Product Control Using Substrate Design

Product Control Using Substrate Design

Author: Pamela Alsabeh

Weinreb amides are synthetically useful organic compounds and have recently gained popularity as directing groups. Efforts have been directed towards C–H functionalization of the amides without loss of the N-alkoxy moiety. Rhodium and palladium-catalyzed oxidative Heck processes with olefins in which the N-alkoxy group tolerates the reactions conditions have been developed.

Riki Das and Manmohan Kapur, Indian Institute of Science Education and Research, Bhopal, India, have found a new class of cyclic Weinreb amides that can be used in Ru-catalyzed oxidative Heck reactions. Previous work from the authors using an identical catalyst system provided products with cleaved N-alkoxy moieties. The amides in this current work kept their synthetic feature intact simply by applying larger 6-and 7-membered cycles (example pictured). The undesired N–O reductive bond cleavage was thus inhibited and the target C–H olefination products were obtained.

The reaction was found to be site-selective, tolerant of a diverse amount of substrates, and provided only the monoolefination products in good yields without any diolefination. Kinetic and deuterium-labelling studies provided some mechanistic insight; the formation of a ruthenacycle is reversible and the reaction is pushed forward by the faster rate of all subsequent steps. The team demonstrates the synthetic utility of the products with further functionalization.


 

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