MS analysis (Scheme 3b). Furthermore, a
linear correlation was observed between the ee values of L1 and
4aa (Scheme 3c).[11] These control experiments suggest that
[Fe(OTf)2•L1]+[OTf]– or [Fe(OTf)2•L1]+[Fe(OTf)4]– and AgOTf
should work as cooperative catalysts for the Conia-ene
cyclization of 3
Although we attempted to crystallize several complexes of
Fe(OTf)3 and chiral ligands L to obtain information on the 3D-
structure of [Fe(OTf)2•L]+, crystals were not formed.
Nevertheless, the crystal structure of a complex of L5 and FeCl3
was unambiguously characterized using X-ray crystallography
(Scheme 4).[12] As expected, this was a cationic iron(III)
complex analogous to 9+. Interestingly, one of two L5 ligands
was coordinated to equatorial–equatorial sites of hexagonal
Fe(III), and the other was coordinated to equatorial–axial
sites.[13]
scope is shown in Table 2.
High reactivity and high
enantioselectivity were observed regardless of the aryl moiety of
N-(prop-2-yn-1-yl)arenesulfonamide 2 (see products 4aa ~ 4ae)
and alkoxy moieties of alkyl 2-methylene-3-oxoalkanoates 1
(see products 4ba and 4ca). Ethyl 2-(2-naphthoyl)acrylate 1d
and ethyl 2-benzoylacrylates 1e ~ 1h substituted with electron-
withdrawing or -donating groups at the para-position were also
applicable as substrates (see products 4ea ~ 4ia). In contrast,
ethyl 2-benzoylacrylates 1j and 1k substituted with a methyl
group at the meta- or ortho-position were not so applicable as
substrates (see products 4ja and 4ka). More interestingly, ethyl
2-(thiophene-2 or 3-carbonyl)- acrylates 1l and 1m and ethyl 2-
(cyclopent- or cyclohex-1-ene-1-carbonyl)acrylates 1n and 1o
were also applicable as substrates (see products 4la ~ 4oa).
However, ethyl 2-(alkanecarbonyl)acrylates such as 1pa and
1qa were not applicable (see products 4pa ~ 4qa).
To demonstrate the synthetic utility of the products, 4aa was
transformed to bicyclic ester 7aa in good yield through (1)
diastereospecific hydroboration to 5aa, (2) diastereospecific
dehydrative cycloetherification and subsequent deprotection of
an N-p-methoxybenzenesulfonyl group to 6aa, and (3) N-tert-
butoxycarbonylation to 7aa (Scheme 2). Moreover, the absolute
(a) 1H NMR analysis
O
O
O
O
N
AgX (1 equiv)
Ph
OEt
Ph
OEt
AgX
CD2Cl2
rt, 15 min
N
MBS
3aa
H
δ 2.07
MBS
H
and relative configurations of products 4aa
~ 7aa were
δ 2.81 (AgNTf2)
δ 2.13 (AgOTf)
determined based on X-ray diffraction analysis of ammonium
salt 8aa, which was generated from 6aa and L-tartaric acid
(Scheme 2).
O
O
(b) ESI-MS analysis
Fe(OTf)3
(2 equiv)
Ph
OEt
P
P
Ph
(20 equiv)
OEt
O
O
O
O
+
+
FeOTf
P
P
Fe(OTf)2
O
CH2Cl2
OH
O
O
O
P
O
P
1. BH3•THF (2 equiv)
0 °C, 3 h
O
P
O
L1
CO2Et
CO2Et
OH
P
Ph
Ph
2. aq. NaOH (5 equiv)
H2O2 (5 equiv)
CH2Cl2
9+
ESI-MS: found 2095.2539
10+
ESI-MS: found 1266.1639
N
N
MBS
MBS
4aa
5aa
0 °C, 0.5 h
64% yield, >99% de
(c) Correlation between the ee values of product 4aa and ligand L1
100
100
Ph
EtO2C
Ph
Boc2O (3 equiv)
aq. NaOH (30 equiv)
O
L1 (5 mol%)
Fe(OTf)3 (10 mol%)
AgOTf (10 mol%)
O
MeSO3H (10 equiv)
80
80
EtO2C
THF
rt, 2.5 h
CF3CO2H/MeSPh (9:1)
rt, 3 h
H
H
3aa
4aa
N
60
60
HN
6aa
CH2Cl2, rt, 4 h
Boc
7aa
62% yield from 5aa
OH
40
40
CO2H
HO2C
20
20
OH
Ph
O
EtO2C
H2+N
0
0
0
20
40
60
80
100
OH
0
20
40
60
80
100
% ee of L1
Ee (%) of L1
H
–O2C
CO2H
OH
8aa
Scheme 3. Control experiments.
Scheme 2. Determination of the absolute configuration of 4aa.
+
Ph
P
Ph
Cl
To understand the reaction mechanism, several control
Cl
O
O
FeCl3
(1 equiv)
Ph
P
Fe
O
Ph
experiments were performed (Scheme 3).
The selective
O
[FeCl4]–
[CHCl3]
activation of an alkynyl group of Michael adduct 8aa with silver(I)
salt was confirmed by 1H NMR analysis (Scheme 3a).[9]
Interestingly, the M+ peak (Found: 2095.2539), which
corresponded to a 1:2 complex 9+ of [Fe(OTf)2]+ and L1, was
detected from a 2:1 molar solution of iron(III) triflate and L1 by
ESI-MS analysis in the positive-ion mode. The triflate anion
released from iron(III) triflate might be stabilized as [Fe(OTf)4]– or
O
P
O
P
Ph
Ph Ph
Ph
CH2Cl2–
CHCl3–
toluene
O
Ph
Ph
P
P Ph
Ph
O
O
L5
Scheme 4. Synthesis of [FeCl2•L52]+[FeCl4]–[CHCl3].
3
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10.1002/anie.202007180
Angewandte Chemie International Edition
COMMUNICATION
Based on this experimental evidence, the following catalytic
cycle can be proposed (Scheme 5). Michael addition of 2 to in
situ- generated cationic 1:1:1 complex A of Fe(III), L5, and 1
in the narrow cavity.
In conclusion, we have succeeded in the first one-pot Michael
addition–enantioselective Conia-ene cyclization tandem reaction
promoted by chiral iron(III)–silver(I) cooperative catalysts. The
Conia-ene cyclization could predominantly accelerate through
this dual activation. On the other hand, retro-Michael reaction
was much slower in the presence of iron(III) catalyst due to the
mild Lewis acidity. Further study is planned to design
cooperative catalysts to broaden the substrate scope, and to
gain deeper insights into the mechanism.
gives active intermediate
B in the presence of AgOTf.
Subsequently, enantioselective Conia-ene cyclization occurs
through B and C to give intermediate D. Finally, product 4 and
A are produced through ligand exchange between D and 1.
To understand the absolute stereochemical outcome, the
favored transition state TS1 is proposed based on an (R)-
configuration of product 4aa and the X-ray crystal structure[11] of
[FeCl2•L52]+[FeCl4]–[CHCl3] (Figure 1). Ligand L4 should be
predominantly coordinated to Fe(III) at equatorial–equatorial
sites. Next, Michael adduct 3aa would be coordinated to Fe(III)
at equatorial–axial sites. TS 1 in the wide cavity would be
sterically favored among four possible transition states.[14] The
favored pathway via TS1 leads to (R)-4aa, as observed
experimentally. Furthermore, other possible transition states in
the narrow cavity might be suppressed due to the steric
hindrance between the 6-substituent (R) of L and N-SO2Ar of 3
Acknowledgements
This research was supported in part by JSPS KAKENHI (Grant
Numbers 15H05755, 15H06266, 17K14484, and 15H05810), the
Toyoaki Scholarship Foundation, the Society of Iodine Science
and MEXT, Japan.
*
Conflict of Interest
+
P
P
Fe(OTf)3
O
O
O
O
O
L4
The authors declare no conflict of interest.
O
O
R1
OR2
R1
OR2
1
Keywords: Michael addition • Conia-ene cyclization • tandem
HN
S
R3
N
*
O
reaction • enantioselective • cooperative catalysis
S
R3
P
P
4
+
AgOTf
O
O
O
O
O
O
2
––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––
R1
OR2
+
Fe(OTf)2
O
[1]
[2]
a) J. M. Conia, P. Le Perchec, Synthesis 1975, 1-19; b) D. Hack, M.
Blümel, P. Chauhan, A. R. Philipps, D. Enders, Chem. Soc. Rev. 2015,
44, 6059-6093.
X–
O
1
*
*
R1
OR2
P
P
P
P
A
Conia-ene type reaction of nitrogen-tethered acetylenic 1,3-
O
O
O
O
A
*
dicarbonyl and related substrates: a) E. Dumez, J. Rodriguez, J.-P.
Dulcère, Chem. Commun. 1997, 1831–1832; b) B. Clique, N. Monteiro,
G. Balme, Tetrahedron Lett. 1999, 40, 1301–1304; c) N. Monteiro, G.
Balme, J. Org. Chem. 2000, 65, 3223–3226; d) S. Azoulay, N. Monteiro,
G. Balme, Tetrahedron Lett. 2002, 43, 9311–9314; e) L. Martinon, S.
Azoulay, N. Monteiro, E. P. Kündig, G. Balme, J. Organomet. Chem.
2004, 689, 3831–3836; f) S. Morikawa, S. Yamazaki, Y. Furusaki, N.
Amano, K. Zenke, K. Kakiuchi, J. Org. Chem. 2006, 71, 3540–3544; g)
T. P. Lebold, A. B. Leduc, M. A. Kerr, Org. Lett. 2009, 11, 3770–3772.
A Conia-ene type reaction of oxygen-tethered acetylenic 1,3-dicarbonyl
substrates: a) X. Marat, N. Monteiro, G. Balme, Synlett 1997, 845–847;
b) M. Cavicchioli, X. Marat, N. Monteiro, B. Hartmann, G. Balme,
Tetrahedron Lett. 2002, 43, 2609–2611; c) M. Nakamura, C. Liang, E.
Nakamura, Org. Lett. 2004, 6, 2015–2017; d) A. B. Leduc, T. P. Lebold,
M. A. Kerr, J. Org. Chem. 2009, 74, 8414–8416.
Fe(OTf)2
O
Fe(OTf)2
X–
HX
O
O
O
R1
OR2
P
P
R1
OR2
O
O
N
S
N
S
R3
Fe(OTf)2
O
R3
O
Ag–OTf
O
O
O
O
B
D
AgOTf
R1
OR2
Ag
OTf–
X–
=
[OTf]– or
[3]
N
S
R3
[Fe(OTf)4]–
O
O
C
Scheme 5. Proposed catalytic cycle.
[4]
[5]
K. Takahashi, M. Midori, K. Kawano, J. Ishihara, S. Hatakeyama,
Angew. Chem. Int. Ed. 2008, 47, 6244–6246.
a) B. K. Corkey, F. D. Toste, J. Am. Chem. Soc. 2005, 127, 17168–
17169; b) T. Yang, A. Ferrali, F. Sladojevich, L. Campbell, D. J. Dixon,
J. Am. Chem. Soc. 2009, 131, 9140–9141; c) A. Matsuzawa, T.
Mashiko, N. Kumagai, M. Shibasaki, Angew. Chem. Int. Ed. 2011, 50,
7616–7619; d) S. Suzuki, E. Tokunaga, D. S. Reddy, T. Matsumoto, M.
Shiro, N. Shibata, Angew. Chem. Int. Ed. 2012, 51, 4131–4135; e) S.
Shaw, J. D. White, J. Am. Chem. Soc. 2014, 136, 13578–13581; f) M.
Blümel, D. Hack, L. Ronkartz, C. Vermeeren, D. Enders, Chem.
Commun. 2017, 53, 3956–3959; g) M. Cao, A. Yesilcimen, M. Wasa, J.
Am. Chem. Soc. 2019, 141, 4199–4203.
R
R
O
O
OTf
Fe
O
OO
O
O
O
O
O
Ph
OEt
TfO
R
R
wide cavity
O
narrow cavity
N
O
S
[6]
For selected reviews on enantioselective cooperative catalysis, see: a)
H. Yamamoto, K. Futatsugi, Angew. Chem., Int. Ed. 2005, 44,
1924−1942; b) D. H. Paull, C. J. Abraham, M. T. Scerba, E. Alden-
Danforth, T. Lectka, Acc. Chem. Res. 2008, 41, 655−633; c) M.
Shibasaki, N. Kumagai, In Cooperative Catalysis: Designing Efficient
AgOTf
(R)-4aa
TS1 (favored)
Ar
Figure 1. Plausible transition state TS1 for the Conia-ene reaction of 3aa.
4
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10.1002/anie.202007180
Angewandte Chemie International Edition
COMMUNICATION
Catalysts for Synthesis, Peters, R., Ed.; Wiley-VCH: New York, 2015;
Chapter 1.
[7]
a) H. Egami, T. Katsuki J. Am. Chem. Soc. 2009, 131,6082–6083; b) H.
Egami, K. Matsumoto, T. Ogura, T. Kunisu, T. Katsuki J. Am. Chem.
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Pappo J. Am. Chem. Soc. 2016, 138, 16553–16560; d) S. Narute, D.
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16680.
[8]
[9]
For additional supporting information, see Section 9 in SI.
G. Fanga, X. Bi, Chem. Soc. Rev. 2015, 44, 8124–8173.
[10] For [Fe(OTf)4]–, see: Farooq, O. Novel Initiators for Cationic
Plomerization. Patent No. EP 0442635B1.
[11] H. B. Kagan, Synlett 2001, 888–899.
[12] For X-ray crystal structure of [FeCl2•L52]+[FeCl4]–[CHCl3], see Section
14 in SI.
[13] E. J. Corey, N. Imai, H. Y. Zhang, J. Am. Chem. Soc. 1991, 113, 728–
729.
[14] For details, see Section 15 in SI.
5
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10.1002/anie.202007180
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
O
O
O
+
R1
OR2
NHPG
O
Fe+(OTf)2L*
O
P
O
P
O
O
R1
CH2Cl2
rt, 3~24 h
O
O
O
R
R
O
O
R2O2C
CO2R2
Fe+ X–
TfO OTf
(5 mol%)
+
AgOTf (10 mol%)
R1
R1
OR2
H
Ag+
N
N
N
Boc
PG
up to 94% ee
R
R
PG
Table of Contents
Cooperative catalysis of Fe(III) and Ag(I): The first one-pot Michael addition–enantioselective Conia-ene cyclization tandem
reaction has been developed by using chiral iron(III)–silver(I) cooperative catalysts. Thus, alkyl 4-methylenepyrrolidine-3-acyl-3-
carboxylates, which can be transformed to β-proline derivatives,are obtained in high yield with high enantioselectivity.
Institute and/or researcher Twitter usernames: @PIodide
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