Synthesis of arylethylamines via C(sp3)–C(sp3) palladium-catalyzed cross-coupling

Rhys A. Lippa, David J. Battersby, John A. Murphy, Tim N. Barrett

Research output: Contribution to journalArticlepeer-review

Abstract

Substituted arylethylamines represent a key structural motif in natural, pharmaceutical, and agrochemical compounds. Access to such scaffolds has been the subject of long-standing synthetic interest. Herein, we report the synthesis of such scaffolds via a palladium-catalyzed C(sp3)-C(sp3) coupling between (chloromethyl)aryls and air-/moisture-stable N,N-dialkylaminomethyltrifluoroborate salts. Rapid hit identification was achieved using microscale high-throughput experimentation and was followed by millimolar-scale reaction parameter optimization. A range of structurally and electronically varied arylethylamine products were obtained in moderate to excellent yields (27-96%, >60 examples). The reaction mechanism is proposed to proceed via formation of a trialkylbenzylammonium species prior to oxidative addition.

Original languageEnglish
Pages (from-to)3583–3604
Number of pages22
JournalJournal of Organic Chemistry
Volume86
Issue number4
Early online date29 Jan 2021
DOIs
Publication statusPublished - 19 Feb 2021

Keywords

  • arylethylamines
  • trialkylbenzylammonium
  • palladium

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