Peri Fluoro Steric Effects: Syntheses and Comparative Acid-Catalyzed Isomerization of the 8-, 9-, and 11-Fluoro-1,2,3,4-tetrahydro-7,12-dimethylbenzanthracenes to Exo Methylene Tautomers

Article abstract of DOI:10.1021/jo00237a023

Facile and regiospecific syntheses for 8-, 9-, and 11-fluoro-1,2,3,4-tetrahydro-7,12-dimethylbenzanthracenes (4, 5, and 7) from 5,6,7,8-tetrahydro-1-naphthaldehyde and the respective 2-(2-fluoro-6-iodophenyl)oxazoline 14, 2-(2-bromo-5-fluorophenyl)oxazoline 15, and 2-(3-fluorophenyl)oxazoline 16 are described.Comparative acid-catalyzed isomerization of these polycyclic aromatic hydrocarbons (PAH) to exo methylene tautomers in refluxing benzene is compared to our previously published studies employing the parent hydrocarbon 1 and the 5-, 6-, and 10-fluoro analogues(2, 3, and 6).The peri steric effect of 11-fluoro compound 7- was the most dramatic, providing 7-exo methylene isomer 45 in nearly quantitative yield.Substitution of fluorine at peri positions 6 and 8 afforded product ratios at equilibrium, whereas the 7-exo methylene tautomers (41 and 42) also were thermodynamically favored over the parent anthracene PAH or the respective 12-exo methylene isomers (48 and 49).Like the unsubstituted PAH 1, where fluorine does not occupy a peri position such as in the 9- and 10-fluoro species 5 and 6, no appreciable quantities of exo methylene tautomers were detected.Comparative ΔG^o values for isomerization of 6-, 8-, and 11-fluoro isomers revealed that sandwiching the C12-CH3 group between the 11-fluoro and C1-CH2 functions in 7 and removing any possible 7-CH2-F interaction in exo methylene product 45 led to a relative relief in steric interaction of approximately 1 kcal/mol.