ABC · Harnessing Carboxylic Acids via ABC – Asymmetric Boronic acid-based Catalysis

Developing new methods to functionalize molecules controlling their stereochemistry is of outmost important in almost any area of chemistry. However, factors such as costs, efficiency, sustainability and waste production are a major concern. As the pharmaceutical industry is increasingly aware of the importance of and greater clinical success in creating biomolecules with 3-D architectures there is a strong impetus to try to develop new efficient and sustainable asymmetric methods. The impact of organocatalysis (the use of small organic molecules to promote asymmetric transformations) has been immense across many aspect of society spanning from the synthesis of pharmaceutical compounds to agrochemicals and materials. However, whilst useful for the activation of compounds such as aldehydes and ketone, this concept cannot be used for the functionalization of carboxylic acids. This limits the development of new and efficient methods because carboxylic acids frequently represent the starting material as well as the final product of many synthetic sequences. This proposal seeks to explore fundamentally new ideas based around rationally designed boron transformations aimed at the development of novel approaches towards asymmetric, transition metal-free functionalization of carboxylic acids. The proposed approach relies on the activation of carboxylic acids by the addition of chiral boronic acids catalysts to generate chiral mono-acyl boronate intermediates. Subsequent addition of a nucleophile (or a diene) would results in highly valued and polyfunctional non-racemic carboxylic acids, amides and thioesters with water as the stoichiometric waste. Preliminary DFT calculations suggest that the asymmetric induction is viable. This proposal is aimed at the career development of applicant by allowing him to establish an independent research career on a scientific area that is expected to have a big impact on the society.