Polarizing the Nazarov Cyclization: The Impact of Dienone Substitution Pattern on Reactivity and Selectivity

The impact of dienone substitution on the Nazarov cyclization has been examined in detail.
Substrates bearing different substituents at each of four positions on the dienone backbone were
systematically probed in order to identify trends leading to higher reactivity and better selectivity.
Desymmetrization of the pentadienyl cation and oxyallyl cation intermediates through placement of polarizing
groups at both the C-2 and C-4 positions was found to be particularly effective. These modifications allowed
cyclizations to occur in the presence of catalytic amounts of mild Lewis acids. It was also found that
stereoconvergent cyclization of mixtures of E and Z isomers of alkylidene β-ketoesters occurred via an
efficient isomerization process that occurred under the reaction conditions.