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. 2014 Feb;6(2):146-50.
doi: 10.1038/nchem.1836. Epub 2014 Jan 5.

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

Kelvin S L Chan  1 , Masayuki Wasa  1 , Ling Chu  1 , Brian N Laforteza  1 , Masanori Miura  1 , Jin-Quan Yu  1
Affiliations

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

Kelvin S L Chan et al. Nat Chem. 2014 Feb.

Abstract

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.

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Conflict of interest statement

Competing Financial Interests

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Ligand-enabled C(sp3)–H activation
a, C–H activation of aliphatic amines directed by strong σ-chelation. b, Unreactive amine substrates in the absence of strong σ-chelation. c, Ligand-enabled γ-C(sp3)–H arylation of amines. ArBPin = arylboronic acid pinacol ester.
Figure 2
Figure 2
Ligand-Enabled Cross-Coupling of C(sp3)–H Bonds with Arylboron Reagents via Pd(II)/Pd(0) Catalysis, and proposed reactive intermediate.
Figure 3
Figure 3
Substrates and products of C-H activation reaction.
Figure 3
Figure 3
Substrates and products of C-H activation reaction.
Figure 3
Figure 3
Substrates and products of C-H activation reaction.
Figure 3
Figure 3
Substrates and products of C-H activation reaction.
Figure 3
Figure 3
Substrates and products of C-H activation reaction.
Figure 3
Figure 3
Substrates and products of C-H activation reaction.
See this image and copyright information in PMC

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