Ligand-enabled cross-coupling of C(sp3)–H bonds with arylboron reagents via Pd(II)/Pd(0) catalysis

• Published in: Nature chemistry Vol. 6; no. 2; pp. 146 - 150
• Main Authors: Chan, Kelvin S. L., Wasa, Masayuki, Chu, Ling, Laforteza, Brian N., Miura, Masanori, Yu, Jin-Quan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2014; Nature Publishing Group
• Subjects: 639/638/403/933; Amines; Amines - chemistry; Amino acids; Amino Acids - chemistry; Analytical Chemistry; Biochemistry; Boron - chemistry; Carbon - chemistry; Catalysis; Chemical bonds; Chemistry; Chemistry/Food Science; Chemists; Coupling (molecular); Cross coupling; Hydrogen - chemistry; Hydrogen bonds; Inorganic Chemistry; Ligands; Optical activity; Organic Chemistry; Palladium - chemistry; Physical Chemistry; Quantum Theory; Reagents; Substrates
• ISSN: 1755-4330; 1755-4349
• DOI: 10.1038/nchem.1836

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. Despite advances in C–H activation reactions in the past decade, the development of suitable ligands that enable catalytic C( sp 3 )–H bond functionalization remains a significant challenge. Here, the discovery of a mono- N -protected amino acid ligand enables Pd( II )-catalysed cross-coupling of C( sp 3 )–H bonds in triflyl-protected amines with arylboron reagents.