Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA, 02467, USA.
Angew Chem Int Ed Engl. 2018 Sep 3;57(36):11654-11661. doi: 10.1002/anie.201805811. Epub 2018 Aug 1.
The first catalytic, broadly applicable, efficient, γ-, diastereo-, and enantioselective method for addition of O-substituted allyl-B(pin) compounds to phosphinoylimines (MEM=methoxyethoxymethyl, pin=pinacolato) is presented. The identity of the most effective catalyst and the optimal protecting group for the organoboron reagent were determined by consideration of the steric and electronic requirements at different stages of the catalytic cycle, namely, the generation of the chiral allylboronate, the subsequent 1,3-borotropic shift, and the addition step. Aryl-, heteroaryl-, alkenyl- and alkyl-substituted vicinal phosphinoylamido MEM-ethers were thus accessed in 57-92 % yield, 89:11 to >98:2 γ:α selectivity, 76:24-97:3 diastereomeric ratio, and 90:10-99:1 enantiomeric ratio. The method is scalable, and the phosphinoyl and MEM groups may be removed selectively or simultaneously. Utility is highlighted by enantioselective synthesis of an NK-1 receptor antagonist.
本文介绍了首例催化、广泛适用、高效、γ-、非对映选择性和对映选择性的方法，用于 O-取代烯丙基-B（pin）化合物与膦酰亚胺（MEM=甲氧基乙氧基甲基，pin=频哪醇酯基）的加成反应。通过考虑不同催化循环阶段的空间和电子要求，确定了最有效催化剂和最佳保护基对有机硼试剂的影响，即手性烯丙基硼酸酯的生成、随后的 1,3-硼迁移和加成步骤。芳基、杂芳基、烯基和烷基取代的毗邻膦酰亚胺基 MEM-醚以 57-92%的产率、89:11 至>98:2 γ:α 选择性、76:24-97:3 非对映体比和 90:10-99:1 对映体比得到。该方法可规模化，并且膦酰基和 MEM 基团可以选择性或同时去除。通过对 NK-1 受体拮抗剂的对映选择性合成突出了该方法的实用性。
