Research Projects

The catalytic alpha-functionalization of aliphatic carboxylic acid synthons, including amides and esters, is a significant synthetic transformation due to their abundance in biologically active compounds, approved drugs, and terrestrial and marine natural products. Conventional approaches, dominated by enolate chemistry, require a strong base in over stoichiometric quantity to obtain a nucleophilic enolate equivalent, which then reacts with an electrophilic partner to give the targeted alpha-functionalized product. However, this requirement often leads to issues of modest chemoselectivity for substrates with multiple competing carbonyl groups and problems in controlling stereoselectivity for complex molecules. Efforts have been made in recent decades to catalytic alpha-functionalization of carboxylic acid equivalents in an atom and step-economic manner. Literature suggests that a functional substituent can be installed at the alpha-position of carboxylic acids in the presence of an oxidant under both transition metal-catalyzed and -free conditions. However, many classes of carboxylic acid derivatives cannot be functionalized using these strategies, and none allow installation of practically abundant functional groups like hydroxy and amine. This proposal proposes novel approaches for catalytic alpha-functionalization of carboxylic acid synthons with adaptable substituents, such as OH, NH2, and SH, which can be directly utilized as the key step for the synthesis of bioactive marine-derived compounds.