Asymmetric Umpolung Aldehyde Reactions

手性亲核卡宾催化醛类反应活性的研究进展， 揭示了新的反应性，并导致新的键断开相关的合成的一些 具有生物学意义的目标。与亲核卡宾反应生成亲电子醛 转化为亲核酰基阴离子等价物，其可以被各种亲电试剂拦截， 形成碳-碳键的新方法。如果使用手性亲核卡宾作为催化剂进行， 我们期望在随后的成键事件中引入不对称性。这些反应将应用于 合成具有挑战性的生物活性天然产物。 本研究的具体目标如下：1）将不对称Stetter反应应用于甾体类化合物 基板产生新的架构和发展多米诺骨牌进程使用这些方法; 2） 开发非对映选择性不对称Stetter反应，这将能够影响形成 3）在单次操作中使用不对称Stetter反应， 血管生成抑制剂氮杂螺烯的合成; 4）设计并执行一种快速的方法， 使用非对映选择性不对称Stetter反应立体化学复合生物碱天冬酰胺; 5)将不对称Stetter反应应用于使用邻醌合成crinamine 1和viridin， 二烯酮作为亲电体; 6）通过利用大的负电荷来探索醛的氧化还原化学 亲核烯烃的氧化电位和内部氧化还原体系。

Expansion of current reactivity umpolung of aldehydes catalyzed by chiral nucleophilic carbenes promises to reveal new reactivity and lead to novel bond disconnections relevant to the synthesis of a number of biologically significant targets. Reaction with a nucleophilic carbene transforms an electrophilic aldehyde into a nuclephile acyl anion equivalent which can be intercepted with a variety of electrophiles, providing a novel means of forming carbon-carbon bonds. If conducted using a chiral nucleophilic carbene as catalyst, we expect to induce asymmetry into the subsequent bond-forming event. These reactions will be applied to the synthesis of challenging, biologically active natural products. The specific goals of this research are as follows: 1) apply the asymmetric Stetter reaction to alkaloidal substrates to generate novel architectures and develop domino processes using these approaches; 2) develop the diastereoselective asymmetric Stetter reaction, which will be able to effect the formation of multiple contiguous stereocenters in a single operation; 3) use the asymmetric Stetter reaction in the synthesis of the angiogenesis inhibitor azaspirene; 4) design and execute a rapid approach to the stereochemically complex alkaloid asparagamine using the diastereoselective asymmetric Stetter reaction; 5) apply the asymmetric Stetter reaction to the synthesis of crinamine 1 and viridin using orthoquinones and dienones as electrophiles; 6) explore aldehyde umpolung redox chemistry by exploiting the large negative oxidation potential of the nucleophilic alkene and internal redox systems.