Hydroxylic additives enhance yield and scalability of silicon-directed Nazarov reaction

As a result of difficulties in scaling up silicon-directed Nazarov cyclization for use in the synthesis of taxane natural products, the effect of additives was examined. Hydroxylic additives were found to convey a consistent beneficial effect on the rate, overall yield, and scalability of these reactions. Optimal conditions (1.5 equiv methanol or water with substoichiometric FeCl3), were successfully applied to a range of β-silyl dienone substrates, including several complex polycyclic examples, as well as simpler dienones previously shown to be low-yielding or completely unreactive under the conventional conditions.