Dr. Socrates B. Munoz
Kansas State University
The direct of carboxylic acids as substrates in catalytic transformations is a highly desirable goal because of their vast structural variety, commercial availability, synthetic availability (great number of preparative methods), physicochemical properties related to storage and handling, and their vast abundance in naturally occurring compounds. Most established synthetic transformations of carboxylic acids (catalytic or otherwise) rely on the use carboxylic acid derivatives such as acyl halides, acid anhydrides, (thio)esters and more recently, activated twisted amides, all of which must pre-synthesized from the parent carboxylic acids. Hence our efforts are being focused on the direct use of carboxylic acids via in-situ activation.
In this context, multiple direct catalytic transformations of carboxylic acids feedstocks giving rise to (fluroalkyl)ketones, aldehydes and acyl fluorides directly, will be delineated in this presentation. Key to the success of these transformations is the use of acyloxyphosphonium ions as acyl electrophiles, readily and conveniently prepared in-situ from parent carboxylic acids and commodity chemicals. The transformations proceed under exceedingly mild conditions in short reaction times and exhibit notable chemoselectivity and functional group compatibility. Late-stage functionalization of active pharmaceutical ingredients (APIs) utilizing this approach will be also presented.