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.

手性亲核癌催化的醛的电流反应性升高有望揭示新的反应性，并导致与许多多个合成有关的新型键断开生物学意义的靶标。与亲核的碳反应转化了亲电醛进入核素酰基阴离子等效物，该阴离子可以用多种电力拦截，提供形成碳碳键的新型手段。如果使用手性亲核碳作为催化剂进行我们期望将不对称性诱导到随后的键形成事件中。这些反应将用于具有挑战性的生物活性天然产品的合成。这项研究的具体目标如下：1）对生物碱应用不对称的Stetter反应底物使用这些方法生成新颖的体系结构并开发多米诺骨牌过程； 2）发展非对映选择性不对称的静态反应，这将能够影响形成单个操作中的多个连续立体中心； 3）在该反应中使用不对称的Stetter反应血管生成抑制剂悬齿的合成； 4）设计并执行快速的方法立体化学上复杂的生物碱白香肠，使用非对映选择性不对称的Stetter反应； 5）使用正喹酮和crinamine 1和viridin的合成，将不对称的静态反应应用硫酮作为电力； 6）通过利用较大的负阴性来探索醛的Umpolung氧化还原化学反应亲核烷烃和内部氧化还原系统的氧化潜力。