A NOVEL CLASS OF DECAHYDROQUINOXALINE-BASED CHIRAL PHOSPHORIC ACIDS

Chiral phosphoric acids (CPAs) have found extensive application in many chemical transformations, becoming invaluable tools for syn thesizing pharmaceuticals and natural products. This study introdu ces 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 pina col coupling of Salen-like bisimines, obtained by condensation of different aromatic aldehydes with enantiopure trans-1,2-diaminocy clohexane. By using two different approaches, a small library of novel CPAs is synthesized, which are successfully employed to cat alyze the Friedel–Crafts addition of indoles to N-tosylimines, yield ing 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. The stereoselective electroreductive intramolecular imino-pinacol coupling has been investigated by an electrochemical approach. The methodology was successfully developed under both batch and continuous flow conditions, and afforded enantiomerically pure products with complete stereoselectivity. Substrates bearing electron-donating or electron-withdrawing groups on the aromatic rings provided good to excellent yields, indicating that both types of substituents are well tolerated under the reaction conditions. Al though modest yields were obtained under flow conditions, the continuous process afforded higher productivities and space-time yields than the batch reactions due to a short residence time. This work provides a mild, efficient, and scalable alternative to traditional methods for the synthesis of tetrasubstituted enantiopure piperazines.