Synthetic study on biologically active polyols using mobility of (diene)Fe(CO)_3 complexes.

利用(二烯)Fe(CO)_3配合物的流动性合成生物活性多元醇的研究。

• 批准号: 11672100
• 负责人: TAKEMOTO Yoshiji
• 金额: $ 2.3万
• 依托单位: KYOTO 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-11672100/
• 关键词: iron-tricarbonyl compound; 1, 3-migration; chiral auxiliary; orthoester; asymmetric synthesis; polyenes; polyols; dihydroxylation; remote stereocontrol; トリエン錯体

1. We have found a convenient method for the transformation of (polyene)Fe(CO)_3 complexes bearing an electron-withdrawing group (aldehyde, ketone, ester, and nitrile) into desired migrated products by treatment with the base such as KN(TMS)_2, LiCH_2CN, and NaH.2. When the Fe(CO)_3 group moves on the polyene side-chain via the 1, 3- or 1, 5-migration, the chirality of (diene)Fe(CO)_3 group was preserved and the reaction proceeds with inversion or retention of configuration, respectively.3. We have succeeded in the diastereoselective dihydroxylation of the umcomplexed olefin with OsO_4 by using chirality of the Fe(CO)_3 group. In addition, regio- and stereoselective introduction of various nucleophiles into the above diol complexes could be carried out under Lewis-acidic conditions via the corresponding orthoester.4. By successive treatment of triene and tetraene Fe(CO)_3 complexes with base-mediated 1, n-maigration and the stereoselective reduction of the ketones, chiral 1, 8- and 1, 10-diols, which could not prepared by the standard procedure, were synthesised stereoselectively.5. With an aim of the asymmetric synthesis of didemnaketal A and macrolactin A, which are known as HIV-1 protease inhibitors, we examined the iterative use of the stereospecific 1, n-migration reaction. Consequently, we have established the asymmetric synthesis of several type of polyols such as 1, 2-syn-2, 3-anti-3, 4-syn-tetraol derivative and 1, 3-anti-diol derivatives.

1。我们找到了一种方便的方法，可以将（Polyene）Fe（CO）_3复合物转化为带有电子吸引力的基团（醛，酮，酯和氮），通过用诸如KN（TMS）_2，LICH_2CN和NAH.2的碱基处理的迁移产物。当Fe（CO）_3组通过1、3或1、5迁移在多烯侧链上移动时，（DIENE）Fe（CO）_3组的手性得出了，并且分别以构型的倒置或保留率进行反应进行。3。通过使用Fe（CO）_3组的手性，我们成功地将UM复合烯烃与OSO_4取代了UM复合烯烃的二羟基化。此外，可以通过相应的矫正器在路易斯 - 酸性条件下进行各种亲核试剂的区域和立体选择性引入上述二醇复合物。4。通过连续治疗三烯和四烯Fe（CO）_3基础介导的1，N-移位以及酮的立体选择性减少，手性1、8和1、10-二醇，无法通过标准程序制备，是标准合成的。5。为了dodemnaketal A和大分裂蛋白A的不对称合成（称为HIV-1蛋白酶抑制剂），我们检查了立体特异性1的迭代使用，即N迁移反应。因此，我们已经建立了几种类型的多元醇的不对称合成，例如1、2-Syn-2、3-抗-3、4-Syn-syn-tetraol衍生物和1、3-抗二醇衍生物。

项目成果

Y.Takemoto et al.: "Stereoselective synthesis of nonracemic 1, 3-amino alcohols from chiral 2-vinylaziridines by InI-Pd(0)-promoted metalation"Tetrahedron Lett.. 41. 1725-1728 (2001)

Y.Takemoto 等人：“通过 InI-Pd(0) 促进的金属化从手性 2-乙烯基氮丙啶立体选择性合成非外消旋 1, 3-氨基醇”Tetrahedron Lett.. 41. 1725-1728 (2001)

Y.Takemoto et al.: "Utility of a diene-tricarbonyliron complex as a chiral auxiliary: regio-and stereocontrolled functionalization of acyclic diene ligands"J.Am.Chem.Soc. 121. 9143-9154 (1999)

Y.Takemoto 等人：“二烯-三羰基铁络合物作为手性助剂的效用：无环二烯配体的区域和立体控制官能化”J.Am.Chem.Soc。

K.Okamoto et al.: "Role of the planar chirality of chiral amino alcohols bearing iron tricarbonyl in asymmetric alkylation of diethylzinc to aldehydes"Tetrahedron : Asymmtry. (in press).

K.Okamoto等人：“带有三羰基铁的手性氨基醇的平面手性在二乙基锌不对称烷基化成醛中的作用”四面体：不对称。

K.Ishii et al.: "Selective synthesis of nonracemic 3-pyrolines and 2,3-cis-2-vinylaziridines from (Z)-amino allylic alcohols : New synthetic route to chiral 3,4-"Svnlett. 228-230 (1999)

K.Ishii 等人：“从 (Z)-氨基烯丙醇选择性合成非外消旋 3-吡咯啉和 2,3-顺-2-乙烯基氮丙啶：手性 3,4-”Svnlett 的新合成路线。

Y.Takemoto: "CAN-Induced Double Ether Formation : Synthesis of trans- and cis-Fused Tricyclic Ethers from 3-Oxabicyclo[3.1.0]hexyl Sulfides"Chem.Commun.. 2515-2516 (1999)

Y.Takemoto：“CAN 诱导的双醚形成：从 3-氧杂双环[3.1.0]己基硫醚合成反式和顺式稠合三环醚”Chem.Commun. 2515-2516 (1999)