Thiazole, Imidazole and Oxazoline Based N,P‐Ligands for Palladium‐Catalyzed Cycloisomerization of 1,6‐Enynes

Abstract

A series of N,P‐ligands were prepared and evaluated in the asymmetric palladium‐catalyzed cycloisomerization of allyl propargyl ether substrates. The reactivity and enantioselectivity of the reaction was shown to be highly dependent on the chiral skeleton of the ligand structures with ee's ranging from 22–99 %. The proton source had a significant impact on the enantioselectivity. The generation of palladium hydride from formic acid led to the highest ee. A selectivity model based on a proposed transition state was used to predict and explain the enantiomeric outcome of the reaction.

Palladium‐Catalyzed Intramolecular Alder‐Ene Type Cycloisomerization Reactions

“…From the transition state model Y, it can be realized that the palladium complex with the ligand 12 experiences steric congestion with the olefin (Scheme 11). [14] On the other hand, the model presented in Z indicates that the palladium complex is situated in a favourable scenario and thus results in the formation of the observed enantiomer. Scheme 11.…”

“…In 2017, Andersson and co-workers developed chiral thiazole, imidazole and oxazoline based N,P-ligands for the synthesis of substituted tetrahydrofurans 11 via palladiumcatalyzed Alder-ene reaction of 1,6-enynes 10 (Scheme 10). [14] Among several other designs considered, the ligands 12 and 13 delivered products in consistent yields and enantioselectivities. The enantioselectivity was realized to be highly dependent on the chiral backbone of ligand structures.…”