Radical fixation of functionalized carbon resources: alpha-sp3C-H carbamoylation of tertiary amines with aryl isocyanates.
A new carbamoylation of tertiary amines is reported. This rare C-H transformation features the direct generation of alpha-aminoalkyl radicals from tertiary amines, followed by the addition of the resultant nucleophilic radicals to isocyanates, enabling unique access to N,N-dialkylated amino acid derivatives. The authors put forward a mechanistic proposal that is based on the isolation of borinamides produced by capturing nitrogen radical intermediates with Et3B. The present transformation provides a novel one-step process for producing mepivacaine, a clinically important local anesthetic, from readily available materials.
Yoshimitsu
Takehiko
T
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan. yoshimit@phs.osaka-u.ac.jp
Matsuda
Kenichi
K
Nagaoka
Hiroto
H
Tsukamoto
Koji
K
Tanaka
Tetsuaki
T
D000588:Amines / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D005609:Free Radicals / Q000737:chemistry; D017953:Isocyanates / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure
D000588:Amines; D000596:Amino Acids; D005609:Free Radicals; D017953:Isocyanates