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

Abstract

Despite diversity in reaction mechanisms, the palladium-catalyzed cyclization of 1,6-enyne generally proceeds in a 5exo 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.

Palladium-Catalyzed Borylative Cyclization and Cyclopropanation of Terminal Alkyne-Derived Enynes

“…On the basis of the developed reactions, a palladium-catalyzed borylative cyclization and cyclopropanation mechanism for the formation of dideuterated cycle 3d was proposed (Scheme b) . The reversible hydrogen and deuterium atom exchange under our palladium catalysis conditions would result in d - 1d formation.…”

Ni‐Catalyzed Enantioselective Difunctionalization of Alkynes to Azepine Derivatives Bearing a Quaternary Center and an Unprotected Imine†

“…[ 16‐17 ] An outstanding study by Tong group detailed a palladium‐catalyzed hydroacyloxylative 7‐endo‐trig cyclization of nitrogen‐tethered 1,6‐enynes through an unusual E ‐to‐ Z vinyl‐Pd(II) isomerization (Scheme 1f). [ 18 ] To the best of our knowledge, this is the only example capable of enantioselectively accessing C(sp 3 )‐rich azepine derivatives through alkyne functionalization. [ 19 ]…”

Chiral spirosiladiphosphines: ligand development and applications in Rh-catalyzed asymmetric hydrosilylation/cyclization of 1,6-enynes with enhanced reactivity

“…In the current study, we chose the Rh-catalyzed asymmetric silylcyclization of 1,6-enynes [13][14][15] as an optimal reaction to challenge the effect of Si-SDPs (Scheme 1A). These reactions, originally developed by Ojima, 13 is a synthetically useful transformation with the one-step formation of a carbon-carbon bond and a carbon-silicon bond.…”