手性硼催化的不对称Nazarov反应

The prevalence of five-membered carbocycles in natural products and other bioactive compounds has provided a major impetus for the development of efficient methods for their construction. Towards this end, the Nazarov cyclization, a stereospecific 4p electrocyclization that converts divinyl ketones into cyclopentenones through a conrotatory cyclization, has distinguished itself as a powerful tool for the synthesis of such compounds. Though initial successes have been achieved for the catalytic enantioselective Nazarov reactions , most of those catalytic systems are still suffering from low activity, low yield and narrow scopes. Furthermore, despite Indane-containing natural products have recently become a prevalent type of natural products with promising pharmaceutical profiles, and the total synthesis of these natural products and their analogues have attracted significant attentions, aryl vinyl ketones which was recognized as a general compounds for the construction of indans, remain difficult substrates with notoriously sluggish reactivity, not to mention the unaddressed issues in controlling enantioselectivity in this type of reactions. Thus, searching for new catalyst system that could achieve high reactivity and enantioselectivity for the Nazarov reaction of divinyl ketones, especially aryl vinyl ketones is still challenging and interesting. This project is attend to investgate chiral boran(III) catalyzed enantioselective Nazarov reactions of divinyl ketones and aryl vinyl ketones to synthesize cyclopentenones and especially indanes. The subject will have a good academic value for the discovery of bioactive indane-containing compounds. It will also provide an efficient methord for the synthesis of optical active natural products containing five-membered carbocycles and other bioactive compounds. It is most important that this project will have a good application prospects in the synthesis of indane-containing chiral drugs.

Nazarov 反应能高效合成多取代环戊烯酮，对合成含五元碳环结构的天然产物及其他生物活性化合物具有十分重要的意义。尽管不对称催化Nazarov反应已取得一定结果，但仍存在反应时间长、收率不高、催化剂种类有限等问题；且合成含茚满结构天然产物的芳基烯基酮的不对称Nazarov反应迄今未有报道，甚至消旋体报道也存在活性低、底物普适性差的问题。因此，发展新的手性催化剂以高效地催化不对称Nazarov反应，特别是芳基烯基酮的反应，是十分具有挑战性和价值的课题。本项目拟研究手性硼催化的二烯酮及芳基烯基酮的不对称Nazarov反应。该项目的成功实施，将为手性环戊烯酮，特别是茚满类化合物的高效合成提供切实可行的方案， 对于发现具有生物活性的新型茚满类化合物具有很好的学术价值，对于含五元碳环结构手性天然产物及其类似物的合成具有很好的指导意义, 对于在合成含含有茚满结构单元的手性药物上也具有较好的应用前景。