Photodynamic Resolution of Racemic Compounds having Axial Chirality

Enantioselective synthesis is the cornerstone of modern synthetic chemistry and a crucial step in the production of fine chemicals like food additives, fragrances, natural products, and pharmaceuticals.

One of the most utilized ligands/ catalysts for these enantioselective reactions is 1,1' - bi-2-napthol ("BINOL"). The most common methods to synthesize these complexes, however, result in the formation of a racemic mixture of R and S isomers. Unfortunately, since only a single isomer of BINOL is needed, the racemic mixture is typically purified through chromatography or recrystallization to achieve the desired isomer, while the other half of the reaction mass is discarded.

The present invention proposes the use of photoisomerization as an alternative strategy to generate enantiomerically pure BINOL. Due to excited state proton transfer (ESPT) BINOL can planarize and isomerize upon photoexcitation. We have invented the use of bulky chiral auxialiary groups to increase the rotational barrier of relaztion selectively for one BINOL atropisomer as a means of preferentially generating one of the BINOL isomers. The identity of the auxiliary group determined both the direction of rotation and the extent of enantiomeric excess observed.

Advantages:

• Photoisomerization can generate a racemic mixture and then preferentially photoconvert to only one of the isomers
• This strategy does not waste 50 percent of the product
• Can be done on large scale with minimal solvent

Applications:

• Chemical companies that sell or use BINOL (Sigma, VWR, Merck, etc.)