Light empowers contra-thermodynamic stereochemical editing

Abstract

Creating, preserving, and manipulating the stereochemistry of organic compounds has long been a cornerstone of modern organic synthetic chemistry, and the synthetic routes are typically designed according to stereoselectivity-determining step that is known as stereochemical logic. As an alternative strategic platform, stereochemical editing, wherein the chiral- or geometry-defining events are decupled from the main scaffold or complexity-forming steps, has the potential for late-stage flexibility in generating isomers from a single compound. However, under many instances, the desired stereochemical editing processes are contra-thermodynamic on ground states and thus unfavorable. Recent research has begun to leverage photocatalysis to yield many potentially generalizable concepts to empower contra-thermodynamic stereochemical editing by providing approach to irreversible elementary steps via excited electronic states and/or by introducing thermochemical biases. A broad range of synthetically valuable contra-thermodynamic stereochemical editing processes were thus invented, including deracemization of racemic chiral molecules, positional alkene isomerization, and dynamic epimerization of sugars and diols. In this review, we highlight how an understanding of the mechanisms of visible-light photocatalysis and of the general reactivity patterns of the photogenerated radical intermediates has been engineered to develop these concepts.

Flipping the Switch on Palladium-Catalyzed Carboiodination: Accessing Kinetic and Thermodynamic Products

“…Accessing all possible stereoisomers through common intermediates is an attractive approach in synthesis, as the physical and biological properties of each epimer may differ. − Typically, stereocenters are installed with the desired relative and absolute configuration at an early stage in a synthesis. , Consequently, accessing other stereoisomers may require restarting the synthetic sequence and modifying reagents or catalysts. Recently, the idea of accessing different diastereomers via stereochemical editing of a single stereocenter has been considered an attractive alternative. , Late-stage modification of select stereocenters has many advantages if high selectivity can be achieved. − The presence of reactive hydrogen atoms at the stereocenter of interest aids in the process, but also limits the scope of this strategy.…”

“…Recently, the idea of accessing different diastereomers via stereochemical editing of a single stereocenter has been considered an attractive alternative. 6,7 Latestage modification of select stereocenters has many advantages if high selectivity can be achieved. 8−11 The presence of reactive hydrogen atoms at the stereocenter of interest aids in the process, but also limits the scope of this strategy.…”