Department of Chemistry, Yale University , P.O. Box 208107, New Haven, Connecticut 06520-8107, United States.
J Org Chem. 2017 Nov 3;82(21):11326-11336. doi: 10.1021/acs.joc.7b02339.
Diarylmethylamido bis(phenols) have been subjected to peptide-catalyzed, enantioselective bromination reactions. Desymmetrization of compounds in this class has been achieved such that enantioenriched products may be isolated with up to 97:3 er. Mechanistically, the observed enantioselectivity was shown to be primarily a function of differential functionalization of enantiotopic arenes, although additional studies unveiled a contribution from secondary kinetic resolution of the product (to afford the symmetrical dibromide) under the reaction conditions. Variants of the tetrapeptide catalyst were also evaluated and revealed a striking observation-enantiodivergent catalysis is observed upon changing the achiral amino acid residue in the catalyst (at the i+2 position) from an aminocyclopropane carboxamide residue (97:3 er) to an aminoisobutyramide residue (33:67 er) under a common set of conditions. An expanded set of catalysts was also evaluated, enabling structure/selectivity correlations to be considered in a mechanistic light.
二芳基甲基酰胺双酚已进行肽催化的对映选择性溴化反应。该类化合物的去对称化已实现，可分离得到对映体过量高达 97:3 的产物。从机理上看，观察到的对映选择性主要是由于对映异构芳环的差异化官能化，尽管进一步的研究揭示了在反应条件下产物的次级动力学拆分（生成对称的二溴化物）的贡献。还评估了四肽催化剂的变体，并观察到一个惊人的现象-在相同条件下，当催化剂（在 i+2 位置）中的非手性氨基酸残基从氨基环丙烷羧酰胺残基（97:3 er）变为氨基异丁酰胺残基（33:67 er）时，会观察到对映异构发散催化。还评估了一组扩展的催化剂，能够从机械角度考虑结构/选择性相关性。
