氮杂环卡宾催化三价碘试剂参与的醛类化合物不对称官能团化反应研究

Carbonyl compounds possessing chiral centers are valuable building block in organic synthesis and have been widely applied in the fields of pharmaceuticals, agrochemicals, and functional materials. Highly enantioselective forming carbon-carbon bond and carbon-hetero bond from various aldehydes to incorporate of important functional groups and construct of complicated ring systems has been achieved through N-heterocyclic carbene (NHC) catalysis under mild and non-toxic conditions. In addition, hypervalent iodine(III) reagents have been used as electrophiles or radical precursors to introduce of various useful functional group, such as fluoroalkyl, azide, diazomethyl, halogen, amide, aryl, vinyl, alkynyl, and nitriles, due to their strong electrophilicity and valuable oxidizing properties, combined with their environment-friendly nature and in many cases commercial availability. We propose that Breslow intermediates, enolates, homoenolates, vinylenolates generated from aldehydes and NHC catalysts react with hypervalent iodine(III) reagents to achieve various highly enantioselective asymmetric α-, β-, or γ-functionalization of aldehydes based on ionic or radical mechanism, providing synthetic useful chiral products.

含有手性中心的各种羰基衍生物，是有机合成中非常有价值的中间体，在制药、农业化学品、以及功能材料等领域具有广泛的应用。氮杂环卡宾催化具有温和无毒等特点，利用该策略可以从醛类化合物出发，在羰基的α-、β-、或γ-位高对映选择性地构建碳-碳键和碳-杂键，引入重要官能团和合成复杂环系结构。另外，三价碘试剂具有强氧化性、强亲电性、环境友好、部分商业可得等特点，可以被用作亲电试剂和自由基前体，引入各种重要官能团，如三氟甲基、全氟烷基、叠氮、重氮甲基、卤素、酰胺、芳基、烯基、炔基、腈基等。基于离子机理或自由基机理，本项目拟利用醛与氮杂环卡宾之间形成的Breslow中间体、以及enolates、homoenolates、vinylenolates等中间体与三价碘试剂之间的反应，实现高对映选择性的羰基α-，β-，或γ-位的各种可能的官能团化，所得到的手性产物在合成中非常有价值。

由于其独特的性质，1,3,4-噁二唑衍生物在药物化学和功能材料领域具有重要的地位。过去的报道往往都利用羰基衍生物，例如芳基酰肼、酰氯、腙、酰基醛、苯乙酮、酮酸为起始原料合成1,3,4-噁二唑杂环。近年来，也有报道从易得的芳基醛与芳基四氮唑发生酰基化反应，直接合成1,3,4-噁二唑杂环。目前已有的方法存在需要强氧化剂和过渡金属、高温、底物范围狭窄等局限性。本项目实现了氮杂环卡宾有机小分子催化的从易得的芳香醛合成1,3,4-噁二唑杂环的新方法。我们发现基于Breslow中间体的亲核性以及α-重氮碘鎓盐的亲电性，氮杂环卡宾催化剂可以促进各种醛与α-重氮碘鎓盐之间的环化。反应条件温和，官能团耐受性好，且杂环产物可以被进一步衍生化，使得此方法更具价值。