Stereoselective isomerisations of 4-(2',5'-dimethoxylphenyl)-2,5-dimethyl-1,3-dioxolanes and their 2'-chloro-5'-methoxyphenyl analogues. Temperature-dependent diastereoselective formation of isochromanes

• Published in: Journal of the Chemical Society, Perkin Transactions 1 no. 22; pp. 3361 - 3370
• Main Authors: Giles, RGF, Rickards, RW, Senanayake, BS
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 21.11.1997
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ACETALS
• ISSN: 0300-922X; 1364-5463
• DOI: 10.1039/a704543c

Stereoselective isomerisations of rel-(2R,4S,5R)-4-(2',5'-dimethoxyphenyl)-2,5-dimethyl-1,3 -dioxolane 1 and the 2:1 epimeric mixture of rel-(2S,4R,5R)- and rel-(2R,4R,SR)-4-(2',5'-dimethoxyphenyl)-2,5-dimethyl-1,3 -dioxolanes 2 and 3 with titanium tetrachloride at -78 degrees C afford rel-(1R,3R,4S)- and rel-(1S,3R,4R)-4-hydroxy-5,8-dimethoxy-1,3-dimethylisochromanes 25 and 30, respectively. The yields are only moderate owing to the competing influence of the 2'-methoxy group in the starting dioxolanes, and are improved significantly when this group is replaced by a 2'-chloro substituent, rel-(2R,4S,5R)-4-(2'Chloro-5' -methoxyphenyl)-2,5-dimethyl-1,3-dioxolane 13 under similar conditions is isomerised smoothly to rel-(1R,3R,4S)-5-chloro-4-hydroxy-8-methoxy-1,3 -dimethylisochromane 34 as the sole reaction product, In contrast the C-2 epimers rel-(2R,4R,5R)- and rel-(2S,4R,5R)-4-(2'-chloro-5'-methoxyphenyl)- 2,5-dimethyl-1,3-dioxolanes 14 and 15 each favour the formation of rel-(1R,3R,4R)-5-chloro-4-hydroxy-8-methoxy-1,3 -dimethylisochromane 36 at -78 degrees C, while at -95 degrees C the 1S product 35 predominates, Dioxolane 14 isomerises more rapidly than its C-2 epimer 15, and both these reactions are under kinetic not thermodynamic control.