Substrate‐Controlled Palladium‐Catalyzed Allylic Alkylations of Chelated Enolates – Scope and Limitations

Abstract

Chelated enolates of amino acid derivatives were found to be excellent nucleophiles for stereoselective palladium-catalyzed allylic alkylations via terminal p-allyl complexes. Neither the olefin geometry (linear substrates) nor the configuration of secondary allylic substrates has an influence on the newly formed stereogenic centre of the amino acid. This is exclusively controlled by the protecting group on the chiral centre. Therefore, depending on the protecting group used, both diastereomeric amino acids can be obtained in a highly stereoselective fashion (up to 96% ds for 1,5 induction) from one allylic alcohol.

Isomerization-Free Allylic Alkylations of Terminal π-Allyl Palladium Complexes

“…In the reaction of TBDMS-protected substrate 5a , we observed not only an excellent induction with respect to the newly formed stereogenic center but also a complete isomerization of the double bond, probably because of steric reasons (entry 1). The high induction obtained is in good agreement with observations made earlier . On the other hand, if the silyl protecting group is replaced by a benzyl group ( 5b ), the olefin geometry stays untouched, but no induction was obtained in this case.…”

“…Very recently, we could also show that in reactions of chiral substrates K the nucleophilic attack on the terminal π-allyl intermediate could be controlled by the stereogenic center in the substrate . The best results were obtained with the sterically high demanding tert -butyldiphenylsilyl protecting group (TBDPS).…”