Study of Chiral Ligand Containing Thioether as Additional Stereochemical Control Element in Metal-Catalyzed Enantioselective Processes

含强施主和弱施主杂原子对的手性非C2对称双齿配体的反式影响已被证明是过渡金属催化的对映选择性过程中的一个强有力的控制因素。在这些配体中，含有硫醚的膦配体(P，S-混合配体)最近引起了越来越多的关注，因为它们的催化剂具有在配位时在硫上产生额外的手性中心的能力(硫手性)作为额外的控制元素。我以前报道了(R)-2-diphenylphosphino-2‘-phenylthio-1，1’-binaphthyl(S-MOP)的合成研究，其中2-溴-2‘-二苯基膦-1，1’-联萘1作为配体合成中亲电亚硫化的关键中间体，与P，S-BINAP混合。这个中间体可以作为一个单磷模板，提供S-MOP配体硫亚单位的结构多样性，然而，它的锂化亲核试剂必须考虑潜在的小种…即使在较低温度下，其轴向手性也更加明显。在这项研究中，为了克服上述缺点，我开发了2-溴-2‘-苯硫基-1，1’-联萘2作为替代合成中间体，它也可以作为单硫模板提供S-MOP配体的一系列磷亚单位。我还将S-MOP应用于钯催化的不对称烯丙基烷基化和Diels-Alder反应，获得了良好的到极好的对映选择性。此外，在钯催化剂的研究过程中，我开发了一种新型的联苯环上含茂金属基膦的R-PHOS，作为钯催化的芳基氯与芳基硼酸的Suzuki-Miyaura反应的支撑配体。特别是，当Pd：R-Phos的比例为1：3时，即使是用于构建高度受阻的四邻位取代联芳基的底物组合，也可以在较短的反应时间内以较低的催化剂负载量获得很好到很好的产率。较少

Trans influence of the chiral non-C2 symmetrical bidentate ligands containing strong and weak donor heteroatom pairs has proven to be a powerful control element in transition metal-catalyzed enantioselective processes. Among such ligands, thioether-containing phosphine ligands (P, S-mixed Ligand) have recently attracted growing attention because catalysts bearing them have the ability to generate an extra chiral center at the sulfur upon coordination (sulfur chirality) as an additional control element. I previously reported the synthetic study of (R)-2-diphenylphosphino-2'-phenylthio-1,1'-binaphthyl (S-MOP) as the P,S-mixed counterpart of BINAP in which 2-bromo-2'-diphenylphosphinyl-1,1'-binaphthyl 1 is intervened as a key intermediate for the electrophilic sulfenylation in the ligand synthesis. This intermediate would serve as a mono-phosphorus template providing structural diversity of the sulfur subunit of S-MOP ligand, however, its lithiated nucleophile must consider potential race … More mization of its axial chirality even at low temperature. In this study, to circumvent the aforementioned drawback, I have developed 2-bromo-2'-phenylthio-1,1'-binaphthyl 2 as the alternative synthetic intermediate, which would also serve as a mono-sulfur template providing an array of the phosphorus subunits of S-MOP ligand. I also applied S-MOP to palladium-catalyzed asymmetric allylic alkylations and Diels-Alder reactions and afforded good to excellent enantioselectivities. In addition, during the course of the study of the development of the palladium catalyst, I have developed a novel biphenylene ring-containing ruthenocene-based phosphine, R-Phos, as a supporting ligand for palladium-catalyzed Suzuki-Miyaura reactions of aryl chlorides with arylboronic acids. In particular, at a 1:3 Pd:R-Phos ratio, substrate combinations even for the construction of highly hindered tetra-ortho-substituted biaryls can be achieved in good to excellent yields with low catalyst loadings in short reaction times. Less