Design and development of monodentate chiral phosphines and their applications to asymmetric synthsese

过渡金属催化的不对称合成是一种高效、环境友好的合成方法，具有广阔的应用前景。此外，过渡金属催化反应中手性配体的设计和开发也是一个极具吸引力和挑战性的课题。我们成功地从市售的1，5-二甲基-1，5-环辛烷出发，经4步或5步合成了新的单齿手性膦（1 R，2S，5 R，6S）-2，6-二甲基-9-苯基-9-磷杂双环[3.3.1]壬烷及其对映体（（+）-和（-）-9-PBN）。利用9-PBN与钯的配位反应，通过不对称烯丙基取代反应，对不对称碳-碳键、碳-氮键和碳-氧键形成反应进行了详细的研究。以双亚苄基钯和（-）-9-PBN为催化剂，1，3-二苯基-2-丙烯基乙酸酯与丙二酸二甲酯进行烯丙基烷基化反应，烯丙基化产物的定量收率为94%ee。研究了将亲核试剂推广到含氮亲核试剂而不是含碳亲核试剂。伯胺和仲胺以及磺酰胺和酰亚胺的钠盐显示出高达98%ee的对映体效力。三烷基硼酸酯在不对称烯丙基取代反应中可作为氧亲核试剂，合成相应的醚类化合物，ee值可达96%。发现2-取代的2-环烯基甲基碳酸酯是不对称烯丙基取代反应的合适底物。

The transition-metal catalyzed asymmetric synthesis is one of the most expedient and environmentally benign processes and attracts attention for practical use. In addition the design and development of chiral ligands for the transition-metal catalyzed reactions are most fascinating and a challenging task. We have succeeded in the development of new monodentate chiral phosphines, (1R, 2S, 5R, 6S)-2,6-dimethyl-9-phenyl-9-phosphabicyclo[3 .3.1]nonane and its enantiomer ((+)- and(-)-9-PBNs) from commercially available 1,5-dimethyl- 1,5-cyclooctadiene in 4 or 5 steps. Utilizing 9-PBNs coordinated with palladium, enantioselective carbon-carbon bond, carbon-nitrogen bond, and carbon-oxygen bond forming reactions through asymmetric allylic substitution reactions have been investigated in detail. The allylic alkylation of 1,3-diphenyl-2- propenyl acetate with dimethyl malonate using the catalyst from bis(benzylidene)palladium and (-)- 9-PBN was found to proceed efficiently and afford the allylated product with 94 %ee in quantitative yield. Extension to nitrogen nucleophiles instead of carbon ones has been investigated. The primary and secondary amines and the sodium salts of the sulfonamides and imide showed the enantiomeric efficacy of up to 98 %ee. Furthermore, trialkyl borates were found to serve as oxygen nucleophiles for asymmetric allylic substitution reaction and afford the corresponding ethers with up to 96 %ee. As further extension of this asymmetric synthesis using 9-PBNs we have investigated reaction of 2-cycloalkenyl esters and found that 2-substituted 2- cycloalkenyl methyl carbonates are suitable substrates for asymmetric allylic substitution reaction.