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

1)尝试二烷氧基钛环与醛的不对称加成反应。以1，6-二炔、钛(O-i-Pr)_4和异丙基氯化镁为原料合成了钛杂环戊二烯，并在光学活性联苯酚存在下与苯甲醛反应。然而，没有观察到不对称诱导。可以得出的结论是，反应介质中存在的大量镁盐应该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是必不可少的。因此，我们放弃了这个项目，转而关注底物控制的不对称环化反应。2)烯和乙炔的分子内不对称环化反应。上一次报道了光学活性的5，6-二烯-1-YNE的环化反应生成的钛环与醛、酮或亚胺以高度区域、立体和非对映选择性的方式反应得到相应的加合物，并且几乎完全保留了起始物质的对映体。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，进而揭示了钛环中烯丙基钛的加成可以严格地用SYN-S_E_2的方式来表示。3)双不饱和酯的不对称环化反应及其在光学活性萜类化合物合成中的应用。去年有报道称，钛催化的具有共轭酯基的烯烃和乙炔的串联环化反应得到了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。这一次，在起始原料中发现了一个烯丙基取代基，很好地控制了环化产物的手性，这被用于d-sabinene的不对称合成，d-sabinene是一种具有环丙烷基的单萜烯。

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.