Asymmetric Umpolung Aldehyde Reactions

手性亲核卡宾催化的醛的当前反应性的扩展有望 揭示了新的反应性，并导致了与许多化合物的合成有关的新的键断开 具有重要生物学意义的目标。与亲核的卡宾反应转化为亲电的醛 转化为可被各种亲电体截留的亲核酰基阴离子当量物，提供 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， 我们预计会在随后的成键事件中诱导不对称。这些反应将应用于 人工合成具有挑战性、生物活性的天然产物。 本研究的具体目标如下：1)将不对称Stetter反应应用于生物碱 使用这些方法生成新的体系结构和开发多米诺进程的基板；2) 发展非对映选择性不对称Stetter反应，它将能够影响 一次操作多个连续的立体中心；3)使用不对称Stetter反应 合成血管生成抑制剂阿司匹林；4)设计并实施一种快速方法 使用非对映选择性不对称Stetter反应的立体化学复杂生物碱天冬酰胺； 5)将不对称Stetter反应应用于邻苯二酚类化合物的合成 6)利用大负极探索乙醛的氧化还原化学。 亲核烯和内部氧化还原体系的氧化电位。

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.