Static to inducibly dynamic stereocontrol: The convergent use of racemic β-substituted ketones.

The synthesis of stereochemically complex molecules in the pharmaceutical and agrochemical industries requires precise control over each distinct stereocenter, a feat that can be challenging and time consuming using traditional asymmetric synthesis. Although stereoconvergent processes have the potential to streamline and simplify synthetic routes, they are currently limited by a narrow scope of inducibly dynamic stereocenters that can be readily epimerized. Here, we report the use of photoredox catalysis to enable the racemization of traditionally static, unreactive stereocenters through the intermediacy of prochiral radical species. This technology was applied in conjunction with biocatalysts such as ketoreductases and aminotransferases to realize stereoconvergent syntheses of stereodefined γ-substituted alcohols and amines from β-substituted ketones

Decarboxylative Trifluoromethylation of Aliphatic Carboxylic Acids

Herein we disclose an efficient method for the conversion of carboxylic acids to trifluoromethyl groups via the combination of photoredox and copper catalysis. This transformation tolerates a wide range of functionality including heterocycles, olefins, alcohols, and strained ring systems. To demonstrate the broad potential of this new methodology for late-stage functionalization, we successfully converted a diverse array of carboxylic acid-bearing natural products and medicinal agents to the corresponding trifluoromethyl analogues

An Expedited Phenotypic Approach Towards Organic Reaction Generality

Reaction generality is crucial in determining the overall impact and usefulness of organic synthetic methods. In contrast, contemporary generalization processes seem unable to meet the growing demand for robust methodology. We sought to develop an accelerated approach towards achieving generality, inspired by phenotypic screening, that rapidly expands the scope and utility of synthetic methods. This approach was validated by example of the metallaphotoredox decarboxylative arylation, resulting in the discovery of a novel additive that overcomes many lingering limitations of this method and has significant mechanistic implications for nickel-catalyzed cross couplings in general