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

过渡金属催化不对称合成是一种最方便、最环保的合成方法，具有广泛的应用前景。此外，设计和开发用于过渡金属催化反应的手性配体是一项极具挑战性的任务。我们已经成功地从市售的1,5-二甲基- 1,5-环二烯中，用4或5步合成了新的单齿手性膦(1R, 2S, 5R, 6S)-2,6-二甲基-9-苯基-9-磷二氯[3.3.1]壬烷及其对映体(（+)-和(-)-9- pbns）。利用钯配位的9-PBNs，详细研究了不对称烯丙基取代反应形成对映选择性碳-碳键、碳-氮键和碳-氧键的反应。以双（苄基）钯和(-)- 9-PBN为催化剂，丙二酸二甲酯与1,3-二苯基-2-丙烯酯的烯丙基烷基化反应进行得很顺利，烯丙基烷基化产物的定量产率为94%。研究了氮亲核试剂代替碳亲核试剂的扩展。叔胺和仲胺以及磺胺和亚胺的钠盐对映体的效能可达98%。此外，三烷基硼酸盐可以作为氧亲核试剂用于不对称烯丙基取代反应，并提供相应的醚，其ee高达96%。作为这种不对称合成的进一步延伸，我们研究了2-环烯基酯的反应，发现2-取代的2-环烯基碳酸甲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.