Pd(0)-Catalyzed Asymmetric 7- Endo Hydroacyloxylative Cyclization of 1,6-Enyne Enabled by an Anion Ligand-Directed Strategy.

Despite diversity in reaction mechanisms, the palladium-catalyzed cyclization of 1,6-enyne generally proceeds in a 5- manner. Herein, we report the development of a Pd(0)-catalyzed hydroacyloxylative cyclization of 1,6-enyne in either 7--trig or 6--trig fashion when paired with an appropriate dihaloacetic acid reactant, such as FHCCOH and ClHCCOH. Using the combination of Pd(dba) and a chiral phosphine ligand, the hydroacyloxylative cyclization of 1,6-enyne bearing a 1,1-disubstituted alkene moiety readily gives highly enantiopure seven-membered heterocycles while the reaction of those having a 1,2-disubstituted alkene affords six-membered rings with moderate enantioselectivity. Preliminary experimental studies suggest a reaction mechanism featuring an unusual -to- vinyl-Pd(II) isomerization and alkene trans-oxypalladation, which is proven to be governed by the rationally selected carboxylate.