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

Olivier Rousseau; Thierry Delaunay; Raphaël Robiette

doi:10.1055/s-0033-1340468

Synlett, Table of Contents

Synlett 2014; 25(4): 519-522
DOI: 10.1055/s-0033-1340468

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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

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Abstract

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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

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References

References and Notes

1a Robiette R, Marchand-Brynaert J. Synlett 2008; 517
1b Hertweck C, Boland W. Tetrahedron 1997; 53: 14651
1c Dorsch D, Kunz E, Helmchen G. Tetrahedron Lett. 1985; 26: 3319
1d Raman N, Jeyamurugan R, Senthilkumar R, Rajkapoor B, Franzblau SG. Eur. J. Med. Chem. 2010; 45: 5438

2a Voet D, Voet JG. Biochemistry . 4th ed. Wiley; Hoboken: 2011
2b Pietruszka J. Chem. Rev. 2003; 103: 1051
2c Behrenswerth A, Volz N, Toräng J, Hinz S, Bräse S, Müller CE. Bioog. Med. Chem. 2009; 17: 2842

For some examples, see:

3a Li J.-L, Kang T.-R, Li R, Wu L, Chen Y.-C. Angew. Chem. Int. Ed. 2010; 49: 6418
3b Spino C, Pesant M, Dory Y. Angew. Chem. Int. Ed. 1998; 37: 3262
3c Dang A.-T, Miller DO, Dawe LN, Bodwell GJ. Org. Lett. 2008; 10: 223
3d Bodwell GJ, Pi Z. Tetrahedron Lett. 1997; 38: 309
3e Dockendorff C, Sahli S, Olsen M, Milhau L, Lautens M. J. Am. Chem. Soc. 2005; 127: 15028

For some examples, see:

4a Hwang SH, Kurth MJ. Tetrahedron Lett. 2002; 43: 53
4b Blumberg LC, Costa B, Goldstein R. Tetrahedron Lett. 2011; 52: 872
4c Lathbury DC, Parsons PJ. J. Chem. Soc., Chem. Commun. 1982; 291

For some examples, see:

5a Davoren JE, Harcken C, Martin SF. J. Org. Chem. 2008; 73: 391
5b Concellon JM, Rodriguez-Solla H, Simal C. Org. Lett. 2007; 9: 2685

For some examples, see:

6a Silva EM. P, Silva AM. S. Synthesis 2012; 44: 3109
6b Oliva CG, Silva AM. S, Paz FA. A, Cavaleiro JA. S. Synlett 2010; 1123
6c Resende DI. S. P, Oliva CG, Silva AM. S, Paz FA. A, Cavaleiro JA. S. Synlett 2010; 115
6d Brebion F, Goddard JP, Fensterbank L, Malacria M. Synthesis 2005; 12449
6e Tissot M, Müller D, Belot S, Alexakis A. Org. Lett. 2010; 12: 2770
6f Belot S, Massaro A, Tenti A, Mordini A, Alexakis A. Org. Lett. 2008; 10: 4557
6g Singh R, Ghosh SK. Org. Lett. 2007; 9: 5071

For some examples, see:

7a Ferrié L, Amans D, Reymond S, Bellosta V, Capdevielle P, Cossy J. Organomet. Chem. 2006; 691: 5456
7b Wojtkielewicz A, Maj J, Morzycki JW. Tetrahedron Lett. 2009; 50: 4734

For some examples, see:

8a Back TG, Rankic DA, Sorbetti JM, Wulff JE. Org. Lett. 2005; 7: 2377
8b Sorbetti JM, Clary KN, Rankinc DA, Wulff JE, Parvez M, Back TG. J. Org. Chem. 2007; 72: 3326

For some examples, see:

9a Nagahama S, Matsumoto A. J. Am. Chem. Soc. 2001; 123: 12176
9b Takasu A, Ishii M, Inai Y, Hirabayashi T. Macromolecules 2003; 36: 7055
9c Matsumoto A, Taketani S. J. Am. Chem. Soc. 2006; 128: 4566

For some examples, see:

10a Shibata Y, Hirano M, Tanaka K. Org. Lett. 2008; 10: 2829
10b Kurahashi T, Shinokubo H, Osuka A. Angew. Chem. Int. Ed. 2006; 45: 6336
10c Keck D, Muller T, Bräse S. Synlett 2006; 3457
10d Yamano Y, Ito M. Org. Biomol. Chem. 2007; 5: 3207
10e Werbel IM, Headen N, Elslager EF. J. Med. Chem. 1967; 10: 366
10f Yavari I, Samzadeh-Kermani AR. S. Tetrahedron Lett. 1998; 39: 6343
10g Trost BM, Pinkerton AB, Seidel M. J. Am. Chem. Soc. 2001; 123: 12466
10h Lyapkalo IM, Webei M, Reiβig H.-U. Eur. J. Org. Chem. 2002; 1015
10i Yoo KS, Yoon CH, Jung KW. J. Am. Chem. Soc. 2006; 128: 16384
10j Palmelund A, Myers EL, Ren Tai L, Tisserand S, Butts CP, Aggarwal VK. Chem. Commun. 2007; 4128

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

12a Keiko NA, Chuvashev YA, Kuznetsova TA, Sherstyannikova LV, Voronkov MG. Russ. Chem. Bull. 1998; 47: 2426
12b Šepac D, Marinić Ž, Portada T, Žinić M, Šunjić V. Tetrahedron 2003; 59: 1159
12c He Y.-H, Hu Y, Guan Z. Synth. Commun. 2011; 41: 1617
12d Yadav JS, Bhunia DC, Singh VK, Srihari SP. Tetrahedron Lett. 2009; 50: 2470
12e Yuan F.-Q, Han F.-S. Org. Lett. 2012; 14: 1218
12f Xu Y.-H, Chok YK, Loh T.-P. Chem. Sci. 2011; 2: 1822
12g Besset T, Kuhl N, Patureau FW, Glorius F. Chem. Eur. J. 2011; 17: 7167
12h Sylla M, Joseph D, Chevallier E, Camara C, Duma F. Synthesis 2006; 1045

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

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

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
18 Okuro K, Alper H. J. Org. Chem. 2012; 77: 4420
19 Molander GA, Rodriguez Rivero M. Org. Lett. 2002; 4: 107
20 Mukherjee H, Martinez CA. ACS Catal. 2011; 1: 1010
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.

Supplementary Material

Supporting Information