Visible-light Photocatalyzed Fluoroalkylation Reactions in Organic Synthesis. Reaction Mechanisms

AL POSTIGO

MENDOZA

Simposio; XXII SINAQO; 2019

SOCIEDAD ARGENTINA DE INVESTIGACION EN QUIMIA ORGANICA

Visible light photocatalysis has evolved over the last decade into a widely employed method in organic synthesis. For many important transformations, such as cross-coupling reactions, homolytic aromatic substitutions, arylations, cycloadditions, ATRA reactions, or fluorinations, photocatalytic variants have been informed. This is accomplished by photocatalysts used in sub-stoichiometric quantities that absorb light in the visible region of the electromagnetic spectrum. In many cases, the photocatalytic reactions proceed under milder reaction conditions, typically at room temperature, and stoichiometric reagents are replaced by simple oxidants or reductants, like air, amines, carbonates or other electron donors. On the other hand, methods for the synthesis of fluorinated systems are high on the agenda of many synthetic chemists within the life science industries. Incorporation of fluorine or fluorinated groups such as trifluoromethyl, perfluoroalkyl, difluoromethyl and other fluorinated scaffolds into pharmaceutical and veterinary drugs to increase their pharmacological properties is nowadays a standard practice. Visible-light photocatalytic protocols are convenient for the late-stage introduction of fluorinated groups into organic substrates. The ?late-stage? introduction of fluorinated groups refers to strategies that enable the incorporation of fluoroalkyl moieties into already-functionalized organic scaffolds ordinarily in a last step of a synthetic route. This approach demands protocols highly-tolerant with the presence of many functional groups, mild reaction conditions, and diverse electronic demands. In this venue is where the employment of photocatalytic reactions plays a dominant role. We will show photocatalytic synthetic strategies to incorporate fluorinated groups such as CF3, CF2, CnF2n+1, etc. into organic and biological relevant substrates such as (hetero)aromatic compounds, carbohydrates, etc. employing organic or organometallic photocatalysts that absorb in the visible region of the electromagnetic spectrum. As photocatalysis is entering a more refined stage of development where the consolidation of experimental and mechanistic studies will play an assertive role in sustaining further innovation we will outline key mechanistic studies for acquiring relevant information. The discussion will use selected case studies to highlight how mechanistic investigations can be instrumental in guiding the invention and development of synthetically useful photocatalytic transformations.References?Late-stage Fluorination of Bioactive Molecules and Biological Relevant Substrates?. Ed. Al Postigo. Copyright ©2019 Elsevier Inc. Netherlands, United Kingdom, United States. ISBN: 978-0-12-8112958-6