Next Article in Journal
Antiproliferative Effect and Ultrastructural Alterations Induced by Psilostachyin on Trypanosoma cruzi
Next Article in Special Issue
Catalytic Asymmetric Nitro-Mannich Reactions with a Yb/K Heterobimetallic Catalyst
Previous Article in Journal
Synthesis of Some New Mono- and Bis-Polycyclic Aromatic Spiro and Bis-Nonspiro-β-Lactams
 
 
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Catalytic Asymmetric 1,4-Additions of β-Keto Esters to Nitroalkenes Promoted by a Bifunctional Homobimetallic Co2-Schiff Base Complex

Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
*
Authors to whom correspondence should be addressed.
Molecules 2010, 15(1), 532-544; https://doi.org/10.3390/molecules15010532
Received: 24 December 2009 / Revised: 18 January 2010 / Accepted: 21 January 2010 / Published: 22 January 2010
(This article belongs to the Special Issue Bifunctional Catalysis)

Abstract

:
Catalytic asymmetric 1,4-addition of β-keto esters to nitroalkenes is described. 2.5 mol % of a homobimetallic Lewis acid/Brønsted base bifunctional Co2-Schiff base complex smoothly promoted the reaction in excellent yield (up to 99%), diastereoselectivity, and enantioselectivity (up to >30:1 dr and 98% ee). Catalyst loading was successfully reduced to 0.1 mol %. Mechanistic studies suggested that intramolecular cooperative functions of the two Co-metal centers are important for high catalytic activity and stereoselectivity.

1. Introduction

Bifunctional concerto asymmetric catalysis is currently a hot research topic in organic synthesis. Various chiral bifunctional metal- and organo-catalysts have been reported over the last decade [1,2,3,4,5]. Bifunctional asymmetric catalysts are useful for realizing high stereoselectivity and catalytic activity via dual activation of both nucleophiles and electrophiles. As part of our ongoing research on this issue, we recently reported the utility of bimetallic Schiff base 1 complexes (Figure 1), whose catalytic properties differ from those of well-established monometallic salen 2 complexes [6,7,8]. By utilizing dinucleating Schiff bases, we developed heterobimetallic Cu/Sm [9], Pd/La [10,11], and Ga/Yb [12] Schiff base complexes, including rare earth metals and homobimetallic Ni2 [13,14,15,16,17,18], Co2 [19], and Mn2 [20] Schiff base 1 complexes and applied them to various enantioselective reactions (for selected examples of related bifunctional bimetallic Schiff base catalysts, see ref [21,22,23,24,25,26,27]). In this manuscript, we report the details of our efforts to expand the utility of bimetallic Schiff base catalysis for catalytic asymmetric 1,4-addition of β-keto esters to nitroalkenes [28,29,30,31,32,33,34,35,36,37,38,39,40,41,42].
Figure 1. Structures of dinucleating Schiff base 1-H4, bimetallic M1/M2 Schiff base complex and monometallic Co-salen 2a2c complexes .
Figure 1. Structures of dinucleating Schiff base 1-H4, bimetallic M1/M2 Schiff base complex and monometallic Co-salen 2a2c complexes .
Molecules 15 00532 g001

2. Results and Discussion

2.1. Homobimetallic Co2-Schiff Base Complex-catalyzed Asymmetric 1,4-Addition to Nitroalkenes

To find a suitable metal combination for the 1,4-addition reaction of β-keto esters to nitroalkenes, we selected nitroalkene 3a and β-keto ester 4a as model substrates for the construction of adjacent quaternary/tertiary carbon stereocenters [34,35,36,37,38,39,40,41,42]. The catalyst screening results are summarized in Table 1. Heterobimetallic Schiff base Cu/Sm and Pd-La complexes smoothly promoted the reaction, but neither diastereoselectivity nor enantioselectivity were satisfactory (entries 1–2). A homobimetallic Ni2-Schiff base 1 complex (Figure 1) [13], which was suitable for 1,2-addition of β-keto esters to imines, gave moderate enantioselectivity (entry 3, 74% ee). Among other metals screened (entries 4–7), a Co2(OAc)2-1 complex[19] gave product 5aa in 95% ee (entry 4). Other homobimetallic Mn2-1 [20], Cu2-1, and Zn2-1 catalysts resulted in poor enantioselectivity (entry 5: 32% ee, entry 6: 12% ee, entry 7: 8% ee). Because the bimetallic Co2(OAc)2-1 catalyst was stable against air and moisture, the reaction was successfully performed using undistilled THF (containing stabilizer and 220 ppm H2O) as a solvent under air atmosphere, and high enantioselectivity was achieved at room temperature with 2.5 mol % catalyst (entry 8). Notably, high yield and enantioselectivity were achieved even without solvent (entry 9, >99% conversion, 97% ee) under an air atmosphere.
Table 1. Screening of bimetallic M1/M2/Schiff base complexes for 1,4-addition of β-keto ester 4a to nitroalkene 3a.
Table 1. Screening of bimetallic M1/M2/Schiff base complexes for 1,4-addition of β-keto ester 4a to nitroalkene 3a.
Molecules 15 00532 i001
EntryM 1M 2cat. (mol %)time (h)solvent (M)Dr b% yield b% ee
1CuSm-OiPr1036THF (0.4)3:1>9923
2PdLa-OiPr1036THF (0.4)4:1>9914 c
3NiNi1036THF (0.4)6:17174
4Co-OAcCo-OAc106THF (0.4)26:18695
5Mn-OAcMn-OAc1036THF (0.4)3:16132
6CuCu1036THF (0.4)9:1612 c
7ZnZn1036THF (0.4)2:1908
8 dCo-OAcCo-OAc2.59THF (2.0)18:19493
9 eCo-OAcCo-OAc2.58neat25:1>9997
a 1.5 equiv of 4a was used in entries 1–7, and 1.1 equiv of 4a in entries 8–9; b Yield and dr were determined by 1H-NMR analysis of crude mixtures; c ent-4aa was obtained in major; d Undistilled THF with stabilizer containing 220 ppm H2O was used; e Reaction was run under an open-air atmosphere.
The substrate scope is summarized in Table 2. Because the Co2(OAc)2-1 catalyst is bench-stable and storable, the catalyst stored under air at room temperature for more than three months was used in Table 2 without loss of selectivity or reactivity. Furthermore, the reactions were performed under neat conditions at room temperature (24–28 °C) under an open-air atmosphere. In entries 1–9, the nitroalkene scope was investigated using β-keto ester 4a. Nitroalkenes 3b3d with an electron-withdrawing substituent on the aromatic ring at the para- or meta-position reacted smoothly, giving products in 88%–94% yield, 30:1–>30:1 dr, and 97%–98% ee after 4–5 h (entries 2–4). The use of ortho-substituted nitroalkene 3e slightly decreased the reactivity (77% yield, 14 h), but high diastereo- and enantioselectivity were maintained (entry 5, 27:1 dr, 94% ee). Nitroalkenes 3f3g with an electron-donating substituent on the aromatic ring as well as β-heteroaryl nitroalkene 3h gave products in high yield and stereoselectivity (entries 6–8). The Co2(OAc)2-1 catalyst also promoted the reaction of less reactive β-alkyl-nitroalkene 3i, giving the product 5ia in 96% yield, >30:1 dr, and 95% ee (entry 9). High diastereo- and enantioselectivity were also achieved with the six-membered ring β-keto ester 4b (entry 10, >30:1 dr and 98% ee). The reaction rate, however, was decreased with β-keto ester 4b, and the product 5bb was obtained in 75% yield after 24 h. Acyclic β-keto ester 4c also gave product 5ac in high enantioselectivity (96% ee), but the reactivity and diastereoselectivity were decreased even with 10 mol % catalyst loading (entry 11, 73% yield, 3.3:1 dr). Trials to reduce catalyst loading are summarized in entries 12–13. Co2(OAc)2-1 catalyst (0.2–0.1 mol %) promoted the reaction of nitroalekene 3b with 4a under highly concentrated conditions (THF, 20 M), while maintaining high enantioselectivity. In entry 12, pure 5ba was isolated in 87% yield and 99% ee by recrystallization without column chromatography purification.
Table 2. Catalytic asymmetric 1,4-addition of β-keto esters to nitroalkenes using Co2(OAc)2-Schiff base 1 complex.a
Table 2. Catalytic asymmetric 1,4-addition of β-keto esters to nitroalkenes using Co2(OAc)2-Schiff base 1 complex.a
Molecules 15 00532 i002
EntryR 134cat. (x mol %)time (h)solvent (y M)5Dr b% yieldc% ee
1Ph3a4a2.58neat5aa25:1>9997
24-Cl-C6H43b4a2.54neat5ba>30:19498
34-Br-C6H43c4a2.55neat5ca>30:19598
43-Br-C6H43d4a2.54neat5da30:18897
52-Br-C6H43e4a2.514neat5ea27:17794
64-MeO-C6H43f4a2.517neat5fa9:19394
74-Me-C6H43g4a2.510neat5ga22:19396
82-furyl3h4a2.53neat5ha>30:19392
9PhCH2CH23i4a2.57neat5ia>30:19695
104-Cl-C6H43b4b2.524neat5bb>30:17598
11dPh3a4c1036neat5ac3.3:17396
124-Cl-C6H43b4a0.224THF (20)5ba>30:187e99
134-Cl-C6H43b4a0.148THF (20)5ba16:19895
a Reaction was performed under neat conditions at room temperature (24–28 °C) under air atmosphere with 1.1 equiv of 4 unless otherwise noted; b Dr was determined by 1H-NMR analysis; c Isolated yield after purification by column chromatography (entries 1–11 and 13); d 2.0 equiv of 4 was used; e 5ba was obtained in pure form by recrystallization of the crude product without column chromatography purification.

2.2. Mechanistic Studies of Homobimetallic Co2(OAc)2-Schiff Base Complex

To gain mechanistic insight into the present homobimetallic Co2-catalysis, negative control experiments using three monometallic Co-salen 2a2c complexes with different substituents were investigated (Scheme 1). In all cases, poor yield, and poor diastereoselectivity and enantioselectivity were observed, suggesting that the bimetallic system is important for high catalytic activity as well as stereoselectivity. In addition, initial rate kinetic studies using nitroalkene 3b and β-keto ester 4a showed first-order dependency on the bimetallic Co2(OAc)2-Schiff base 1 complex (Figure 2). There was a linear relationship between the enantiomeric excess of the Co2(OAc)2-1 catalyst and product 5aa (Figure 3). The results shown in Figure 2 and Figure 3 suggested that the active species in the present reaction would be a monomeric Co2(OAc)2-1 catalyst. Thus, the intramolecular concerto functions of the two Co metal centers are likely important in the present system, rather than intermolecular concerto function of the two catalysts, which was reported for mono-metallic Co-salen complexes [8]. The postulated catalytic cycle of the reaction is shown in Scheme 2. We assume that β-keto ester would coordinate to sterically less hindered outer Co-metal center of the Co2(OAc)2-1 catalyst. One of Co-aryloxide (or Co-acetate) would deprotonate α-proton of β-keto esters to generate Co-enolate. Inner Co-metal center would act as a Lewis acid to activate nitroalkenes in a similar manner as observed in the monomeric Co-salen system. 1,4-Addition via bimetallic transition state followed by protonation affords products and regenerates the Co2(OAc)2-1 catalyst.
Scheme 1. Negative control experiments using monomoetallic Co-salen 2a2c complexes.
Scheme 1. Negative control experiments using monomoetallic Co-salen 2a2c complexes.
Molecules 15 00532 g004
Figure 2. Initial rate kinetic studies of bimetallic Co2(OAc)2-1 catalyst.
Figure 2. Initial rate kinetic studies of bimetallic Co2(OAc)2-1 catalyst.
Molecules 15 00532 g002
Figure 3. Linear relationship between% ee of bimetallic Co2(OAc)2-1 catalyst and% ee of product 5aa.
Figure 3. Linear relationship between% ee of bimetallic Co2(OAc)2-1 catalyst and% ee of product 5aa.
Molecules 15 00532 g003
Scheme 2. Postulated catalytic cycle of the reaction.
Scheme 2. Postulated catalytic cycle of the reaction.
Molecules 15 00532 g005

3. Experimental

3.1. General

Infrared (IR) spectra were recorded on a JASCO FT/IR 410 Fourier transform infrared spectrophotometer. NMR spectra were recorded on JEOL JNM-LA500 spectrometer, operating at 500 MHz for 1H-NMR and 125.65 MHz for 13C-NMR. Chemical shifts in CDCl3 were reported in the δ scale relative to CHCl3 (7.24 ppm) for 1H-NMR. For 13C-NMR, chemical shifts were reported on the δ scale relative to CHCl3 (77.0 ppm) as an internal reference. Column chromatography was performed with silica gel Merck 60 (230–400 mesh ASTM). Optical rotations were measured on a JASCO P-1010 polarimeter. ESI mass spectra were measured on Waters micromass ZQ (for LRMS) and JEOL JMS-T100LC AccuTOF spectrometer (for HRMS). FAB mass spectra (for HRMS) were measured on a JEOL JMS-700 spectrometer. The enantiomeric excess (ee) was determined by HPLC analysis. HPLC was performed on JASCO HPLC systems consisting of the following: pump, PU-2080 plus; detector, UV-2075 plus, measured at 254 nm; column, DAICEL CHIRALCEL OD, CHIRALCEL OD-H, or CHIRALPAK AD-H; mobile phase, hexane/2-propanol. Anhydrous Co(OAc)2 was purchased from Aldrich and used as received.

3.2. Preparation of Co(III)2(OAc)2-Schiff Base 1 Complex

To a solution of (R)-Schiff base ligand 1-H4 (1049 mg, 2.0 mmol) in EtOH (20 mL), was added Co(OAc)2 (708 mg, 4.0 mmol), and the mixture was stirred under air atmosphere for 12 h under reflux. After cooling down to room temperature, H2O (10 mL) was added to the mixture and the mixture was stirred for 1 h at room temperature under air atmosphere. The precipitate (Co2(OAc)2-1 complex) was collected by filtration. Then, the solid was washed with H2O (×3), EtOH/hexane = 1:1 (×3), and Et2O. The solid was dried under reduced pressure to afford the Co2(OAc)2-Schiff base 1 complex (1.047 g, 66% yield) as a brown solid. The complex was used for the asymmetric reaction without further purification, and was stored under air at room temperature. Catalytic activity did not change for at least 6 months. Results in Tables 2 and 3 were collected using the Co2(OAc)2-1 complex stored for over 3 months. The structure was assigned to be Co2(OAc)2-1•2H2O based on elemental analysis after recrystallization from THF/AcOEt. Anal. Calcd. for C38H30Co2N2O10 [Co2(OAc)2-1•2H2O]: C, 57.59; H, 3.82; N, 3.53; Found: C, 57.84; H, 3.76; N, 3.58.

3.3. General Procedure for Catalytic Asymmetric 1,4-Additions of β-Keto Esters to Nitroalkenes under Solvent-Free Conditions

To a vial were added Co2/Schiff base 1 catalyst (7.92 mg, 0.01 mmol) and β-keto ester 4a (55.3 µL, 0.44 mmol). After stirring the mixture for 5 min at room temperature, nitroalkene 3b (73.4 mg, 0.4 mmol) was added at room temperature. The reaction mixture was stirred for 4 h at room temperature under air atmosphere, and the crude residue was analyzed by 1H-NMR to determine the diastereomeric ratio. The reaction mixture was purified by silica gel flash column chromatography (hexane/ethyl acetate = 3/1) to afford 5ba (122.8 mg, 94% yield) as a colorless solid.
(1S)-1-[(1R)-2-Nitro-1-phenylethyl]-2-oxo-cyclopentanecarboxylic Acid Methyl Ester (5aa) [34,35,37]. 5aa is a known compound. colorless oil; IR (neat) ν 2956, 1751, 1725, 1552, 1230, 1149 cm−1; 1H NMR (CDCl3) δ 1.76–2.06 (m, 4H), 2.30–2.40 (m, 2H), 3.74 (s, 3H), 4.06 (dd, J = 4.0, 11.0 Hz, 1H), 4.99 (dd, J = 11.0, 13.8 Hz, 1H), 5.14 (dd, J = 4.0, 13.8 Hz, 1H) , 7.20–7.32 (m, 5H); 13C NMR (CDCl3) δ 19.3, 31.0, 37.9, 46.1, 53.0, 62.4, 76.3, 128.3, 128.8, 129.2, 135.2, 169.7, 212.2; ESI-MS m/z 314 [M+Na]+; [α]D21.0 +41.7 (c 0.844, CHCl3); HPLC (DAICEL CHIRALCEL OD, hexane/2-propanol = 90/10, flow 1.0 mL/min, detection at 220 nm) tR 14.8 min (major) and 21.5 min (minor). Relative configuration of 5aa was determined by comparing the 1H-NMR and 13C-NMR data with the reported data. Absolute configuration of 5aa was determined by comparison of the sign of optical rotation with the reported data. Lit. [α]D25 + 36.5 (c, 0.84, CHCl3) [34,35].
(1S)-1-[(1R)-1-(4-Chlorophenyl)-2-nitroethyl]-2-oxo-cyclopentanecarboxylic Acid Methyl Ester (5ba) [37]. Colorless solid; IR (KBr) ν 2960, 1724, 1554, 1218 cm−1; 1H-NMR (CDCl3) δ 1.76–1.95 (m, 3H), 1.97–2.08 (m, 1H), 2.28–2.40 (m, 2H), 3.71 (s, 3H), 4.00 (dd, J = 4.0, 11.0 Hz, 1H), 4.93 (dd, J = 11.0, 13.7 Hz, 1H), 5.11 (dd, J = 4.0, 13.7 Hz, 1H), 7.15–7.20 (m, 2H), 7.22–7.27 (m, 2H); 13C NMR (CDCl3) δ 19.2, 31.2, 37.8, 45.5, 53.0, 62.1, 76.1, 128.9, 130.6, 133.8, 134.2, 169.6, 212.1; ESI-MS m/z 348, 350 [M+Na]+; HRMS calcd. for C15H16ClNO5Cs [M+Cs]+: 457.9771, found 457.9763; [α]D25.6 +42.6 (c 1.05, CHCl3); HPLC (DAICEL CHIRALCEL OD, hexane/2-propanol = 90/10, flow 1.0 mL/min, detection at 220 nm) tR 20.3 min (major) and 34.5 min (minor).
(1S)-1-[(1R)-1-(4-Bromophenyl)-2-nitroethyl]-2-oxo-cyclopentanecarboxylic Acid Methyl Ester (5ca). Colorless solid; IR (KBr) ν 2958, 1756, 1720, 1552, 1232, 1155 cm−1; 1H-NMR (CDCl3) δ 1.77–1.99 (m, 3H), 2.00–2.12 (m, 1H), 2.31–2.42 (m, 2H), 3.73 (s, 3H), 4.00 (dd, J = 4.0, 11.5 Hz, 1H), 4.95 (dd, J = 11.5, 14.4 Hz, 1H), 5.12 (dd, J = 4.0, 13.4 Hz, 1H), 7.12–7.16 (m, 2H), 7.40–7.44 (m, 2H); 13C-NMR (CDCl3) δ 19.2, 31.1, 37.7, 45.5, 52.9, 62.0, 76.0, 122.3, 130.9, 131.8, 134.2, 169.5, 212.0; ESI-MS m/z 392, 394 [M+Na]+; HRMS calcd. for C15H16BrNO5Cs [M+Cs]+: 501.9266, found 501.9274; [α]D25.6 +40.2 (c 1.08, CHCl3); HPLC (DAICEL CHIRALCEL OD, hexane/2-propanol = 90/10, flow 1.0 mL/min, detection at 220 nm) tR 25.0 min (major) and 37.6 min (minor).
(1S)-1-[(1R)-1-(3-Bromophenyl)-2-nitroethyl]-2-oxo-cyclopentanecarboxylic Acid Methyl Ester (5da). Colorless oil; IR (neat) ν 2922, 1751, 1726, 1554, 1230, 1147 cm−1; 1H-NMR (CDCl3) δ 1.82–1.98 (m, 3H), 2.08–2.17 (m, 1H), 2.31–2.44 (m, 2H), 3.74 (s, 3H), 3.94 (dd, J = 4.0, 11.0 Hz, 1H), 4.97 (dd, J = 11.0, 13.7 Hz, 1H), 5.17 (dd, J = 3.7, 13.7 Hz, 1H), 7.15–7.21 (m, 2H), 7.39–7.43 (m, 2H); 13C-NMR (CDCl3) δ 19.2, 31.5, 37.7, 45.7, 53.0, 62.0, 76.0, 122.7, 128.0, 130.2, 131.4, 132.2, 137.7, 169.6, 212.0; ESI-MS m/z 392, 394 [M+Na]+; HRMS calcd. for C15H16BrNO5Cs [M+Cs]+: 501.9266, found 501.9272; [α]D25.6 +13.1 (c 0.993, CHCl3); HPLC (DAICEL CHIRALCEL OD, hexane/2-propanol = 90/10, flow 1.0 mL/min, detection at 220 nm) tR 21.7 min (major) and 27.2 min (minor).
(1S)-1-[(1S)-1-(2-Bromophenyl)-2-nitroethyl]-2-oxo-cyclopentanecarboxylic Acid Methyl Ester (5ea) [37]. Yellow solid; IR (KBr) ν 2960, 1724, 1554, 1242 cm−1; 1H-NMR (CDCl3) δ 1.85–1.98 (m, 2H), 2.04–2.15 (m, 1H), 2.16–2.24 (m, 1H), 2.44–2.50 (m, 2H), 3.72 (s, 3H), 4.48 (dd, J = 3.5, 10.7 Hz, 1H), 5.03 (dd, J = 10.7, 13.7 Hz, 1H), 5.45 (dd, J = 3.5, 13.7 Hz, 1H), 7.11 (ddd, J = 1.5, 7.5, 8.0 Hz, 1H), 7.28 (ddd, J = 1.2, 7.5, 8.0 Hz, 1H), 7.49 (dd, J = 1.5, 8.0 Hz, 1H), 7.55 (dd, J = 1.2, 8.0 Hz, 1H); 13C-NMR (CDCl3) δ 19.2, 32.8, 37.7, 43.7, 52.8, 62.0, 76.9, 126.6, 128.2, 128.8, 129.5, 133.4, 136.3, 169.8, 212.4; ESI-MS m/z 392, 394 [M+Na]+; HRMS calcd. for C15H16BrNO5Cs [M+Cs]+: 501.9266, found 501.9272; [α]D25.6 –22.9 (c 0.926, CHCl3); HPLC (DAICEL CHIRALCEL OD, hexane/2-propanol = 90/10, flow 1.0 mL/min, detection at 220 nm) tR 14.8 min (major) and 21.3 min (minor).
(1S)-1-[(1R)-1-(4-Methoxyphenyl)-2-nitroethyl]-2-oxo-cyclopentanecarboxylic Acid Methyl Ester (5fa) [37]. Yellow solid; 1H-NMR (CDCl3) δ 1.75–2.07 (m, 4H), 2.27–2.43 (m, 2H), 3.73 (s, 3H), 3.75 (s, 3H), 4.03 (dd, J = 4.0, 11.0 Hz, 1H), 4.94 (dd, J = 11.0, 13.4 Hz, 1H), 5.08 (dd, J = 4.0, 13.4 Hz, 1H), 6.78–6.83 (m, 2H), 7.11–7.16 (m, 2H); 13C-NMR (CDCl3) δ 19.2, 30.7, 37.9, 45.4, 52.9, 55.0, 62.5, 76.4, 114.0, 126.8, 130.3, 159.2, 169.8, 212.3; ESI-MS m/z 344 [M+Na]+; HRMS calcd. for C16H19NO6Cs [M+Cs]+: 454.0267, found 454.0271; [α]D26.4 +38.8 (c 0.210, CHCl3); HPLC (DAICEL CHIRALCEL OD, hexane/2-propanol = 90/10, flow 1.0 mL/min, detection at 220 nm) tR 22.8 min (major) and 28.5 min (minor).
(1S)-1-[(1R)-1-(4-Methylphenyl)-2-nitroethyl]-2-oxo-cyclopentanecarboxylic Acid Methyl Ester (5ga) [37]. Colorless oil; IR (neat) ν 2956, 1751, 1725, 1554, 1230, 1149 cm−1; 1H-NMR (CDCl3) δ 1.75–2.06 (m, 4H) , 2.28 (s, 3H), 2.28–2.40 (m, 2H), 3.74 (s, 3H), 4.03 (dd, J = 4.0, 11.0 Hz, 1H), 4.96 (dd, J = 11.0, 13.8 Hz, 1H), 5.11 (dd, J = 4.0, 13.8 Hz, 1H) , 7.02–7.12 (m, 4H); 13C-NMR (CDCl3) δ 19.2, 20.9, 30.8, 37.9, 45.7, 52.9, 62.4, 76.3, 129.0, 129.4, 131.9, 137.9, 169.7, 212.2; ESI-MS m/z 328 [M+Na]+; HRMS calcd. for C16H19NO5Cs [M+Cs]+: 438.0318, found 438.0329; [α]D26.0 +24.0 (c 1.04, CHCl3); HPLC (DAICEL CHIRALCEL OD, hexane/2-propanol = 90/10, flow 1.0 mL/min, detection at 220 nm) tR 14.0 min (major) and 18.4 min (minor).
(1S)-1-[(1R)-1-Furan-2-yl-2-nitroethyl]-2-oxo-cyclopentanecarboxylic Acid Methyl Ester (5ha). Yellow solid; IR (KBr) ν 2962, 1752, 1718, 1554, 1238, 1145, cm−1; 1H-NMR (CDCl3) δ 1.66–1.77 (m, 1H), 1.89–2.01 (m, 2H), 2.06–2.14 (m, 1H), 2.28–2.38 (m, 1H), 2.42–2.49 (m, 1H), 3.73 (s, 3H), 4.40 (dd, J = 4.3, 10.0 Hz, 1H), 4.87 (dd, J = 10.0, 13.4 Hz, 1H), 4.91 (dd, J = 4.3, 13.4 Hz, 1H), 6.16 (brd, J = 3.4 Hz, 1H), 6.25–6.29 (dd, J = 1.9, 3.4 Hz, 1H), 7.29–7.32 (m, 1H); 13C-NMR (CDCl3) δ 19.3, 30.0, 37.8, 40.3, 53.0, 61.7, 74.3, 109.9, 110.7, 142.6, 148.9, 169.3, 211.9; ESI-MS m/z 304 [M+Na]+; HRMS calcd. for C13H15NNaO6 [M+Na]+: 304.0797, found 304.0787; [α]D25.6 +64.4 (c 1.03, CHCl3); HPLC (DAICEL CHIRALCEL OD, hexane/2-propanol = 90/10, flow 1.0 mL/min, detection at 220 nm) tR 12.8 min (major) and 20.0 min (minor).
(1S)-1-[(2R)-1-Nitro-4-phenylbutan-2-yl]-2-oxo-cyclopentanecarboxylic Acid Methyl Ester (5ia). Colorless solid; IR (KBr) ν 2951, 2927, 1734, 1711, 1545, 1232 cm−1; 1H-NMR (CDCl3) δ 1.57–1.67 (m, 1H), 1.74–2.02 (m, 4H), 2.22–2.32 (m, 1H), 2.36–2.44 (m, 1H), 2.51–2.59 (m, 2H), 2.68–2.77 (m, 1H), 2.81–2.88 (m, 1H), 3.68 (s, 3H), 4.44 (dd, J = 5.5, 14.0 Hz, 1H), 4.95 (dd, J = 5.2, 14.0 Hz, 1H), 7.11–7.15 (m, 2H), 7.17–7.23 (m, 1H), 7.24–7.31 (m, 2H); 13C-NMR (CDCl3) δ 19.2, 31.2, 32.4, 33.9, 38.0, 39.9, 52.7, 62.7, 76.2, 126.3, 128.3, 128.5, 140.5, 169.8, 213.1; ESI-MS m/z 342 [M+Na]+; HRMS calcd. for C17H21NNaO5 [M+Na]+: 342.1317, found 342.1325; [α]D25.5 +76.2 (c 1.08, CHCl3); HPLC (DAICEL CHIRALCEL AD-H, hexane/2-propanol = 4/1, flow 1.0 mL/min, detection at 220 nm) tR 7.3 min (major) and 7.9 min (minor).
(1S)-1-[(1R)-1-(4-Chlorophenyl)-2-nitroethyl]-2-oxo-cyclohexanecarboxylic Acid Methyl Ester (5bb). Colorless oil; IR (neat) ν 2951, 1712, 1554, 1492, 1236 cm−1; 1H-NMR (CDCl3) δ 1.44–1.52 (m, 1H), 1.54–1.78 (m, 3H), 1.99–2.06 (m, 1H), 2.09–2.16 (m, 1H), 2.41–2.55 (m, 2H), 3.73 (s, 3H), 3.98 (dd, J = 3.4, 11.3 Hz, 1H), 4.74 (dd, J = 11.3, 13.4 Hz, 1H), 5.01 (dd, J = 3.4, 13.4 Hz, 1H), 7.09–7.12 (m, 2H), 7.24–7.29 (m, 2H); 13C-NMR (CDCl3) δ 22.3, 27.7, 36.9, 41.3, 47.2, 52.6, 63.0, 77.3, 126.7, 130.7, 133.9, 134.2, 170.0, 206.7; ESI-MS m/z 362, 364 [M+Na]+; HRMS calcd. for C16H18ClNO5Cs [M+Cs]+: 471.9928, found 471.9925; [α]D26.5 –73.0 (c 1.03, CHCl3); HPLC (DAICEL CHIRALCEL OD-H, hexane/2-propanol = 90/10, flow 1.0 mL/min, detection at 220 nm) tR 13.4 min (major) and 8.9 min (minor).
(2S,3R)-Ethyl 2-acetyl-2-methyl-4-nitro-3-phenylbutanoate (5ac). Colorless oil; IR (neat) ν 2923, 1734, 1710, 1552, 1093, 701 cm−1; 1H-NMR (CDCl3) δ 1.21 (s, 3H), 1.29 (t, J = 7.3Hz, 3H), 2.15 (s, 3H), 4.12 (dd, J = 3.4, 11 Hz, 1H), 4.26 (q, J = 7.3 Hz, 2H), 4.87 (dd, J = 3.4, 13.4 Hz, 1H), 4.94 (dd, J = 11, 13.4 Hz, 1H), 7.08–7.15 (m, 2H), 7.25–7.31 (m,3H); 13C-NMR (CDCl3) δ 14.0, 20.1, 26.5, 47.7, 62.1, 62.5, 77.5, 128.4, 128.8, 129.0, 135.4, 171.2, 204.2; ESI-MS m/z 316 [M+Na]+; HRMS calcd. for C15H19NNaO5 [M+Na]+: 316.1161, found 316.1156; [α]D25.0 –53.1 (c 0.20, CHCl3); HPLC (DAICEL CHIRALCEL OD, hexane/2-propanol = 40/10, flow 1.0 mL/min, detection at 220 nm) tR 7.1 min (major) and 19.2 min (minor).

4. Conclusions

In summary, we developed a highly enantioselective catalytic asymmetric 1,4-addition of β-keto esters to nitroalkenes for the construction of adjacent quaternary/tertiary carbon stereocenters. Bifunctional Co2-Schiff base 1 complex smoothly promoted the reaction in excellent yield (up to 99%), diastereoselectivity, and enantioselectivity (up to >30:1 dr and 98% ee). Catalyst loading was successfully reduced to 0.1 mol %. Mechanistic studies suggested that intramolecular cooperative functions of the two Co-metal centers are important for high catalytic activity and stereoselectivity.

Acknowledgements

This work was supported by Grant-in-Aid for Scientific Research on Priority Areas (No. 20037010, Chemistry of Concerto Catalysis) from MEXT, Takeda Science Foundation, and Kato Memorial Bioscience Foundation.
  • Sample Availability: Samples of the compounds Co2(OAc)2-1 and Ni2-1 are available from the authors.

References and Notes

  1. Shibasaki, M.; Kanai, M.; Matsunaga, S.; Kumagai, N. Recent progress in asymmetric bifunctional catalysis using multimetallic systems. Acc. Chem. Res. 2009, 42, 1117–1127. [Google Scholar] [CrossRef]
  2. Matsunaga, S.; Shibasaki, M. Multimetallic bifunctional asymmetric catalysis based on proximity effect control. Bull. Chem. Soc. Jpn. 2008, 81, 60–75. [Google Scholar] [CrossRef]
  3. Mukherjee, S.; Yang, J.W.; Hoffmann, S.; List, B. Asymmetric enamine catalysis. Chem. Rev. 2007, 107, 5471–5569. [Google Scholar] [CrossRef]
  4. Taylor, M.S.; Jacobsen, E.N. Asymmetric catalysis by chiral hydrogen-bond donors. Angew. Chem., Int. Ed. 2006, 45, 1520–1543. [Google Scholar] [CrossRef]
  5. Yamamoto, H.; Futatsugi, K. “Designer acids”: combined acid catalysis for asymmetric synthesis. Angew. Chem., Int. Ed. 2005, 44, 1924–1942. [Google Scholar] [CrossRef]
  6. Katsuki, T. Unique asymmetric catalysis of cis-β metal complexes of salen and its related Schiff-base ligands. Chem. Soc. Rev. 2004, 33, 437–444. [Google Scholar]
  7. Cozzi, P.G. Metal-salen Schiff base complexes in catalysis: practical aspects. Chem. Soc. Rev. 2004, 33, 410–421. [Google Scholar]
  8. Jacobsen, E.N. Asymmetric catalysis of epoxide ring-opening reactions. Acc. Chem. Res. 2000, 33, 421–431. [Google Scholar] [CrossRef]
  9. Handa, S.; Gnanadesikan, V.; Matsunaga, S.; Shibasaki, M. syn-Selective catalytic asymmetric nitro-Mannich reactions using a heterobimetallic Cu-Sm-Schiff base complex. J. Am. Chem. Soc. 2007, 129, 4900–4901. [Google Scholar] [CrossRef]
  10. Handa, S.; Nagawa, K.; Sohtome, Y.; Matsunaga, S.; Shibasaki, M. A heterobimetallic Pd/La/Schiff base complex for anti-selective catalytic asymmetric nitroaldol reactions and applications to short syntheses of β-adrenoceptor agonists. Angew. Chem., Int. Ed. 2008, 47, 3230–3233. [Google Scholar] [CrossRef]
  11. Sohtome, Y.; Kato, Y.; Handa, S.; Aoyama, N.; Nagawa, K.; Matsunaga, S.; Shibasaki, M. Stereodivergent catalytic doubly diastereoselective nitroaldol reactions using heterobimetallic complexes. Org. Lett. 2008, 10, 2231–2234. [Google Scholar] [CrossRef]
  12. Mihara, H.; Xu, Y.; Shepherd, N.E.; Matsunaga, S.; Shibasaki, M. A heterobimetallic Ga/Yb-Schiff base complex for catalytic asymmetric α-addition of isocyanides to aldehydes. J. Am. Chem. Soc. 2009, 131, 8384–8385. [Google Scholar]
  13. Chen, Z.; Morimoto, H.; Matsunaga, S.; Shibasaki, M. A bench-stable homodinuclear Ni2-Schiff base complex for catalytic asymmetric synthesis of α-tetrasubstituted anti-α,β-diamino acid surrogates. J. Am. Chem. Soc. 2008, 130, 2170–2171. [Google Scholar] [CrossRef]
  14. Chen, Z.; Yakura, K.; Matsunaga, S.; Shibasaki, M. Direct catalytic asymmetric Mannich-type reaction of β-keto phosphonate using a dinuclear Ni2-Schiff base complex. Org. Lett. 2008, 10, 3239–3242. [Google Scholar] [CrossRef]
  15. Xu, Y.; Lu, G.; Matsunaga, S.; Shibasaki, M. Direct anti-selective catalytic asymmetric Mannich-type reactions of α-ketoanilides for the synthesis of γ-amino amides and azetidine-2-amides. Angew. Chem., Int. Ed. 2009, 48, 3353–3356. [Google Scholar] [CrossRef]
  16. Mouri, S.; Chen, Z.; Matsunaga, S.; Shibasaki, M. Direct catalytic asymmetric aldol reaction of β-keto esters with formaldehyde promoted by a dinuclear Ni2-Schiff base complex. Chem. Commun. 2009, 5138–5140. [Google Scholar]
  17. Kato, Y.; Chen, Z.; Matsunaga, S.; Shibasaki, M. Catalytic asymmetric synthesis of nitrogen-containing gem-bisphosphonates using a dinuclear Ni2-Schiff base complex. Synlett 2009, 1635–1638. [Google Scholar]
  18. Mouri, S.; Chen, Z.; Mitsunuma, H.; Furutachi, M.; Matsunaga, S.; Shibasaki, M. Catalytic asymmetric synthesis of 3-aminooxindoles: enantiofacial selectivity switch in bimetallic vs. monometallic Schiff base catalysis. J. Am. Chem. Soc. 2010, 132. [Google Scholar] [CrossRef]
  19. Chen, Z.; Furutachi, M.; Kato, Y.; Matsunaga, S.; Shibasaki, M. A stable homodinuclear biscobalt(III)-Schiff base complex for catalytic asymmetric 1,4-additions of β-keto esters to alkynones. Angew. Chem. Int. Ed. 2009, 48, 2218–2220. [Google Scholar]
  20. Kato, Y.; Furutachi, M.; Chen, Z.; Mitsunuma, H.; Matsunaga, S.; Shibasaki, M. A homodinuclear Mn(III)2-Schiff base complex for catalytic asymmetric 1,4-additions of oxindoles to nitroalkenes. J. Am. Chem. Soc. 2009, 131, 9168–9169. [Google Scholar]
  21. Annamalai, V.; DiMauro, E.F.; Carroll, P.J.; Kozlowski, M.C. Catalysis of the Michael addition reaction by late transition metal complexes of BINOL-derived salens. J. Org. Chem. 2003, 68, 1973–1981. [Google Scholar] [CrossRef]
  22. Gao, J.; Woolley, F.R.; Zingaro, R.A. Catalytic asymmetric cyclopropanation at a chiral platform. Org. Biomol. Chem. 2005, 3, 2126–2128. [Google Scholar] [CrossRef]
  23. Yang, M.; Zhu, C.; Yuan, F.; Huang, Y.; Pan, Y. Enantioselective ring-opening reaction of meso-epoxides with ArSeH catalyzed by heterometallic Ti−Ga−salen system. Org. Lett. 2005, 7, 1927–1930. [Google Scholar] [CrossRef]
  24. Li, W.; Thakur, S.S.; Chen, S.-W.; Shin, C.-K.; Kawthekar, R.B.; Kim, G.-J. Synthesis of optically active 2-hydroxy monoesters via-kinetic resolution and asymmetric cyclization catalyzed by heterometallic chiral (salen) Co complex. Tetrahedron Lett. 2006, 47, 3453–3457. [Google Scholar]
  25. Mazet, C.; Jacobsen, E.N. Dinuclear {(salen)Al} complexes display expanded scope in the conjugate cyanation of α,β-unsaturated imides. Angew. Chem., Int. Ed. 2008, 47, 1762–1765. [Google Scholar] [CrossRef]
  26. Hirahata, W.; Thomas, R.M.; Lobkovsky, E.B.; Coates, G.W. Enantioselective polymerization of epoxides: a highly active and selective catalyst for the preparation of stereoregular polyethers and enantiopure epoxides. J. Am. Chem. Soc. 2008, 130, 17658–17659. [Google Scholar]
  27. Wu, B.; Gallucci, J.C.; Parquette, J.R.; RajanBabu, T.V. Enantioselective desymmetrization of meso-aziridines with TMSN3 or TMSCN catalyzed by discrete yttrium complexes. Angew. Chem., Int. Ed. 2009, 48, 1126–1129. [Google Scholar] [CrossRef]
  28. Berner, O.M.; Tedeschi, L.; Enders, D. Asymmetric Michael additions to nitroalkenes. Eur. J. Org. Chem. 2002, 1877–1894. [Google Scholar]
  29. Tsogoeva, S.B. Recent advances in asymmetric organocatalytic 1,4-conjugate additions. Eur. J. Org. Chem. 2007, 1701–1716. [Google Scholar] [CrossRef]
  30. Christoffers, J.; Koripelly, G.; Rosiak, A.; Rössle, M. Recent advances in metal-catalyzed asymmetric conjugate additions. Synthesis 2007, 1279–1300. [Google Scholar]
  31. Ji, J.; Barnes, D.M.; Zhang, J.; King, S.A.; Wittenberger, S.J.; Morton, H.E. Catalytic enantioselective conjugate addition of 1,3-dicarbonyl compounds to nitroalkenes. J. Am. Chem. Soc. 1999, 121, 10215–10216. [Google Scholar] [CrossRef]
  32. Watanabe, M.; Ikagawa, A.; Wang, H.; Murata, K.; Ikariya, T. Catalytic enantioselective Michael addition of 1,3-dicarbonyl compounds to nitroalkenes catalyzed by well-defined chiral Ru amido complexes. J. Am. Chem. Soc. 2004, 126, 11148–11149. [Google Scholar] [CrossRef]
  33. Evans, D.A.; Mito, S.; Seidel, D. Scope and mechanism of enantioselective Michael additions of 1,3-dicarbonyl compounds to nitroalkenes catalyzed by nickel(II)−diamine complexes. J. Am. Chem. Soc. 2007, 129, 11583–11592. [Google Scholar] [CrossRef]
  34. Li, H.; Wang, Y.; Tang, L.; Wu, F.; Liu, X.; Guo, C.; Foxman, B.M.; Deng, L. Stereocontrolled creation of adjacent quaternary and tertiary stereocenters by a catalytic conjugate addition. Angew. Chem. Int. Ed. 2005, 44, 105–108. [Google Scholar] [CrossRef]
  35. Okino, T.; Hoashi, Y.; Furukawa, T.; Xu, X.; Takemoto, Y. Enantio- and diastereoselective Michael reaction of 1,3-dicarbonyl compounds to nitroolefins catalyzed by a bifunctional thiourea. J. Am. Chem. Soc. 2005, 127, 119–125. [Google Scholar]
  36. Malerich, J.P.; Hagihara, K.; Rawal, V.H. Chiral squaramide derivatives are excellent hydrogen bond donor catalysts. J. Am. Chem. Soc. 2008, 130, 14416–14417. [Google Scholar] [CrossRef]
  37. Zhang, Z.-H.; Dong, X.-Q.; Chen, D.; Wang, C.J. Fine-tunable organocatalysts bearing multiple hydrogen-bonding donors for construction of adjacent quaternary and tertiary stereocenters via a Michael reaction. Chem. Eur. J. 2008, 14, 8780–8783. [Google Scholar]
  38. Luo, J.; Xu, L.W.; Hay, R.A.S.; Lu, Y. Asymmetric Michael addition mediated by novel Cinchona alkaloid-derived bifunctional catalysts containing sulfonamides. Org. Lett. 2009, 11, 437–440. [Google Scholar]
  39. Chen, F.-X.; Shao, C.; Liu, Q.; Gong, P.; Liu, C.-L.; Wang, R. Asymmetric Michael addition of trisubstituted carbanion to nitroalkenes catalyzed by sodium demethylquinine salt in water. Chirality 2009, 21, 600–603. [Google Scholar] [CrossRef]
  40. Jiang, X.; Zhang, Y.; Liu, X.; Zhang, G.; Lai, L.; Wu, L.; Zhang, J.; Wang, R. Enantio- and diastereoselective asymmetric addition of 1,3-dicarbonyl compounds to nitroalkenes in a doubly stereocontrolled manner catalyzed by bifunctional Rosin-derived amine thiourea catalysts. J. Org. Chem. 2009, 74, 5562–5567. [Google Scholar] [CrossRef]
  41. Yu, Z.; Liu, X.; Zhou, L.; Lin, L.; Feng, X. Bifunctional guanidine via an amino amide skeleton for asymmetric Michael reactions of β-ketoesters with nitroolefins: a concise synthesis of bicyclic β -amino acids. Angew. Chem., Int. Ed. 2009, 48, 5195–5198. [Google Scholar] [CrossRef]
  42. Almasi, D.; Alonso, D.A.; Gómez-Bengoa, E.; Nájera, C. Chiral 2-aminobenzimidazoles as recoverable organocatalysts for the addition of 1,3-dicarbonyl compounds to nitroalkenes. J. Org. Chem. 2009, 74, 6163–6168. [Google Scholar] [CrossRef]

Share and Cite

MDPI and ACS Style

Furutachi, M.; Chen, Z.; Matsunaga, S.; Shibasaki, M. Catalytic Asymmetric 1,4-Additions of β-Keto Esters to Nitroalkenes Promoted by a Bifunctional Homobimetallic Co2-Schiff Base Complex. Molecules 2010, 15, 532-544. https://doi.org/10.3390/molecules15010532

AMA Style

Furutachi M, Chen Z, Matsunaga S, Shibasaki M. Catalytic Asymmetric 1,4-Additions of β-Keto Esters to Nitroalkenes Promoted by a Bifunctional Homobimetallic Co2-Schiff Base Complex. Molecules. 2010; 15(1):532-544. https://doi.org/10.3390/molecules15010532

Chicago/Turabian Style

Furutachi, Makoto, Zhihua Chen, Shigeki Matsunaga, and Masakatsu Shibasaki. 2010. "Catalytic Asymmetric 1,4-Additions of β-Keto Esters to Nitroalkenes Promoted by a Bifunctional Homobimetallic Co2-Schiff Base Complex" Molecules 15, no. 1: 532-544. https://doi.org/10.3390/molecules15010532

Article Metrics

Back to TopTop