Download PDF
Synlett 2014; 25(4): 519-522
DOI: 10.1055/s-0033-1340468
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Monosubstituted 1,1-Dicarbonyl Ester 1,3-Dienes

Olivier Rousseau
Institute of Condensed Matter and Nanosciences, Université catholique de Louvain, Place Louis Pasteur 1, L4.01.02, 1348 Louvain-la-Neuve, Belgium   Fax: +32(0)10474168   Email: raphael.robiette@uclouvain.be
,
Thierry Delaunay
Institute of Condensed Matter and Nanosciences, Université catholique de Louvain, Place Louis Pasteur 1, L4.01.02, 1348 Louvain-la-Neuve, Belgium   Fax: +32(0)10474168   Email: raphael.robiette@uclouvain.be
,
Raphaël Robiette*
Institute of Condensed Matter and Nanosciences, Université catholique de Louvain, Place Louis Pasteur 1, L4.01.02, 1348 Louvain-la-Neuve, Belgium   Fax: +32(0)10474168   Email: raphael.robiette@uclouvain.be
› Author Affiliations
Further Information

Publication History

Received: 02 November 2013

Accepted after revision: 23 November 2013

Publication Date:
20 December 2013 (online)

    Permissions and Reprints All articles of this category


Abstract

The synthesis of various electron-deficient 1,1-dicarbonyl ester 1,3-dienes substituted in position 2 or 3 of the diene moiety has been developed.

Keywords

bromine - condensation - cross-coupling - 1,3-dienes - malonates

Supporting Information

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

  • References and Notes

  • 11 For a review on the synthesis of electron-poor dienes, see: Minbiole KP. C. In Science of Synthesis . Vol. 46. Rawal VH, Kozmin SA. Thieme; Stuttgart: 2009: 147
    Search in Google Scholar
  • 13 To the best of our knowledge, no example of 1,1-dicarbonyl 1,3-dienes monosubstituted in position 2 have been reported thus far. For some examples of 2,4-disubstituted 1,1-dicar-bonyl 1,3-dienes, see ref. 10e–g.
    • 14a Chen H, Lyzy J.-P, Gresh N, Garbay C. Eur. J. Org. Chem. 2006; 2329
    • 14b Lehnert W. Tetrahedron 1973; 26: 635
      Search in Google Scholar

      For other syntheses of 3-subsituted 1,1-dicarbonyl 1,3-dienes, see:
    • 15a Matsuki T, Hu NX, Aso Y, Otsubo T, Ogura F. Bull. Chem. Soc. Jpn. 1989; 2105
    • 15b Trost BM, Vercauteren J. Tetrahedron Lett. 1985; 26: 131
      Search in Google Scholar
  • 16 All our attempts to trap the alkoxide intermediate in situ failed.
  • 17 Wang J, Zhou Y, Zhang L, Li Z, Chen X, Liu H. Org. Lett. 2013; 15: 1508
    CrossrefSearch in Google Scholar
  • 18 Okuro K, Alper H. J. Org. Chem. 2012; 77: 4420
    CrossrefSearch in Google Scholar
  • 19 Molander GA, Rodriguez Rivero M. Org. Lett. 2002; 4: 107
    CrossrefPubMedSearch in Google Scholar
  • 20 Mukherjee H, Martinez CA. ACS Catal. 2011; 1: 1010
    CrossrefSearch in Google Scholar
  • 21 General procedures are reported below while characterization of all synthesized compounds (dienes and intermediates) is given in the Supporting Information. Synthesis of Dimethyl (2-Methylprop-2-en-1-ylidene)malonate (2a): In a round-bottomed flask was added THF (12 mL), under argon. A solution of TiCl4 (6 mmol) in CCl4 (1.5 mL) was then added, slowly, at 0 °C. After 10 min, methacrolein (3 mmol) and dimethyl malonate (1.5 mmol) were added dropwise. The solution was stirred at 0 °C for 20 min. Pyridine (12 mmol) was then added dropwise and the solution was allowed to warm to r.t. After 16 h of stirring, the reaction mixture was diluted with Et2O (10 mL) and H2O (10 mL). The phases were separated and the aqueous phase was extracted with Et2O (2 × 10 mL). The organic phases were combined, washed with a sat. NaHCO3 solution (10 mL) and then brine (10 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. Typical Procedure for the Knoevenagel Condensation Reaction (3 → 4): In a one-necked round-bottomed flask were added malonate (93 mmol) and aldehyde 3 (110 mmol) in absolute EtOH (40 mL). AcOH (17 mmol) and piperidine (13 mmol) were then added dropwise. The solution was heated at reflux for 48 h (110 °C). The by-product was then distilled in a Kugelrohr apparatus under reduced pressure to yield the diene in an excellent yield. Typical Procedure for the Bromination Reaction (4 → 5): In a one-necked round-bottomed flask were added diethyl malonate compound 4 (8 mmol) and bromine (10 mmol) in CCl4 (8 mL), at 0 °C. The reaction mixture was stirred at this temperature for 1 h and then at r.t. for 4 h. The reaction mixture was diluted with CH2Cl2 (10 mL), then washed with a solution of 1 M NaOH (10 mL) and brine (10 mL). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure to provide the desired compound in a good yield. Typical Procedure for the Elimination Reaction (5 → 6): In a one-necked round-bottomed flask, under argon atmosphere, was added the dibromo compound 5 (2.4 mmol) in CH2Cl2 (20 mL) at 0 °C. DBU (3.5 mmol) was then added slowly and the reaction mixture was stirred at 0 °C for 30 min. It was then diluted with CH2Cl2 (20 mL) and H2O (20 mL). A solution of 1 M HCl (10 mL) was added and the two phases were separated. The organic phase was dried over MgSO4, filtered and concentrated. The compound was relatively unstable and was therefore engaged immediately in the next step without further purification. Typical Procedure for the Suzuki Reaction (6 → 7): In a one-necked round-bottomed flask, under argon atmosphere, were added the monobromo compound 6 (3.6 mmol), potassium vinyltrifluoro-borate (4.3 mmol) and PdCl2dppf (0.18 mmol) in a solution of EtOH (20 mL) and Et3N (5.3 mmol) previously degassed. The reaction mixture was heated at 40 °C for 16 h and then concentrated under vacuum. The residue was diluted with EtOAc (40 mL), washed successively with H2O (20 mL), a solution of sat. NH4Cl (20 mL), and brine (20 mL). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography with a mixture of cyclohexane and EtOAc. Typical Procedure for Michael Addition (4 → 8): CuI (2.8 mmol) was dissolved in THF (20 mL) under inert atmosphere. A 0.583 M solution of vinylmagnesium bromide in THF (10.1 mL, 5.9 mmol) was added dropwise at 0 °C and the reaction mixture was stirred for 45 min at this temperature. A solution of compound 4 (2.3 mmol) in THF (20 mL) was then added dropwise at –78 °C. The reaction mixture was stirred overnight (the cooling bath warming slowly to r.t.). The reaction was quenched with a sat. NH4Cl solution (5 mL) and diluted with H2O (10 mL) and Et2O (50 mL). After layers separation, the aqueous phase was extracted with Et2O (2 × 30 mL). The combined organic layers were washed with brine, dried over MgSO4, and finally concentrated under reduced pressure. The residue was purified by flash chromatography (EtOAc–cyclohexane, 10:90) to give the desired product. Typical Procedure for Double Bond Reformation (8 → 7): Compound 8 (1 mmol) was dissolved in DMF (5 mL) under inert atmosphere. NaH (60% dispersion in mineral oil; 1.2 mmol) was then added at 0 °C. The mixture was stirred for 1 h at r.t. (= solution A). In another flask PhSeCl (2 mmol) was dissolved in DMF (5 mL). This solution was cooled to –10 °C, and then added, very slowly (over 2 h) to solution A. This mixture was stirred for two more hours at –10 °C and then for 2 h at 0 °C. H2O2 (30% solution in H2O; 15 mmol) was added at 0 °C and the solution was stirred for 30 min at this temperature. The reaction was quenched with a sat. NaHCO3 solution (5 mL), diluted with H2O (20 mL) and extracted with EtOAc (2 × 20 mL). The combined organic layers were washed with H2O (10 mL), brine (10 mL), dried over MgSO4, and concentrated under reduced pressure. The residue was purified by flash chromatography (5:95 → 10:90, EtOAc–cyclohexane) to give the desired product.