Carboxylic Acids as Building Blocks in Catalytic Asymmetric Reactions

Catalytic asymmetric transformation is a powerful strategy for the introduction of chirality to synthesize diverse nonracemic molecular entities. Chiral molecules play a significant role in the pharmaceutical area, as 50% of current drugs that are in use and 80% of the developing drugs are chiral. Asymmetric catalysis has been explored tremendously by synthetic organic chemists, and still continuous efforts are being directed toward advanced discoveries. The role of carboxylic acids as building blocks in catalytic asymmetric reactions is an emerging area. Carboxylic acids are known for their robustness and thus low reactivity. They are widely available, yet quite challenging substrates for catalytic asymmetric synthesis. The catalyst required for this kind of transformation must withstand acidic as well as oxidizing conditions. Catalyst and reaction design are required to break the glass ceiling of low reactivity of the acid substrates to ensure the useful transformation becomes successful. At the same time, high stereoselectivity needs to be achieved with complete control. Because of these challenges, carboxylic acids are highly intriguing substrates in the asymmetric catalysis research area, and more interesting methods are developing. There have been many important advancements in the last three decades. These literature reports show that carboxylic acids can act as both C- and O-nucleophiles. Furthermore, they can also be employed as electrophiles in asymmetric reactions under catalytic conditions. Brilliant application of catalyst and reaction designs made these transformations possible. This review article summarizes all these important developments on the use of carboxylic acids as building blocks in asymmetric catalysis.