Synlett, Inhaltsverzeichnis Synlett 2013; 24(3): 363-368DOI: 10.1055/s-0032-1318130 letter © Georg Thieme Verlag Stuttgart · New York Stereocontrolled Routes to 4-Methoxypentadienoates for Use in Natural Product Synthesis Philip G. E. Craven Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK Fax: +44(1904)324523 eMail: richard.taylor@york.ac.uk , Richard J. K. Taylor* Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK Fax: +44(1904)324523 eMail: richard.taylor@york.ac.uk › Institutsangaben Artikel empfehlen Abstract Artikel einzeln kaufen Alle Artikel dieser Rubrik Abstract Mild and efficient routes to (E,E)- and (E,Z)-4-methoxypentadienoic acid esters from readily accessible γ,δ-epoxydienoates are described. The crucial epoxide methanolysis can be carried out in stereocomplementary ways by the use of either acid-mediated or palladium-catalysed procedures, the latter procedure proving preferable in most cases. Key words Key wordsepoxides - stereoselective synthesis - palladium catalysis - acid catalysis - diene synthesis Volltext Referenzen References and Notes 1 Motohashi K, Hwang J.-H, Sekido Y, Takagi M, Shin-ya K. Org. Lett. 2009; 11: 285 2 Schlegel B, Groth I, Gräfe U. J. Antibiot. 2000; 53: 425 3 Chen Y, Huang J, Liu B. Tetrahedron Lett. 2010; 51: 4655 4 Craven PG. E, Taylor RJ. K. Tetrahedron Lett. 2012; 53: 5422 5 Voyle M, Kyler KS, Arseniyadis S, Dunlap NK, Watt DS. J. Org. Chem. 1983; 48: 470 6a Tsuboi S, Masuda T, Takeda A. J. Org. Chem. 1982; 47: 4478 6b Uchida K, Ishigami K, Watanabe H, Kitahara T. Tetrahedron 2007; 63: 1281 7 Yu X.-Q, Yoshimura F, Ito F, Susaki M, Hirai A, Tanino K, Miyashita M. Angew. Chem. Int. Ed. 2008; 47: 750 8 General Procedure for the Acid-Promoted Epoxide Ring Opening To a stirred solution of epoxide (1.0 equiv) in MeOH (0.1 M) was added a catalytic amount of concd H2SO4. The resulting solution was stirred at r.t. until complete as monitored by TLC. After this time, the reaction mixture was quenched with brine and extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The resulting crude material was purified by flash column chromatography to afford the desired alcohol. 9 General Procedure for the Pd(0)-Mediated Epoxide Ring Opening To a stirred solution of epoxide (1.0 equiv) and B(OMe)3 (1.2 equiv) in THF (0.2 M) at r.t. was added Pd(PPh3)4 (10 mol%). The resulting solution was stirred at r.t. until complete as monitored by TLC. After this time, the reaction mixture was quenched with NaHCO3 (sat. aq solution) and diluted with EtOAc. The aqueous layer was extracted with EtOAc (3 ×). The combined organics were washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. The resulting crude material was purified by flash column chromatography to afford the desired alcohol. 10 General Procedure for the Mesylation and Elimination Sequence To a stirred solution of alcohol (1.0 equiv) in CH2Cl2 (0.15 M) at r.t. was added MsCl (1.5 equiv) followed by Et3N (3.0 equiv). The resulting solution was stirred at r.t. for 2 h. After this time, the reaction mixture was diluted with brine (20 mL). The aqueous layer was extracted with CH2Cl2 (2×). The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The resulting crude mesylate (1.0 equiv) was redissolved in CH2Cl2 (0.1 M), and DBU (1.2 equiv) was added at r.t. The resulting solution was stirred at r.t. until complete as monitored by TLC. After this time, the reaction mixture was quenched with 10% HCl and diluted with H2O and CH2Cl2, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (2 ×). The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. The resulting crude material was purified by flash column chromatography to afford the desired diene. 11 Methyl (2E,4E)-4-Methoxyhepta-2,4-dienoate [(E,E)-13a] IR (film): νmax = 1712 (C=O), 1645 (C=C) cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.03 (3 H, t, J = 7.5 Hz), 2.20–2.28 (2 H, m), 3.57 (3 H, s), 3.74 (3 H, s), 4.98 (1 H, t, J = 7.9 Hz), 6.21 (1 H, d, J = 15.0 Hz), 7.45 (1 H, d, J = 15.0 Hz) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.2, 19.7, 54.3, 59.8, 111.9, 117.6, 135.0, 150.0, 167.4 ppm. MS: m/z = 171 [MH]+, 193 [MNa]+. ESI-HRMS: m/z calcd for C9H15O3: 171.1016; found [MH+]: 171.1013 (1.5 ppm error). 12 Methyl (2E,4Z)-4-Methoxyhepta-2,4-dienoate [(E,Z)-13a] IR (film): νmax = 1715 (C=O), 1639 (C=C) cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.04 (3 H, t, J = 7.6 Hz), 2.26 (2 H, q, J = 7.6 Hz), 3.62 (3 H, s), 3.76 (3 H, s), 5.39 (1 H, t, J = 7.6 Hz), 6.02 (1 H, d, J = 15.5 Hz), 7.03 (1 H, d, J = 15.5 Hz) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.4, 19.3, 51.4, 59.8, 116.0, 130.3, 140.9, 152.7, 167.4 ppm. MS: m/z = 171 [MH]+, 193 [MNa]+. ESI-HRMS: m/z calcd for C9H15O3: 171.1016; found [MH+]: 171.1013 (1.5 ppm error).
