Palladium-Catalyzed α-Arylation of Dimethyl Malonate and Ethyl Cyanoacetate with o-Alkoxybromobenzenes for the Synthesis of Phenylacetic Acid, Esters and Phenylacetonitriles

Abstract

α-Aryl malonate and α-aryl cyano acetate moieties are found in the structures of many bioactive compounds. They are also key intermediates for the synthesis of many compounds such as isoflavonoids. In this work, we synthesized these compounds, with different patterns of substitution, starting with the palladium-catalyzed reaction of o-alkoxybromoarenes with dimethyl malonate or ethyl cyanoacetate. Under the conditions applied, moderate to good yields of arylmalonate monoesters, phenylacetic esters or acids, and benzylnitrile derivatives were obtained.

Recent advances in palladium‐catalyzed α‐arylation reactions

“…Cívicosa et al proposed an approach for the α-arylation of ethylcyanoacetate and dimethylmalonate by employing o-alkoxy-bromoarenes as the arylating agents. 57 The reaction was catalyzed by Pd 2 (dba) 3 in toluene at 70 C (Scheme 29). The products thus obtained, aryl malonates and aryl cyanoacetates, could be converted into phenylacetic acids or the corresponding methyl esters and aryl acetonitriles, respectively.…”

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

“…The α-arylated carboxylic acid derivatives are a ubiquitous class of compounds that constitutes the backbone for various nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen. − Organic structures with an all-carbon quaternary center pose unique importance because of their bioactivities and constraint arrangements. , α-Arylation of carbon nucleophiles to generate quaternary carbon centers and enrich molecular complexity has attracted significant attention, furnishing a vast range of arylated organic molecules with medicinal importance, such as methadone, isopropamide, and diphenoxylate (Scheme A). − …”