Wednesday, April 22, 2020

CLAISEN CONDENSATION

Acetoacetic-Ester Condensation
Claisen Condensation




The Claisen Condensation between esters containing α-hydrogens, promoted by a base such as sodium ethoxide, affords β-ketoesters. The driving force is the formation of the stabilized anion of the β-keto ester. If two different esters are used, an essentially statistical mixture of all four products is generally obtained, and the preparation does not have high synthetic utility.


However, if one of the ester partners has enolizable α-hydrogens and the other does not (e.g., aromatic esters or carbonates), the mixed reaction (or crossed Claisen) can be synthetically useful. If ketones or nitriles are used as the donor in this condensation reaction, a β-diketone or a β-ketonitrile is obtained, respectively.
The use of stronger bases, e.g. sodium amide or sodium hydride instead of sodium ethoxide, often increases the yield.
The intramolecular version is known as Dieckmann Condensation.



Mechanism of the Claisen Condensation










Recent Literature




General, Robust, and Stereocomplementary Preparation of α,β-Disubstituted α,β-Unsaturated Esters



Direct Carbon-Carbon Bond Formation via Chemoselective Soft Enolization of Thioesters: A Remarkably Simple and Versatile Crossed-Claisen Reaction Applied to the Synthesis of LY294002



Mild and Efficient Pentafluorophenylammonium Triflate (PFPAT)-Catalyzed C-Acylations of Enol Silyl Ethers or Ketene Silyl (Thio)Acetals with Acid Chlorides




Powerful Ti-Crossed Claisen Condensation between Ketene Silyl Acetals or Thioacetals and Acid Chlorides or Acids




Synthesis of Trifluoromethyl Ketones via Tandem Claisen Condensation and Retro-Claisen C-C Bond-Cleavage Reaction




Consecutive Michael-Claisen Process for Cyclohexane-1,3-dione Derivative (CDD) Synthesis from Unsubstituted and Substituted Acetone




"One-Pot" Synthesis of 4-Substituted 1,5-Diaryl-1H-pyrazole-3-carboxylic Acids via a MeONa/LiCl-Mediated Sterically Hindered Claisen Condensation-Knorr Reaction-Hydrolysis Sequence

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