Arylation of Diethyl Acetamidomalonate with Diaryliodonium Salts En Route to α-Arylglycines

Abstract

Diethyl acetamidomalonate (DEAM) has been widely used for the synthesis of α-amino acids via C-alkylation under basic conditions followed by hydrolysis/decarboxylation. In contrast, the C-arylation of this reagent remains undeveloped. Herein, we report a novel strategy for the synthesis of racemic αarylglycines based on the selective arylation of DEAM with diaryliodonium salts under mild, transition metal-free conditions. The reaction features good functional group tolerance and easy scalability and is applicable to the chemoselective C−H-modification of arenes including approved drugs, thus enabling a straightforward approach to complex α-arylglycines that would be challenging to make otherwise.

Transition-Metal-Free C-Diarylations to Reach All-Carbon Quaternary Centers

“…The primary challenges for the synthesis of quaternary carbon centers are steric congestion and conformational restrictions . Quaternary α-monoarylated centers can be obtained from β-dicarbonyl compounds and nitroalkanes via transition metal catalysis, − and metal-free strategies include S N Ar, aryne chemistry, and sulfoxide-mediated arylation. ,− Diaryl­iodonium salts, which are mild electrophilic arylating reagents, − have also proved efficient in metal-free α-arylation of β-keto esters, malonates, and nitroalkanes. − …”