Tandem Oxidative Derivatization of Nitrene Insertion Products for the Highly Diastereoselective Synthesis of 1,3‐aminoalcohols

Abstract

Transition-metal-catalyzed nitrene insertion into tertiary C-H bonds located at stereogenic carbons often results in mixtures of diastereomeric products, especially if the reaction proceeds through a concerted pathway. In this communication, we report a solution to this problem that invokes a one-pot, silver-catalyzed C-H nitrene transfer reaction. Nitrene insertion is followed by facile oxidation of the amine to an imine and nucleophilic addition to furnish α-tertiary amine 1,3-aminoalcohol products in high diastereoselectivities. The silver catalyst, PhIO oxidant, and TEMPO additive are crucial to success in this unusual oxidation, which is proposed to occur via hydrogen-atom abstraction from pre-activation of the initial nitrene insertion product by additional oxidant.

Progress on the Synthesis of 1,3-Amino Alcohol

“…表 2 手性腙与醛的加成反应 Table 2 [24] 的方式提高了反应的非对映选择性. 2017 年, Schomaker 课题组 [25] R = p-t Bu, 91%, dr 7.1:1 R = p-Cl, 88%, dr 7.0:1 R = p-CO 2 Me, 91%, dr 7.1:1 R = p-NO 2 , 95%, dr 3.6:1 R = p-CN, 84%, dr 4.0:1 R = m-OMe, 90%, dr 7.4:1 R = m-Cl, 87%, dr 6.7:1 R = m-NO 2 , 89%, dr 6.0:1 R = o-Me, 93%, dr…”