铑催化烯基氮杂张力环与非活化不饱和烃的环加成及环化反应研究

Heterocycles, especially N-heterocycles, play a significant role in the development of modern human society. Due to this, the synthesis of N-heterocycles has long been the subject of intense study in modern organic synthesis. Among these methods, the design and development of new cycloaddition reactions with available substrates in terms of minimization of synthetic steps together with maximization of target-relevant complexity offer tremendous opportunities for the ideal synthesis of N-heterocycles. Vinyl aziridines and vinyl azetidines are easily available, versatile synthons that are commonly used as three and four-atom components in transition-metal-catalyzed [3+2] and [4+2] cycloadditions with activitated unsaturated hydrocarbons, respectively. However, the example of vinyl aziridines and vinyl azetidines as a heteroatom-containing five and six-atom partner respectively in cycloaddition reaction with unactivitated unsaturated hydrocarbons is extremely rare. Based on our previous works, we will develop a series of rhodium catalyst-controlled divergent cycloadditions & cyclizations reactions ([5+2+1] versus [5+1], [5+2] versus [3+2], [6+2] versus [4+2]) of vinyl aziridines and vinyl azetidines with unactivitated unsaturated hydrocarbons, which will also develop a highly efficient and atom-economic method for the synthesis of N-heterocycles, especially azepane and azocane derivatives, with impressive levels of region-, diastereo- and enantiocontrol.

杂环化合物尤其是氮杂环化合物对现代社会的发展具有重要作用。正因为此，对氮杂环的合成一直是有机化学研究的热点和焦点。从简单易得的原料出发设计和发展新型的环加成和环化反应可为氮杂环的制备提供理想的合成方法。烯基氮杂环丙烷/环丁烷类化合物是一类高活性的有机合成子，方便易得。它们一般被认为只能分别作为三和四原子组分与活化的不饱和烃发生[3+2]和[4+2]环加成反应。而将其分别作为五和六原子组分与非活化的不饱和烃发生环加成反应的研究却相对较少。基于我们前期的工作，在本项目中我们将通过铑催化剂的调控发展一类新型的烯基氮杂环丙烷/环丁烷与非活化的不饱和烃的[5+2+1]、[5+1]、[5+2]、[3+2]、[6+2]和[4+2]环加成及其环化反应，并实现对这类环化反应的区域选择性、非对映选择性和对映选择性的调控。为氮杂环尤其是七元及八元氮杂环的构建提供一个高效、高选择性和原子经济性的合成方法。

杂环化合物尤其是氮杂环化合物对现代社会的发展具有重要作用。正因为此，对氮杂环的合成一直是有机化学研究的热点和焦点。从简单易得的原料出发设计和发展新型的环加成和环化反应可为氮杂环的制备提供理想的合成方法。烯基氮杂环丙烷化合物是一类高活性的有机合成子，方便易得。一般被认为只能与缺电子的烯烃发生[3+2]环加成反应。能否实现其与富电子烯烃的[3+2]环加成反应或发展新的反应模式和环加成组分丰富其[3+X]环加成化学则是没有很好解决的科学问题。基于我们前期的工作，在本项目中我们通过铑催化剂的调控，发展了烯基氮杂环丙烷与1）烯醇硅醚的[3+2]和[3+4]环加成反应；2）与肟醚和炔胺的[3+2]反应；3）与环状甲亚胺叶立德的[3+3]反应；并通过手性转移策略为5元、6元氮杂环，尤其是手性7元氮杂环的构建提供一个高效、高选择性和原子经济性的合成方法。此外，我们还实现了烯基氮杂环丙烷与苯酚衍生物及吲哚的立体专一性开环反应，并利用我们发展的方法学，实现了2个药物活性分子的形式合成；以及发展了烯基环氧-炔的杂[5+2]环加成反应及其串联反应。