Anodic Cyclization of Dimethyl 2-(3-Oxo-3-arylpropyl) Malonates into the Corresponding Dimethyl 2-Aroylcyclopropane-1,1-dicarboxylates

Mitsuhiro Okimoto; Haruki Yamamori; Kousuke Ohashi; Masayuki Hoshi; Takashi Yoshida

doi:10.1055/s-0033-1339198

Synlett, Table of Contents

Synlett 2013; 24(12): 1568-1572
DOI: 10.1055/s-0033-1339198

letter

Anodic Cyclization of Dimethyl 2-(3-Oxo-3-arylpropyl) Malonates into the Corresponding Dimethyl 2-Aroylcyclopropane-1,1-dicarboxylates

Mitsuhiro Okimoto*

Department of Biotechnology and Environmental Chemistry, Kitami Institute of Technology, 165 Koen-cho, Kitami, Hokkaido 090-8507, Japan Fax: +81(0157)24-7719 Email: okimotmt@mail.kitami-it.ac.jp

,

Haruki Yamamori

Department of Biotechnology and Environmental Chemistry, Kitami Institute of Technology, 165 Koen-cho, Kitami, Hokkaido 090-8507, Japan Fax: +81(0157)24-7719 Email: okimotmt@mail.kitami-it.ac.jp

,

Kousuke Ohashi

Department of Biotechnology and Environmental Chemistry, Kitami Institute of Technology, 165 Koen-cho, Kitami, Hokkaido 090-8507, Japan Fax: +81(0157)24-7719 Email: okimotmt@mail.kitami-it.ac.jp

,

Masayuki Hoshi

Department of Biotechnology and Environmental Chemistry, Kitami Institute of Technology, 165 Koen-cho, Kitami, Hokkaido 090-8507, Japan Fax: +81(0157)24-7719 Email: okimotmt@mail.kitami-it.ac.jp

,

Takashi Yoshida

Department of Biotechnology and Environmental Chemistry, Kitami Institute of Technology, 165 Koen-cho, Kitami, Hokkaido 090-8507, Japan Fax: +81(0157)24-7719 Email: okimotmt@mail.kitami-it.ac.jp

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Abstract

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Abstract

A variety of dimethyl 2-(3-oxo-3-arylpropyl)malonates were electrooxidized in methanol, in the presence of potassium iodide and a base or a neutral salt, to give the corresponding cyclized dimethyl 2-aroylcyclopropane-1,1-dicarboxylates in moderate to good yields. The reactions were carried out under extremely mild reaction conditions, in which the optimal amount of electrolytic current varied from 2.12–2.41 F·mol^–1 depending on the substrates. The reaction presumably proceeds via a two-electron oxidation process, in which iodide ions play an important role as the electron carrier between the anode and the substrate.

Key words

oxidation - electron transfer - radicals - cyclization - substituent effects - ring closure - green chemistry - iodine

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References

References and Notes

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8 General Procedures3-Bromo-1-arylpropan-1-ones were prepared via typical Friedel–Crafts acylation,⁹ using commercially available 3-bromopropionyl chloride and aromatic compounds in the presence of AlCl₃ at <45 °C. Dimethyl 2-(3-oxo-3-arylpropyl)malonates 1 were prepared by mixing the corresponding bromo aryl ketone and dimethyl malonate with a slight excess (1.1 equiv) of NaOMe in MeOH for ca. 40 min at r.t.¹⁰ Preparative-scale electrooxidations were carried out in a tall 50 mL beaker equipped with a fine frit cup as the cathode compartment with a nickel coil cathode, along with a cylindrical platinum net anode (height: 35 mm, diameter: 30 mm, 50 mesh).Typical ProceduresA solution of dimethyl 2-(3-oxo-3-benzoylpropyl)malonates 1a (1.32 g, 5 mmol) in MeOH (40 mL) containing KI (0.83 g, 5.0 mmol) and NaOMe (2.0 mmol) was electrooxidized under a constant current (0.3 A) at ca. 15 °C with magnetic stirring. During the course of the electrooxidation, the composition of the reaction mixture was monitored using GC and/or TLC analyses. Passage of the electric current was maintained until the formation of the product was no longer detected. The reaction mixture was concentrated in vacuo at approximately 50 °C to near dryness. The resulting residue was treated with brine (ca. 30 mL), then extracted with Et₂O (3 × 50 mL). The combined ether solution was washed with Na₂S₂O₃ aq solution (15 wt%, 30 mL), and dried overnight over Na₂SO₄. After removal of the solvent in vacuo, the crude product was purified using silica gel column chromatography (height, 300 mm; diameter, 15 mm) with CH₂Cl₂ as the eluent to afford product 2a as a viscous oil (0.96 g, 72%). The electrooxidation products were characterized using HRMS, IR, ¹H NMR, and ¹³C NMR spectroscopy.Dimethyl 2-Benzoylcyclopropane-1,1-dicarboxylate (2a)Yield 0.94 g (72%); colorless, cubic crystals, mp 25–27 °C (from MeOH); R_f = 0.58 (silica gel; Et₂O–n-hexane, 2:1). IR (neat): 2955, 1738 (vs), 1732 (vs), 1681 (vs), 1597, 1436, 1336, 1276, 1212, 1132, 704 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.79 (dd, J = 8.5, 4.1 Hz, 1 H, CH), 2.22 (dd, J = 6.9 4.4 Hz, 1 H, CH), 3.57 (dd, J = 8.0, 7.9 Hz, 1 H, CH), 3.69 (s, 3 H, CH₃O), 3.80 (s, 3 H, CH₃O), 7.45–7.53 (m, 3 H, arom.), 7.97–8.30 (m, 2 H, arom.). ¹³C NMR (100 MHz, CDCl₃): δ = 21.09 (CH₂), 31.00 (CH), 39.03 (C), 52.85 (CH₃), 53.31 (CH₃), 128.40 (CH), 128.71 (CH), 133.60 (CH), 137.00 (C), 166.47 (CO), 169.47 (CO), 194.79 (CO). MS (EI, 70 eV): m/z (%) = 262 [M⁺] (2), 231 [M⁺ – CH₃O] (46), 230 (68), 203 [M⁺ – CO₂CH₃] (24), 202 (63), 171 (19), 144 [M⁺ – 2 × CO₂CH₃] (9), 106 (19), 105 [C₆H₅CO] (100), 77 [C₆H₅] (53). HRMS: m/z [M⁺] calcd for C₁₄H₁₄O₅: 262.0841; found: 262.0802.Dimethyl 2-(4-Methylbenzoyl)cyclopropane-1,1-dicarboxylate (2b)Yield 0.99 g (72%); colorless, fine cubic crystals, mp 91–93 °C (from MeOH); R_f = 0.62 (silica gel; Et₂O–n-hexane, 2:1). IR (KBr): 2953, 1746 (vs), 1732 (vs), 1665 (vs), 1294, 1234, 1220, 1199, 1184, 963 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.77 (dd, J = 8.7, 4.4 Hz, 1 H, CH), 2.21 (dd, J = 6.9, 4.4 Hz, 1 H, CH), 2.42 (s, 3 H, CH₃), 3.55 (dd, J = 8.7, 6.8 Hz, 1 H, CH), 3.69 (s, 3 H, CH₃O), 3.81 (s, 3 H, CH₃O), 7.28 (d, J = 8.3 Hz, 2 H, arom.), 7.90 (d, J = 8.3 Hz, 2 H, arom.). ¹³C NMR (100 MHz, CDCl₃): δ = 21.11 (CH₂), 21.72 (CH₃), 30.95 (CH), 38.86 (C), 52.85 (CH₃), 53.29 (CH₃), 128.54 (CH), 129.38 (CH), 134.51 (C), 144.56 (C), 166.56 (CO), 169.61 (CO), 194.29 (CO). MS (EI, 70 eV): m/z (%) = 276 [M⁺] (16), 245 [M⁺ – CH₃O] (44), 244 (65), 217 [M⁺ – CO₂CH₃] (21), 216 (63), 185 (21), 158 [M⁺ – 2 × CO₂CH₃] (10), 120 (26), 119 [CH₃C₆H₄CO] (100), 91 [CH₃C₆H₄] (68). HRMS: m/z [M⁺] calcd for C₁₅H₁₆O₅: 276.0998; found: 276.1001.Dimethyl 2-(3,4-dimethylbenzoyl)cyclopropane-1,1-dicarboxylate (2c)Yield 1.10 g (76%); colorless, fine cubic crystals, mp 65–67 °C (from MeOH); R_f = 0.60 (silica gel; Et₂O–n-hexane, 2:1). IR (KBr): 2954, 1757 (vs), 1741 (vs), 1662 (vs), 1438, 1279, 1245, 1212 (vs), 1166, 1138 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.76 (dd, J = 8.7, 4.4 Hz, 1 H, CH), 2.19 (dd, J = 6.9, 4.1 Hz, 1 H, CH), 2.32 (br s, 6 H, 2 × CH₃), 3.55 (dd, J = 8.7, 7.1 Hz, 1 H, CH), 3.69 (s, 3 H, CH₃O), 3.80 (s, 3 H, CH₃O), 7.18–7.30 (m, 1 H, arom.), 7.70–7.82 (m, 2 H, arom.). ¹³C NMR (100 MHz, CDCl₃): δ = 19.77 (CH₃), 20.08 (CH₃), 21.17 (CH₂), 30.92 (CH), 38.87 (C), 52.81 (CH₃), 53.25 (CH₃), 126.23 (CH), 129.43 (CH), 129.92 (CH), 134.91 (C), 137.09 (C), 143.31 (C), 166.57 (CO), 169.64 (CO), 194.46 (CO). MS (EI, 70 eV): m/z (%) = 290 [M⁺] (33), 259 [M⁺ – CH₃O] (26), 258 (33), 231 [M⁺ – CO₂CH₃] (14), 230 (41), 199 (17), 172 [M⁺ – 2 × CO₂CH₃] (8), 134 (24), 133 [(CH₃)₂C₆H₃CO] (100), 105 [(CH₃)₂C₆H₃] (34). HRMS: m/z [M⁺] calcd for C₁₆H₁₈O₅: 290.1154; found: 290.1149.Dimethyl 2-(4-Methoxybenzoyl)cyclopropane-1,1-dicarboxylate (2d)Yield 1.12 g (77%); colorless, fine cubic crystals, mp 59–61 °C (from MeOH); R_f = 0.46 (silica gel; Et₂O–n-hexane, 2:1). IR (KBr): 2954, 1737 (vs), 1732 (vs), 1667 (vs), 1599 , 1265, 1237 , 1214 , 1171 (vs), 1131, 1025 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.75 (dd, J = 8.4, 4.1 Hz, 1 H, CH), 2.20 (dd, J = 6.9, 4.1 Hz, 1 H, CH), 3.53 (dd, J = 8.7, 6.8 Hz, 1 H, CH), 3.69 (s, 3 H, CH₃O), 3.80 (s, 3 H, CH₃O), 3.87 (s, 3 H, CH₃O), 6.95 (d, J = 8.8 Hz, 2 H, arom.), 7.99 (d, J = 8.8 Hz, 2 H, arom.). ¹³C NMR (100 MHz, CDCl₃): δ = 20.98 (CH₂), 30.80 (CH), 38.68 (C), 52.81 (CH₃), 53.26 (CH₃), 55.53 (CH₃), 113.88 (CH), 130.04 (CH), 130.79 (C), 163.97 (C), 166.61 (CO), 169.66 (CO), 192.93 (CO). MS (EI, 70 eV): m/z (%) = 292 [M⁺] (36), 261 [M⁺ – CH₃O] (24), 260 (18), 232 (30), 201 (19), 174 [M⁺ – 2 × CO₂CH₃] (8), 136 (24), 135 [CH₃OC₆H₄CO] (100), 107 [CH₃OC₆H₄] (19), 92 (20). HRMS: m/z [M⁺] calcd for C₁₅H₁₆O₆: 292.0947; found: 292.0943.Dimethyl 2-(2-Methoxy-5-methylbenzoyl)cyclopropane-1,1-dicarboxylate (2e)Yield 0.95 g (62%); colorless, fine cubic crystals, mp 89–91 °C (from MeOH); R_f = 0.49 (silica gel; Et₂O–n-hexane, 2:1). IR (KBr): 2952, 1734 (vs), 1668 (vs), 1497 , 1437, 1285 1252 (vs), 1212, 1168, 1131 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.74 (dd, J = 8.7, 4.3 Hz, 1 H, CH), 2.20 (dd, J = 7.1, 4.2 Hz, 1 H, CH), 2.29 (s, 3 H, CH₃), 3.69 (dd, J = 8.5, 7.1 Hz, 1 H, CH), 3.71 (s, 3 H, CH₃O), 3.78 (s, 3 H, CH₃O), 3.87 (s, 3 H, CH₃O), 6.87–6.90 (m, H, arom.), 7.26–7.46 (m, 2 H, arom.). ¹³C NMR (100 MHz, CDCl₃): δ = 20.21 (CH₃), 21.23 (CH₂), 35.70 (CH), 39.16 (C), 52.78 (CH₃), 53.05 (CH₃), 55.91 (CH₃), 111.8 (CH), 127.67 (C), 130.01(CH), 130.63 (C), 134.78 (CH), 157.19 (C), 166.86 (CO), 169.79 (CO), 196.72 (CO). MS (EI, 70 eV): m/z (%) = 306 [M⁺] (19), 275 [M⁺ – CH₃O] (13), 243 (7), 236 (9), 162 (46), 161 (13), 150 (18), 149 [CH₃, CH₃OC₆H₃CO] (100), 106 [CH₃OC₆H₃] (9), 91 (21). HRMS: m/z [M⁺] calcd for C₁₆H₁₈O₆: 306.1103; found: 306.1111.Dimethyl 2-(2-methyl-5-bromobenzoyl)cyclopropane-1,1-dicarboxylate (2f)Yield 1.03 g (58%); colorless, fine cubic crystals, mp 92–94 °C (from MeOH); R_f = 0.61 (silica gel; Et₂O–n-hexane, 2:1). IR (KBr): 2953, 1744 (vs), 1728 (vs), 1666 (vs), 1436, 1295 (vs), 1220, 1184, 1145, 963 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.77 (dd, J = 8.5, 4.1 Hz, 1 H, CH), 2.22 (dd, J = 6.8, 4.1 Hz, 1 H, CH), 2.43 (s, 3 H, CH₃), 3.55 (dd, J = 8.7, 6.9 Hz, 1 H, CH₎, 3.69 (s, 3 H, CH₃O), 3.80 (s, 3 H, CH₃O), 7.26–7.31 (m, 1 H, arom.), 7.65–7.93 (m, 2 H, arom.). ¹³C NMR (100 MHz, CDCl₃): δ = 21.12 (CH₂), 21.72 (CH₃), 30.95 (CH), 38.86 (C), 52.85 (CH₃), 53.29 (CH₃), 127.14 (C), 128.55 (CH), 129.38 (CH), 130.37 (CH), 134.51 (C), 144.56 (C), 166.56 (CO), 169.61 (CO), 194.29 (CO). MS (EI, 70 eV): m/z (%) = 356 [M⁺, ⁸¹Br] (13), 354 [M⁺, ⁷⁹Br] (13), 325 [M⁺, ⁸¹BrOCH₃] (17), 324 (27), 323 [M⁺, ⁷⁹BrOCH₃] (16), 322 (26), 297 [M⁺, ⁸¹BrCO₂CH₃] (10), 296 (37), 295 [M⁺, ⁷⁹BrCO₂CH₃] (11), 294 (38), 199 [⁸¹BrCH₃C₆H₃CO] (99), 197 [⁷⁹BrCH₃C₆H₃CO] (100), 171 [⁸¹BrCH₃C₆H₃] (24), 169 [⁷⁹BrCH₃C₆H₃] (22), 90 (21), 89 (17). HRMS: m/z [M⁺] calcd for C₁₅H₁₅ ⁸¹BrO₅: 356.0082; found: 356.0066. HRMS: m/z [M⁺] calcd for C₁₅H₁₅ ⁷⁹BrO₅: 354.0103; found: 354.0085. Dimethyl 2-(4-Fluorobenzoyl)cyclopropane-1,1-dicarboxylate (2g)Yield 1.02 g (73%); viscous oily liquid; R_f = 0.61 (silica gel; Et₂O–n-hexane, 2:1). IR (neat): 2955, 1737 (vs), 1732 (vs), 1678 (vs), 1598, 1508, 1437, 1276, 1216 (vs), 1157, 1131 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.79 (dd, J = 8.7, 4.4 Hz, 1 H, CH), 2.23 (dd, J = 6.9, 4.4 Hz, 1 H, CH), 3.52 (dd, J = 8.5, 6.7 Hz, 1 H, CH), 3.69 (s, 3 H, CH₃O), 3.81 (s, 3 H, CH₃O), 7.08–7.21 (m, 2 H, arom.), 7.99–8.08 (m, 2 H, arom.). ¹³C NMR (100 MHz, CDCl₃): δ = 21.03 (CH₂), 30.89 (CH), 39.05 (C), 52.92 (CH₃), 53.38 (CH₃), 115.90 (d, J _C–F = 88 Hz, CH), 131.15 (d, J _C–F = 38 Hz, CH), 133.43 (d, J _C–F = 12 Hz, C), 166.08 (d, J _C–F = 255 Hz, C), 166.41 (CO), 169.43 (CO), 193.18 (CO). MS (EI, 70 eV): m/z (%) = 280 [M⁺] (7), 249 [M⁺ – CH₃O] (38), 248 (59), 221 [M⁺ – CO₂CH₃] (28), 220 (65), 189 (28), 162 [M⁺ – 2 × CO₂CH₃] (17), 133 (24), 123 [FC₆H₄CO] (100), 95 [FC₆H₄] (48). HRMS: m/z [M⁺] calcd for C₁₄H₁₃FO₅: 280.0747; found: 280.0759.Dimethyl 2-(4-Chlorobenzoyl)cyclopropane-1,1-dicarboxylate (2h)Yield 0.79 g (53%); colorless, fine needle crystals, mp 58–60 °C (from MeOH); R_f = 0.65 (silica gel; Et₂O–n-hexane, 2:1). IR (neat): 2954, 1738 (vs), 1732 (vs), 1678 (vs), 1589, 1436, 1403, 1275, 1214 (vs), 1131, 1091 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.79 (dd, J = 8.7, 4.4 Hz, 1 H, CH), 2.23 (dd, J = 6.9, 4.4 Hz, 1 H, CH), 3.50 (dd, J = 8.7, 6.9 Hz, 1 H, CH), 3.68 (s, 3 H, CH₃O), 3.81 (s, 3 H, CH₃O), 7.46 (d, J = 8.7 Hz, 2 H, arom.), 7.94 (d, J = 8.7 Hz, 2 H, arom.). ¹³C NMR (100 MHz, CDCl₃): δ = 21.00 (CH₂), 30.90 (CH), 39.14 (C), 52.92 (CH₃), 53.38 (CH₃), 129.00 (C), 129.82 (CH), 135.37 (CH), 140.08 (C), 166.33 (CO), 169.39 (CO), 193.61 (CO). MS (EI, 70 eV): m/z (%) = 298 [M⁺,³⁷Cl] (4), 296 [M⁺, ³⁵Cl] (12), 267 [M⁺, ³⁷ClOCH₃ (15)], 266 (31), 265 [M⁺, ³⁵ClOCH₃] (44), 264 (56), 239 [M⁺, ³⁷ClCO₂CH₃] (9), 238 (32), 237 [M⁺, ³⁵ClCO₂CH₃] (27), 236 (67), 207 (8), 205 (23), 180 [M⁺, ³⁷Cl – 2 × CO₂CH₃] (5), 178 [M⁺, ³⁵Cl – 2 × CO₂CH₃] (15), 141 [³⁷ClC₆H₄CO] (56), 139 [³⁵ClC₆H₄CO], (100) 113 [³⁷ClC₆H₄] (28), 111 [³⁵ClC₆H₄] (53). HRMS: m/z [M⁺] calcd for C₁₄H₁₃ ³⁷ClO₅: 298.0422; found: 298.0409. HRMS: m/z [M⁺] calcd for C₁₄H₁₃ ³⁵ClO₅: 296.0452; found: 296.0435.Dimethyl 2-(4-Bromobenzoyl)cyclopropane-1,1-dicarboxylate (2i)Yield 1.26 g (74%); colorless, fine powder, mp 56–58 °C (from MeOH); R_f = 0.64 (silica gel; Et₂O–n-hexane, 2:1). IR (neat): 2954, 1733 (vs), 1677 (vs), 1585, 1439, 1334, 1276 (vs), 1215, 1131, 1070 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.79 (dd, J = 8.5, 4.4 Hz, 1 H, CH), 2.22 (dd, J = 6.9, 4.4 Hz, 1 H, CH), 3.49 (dd, J = 8.6, 6.9 Hz, 1 H, CH), 3.69 (s, 3 H, CH₃O), 3.81 (s, 3 H, CH₃O), 7.63 (d, J = 8.7 Hz, 2 H, arom.), 7.86 (d, J = 8.7 Hz, 2 H, arom.). ¹³C NMR (100 MHz, CDCl₃): δ = 21.01 (CH₂), 30.86 (CH), 39.13 (C), 52.92 (CH₃), 53.38 (CH₃), 128.90 (C), 129.89 (CH), 131.52 (CH), 135.68 (C), 166.28 (CO), 169.33 (CO), 193.77 (CO). MS (EI, 70 eV): m/z (%) = 342 [M⁺, ⁸¹Br] (33), 340 [M⁺, ⁷⁹Br] (34), 310 (59), 308 (58), 283 [M⁺, ⁸¹BrCO₂CH₃] (100), 282 (36), 281 [M⁺, ⁷⁹BrCO₂CH₃] (100), 280 (37), 251 (41), 249 (39), 224 [M⁺, ⁸¹Br – 2 × CO₂CH₃] (25), 222 [M⁺, ⁷⁹Br – 2 × CO₂CH₃] (25), 185 [⁸¹BrC₆H₄CO] (62), 183 [⁷⁹BrC₆H₄CO] (63), 157 [⁸¹BrC₆H₄] (28), 155 [⁷⁹BrC₆H₄] (27), 115 (30). HRMS: m/z [M⁺] calcd for C₁₄H₁₃ ⁸¹BrO₅: 341.9926; found: 341.9978. HRMS: m/z [M⁺] calcd for C₁₄H₁₃ ⁷⁹BrO₅: 339.9946; found: 339.9952.
9 Fuson RC, Walker JT. Org. Synth., Coll. Vol. II . John Wiley and Sons; New York: 1943: 169
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