Synthesis Of Chiral BINAM Derivatives

BINAM derivatives are highly useful chiral biaryls, and several well-establishedBINAM-based catalysts have been developed for asymmetric catalysis. However, the lackof general synthetic methods hampers their exploitation up to their full potential.Stereoselective attempts towards enantiopure BINAM derivatives are rare and theirpreparation mainly relies on a classical resolution, although a moderately enantioselectiveoxidative homocoupling of2-naphthylamines has been reported. Unlike the BINOLsystem, an oxidative coupling approach is not effective and gives only limited success. Anacid-catalyzed [3,3]-rearrangement of diaryl hydrazines may potentially be a powerful andgeneral approach to either racemic or optically active BINAM derivatives. Indeed, veryrecently, the groups of Kürti and List developed independently the highly enantioselectivesynthesis of biaryl amines using the chiral phosphoric acids catalyzed[3,3]-rearrangement.Unfortunately, this methodology, from a practical view, is limited bythe difficult accessibility of the starting diaryl hydrazines and chiral phosphoric acids. Stereoselective, convenient and powerful synthetic approach to structurally diverseBINAM derivatives will have a profound impact on the discovery of new biaryl-typechiral ligands and catalysts. Herein, we describe an efficient and practical synthesis ofBINAM derivatives by diastereoselective [3,3]-rearrangement.1. Metal catalyzed cross-coupling reaction, screened the combination of different ligandand metal, reaction temperature, reaction time and solvent, etc., we get the best reactioncondition, the highest yield.2. In the intramolecular rearrangement reaction, we have screened different acid, solvent,reaction temperature and reaction time, etc., to get the optimum reaction conditions, makesthe least impurities and the highest yield3. Explores the amide bond hydrolysis conditions, respectively using acid hydrolysis andalkali hydrolysis to get product naphthylamine and its derivatives, acid hydrolysisproducts has impurities generated, alkali hydrolysis reaction, high yield. Use HPLC todetect the ee to be above99%.This thesis designed and synthesized the optical activity of naphthylamine and itsderivatives, provides a feasible effective synthesis methods to obtain chiral naphthylamineand its derivatives, and laid the foundation for its further application.