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DOI: 10.1055/s-0028-1083524
Regioselective Synthesis of Polyketide-Type Phenols by Formal [3+3]-Cyclocondensations of 1,3-Bis(silyloxy)-1,3-butadienes with 3-Oxoorthoesters
Publication History
Publication Date:
01 October 2008 (online)
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Abstract
A variety of 4-methoxysalicylates and related polyketide-type phenols are regioselectively prepared by the first formal [3+3]-cyclocondensations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-oxoorthoesters.
Key words
arenes - cyclizations - regioselectivity - silyl enol ethers
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References and Notes
Typical Procedure for the Synthesis of Methyl 2-hydroxy-4-methoxy-6-( n -propyl)benzoate (6e): To a CH2Cl2 solution (2 mL) of 4c (0.191 g, 1.0 mmol) and 5a (0.521 g, 2.0 mmol) was added TiCl4 (0.11 mL, 1.0 mmol) at -78 ˚C under an argon atmosphere. The temperature of the reaction mixture was allowed to rise to 20 ˚C during 14 h with stirring. To the mixture was added hydrochloric acid (10%, 10 mL). The organic and the aqueous layer were separated and the latter was extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were dried (Na2SO4), filtered and the filtrate was concentrated in vacuo. After column chromatography (silica gel; heptanes-EtOAc, 1:1), 6e was obtained as a colorless oil (92 mg, 42%); R f 0.88 (heptanes-EtOAc, 1:1). ¹H NMR (250 MHz, CDCl3): δ = 11.73 (s, 1 H, OH), 6.33 (s, 1 H, ArH), 6.30 (s, 1 H, ArH), 3.93 (s, 3 H, OMe), 3.38 (s, 3 H, OMe), 2.83 (t, ³ J = 7.7 Hz, 2 H, ArCH2), 1.49-1.63 (m, 2 H, CH 2CH3), 0.95 (t, ³ J = 7.4 Hz, 3 H, Me). ¹³C NMR (63 MHz, CDCl3): δ = 172.0 (C=O), 165.5, 163.9 (CO), 147.7 (C), 110.7 (CH), 104.6 (C), 98.7 (CH), 55.3, 51.8 (OMe), 38.9 (ArCH2), 24.9 (CH2CH3), 14.2 (Me). IR (ATR): 2956 (br m), 2871 (w), 2846 (w), 1649 (s), 1611 (s), 1575 (s) cm-¹. MS (EI, 70 eV): m/z (%) = 224 (33) [M+], 192 (100), 164 (34), 135 (45). Anal. Calcd for C12H16O4 (224.26): C, 64.27; H, 7.19. Found: C, 64.27; H, 7.39.
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