Ligand-enabled cross-coupling of C(sp3)-H bonds with arylboron reagents via Pd(II)/Pd(0) catalysis.
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.
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
Kelvin S L
KS
Chan
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
Masayuki
M
Wasa
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
Ling
L
Chu
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
Brian N
BN
Laforteza
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
Masanori
M
Miura
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
Jin-Quan
JQ
Yu
D000588:Amines / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D001895:Boron / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D006859:Hydrogen / Q000737:chemistry; D008024:Ligands; D010165:Palladium / Q000737:chemistry*; D011789:Quantum Theory
D000588:Amines; D000596:Amino Acids; D008024:Ligands; D010165:Palladium; D002244:Carbon; D006859:Hydrogen; D001895:Boron