Synthesis Of 1,2,3,4-Tetrahydroquinoxalines With Cooperative Catalysis By Lewis Acid And Iridium

1,2,3,4-Tetrahydroquinoxalines represent an important class of nitrogen containing heterocyclic compounds,which have found widespread applications in a great number of pharmaceutically and biologically active substances.Although this compound is very important,the efficient routes for the synthesis of it are limited.Numerous attempts have been made to seek effective methods to synthesize1,2,3,4-tetrahydroquinoxalines and their derivatives in racemic or enantiopure form.Among them,one of the most straightforward strategies is the hydrogenation of quinoxalines by the use of hydrogen molecule.Despite the impressive progress,these methods are generally performed under high pressure of hydrogen or require at least stoichiometric amount of reductant,and meanwhile generate large amount of wastes.Hence,it is of great importance to develop an atom-economical and sustainable synthetic route to produce 1,2,3,4-tetrahydroquinoxalines from readily available starting materials.Inspired by these pioneer work,we proposed a tandem catalysis which consists of following processes: 1)Lewis acid-catalyzed aminolysis of epoxides with1,2-benzenediamine derivatives affords amino alcohol intermediate;2)transition metal-catalyzed intramolecular N-heterocyclization of amino alcohol generates the corresponding 1,2,3,4-tetrahydroquinoxaline via borrowing hydrogen methodology.We have achieved excellent results after a series of experiments.Herein,we report the synthesis of 1,2,3,4-tetrahydroquinoxalines from readily available epoxides and1,2-diaminobenzenes by a cooperative catalysis of Lewis acid and iridium complex.Under the standard reaction condition,a variety of 1,2,3,4-tetrahydroquinoxalines could be obtained in moderate to good yields.This strategy was also applied for theasymmetric synthesis of 2-aryl-and 2-alkyl-substituted-tetrahydroquinoxalines and2-alkyl-substituted chiral tetrahydroquinoxalines which have high enantioselectivity.This method provides a new idea for practical production and has profound significance.