Next‐gen catalysts: introducing C2 symmetrical chiral phosphoric acids on a decahydroquinoxaline scaffold

Chiral phosphoric acids (CPAs) have found extensive application in many chemical transformations, becoming invaluable tools for synthesizing pharmaceuticals and natural products. This study introduces a novel class of CPAs based on a chiral decahydroquinoxaline scaffold. The synthetic strategy for the construction of the chiral backbone involves as a key step a completely stereoselective pinacol coupling of Salen-like bisimines, obtained by condensation of different aromatic aldehydes with enantiopure trans-1,2-diaminocyclohexane. By using two different approaches, a small library of novel CPAs is synthesized, which are successfully employed to catalyze the Friedel–Crafts addition of indoles to N-tosylimines, yielding the desired enantioenriched products in high yield and up to 97% ee. The new enantiopure Brønsted acids are highly tunable, can be efficiently prepared in four steps from inexpensive materials, and exhibit high chemical and stereochemical efficiency, in some instances exceeding results obtained from traditional CPAs based on binaphthol scaffolds.