Iridium-Catalyzed Enantioselective Allylic Substitution of Enol Silanes from Vinylogous Esters and Amides

The enol silanes of vinylogous esters
and amides are classic dienes
for Diels–Alder reactions. Here, we report their reactivity
as nucleophiles in Ir-catalyzed, enantioselective allylic substitution
reactions. A variety of allylic carbonates react with these nucleophiles
to give allylated products in good yields with high enantioselectivities
and excellent branched-to-linear ratios. These reactions occur with
KF or alkoxide as the additive, but mechanistic studies suggest that
these additives do not activate the enol silanes. Instead, they serve
as bases to promote the cyclometalation to generate the active Ir
catalyst. The carbonate anion, which was generated from the oxidative
addition of the allylic carbonate, likely activates the enol silanes
to trigger their activity as nucleophiles for reactions with the allyliridium
electrophile. The synthetic utility of this method was illustrated
by the synthesis of the anti-muscarinic drug, fesoterodine.