New Polarity Reversal Strategies for Organic Synthesis

描述（由申请人提供）：使用路易斯碱（亲核试剂）作为催化剂的新型有机反应受到的关注远远少于路易斯酸催化或过渡金属催化的相应领域。然而，这种刘易斯碱基策略可以获得创新的和不同的反应模式，这是现有的催化方法无法实现的。这些研究的长期目标是开发由刘易斯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。我们的方法侧重于充分开发我们最近发现的亲核催化羰基阴离子加成反应，采用酰基硅烷和a-酮酸。这些过程依赖于酰基硅烷和a-酮酸在暴露于正确的催化添加物时是可行的羰基阴离子前体的洞察力。使用酰基硅烷和a-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苯甲酸形成的潜在问题。此外，利用非手性和手性路易斯碱从这些前体产生的阴离子将被添加到前手性亲电试剂中，以产生高价值的化合物，这些化合物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非常重要。本提案的其他相关重点包括发现和发展两个相关的Umpolung反应：催化纯烯醇酯加成和立体选择性乙烯羰基阴离子加成。这些新颖、非常规的成键策略在有效获取目标导向或多样性导向分子方面具有巨大的潜力。提出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中的普遍适用性。这些过程中的每一个都有机制方面的探索，这将提供有关亲核催化过程的一般信息。此外，新的路易斯碱催化剂（手性和非手性）的开发也得到了重视，以使我们目前的许多反应具有立体选择性。

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.