DEVELOPMENT OF CATALYTIC ASYMMETRIC REACTIONS USING LANTANOIDS

使用 Lantanoids 催化不对称反应的发展

• 批准号: 13672207
• 负责人: NISHIDA Atsushi
• 金额: $ 1.73万
• 依托单位: CHIBA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672207/
• 关键词: Asymmetric Diels-Alder reactions; BINAMIDE; Yb(OTf)_3; sarkomycin; TXA2 antagonist; allylic halogenation; Pictet-Spengler reaction; サルコマイシン; トロンボキサンA_2拮抗剤; NBS; Fischerインドール合成; ピロロインドール; シロキシジエン; 軸不斉配位子; 2,2'-diaminobinaphthalene; 不斉Diels-A

1) Asymmetric Diels-Alder reactions of cyclopentadiene and several dienophiles catalyzed by a chiral ytterbium complex prepared by a noble axially asymmetric chiral ligand, BINAMIDE and Yb(OTf)_3 were investigated.The reaction with bromoacryloyl amide afforded cyclo-adduct in 97% yield with 98% de and with 93% ee. The adduct was converted cyclosarkomycin, a key intermediate for the synthesis of antitumor antibiotics sarkomycin (overall 6%, 10 steps). Although a diastereoselective synthesis of optically active cyclosarkomycin has been reported, this is the first catalytic enentioselective synthesis cyclosarkomycin.The reaction with a fumaric acid derivative gave a mixture of adduct in 83% yield with 52% de and with 84% ee. The adduct was converted to a key intermediate for the synthesis of TXA2 antagonist, ONO-8809 which was developed by Ono company. This fumaric acid derivative also reacted with siloxydiene to give a cyclohexene derivative with low enantioselectivity (13% ee).2) A new allylic halogenation and Pictet-Spengler reaction of imines, both catalyzed by Yb(OTf)_3 were developed. Asymmetric version of these reactions will be developed in future.

1）环戊二烯和几种二氧化硅的不对称Diel-Alder反应由手性ytterbium复合物催化，该复合物是由贵族轴向不对称的手性配体，比胺和Yb（OTF）_3催化的。 EE。该加合物被转化为环霉素，这是合成抗肿瘤抗生素sarkomycin（总体6％，10步）的关键中间体。尽管已经报道了光学活性环霉素的非对映选择性合成，但这是第一个催化促进性合成环霉素。与富马酸衍生物的反应赋予了83％的收益率与52％DE的加合物的混合物，并以52％DE和84％的EE。该加合物被转换为由Ono Company开发的TXA2拮抗剂Ono-8809的合成的关键中间体。该富马酸衍生物还与硅氧基反应，给出了具有低对映选择性的环己烯衍生物（13％EE）.2）一种新的烯丙基卤素化和在YB（OTF）催化的基因因的新烯丙基卤代反应和Pictet-spenger反应。这些反应的不对称版本将来会开发。

项目成果

Riichiro Tsuji, Masamichi Yamanaka, Atsushi Nishida, Masako Nakagawa: "Pictet-Spengler Reaction of Nitrones and Imines Catalyzed by Yb(OTf)_3-TMSCI"Chem. Lett. 428-429 (2002)

Riichiro Tsuji、Masamichi Yamanaka、Atsushi Nishida、Masako Nakakawa：“Yb(OTf)_3-TMSCI 催化的硝酮和亚胺的 Pictet-Spengler 反应”Chem。

Masamichi Yamanaka, Atsushi Nishida, Masako Nakagawa: "Imino Ene Reaction Catalyzed by Ytterbium(III) Triflate and TMSCl or TMSOTf"J. Org.Chem.. 68. 3112-3120 (2003)

Masamichi Yamanaka、Atsushi Nishida、Masako Nakakawa：“三氟甲磺酸镱 (III) 和 TMSCl 或 TMSOTf 催化的亚氨基烯反应”J。

Mitsuhiro Arisawa, Yuko Ando, Masamichi Yamanaka, Masako Nakagawa, Atsushi Nishida: "Novel Synthetic Method for 2,3-Dihydro-3-halo-3-methylindole from N-Acetyl-2-isopropenylaniline by Intramolecular Haloamination"Synlett. 1514-1516 (2002)

Mitsuhiro Arisawa、Yuko Ando、Masamichi Yamanaka、Masako Nakakawa、Atsushi Nishida：“通过分子内卤化从 N-乙酰基-2-异丙烯基苯胺合成 2,3-二氢-3-卤代-3-甲基吲哚的新方法”Synlett。

Mitsuhiro Arisawa, Yuko Ando, Masamichi Yamanaka, Masako Nakagawa, Atsushi Nishida: "Novel Synthetic Method for 2,3-Dihydro-3-halo-3-methylindole from N-Acetyl-2-isopropenylaniline by Intramolecular Haloamination"Synlett. No.9. 1514-1516 (2002)

Mitsuhiro Arisawa、Yuko Ando、Masamichi Yamanaka、Masako Nakakawa、Atsushi Nishida：“通过分子内卤化从 N-乙酰基-2-异丙烯基苯胺合成 2,3-二氢-3-卤代-3-甲基吲哚的新方法”Synlett。

Riichiro Tsuji, Masako Nakagawa, Atsushi Nishida: "Efficient Synthetic Approach to Optically Active β-Carboline Derivatives via Pictet-Spengler Reaction Promoted by Trimethylchlorosilane"Tetrahedron Asymmetry. 14. 177-180 (2003)

Riichiro Tsuji、Masako Nakakawa、Atsushi Nishida：“通过三甲基氯硅烷促进的 Pictet-Spengler 反应实现光学活性 β-咔啉衍生物的高效合成方法”四面体不对称性。