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

在本研究计画中，我们将注意力集中在双齿刘易斯酸化学上。（2，7-二甲基-1，8-联苯二氧基）双（二甲基铝）可以成功地制备为双齿刘易斯酸，用于与羰基底物同时配位。高，同时协调能力的双齿有机铝试剂对羰基强调与相应的单齿试剂相比，其特征在于通过评估双亲电活化的还原和Mukaiyama羟醛缩合反应中的酮基底物。双齿刘易斯酸在有机合成中的另一个有趣的特征是甲硅烷基烯酮缩醛与苄叉丙酮的区域和立体控制的Michael加成，其中双齿铝刘易斯酸表现出与单齿对应物完全相反的E选择性。（蒽醌-1，8-二氧基）双（三异丙氧基钛）也被成功地开发为双齿刘易斯酸催化剂，用于同时协调 ...更多信息 与羰基底物的反应。使用几个合成实施例强调了双齿Ti催化剂对羰基的高双活化能力（即，酮还原和醛烯丙基化反应）的性能比较用13 C NMR谱表征了这些双齿铝和钛试剂与DMF作为羰基底物的同时配位络合物的形成。成功地设计了一种新的手性双齿Ti（LV）配合物，从而允许这种羰基的精确对映体区分，用于醛与烯丙基三丁基锡的新的催化的、实用的对映选择性烯丙基化。所需的手性双齿Ti（IV）催化剂可以通过将市售的四异丙醇钛和（S）-联萘二甲酸依序加入到2，2 ′-双（三苯甲基氨基）二苯甲酮衍生物中而容易地制备。这些手性双齿钛催化剂表现出一致的高不对称诱导以及各种醛的高化学产率。本发明的对映选择性烯丙基化在其他羰基部分如酮、酯和酰胺官能团的存在下是高度化学选择性的，如通过具有优异的化学选择性和对映选择性的4-乙酰氧基-3-乙酰基苯甲醛的烯丙基化所例示的。少

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