双功能催化剂作用下的不对称Hosomi-Sakurai反应研究

Hosomi-Sakurai reaction is one of the effective methods to construct C-C bond and synthesize homoallylic alcohols/amines. At present, The hot topic and the challenge in Hosomi-Sakurai reaction is to choose the proper catalyst system to realize the effective transformation of less toxic allyl silicon reagents to homoallylic alcohol analogues. In this project, considering the low reactivity of silicon reagents, three types of double function catalysts, "synergistic catalyst", "double activation catalyst" and "double functional group catalyst" are designed and will be applied in catalytic asymmetric Hosomi-Sakurai reactions. The mechanism will be proposed on the basis of experimental results and the synergistic effect between the double function catalyst and the substrate. The reaction conditions, the substituent effects of the substrate, and the law of non-bonded interaction between the double function catalyst and the substrate will be intensively studied to realize the Hosomi-Sakurai reaction with efficiency and high enantioselectivity. Once the project put into effect, it will contribute to the in-depth study of the double function catalyst system, provide effective methods for green synthesis of homoallyl analogues, and afford theoretical guidance for making Hosomi-Sakurai reaction as an effective method in target synthesis and building complex organic molecules.

Hosomi-Sakurai反应是构筑碳碳键和合成高烯丙醇/胺类化合物的有效途径之一。在合适的催化体系作用下,由低毒性的烯丙基硅试剂高效合成高烯丙醇/胺类化合物是研究Hosomi-Sakurai反应的热点及难点。针对烯丙基硅试剂活性低的特点，申请者基于Lewis酸活化理论及双官能团催化的活化策略，设计合成"协同"﹑"双活化"及"双官能团"三种类型的双功能催化剂并将其应用于不对称Hosomi-Sakurai反应，在此基础上对双功能催化剂的作用机理进行研究。通过深入探讨反应条件、底物取代程度、催化剂与底物间的多种非键相互作用规律实现高产率及高对映选择性的Hosomi-Sakurai反应。该项目的实施将有助于对双功能催化体系进行深入研究，为高烯丙基醇/胺类化合物的高效绿色合成提供新方法，为进一步发展Hosomi-Sakurai反应在目标导向化合物合成及复杂有机分子构筑中的应用提供理论指导。

Hosomi-Sakurai 反应是构筑碳碳键和合成高烯丙醇/胺类化合物的有效途径之一。本项目分别在多种催化剂作用下，实现了高烯丙基醇/胺类化合物的高效合成。首先，针对烯丙基硅试剂活性低的特点，设计合成BINOL-TiF4、酸活化CBS、BINAP-AgF、M(OTf)n-PyBox等具有“协同”﹑“双活化”及“双官能团”催化剂并将其应用于醛的不对称Hosomi-Sakurai 反应，在此基础上对双功能催化剂的作用机理进行研究。其次，以三甲基烯丙基硅为亲核试剂，在Bi(OTf)3作用下完成了醛及靛红的高效烯丙基化反应；在FeCl3/TMSCl作用下完成了Hosomi-Sakurai-Prins环化串联反应；在分子碘作用下完成查尔酮的烯丙基化反应，合成了δ, ε-不饱和酮类化合物，并探索了四氢吡喃类化合物的合成。再次，以三氯烯丙基硅烷为亲核试剂，在树枝状分子催化剂作用下完成了醛和腙的烯丙基化反应。该项目的实施实现了双功能催化体系在催化Hosomi-Sakurai反应中的深入研究，并为高烯丙基醇/胺类化合物的高效绿色合成提供了有效方法。