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

单齿手性膦的设计、开发及其在不对称合成中的应用

• 批准号: 09470480
• 负责人: HAMADA Yasumasa
• 金额: $ 4.16万
• 依托单位: CHIBA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470480/
• 关键词: monodentate chiral phosphine; asymmetric allylic substitution reaction; palladium; trialkyl borates; 2-cycloalkenyl ester

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.

过渡金属催化的不对称合成是最方便、环境友好的方法之一，并在实际应用中引起了人们的关注。此外，用于过渡金属催化反应的手性配体的设计和开发是最令人着迷且具有挑战性的任务。我们通过 4 或 5 个步骤，从市售的 1,5-二甲基-1,5-环辛二烯中成功开发出新型单齿手性膦，(1R, 2S, 5R, 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-PBNs）。利用与钯配位的9-PBN，通过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-氧键的反应已被详细研究。发现使用双(亚苯亚甲基)钯和(-)-9-PBN作为催化剂，1,3-二苯基-2-丙烯基乙酸酯与丙二酸二甲酯的烯丙基烷基化反应可以有效进行，并以定量产率得到94%ee的烯丙基化产物。已经研究了扩展到氮亲核试剂而不是碳亲核试剂。伯胺和仲胺以及磺酰胺和酰亚胺的钠盐显示出高达 98%ee 的对映体功效。此外，硼酸三烷基酯被发现可作为不对称烯丙基取代反应的氧亲核试剂，并提供高达 96%ee 的相应醚。作为使用 9-PBN 的这种不对称合成的进一步扩展，我们研究了 2-环烯基酯的反应，并发现 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。

项目成果

Hamada, Y.; Matsuura, F.; Oku, M.; Hatano, K.; Shioiri, T.: "Synthesis and Application of New Chiral Bidentate Phosphine, 2,7-Di-tert-butyl-9,9-dimethyl-4,5-bis (methylphenylphosphino) xanthene." Tetrahedron Letters. 38. 8961-8964 (1997)

滨田，Y.；

Hamada, Y. ; Matsuura, F. ; Oku, M. ; Hatano, K. ; Shioiri, T: "Synthesis and Application of New Chiral Bidentate Phosphine, 2,7-Di-tert-butyl-9,9-dimethyl-4,5-bis(methylphenylphosphino)xanthene." Tetrahedron Letters. 38. 8961-8964 (1997)

滨田，Y.；

Hamada, Y., Seto, N., Ohmori, H., & Hatano, K.: "New Monodentate Chiral Phosphine, 2.6-Dimethyle-9-phenyl-9-phosphabicyclo [3.3.1] nonane (9-PBN) : Application to Asymmetric Allylic Substitution Reaction." Tetrahedron Letters. 37. 7565-7568 (1996)

滨田，Y.，濑户，N.，大森，H.，

Hamada,Y.,Seto,N.,Ohmori,H.,& Hatano,K.: "New Monodentate Chiral Phosphine,2.6-Dimethyl-9-phenyl-9-phosphabicyclo[3.3.1]nonane(9-PBN):Application to Asymmetric Allylic Substitution Reaction." Tetrahedron Letters. 37. 7565-7568 (1996)

滨田 Y.、濑户 N.、大森 H.、

Hamada, Y., Seto, N., Ohmori, H., & Hatano, K.: "New Monodentate Chiral Phosphine, 2.6-Dimethyl-9-phenyl-9-phosphabicyclo[3.3.1]nonane (9-PBN) : Application to Asymmetric Allylic Substitution Reaction." Tetrahedron Letters. 37. 7565-7568 (1996)

滨田，Y.，濑户，N.，大森，H.，