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

含有强弱给体杂原子对的手性非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强有力的控制元素。在这些配体中，含硫醚的膦配体（P，S-混合配体）最近引起了越来越多的关注，因为带有它们的催化剂具有在配位时在硫处产生额外的手性中心（硫手性）作为额外的控制元素的能力。我以前报道了（R）-2-二苯基膦基-2 '-苯硫基-1，1'-联萘（S-MOP）作为BINAP的P，S-混合对应物的合成研究，其中2-溴-2 '-二苯基膦基-1，1'-联萘1作为亲电亚磺酰化的关键中间体介入配体合成。该中间体可作为单磷模板，提供S-MOP配体的硫亚基的结构多样性，然而，其锂化亲核试剂必须考虑潜在的竞争 ...更多信息 即使在低温下也能保持其轴向手性。在本研究中，为了克服上述缺点，我开发了2-溴-2 '-苯硫基-1，1'-联萘2作为替代的合成中间体，其也可以作为提供S-MOP配体的磷亚基阵列的单硫模板。我还将S-MOP应用于钯催化的不对称烯丙基烷基化反应和Diels-Alder反应，并提供了良好的对映选择性。此外，在研究钯催化剂的开发过程中，我开发了一种新的含联苯环的基于二茂茂烯的膦，R-Phos，作为钯催化的芳基氯与芳基硼酸的Suzuki-Miyaura反应的支持配体。特别地，在1：3的Pd：R-Phos比率下，甚至对于高度受阻的四邻位取代的联芳基化合物的构建，可以在短的反应时间内以良好至优异的产率和低的催化剂负载量实现底物组合。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