Visible‐Light‐Driven Catalytic Deracemization of Secondary Alcohols

Abstract

Deracemization of racemic chiral compounds is an attractive approach in asymmetric synthesis,b ut its development has been hindered by energetic and kinetic challenges. Here we describe ac atalytic deracemization method for secondary benzylic alcohols which are important synthetic intermediates and end products for many industries.Driven by visible light only,t his method is based on sequential photochemical dehydrogenation followed by enantioselective thermal hydrogenation. The combination of ah eterogeneous dehydrogenation photocatalyst and ac hiral molecular hydrogenation catalyst is essential to ensure two distinct pathwaysfor the forwarda nd reverse reactions.T hese reactions convert al arge number of racemic aryl alkyla lcohols into their enantiomerically enriched forms in good yields and enantioselectivities.

Light empowers contra-thermodynamic stereochemical editing

“…Because of the good compatibility of photocatalysis 34 , the combination of powerful redox-and bond-formation transformations of photocatalysis with the catalytic power and excellent enantioselectivities of transition metal catalysts and enzymes in functional group interconversions, also constitutes an emerging field for deracemization of racemic chiral compounds. For instance, the Hu group disclosed an interesting visible-light-driven one-pot deracemization of secondary alcohols by a sequential irreversible photochemical dehydrogenation and an enantioselective thermal hydrogenation, using a combination of Ni-modified cadmium sulphide and Noyori's Ru-based chiral hydrogenation catalyst 35 . Recenlty, Glueck, Winkler, and co-workers reported a concurrent photocatalytic oxidation and biocatalytic reduction procedure for cyclic deracemization 36 .…”

Deracemization through Sequential Photoredox‐Neutral and Chiral Brønsted Acid Catalysis

“…A dicyanopyrazine‐derived chromophore (DPZ) [30–32] as the photocatalyst is responsible for performing two SET events with a variety of α ‐amino esters and other important α‐amino variants. Although the resultant prochiral anion intermediates can readily undergo a non‐catalytic protonation process to regenerate racemic substrates, [33] the eventual accumulation of enantiomers is achieved with up to >99.5 % enantiomeric excess (ee), which is completely determined by the stereocontrol efficiency of the chiral catalyst to reconstruct C−H bonds. In addition, this method has been proven to be effective in the synthesis of enantioenriched α ‐deuterated‐ α ‐amino esters.…”

Deracemization of racemic alcohols combining photooxidation and biocatalytic reduction

“…7 Hu's lab has developed a catalytic deracemization method for secondary benzylic alcohols which is based on sequential photochemical dehydrogenation followed by enantioselective thermal hydrogenation. 8 Although these elegant methods have been reported, developing other efficient methods to extend the tool library of alcohol deracemization is still meaningful.…”