The Suzuki–Miyaura Cross-Coupling–Claisen Rearrangement–Cross-Metathesis Approach to Prenylated Isoflavones

Isoflavones
were synthesized via Suzuki–Miyaura coupling
of 3-iodochromones and para-methoxybenzene- and para-phenolboronic acid. In our hands, conditions commonly
used for similar cross couplings turned out to be unsuccessful or
difficult to reproduce, for example, due to the unplanned partial
cleavage of MOM-protecting groups. Using Pd(dba)2 as a
precatalyst and tricyclohexylphosphine as an activating ligand, reliable
cross-coupling conditions were identified. In all cases, notably higher
yields of isoflavones were obtained with para-phenolboronic
acid than with para-methoxybenzene boronic acid.
This observation and the commercial availability of para-phenolboronic acid suggest that for the synthesis of the important
3′-prenyl- or 3′,5′-diprenylisoflavone substitution
pattern a synthetic route that introduces the prenyl substituents
after the Pd-catalyzed cross-coupling step, thereby avoiding laborious
and protecting-group-intensive multistep syntheses of C-prenylated arene boronic acids, is advantageous.