Ligand-Controlled C(sp 3 )–H Arylation and Olefination in Synthesis of Unnatural Chiral α–Amino Acids

作者：Jian Feng He, Suhua Li, Youqian Deng, Haiyan Fu, Brian Ngo Laforteza, Jillian E. Spangler, Anna Homs, Jin‐Quan Yu · 发表于：Science · 年份：2014 · DOI：10.1126/science.1249198 · 被引用次数：506 · 研究领域：Catalytic C–H Functionalization Methods、Synthesis and Catalytic Reactions、Asymmetric Hydrogenation and Catalysis

The use of ligands to tune the reactivity and selectivity of transition metal catalysts for C(sp(3))-H bond functionalization is a central challenge in synthetic organic chemistry. Herein, we report a rare example of catalyst-controlled C(sp(3))-H arylation using pyridine and quinoline derivatives: The former promotes exclusive monoarylation, whereas the latter activates the catalyst further to achieve diarylation. Successive application of these ligands enables the sequential diarylation of a methyl group in an alanine derivative with two different aryl iodides, affording a wide range of β-Ar-β-Ar'-α-amino acids with excellent levels of diastereoselectivity (diastereomeric ratio > 20:1). Both configurations of the β-chiral center can be accessed by choosing the order in which the aryl groups are installed. The use of a quinoline derivative as a ligand also enables C(sp(3))-H olefination of a protected alanine.