Syntheses of 6,7‐Benzotropolone by Using Ring‐Closing Metathesis Variants Obviating a Strongly Acidic Hydrolysis Thereafter

Abstract

AbstractA Wittig reaction of 3‐hydroxyphtalide (11) gave ortho‐styrene‐2‐carboxylic acid (12). Its Weinreb amide 13 acylated heterosubstituted methyllithiums. This led to aryl “methyl” ketones whose sp3‐carbon was substituted by Cl+OMe (in 14 a), 2×Cl (in 14 b), OtBu (in 17 a), SPh (in 17 b) or SO2Ph (in 17 c). The enolates of these ketones were C‐allylated. This furnished the benzene‐fused nona‐1,8‐dienones 7 a–b and 9 a–c, respectively. Ring‐closing metatheses provided the corresponding benzocycloheptadienones 8 a‐b and 10 a–c. Their ketone moieties were α,α‐disubstituted (in 8 a–b) or α‐monosubstituted (in 10 a–c). Each substitution pattern allowed to generate the hydroxyenone motif of the corresponding benzocycloheptatrienone—or 6,7‐benzotropolone—6 a: The MeO‐ and PhS‐containing benzocycloheptadienone 8 a gave 6,7‐benzotropolone methyl ether (15) by sulfoxide formation and pyrolysis; 15 was demethylated with BCl3. The same intermediate resulted from the dichlorobenzocycloheptadienone 8 b and NaOMe. The benzocycloheptadienone 10 a was de(tert‐butylated) with formic acid; a subsequent Pfitzner‐Moffatt oxidation completed 6,7‐benzotropolone (6 a) once more. The PhS‐containing benzocycloheptadienone 10 b was α‐acetoxylated with Pb(OAc)4; the resulting O,S‐acetal gave 6,7‐benzotropolone (6 a) by hydrolysis. The PhSO2‐containing substrate 10 c was deprotonated whereupon an oxidation with Me3Si−O−O−SiMe3 gave 6,7‐benzotropolone (6 a).