Enantioselective Synthesis Of Compounds With Multiple Elements Of Chirality

A molecule is called chiral if it cannot be superposed on its mirror image by any combination of rotations and translations.The phenomenon of chirality widely exists in natural products as well as pharmaceuticals and deeply affects their physical and chemical properties.To develop a simple way to synthesize chiral molecule efficiently has become one of the hottest research topics in recent decades.The former researches were mostly focus on how to build a structure with only one stereocenter.The researches on the synthesis of compounds bearing more and contiguous stereocenters or other forms of chirality(such as axial chirality)were relatively fewer and the present methods mostly include multiple different reaction steps.This dissertation was divided in two parts and introduces two of my researches regarding the just mentioned problem.Enantioselective Synthesis of anti-syn-Trihalides and anti-syn-anti-Tetrahali des via Asymmetric?-Elimination.Halogens are important class of basic elements;they exist in many pharmaceutics and functional materials.One of the very important research fields in organic chemistry is the asymmetric synthesis of halide-bearing stereocenters.Previous research mostly focused on the synthesis of compound with only one halide-bearing stereocenter.The research of the asymmetric synthesis of compounds with contiguous halide-bearing stereocenters(three or more)remained blank.In this dissertation several new ways to the diastereoselective synthesis of racemic anti-syn-trihalides and anti-syn-anti-tetrahalides have been developed.Through asymmetric?-elimination,these compounds could be kinetically resoluted,thus affording the structure containing contiguous halide-bearing stereocenters.Under the optimized conditions,these reactions processed very efficiently with high stereoselectivities.The S value could up to more than 50.The ee values of the products of the asymmetric kinetic resolution,?,?-dihalo-?-halo ketones,could up to 86%with E/Z>20:1.Meanwhile,the ee value of substrates left after kinetic resolution,anti-syn-trihalides and anti-syn-anti-tetrahalides could up to>99%.In the substrate scope,we tested about 35 different substrates altogether,they all went smoothly.The development of this method provides a brand-new way for the asymmetric synthesis of compounds containing multiple halide-bearing stereocenters.Enantioselective Synthesis of Axial Chiral Styrenes with Multiple Chiral Axes.The asymmetric synthesis of atropisomers is one of the most popular research fields in organic chemistry.Traditional atropisomers including axially chiral biaryls,and their synthetic methods have been well-established.Axially chiral styrene is a new kind of axial chiral structure.This new structure was recently found and established.Since it is very difficult to synthesizing enantioselectively,few successful examples have been reported.In this dissertation,we accomplish the asymmetric synthesis of vicinal diaxial styrenes and multiaxis system bearing two to three chiral axes for the first time.We designed a series of new precursors of the VQM(vinylidene ortho-quinone methide)intermediate.These precursors sharing the same ortho alkynyl substituted naphthol core skeleton and could tautomerize to the new type of tetra-substituted VQM species under the basic condition of cinchona alkaloid(the quinine-derived squaramide type).These new type of tetra-substituted VQM intermediates are highly active with multiple reaction sites.When reacting with a suitable nucleophilic reagent(Ph SO₂H)and electrophilic reagent(NIS)under the catalysis of quinine-derived squaramide,these VQM intermediates could successfully afford the above mentioned chiral vicinal diaxial styrenes with high yields and stereoselectivies.In the substrate scope,we accomplished the synthesis of the 33 compounds with two contiguous chiral axes,10 compounds with three contiguous chiral axes and their absolute configurations were determined by single crystal X-ray crystallographic analysis.The reaction mechanism was studied by control experiments.The establishment of these new type of axial chiral structures will provide a new direction for the design of new chiral catalyst as well as the development of new drugs.