NOVEL MACROCYCLES FROM METAL-CATALYZED OXIDATIVE CYCLIZATIONS OF A,C-BILADIENE SALTS

From the metal-promoted oxidative cyclization of several 1,19-disubstituted a,c-biladiene dihydrobromide salts, a number of novel macrocycles were prepared. For example, the cyclization of 1,-19-bis(2-(methoxycarbonyl)ethyl)-2,3,7,8,12,13,17,18-octamethyl-a,c-biladiene dihydrobromide salt (10) with copper(II) acetate afforded copper(II) 20-((methoxycarbonyl)methyl)-1-(2-(methoxycarbonyl)ethyl)-2,3,7,8,12,13,17,18-octamethyl-1,20-dihydroporphyrin (13) (39% yield), which, upon demetalation, yielded the metal-free 20-((methoxycarbonyl)methyl)-1-(2-(methoxycarbonyl)ethyl)-2,3,7,8,12,13,17,18-octamethyl-1,20-dihydroporphyrin (14) (48% yield). With the substrate 19-((ethoxycarbonyl)methyl)-1-(2-(methoxycarbonyl)ethyl)-2,3,7,8,12,13,17,18-octamethyl-a,c-biladiene dihydrobromide (15), the metal-catalyzed cyclization process produced copper(II) 20-(ethoxycarbonyl)-1-(2-(methoxycarbonyl)ethyl)-2,3,7,8,12,13,17,18-octamethyl-1,20-dihydroporphyrin (18) (27 % yield) and copper(II) 20-(ethoxycarbonyl)-2-(2-(methoxycarbonyl)ethyl)-2,7,8,12,13,17,18-heptamethyl-3-methylidene-2,3-dihydroporphyrin (23) (19 % yield). Upon demetalation of the copper dihydroporphyrin 18, 20'-(ethoxycarbonyl)-20-(2-(methoxycarbonyl)ethyl)-2,3,7,8,12,13,17,18-octamethyl-20'-homoporphyrin (28) (16.5 % yield) was isolated; demetalation of copper(II) 20-(ethoxycarbonyl)-2-(2-(methoxycarbonyl)ethyl)-2,7,8,12,13,17,18-heptamethyl-3-methylidene-2,3-dihydroporphyrin (23) yielded the free base 20-(ethoxycarbonyl)-2-(2-(methoxycarbonyl)ethyl)-2,7,8,12,13,17,18-heptamethyl-3-methylidene-2,3-dihydroporphyrin (25) (24% yield). Using chromium(III) hydroxy acetate as the oxidant (in place of copper(II)), 1,2,3,7,8,12,13,17,18-nonamethyl-1,20-dihydroporphyrin (5) (55-62%) was obtained from the 1,2,3,7,8,12,13,17,18,19-decamethyl-a,c-biladiene salt 3. Mechanisms of macrocycle formation from a,c-biladiene salts, promoted by either copper(II) or chromium(III), appear to proceed via pathways closely resembling the electrochemical cyclization reaction of 1,19-dimethyl-a,c-biladiene salts.