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...

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Published in:Organic process research & development 2017-10, Vol.21 (10), p.1625-1632
Main Authors: Smejkal, Tomas, Gopalsamuthiram, Vijayagopal, Ghorai, Sujit K, Jawalekar, Anup M, Pagar, Dinesh, Sawant, Krishna, Subramanian, Srinivas, Dallimore, Jonathan, Willetts, Nigel, Scutt, James N, Whalley, Louisa, Hotson, Matthew, Hogan, Anne-Marie, Hodges, George
Format: Article
Language:English
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Summary: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.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.7b00241