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

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