Optimization of Manganese Coupling Reaction for Kilogram-Scale Preparation of Two Aryl-1,3-dione Building Blocks

Aryl-1,3-diones represent a promising new class of herbicidal acetyl-CoA carboxylase (ACCase) inhibitors. The original synthesis of this structural motif employed in the research phase involved a selenium oxide mediated oxidation, the use of diazoacetate and aryl lead reagents, and a low temperature oxidation of an aryl lithium intermediate, so it was not well suited to large scale synthesis. For kilogram scale synthesis of the two aryl-1,3-dione building blocks (3 and 4), we developed an alternative route which employs a manganese or manganese-copper catalyzed alkyl Grignard coupling and a semi-pinacol rearrangement of an epoxide as the key steps. The optimized conditions could be of general interest as scalable methods for the synthesis of 2-alkyl substituted benzaldehydes and of 2-aryl-1,3-diones.