Stereoselective isomerisations of 4-(3',5'-dimethoxyphenyl)-2,5-dimethyl-1,3-dioxolanes. Temperature-dependent formation of either isochromanes or dihydroisobenzofurans

• Published in: J. Chem. Soc., Perkin Trans. 1 no. 18; pp. 2241 - 2248
• Main Authors: Giles, RGF, Rickards, RW, Senanayake, BS
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 21.09.1996
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; NAPHTHOPYRANS; CHIRAL DIOXANE ACETALS; RING-CLOSURE; ISOMERIZATION
• ISSN: 0300-922X; 1364-5463
• DOI: 10.1039/p19960002241

Stereoselective isomerisation of rel-(2R,4S,5R)-4-(3',5'-dimethoxyphenyl)-2,5-dimethyl-1,3-dioxolane 7 with titanium tetrachloride affords rel-(1R,3R,4S)-4-hydroxy-6,8-dimethoxy-1,3-dimethylisochromane 19 and its C-1 epimer 20 in high yield, The former predominates at a reaction temperature of -78 degrees C and the latter at -30 degrees C, Similar isomerisation of the 1:1 mixture of rel-(2S,4R,5R)- and rel-(2R,4R,5R)-4-(3',5'-dimethoxyphenyl)-2,5-dimethyl- 1,3-dioxolanes 8 and 9 gives rel-(1R,3R,4R)-4-hydroxy-6,8-dimethoxy-1,3-dimethylisochromane 29 and its C-1 epimer 31, with the latter predominating at both -78 and -30 degrees C. At 0 degrees C, dioxolane 7 is isomerised to re[-(1S,1'R,3R)-1-(1'-hydroxyethyl)4,6-dimethoxy-3-methyl- 1,3-dihydroisobenzofuran 25 and its C-3 epimer 26 as the sole reaction products in a 10:1 ratio, Dioxolanes 8 and 9 are similarly converted into rel-(1R,1'R,3S)-1-(1'-hydroxyethyl)-4,6-dimethoxy-3-methyl-1,3-dihydroisobenzofuran 32 and its C-3 epimer 33, These furans probably arise through further isomerisation of the intermediate isochromanes at the higher reaction temperatures.