EaStCHEM, School of Chemistry, University of St Andrews , North Haugh, St Andrews KY16 9ST, U.K.
J Am Chem Soc. 2017 Aug 30;139(34):11895-11902. doi: 10.1021/jacs.7b05619. Epub 2017 Aug 22.
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.
已开发出一种使用 Pd 和异硫脲催化的串联接力催化协议，用于从易得的 N,N-二取代甘氨酸芳基酯和烯丙基磷酸酯对映选择性合成含有两个手性中心的α-氨基酸衍生物。优化后的工艺使用稳定的琥珀酰亚胺基 Pd 前催化剂 (FurCat) 促进 Pd 催化的烯丙基铵盐从烯丙基磷酸酯和甘氨酸芳基酯生成。随后，异硫脲苯并四唑原位对映选择性 [2,3]-σ重排催化形成具有高非对映选择性和对映选择性的 syn-α-氨基酸衍生物。该方法使用 4-硝基苯甘氨酸酯最为有效，并能耐受各种取代肉桂基和苯乙烯基烯丙基乙基磷酸酯。在不影响立体选择性的情况下，挑战性的不对称 N-烯丙基-N-甲基甘氨酸酯也能在催化接力条件下耐受。
