Enantioselective Synthesis Of Nitrogen-Containing Optically Active Compounds Catalyzed By Novel Chiral Phosphoric Acids

Chiral phosphoric acids(CPAs),which represent powerful,economically feasible tools for the preparation of optically active organic molecules,have emerged as a widely used class of versatile Br(?)nsted acid catalysts for many enantioselective transformations.CPAs have many advantages,such as easy accessibility,appropriate acidity to capture electrophilic components,modular nature,stability towards oxidation and hydrolysis,and so on.In this dissertation,we firstly reviewed the research progress of chiral phosphoric acids,and then reported the SPA-catalyzed synthesis of optically active tetrahydro-?-carboline derivatives.Afterwards,a novel class of planar chiral phosphoric acids(denoted as PPAs)based on[2.2]paracyclophane backbone were designed and synthesized.Subsequently,the application of PPAs in the synthesis of optically active 3-indolylmethanamine derivatives was described.The main contents are summarized as follows:1.An enantioselective aza-Friedel-Crafts alkylation reaction of indoles with 1-trifluoromethyl-3,4-dihydro-?-carbolines catalyzed by a chiral spirocyclic phosphoric acid has been realized.This protocol provides a facile and efficient access to functionalized tetrahydro-?-carbolines with a CF3-and indole-containing quaternary stereocenter in good yields(61-86%)and good to excellent enantioselectivities(75-96%ee).The reaction involves a simple scalable experimental procedure.A possible reaction mechanism was proposed.The absolute configuration of the product 2.32de was determined to be S by the X-ray diffraction analysis.2.A new type of robust planar chiral phosphoric acids bearing a[2.2]paracyclophane scaffold was synthesized from commercially available starting materials.Firstly,starting from 4-bromo-3-methoxyphenol,four boronic acid pinacolesters were afforded in three-step reaction procedure,including Suzuki coupling,esterification and Suzuki coupling,with a total yield of 76-86%.Next,starting from the commercially available(RP)-3.3 and the boronic acid pinacolesters or arylboronic acid,the new planar chiral phosphoric acids were synthesized in five-steps transformation,including Suzuki coupling,demethylation,cyclization,oxidation,hydrolysis,with a total yield of 16-57%.The absolute configuration of a key intermediate 3.7b was confirmed by X-ray diffraction analysis.3.The asymmetric aza-Friedel-Crafts reactions between cinnamaldehyde-derived N-tosylimines and indoles catalyzed by planar chiral phosphoric acids bearing a[2.2]paracyclophane scaffold has been developed.This protocol provides a mild method to various enantioenriched styryl indolylmethanamine derivatives in good yields(up to>99%)with excellent enantioselectivities(up to>99%ee)under the optimal conditions,and involves a simple scalable experimental procedure.The absolute configuration of the product 4.26ba was determined to be S by the X-ray diffraction analysis.A wide range of N-tosylimines,derived from heteroaromatic and aromatic aldehydes,were also found to be suitable substrates,leading to the corresponding 3-indolylmethanamines in high yields with excellent enantioselectivities under the optimal reaction conditions.