Synthesis of Arylethylamines via C(sp3)–C(sp3) Palladium-Catalyzed Cross-Coupling

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...

Full description

Saved in:
Bibliographic Details
Published inJournal of organic chemistry Vol. 86; no. 4; pp. 3583 - 3604
Main Authors Lippa, Rhys A, Battersby, David J, Murphy, John A, Barrett, Tim N
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 19.02.2021
Amer Chemical Soc
Subjects
agrochemicals
Chemistry
Chemistry, Organic
cross-coupling reactions
organic chemistry
Physical Sciences
reaction mechanisms
Science & Technology
Online AccessGet full text

Cover

More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-3263
1520-6904
1520-6904
DOI:10.1021/acs.joc.0c02958