Department of Chemistry , Oklahoma State University , Stillwater , Oklahoma 74078 , United States.
Org Lett. 2018 Nov 16;20(22):7239-7244. doi: 10.1021/acs.orglett.8b03161. Epub 2018 Nov 2.
The enolate monoanion of amino esters is explored, and the first catalytic Michael addition of α-amino esters is demonstrated. These studies indicate that the acidity of the αC-H is the primary factor determining reactivity. Thus, polyfluorophenylglycine amino esters yield novel α-amino esters in the presence of a catalytic amount of a guanidine-derived base and Michael acceptors. Reactivity requires an acidic N-H, which is accomplished using common protecting groups such as N-Bz, N-Boc, and N-Cbz. Calculations and labeling experiments provide insight into the governing principles in which a key C-to-N proton transfer occurs, resulting in an expansion of the scope to include a number of natural amino esters. The study culminates with a late-stage functionalization of peptidic γ-secretase inhibitor, DAPT.
本文探索了氨基酸酯的烯醇单负离子，并首次展示了 α-氨基酸酯的催化迈克尔加成反应。这些研究表明，αC-H 的酸性是决定反应性的主要因素。因此，在催化量的胍衍生碱和迈克尔受体存在下，多氟苯基甘氨酸氨基酸酯可以得到新型的 α-氨基酸酯。反应需要酸性的 N-H，这可以通过使用常见的保护基如 N-Bz、N-Boc 和 N-Cbz 来实现。计算和标记实验提供了对控制原则的深入了解，其中发生了关键的 C-N 质子转移，从而扩大了范围，包括许多天然氨基酸酯。该研究的高潮是对肽 γ-分泌酶抑制剂 DAPT 的晚期功能化。
