A general synthetic route to chiral dihydroxy-9,9′-spirobifluorenes

C₂-Symmetric 9,9′-spirobifluorenes with 2,2′-, 3,3′-, and 4,4′-dihydroxyls were conveniently prepared from 1,2-dibromobenzene. The palladium-catalyzed coupling reaction of 1,2-dibromobenzene with methoxyphenylmagnesium bromide or methoxyphenylboronic acid provided methoxy substituted 2-bromobiphenyls. Lithium-bromine exchange with n-butyllithium, followed by reaction with dimethyl carbonate afforded di2-(methoxyphenyl)phenyl]ketones as the key intermediates. A continuous ring-closure induced by a strong Lewis acid and demethylation gave dihydroxy-9,9′-spirobifluorenes. The racemic dihydroxy products were resolved by inclusion crystallization using chiral resolving reagents or separated by chiral HPLC.