氮杂环卡宾(N-Heterocyclic Carbene, NHC)催化下联烯酸酯参与的串联环化

The tertiary amine or tertiary phosphine-catalyzed formal [2+4], [3+2], [4+2], [4+1] and [4+3] annulations involving allenoates acting as C2, C3 or C4 synthons showed that the chemical and regional selectivities of these reactions were heavily dependent on the structures and properties of catalysts. In contrast, there are only a few reports describing the catalytic effect of NHCs (N-Heterocyclic Carbenes) on these transformations. Our preliminary study showed that NHC could promote the efficient assembly of pyran through [2+4] cyclizations of allenoates with chalcones and chemical and regional selectivity of these reactions were obviously different from the system catalyzed by tertiary phosphines or tertiary amines. This project will focus on the catalytic features of NHCs demonstrated by the cascade annulations of allenoates and their derivatives bearing β'-H or β'(δ) leaving groups. We expect that the selectivities of these reactions may be tuned by the modifications of the structures and properties of substrates and catalysts, which can afford some strategies for the discoveries of new domino reactions and controllable syntheses. The fulfillment of this project will not only highlight the unique catalytic activity and efficiency of NHCs for these reactions but also provide some new facile accesses to the important heterocyclic frameworks, and enrich and develop the chemistry of allenoates and NHC catalysis.

联烯酸酯作为C2、C3、C4合成子，在叔膦、叔胺的催化下发生形式上的[2+4]、[3+2]、[4+2]、[4+1]、[4+3]等环化时，反应的化学及区域选择性高度依赖于催化剂的结构与性质。然而，氮杂环卡宾(N-Heterocyclic Carbene, NHC)对这些反应的催化研究开展较少。我们的初步探索表明，NHC也能促进联烯酸酯与查尔酮发生[2+4]反应，构建吡喃环。与叔膦、叔胺催化的反应相比，其化学及区域选择性明显不同。本项目将研究NHC催化下联烯酸酯、带有β'-H及β'(δ)位离去基团的联烯酸酯等底物参与的串联环化反应，通过对底物和催化剂的结构与性质进行适当的调整，有望调控反应的选择性，为发现新的串联反应和控制性合成提供有效的思路和策略，为重要环状骨架的构建提供高效方法。本项目的实施将不仅凸显NHC在催化这类反应中的独特性和优越性，而且将丰富和发展联烯酸酯化学和NHC催化化学。

自联烯酸酯参与的陆氏[3+2]环化反应报道以来，叔膦和叔胺等Lewis碱促进的联烯酸酯转化反应广泛应用于有机合成中。氮杂环卡宾（N-Heterocyclic Carbene, NHC）也是一种Lewis碱，理应像叔膦或者叔胺一样，催化联烯酸酯参与的反应。我们的前期工作表明，NHC可以催化联烯酸酯与查尔酮发生[4+2]环化，构建吡喃骨架，其区域选择性迥异于叔膦或者叔胺催化的体系。因此，探索NHC促进的联烯酸酯转化，可以为寻找新反应提供基础，具有重要的研究价值。.在本项目的支持下，我们首先与郑州大学的魏东辉教授开展合作，通过DFT计算阐明了不同 Lewis碱催化联烯酸酯与查尔酮发生反应时选择性差异的来源。随后，探索了NHC催化下联烯酸酯与含氮亲核试剂的区域专一性加成反应、MBH酯对联烯酸酯区域专一性烯丙基化反应。为了探索NHC催化下联烯酸酯与查尔酮发生[2+4]环化反应的应用范围，我们尝试了联烯酸酯与吡咯啉酮衍生物的[2+4]环化反应，为高取代吡喃并吡咯的合成提供了条件温和、原子经济性高的新方法。叔膦或叔胺催化下，具有γ-H的炔酸酯和联烯酸酯具有相类似的反应活性。我们探索了NHC催化下炔酸酯与查尔酮的[2+4]环化，为吡喃骨架的构建提供了新途径。腈是有机合成中一类重要的原料，我们实现了NHC催化下磺酰醛亚胺脱磺酰基转化为腈。此外，我们还研究了NHC催化下α-溴代烯醛的串联环化，实现了萘并吡喃的构建。温度对反应的选择性有至关重要的影响，我们研究了温度对α-溴代烯醛与烯胺酮的[3+3]环化反应的区域选择性影响。光催化的有机反应在有机合成领域很受重视。我们发展了NHC催化下光促进的α-重氮酮与糖精衍生的氮杂二烯的高对映和非对映选择性不对称[4+2]环化反应。这些工作对于丰富和发展联烯酸酯化学及NHC催化具有重要意义。.项目执行期间，共计发表学术论文10篇，培养了硕士研究生6名。.基于本项目的工作，项目负责人参加了1次国内的学术会议。