Ligand-Enabled γ-C(sp3)-H Cross-Coupling of Nosyl-Protected Amines with Aryl- and Alkylboron Reagents

Abstract

© 2017 American Chemical Society. Pd(II)-catalyzed γ-C(sp3)-H cross-coupling of 4-nitrobenzenesulfonyl (Ns)-protected amines is realized using both arylboron and alkylboron coupling partners. An acetyl-protected aminomethyl oxazoline (APAO) ligand is found to enable the C(sp3)-H arylation reaction, whereas mono-N-protected amino acid (MPAA) ligands promote the C(sp3)-H cross-coupling with various alkylboron reagents. Notably, the APAO-promoted C-H arylation reactions afford high diastereoselectivity (>20:1), providing a useful method for modifying chiral amines. The use of a common nosyl protecting group to direct C(sp3)-H activation significantly improves the practicality of this transformation, as demonstrated by the gram-scale stereoselective synthesis of γ-aryl- and γ-alkyl-α-amino acids.