Pd(0)-Catalyzed Asymmetric 7-<i>Endo</i> Hydroacyloxylative Cyclization of 1,6-Enyne Enabled by an Anion Ligand-Directed Strategy
Ming Dong, Linjun Qi, Jinlong Qian, Shuling Yu, Xiaofeng Tong
Abstract
Despite diversity in reaction mechanisms, the palladium-catalyzed cyclization of 1,6-enyne generally proceeds in a 5- exo manner. Herein, we report the development of a Pd(0)-catalyzed hydroacyloxylative cyclization of 1,6-enyne in either 7- endo -trig or 6- exo -trig fashion when paired with an appropriate dihaloacetic acid reactant, such as F 2 HCCO 2 H and Cl 2 HCCO 2 H. Using the combination of Pd 2 (dba) 3 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 E -to- Z vinyl-Pd(II) isomerization and alkene trans-oxypalladation, which is proven to be governed by the rationally selected carboxylate.