224779-00-4Relevant academic research and scientific papers
Application of chiral mixed phosphorus/sulfur ligands to palladium-catalyzed allylic substitutions
Evans, David A.,Campos, Kevin R.,Tedrow, Jason S.,Michael, Forrest E.,Gagne, Michel R.
, p. 7905 - 7920 (2007/10/03)
A modular approach to the synthesis of a class of mixed phosphorus/sulfur ligands was designed to identify important ligand structural features for enantioselective palladium-catalyzed allylic subsitutions of acyclic and cyclic ayllic esters. After a systematic variation of the ligand substituents at sulfur, phosphorus, and the ligand backbone, ligand 11k was found to be optimal in the palladium-catalyzed allylic substitution of 1,3-diphenylpropenyl acetate with dimethyl malonate or benzylamine in high yield and excellent enantioselectivity (95-98% ee). A similar optimization of the mixed phosphorus/sulfur ligand for the palladium-catalyzed allylic substitution of cycloalkenyl acetates showed that 49g afforded the highest enantioselectivities (91-97% ee). Application of this methodology to heterocyclic substrates was developed as an efficient approach to the enantioselective synthesis of 3-substituted piperidines and dihydrothiopyrans. Models for asymmetric induction are discussed based on the absolute stereochemistry of the products, X-ray crystallographic data, and NMR spectroscopic data for relevant π-allyl complexes.
