镍催化炔烃三组分偶联反应构建官能化四碳取代烯烃的研究

Alkynes have versatile chemical reactivities and thereby their catalytic transformations played vital roles in modern organic synthesis. Transition-metal-catalyzed (mainly palladium) sequential incorporation of two carbon groups across the internal alkynes paved an effective avenue for the synthesis of tetracarbon-substituted alkenes. The efficiency would be remarkably improved if the two-step strategy can be performed in one-pot fashion. However, it’s usually difficult to inhibit the binary coupling side products as well as to coordinate the multiple elementary reactions, so limited examples were reported. Nickel is similar to palladium in nature and has long been deemed as an inexpensive surrogate for palladium. In recent years, however, the inherence of nickel has been found to contribute to many new catalytic reactions which are specific to nickel catalysis. This applicant is fully aware of the uniqueness of nickel through the earlier research on nickel-catalyzed olefin dicarbonfunctionalization reactions. Accordingly, the current project is proposed to study nickel-catalyzed three-component coupling of internal alkynes, functionalized electrophiles and organometallic reagents towards the synthesis of tetrasubstituted alkenes. This project utilizes the stereospecific syn-insertion of alkynes into C-M bonds to control Z/E of the products. Meanwhile, effective strategies were adopted to achieve regioselective difunctionalization of the unequally substituted internal alkynes. Chiral catalysts would also be explored to achieve an asymmetric version of this three-component coupling reaction.

炔烃具有丰富的反应性能，它们的催化转化在现代有机合成中占有十分重要的地位。从内炔出发，利用过渡金属(主要是Pd)催化的偶联反应，分步先后引入两个含碳基团是合成四碳取代烯烃的一种有效途径。该策略中两步如果若能一锅法实现，效率将大幅提高；但抑制三组分偶联中两组分偶联的副产物、协调多步基元反应的难度较大，因而成功的例子不多。Ni与Pd性质相近，长期仅被当作Pd的廉价替代物。但近些年研究发现：Ni的独特性质使其能够催化许多其他金属不能催化的反应。申请人充分认识到Ni的这些特点，以前期从事的Ni催化的烯烃双碳官能化研究为背景基础，提出了本项目：研究Ni催化内炔烃、官能化的亲电试剂和金属试剂三组分偶联反应，用以合成官能化的四碳取代烯烃。利用炔烃插入碳金属键的高立体专一性实现Z/E控制，采用有效策略实现不对称取代的内炔的区域选择性双官能化，并尝试利用手性催化剂实现不对称催化的三组分偶联反应。

炔烃具有丰富的反应性能，它们的催化转化在现代有机合成中占有十分重要的地位。从内炔出发，利用过渡金属(主要是Pd)催化的偶联反应，分步先后引入两个含碳基团是合成四碳取代烯烃的一种有效途径。该策略中两步如果若能一锅法实现，效率将大幅提高；但抑制三组分偶联中两组分偶联的副产物、协调多步基元反应的难度较大，因而成功的例子不多。Ni与Pd性质相近，长期仅被当作Pd的廉价替代物。但近些年研究发现：Ni的独特性质使其能够催化许多其他金属不能催化的反应。在本项目中，我们研究Ni催化内炔烃、官能化的亲电试剂和金属试剂三组分偶联反应，合成了官能化的四碳取代烯烃。利用炔烃插入碳金属键的高立体专一性实现Z/E控制，采用有效策略实现不对称取代的内炔的区域选择性双官能化。我们利用烯丙醇作为最具经济性的烯丙基化试剂、三甲基铝作为甲基化试剂，实现了镍催化的高选择性的烯丙基甲基化，高效合成了一系列1,4-二烯结构。此外，我们还开发了镍催化的N-酰基苯并三氮唑类化合物的酰胺键活化反应，实现了它们与硝基化合物的还原酰胺化反应；N-酰基苯并三氮唑类化合物与环氧化合物在三甲基硅烷卤代物的作用下发生开环偶联反应，合成了具有重要合成价值的β-卤代羧酸酯类化合物。