Pd‐Catalyzed Stereodivergent Allylic Amination of α‐Tertiary Allylic Alcohols towards α,β‐Unsaturated γ‐Amino Acids

Abstract

Tertiary allylic alcohols were conveniently converted into either (Z)‐ or (E)‐configured α,β‐unsaturated γ‐amino acids by treatment with secondary amines under Pd catalysis at ambient conditions. The key to control the stereochemical course of these formal allylic aminations was the presence of a suitable diphosphine ligand, with dppp [1,3‐bis(diphenylphosphino)propane, L12] providing high yields and selectivities for the (Z) isomers, whereas the bis[(2‐diphenylphosphino)phenyl]ether (DPEPhos) derivative L1′ allowed for selective formation of the corresponding (E) isomeric products. This ligand‐controlled, stereodivergent protocol thus shows promise for the stereoselective preparation of allylic amine products from a common substrate precursor.

Vinyl and Alkynyl Substituted Heterocycles as Privileged Scaffolds in Transition Metal Promoted Stereoselective Synthesis

“…This procedure is operationally simple, can be carried out at rt and delivers interesting building blocks for pharmaceutical development from accessible precursors. When the procedure involves secondary amines (R 2 NH), an interesting stereodivergent synthesis of γ-amino acids can be realized . Reoptimization of the initial procedure using diphosphine ligand L4 provided conditions that maximize the yield and stereocontrol toward ( Z ) configured products 20 with good levels of stereoselectivities and appreciable yields; both stereoisomers are separable by column purification.…”

“…When the procedure involves secondary amines (R 2 NH), an interesting stereodivergent synthesis of γ-amino acids can be realized. 45 Reoptimization of the initial procedure using diphosphine ligand L4 provided conditions that maximize the yield and stereocontrol toward ( Z ) configured products 20 with good levels of stereoselectivities and appreciable yields; both stereoisomers are separable by column purification. The synthesis of compound 20 is facilitated by a combination of Pd(TFA) 2 (TFA = trifluoroacetate) and the diphosphine dppp (1,3-diphenylphosphino-propane, bite angle 91.6°).…”