Weinreb Amide Based Building Block for Convenient Access to Vinyl Ketones

Praveen Kumar Tiwari; Indrapal Singh Aidhen

doi:10.1055/s-0033-1338962

Synlett, Table of Contents

Synlett 2013; 24(14): 1777-1780
DOI: 10.1055/s-0033-1338962

letter

Weinreb Amide Based Building Block for Convenient Access to Vinyl Ketones

Praveen Kumar Tiwari

Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, India Fax: +91(44)22574202 Email: isingh@iitm.ac.in

,

Indrapal Singh Aidhen*

Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, India Fax: +91(44)22574202 Email: isingh@iitm.ac.in

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Abstract

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Abstract

A new strategy for the synthesis of vinyl ketones has been achieved. Hitherto unknown and easily accessible, β-phenylseleno-N-methoxy-N-methylpropanamide, obtained through two simple reactions, served as a building block for convenient access to vinyl ketones. The N-methoxy-N-methyl amide moiety ensured no overaddition of the Grignard reagent and, hence, the excellent formation of β-phenylseleno ketones; oxidative work-up with hydrogen peroxide provided ready access to the vinyl ketones with concomitant loss of phenylselanol.

Key words

Weinreb amide - selenoxide elimination - Grignard reaction - oxidation - vinyl ketone

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References

References and Notes

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For reviews on the applications of Weinreb amides, see:

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8 Preparation of compound 8: NaBH₄ (1.58 g, 41.5 mmol) was added portionwise to a stirred solution of diphenyldiselenide (5.97 g, 19.1 mmol) in absolute EtOH (100 mL) under nitrogen at 0 °C (addition of NaBH₄ was exothermic with rapid evolution of hydrogen gas). After complete addition of NaBH₄, within 15 min the reaction medium became colourless. When the evolution of hydrogen ceased, a solution of 12 (6.22 g, 31.9 mmol) in absolute EtOH (11 mL) was added dropwise at 0 °C. The reaction mixture was stirred over a period of 4 h and monitored by TLC. Upon completion of the reaction, brine (10 mL) was added and the solvent was evaporated under vacuum. The residue was dissolved in EtOAc (100 mL) and washed with H₂O (3 × 20 mL) and brine. The organic layer was separated, dried over Na₂SO₄, evaporated under vacuum and purified by silica gel column chromatography (EtOAc–hexane, 20%) to afford 8 8.67g (90%) as a pale-yellow liquid.

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11 Compound 8: Yield: 8.67 g (90%); R_f = 0.62 (hexane–EtOAc, 9:1). ¹H NMR (400 MHz, CDCl₃): δ = 2.86 (t, J = 7.6 Hz, 2 H, COCH₂), 3.18–3.15 (m, 5 H, SeCH₂, NCH₃), 3.61 (s, 3 H, OCH₃), 7.25–7.30 (m, 3 H, ArH), 7.52–7.55 (m, 2 H, ArH). ¹³C NMR (125 MHz, CDCl₃): δ = 21.7 (COCH₂), 32.2 (NCH₃), 33.0 (SeCH₂), 61.3 (OCH₃), 127.0 (ArCH), 129.1 (ArCH), 130.0 (ArC), 132.7 (ArCH), 172.9 (CO, amide). IR (CHCl₃): 2972, 2940, 2433, 2400, 2350, 1655, 1579, 1525, 1520, 1502 cm^–1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₁H₁₅NNaO₂Se: 296.0166; found: 296.0171.

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13 Preparation of Grignard Reagent and Synthesis of 9a–l; General Procedure: Grignard reagent was prepared from 1-bromooctane (1.92 g, 9.93 mmol) and magnesium (0.24 g, 9.93 mmol, activated with iodine/methyl iodide) in anhydrous THF (10 mL) at 55 °C. After complete consumption of magnesium, the solution was allowed to cool to r.t. and the resulting solution was slowly added to 8 (0.90 g, 3.31 mmol) dissolved in THF (3 mL) at −10 °C and stirring was continued for 2 h. Sat. NH₄Cl was added cautiously at 0 °C, and reaction mixture was extracted with EtOAc. The combined organic layers were dried over anhydrous Na₂SO₄, concentrated, and purified by silica gel column chromatography (EtOAc–hexane, 2%), which afforded 9a (0.77 g, 72%) as a yellow liquid. R_f = 0.65 (hexane–EtOAc, 9.5:0.5). ¹H NMR (500 MHz, CDCl₃): δ = 0.87 (t, J = 7.0 Hz, 3 H, CH₃), 1.25–1.30 (m, 10 H), 1.52–1.57 (m, 2 H, CH₂), 2.36 (t, J = 7.5 Hz, 2 H, CH₂), 2.81 (t, J = 7.5 Hz, 2 H, CH₂), 3.07 (t, J = 7.5 Hz, 2 H, CH₂), 7.24–7.28 (m, 3 H, ArH), 7.48–7.50 (m, 2 H, ArH). ¹³C NMR (125 MHz, CDCl₃): δ = 14.2 (CH₃), 20.7 (CH₂), 22.7 (CH₂), 23.8 (CH₂), 29.2 (CH₂), 29.3 (CH₂), 29.4 (CH₂), 31.9 (CH₂), 43.1 (CH₂), 43.2 (CH₂), 127.2 (ArCH), 129.2 (ArCH), 129.9 (ArC), 132.9 (ArCH), 209.7 (CH₂CO). IR (CHCl₃): 2929, 2856, 2400, 1712, 1579, 1524, 1477, 1438, 1375 cm^–1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₇H₂₆NaOSe: 349.1047; found: 349.1047.1-(Phenylselanyl)tetradecan-3-one (9b): Yield: 0.40 g (60%); yellow liquid; R_f = 0.64 (hexane–EtOAc, 9.5:0.5). ¹H NMR (400 MHz, CDCl₃): δ = 0.87 (t, J = 7.2 Hz, 3 H, CH₃), 1.24 (s, 16 H), 1.52–1.57 (m, 2 H, CH₂), 2.36 (t, J = 7.6 Hz, 2 H, CH₂), 2.81 (t, J = 7.2 Hz, 2 H, CH₂), 3.07 (t, J = 7.2 Hz, 2 H, CH₂), 7.24–7.28 (m, 3 H, ArH), 7.47–7.50 (m, 2 H, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 14.2 (CH₃), 20.7 (CH₂), 22.8 (CH₂), 23.8 (CH₂), 29.3 (CH₂), 29.4 (CH₂), 29.5 (CH₂), 29.6 (CH₂), 29.7 (CH₂), 32.0 (CH₂), 43.1 (CH₂), 43.2 (CH₂), 127.2 (ArCH), 129.2 (ArCH), 129.9 (ArC), 132.9 (ArCH), 209.7 (CH₂CO). IR (CHCl₃): 2928, 2875, 2401, 1711, 1581, 1524, 1473 cm^–1.1-Phenyl-3-(phenylselanyl)propan-1-one (9c): Yield: 1.92 g (72%); colourless solid; mp 61–63 °C; R_f = 0.65 (hexane–EtOAc, 9.5:0.5). ¹H NMR (500 MHz, CDCl₃): δ = 3.17 (t, J = 7.5 Hz, 2 H, COCH₂), 3.32 (t, J = 7.5 Hz, 2 H, SeCH₂), 7.17–7.22 (m, 3 H, ArH), 7.35–7.38 (m, 2 H, ArH), 7.44–7.50 (m, 3 H, ArH), 7.82–7.83 (m, 2 H, ArH). ¹³C NMR (125 MHz, CDCl₃): δ = 21.2 (COCH₂), 39.5 (SeCH₂), 127.2 (ArCH), 128.1 (ArCH), 128.7 (ArCH), 129.3 (ArCH), 129.9 (ArC), 132.9 (ArCH), 133.4 (ArCH), 136.6 (ArC), 198.7 (CH₂CO). IR (CHCl₃): 2401, 1684, 1599, 1579, 1524, 1477, 1448, 1438, 1344 cm^–1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₅H₁₄NaOSe: 313.0108; found: 313.0104. Anal. Calcd for C₁₅H₁₄OSe: C, 62.29; H, 4.88. Found: 62.52; H, 4.97.3-(Phenylselanyl)-1-(p-tolyl)propan-1-one (9d): Yield: 0.52 g (64%); colourless solid; mp 73–75 °C; R_f = 0.65 (hexane–EtOAc, 9.5:0.5). ¹H NMR (400 MHz, CDCl₃): δ = 2.40 (s, 3 H, CH₃), 3.24 (t, J = 7.2 Hz, 2 H, COCH₂), 3.36 (t, J = 7.2 Hz, 2 H, SeCH₂), 7.22–7.28 (m, 5 H, ArH), 7.51–7.53 (m, 2 H, ArH), 7.80 (d, J = 8.0 Hz, 2 H, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 21.3 (COCH₂), 21.7 (CH₃), 39.4 (SeCH₂), 127.1 (ArCH), 128.2 (ArCH), 129.2 (ArCH), 129.4 (ArCH), 130.0 (ArC), 132.9 (ArCH), 134.1 (ArC), 144.2 (ArC), 198.4 (CH₂CO). IR (CHCl₃): 2401, 1679, 1607, 1579, 1522, 1477, 1423, 1339, 1218 cm^–1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₆NaOSe: 327.0264; found: 327.0255.1-(4-Methoxyphenyl)-3-(phenylselanyl)propan-1-one (9e): Yield: 0.97 g (75%); colourless solid; mp 83–85 °C; R_f = 0.65 (hexane–EtOAc, 9.5:0.5). ¹H NMR (500 MHz, CDCl₃): δ = 3.17 (t, J = 7.0 Hz, 2 H, COCH₂), 3.27 (t, J = 7.0 Hz, 2 H, SeCH₂), 3.79 (s, 3 H, OCH₃), 6.82–6.85 (m, 2 H, ArH), 7.17–7.22 (m, 3 H, ArH), 7.44–7.46 (m, 2 H, ArH), 7.80–7.83 (m, 2 H, ArH). ¹³C NMR (125 MHz, CDCl₃): δ = 21.5 (COCH₂), 39.1 (SeCH₂), 55.6 (OCH₃), 113.9 (ArCH), 127.1 (ArCH), 129.2 (ArCH), 129.7 (ArC), 130.1 (ArC), 130.4 (ArCH), 132.9 (ArCH), 163.7 (ArC), 197.2 (CH₂CO). IR (CHCl₃): 2401, 1674, 1601, 1577, 1510, 1477, 1420 cm^–1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₆NaO₂Se: 343.0213; found: 343.0202. Anal. Calcd for C₁₆H₁₆O₂Se: C, 60.19; H, 5.05. Found: 60.76; H, 4.93.1-(4-Fluorophenyl)-3-(phenylselanyl)propan-1-one (9f): Yield: 67% (0.68 g); colourless crystalline solid; mp 93–95 °C; R_f = 0.65 (hexane–EtOAc, 9.5:0.5). ¹H NMR (500 MHz, CDCl₃): δ = 3.23 (t, J = 7.0 Hz, 2 H, COCH₂), 3.36 (t, J = 7.0 Hz, 2 H, SeCH₂), 7.08–7.13 (m, 2 H, ArH), 7.25–7.29 (m, 3 H, ArH), 7.50–7.53 (m, 2 H, ArH), 7.90–7.94 (m, 2 H, ArH). ¹³C NMR (125 MHz, CDCl₃): δ = 21.1 (COCH₂), 39.4 (SeCH₂), 115.8 (d, J = 21.7 Hz, ArCH), 127.3 (ArCH), 129.3 (ArCH), 129.8 (ArC), 130.8 (d, J = 9.37 Hz, ArCH), 131.6 (ArC), 133.0 (ArCH), 165.9 (d, J = 253.7 Hz, ArCF), 197.1 (CH₂CO). IR (CHCl₃): 2400, 2344, 1683, 1600, 1509, 1477, 1420, 1340, 1216 cm^–1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₅H₁₃FNaOSe: 331.0013; found: 331.0008.1-(4-Chlorophenyl)-3-(phenylselanyl)propan-1-one (9g): Yield: 0.76 g (71%); colourless crystalline solid; mp 95–97 °C; R_f = 0.65 (hexane–EtOAc, 9.5:0.5). ¹H NMR (400 MHz, CDCl₃): δ = 3.23 (t, J = 6.8 Hz, 2 H, COCH₂), 3.36 (t, J = 6.8 Hz, 2 H, SeCH₂), 7.26–7.28 (m, 3 H, ArH), 7.39–7.43 (m, 2 H, ArH), 7.50–7.53 (m, 2 H, ArH), 7.81–7.85 (m, 2 H, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 21.1 (COCH₂), 39.5 (SeCH₂), 127.3 (ArCH), 129.1 (ArCH), 129.3 (ArCH), 129.5 (ArCH), 129.8 (ArC), 133.0 (ArCH), 134.9 (ArC), 139.8 (ArC), 197.5 (CH₂CO). IR (CHCl₃): 2400, 1683, 1590, 1524, 1478, 1436, 1402, 1340, 1217 cm^–1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₅H₁₃ClNaOSe: 346.9718; found: 346.9728.3-(Phenylselanyl)-1-(2-thienyl)propan-1-one (9h): Yield: 0.63 g (65%); pink solid; mp 57–59 °C; R_f = 0.65 (hexane–EtOAc, 9.5:0.5). ¹H NMR (400 MHz, CDCl₃): δ = 3.24 (t, J = 6.8 Hz, 2 H, COCH₂), 3.31 (t, J = 6.8 Hz, 2 H, SeCH₂), 7.10 (t, J = 4.4 Hz, 1 H, ArH), 7.26–7.28 (m, 3 H, ArH), 7.52–7.54 (m, 2 H, ArH), 7.63 (d, J = 4.8 Hz, 2 H, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 21.3 (COCH₂), 40.1 (SeCH₂), 127.3 (ArCH), 128.2 (ArCH), 129.3 (ArCH), 129.7 (ArC), 132.1 (ArCH), 133.1 (ArCH), 134.0 (ArCH), 143.9 (ArC), 191.5 (CH₂CO). IR (CHCl₃): 2401, 1661, 1579, 1518, 1477, 1416, 1359, 1336, 1213 cm^–1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₃H₁₂NaOSSe: 318.9672; found: 318.9686. Anal. Calcd for C₁₃H₁₂OSSe: C, 52.88; H, 4.10. Found: 53.09; H, 4.01.1-(3,4-Dichlorophenyl)-3-(phenylselanyl)propan-1-one (9i): Yield: 0.80 g (68%); light-yellow crystalline solid; mp 61–63 °C; R_f = 0.65 (hexane–EtOAc, 9.5:0.5). ¹H NMR (400 MHz, CDCl₃): δ = 3.18 (t, J = 6.8 Hz, 2 H, COCH₂), 3.30 (t, J = 6.8 Hz, 2 H, SeCH₂), 7.24 (s, 3 H, ArH), 7.48 (d, J = 6.4 Hz, 3 H, ArH), 7.67 (d, J = 4.4 Hz, 1 H, ArH), 7.92 (s, 1 H, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 20.9 (COCH₂), 39.5 (SeCH₂), 127.1 (ArCH), 127.4 (ArCH), 129.3 (ArCH), 129.6 (ArC), 130.1 (ArCH), 130.9 (ArCH), 133.1 (ArCH), 133.5 (ArC), 136.1 (ArC), 138.0 (ArC), 196.5 (CH₂CO). IR (CHCl₃): 2400, 1693, 1582, 1556, 1523, 1478, 1439, 1390, 1336 cm^–1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₅H₁₂Cl₂NaOSe: 380.9328; found: 380.9316.3-(Phenylselanyl)-1-(3,4,5-trimethoxyphenyl)propan-1-one (9j): Yield: 0.43 g (62%); yellow viscous liquid; R_f = 0.35 (hexane–EtOAc, 9.5:0.5). ¹H NMR (400 MHz, CDCl₃): δ = 3.24 (t, J = 6.8 Hz, 2 H, COCH₂), 3.36 (t, J = 6.8 Hz, 2 H, SeCH₂), 3.88 (s, 6 H, 2 × OCH₃), 3.90 (s, 3 H, OCH₃), 7.15 (s, 2 H, ArH), 7.25–7.29 (m, 3 H, ArH), 7.51–7.54 (m, 2 H, ArH). ¹³C NMR (100 MHz, CDCl₃): δ = 21.4 (COCH₂), 39.1 (SeCH₂), 56.3 (OCH₃), 61.0 (OCH₃), 105.5 (ArCH), 127.2 (ArCH), 129.2 (ArCH), 129.9 (ArC), 131.8 (ArC), 132.8 (ArCH), 142.8 (ArC), 153.1 (ArC), 197.5 (CH₂CO). IR (CHCl₃): 2941, 2840, 2401, 1676, 1585, 1505, 1462, 1415, 1345 cm^–1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₈H₂₀NaO₄Se: 403.0424; found: 403.0420.
14 Preparation of vinyl ketones 1a–l; General procedure: To a solution of 9a (0.20 g, 0.62 mmol) in THF (3 mL), 30% H₂O₂ (0.15 mL, 4.92 mmol) was added at 0 °C. Within 10 min, the reaction mixture became deep-yellow (the progress of the reaction was monitored by TLC) and after 30 min, aq Na₂S₂O₃ (0.1 M, 3 mL) was added and the solvent was evaporated under reduced pressure. The residue was dissolved in CH₂Cl₂ (15 mL) and washed with H₂O (3 × 4 mL) and the organic layer was separated, dried over Na₂SO₄, and concentrated. The product was purified by silica gel column chromatography (EtOAc–hexane, 1%) to afford 1a (93 mg, 90%) as a yellow liquid. R_f = 0.68 (hexane–EtOAc, 9.5:0.5). ¹H NMR (400 MHz, CDCl₃): δ = 0.86 (t, J = 6.8 Hz, 3 H, CH₃), 1.26–1.29 (m, 10 H), 1.59–1.64 (m, 2 H, CH₂), 2.56 (t, J = 7.2 Hz, 2 H, CH₂), 5.79 (d, J = 10.8 Hz, 1 H, =CH _bH_c), 6.20 (d, J = 17.6 Hz, 1 H, =CH_b H _c), 6.34 (dd, J = 10.8, 17.6 Hz, 1 H, COCH _a). ¹³C NMR (100 MHz, CDCl₃): δ = 14.2 (CH₃), 22.7 (CH₂), 24.1 (CH₂), 29.2 (CH₂), 29.4 (CH₂), 29.5 (CH₂), 31.9 (CH₂), 39.8 (CH₂), 127.9 (CH), 136.7 (=CH₂), 201.2 (CO). IR (CHCl₃): 2931, 2865, 2408, 1686, 1617, 1524, 1456, 1410, 1218 cm^–1.Tetradec-1-en-3-one (1b): Yield: 135 mg (83%); yellow liquid; R_f = 0.58 (hexane–EtOAc, 9.5:0.5). ¹H NMR (400 MHz, CDCl₃): δ = 0.87 (t, J = 6.8 Hz, 3 H, CH₃), 1.25–1.29 (m, 16 H), 1.59–1.64 (m, 2 H, CH₂), 2.57 (t, J = 7.6 Hz, 2 H, CH₂), 5.81 (dd, J = 1.2, 10.4 Hz, 1 H, =CH _bH_c), 6.21 (dd, J = 1.2, 17.6, Hz, 1 H, =CH_b H _c), 6.35 (dd, J = 10.8, 17.6 Hz, 1 H, COCH _a). ¹³C NMR (100 MHz, CDCl₃): δ = 14.2 (CH₃), 22.8 (CH₂), 24.1 (CH₂), 29.4 (CH₂), 29.47 (CH₂), 29.5 (CH₂), 29.6 (CH₂), 29.7 (CH₂), 32.0 (CH₂), 39.8 (CH₂), 128.0 (=CH), 136.7 (=CH₂), 201.3 (CH₂CO). IR (CHCl₃): 2928, 2855, 2401, 1679, 1614, 1524, 1464, 1405 cm^–1.¹H and ¹³C NMR spectra of synthesized vinyl ketones 1a–l have been included in the Supporting Information. The spectral data for vinyl ketones 1c,^2b 1d ^15a and 1e ^15b were consistent with those reported in the literature.

15a Cai M, Zheng G, Ding G. Green Chem. 2009; 11: 1687
15b Aranha RM, Bowser AM, Madalengoitia JS. Org. Lett. 2009; 11: 575

Supplementary Material

Supporting Information