Tandem Palladium and Isothio­urea Relay Catalysis: Enantioselective Synthesis of α‑Amino Acid Derivatives via Allylic Amination and [2,3]-Sigmatropic Rearrangement

A tandem relay catalytic protocol using both Pd and isothio­urea catalysis has been developed for the enantio­selective synthesis of α-amino acid derivatives containing two stereo­genic centers from readily accessible N,N-disubstituted glycine aryl esters and allylic phosphates. The optimized process uses a bench-stable succin­imide-based Pd precatalyst (FurCat) to promote Pd-catalyzed allylic ammonium salt generation from the allylic phosphate and the glycine aryl ester. Subsequent in situ enantio­selective [2,3]-sigmatropic rearrangement catalyzed by the isothio­urea benzo­tetramisole forms syn-α-amino acid derivatives with high diastereo- and enantio­selectivity. This methodology is most effective using 4-nitrophenyl­glycine esters and tolerates a variety of substituted cinnamic and styrenyl allylic ethyl phosphates. The use of challenging unsymmetrical N-allyl-N-methylglycine esters is also tolerated under the catalytic relay conditions without compromising stereo­selectivity.