Practical Cyclization of Carbon-Carbon Multiple Bonds with Titanium (II) Reagent. -Application and Extension to Asymmetric Synthesis

使用钛 (II) 试剂进行碳-碳多重键的实际环化。

• 批准号: 08651020
• 负责人: URABE Hirokazu
• 金额: $ 1.15万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08651020/
• 关键词: Acetylene; Allene; Tetraisopropyl orthotitanate; Asymmetric synthesis; Allyltitanium reagent; Bicyclo [3.3.0] octanone; Bicyclo [3.1.0] hexane; Sabinene; ジエン

1) Attempted asymmetric addition of dialkoxytitanacycle to aldehydes. Titanacyclopentadiene prepared from a 1,6-diyne, Ti (O-i-Pr)_4, and i-PrMgCl was allowed to react with benzaldehyde in the presence of optically active binaphthol. However, no asymmetric induction was observed. It could be concluded that a large quantity of the magnesium salts present in the reaction media should hinder organization of a chiral titanium intermediate that is essential for the high level of asymmetric addition. Thus, we abandoned this project and turned our attention to substrate-controlled asymmetric cyclization. 2) Intramolecular asymmetric cyclization of allene and acetylene. It was reported last time that the titanacycles generated by the cyclization of optically active 5,6-dien-1-ynes react with aldehydes, ketones, or imines to give the corresponding adducts in a highly regio-, stereo-, and diastereoselective manner and with nearly complete retention of the enantiopurity of the starting material. In order to clarify the stereochemical course of this reaction, the absolute stereochemistry of the products was elucidated, which in turn, revealed that the addition of allyltitanium moiety in the titanacycle could be strictly expressed in terms of syn-S_E2' fashion. 3) Asymmetric cyclization of bis-unsaturated esters and its application to the synthesis of optically active terpenes. It was reported last year that the titanium-mediated tandem cyclization of olefins and acetylenes having a conjugated ester group affords 1-bicyclo [3.3.0] octen-3-ones (or-octan-3-ones) and bicyclo [3.1.0] hexane structures. This time, an allylic substituent in the starting material was found to nicely control the Chirality of the cyclization product, which was utilized in an asymmetric synthesis of d-sabinene, a monoterpene having a cyclopropane moiety.

1）尝试将二烷氧基钛环不对称加成到醛上。由1,6-二炔、Ti(O-i-Pr)_4和i-PrMgCl制备的环戊二烯钛在光学活性联萘酚存在下与苯甲醛反应。然而，没有观察到不对称诱导。可以得出结论，反应介质中存在的大量镁盐会阻碍手性钛中间体的组织，而手性钛中间体对于高水平的不对称加成至关重要。因此，我们放弃了这个项目，并将注意力转向底物控制的不对称环化。 2）丙二烯和乙炔的分子内不对称环化。上次报道光学活性5,6-二烯-1-炔环化生成的钛环与醛、酮或亚胺以高度区域、立体和非对映选择性方式反应生成相应的加合物，几乎完全保留了起始材料的对映体纯度。为了阐明该反应的立体化学过程，阐明了产物的绝对立体化学，从而揭示了钛环中烯丙基钛部分的加成可以严格地以syn-S_E2'方式表达。 3）双不饱和酯的不对称环化及其在光学活性萜烯合成中的应用。去年有报道称，钛介导的具有共轭酯基的烯烃和乙炔的串联环化得到1-双环[3.3.0]辛烯-3-酮（或-辛烷-3-酮）和双环[3.1.0] ] 己烷结构。这次，我们发现起始材料中的烯丙基取代基可以很好地控制环化产物的手性，该环化产物可用于不对称合成d-桧烯（一种具有环丙烷部分的单萜）。

项目成果

Titanium and Zirconium in Organic Synthesis

• DOI: 10.1002/3527600671
• 发表时间: 2002-05-29
• 作者: I. Marek