• 10.1021/ol200575c
  • Organic Letters
  • Volume 13
  • May 2011
  • pp 2322-2325

Mild Decarboxylative Activation of Malonic Acid Derivatives by 1,1′-Carbonyldiimidazole

Wide versatility and good reproducibility

Details


This work by Lafrance and co-work represents a very mild means to induce the decarboxylation of malonic acid derivatives with 1,1-carbonyldiimidazole (CDI). The reactive intermediate carbonyl imidazole moiety can be trapped with various nucleophiles in an effcient one-pot process that leads to synthetically and biologically important amides, Weinreb amides, esters or carboxylic acids.

One of my projects involved a multi-step synthesis. For one step, I needed to find a way to convert a malonic acid derivative into its corresponding Weinreb amide under very mild reaction conditions since my substrate contained mutiple functionalities which might undergo decomposition under harsh reaction conditions. It is well known that traditional decarboxylation is usually performed under harsh thermal conditions (up to 200 degree Celsius) and therefore I had recourse to this methodology to realize the transformation. Particularly, the synthesis of 1e using the procedure reported in this paper was attempted and it worked like a charm except that a longer reaction time (12 h instead of 7 h reported in the paper) was needed to ensure the completion of the reaction. In addition, most of the work-up procedures could be skipped. After the reaction completed (12 h), upon the evaporation of the solvent (THF), the residue was directly loaded on the silica gel column with dichloromethane and eluted with EtOAc:hexanes (1:3) (Rf = 0.4) to give the desired Weinreb amide in 87% yield (85% in the paper). Later, this methodolody was applied to my complicated substrates and it worked smoothly, suggesting wide versatility and good reproducibility of this method.



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