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.通过碱KN(TMS)_2、LiH_2CN和NaH_2的处理，我们找到了一种简便的方法，可以将含吸电子基团的(多烯)Fe(CO)_3络合物(醛、酮、酯和腈)转化为所需的迁移产物。当Fe(CO)_3基团通过1，3-或1，5-迁移在多烯侧链上移动时，(二烯)Fe(CO)_3基团的手性被保留，反应分别进行构型反转或保留。我们利用Fe(CO)_3基团的手性，成功地实现了未络合的烯烃与OSO_4的非对映选择性双羟基化反应。此外，在Lewis-酸性条件下，各种亲核试剂可以通过相应的邻位酯进行区域和立体选择性的引入到上述二醇配合物中。通过对三烯和四烯Fe(CO)_3络合物的碱基转移和酮的立体选择性还原，立体选择性地合成了用标准方法不能合成的手性1，8-和1，10-二醇。为了不对称合成HIV-1蛋白水解酶抑制剂，我们研究了立体特异性1，n-迁移反应的迭代应用。因此，我们建立了几种类型的多元醇的不对称合成方法，如1，2-芳基-2，3-抗-3，4-芳基四醇衍生物和1，3-抗二醇衍生物。

项目成果

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。

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)

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。

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。

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)