Asymmetric Umpolung Aldehyde Reactions

不对称醛醛反应

基本信息

批准号：
7488917
负责人：
Tomislav Rovis
金额：
$ 21万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-05 至 2010-04-30
项目状态：
已结题

项目摘要

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.

手性亲核卡宾催化的醛的当前反应性的扩展有望揭示新的反应性并导致与许多合成相关的新的键断裂具有生物学意义的目标。与亲核卡宾反应转化为亲电醛转化为亲核酰基阴离子等价物，可以用多种亲电子试剂拦截，从而提供形成碳-碳键的新方法。如果使用手性亲核卡宾作为催化剂进行，我们期望在随后的成键事件中引入不对称性。这些反应将被应用到具有挑战性的、具有生物活性的天然产物的合成。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颖的架构并开发多米诺骨牌过程的基板； 2）发展非对映选择性不对称Stetter反应，这将能够影响形成一次操作中多个连续的立体中心； 3）使用不对称Stetter反应血管生成抑制剂氮杂螺环的合成； 4）设计并执行快速方法使用非对映选择性不对称Stetter反应合成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，作为亲电子试剂的二烯酮； 6）利用大负值探索醛的氧化还原化学亲核烯烃和内部氧化还原系统的氧化电位。