The Application of Flow Chemistry for the Synthesis of Alkyl Sodium Compounds and Their Transformations with Weinreb Amides and Carboxylic Acids.

Herein, we describe the application of a flow system for the generation of a soluble organo sodium compound and the transformation of this primary nucleophile with various Weinreb amides for the synthesis of alkyl-aryl ketones. Thereafter, the generation of secondary sodium intermediates, such as benzylic sodium nucleophiles or ortho-metalated sodium nucleophiles from various carbon pre-nucleophiles, is described. These transformations generated more complex ketones, and in this investigation the key aspect was to identify factors for the chemoselective and regioselective C-H deprotonation of concurring sites within the starting material. Finally, the direct synthesis of ketones from carboxylic acids and the organo sodium compound is described, revealing interesting aspects regarding the nucleophilicity and basicity of the alkyl sodium reagent.