Development of highly efficient asymmetric synthesis process directed for "racemic switch" of the racemic medicines

本研究的目的是建立一种方法：1)通过催化分解，简单制备具有构象刚性和空间充塞的三环“顶”2-恶唑烷酮、2-咪唑烷酮和2-噻唑烷酮作为极强的手性助剂；2)与上述三环化合物及其衍生物衍生的双环2-氨基醇、1,2-二胺和2-氨基硫醇进行优异的不对称反应。用于外消旋药物的“外消旋开关”。通过动力学拆分容易获得高效的手性助剂用恶唑烷类催化剂进行动力学拆分，容易得到旋光性“顶”的2-恶唑烷酮、2-咪唑烷酮和2-噻唑烷酮。应用高效的手性“顶”配体由相应的三环化合物衍生的双环“顶”2-氨基醇、1,2-二胺和2-氨基硫醇已被证明是以下金属催化不对称反应的优秀手性配体：(1)恶唑硼烷-硼烷体系（“2-氨基醇”配体）对酮进行不对称硼烷还原。(2)实用的多用途手性合成物4,5-二氧基-2-咪唑烷酮（“2-氨基醇”配体）。(3)钌（II）催化酮（“顺-1,2-二胺”配体）的不对称转移加氢反应。(4)Pd （II）催化的烯丙酸酯（“2-氨基硫醇”配体）的不对称烷基化反应。(5)Cu （II）催化不对称Diels-Alder反应（“2-氨基硫醇”配体）。

The aim of this research is to establish the methodology for i) simple preparation of tricyclic "roofed" 2-oxazolidinones, 2-imidazolidinones and 2-thiazolidinones with conformational rigidity and steric congestion as extremely powerful chiral auxiliaries by catalytic resolution, and ii) excellent asymmetric reactions with bicyclic 2-amino alcohols, 1,2-diamines and 2-aminothiols derived from the above tricyclic compounds and their derivatives, directed for "racemic switch" of the racemic medicines.1.Easy access to highly efficient chiral auxiliaries by kinetic resolutionThe optically active "roofed" 2-oxazolidinones, 2-imidazolidinones and 2-thiazolidinones were readily obtained from kinetic resolution with oxazaborolidine catalysts.2.Application of highly efficient chiral "roofed" ligandsBicyclic "roofed" 2-amino alcohols, 1,2-diamines and 2-aminothiols derived from the corresponding tricyclic compounds have been proven to be good to excellent chiral ligands for following metal-catalyzed asymmetric reactions :(1)Asymmetric borane reduction of ketones with oxazaborolidine-borane system ("2-Aminoalcohol" ligands).(2)Practical synthesis of versatile chiral synthons, 4,5-dialkoxy-2-imidazolidinone ("2-Aminoalcohol" ligands).(3)Ruthenium (II)-catalyzed asymmetric transfer hydrogenation of ketones ("cis-1,2-Diamine" ligands).(4)Pd (II)-catalyzed asymmetric alkylation of allylacetates ("2-Aminothiol" ligands).(5)Cu (II)-catalyzed asymmetric Diels-Alder reaction ("2-Aminothiol" ligands).