New Polarity Reversal Strategies for Organic Synthesis

描述（由申请人提供）：采用刘易斯碱（亲核试剂）作为催化剂的新有机反应受到的关注远少于相应领域的刘易斯酸催化或过渡金属催化。然而，这种刘易斯基础策略可以获得这些已建立的催化方法无法实现的创新和不同的反应模式。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。我们的方法集中在充分发展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α-酮酸。这些方法依赖于这样的认识，即当暴露于正确的催化添加时，酰基硅烷和α-酮酸是可行的羰基阴离子前体。使用酰基硅烷和α-酮酸作为实用的酰基阴离子前体避免了当使用醛作为酰基阴离子前体时引起的苯偶姻形成的潜在问题。此外，使用非手性和手性刘易斯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高价值的化合物，所述高价值的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。该提案的其他相关重点包括两个相关的Umpolung反应的发现和发展：催化高烯醇化物加成和立体选择性乙烯基羰基阴离子加成。这些新颖的、非常规的键形成策略具有显著的潜力，可以有效地获得目标导向或多样性导向的感兴趣分子。拟议的研究探讨了我们的有机催化羰基阴离子策略的普遍适用性，用于快速合成直接影响人类健康的分子。这些过程中的每一个都有机理方面的探索，这将提供有关亲核催化过程的一般信息。此外，一个强有力的重点已放在发展新的刘易斯碱催化剂（非手性和手性），以使我们目前的许多反应的立体选择性。

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.