Tandem palladium and isothiourea relay catalysis : enantioselective synthesis of α-amino acid derivatives via allylic amination and [2,3]-sigmatropic rearrangement
The research leading to these results (S.S.M.S.) has received funding from the European Union (Marie Curie ITN “SubiCat” PITN-GA-2013-607044) and the ERC under the European Union's Seventh Framework Programme (FP7/2007-2013)/E.R.C. grant agreement no 279850 (T.H.W., J.E.T.). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.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.Publisher PDFPeer reviewe
