ß-Phenethylamine Synthesis: N-Pyridinium Aziridines as Latent Dual Electrophiles.
Angew Chem Int Ed Engl
; 63(31): e202406335, 2024 Jul 29.
Article
in En
| MEDLINE
| ID: mdl-38699820
ABSTRACT
ß-Phenethylamines are widely represented in biologically and pharmacologically active organic small molecules. Here, we introduce N-pyridinium aziridines as latent dual electrophiles for the synthesis of ß-phenethylamines. Bromide-promoted ring opening generates ß-halopyridinium amines. Selective Ni-catalyzed C-C cross-coupling between organozinc nucleophiles and the benzylic C-Br electrophile affords a diverse family of ß-functionalized phenethylaminopyridinium salts, and coupling is stereoconvergent in the presence of chiral ligands. Subsequent Ni-catalyzed reductive N-N bond activation within the ß-functionalized phenethylaminopyridinium salts furnishes the products of formal olefin carboamination. Other reductive N-N cleavage reactions are demonstrated to provide access to free primary amines, alkylated amines, heterocycles, and products derived from N-centered radical chemistry. The developed reaction sequence can be implemented in the context of complex molecules and natural product derivatives. Together, the described results provide a general and modular synthesis of ß-phenethylamines and significantly expand the utility of N-pyridinium aziridines as linchpins in chemical synthesis.
Full text:
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Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Angew Chem Int Ed Engl
Year:
2024
Document type:
Article