The carbonyl group is a structural motif common in a diverse range of natural products and pharmaceutical agents used to treat human diseases. This project involves the systematic expansion of hydroacylation as an ideal and powerful strategy for making carbonyl-containing compounds, including both esters and ketones. This innovative approach will lead to step- and atom-economical, sustainable, and stereoselective methods that greatly bolster our ability to access molecules relevant to human health, including enantiopure heterocycles and polyketides. In addition, these studies will provide efficient ways to make building blocks that can be elaborated to bioactive structures. Besides the practical value, this project will provide fundamental insights into the use of various catalysts, including rhodium, ruthenium, cobalt, and nickel, for the activation and functionalization of carbon-hydrogen bonds-a long standing challenge in modern organic chemistry.
Our ability to discover new medicines and subsequently prepare these medicines on large-scale relies on the availability of versatile and practical methods for building organic molecules. In this context, hydroacylation is an ideal, environmentally friendly, and powerful way to transform simple compounds (e.g., aldehydes) into a wide range of valuable building blocks and final targets. By both rationale design and experimental observation, this project will transform hydroacylation into a broadly useful tool for building molecular structures relevant to understanding biology and treating human disease.
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