New Polarity Reversal Strategies for Organic Synthesis

描述(申请人提供)：与路易斯酸催化或过渡金属催化相比，使用路易斯碱(亲核试剂)作为催化剂的新的有机反应受到的关注要少得多。然而，这种Lewis碱策略可以获得创新的和不同的反应模式，这是这些已有的催化方法无法实现的。这些研究的长期目标是开发由Lewis碱催化的新的极性反转反应(Umpolung)，并揭示指导它们的基本相互作用/特征。我们的方法集中在充分发展我们最近发现的亲核试剂催化的使用酰基硅烷和a-酮酸的羰基阴离子加成反应。这些过程依赖于这样的见解，即当暴露在正确的催化加成时，酰基硅烷和a-酮酸是可行的羰基阴离子前体。使用酰基硅烷和α-酮酸作为实际的酰基阴离子前体，避免了使用醛作为酰基阴离子前体时产生的安息香生成的潜在问题。此外，使用非手性和手性Lewis碱从这些前体产生的阴离子将被添加到前手性亲电体中，以产生在构建改善健康的材料(如药物和用作生物探针的化合物)中极其重要的高价值化合物。这项提议的其他相关焦点包括两个相关Umpolung反应的发现和发展：催化高烯酸加成和立体选择性乙烯基酮基阴离子加成。这些新颖的、非传统的成键策略在有效地获得目标导向或多样性导向的感兴趣分子方面具有巨大的潜力。这项拟议的研究探索了我们的有机催化羰基阴离子策略在快速合成直接影响人类健康的分子方面的普遍适用性。这些过程中的每一个都有需要探索的机械方面，这将提供关于亲核试剂催化的过程的一般信息。此外，为了使我们目前的许多反应具有立体选择性，人们非常重视开发新的Lewis碱催化剂(非手性和手性)。

DESCRIPTION (provided by applicant): New organic reactions that employ Lewis bases (nucleophiles) as catalysts have received much less attention than the corresponding areas of Lewis acid catalysis or transition metal catalysis. However, this Lewis base strategy can access innovative and different reactivity patterns unattainable with these established catalysis approaches. The long range goals of these studies are to develop new polarity reversal reactions (Umpolung) catalyzed by Lewis bases and to uncover the fundamental interactions/characteristics that guide them. Our approach focuses on fully developing our recently discovered nucleophile-catalyzed carbonyl anion addition reaction employing acylsilanes and a-keto acids. These processes rely on the insight that acylsilanes and a-keto acids are viable carbonyl anion precursors when exposed to the correct catalytic additions. The use of acylsilanes and a-keto acids as practical acyl anion precursors avoids the potential problem of benzoin formation incurred when using aldehydes as acyl anion precursors. Furthermore, the anions generated from these precursors using achiral and chiral Lewis bases will be added to prochiral electrophiles to produce high value compounds that are immensely important in the construction of health- improving materials such as Pharmaceuticals and compounds to be used as biological probes. Additional related focuses of this proposal include the discovery and development of two related Umpolung reactions: catalytic homoenolate additions and stereoselective vinylogous carbonyl anion additions. These novel, unconventional bond-forming strategies have significant potential to efficiently access target-oriented or diversity-oriented molecules of interest. The proposed research explores the general applicability our organocatalytic carbonyl anion strategies for rapidly synthesizing molecules that directly impact human health. Each of these processes has mechanistic aspects to explore that will provide general information regarding nucleophile-catalyzed processes. In addition, a strong emphasis has been placed on the development of new Lewis base catalysts (achiral and chiral) in order to render many of our current reactions stereoselective.