Tandem Inter-/intramolecular Coupling Mediated by a Ti(II) Reagent : One-step Multibond-forming Reactions

我们开发了高效的二价钛试剂介导的不饱和化合物的分子间和分子内环化反应。在这些反应的基础上，本项目开发了钛(II)介导的不饱和化合物分子间和分子内的串联或多米诺偶联反应，使不饱和化合物能够在一锅中形成多个键，然后1，4-二炔与钛(II)试剂和烯丙基化合物反应得到烯丙基钛酸酯中间体，再与另一个等价物钛(II)试剂反应，以较高的产率得到环状双钛有机分子，再与H+、D+、I+和醛等亲电试剂反应，得到相应的水解、重水解、碘解和羰基加成反应。该方法被应用于分子内/分子内的多米诺反应，如官能化的2，7-烯炔的环化反应，合成了双环[3.3.0]-，[4.3.0]-碳和杂环化合物。考虑到所开发的反应的效率、经济优势和/或高的立体选择性，以及钛(II)试剂的无毒和廉价，我们相信该方法可能在有机合成中作为一种强有力的工具。

We have developed efficient inter-and intramolecular cyclization reactions of unsaturated compounds mediated by a divalent titanium reagent. Based on these reactions, in this project we developed Ti(II)-mediated tandem or domino inter-and intramolecular coupling reactions of unsaturated compounds which enable multiple bond-forming in one-pot.Thus, 1,4-diynes reacted with the Ti(II)-reagent and allylic compounds to provide allyltitanated intermediate and this was further reacted with one more equivalent of the Ti(II)-reagentin situto provide cyclic bistitanated organic molecule in good yield, which was reacted with a various kind of electrophiles such as H+, D+, I+ and aldehydes to afford the corresponding hydrolysis, deuteriolysis, iodolysis and carbonyl addition compounds. The reactions involved maximum five-bond forming in a single vessel.Extensively, the method was applied to intra-/intramolecular domino reactions such as bicyclization of functionalized 2,7-enynes to bicyclo[3.3.0]-, [4.3.0]-carbo-and heterocyclic compounds.Considering efficiency, economical advantage and/or high stereoselectivity of the reactions developed here and also non-toxity and inexpensiveness of the Ti(II)-reagent, we believe that the methods might be useful as a powerful tool in organic synthesis.