Biomimetic Asymmetric Reduction Based on the Regenerable Coenzyme NAD(P)H Models

Area of Science:

• Organic Chemistry
• Catalysis
• Biomimetic Chemistry

Background:

• Nature utilizes coenzyme NAD(P)H for biocatalytic reduction, involving hydrogen and electron transfer.
• Previous non-regenerable NAD(P)H mimics suffered from poor atom economy and difficult product separation.
• Development of efficient, regenerable NAD(P)H models is crucial for advancing organic synthesis.

Purpose of the Study:

• To design and synthesize regenerable achiral and chiral NAD(P)H models.
• To apply these models in biomimetic asymmetric reduction (BMAR) reactions.
• To overcome limitations of existing NAD(P)H mimics and improve synthetic efficiency.

Main Methods:

• Synthesis of regenerable achiral NAD(P)H models (dihydrophenanthridine, dihydropyrroloquinoxaline).
• Application of achiral models in BMAR of imines and heteroaromatics with ruthenium catalysts and chiral phosphoric acid.
• Design and synthesis of regenerable chiral NAD(P)H models (CYNAM, FENAM) with planar chirality for BMAR.

Main Results:

• Achiral models successfully reduced imines and heteroaromatics but required tedious chiral catalyst screening.
• Chiral NAD(P)H models enabled asymmetric reduction using simple achiral catalysts, with enantioselectivity originating from the model.
• The developed methodology efficiently reduced challenging electron-deficient tetrasubstituted alkenes and various imines/heteroaromatics.

Conclusions:

• Regenerable chiral NAD(P)H models offer an efficient strategy for synthesizing chiral building blocks and bioactive molecules.
• This approach simplifies asymmetric reduction processes by utilizing readily available achiral catalysts.
• The study provides significant implications for biomimetic asymmetric catalysis and synthetic methodology development.