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

1)二烷氧基钛酸酯与醛的不对称加成反应。以1，6-二炔、Ti（O-i-Pr）_4和i-PrMgCl为原料，在光学活性联萘存在下，与苯甲醛反应合成了钛环戊二烯。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应该阻碍手性钛中间体的组织，这对于高水平的不对称加成是必要的。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反应。上次报道了由光学活性的5，6-二烯-1-炔环化产生的钛环与醛、酮或亚胺反应，以高度区域选择性、立体选择性和非对映选择性的方式得到相应的加合物，并且几乎完全保留了起始原料的对映纯度。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，从而揭示了钛酰亚胺中烯丙基钛的加成反应严格地以syn-S_E ~（2 '）方式表示。3)双不饱和酯的不对称环化反应及其在光学活性萜烯合成中的应用。去年报道了具有共轭酯基的烯烃和乙炔的钛介导的串联环化得到1-双环[3.3.0]辛烯-3-酮（或-辛-3-酮）和双环[3.1.0]己烷结构。这一次，发现起始材料中的烯丙型取代基可以很好地控制环化产物的手性，该产物用于d-桧烯（一种具有环丙烷部分的单萜）的不对称合成。

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.