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. 2017 Feb 1;56(6):1506-1509.
doi: 10.1002/anie.201610580. Epub 2017 Jan 3.

Ligand-Enabled β-C-H Arylation of α-Amino Acids Without Installing Exogenous Directing Groups

Gang Chen  1 , Zhe Zhuang  1 , Gen-Cheng Li  1 , Tyler G Saint-Denis  1 , Yi Hsiao  2 , Candice L Joe  2 , Jin-Quan Yu  1
Affiliations

Ligand-Enabled β-C-H Arylation of α-Amino Acids Without Installing Exogenous Directing Groups

Gang Chen et al. Angew Chem Int Ed Engl. .

Abstract

Herein we report acid-directed β-C(sp3 )-H arylation of α-amino acids enabled by pyridine-type ligands. This reaction does not require the installation of an exogenous directing group, is scalable, and enables the preparation of Fmoc-protected unnatural amino acids in three steps. The pyridine-type ligands are crucial for the development of this new C(sp3 )-H arylation.

Keywords: C−H activation; amino acids; arylation; palladium; pyridine ligands.

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Figures

Figure 1
Figure 1
Plausible mechanism for C(sp3)–H ary lation.
Scheme 1
Scheme 1
Ary lation of α-Amino Acids
Scheme 2
Scheme 2
Preliminary Discovery for Ligand-Promoted C–H Ary lation
Scheme 3
Scheme 3
Gram-Scale Synthesis of Unnatural Amino Acid.
See this image and copyright information in PMC

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