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Synlett 2013; 24(14): 1777-1780
DOI: 10.1055/s-0033-1338962
letter
© Georg Thieme Verlag Stuttgart · New York

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
› Author Affiliations
Further Information

Publication History

Received: 16 April 2013

Accepted after revision: 12 June 2013

Publication Date:
19 July 2013 (online)

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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

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

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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%); Rf = 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. Rf = 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; Rf  = 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; Rf = 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; Rf = 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; Rf = 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; Rf = 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; Rf = 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; Rf  = 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; Rf = 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; Rf = 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. Rf  = 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 bHc), 6.20 (d, J = 17.6 Hz, 1 H, =CHb 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; Rf  = 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 bHc), 6.21 (dd, J = 1.2, 17.6, Hz, 1 H, =CHb 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.
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