Catalytic Deracemization Reactions

Abstract

Deracemization, which converts a racemate into its single enantiomer without separation of the intermediate, has gained renewed interest in asymmetric synthesis with its inherent atomic economy and high efficiency. However, this ideal process requires selective energy input and delicate reaction design to surmount the thermodynamical and kinetical constraints. With the rapid development of asymmetric catalysis, many catalytic strategies in concert with exogenous energy input have been exploited to facilitate this nonspontaneous enantioenrichment. In this perspective, we will discuss the basic ideas to accomplish catalytic deracemization, categorized by the three major exogenous energy sources including chemical (redox)-, photo- and mechanical energy from attrition. Emphasis will be given to the catalytic features and the underlying deracemization mechanism together with perspectives on future development.

Photocatalyzed Enantioselective Functionalization of C(sp3)–H Bonds

“…Deracemization, which converts a racemate compound into its single enantiomer, is an attractive strategy for accessing enantioenriched compounds. − In 2019, the Miller and Knowles group developed an elegant deracemization method that enabled racemic amine derivatives to spontaneously transform into optically enriched amines with the irradiation of visible light in the presence of three different molecular catalysts (Scheme ). This reaction underwent a sequential photodriven SET/deprotonation/HAT process, which was used to break and reconstruct a stereogenic C­(sp 3 )–H bond.…”

Enantioselective organocatalytic strategies to access noncanonical α-amino acids

“…As a result, no net deracemization can be accomplished without an external perturbation that circumvents the principle of microscopic reversibility. 152 Thus, a deracemization reaction must comprise two half-reactions that are opposite in reaction direction and have distinct mechanistic pathways. At least one of these should operate enantioselectively.…”

Organic Synthesis Away from Equilibrium: Contrathermodynamic Transformations Enabled by Excited-State Electron Transfer

“…These dual limitations are challenging to address and relatively few thermal catalytic deracemization reactions have been reported to date. Most of these protocols make use of chemically compatible or phase-separated combinations of oxidants and reductants that can drive the reversible formation and consumption of a common achiral intermediate . While effective, the scope and generality of these methods are often limited by the compatibility of these oxidant and reductant pairs.…”