Catalytic activation and derivatization of methyl esters

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The world's most important agrochemicals, pharmaceuticals, and polymers are organic molecules, the vast majority of which are prepared by chemical synthesis. The diverse properties of these molecules derives from the nature and spatial relationship of the functional groups embedded within the carbon-based scaffold. The amide bond is undoubtedly one of the most important functional groups, providing molecules such as peptides and polymers with structural rigidity and the ability to interact with other organic matter. It has been estimated that up to 20% of all chemical reactions done in the world involve the synthesis of an amide. Despite the great importance of amides, the most common methods to synthesize this functional group are surprisingly archaic and wasteful. The Newman lab has recently developed a new catalytic method to form amide bonds from simple and abundant ester and amine precursors. This new method has the potential to provide a more cost effective means for preparing important agrochemicals and pharmaceuticals. However, the current catalyst system suffers from a number of limitations such as the requirement for large amounts of the catalyst, long reaction times, and high temperatures. These problems will need to be solved before potential industrial implementation. Furthermore, the underlying mechanistic discovery that metal catalysts can activate ester starting materials towards substitution chemistry has immense potential to improve the way that we access many other important functional groups. Ketones, aryl amines, aldehydes, AND aryl boronates may be readily accessible using cross-coupling of methyl esters. This research project will seek to accomplish two goals. (1) To gain mechanistic understanding of the newly discovered amide bond formation and use that knowledge to improve the catalyst to the point of industrial viability. (2) To exploit the catalytic activation of esters to make other important organic molecules. Success in these areas will decrease the cost of currently utilized agrochemicals, expand the pipeline of newly developed agrochemicals and pharmaceuticals, and reduce waste generated in chemical manufacturing plants.****