Site-selective C-H arylation of primary aliphatic amines enabled by a catalytic transient directing group

Yongbing Liu, Haibo Ge

Research output: Contribution to journalArticle

149 Scopus citations

Abstract

Transition-metal-catalysed direct C-H bond functionalization of aliphatic amines is of great importance in organic and medicinal chemistry research. Several methods have been developed for the direct sp 3 C-H functionalization of secondary and tertiary aliphatic amines, but site-selective functionalization of primary aliphatic amines in remote positions remains a challenge. Here, we report the direct, highly site-selective γ-arylation of primary alkylamines via a palladium-catalysed C-H bond functionalization process on unactivated sp 3 carbons. Using glyoxylic acid as an inexpensive, catalytic and transient directing group, a wide array of γ-arylated primary alkylamines were prepared without any protection or deprotection steps. This approach provides straightforward access to important structural motifs in organic and medicinal chemistry without the need for pre-functionalized substrates or stoichiometric directing groups and is demonstrated here in the synthesis of analogues of the immunomodulatory drug fingolimod directly from commercially available 2-amino-2-propylpropane-1,3-diol.

Original languageEnglish
Pages (from-to)26-32
Number of pages7
JournalNature Chemistry
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2017

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