Ethyl 2-oxo-1-[2-oxo-2-(4-nitrophenyl)ethyl]cyclopentane-1-carboxylate (3ac). According to GPC CeCl3 · 7 H2O (12 mg, 32 µmol) was added to a mixture of β- ...
Eur. J. Org. Chem. 2016 · ISSN 1099–0682 SUPPORTING INFORMATION DOI: 10.1002/ejoc.201600057 Title: Synthesis of 1,4-Diketones from β-Oxo Esters and Enol Acetates by Cerium-Catalyzed Oxidative Umpolung Reaction Author(s): Irina Geibel, Jens Christoffers*
Table of Contents 1. General Information
S1
2. Experimental procedures and characterization of compounds
S2
2.1 Overview of starting materials 1 and 4
S2
2.2 Preparation of β-oxo esters 1a–j
S3
2.3 Preparation of enol esters 4b–e
S9
2.4 Cerium-catalyzed synthesis of 1,4-diketones 3aa–3jb
S11
3. References
S27
4. NMR Spectra
S29
1. General Information
All starting materials and solvents were commercially available. Solvents [hexanes, bp. 40–60°C, tert-butyl methyl ether (MTBE), methylene chloride (DCM), ethyl acetate, chloroform, methanol] used for column chromatography were distilled prior to use. All known compounds were identified by appropriate techniques such as 1H NMR, 13 C{1H} NMR and compared with previously reported data. All unknown compounds were characterized by 1H NMR, 13C{1H} NMR, IR and HRMS. Chromatography: Preparative column chromatography was carried out using Merck SiO2 (35–70 µm, type 60 A). Thin-layer chromatography was performed on Merck aluminum plates coated with SiO2 F254 with visualization by ultraviolet light (254 nm) and/or heating the plate after staining with a cerium(IV)-sulfate/phosphomolybdic acid solution. Nuclear Magnetic Resonance Spectroscopy: 1H,
19
F{1H} and
13
C{1H} NMR spectra
were acquired on a Bruker Avance DRX 500 instrument and were internal referenced to residual solvent peaks in CDCl3 (δH = 7.26 ppm; δC = 77.0 ppm) or versus a CF3COOH external standard (δF = 0 ppm). Multiplicities are designated using the following abbreviations as well as their combinations: singlet (s), doublet (d), triplet (t), quartet (q), multiplet (m), and broad signal (br). Multiplicities of carbon signals were determined with DEPT135 experiments. Coupling constants (J) are measured to the nearest 0.1 Hz and are presented as observed. S1
Mass Spectrometry: High-resolution mass spectra (HRMS) were recorded on a Waters Micromass Q-TOF Premier (electrospray ionization: ESI, positive mode) spectrometer. The parent ion [M+H+] or [M+Na+] is calculated to four decimal places from the molecular formula. Infrared Spectroscopy: Absorption spectra were obtained on a Bruker Tensor 27 spectrometer equipped with a MKII “Golden Gate” single reflection diamond ATRunit. Wavelengths are quoted in wavenubers (cm–1). Only selected, characteristic IR absorption data are provided for each unknown compound.
2. Experimental procedures and characterization of compounds 2.1 Overview of starting materials: β-oxo esters 1 and enol esters 4
S2
OAc OAc
OAc
OAc
OAc
Me
tBu
Ph NO2
4a
4b
OMe 4d
4c
4e
2.2 Preparation of β-oxo esters 1d-j O
CO(OR)2 (5.0-10 equiv.)
O
NaH (2.1 equiv.) X
Y
THF, reflux, 30 min-16 h
CO2R X
Y
General procedure A (GPA):[S1] A solution of ketone (1.0 equiv.) in abs. THF (1 L/mol ketone) was added dropwise to a stirred solution of dialkyl carbonate (5.0-10 equiv.) in abs. THF (2 L/mol ketone) containing NaH (60% dispersion in mineral oil, 2.1 equiv.) under a nitrogen atmosphere. The mixture was heated to reflux (30 min to 16 h), cooled in an ice-bath and then acidified with 1 mol/L hydrochloric acid (1.5 L/mol ketone). The residue was then extracted with Et2O (3 x 5 L/mol ketone). The combined organic layers were dried over MgSO4, filtered and the solvent was removed in vacuo. The crude product was purified by column chromatography to give the β-oxo ester 1.
Methyl 1-indanone-2-carboxylate (1d)
According to GPA a solution of 1-indanone (5.00 g, 37.8 mmol) in abs. THF (40 ml) was added dropwise to a stirred suspension of NaH (60% dispersion in mineral oil, 3.18 g, 79.4 mmol) in THF (80 ml) containing dimethyl carbonate (17.0 g, 189 mmol). The mixture was heated to reflux for 2 h to yield the title compound 1d (6.69 g, 35.2 mmol, 93%) after chromatography (hexanes/MTBE 5:1, Rf = 0.21) as a light brown solid, mp. 58°C. The product was isolated as a mixture of keto and enol tautomer (ratio 6:1 by 1H NMR). 1H NMR (500 MHz, CDCl3), keto tautomer: δ = 3.36 (dd, J = 17.2 Hz, J = 8.3 Hz, 1H), 3.55 (dd, J = 17.3 Hz, J = 4.0 Hz, 1H), 3.73 (dd, J = 8.3 Hz, J S3
= 4.1 Hz, 1H), 3.78 (s, 3H), 7.38 (t, J = 7.5 Hz, 1H), 7.49 (d, J = 7.7 Hz, 1H), 7.61 (td, J = 7.6 Hz, J = 1.0 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H) ppm; enol tautomer: δ = 3.50 (s, 2H), 3.84 (s, 3H), 7.35–7.38 (m, 1H), 7.42 (td, J = 7.3 Hz, J = 1.2 Hz, 1H), 7.45 (d, J = 7.3 Hz, 1H), 7.60–7.64 (m, 1H), 10.36 (br s, 1H) ppm.
13
C{1H} NMR (125 MHz,
CDCl3), keto tautomer: δ = 30.19 (CH2), 52.70 (CH), 53.06 (CH3), 124.61 (CH), 126.48 (CH), 127.74 (CH), 135.11 (C), 135.39 (CH), 153.52 (C), 169.46 (C), 199.34 (C) ppm; enol tautomer: δ = 32.43 (CH2), 51.15 (CH3), 102.10 (C), 120.66 (CH), 124.66 (CH), 126.75 (CH), 129.33 (CH), 136.75 (C), 143.12 (C), 153.52 (C), 169.63 (C) ppm. The data were in accordance with literature values.[S2]
Methyl 5,6-dimethoxy-1-indanone-2-carboxylate (1e)
According to GPA a solution of 5,6-dimethoxy-1-indanone (2.00 g, 10.4 mmol) in abs. THF (10 ml) was added dropwise to a stirred suspension of NaH (60% dispersion in mineral oil, 874 mg, 21.8 mmol) in THF (20 ml) containing dimethyl carbonate (4.68 g, 52.0 mmol). The mixture was heated to reflux for 4 h to yield the title compound 1e (2.37 g, 9.46 mmol, 91%) after recrystallization from ethanol as a beige solid, mp. 162°C. 1H NMR (500 MHz, CDCl3): δ = 3.27 (dd, J = 17.0 Hz, J = 7.9 Hz, 1H), 3.45 (ddd, J = 16.9 Hz, J = 3.5 Hz, J = 0.8 Hz, 1H), 3.72 (dd, J = 7.9 Hz, J = 3.5 Hz, 1H), 3.79 (s, 3H), 3.90 (s, 3H), 3.98 (s, 3H), 6.90 (s, 1H), 7.16 (s, 1H) ppm.
13
C{1H} NMR
(125 MHz, CDCl3): δ = 30.05 (CH2), 52.69 (CH3), 53.43 (CH3), 56.15 (CH3), 56.31 (CH), 104.94 (CH), 107.29 (CH), 127.99 (C), 149.17 (C), 149.86 (C), 156.17 (C), 169.87 (C), 197.84 (C) ppm. The data were in accordance with literature values.[S3]
Methyl 6-(trifluoromethyl)-1-indanone-2-carboxylate (1f)
According to GPA a solution of 6-trifluoromethyl-1-indanone (500 mg, 2.50 mmol) in abs. THF (3 ml) was added dropwise to a stirred suspension of NaH (60% dispersion
S4
in mineral oil, 275 mg, 5.50 mmol) in THF (5 ml) containing dimethyl carbonate (1.13 g, 12.5 mmol). The mixture was stirred at ambient temperature for 2 h to yield the title compound 1f (511 mg, 1.98 mmol, 80%) after chromatography (hexanes/MTBE 1:1, Rf = 0.39) as a light beige solid, mp. 112°C. The product was isolated as a mixture of keto and enol tautomer (ratio 1:0.7 by 1H NMR). 1H NMR (500 MHz, CDCl3), keto tautomer: δ = 3.44 (dd, J = 17.7 Hz, J = 8.4 Hz, 1H), 3.64 (dd, J = 17.6 Hz, J = 4.1 Hz, 1H), 3.80–3.82 (m, 1H), 3.81 (s, 3H), 7.64–7.68 (m, 1H), 7.87 (d, J = 8.0 Hz, 1H), 8.04 (s, 1H) ppm; enol tautomer: δ = 3.58 (s, 2H), 3.87 (s, 3H), 7.57 (d, J = 7.9 Hz, 1H), 7.64–7.68 (m, 1H), 7.89 (s, 1H), 10.27 (br s, 1H) ppm.
13
C{1H} NMR (125 MHz,
CDCl3), keto tautomer: δ = 30.33 (CH2), 52.92 (CH), 53.31 (CH3), 121.96 (q, 3JCF = 3.6 Hz, CH), 123.58 (q, 1JCF = 272.3 Hz, CF3), 127.32 (CH), 130.83 (q, 2JCF = 33.1 Hz, C), 131.82 (q, 3JCF = 3.4 Hz, CH), 135.66 (C), 156.62 (C), 168.81 (C), 197.98 (C) ppm; enol tautomer: δ = 32.74 (CH2), 51.41 (CH3), 103.73 (C), 117.81 (q, 3JCF = 3.6 Hz, CH), 124.15 (q, 1JCF = 272.4 Hz, CF3), 125.06 (CH), 126.00 (q, 3JCF = 3.4 Hz, CH), 129.72 (q, 2JCF = 32.5 Hz, C), 137.55 (C), 146.41 (C), 168.14 (C), 169.23 (C) ppm.
19
F{1H} NMR (470 MHz, CDCl3), keto tautomer: δ = –62.60 (s, CF3) ppm; enol
tautomer: δ = –62.12 (s, CF3) ppm. IR (ATR): λ–1 = 3061 (w), 2962 (w), 1722 (m), 1659 (m), 1584 (m), 1446 (m), 1322 (s), 1270 (s), 1221 (m), 1153 (m), 1109 (vs), 1106 (vs), 1058 (m), 905 (m), 778 (m) cm–1. HRMS (ESI): calcd. 259.0576 (for C12H10F3O3+); found 259.0574 [M+H+]. Methyl 4-bromo-1-indanone-2-carboxylate (1g)
According to GPA a solution of 4-bromo-1-indanone (2.00 g, 9.48 mmol) in abs. THF (10 ml) was added dropwise to a stirred suspension of NaH (60% dispersion in mineral oil, 796 mg, 19.9 mmol) in THF (20 ml) containing dimethyl carbonate (4.27 g, 47.4 mmol). The mixture was heated to reflux for 30 min to yield the title compound 1g (2.49 g, 9.25 mmol, 98%) after chromatography (hexanes/MTBE 1:1, Rf = 0.50) as a brown solid, mp. 76°C. The product was isolated as a mixture of keto and enol tautomer (ratio 2:1 by 1H NMR). 1H NMR (500 MHz, CDCl3), keto tautomer: δ = 3.32 (dd, J = 17.9 Hz,
S5
J = 8.3 Hz, 1H), 3.50 (dd, J = 18.1 Hz, J = 3.8 Hz, 1H), 3.77 (dd, J = 8.3 Hz, J = 4.0 Hz, 1H), 3.80 (s, 3H), 7.31 (t, J = 7.9 Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.79 (dd, J = 7.9 Hz, J = 0.9 Hz, 1H) ppm; enol tautomer: δ = 3.47 (s, 2H), 3.87 (s, 3H), 7.25–7.33 (m, 1H), 7.55 (dd, J = 8.0 Hz, J = 0.9 Hz, 1H), 7.59 (dd, J = 7.6 Hz, J = 0.9 Hz, 1H), 10.28 (br s, 1H) ppm.
13
C{1H} NMR (125 MHz, CDCl3), keto tautomer: δ = 31.35 (CH2), 52.90
(CH3), 53.03 (CH), 121.96 (C), 123.48 (CH), 129.58 (CH), 137.13 (C), 138.17 (CH), 153.18 (C), 168.95 (C), 198.56 (C) ppm; enol tautomer: δ = 34.04 (CH2), 51.38 (CH3), 102.88 (C), 119.64 (C), 119.80 (CH), 128.73 (CH), 132.33 (CH), 138.44 (C), 138.81 (C), 143.04 (C), 168.95 (C) ppm. The data were in accordance with literature values.[S4]
Ethyl 1-tetralone-2-carboxylate (1h)
According to GPA a solution of 1-tetralone (5.91 g, 40.0 mmol) in abs. THF (40 ml) was added dropwise to a stirred suspension of NaH (60% dispersion in mineral oil, 3.36 g, 84.0 mmol) in THF (60 ml) containing diethyl carbonate (9.50 g, 80.0 mmol). The mixture was heated to reflux for 16 h to yield the title compound 1h (8.73 g, 40.0 mmol, quant.) without further purification as a light brown oil. The product was isolated as a mixture of keto and enol tautomer (ratio almost 1:1 by 1H NMR). 1H NMR (500 MHz, CDCl3), keto tautomer: δ = 1.29 (t, J = 7.2 Hz, 3H), 2.36 (ddt, J = 13.5 Hz, J = 5.9 Hz, J = 4.7 Hz, 1H), 2.50 (dddd, J = 13.4 Hz, J = 10.4 Hz, J = 9.5 Hz, J = 4.7 Hz, 1H), 2.95–3.04 (m, 1H), 3.05 (tt, J = 16.8 Hz, J = 5.3 Hz, 1H), 3.59 (dd, J = 10.4 Hz, J = 4.7 Hz, 1H), 4.21–4.28 (m, 2H), 7.17 (dt, J = 7.2 Hz, J = 1.0 Hz, 1H), 7.24 (d, J = 7.7 Hz, 1H), 7.48 (td, J = 7.5 Hz, J = 1.5 Hz, 1H), 8.05 (dd, J = 7.9 Hz, J = 1.5 Hz, 1H) ppm; enol tautomer: δ = 1.35 (t, J = 7.2 Hz, 3H), 2.57 (dd, J = 8.7 Hz, J = 6.8 Hz, 2H), 2.81 (dd, J = 8.8 Hz, J = 6.7 Hz, 2H), 4.28 (q, J = 7.1 Hz, 2H), 7.28 (dd, J = 7.5 Hz, J = 1.5 Hz, 1H), 7.32 (td, J = 7.4 Hz, J = 1.5 Hz, 1H), 7.82 (dd, J = 7.5 Hz, J = 1.6 Hz, 1H), 12.48 (br s, 1H) ppm. 13C{1H} NMR (125 MHz, CDCl3), keto tautomer: δ = 14.13 (CH3), 26.36 (CH2), 27.60 (CH2), 54.54 (CH), 61.20 (CH2), 126.83 (CH), 127.69 (CH), 128.73 (CH), 131.79 (C), 133.76 (CH), 143.59 (C), 170.13 (C), 193.13 (C) ppm; enol tautomer: δ = 14.28 (CH3), 20.52 (CH2), 27.76 (CH2), 60.47 (CH2), 96.98 (C), 124.26 (CH), 126.50 (CH), 127.33 (CH), 130.04 (C), 130.40 (CH), 139.34 (C), 164.96 (C), 172.69 (C) ppm. The data were in accordance with literature values.[S1] S6
Methyl 6-methoxy-1-tetralone-2-carboxylate (1i)
According to GPA a solution of 6-methoxy-1-tetralone (2.00 g, 11.4 mmol) in abs. THF (10 ml) was added dropwise to a stirred suspension of NaH (60% dispersion in mineral oil, 958 mg, 23.9 mmol) in THF (20 ml) containing dimethyl carbonate (10.3 g, 114 mmol). The mixture was heated to reflux for 3.5 h to yield the title compound 1i (2.51 g, 10.7 mmol, 94%) after chromatography (hexanes/MTBE 1:1, Rf = 0.49) as a colorless solid, mp. 88°C. The product was isolated as a mixture of keto and enol tautomer (ratio 5:1 by 1H NMR). 1H NMR (500 MHz, CDCl3), keto tautomer: δ = 2.31 (ddt, J = 13.4 Hz, J = 6.1 Hz, J = 4.7 Hz, 1H), 2.46 (dtd, J = 13.6 Hz, J = 9.8 Hz, J = 4.7 Hz, 1H), 2.93 (ddd, J = 16.8 Hz, J = 9.5 Hz, J = 4.6 Hz, 1H), 3.01 (dt, J = 16.8 Hz, J = 5.3 Hz, 1H), 3.56 (dd, J = 10.2 Hz, J = 4.7 Hz, 1H), 3.76 (s, 3H), 3.84 (s, 3H), 6.67 (d, J = 2.6 Hz, 1H), 6.82 (dd, J = 8.8 Hz, J = 2.6 Hz, 1H), 8.00 (d, J = 8.8 Hz, 1H) ppm; enol tautomer: δ = 2.54 (dd, J = 8.8 Hz, J = 6.7 Hz, 2H), 2.75 (dd, J = 8.8 Hz, J = 6.7 Hz, 2H), 3.79 (s, 3H), 3.81 (s, 3H), 6.68 (d, J = 2.6 Hz, 1H), 6.78 (dd, J = 8.6 Hz, J = 2.6 Hz, 1H), 7.72 (d, J = 8.6 Hz, 1H), 12.45 (br s, 1H) ppm.
13
C{1H} NMR
(125 MHz, CDCl3), keto tautomer: δ = 26.37 (CH2), 27.94 (CH2), 52.22 (CH3), 54.12 (CH3), 55.41 (CH), 112.50 (CH), 113.42 (CH), 125.18 (C), 130.19 (CH), 146.12 (C), 163.90 (C), 170.79 (C), 191.70 (C) ppm; enol tautomer: δ = 20.49 (CH2), 28.14 (CH2), 51.43 (CH3), 55.24 (CH3), 94.70 (C), 111.59 (CH), 113.08 (CH), 122.72 (C), 126.09 (CH), 141.68 (C), 161.45 (C), 165.43 (C), 173.02 (C) ppm. The data were in accordance with literature values.[S5]
S7
Methyl 4-chromanone-3-carboxylate (1j)
According to a literature procedure[S6] a solution of 4-chromanone (1.50 g, 10.1 mmol) in abs. THF (10 ml) was added dropwise to a stirring mixture of nBuLi (8.0 ml of a 2.5 mol/L solution in hexane, 20 mmol) and HMDS (20 mmol, 4.2 ml) in abs. THF (40 ml) under a nitrogen atmosphere at –78°C. After 90 min NCCO2Me (1.71 g, 20.2 mmol) was added dropwise and the mixture was stirred for 30 min. Subsequently, the reaction mixture was warmed to ambient temperature and diluted with a saturated aqueous NH4Cl solution (100 ml). After extraction with Et2O (3 x 40 ml), the combined organic layers were dried over MgSO4, filtered and the solvent was removed in vacuo. Purification by column chromatography (hexanes/EtOAc 3:2, Rf = 0.49) gave the title compound 1j (2.04 g, 9.88 mmol, 98%) as a light pink oil. The product was isolated as a mixture of keto and enol tautomer (ratio 3:1 by 1H NMR). 1
H NMR (500 MHz, CDCl3), keto tautomer: δ = 3.77 (dd, J = 8.3 Hz, J = 4.5 Hz, 1H),
3.80 (s, 3H), 4.64 (dd, J = 11.7 Hz, J = 4.5 Hz, 1H), 4.81 (dd, J = 11.6 Hz, J = 8.3 Hz, 1H), 6.98–7.02 (m, 1H), 7.06 (ddd, J = 8.0 Hz, J = 7.1 Hz, J = 1.0 Hz, 1H), 7.51 (ddd, J = 8.8 Hz, J = 7.2 Hz, J = 1.8 Hz, 1H), 7.94 (dd, J = 7.9 Hz, J = 1.8 Hz, 1H) ppm; enol tautomer: δ = 3.84 (s, 3H), 4.97 (s, 2H), 6.88 (dd, J = 8.3 Hz, J = 1.2 Hz, 1H), 6.98–7.02 (m, 1H), 7.33 (ddd, J = 8.2 Hz, J = 7.4 Hz, J = 1.7 Hz, 1H), 7.67 (dd, J = 7.8 Hz, J = 1.7 Hz, 1H), 11.95 (br s, 1H) ppm.
13
C{1H} NMR (125 MHz, CDCl3), keto
tautomer: δ = 52.52 (CH3), 52.73 (CH), 68.20 (CH2), 117.95 (CH), 120.52 (C), 121.87 (CH), 127.64 (CH), 136.43 (CH), 161.43 (C), 167.68 (C), 186.85 (C) ppm; enol tautomer: δ = 51.69 (CH3), 63.80 (CH2), 91.78 (C), 116.48 (CH), 118.27 (C), 121.49 (CH), 124.58 (CH), 124.59 (C), 133.11 (CH), 157.73 (C), 162.81 (C) ppm. The data were in accordance with literature values.[S7]
S8
2.3 Preparation of enol esters 4b-e OAc Me O Me
(1.0-2.0 equiv.) R
conc. H2SO4 (0.8 mol%)
OAc R
General procedure B (GPB): The compounds were prepared according to the method of Hagemeyer and Hull.[S8] Isopropenyl acetate (4a) (1.0 to 2.0 equiv.) was heated to reflux with the ketone (1.0 equiv.) in the presence of 0.8 mol% of conc. sulfuric acid. The acetone formed was distilled off continuously. Afterwards the residue was purified by distillation or by column chromatography to give the corresponding enol esters 4.
1-Phenylvinyl acetate (4b)
According to GPB a mixture of acetophenone (12.0 g, 100 mmol), isopropenyl acetate (10.0 g, 100 mmol) and four drops of conc. sulfuric acid was heated to reflux for 18 h to yield the title compound 4b (7.95 g, 49.1 mmol, 49%) after distillation as a colorless oil, b.p. 71°C at 1.3 mbar. 1H NMR (500 MHz, CDCl3): δ = 2.28 (s, 3H), 5.03 (d, J = 2.2 Hz, 1H), 5.49 (d, J = 2.2 Hz, 1H), 7.30–7.39 (m, 3H), 7.44–7.50 (m, 2H) ppm.
13
C{1H} NMR (125 MHz, CDCl3): δ = 20.79 (CH3), 101.98 (CH2), 124.70 (2 CH),
128.38 (2 CH), 128.80 (CH), 134.09 (C), 152.79 (C), 168.92 (C) ppm. The data were in accordance with literature values.[S9]
1-(4'-Nitrophenyl)vinyl acetate (4c)
According to GPB a mixture of 4'-nitroacetophenone (1.65 g, 10.0 mmol), isopropenyl acetate (2.01 g, 20.0 mmol) and four drops of conc. sulfuric acid was heated to reflux for 3 d to yield the title compound 4c (915 mg, 4.42 mmol, 44%) after chromatography (hexanes/MTBE 1:1, Rf = 0.41) as a colorless oil. 1H NMR (500 MHz, CDCl3): S9
δ = 2.30 (s, 3H), 5.25 (d, J = 2.6 Hz, 1H), 5.65 (d, J = 2.6 Hz, 1H), 7.60–7.63 (m, 2H), 8.19–8.22 (m, 2H) ppm.
13
C{1H} NMR (125 MHz, CDCl3): δ = 20.88 (CH3), 106.06
(CH2), 123.87 (2 CH), 125.65 (2 CH), 140.43 (C), 147.81 (C), 150.94 (C), 168.74 (C) ppm. The data were in accordance with literature values.[S10]
1-(4'-Methoxyphenyl)vinyl acetate (4d)
According to GPB a mixture of 4'-methoxyacetophenone (15.0 g, 100 mmol), isopropenyl acetate (10.0 g, 100 mmol) and five drops of conc. sulfuric acid was heated to reflux for 24 h to yield the title compound 4d (8.86 g, 46.1 mmol, 46%) after chromatography (hexanes/MTBE 2:1, Rf = 0.40) as a colorless solid, mp. 76°C. 1H NMR (500 MHz, CDCl3): δ = 2.27 (s, 3H), 3.81 (s, 3H), 4.92 (d, J = 2.2 Hz, 1H), 5.36 (d, J = 2.2 Hz, 1H), 6.86–6.88 (m, 2H), 7.38–7.41 (m, 2H) ppm.
13
C{1H} NMR (125 MHz,
CDCl3): δ = 20.99 (CH3), 55.29 (CH3), 113.88 (CH2), 126.26 (2 CH), 126.82 (C), 152.69 (C), 160.14 (C), 169.12 (C) ppm. The data were in accordance with literature values.[S10]
2-Acetoxy-3,3-dimethyl-1-butene (4e)
According to the GPB a mixture of 3,3-dimethylbutan-2-one (10.0 g, 100 mmol), isopropenyl acetate (11.0 g, 110 mmol) and four drops of conc. sulfuric acid was heated to reflux for 16 h to yield the title compound 4e (2.01 g, 14.1 mmol, 14%) after column chromatography (hexanes/MTBE 2:1, Rf = 0.36) as a colorless liquid. 1H NMR (500 MHz, CDCl3): δ = 1.07 (s, 9H), 2.15 (s, 3H), 4.61 (d, J = 2.1 Hz, 1H), 4.85 (d, J = 2.2 Hz, 1H) ppm.
13
C{1H} NMR (125 MHz, CDCl3): δ = 21.02 (CH3), 27.70 (3 CH3),
36.00 (C), 99.01 (CH2), 162.49 (C), 169.11 (C) ppm. The data were in accor-dance with literature values.[S11]
S10
2.4 Cerium-catalyzed synthesis of 1,4-diketones 3aa–3jb O2 (air)
O CO2R3
R1 R2
1x
OAc
2.5 mol% CeCl3 . 7 H2O
R
TFE, 40-50 °C, 16-18 h
+
4y 1.3-5.0 equiv.
O
O
R
R1 R2 CO2R3 3xy
General procedure C (GPC): CeCl3 · 7 H2O (2.5 mol%) was added to a mixture of oxo ester 1x (1.0 equiv.) and enol ester 4y (1.3 to 5.0 equiv.) in 2,2,2-trifluoroethanol (TFE, ca. 1 L/mol β-oxo ester), and the reaction mixture was stirred at 40–50°C for 16–18 h under an atmospheric of air. After removal of all volatile materials in vacuo, the residue was chromatographed on SiO2 to yield the 1,4-diketones 3xy. Ethyl 2-oxo-1-(2-oxopropyl)cyclopentane-1-carboxylate (3aa)
According to GPC CeCl3 · 7 H2O (12 mg, 32 µmol) was added to a mixture of β-oxo ester 1a (200 mg, 1.28 mmol) and enol ester 4a (641 mg, 6.40 mmol, 5 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 50°C for 18 h. Purification by column chromatography [SiO2, hexanes/MTBE 3:1 → 1:1, Rf(1:1) = 0.31] gave the title compound 3aa (142 mg, 675 µmol, 53%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.20 (t, J = 7.1 Hz, 3H), 1.97–2.04 (m, 2H), 2.06–2.12 (m, 1H), 2.10 (s, 3H), 2.41–2.47 (m, 2H), 2.50–2.54 (m, 1H), 2.92 (d, J = 18.6 Hz, 1H), 3.17 (d, J = 18.6 Hz, 1H), 4.11 (q, J = 7.1 Hz, 2H) ppm.
13
C{1H} NMR (125 MHz, CDCl3): δ =
14.04 (CH3), 19.87 (CH2), 30.04 (CH3), 33.32 (CH2), 37.69 (CH2), 47.56 (CH2), 57.49 (C), 61.68 (CH2), 170.62 (C), 205.36 (C), 214.78 (C) ppm. The data were in accordance with literature values.[S12]
S11
Ethyl 2-oxo-1-(2-oxo-2-phenylethyl)cyclopentane-1-carboxylate (3ab)
According to GPC CeCl3 · 7 H2O (12 mg, 32 µmol) was added to a mixture of β-oxo ester 1a (201 mg, 1.28 mmol) and enol ester 4b (415 mg, 2.56 mmol, 2 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 40°C for 18 h. Purification by column chromatography (SiO2, hexanes/MTBE 2:1, Rf = 0.28) gave the title compound 3ab (127 mg, 462 µmol, 36%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.21 (t, J = 7.1 Hz, 3H), 2.04–2.20 (m, 3H), 2.47–2.53 (m, 1H), 2.56–2.66 (m, 2H), 3.46 (d, J = 18.5 Hz, 1H), 3.83 (d, J = 18.5 Hz, 1H), 4.15 (q, J = 7.1 Hz, 2H), 7.42–7.45 (m, 2H), 7.53–7.57 (m, 1H), 7.91–7.93 (m, 2H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 13.97 (CH3), 19.82 (CH2), 33.37 (CH2), 37.71 (CH2), 43.44 (CH2), 57.44 (C), 61.61 (CH2), 127.99 (2 CH), 128.60 (2 CH), 133.42 (CH), 136.29 (C), 170.65 (C), 196.69 (C), 215.00 (C) ppm. The data were in accordance with literature values.[S13]
Ethyl 2-oxo-1-[2-oxo-2-(4-nitrophenyl)ethyl]cyclopentane-1-carboxylate (3ac)
According to GPC CeCl3 · 7 H2O (12 mg, 32 µmol) was added to a mixture of β-oxo ester 1a (156 mg, 1.00 mmol) and enol ester 4c (269 mg, 1.30 mmol, 1.3 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 50°C for 18 h. Purification by column chromatography (SiO2, hexanes/MTBE 1:1, Rf = 0.30) gave the title compound 3ac (61 mg, 191 µmol, 19%) as a light yellow oil. 1H NMR (500 MHz, CDCl3): δ = 1.23 (t, J = 7.1 Hz, 3H), 2.08–2.15 (m, 2H), 2.19–2.24 (m, 1H), 2.55–2.59 (m, 2H), 2.67–2.70 (m, 1H), 3.45 (d, J = 18.6 Hz, 1H), 3.85 (d, J = 18.6 Hz, 1H), 4.15–4.21 (m, 2H), 8.09–8.12 (m, 2H), 8.30–8.33 (m, 2H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 13.99 (CH3), 19.82 (CH2), 33.39 (CH2), 37.62 (CH2), 43.68 (CH2), 57.49 (C), 61.88 (CH2), 123.89 (2 CH), 129.09 (2 CH), 140.70 (C), 150.49 (C), 170.38 (C), 195.39 (C), 214.58 (C) ppm. IR (ATR): λ–1 = 2961 (w), 2023 (m), 1752 (s), 1723 (vs), 1695 (s),
S12
1528 (s), 1404 (w), 1346 (s), 1217 (m), 1166 (m), 1021 (m), 855 (m), 747 (w) cm–1. HRMS (ESI): calcd. 342.0948 (for C16H17NNaO6+); found 342.0950 [M+Na+]. Ethyl 2-oxo-1-[2-oxo-2-(4-methoxyphenyl)ethyl]cyclopentane-1-carboxylate (3ad)
According to GPC CeCl3 · 7 H2O (12 mg, 32 µmol) was added to a mixture of β-oxo ester 1a (199 mg, 1.28 mmol) and enol ester 4d (320 mg, 1.66 mmol, 1.3 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 50°C for 17 h. Purification by column chromatography (SiO2, hexanes/MTBE 2:1, Rf = 0.17) gave the title compound 3ad (70 mg, 219 µmol, 17%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.22 (t, J = 7.1 Hz, 3H), 2.04–2.19 (m, 3H), 2.42–2.53 (m, 1H), 2.57–2.65 (m, 2H), 3.43 (d, J = 18.3 Hz, 1H), 3.78 (d, J = 18.3 Hz, 1H), 3.85 (s, 3H), 4.15 (q, J = 7.1 Hz, 2H), 6.89–6.92 (m, 2H), 7.89–7.92 (m, 2H) ppm.
13
C{1H} NMR (125 MHz, CDCl3): δ =
13.95 (CH3), 19.80 (CH2), 33.39 (CH2), 37.73 (CH2), 43.14 (CH2), 55.44 (CH3), 57.45 (C), 61.55 (CH2), 113.71 (2 CH), 129.40 (C), 130.28 (2 CH), 163.68 (C), 170.79 (C), 195.14 (C), 215.20 (C) ppm. The data were in accordance with literature values.[S13]
Ethyl 2-oxo-1-(2-oxopropyl)cyclohexane-1-carboxylate (3ba)
According to GPC CeCl3 · 7 H2O (12 mg, 32 µmol) was added to a mixture of β-oxo ester 1b (218 mg, 1.28 mmol) and enol ester 4a (641 mg, 6.40 mmol, 5 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 50°C for 18 h. Purification by column chromatography [SiO2, hexanes/MTBE 3:1 → 1:1, Rf(1:1) = 0.37] gave the title compound 3ba (77 mg, 340 µmol, 27%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.24 (t, J = 7.1 Hz, 3H), 1.64–1.74 (m, 4H), 1.97–2.03 (m, 1H), 2.15 (s, 3H), 2.32–2.36 (m, 1H), 2.42–2.46 (m, 1H), 2.73–2.80 (m, 1H), 2.80 (d, J = 17.1 Hz, 1H), 2.85 (d, J = 17.1 Hz, 1H), 4.14–4.24 (m, 2H) ppm.
13
C{1H} NMR (125 MHz,
CDCl3): δ = 14.08 (CH3), 22.06 (CH2), 26.94 (CH2), 30.43 (CH3), 36.80 (CH2), 40.59 S13
(CH2), 48.23 (CH2), 59.37 (C), 61.60 (CH2), 171.99 (C), 205.53 (C), 207.48 (C) ppm. The data were in accordance with literature values.[S14]
Ethyl 2-oxo-1-(2-oxo-2-phenylethyl)cyclohexane-1-carboxylate (3bb)
According to GPC CeCl3 · 7 H2O (12 mg, 32 µmol) was added to a mixture of β-oxo ester 1b (217 mg, 1.28 mmol) and enol ester 4b (415 mg, 2.56 mmol, 2 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 50°C for 17 h. Purification by column chromatography [SiO2, hexanes/MTBE 3:1 → 1:1, Rf(1:1) = 0.41] gave the title compound 3bb (171 mg, 593 µmol, 46%) as a colorless solid, mp. 89°C. 1H NMR (500 MHz, CDCl3): δ = 1.25 (t, J = 7.1 Hz, 3H), 1.74–1.85 (m, 4H), 2.04–2.09 (m, 1H), 2.44–2.48 (m, 1H), 2.49–2.54 (m, 1H), 2.83 (ddd, J = 14.5 Hz, J = 12.9 Hz, J = 6.4 Hz, 1H), 3.37 (d, J = 17.4 Hz, 1H), 3.55 (d, J = 17.4 Hz, 1H), 4.17–4.27 (m, 2H), 7.42–7.45 (m, 2H), 7.52–7.56 (m, 1H), 7.93–7.95 (m, 2H) ppm.
13
C{1H} NMR (125
MHz, CDCl3): δ = 13.98 (CH3), 21.95 (CH2), 26.75 (CH2), 36.67 (CH2), 40.47 (CH2), 43.94 (CH2), 58.84 (C), 61.45 (CH2), 127.97 (2 CH), 128.45 (2 CH), 133.03 (CH), 136.74 (C), 171.95 (C), 196.89 (C), 207.22 (C) ppm. The data were in accordance with literature values.[S15]
Methyl 2-oxo-1-(2-oxopropyl)cycloheptane-1-carboxylate (3ca)
According to GPC CeCl3 · 7 H2O (12 mg, 32 µmol) was added to a mixture of β-oxo ester 1c (219 mg, 1.28 mmol) and enol ester 4a (642 mg, 6.40 mmol, 5 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 50°C for 18 h. Purification by column chromatography [SiO2, hexanes/MTBE 3:1 → 1:1, Rf(1:1) = 0.34] gave the title compound 3ca (81 mg, 358 µmol, 28%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.24–1.31 (m, 1H), 1.47–1.59 (m, 2H), 1.65–1.76 (m, 2H), 1.80–1.86 (m, 1H), 2.00 (ddd, J = 15.0 Hz, J = 9.9 Hz, J = 1.4 Hz, 1H), 2.16 (ddd, J = 15.0 Hz, J = 9.7 Hz, J = 1.2 Hz, 1H), 2.17 (s, 3H), 2.53 (ddd, J = 12.4 Hz, J = 8.4 Hz, J = 2.4 Hz, S14
1H), 2.73 (d, J = 17.4 Hz, 1H), 2.83 (ddd, J = 12.5 Hz, J = 10.9 Hz, J = 2.7 Hz, 1H), 3.16 (d, J = 17.4 Hz, 1H), 3.71 (s, 3H) ppm.
13
C{1H} NMR (125 MHz, CDCl3): δ =
24.95 (CH2), 26.31 (CH2), 30.38 (CH3), 30.43 (CH2), 33.62 (CH2), 41.99 (CH2), 48.50 (CH2), 52.57 (CH3), 61.62 (C), 172.64 (C), 205.80 (C), 209.30 (C) ppm. The data were in accordance with literature values.[S16]
Methyl 2-oxo-1-(2-oxo-2-phenylethyl)cycloheptan-1-carboxylate (3cb)
According to GPC CeCl3 · 7 H2O (12 mg, 32 µmol) was added to a mixture of β-oxo ester 1c (218 mg, 1.28 mmol) and enol ester 4b (311 mg, 1.92 mmol, 1.5 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 50°C for 16 h. Purification by column chromatography [SiO2, hexanes/MTBE 3:1 → 2:1, Rf(2:1) = 0.26] gave the title compound 3cb (164 mg, 571 µmol, 45%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.29 (dt, J = 13.8 Hz, J = 9.8 Hz, 1H), 1.48–1.61 (m, 2H), 1.66–1.75 (m, 2H), 1.78–1.87 (m, 1H), 2.10 (dd, J = 15.1 Hz, J = 9.4 Hz, 1H), 2.29 (dd, J = 15.1 Hz, J = 10.2 Hz, 1H), 2.56 (ddd, J = 12.3 Hz, J = 8.3 Hz, J = 2.4 Hz, 1H), 2.87 (ddd, J = 13.6 Hz, J = 11.0 Hz, J = 2.7 Hz, 1H), 3.26 (d, J = 17.7 Hz, 1H), 3.70 (s, 3H), 3.84 (d, J = 17.7 Hz, 1H), 7.40–7.45 (m, 2H), 7.51–7.54 (m, 1H), 7.92–7.95 (m, 2H) ppm. 13
C{1H} NMR (125 MHz, CDCl3): δ = 24.70 (CH2), 26.11 (CH2), 30.23 (CH2), 32.95
(CH2), 41.56 (CH2), 43.80 (CH2), 52.37 (CH3), 61.38 (C), 127.89 (2 CH), 128.42 (2 CH), 133.06 (CH), 136.54 (C), 172.34 (C), 197.14 (C), 208.87 (C) ppm. The data were in accordance with literature values.[S17]
Methyl 2-(2-oxopropyl)-1-indanone-2-carboxylate (3da)
According to GPC CeCl3 · 7 H2O (15 mg, 40 µmol) was added to a mixture of β-oxo ester 1d (300 mg, 1.58 mmol) and enol ester 4a (317 mg, 3.16 mmol, 2 equiv.) in TFE (1.2 ml), and the reaction mixture was stirred at 50°C for 18 h. Purification by co-
S15
lumn chromatography (SiO2, hexanes/MTBE 1:1, Rf = 0.20) gave the title compound 3da (345 mg, 1.40 mmol, 89%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 2.18 (s, 3H), 2.81 (d, J = 18.4 Hz, 1H), 3.07 (d, J = 17.6 Hz, 1H), 3.57 (d, J = 18.4 Hz, 1H), 3.63 (s, 3H), 3.94 (d, J = 17.6 Hz, 1H), 7.38 (t, J = 7.5 Hz, 1H), 7.47 (d, J = 7.7 Hz, 1H), 7.62 (td, J = 7.5 Hz, J = 1.2 Hz, 1H), 7.75 (d, J = 7.6 Hz, 1H) ppm.
13
C{1H}
NMR (125 MHz, CDCl3): δ = 29.88 (CH3), 37.86 (CH2), 47.89 (CH2), 52.89 (CH3), 58.14 (C), 124.76 (CH), 126.34 (CH), 127.67 (CH), 134.57 (C), 135.46 (CH), 153.56 (C), 170.21 (C), 201.31 (C), 205.33 (C) ppm. IR (ATR): λ–1 = 2955 (w), 1708 (vs), 1608 (w), 1434 (w), 1364 (w), 1284 (m), 1203 (m), 1169 (s), 1082 (w), 925 (m), 748 (m), 690 (w) cm–1. HRMS (ESI): calcd. 247.0966 (for C14H15O4+); found 247.0977 [M+H+].
Methyl 2-(2-oxo-2-phenylethyl)-1-indanone-2-carboxylate (3db)
According to GPC CeCl3 · 7 H2O (15 mg, 40 µmol) was added to a mixture of β-oxo ester 1d (228 mg, 1.20 mmol) and enol ester 4b (389 mg, 2.40 mmol) in TFE (1 ml), and the reaction mixture was stirred at 50°C for 18 h. Purification by column chromatography (SiO2, hexanes/MTBE 2:1, Rf = 0.27) gave the title compound 3db (304 mg, 0.99 mmol, 82%) as a colorless solid, mp. 131°C. 1H NMR (500 MHz, CDCl3): δ = 3.12 (d, J = 17.6 Hz, 1H), 3.40 (d, J = 18.3 Hz, 1H), 3.65 (s, 3H), 4.07 (d, J = 17.6 Hz, 1H), 4.20 (d, J = 18.4 Hz, 1H), 7.39–7.46 (m, 3H), 7.50 (d, J = 7.7 Hz, 1H), 7.54–7.58 (m, 1H), 7.62–7.65 (m, 1H), 7.80 (d, J = 7.7 Hz, 1H), 7.94–7.96 (m, 2H) ppm.
13
C{1H}
NMR (125 MHz, CDCl3): δ = 38.04 (CH2), 43.89 (CH2), 52.94 (CH3), 58.17 (C), 124.73 (CH), 126.36 (CH), 127.66 (CH), 128.01 (2 CH), 128.58 (2 CH), 133.47 (CH), 134.65 (C), 135.46 (CH), 136.04 (C), 153.61 (C), 170.29 (C), 196.76 (C), 201.55 (C) ppm. The data were in accordance with literature values.[S18]
S16
Methyl 2-[2-oxo-2-(4-nitrophenyl)ethyl]-1-indanone-2-carboxylate (3dc)
According to GPC CeCl3 · 7 H2O (7 mg, 20 µmol) was added to a mixture of β-oxo ester 1d (150 mg, 0.79 mmol) and enol ester 4c (246 mg, 1.19 mmol, 1.5 equiv.) in TFE (0.6 ml), and the reaction mixture was stirred at 40°C for 17 h. Purification by twofold column chromatography (SiO2; 1. hexanes/MTBE 2:1, Rf = 0.27; 2. DCM, Rf = 0.43) gave the title compound 3dc (159 mg, 0.45 mmol, 57%) as a colorless solid, mp. 117°C. 1H NMR (500 MHz, CDCl3): δ = 3.16 (d, J = 17.6 Hz, 1H), 3.39 (d, J = 18.5 Hz, 1H), 3.65 (s, 3H), 4.05 (d, J = 17.6 Hz, 1H), 4.21 (d, J = 18.5 Hz, 1H), 7.42 (td, J = 7.7 Hz, J = 1.0 Hz, 1H), 7.50–7.52 (m, 1H), 7.65 (td, J = 7.4 Hz, J = 1.2 Hz, 1H), 7.79 (d, J = 7.7 Hz, 1H), 8.10–8.13 (m, 2H), 8.28–8.30 (m, 2H) ppm.
13
C{1H}
NMR (125 MHz, CDCl3): δ = 37.92 (CH2), 44.07 (CH2), 53.08 (CH3), 58.06 (C), 123.84 (2 CH), 124.85 (CH), 126.38 (CH), 127.84 (CH), 129.12 (2 CH), 134.50 (C), 135.69 (CH), 140.47 (C), 150.47 (C), 153.48 (C), 170.08 (C), 195.59 (C), 201.08 (C) ppm. IR (ATR): λ–1 = 3081 (w), 2956 (w), 1741 (s), 1712 (vs), 1698 (s), 1607 (m), 1527 (s), 1438 (w), 1346 (s), 1277 (m), 1244 (m), 1210 (s), 1037 (w), 856 (m), 746 (m) cm–1. HRMS (ESI): calcd. 354.0972 (for C19H16NO6+); found 354.0989 [M+H+]. Methyl 2-[2-oxo-2-(4-methoxyphenyl)ethyl]-1-indanone-2-carboxylate (3dd)
According to GPC CeCl3 · 7 H2O (11 mg, 32 µmol) was added to a mixture of β-oxo ester 1d (243 mg, 1.28 mmol) and enol ester 4d (369 mg, 1.92 mmol, 1.5 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 40°C for 17 h. Purification by column chromatography (SiO2, hexanes/MTBE/CHCl3 2:1:1, Rf = 0.26) gave the title compound 3dd (195 mg, 0.58 mmol, 45%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 3.12 (d, J = 17.6 Hz, 1H), 3.37 (d, J = 18.2 Hz, 1H), 3.66 (s, 3H), 3.85 (s, S17
3H), 4.06 (d, J = 17.6 Hz, 1H), 4.14 (d, J = 18.2 Hz, 1H), 6.90–6.93 (m, 2H), 7.38–7.42 (m, 1H), 7.49 (dt, J = 7.8 Hz, J = 1.0 Hz, 1H), 7.63 (td, J = 7.5 Hz, J = 1.2 Hz, 1H), 7.80 (d, J = 7.7 Hz, 1H), 7.91–7.94 (m, 2H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 38.12 (CH2), 43.64 (CH2), 52.94 (CH3), 55.44 (CH3), 58.27 (C), 113.74 (2 CH), 124.73 (CH), 126.37 (CH), 127.63 (CH), 129.22 (C), 130.35 (2 CH), 134.76 (C), 135.42 (CH), 153.67 (C), 163.75 (C), 170.43 (C), 195.21 (C), 201.75 (C) ppm. IR (ATR): λ–1 = 2952 (w), 1742 (s), 1711 (s), 1676 (s), 1601 (vs), 1511 (w), 1261 (m), 1227 (m), 1172 (s), 1029 (w), 832 (w), 758 (w) cm–1. HRMS (ESI): calcd. 339.1227 (for C20H19O5+); found 339.1214 [M+H+].
Methyl 2-(3,3-dimethyl-2-oxobutyl)-1-indanone-2-carboxylate (3de) O
O
tBu
CO2Me
According to GPC CeCl3 · 7 H2O (8 mg, 20 µmol) was added to a mixture of β-oxo ester 1d (154 mg, 0.81 mmol) and enol ester 4e (150 mg, 1.05 mmol, 1.3 equiv.) in TFE (0.7 ml), and the reaction mixture was stirred at 45°C for 18 h. Purification by column chromatography (SiO2, hexanes/MTBE 1:1, Rf = 0.47) gave the title compound 3de (18 mg, 62 µmol, 8%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.17 (s, 9H), 2.90 (d, J = 18.5 Hz, 1H), 2.96 (d, J = 17.6 Hz, 1H), 3.64 (s, 3H), 3.71 (d, J = 18.6 Hz, 1H), 3.98 (d, J = 17.6 Hz, 1H), 7.40 (t, J = 7.3 Hz, 1H), 7.48 (d, J = 7.7 Hz, 1H), 7.63 (td, J = 7.4 Hz, J = 1.2 Hz, 1H), 7.78 (d, J = 7.7 Hz, 1H) ppm.
13
C{1H} NMR (125
MHz, CDCl3): δ = 26.47 (2 CH3), 38.16 (CH2), 42.46 (CH2), 44.05 (C), 52.90 (CH3), 58.15 (C), 124.79 (CH), 126.38 (CH), 127.68 (CH), 134.73 (C), 135.45 (CH), 153.62 (C), 170.35 (C), 201.78 (C), 213.27 (C) ppm. IR (ATR): λ–1 = 2958 (w), 2929 (w), 1743 (s), 1709 (vs), 1608 (w), 1464 (w), 1284 (w), 1210 (w), 1178 (w), 1068 (w), 759 (w) cm– 1
. HRMS (ESI): calcd. 289.1434 (for C17H21O4+); found 289.1439 [M+H+].
S18
Methyl 5,6-dimethoxy-2-(2-oxopropyl)-1-indanone-2-carboxylate (3ea)
According to GPC CeCl3 · 7 H2O (7 mg, 20 µmol) was added to a mixture of β-oxo ester 1e (200 mg, 0.80 mmol) and enol ester 4a (160 mg, 1.60 mmol, 2 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 40°C for 18 h. Purification by twofold column chromatography (SiO2; 1. MTBE, Rf = 0.31; 2. DCM/MeOH 20:1, Rf = 0.44) gave the title compound 3ea (107 mg, 349 µmol, 44%) as a colorless solid, mp. 129°C. 1H NMR (500 MHz, CDCl3): δ = 2.14 (s, 3H), 2.69 (d, J = 18.4 Hz, 1H), 2.92 (d, J = 17.4 Hz, 1H), 3.55 (d, J = 18.4 Hz, 1H), 3.60 (s, 3H), 3.83 (d, J = 17.4 Hz, 1H), 3.84 (s, 3H), 3.93 (s, 3H), 6.85 (s, 1H), 7.10 (s, 1H) ppm.
13
C{1H} NMR (125 MHz,
CDCl3): δ = 29.85 (CH3), 37.52 (CH2), 47.85 (CH2), 52.76 (CH3), 55.95 (CH3), 56.18 (CH3), 58.39 (C), 104.76 (CH), 107.08 (CH), 126.85 (C), 149.25 (C), 149.59 (C), 156.13 (C), 170.38 (C), 199.59 (C), 205.59 (C) ppm. IR (ATR): λ–1 = 2953 (w), 1737 (s), 1696 (vs), 1591 (m), 1503 (s), 1464 (m), 1314 (vs), 1271 (vs), 1221 (m), 1113 (m), 1043 (m), 867 (w), 734 (w) cm–1. HRMS (ESI): calcd. 307.1176 (for C16H19O6+); found 307.1176 [M+H+].
Methyl 5,6-dimethoxy-2-(2-oxo-2-phenylethyl)-1-indanone-2-carboxylate (3eb)
According to GPC CeCl3 · 7 H2O (8 mg, 21 µmol) was added to a mixture of β-oxo ester 1e (200 mg, 0.80 mmol) and enol ester 4b (194 mg, 1.20 mmol, 1.5 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 40°C for 16 h. Purification by column chromatography (SiO2, DCM/EtOAc 2:1, Rf = 0.27) gave the title compound 3eb (279 mg, 0.76 mmol, 95%) as a colorless solid, mp. 148°C. 1H NMR (500 MHz, CDCl3): δ = 3.00 (d, J = 17.5 Hz, 1H), 3.30 (d, J = 18.5 Hz, 1H), 3.65 (s, 3H), 3.89 (s, 3H), 3.96 (s, 3H), 3.99 (d, J = 17.5 Hz, 1H), 4.20 (d, J = 18.3 Hz, 1H), 6.90 (s, 1H), 7.18 (s, 1H), 7.42–7.45 (m, 2H), 7.53–7.56 (m, 1H), 7.93–7.97 (m, 2H) ppm. S19
13
C{1H}
NMR (125 MHz, CDCl3): δ = 37.81 (CH2), 43.91 (CH2), 52.87 (CH3), 56.02 (CH3), 56.23 (CH3), 58.56 (C), 104.87 (CH), 107.17 (CH), 127.08 (C), 127.99 (2 CH), 128.56 (2 CH), 133.40 (CH), 136.12 (C), 149.35 (C), 149.65 (C), 156.18 (C), 170.53 (C), 197.00 (C), 199.84 (C) ppm. IR (ATR): λ–1 = 3080 (w), 2924 (w), 2839 (w), 1727 (m), 1691 (vs), 1589 (s), 1471 (m), 1453 (m), 1433 (m), 1318 (vs), 1264 (s), 1040 (m), 911 (m), 794 (w), 762 (s), 707 (w) cm–1. HRMS (ESI): calcd. 391.1152 (for C21H20NaO6+); found 391.1166 [M+Na+].
Methyl 2-(2-oxopropyl)-6-trifluoromethyl-1-indanone-2-carboxylate (3fa)
CeCl3 · 7 H2O (5 mg, 13 µmol) was added to a mixture of β-oxo ester 1f (150 mg, 0.58 mmol) and enol ester 4a (116 mg, 1.16 mmol, 2 equiv.) in TFE (0.5 ml), and the reaction mixture was stirred at 50°C for 18 h. All volatile materials were removed in vacuo. Purification by column chromatography (SiO2, MTBE, Rf = 0.48) gave a mixture of the title compound 3fa and the respective α-hydroxylated product. This mixture was treated with Ac2O (310 mg, 3.01 mmol), DMAP (13 mg, 107 µmol) and Et3N (111 mg, 1.10 mmol) in DCM (2 ml) and stirred at ambient temperature for 2 d. Purification by column chromatography (SiO2, MTBE, Rf = 0.51) gave the title compound 3fa (121 mg, 385 µmol, 66%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 2.18 (s, 3H), 3.01 (d, J = 18.7 Hz, 1H), 3.14 (d, J = 17.9 Hz, 1H), 3.55 (d, J = 18.6 Hz, 1H), 3.64 (s, 3H), 3.92 (d, J = 17.8 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.85 (dd, J = 8.1 Hz, J = 1.7 Hz, 1H), 8.01 (d, J = 1.8 Hz, 1H) ppm.
13
C{1H} NMR (125 MHz, CDCl3): δ =
29.74 (CH3), 37.87 (CH2), 47.73 (CH2), 53.09 (CH3), 58.34 (C), 121.91 (q, 3JCF = 3.9 Hz, CH), 123.63 (q, 1JCF = 272.5 Hz, CF3), 127.05 (CH), 130.55 (q, 2JCF = 33.1 Hz, C), 131.71 (q, 3JCF = 3.5 Hz, CH), 135.32 (C), 156.54 (C), 169.76 (C), 200.19 (C), 205.14 (C) ppm.
19
F{1H} NMR (470 MHz, CDCl3): δ = –62.54 (s, CF3) ppm. IR (ATR):
λ–1 = 2924 (w), 1747 (m), 1718 (vs), 1626 (m), 1331 (m), 1256 (m), 1169 (m), 1125 (s), 1058 (w), 898 (w), 842 (w) cm–1. HRMS (ESI): calcd. 337.0658 (for C15H13F3NaO4+); found 337.0669 [M+Na+].
S20
Methyl 2-(2-oxo-2-phenylethyl)-6-trifluoromethyl-1-indanone-2-carboxylate (3fb)
According to GPC CeCl3 · 7 H2O (5 mg, 13 µmol) was added to a mixture of β-oxo ester 1f (150 mg, 0.58 mmol) and enol ester 4b (188 mg, 1.16 mmol, 2 equiv.) in TFE (0.5 ml), and the reaction mixture was stirred at 40°C for 18 h. Purification by column chromatography (SiO2, DCM/hexanes 2:1, Rf = 0.32) gave the title compound 3fb (155 mg, 412 µmol, 71%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 3.20 (d, J = 17.8 Hz, 1H), 3.61 (d, J = 18.5 Hz, 1H), 3.67 (s, 3H), 4.04 (d, J = 17.8 Hz, 1H), 4.17 (d, J = 18.5 Hz, 1H), 7.44–7.48 (m, 2H), 7.58 (tt, J = 7.6 Hz, J = 1.3 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.88 (dd, J = 8.0 Hz, J = 1.7 Hz, 1H), 7.94–7.97 (m, 2H), 8.07–8.09 (m, 1H) ppm.
13
C{1H} NMR (125 MHz, CDCl3): δ = 38.09 (CH2), 43.75 (CH2), 53.19
(CH3), 58.43 (C), 121.94 (q, 3JCF = 4.2 Hz, CH), 123.66 (q, 1JCF = 272.5 Hz, CF3), 127.09 (CH), 128.09 (2 CH), 128.71 (2 CH), 130.52 (q, 2JCF = 33.0 Hz, C), 131.72 (q, 3
JCF = 4.0 Hz, CH), 133.72 (CH), 135.50 (C), 135.84 (C), 156.58 (C), 169.97 (C),
196.59 (C), 200.46 (C) ppm.
19
F{1H} NMR (470 MHz, CDCl3): δ = –62.48 (s, CF3)
ppm. IR (ATR): λ–1 = 3061 (w), 2957 (w), 1747 (s), 1719 (vs), 1685 (s), 1626 (m), 1450 (w), 1330 (s), 1257 (m), 1203 (m), 1180 (m), 1125 (vs), 1058 (m), 908 (w), 754 (m) cm–1. HRMS (ESI): calcd. 399.0815 (for C20H15F3NaO4+); found 399.0814 [M+Na+].
Methyl 4-bromo-2-(2-oxopropyl)-1-indanone-2-carboxylate (3ga)
According to GPC CeCl3 · 7 H2O (7 mg, 19 µmol) was added to a mixture of β-oxo ester 1g (200 mg, 0.74 mmol) and enol ester 4a (149 mg, 1.49 mmol, 2 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 45°C for 18 h. Purification by column chromatography (SiO2, hexanes/MTBE 1:1, Rf = 0.34) gave the title compound 3ga (138 mg, 424 µmol, 57%) as a colorless solid, mp. 108°C. 1H NMR (500 MHz, CDCl3): δ = 2.17 (s, 3H), 2.94 (d, J = 18.6 Hz, 1H), 2.97 (d, J = 18.0 Hz, 1H), 3.52 (d, J = 18.6 S21
Hz, 1H), 3.63 (s, 3H), 3.82 (d, J = 18.0 Hz, 1H), 7.29 (tt, J = 7.6 Hz, J = 0.8 Hz, 1H), 7.69 (dd, J = 7.6 Hz, J = 1.0 Hz, 1H), 7.77 (dd, J = 7.7 Hz, J = 1.0 Hz, 1H) ppm. 13
C{1H} NMR (125 MHz, CDCl3): δ = 29.73 (CH3), 38.89 (CH2), 47.86 (CH2), 53.05
(CH3), 57.93 (C), 121.73 (C), 123.46 (CH), 129.41 (CH), 136.67 (C), 138.10 (CH), 152.99 (C), 169.79 (C), 200.69 (C), 205.06 (C) ppm. IR (ATR): λ–1 = 2954 (w), 1745 (m), 1714 (vs), 1598 (w), 1457 (w), 1259 (m), 1201 (w), 1169 (m), 1083 (w), 933 (w), 781 (m), 735 (w) cm–1. HRMS (ESI): calcd. 325.0070 (for C14H14BrO4+); found 325.0086 [M+H+].
Methyl 4-bromo-2-(2-oxo-2-phenylethyl)-1-indanone-2-carboxylate (3gb)
According to GPC CeCl3 · 7 H2O (7 mg, 19 µmol) was added to a mixture of β-oxo ester 1g (201 mg, 0.74 mmol) and enol ester 4b (241 mg, 1.49 mmol, 2 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 45°C for 18 h. Purification by column chromatography (SiO2, DCM, Rf = 0.48) gave the title compound 3gb (189 mg, 488 µmol, 66%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 3.05 (d, J = 18.0 Hz, 1H), 3.54 (d, J = 18.5 Hz, 1H), 3.68 (s, 3H), 3.95 (d, J = 18.0 Hz, 1H), 4.17 (d, J = 18.5 Hz, 1H), 7.33 (t, J = 7.7 Hz, 1H), 7.44–7.48 (m, 2H), 7.58 (tt, J = 7.4 Hz, J = 1.3 Hz, 1H), 7.77 (dd, J = 7.6 Hz, J = 0.9 Hz, 1H), 7.81 (dd, J = 7.7 Hz, J = 0.9 Hz, 1H), 7.95–7.97 (m, 2H) ppm.
13
C{1H} NMR (125 MHz, CDCl3): δ = 39.16 (CH2), 43.90
(CH2), 53.15 (CH3), 58.11 (C), 121.83 (C), 123.52 (CH), 128.10 (2 CH), 128.67 (2 CH), 129.46 (CH), 133.64 (CH), 135.90 (C), 136.92 (C), 138.13 (CH), 153.09 (C), 170.02 (C), 196.51 (C), 200.97 (C) ppm. IR (ATR): λ–1 = 3068 (w), 2954 (w), 1745 (s), 1717 (vs), 1684 (s), 1597 (m), 1449 (m), 1355 (w), 1260 (m), 1221 (m), 1201 (m), 1179 (m), 1121 (m), 1038 (w), 782 (w), 757 (m) cm–1. HRMS (ESI): calcd. 387.0226 (for C19H16BrO4+); found 387.0234 [M+H+].
S22
Ethyl 2-(2-oxopropyl)-1-tetralone-2-carboxylate (3ha)
According to GPC CeCl3 · 7 H2O (11 mg, 30 µmol) was added to a mixture of β-oxo ester 1h (262 mg, 1.20 mmol) and enol ester 4a (239 mg, 2.40 mmol, 2 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 50°C for 18 h. Purification by column chromatography (SiO2, hexanes/MTBE 1:1, Rf = 0.27) gave the title compound 3ha (54 mg, 197 µmol, 17%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 1.13 (t, J = 7.1 Hz, 3H), 2.22 (s, 3H), 2.42 (ddd, J = 13.5 Hz, J = 5.1 Hz, J = 4.1 Hz, 1H), 2.47 (ddd, J = 13.8 Hz, J = 11.4 Hz, J = 4.8 Hz, 1H), 2.87 (dt, J = 17.3 Hz, J = 4.4 Hz, 1H), 2.99 (d, J = 17.4 Hz, 1H), 3.05 (ddd, J = 16.9 Hz, J = 11.5 Hz, J = 5.5 Hz, 1H), 3.08 (d, J = 17.4 Hz, 1H), 4.10–4.19 (m, 2H), 7.20 (d, J = 7.7 Hz, 1H), 7.30 (t, J = 7.6 Hz, 1H), 7.45 (td, J = 7.5 Hz, J = 1.4 Hz, 1H), 8.01 (dd, J = 7.9 Hz, J = 1.4 Hz, 1H) ppm.
13
C{1H} NMR
(125 MHz, CDCl3): δ = 13.85 (CH3), 26.06 (CH2), 30.45 (CH3), 31.78 (CH2), 47.29 (CH2), 56.27 (C), 61.52 (CH2), 126.71 (CH), 127.80 (CH), 128.55 (CH), 132.09 (C), 133.33 (CH), 142.80 (C), 171.68 (C), 194.89 (C), 205.12 (C) ppm. IR (ATR): λ–1 = 2982 (w), 1721 (vs), 1701 (vs), 1601 (m), 1455 (m), 1240 (m), 1225 (m), 1183 (m), 1166 (m), 1022 (w), 918 (w), 745 (m) cm–1. HRMS (ESI): calcd. 275.1278 (for C16H19O4+); found 275.1276 [M+H+]. The compound was reported in literature, but insufficiently characterized.[S19]
Ethyl 2-(2-oxo-2-phenylethyl)-1-tetralone-2-carboxylate (3hb)
According to GPC CeCl3 · 7 H2O (11 mg, 30 µmol) was added to a mixture of β-oxo ester 1h (261 mg, 1.20 mmol) and enol ester 4b (292 mg, 1.80 mmol, 1.5 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 40°C for 18 h. Purification by column chromatography (SiO2, hexanes/MTBE 2:1 → 1:1, Rf(1:1) = 0.43) gave the title compound 3hb (279 mg, 0.83 mmol, 69%) as a pale yellow oil. 1H NMR (500 MHz, CDCl3): δ = 1.16 (t, J = 7.1 Hz, 3H), 2.52 (ddd, J = 13.6 Hz, J = 4.8 Hz, J = 4.0 Hz, 1H), 2.62 (ddd, J = 13.5 Hz, J = 11.6 Hz, J = 4.7 Hz, 1H), 2.91 (dt, J = 17.2 Hz, J = S23
4.4 Hz, 1H), 3.14 (ddd, J = 16.8 Hz, J = 11.6 Hz, J = 4.9 Hz, 1H), 3.64 (d, J = 17.6 Hz, 1H), 3.71 (d, J = 17.6 Hz, 1H), 4.15–4.24 (m, 2H), 7.23 (d, J = 7.7 Hz, 1H), 7.32 (t, J = 7.6 Hz, 1H), 7.43–7.49 (m, 3H), 7.54–7.57 (m, 1H), 7.96–7.98 (m, 2H), 8.07 (dd, J = 7.9 Hz, J = 1.4 Hz, 1H) ppm.
13
C{1H} NMR (125 MHz, CDCl3): δ = 13.91
(CH3), 26.14 (CH2), 31.63 (CH2), 43.15 (CH2), 56.01 (C), 61.56 (CH2), 126.74 (CH), 127.91 (CH), 128.04 (2 CH), 128.50 (2 CH), 128.58 (CH), 132.19 (C), 133.14 (CH), 133.33 (CH), 136.68 (C), 142.82 (C), 171.89 (C), 194.85 (C), 196.52 (C) ppm. IR (ATR): λ–1 = 3060 (w), 2981 (w), 1728 (s), 1682 (vs), 1599 (m), 1449 (m), 1232 (m), 1210 (m), 1181 (m), 1017 (m), 743 (m), 690 (m) cm–1. HRMS (ESI): calcd. 337.1434 (for C21H21O4+); found 337.1431 [M+H+]. Ethyl 2-[2-oxo-2-(4-methoxyphenyl)ethyl]-1-tetralone-2-carboxylate (3hd)
According to GPC CeCl3 · 7 H2O (12 mg, 30 µmol) was added to a mixture of β-oxo ester 1h (279 mg, 1.28 mmol) and enol ester 4d (369 mg, 1.92 mmol, 2 equiv.) in TFE (1 ml), and the reaction mixture was stirred at 40°C for 18 h. Purification by column chromatography (SiO2, DCM/MeOH 20:1, Rf = 0.68) gave the title compound 3hd (169 mg, 461 µmol, 36%) as a yellow oil. 1H NMR (500 MHz, CDCl3): δ = 1.15 (t, J = 7.1 Hz, 3H), 2.50 (dt, J = 13.5 Hz, J = 4.5 Hz, 1H), 2.62 (ddd, J = 13.5 Hz, J = 11.6 Hz, J = 4.7 Hz, 1H), 2.90 (dt, J = 17.2 Hz, J = 4.4 Hz, 1H), 3.13 (ddd, J = 16.8 Hz, J = 11.6 Hz, J = 4.8 Hz, 1H), 3.61 (d, J = 17.5 Hz, 1H), 3.66 (d, J = 17.5 Hz, 1H), 3.84 (s, 3H), 4.13–4.23 (m, 2H), 6.90–6.93 (m, 2H), 7.22 (d, J = 7.6 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.46 (td, J = 7.5 Hz, J = 1.5 Hz, 1H), 7.92–7.95 (m, 2H), 8.06 (dd, J = 7.8 Hz, J = 1.4 Hz, 1H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 13.90 (CH3), 26.13 (CH2), 31.52 (CH2), 42.81 (CH2), 55.39 (CH3), 55.90 (C), 61.48 (CH2), 113.61 (2 CH), 126.69 (CH), 127.87 (CH), 128.56 (CH), 129.72 (C), 130.31 (2 CH), 132.20 (C), 133.25 (CH), 142.82 (C), 163.49 (C), 171.95 (C), 194.92 (C), 194.93 (C) ppm. IR (ATR): λ–1 = 2979 (w), 2936 (w), 1729 (s), 1678 (vs), 1560 (vs), 1509 (m), 1357 (m), 1260 (m), 1237 (m), 1170 (vs), 1021 (m), 836 (m), 743 (m) cm–1. HRMS (ESI): calcd. 389.1359 (for C22H22NaO5+); found 389.1357 [M+Na+]. S24
Methyl 6-methoxy-2-(2-oxopropyl)-1-tetralone-2-carboxylate (3ia)
CeCl3 · 7 H2O (8 mg, 20 µmol) was added to a mixture of β-oxo ester 1i (200 mg, 0.85 mmol) and enol ester 4a (171 mg, 1.71 mmol, 2 equiv.) in TFE (0.8 ml), and the reaction mixture was stirred at 50°C for 18 h. All volatile materials were removed in vacuo. Purification by column chromatography (SiO2, MTBE, Rf = 0.39) gave a mixture of the title compound 3ia and the respective α-hydroxylated product. This mixture was treated with Ac2O (749 mg, 7.27 mmol), DMAP (32 mg, 261 µmol) and Et3N (263 mg, 2.60 mmol) in DCM (5 ml) and stirred at ambient temperature for 2 d. Purification by column chromatography (SiO2, MTBE/hexanes 2:1, Rf = 0.19) gave the title compound 3ia (55 mg, 189 µmol, 22%) as a colorless solid, mp. 112°C. The NMR spectra show a residual amount of an impurity (see page S62). 1H NMR (500 MHz, CDCl3): δ = 2.22 (s, 3H), 2.43–2.46 (m, 2H), 2.82 (dt, J = 17.2 Hz, J = 4.4 Hz, 1H), 2.95–3.05 (m, 1H), 3.01 (d, J = 17.4 Hz, 1H), 3.06 (d, J = 17.4 Hz, 1H), 3.68 (s, 3H), 3.85 (s, 3H), 6.66 (d, J = 2.5 Hz, 1H), 6.83 (dd, J = 8.7 Hz, J = 2.6 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 26.52 (CH3), 30.54 (CH2), 31.79 (CH2), 47.46 (CH2), 52.63 (CH3), 55.43 (CH3), 56.14 (C), 112.47 (CH), 113.42 (CH), 125.46 (C), 130.49 (CH), 145.51 (C), 163.68 (C), 172.43 (C), 193.42 (C), 205.29 (C) ppm. IR (ATR): λ–1 = 2954 (w), 2845 (w), 1736 (s), 1680 (m), 1601 (vs), 1355 (w), 1257 (s), 1225 (m), 1030 (w), 839 (w) cm–1. HRMS (ESI): calcd. 291.1227 (for C16H19O5+); found 291.1228 [M+H+]. The compound was reported in literature, but insufficiently characterized.[S20]
Methyl 6-methoxy-2-(2-oxo-2-phenylethyl)-1-tetralone-2-carboxylate (3ib)
According to GPC CeCl3 · 7 H2O (8 mg, 20 µmol) was added to a mixture of β-oxo ester 1i (201 mg, 0.85 mmol) and enol ester 4b (207 mg, 1.28 mmol, 1.5 equiv.) in TFE (0.8 ml), and the reaction mixture was stirred at 40°C for 17 h. Purification by S25
column chromatography (SiO2, MTBE/hexanes 2:1, Rf = 0.40) gave the title compound 3ib (168 mg, 477 µmol, 56%) as a colorless solid, mp. 141°C. 1H NMR (500 MHz, CDCl3): δ = 2.51 (dt, J = 13.4 Hz, J = 4.6 Hz, 1H), 2.58 (ddd, J = 13.4 Hz, J = 11.3 Hz, J = 4.6 Hz, 1H), 2.85 (dt, J = 17.2 Hz, J = 4.4 Hz, 1H), 3.11 (ddd, J = 16.7 Hz, J = 11.3 Hz, J = 4.4 Hz, 1H), 3.60 (d, J = 17.6 Hz, 1H), 3.71 (d, J = 17.6 Hz, 1H), 3.71 (s, 3H), 3.83 (s, 3H), 6.68 (d, J = 2.5 Hz, 1H), 6.84 (dd, J = 8.8 Hz, J = 2.6 Hz, 1H), 7.41–7.45 (m, 2H), 7.53–7.56 (m, 1H), 7.94–7.98 (m, 2H), 8.03 (d, J = 8.8 Hz, 1H) ppm.
13
C{1H} NMR (125 MHz, CDCl3): δ = 26.49 (CH3), 31.53 (CH2), 43.19 (CH2),
52.55 (C), 55.35 (CH3), 55.78 (CH3), 112.43 (CH), 113.37 (CH), 125.47 (C), 127.99 (2 CH), 128.45 (2 CH), 130.45 (CH), 133.09 (CH), 136.63 (C), 145.46 (C), 163.60 (C), 172.50 (C), 193.27 (C), 196.56 (C) ppm. IR (ATR): λ–1 = 3061 (w), 2949 (w), 1732 (s), 1676 (s), 1598 (vs), 1448 (m), 1255 (s), 1213 (s), 1030 (w), 755 (m), 690 (m) cm–1. HRMS (ESI): calcd. 353.1384 (for C21H21O5+); found 353.1381 [M+H+]. Methyl 3-(2-oxopropyl)-4-chromanone-3-carboxylate (3ja)
CeCl3 · 7 H2O (8 mg, 20 µmol) was added to a mixture of β-oxo ester 1j (170 mg, 0.82 mmol) and enol ester 4a (165 mg, 1.65 mmol, 2 equiv.) in TFE (0.8 ml), and the reaction mixture was stirred at 50°C for 18 h. All volatile materials were removed in vacuo. Purification by column chromatography (SiO2, hexanes/MTBE 3:2, Rf = 0.33) gave a mixture of the title compound 3ja and the respective α-hydroxylated product. This mixture was treated with Ac2O (202 mg, 1.96 mmol), DMAP (9 mg, 70 µmol) and Et3N (71 mg, 0.70 mmol) in DCM (2 ml) and stirred at ambient temperature for 2 d. Purification by column chromatography (SiO2, hexanes/MTBE 4:2, Rf = 0.18) gave the title compound 3ja (134 mg, 0.51 mmol, 62%) as a colorless oil. 1H NMR (500 MHz, CDCl3): δ = 2.21 (s, 3H), 3.01 (s, 2H), 3.73 (s, 3H), 4.73 (d, J = 11.5 Hz, 1H), 4.79 (d, J = 11.5 Hz, 1H), 6.97 (dd, J = 8.4 Hz, J = 1.0 Hz, 1H), 7.04 (ddd, J = 8.1 Hz, J = 7.2 Hz, J = 1.1 Hz, 1H), 7.49 (ddd, J = 8.6 Hz, J = 7.2 Hz, J = 1.8 Hz, 1H), 7.89 (dd, J = 7.9 Hz, J = 1.8 Hz, 1H) ppm.
13
C{1H} NMR (125 MHz, CDCl3): δ = 30.31 (CH3), 42.16 (CH2),
52.92 (CH2), 55.47 (C), 71.03 (CH2), 117.79 (CH), 119.88 (C), 121.92 (CH), 127.90 (CH), 136.23 (CH), 161.15 (C), 169.45 (C), 189.07 (C), 204.34 (C) ppm. IR (ATR): λ–1 S26
= 2954 (w), 1737 (s), 1693 (vs), 1606 (vs), 1479 (s), 1466 (s), 1302 (m), 1230 (m), 1217 (m), 1039 (m), 1019 (m), 761 (m), 642 (w) cm–1. HRMS (ESI): calcd. 263.0914 (for C14H15O5+); found 263.0915 [M+H+]. Methyl 3-(2-oxo-2-phenylethyl)-4-chromanone-3-carboxylate (3jb)
According to GPC CeCl3 · 7 H2O (8 mg, 20 µmol) was added to a mixture of β-oxo ester 1j (170 mg, 0.82 mmol) and enol ester 4b (200 mg, 1.23 mmol, 1.5 equiv.) in TFE (0.8 ml), and the reaction mixture was stirred at 40°C for 18 h. Purification by column chromatography (SiO2, hexanes/MTBE/CHCl3 2:1:1, Rf = 0.46) gave the title compound 3jb (205 mg, 0.63 mmol, 77%) as a colorless solid, mp. 132°C. 1H NMR (500 MHz, CDCl3): δ = 3.55 (d, J = 17.9 Hz, 1H), 3.66 (d, J = 18.0 Hz, 1H), 3.76 (s, 3H), 4.84 (d, J = 11.6 Hz, 1H), 4.93 (d, J = 11.6 Hz, 1H), 6.99 (dd, J = 8.3 Hz, J = 1.0 Hz, 1H), 7.07 (ddd, J = 8.1 Hz, J = 7.2 Hz, J = 1.8 Hz, 1H), 7.42–7.47 (m, 2H), 7.51 (ddd, J = 8.7 Hz, J = 7.2 Hz, J = 1.8 Hz, 1H), 7.55–7.59 (m, 1H9, 7.92–7.96 (m, 3H) ppm. 13C{1H} NMR (125 MHz, CDCl3): δ = 38.16 (CH2), 52.91 (CH3), 55.30 (C), 71.08 (CH2), 117.84 (CH), 119.94 (C), 121.93 (CH), 127.98 (CH), 128.06 (2 CH), 128.62 (2 CH), 133.55 (CH), 136.13 (C), 136.24 (CH), 161.17 (C), 169.55 (C), 189.20 (C), 195.21 (C) ppm. IR (ATR): λ–1 = 2961 (w), 2917 (w), 1731 (s), 1687 (vs), 1605 (m), 1463 (m), 1297 (vs), 1148 (m), 1113 (m), 1020 (m), 833 (m), 758 (s), 735 (m) cm–1. HRMS (ESI): calcd. 325.1071 (for C19H17O5+); found 325.1067 [M+H+]. 3.
References
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W. Yang, X. Sun, W. Yu, R. Rai, J. R. Deschamps, L. A. Mitchell, C. Jiang, A. D. MacKerell, F. Xue, Org. Lett. 2015, 17, 3070–3073.
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[S10] L. Panella, B. L. Feringa, J. D. de Vries, A. J. Minnaard, Org. Lett. 2005, 7, 4177–4180. [S11] T. M. Konrad, P. Schmitz, W. Leitner, G. Francio, Chem. Eur. J. 2013, 19, 13299–13303. [S12] a) Y. Hori, T. Mitsudo, Y. Watanabe, J. Organomet. Chem. 1987, 321, 397– 408; b) D. K. Klipa, H. Hart, J. Org. Chem. 1981, 46, 2815–2816. [S13] R. Pflantz, P. Tielmann, M. Rössle, C. Hoenke, J. Christoffers, Eur. J. Org. Chem. 2007, 3227–3238. [S14] J. Christoffers, T. Werner, S. Unger, W. Frey, Eur. J. Org. Chem. 2003, 425– 431. [S15] P.-H. Chiu, M. P. Sammes, Tetrahedron 1990, 46, 3439–3456. [S16] E. Polo, R. M. Bellabarba, G. Prini, O. Traverso, M. L. H. Green, J. Organomet. Chem. 1999, 577, 211–218. [S17] M. Rössle, T. Werner, W. Frey, J. Christoffers, Eur. J. Org. Chem. 2005, 5031–5038. [S18] F. Behler, F. Habecker, W. Saak, T. Klüner, J. Christoffers, Eur. J. Org. Chem. 2011, 4231–4240. [S19] E. Brown, M. Ragault, J. Touet, Bull. Soc. Chim. Fr. 1971, 2195–2203. [S20] R. E. Juday, B. Bukwa, K. Kaiser, G. Webb, J. Med. Chem. 1970, 13, 314– 317.
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4.
NMR Spectra
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