Use of Silyl Glyoxylates in Tandem Vinylation/Brook Rearrangement/Adol Reactions

描述(申请人提供)：串联反应和多组分偶联长期以来一直是有机合成的理想目标，因为它们可以快速有效地从较简单的起始材料形成复杂的分子。该项目的长期目标是设计非对映和对映选择性反应，可用于天然产品和与药物相关的构建块的合成设计。这项提议集中于从硅基乙氧基酸酯、乙烯基格氏反应和醛的多米诺骨牌反应中生成a，(3-二羟基，v-手性羰基化合物)。具体地说，提出的战略是： I)通过使用8-苯基-薄荷醇、缬氨醇和苯丙氨醇等酯基官能团来制备手性硅乙醛酸酯，以考察对映体选择性的诱导； Ii)研究手性格氏配体对映体选择性的诱导，如(-)-司马豆碱、反式-1，2-二氨基环己烷和/V，A/-二甲基伪麻黄碱。 三)评估添加到前手性醛(如三丁二醛)，然后使用阳离子Rh或Ir物种进行对映选择性羟基定向氢化的可能性； 四)在迄今为止最简明的抗真菌、植物毒性天然产物交链孢子酸的合成中使用上述方法。 许多治疗药物要么是天然产品本身，要么来自天然产品，最常见的是具有特定取向(立体化学)的键和官能团。这项研究的目的是通过一次组装多个片段，以一种简洁的方式获得这些潜在药物的一部分，并完成立体化学完整性。通过快速构建这些组分，可以更快地合成潜在的药物进行进一步研究。

DESCRIPTION (provided by applicant): Tandem reactions and multicomponent couplings have long been a desirable goal for organic synthesis, as they quickly and efficiently fashion complex molecules from simpler starting materials. The long term goal of this project is to devise diastereo- and enantioselective reactions that can be used in the synthetic design of natural products and pharmaceutically relevant building blocks. This proposal focuses on the generation of a,(3-dihydroxy, v-chiral carbonyl compounds from the domino reaction of silylglyoxylates, vinyl Grignard, and aldehydes. Specifically the strategy presented is to: i) examine induction of enantioselectivity by making a chiral silylglyoxylate via the ester functionality such as usage of 8-phenyl-menthol, valinol, and phenylalaninol; ii) examine induction of enantioselectivity via chiral Grignard ligands such as (-)-sparteine, trans- 1,2-diaminocyclohexane, and /V,A/-dimethylpseudoephedrine. iii) assess the potential for addition to prochiral aldehydes (e.g. tiglic aldehyde) followed by enantioselective hydroxyl-directed hydrogenation using cationic rhodium or iridium species; iv) utilize the aforementioned methodology in the most concise synthesis to date of the antifungal, phytotoxic natural product alternaric acid. A wide number of therapeutics are either natural products themselves or derived from natural products, most often with specific orientations (stereochemistry) of bonds and functional groups. This research aims to access portions of these would-be Pharmaceuticals in a succinct manner via assembly of multiple segments at one time, complete with stereochemical integrity. Through rapid construction of these components, potential medicines can be synthesized more quickly for further study.