Kinetics, Thermodynamics, and Emergence in Stereoediting Reactions

Area of Science:

• Organic Chemistry
• Stereochemistry
• Catalysis

Background:

• Selective formation of stereoisomers is a major challenge in organic synthesis.
• Stereochemistry is typically fixed during bond formation, limiting flexibility in accessing complex molecules.
• Revising stereochemistry post-synthesis offers a pathway to more challenging targets from accessible precursors.

Purpose of the Study:

• To develop stereocenter editing tools for predictable and tunable interconversion of stereoisomers.
• To leverage radical intermediates and photoredox catalysis for mild and efficient stereoediting.
• To apply these methods to challenging synthetic problems, including rare sugar synthesis and tertiary stereocenter revision.

Main Methods:

• Utilizing sequential hydrogen atom abstraction and donation steps via radical intermediates.
• Employing photoredox catalysis to generate reactive radicals under mild conditions.
• Investigating catalyst control to achieve out-of-equilibrium, kinetically controlled product distributions.

Main Results:

• Developed stereoediting methods for secondary alcohol stereocenters, enabling tunable site- and stereocontrol.
• Extended stereoediting to unactivated tertiary stereocenters, offering new synthetic flexibility.
• Demonstrated applications in rare sugar synthesis and constitutional isomerization, including alkene isomerization.

Conclusions:

• Stereocenter editing provides precise, late-stage control over molecular stereochemistry.
• These methods can fundamentally transform the logic of stereodefined synthesis.
• The developed tools offer significant potential for accessing complex chiral molecules.