Design of Metal Artificial Enzymes and the Application to Fine Organic Synthesis

金属人工酶的设计及其在精细有机合成中的应用

• 批准号: 08404049
• 负责人: MARUOKA Keiji
• 金额: $ 26.11万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08404049/
• 关键词: bidentate Lewis acid; organoaluminum reagent; bidentate titanium catalyst; Mukaiyama aldol reaction; chiral binaphthol; chiral titaniumu catalyst; asymmetric allylation; エナンチオ選択性; 実用的不斉合成; カルボニル化合物; チタン; ケトン還元; アリル化; エポキシド; 有機アルミニウム; N, N-ジ

In this research project, we focused our attention on the bidentate Lewis acid chemistry. (2,7-Dimethyl-1, 8-biphenylenedioxy)bis(dimethylaluminum) can be successfully prepared as a bidentate Lewis acid for the simultaneous coordination to carbonyl substrates. The high, simultaneous coordination ability of the bidentate organoaluminum reagent toward carbonyls is emphasized in comparison with the corresponding monodentate reagent, and characterized by evaluating the double electrophilic activation of ketonic substrates in the reduction and Mukaiyama aldol reaction. Another interesting feature of the bidentate Lewis acid in organic synthesis is the regio- and stereocontrolled Michael addition of a silyl ketene acetal to benzalacetone, where bidentate aluminum Lewis acid exhibits the totally opposite E selectivity to a monodentate counterpart.(Anthraquinone-1, 8-dioxy)bis(triisopropoxytitanium) was also successfully developed as a bidentate Lewis acid catalyst for the simultaneous coordin … More ation to carbonyl substrates. The high double-activation ability of the bidentate Ti catalyst toward carbonyls is emphasized using several synthetic examples (i.e., ketone reduction and aldehyde allylation) in comparison with the corresponding monodentate Ti catalyst The simultaneous coordination complex formation of these bidentate aluminum and titanium reagents with DMF as a carbonyl substrate is characterized by 13C NMR spectroscopy.A new, chiral bidentate Ti(LV) complex was successfully designed and can be utilized for simultaneous coordination to aldehyde carbonyls, thereby allowing the precise enantioface discrimination of such carbonyls for a new catalytic, practical enantioselective allylation of aldehydes with allyltributyltin. The requisite chiral bidentate Ti(IV) catalysts can be readily prepared by adding commercially available titanium tetraisopropoxide and (S)-binaphthol sequentially to 2,2'-bis(tritylamino)benzophenone derivatives. These chiral bidentate Ti catalysts exhibit uniformly high asymmetric induction as well as high chemical yields for various aldehydes. The present enantioselective allylation is highly chemoselective in the presence of other carbonyl moieties such as ketone, ester, and amide functionalities as exemplified by the allylation of 4-acetoxy-3-acetylbenzaldehyde with excellent chemo- and enantioselectivity. Less

本课题主要研究双齿刘易斯酸化学。（2,7-二甲基- 1,8 -联苯二氧基）双（二甲基铝）可以成功地制备成双齿刘易斯酸，同时与羰基底物配位。与单齿试剂相比，强调了双齿有机铝试剂对羰基的高同时配位能力，并通过评价酮类底物在还原和Mukaiyama醛醇反应中的双亲电活化来表征。双齿刘易斯酸在有机合成中的另一个有趣的特点是，在苯甲丙酮上，双齿铝刘易斯酸表现出与单齿铝刘易斯酸完全相反的E选择性。（蒽醌- 1,8 -二氧基）双（三异丙氧基钛）也成功地作为双齿刘易斯酸催化剂与羰基底物同时配位。通过几个合成实例（即酮还原和醛烯丙化）与相应的单齿钛催化剂的比较，强调了双齿钛催化剂对羰基的高双活化能力。这些双齿铝钛试剂以DMF作为羰基底物同时形成配位配合物，并通过13C NMR进行了表征。成功设计了一种新的手性双齿Ti（LV）配合物，该配合物可用于醛基羰基的同时配位，从而可以对这些羰基进行精确的对映面识别，从而实现一种新的催化的、实用的烯丙基三丁基锡对映选择性醛基烯丙基化反应。通过将市售的四异丙醇钛和(S)-联萘酚依次加入2,2'-双（三氨基）二苯甲酮衍生物中，可以很容易地制备出所需的手性双齿钛（IV）催化剂。这些手性双齿钛催化剂对各种醛具有均匀的高不对称诱导和高化学产率。目前的对映选择性烯丙基化在其他羰基部分（如酮、酯和酰胺）存在时具有高度的化学选择性，例如4-乙酰氧基-3-乙酰苯甲醛的烯丙基化具有优异的化学和对映选择性。少

项目成果

T.Ooi: "Simultaneous Coordination and Double Activation Phenomena of Carbonyl and Epoxy Oxygens by Bis-Titanium Reagent as a Bidentate Lewis Acid Catalyst" Tetrahedron Lett.Vol.39, No.22. 3729-3732 (1998)

T.Ooi：“双钛试剂作为双齿路易斯酸催化剂对羰基和环氧氧的同时配位和双重活化现象”Tetrahedron Lett.Vol.39，No.22。

Takashi Ooi: "Bidentate Organoaluminum Lewis Acids for Selective Activation of Carbonyl over Acetal Functionality : Chemoselective Functionalization" Tetrahedron Lett.38・42. 7403-7406 (1997)

Takashi Ooi：“二齿有机铝路易斯酸对缩醛官能团的选择性活化：化学选择性官能化”Tetrahedron Lett.38・42（1997）。

T.Ooi: "(2,7-Dimethyl-1,8-biphenylenedioxy) bis (dimethyl-aluminum) as a Bidentate Lewis Acid : Its Reactivity and Selectivity in Organic Synthesis" J.Am.Chem.Soc.Vol.118, No.45. 11307-11308 (1996)

T.Ooi：“（2,7-二甲基-1,8-联苯二氧基）双（二甲基铝）作为双齿路易斯酸：其在有机合成中的反应性和选择性”J.Am.Chem.Soc.Vol.118，

Takashi Ooi: "Simultaneous Coordination and Double Activation Phenomena of Carbonyl and Epoxy Oxygens by Bis-Titanium Reagent as a Bidentate Lewis Acid Catalyst" Tetrahedron Lett.39・22. 3729-3732 (1998)

Takashi Ooi：“双钛试剂作为双齿路易斯酸催化剂的羰基和环氧氧的同时配位和双重活化现象”Tetrahedron Lett.39・22（1998）。

Takashi Ooi: "A Highly Efficient, Catalytic Procedure for the Meerwein-Ponndorf-Verley Reduction Using a Novel Bidentate Aluminum Catalyst" Angew.Chem.Int.Ed.Engl.37・17. 2347-2349 (1998)

Takashi Ooi：“使用新型双齿铝催化剂进行 Meerwein-Ponndorf-Verley 还原的高效催化程序”Angew.Chem.Int.Ed.Engl.37・17（1998）。