Synthesis of New Axially Chiral Ligand Library and Application to Asymmetric Synthesis of Biologically Active Compounds.

新型轴向手性配体库的合成及其在生物活性化合物不对称合成中的应用。

• 批准号: 11672098
• 负责人: NISHIDA Atsushi
• 金额: $ 2.5万
• 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: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672098/
• 关键词: 1, 1'-(2, 2'-bisamino) binaphthalene; axial asymmetry; ytterbiumu (III) triflate; asymmetric Diels-Alder reaction; olefin metathesis; macrolactam; imino ene reaction; sarkomycin; 1,1'-(2,2'-ビスアミノ)ビナフタレン; ルイス酸; マンニッヒ反応

Amide derivatives of 1,1'- (2, 2'-bisamino) binaphthalene were prepared and examined their ability as a chiral ligand for asymmetric synthesis. 1, 1'- (2, 2'-Bisbenzoylamino) binaphthalene (BINAMIDE) complexed with Yb(OTf)_3 in the presence of tertiary amine. The complex catalyzed asymmetric Diels-Alder reaction between crotonyl imide and cyclopentadine with high diastereo-and enantioselectivity (endo/exo=>95 : 5, >95% e.e.). A substituent on the phenyl ring influenced the activity and selectivity. We also found that dryness of Yb(OTf)_3 is important to obtain active catalyst. Catalytic asymmetric formal total synthesis of antibiotics, sarkomycin was accomplished. A key step of the synthesis was catalytic asymmetric Diels-Alder reaction of bromoacryimide and cyclopentadiene using BINAMIDE complex.The structure of the active catalyst is not clear now. Cyclic derivatives of BINAMIDE were prepared, in which two acyl groups were connected by ring closing metathesis (RCM). Crystallization and X-ray analysis of the rigid catalyst is under investigation.We also found that Yb(OTf)_3-TMSCl catalyze imino ene reaction of tosylimine and methylstylene to give homoallyl amines.

合成了1，1‘-(2，2’-双氨基)联苯的酰胺类化合物，并考察了它们作为不对称合成手性配体的能力。在叔胺存在下，1，1‘-(2，2’-二苯甲酰氨基)联苯(BINAMIDE)与Yb(OTf)_3形成络合物。该配合物催化巴豆酰亚胺与环戊二胺之间的不对称Diels-Alder反应，具有很高的非对映选择性和对映体选择性(endo/exo=&gt；95：5，&gt；95%e.e.)。苯环上的取代基对活性和选择性有影响。我们还发现Yb(OTf)_3的干燥性是获得活性催化剂的重要因素。完成了抗生素、肉霉素的催化不对称全合成。合成的关键步骤是联胺络合物催化溴丙烯酰亚胺和环戊二烯的不对称Diels-Alder反应，目前活性催化剂的结构尚不清楚。合成了联苯双胺的环状衍生物，其中两个酰基通过环合复分解(RCM)相连。我们还发现Yb(OTf)_3-TMSCl催化对甲苯磺胺和甲苯的亚米诺反应生成高烯丙基胺。

项目成果

Atsushi Nishida: "Enantioselective Diels-Alder Reaction Catalyzed by Chiral 1,1'-(2,2'-Bisacylamino) binaphthalene-Ytterbium Complex"Tetrahedron Letters. 40・8. 1555-1558 (1999)

Atsushi Nishida：“手性 1,1-(2,2-双酰氨基)联萘镱络合物催化的对映选择性 Diels-Alder 反应”四面体快报 40・8 (1999)。

Masamichi Yamanaka: "Ytterbium(III) Triflate/TMS-Cl : Efficient Catalyst for the lmino Ene Reaction"Organic Letters. 2・1. 159-161 (2000)

山中正道：“镱(III)三氟甲磺酸盐/TMS-Cl：亚米诺烯反应的高效催化剂”有机快报2·1（2000）。

Atsushi Nishida: "Enantioselective Diels-Alder Reaction Catalyzed by Chiral 1,1-(2,2-Bisacylamino) binaphthalene-Ytterbium Complex"Tetrahedron Letters. 40・8. 1555-1558 (1999)

Atsushi Nishida：“手性 1,1-(2,2-双酰氨基)联萘镱络合物催化的对映选择性 Diels-Alder 反应”四面体快报 40・8 (1999)。

Masamichi Yamanaka: "Ytterbium(III) Triflate/TMS-Cl; Efficient Catalyst for the Imino Ene Reaction"Organic Letters. 2・1. 159-161 (2000)

山中正道：“镱（III）三氟甲磺酸盐/TMS-Cl；亚氨基烯反应的高效催化剂”有机快报 2・1（2000）。

Mitsuhiro Arisawa: "Concise Synthesis of Azacycloundecenes using Ring-closing Metathesis (RCM)."J.Chem.Soc., Perkin Trans.I.. ・12. 1873-1876 (2000)

Mitsuhiro Arisawa：“使用闭环复分解 (RCM) 的氮杂环十一烯的简明合成。”J.Chem.Soc.，Perkin Trans.I.. ・12.1873-1876 (2000)