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

1)尝试二氧钛环与醛的不对称加成。由1,6-二炔、Ti (O-i-Pr)_4和i-PrMgCl制备的钛环戊二烯在旋光性双酚存在下与苯甲醛反应。然而，没有观察到不对称诱导。由此可见，大量的镁盐存在于反应介质中，会阻碍手性钛中间体的组织，而手性钛中间体是高水平不对称加成所必需的。因此，我们放弃了这个项目，将注意力转向底物控制的不对称环化。2)分子内烯和乙炔的不对称环化。上次报道了由具有光学活性的5,6-二烯-1-炔环化生成的钛环与醛、酮或亚胺以高度的区域选择性、立体选择性和非对映选择性的方式生成相应的加合物，并且几乎完全保留了起始材料的对映不纯性。为了阐明该反应的立体化学过程，对产物的绝对立体化学进行了分析，结果表明钛环中烯丙基钛部分的加成可以严格地用syn-S_E2的方式来表达。3)双不饱和酯的不对称环化及其在旋光性萜合成中的应用。去年报道了钛介导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]辛烷-3- 1（或辛烷-3- 1）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，可以很好地控制环化产物的手性，这被用于不对称合成d-sabinene，一种具有环丙烷部分的单萜烯。

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.