Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
Nat Chem. 2014 Feb;6(2):146-50. doi: 10.1038/nchem.1836. Epub 2014 Jan 5.
There have been numerous developments in C-H activation reactions in the past decade. Attracted by the ability to functionalize molecules directly at ostensibly unreactive C-H bonds, chemists have discovered reaction conditions that enable reactions of C(sp(2))-H and C(sp(3))-H bonds with a variety of coupling partners. Despite these advances, the development of suitable ligands that enable catalytic C(sp(3))-H bond functionalization remains a significant challenge. Herein we report the discovery of a mono-N-protected amino acid ligand that enables Pd(II)-catalysed coupling of γ-C(sp(3))-H bonds in triflyl-protected amines with arylboron reagents. Remarkably, no background reaction was observed in the absence of ligand. A variety of amine substrates and arylboron reagents were cross-coupled using this method. Arylation of optically active substrates derived from amino acids also provides a potential route for preparing non-proteinogenic amino acids.
在过去的十年中，C-H 键活化反应有了很多发展。化学家们被直接在表面惰性的 C-H 键上官能团化分子的能力所吸引，发现了使 C(sp(2))-H 和 C(sp(3))-H 键与各种偶联伙伴反应的反应条件。尽管取得了这些进展，但开发能够实现催化 C(sp(3))-H 键官能化的合适配体仍然是一个重大挑战。在此，我们报告了一种单 N-保护氨基酸配体的发现，该配体能够使三氟甲磺酸酯保护的胺中的 γ-C(sp(3))-H 键与芳基硼酸试剂发生钯(II)催化偶联。值得注意的是，在没有配体的情况下，没有观察到背景反应。使用这种方法可以交叉偶联各种胺底物和芳基硼酸试剂。由氨基酸衍生的光学活性底物的芳基化也为制备非蛋白质氨基酸提供了一种潜在途径。
