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

Stéphanie S.M. Spoehrle, Thomas H. West, James E. Taylor, Alexandra M.Z. Slawin, Andrew D. Smith

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)11895-11902
Number of pages8
JournalJournal of the American Chemical Society
Volume139
Issue number34
Early online date1 Aug 2017
DOIs
Publication statusPublished - 30 Aug 2017

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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