Highly Stereoselective Construction of Carbon-Carbon Bonds Using Phosphonyl and Phosphoramidite Auxiliaries (Chemistry)

使用膦酰基和亚磷酰胺助剂高度立体选择性构建碳-碳键（化学）

• 批准号: 8720270
• 负责人: Slayton Evans
• 金额: $ 22.14万
• 依托单位: University of North Carolina at Chapel Hill
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1991-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8720270&HistoricalAwards=false
• 关键词: Highly; Stereoselective; Construction; Carbon; Bonds

This research is being supported by the Organic and Macromolecular Chemistry Program. The synthesis of the complex structures that occur in nature requires the development of highly specific reactions. This work will produce new reagents based on the unique reactivity produced by a phosphorous atom. Investigations centering on (i) highly stereoselective Aldol reactions (both acid and base-mediated) with alpha-acylphosphonate diesters, (ii) stereochemical control of the Mukaiyama-Michael reaction, and (iii) the stereoselective alkylations of chiral phosphoramidite homoenolate anion synthons are described. The central feature of this three-part research program is the establishment of a highly stereoselective methodology for construction of carbon-carbon bonds within acyclic molecules. Both high diastereofacial and enantiofacial selectivity is predicted based on the stereochemistry and steric bulk of the auxiliary as well as intramolecular metal ion complexation ability. Specifically, the metal anions of alpha-acyl-1,3,2-dioxaphosphonates are used to control enolate geometry and diasteromer preference when alkylated. Introduction of chirality into the 1,3,2-dioxaphosphonyl skeleton creates potential for asymmetry transfer from the chiral auxiliary. Examination of transition state models provide insight into factors likely to control diastereoselectivy. Finally, condensation of chiral phosphoramidities derived from (1S,2R)-(+)-ephedrine and (E)-3-phenylpropenal or crotonaldehyde provide substrates suitable for chelation-controlled enantioselective alkylation of the prochiral organometallic intermediate.

这项研究得到了有机和 高分子化学计划。 配合物的合成 自然界中存在的结构需要发展 非常特殊的反应。 这项工作将产生新的试剂 基于磷原子产生的独特反应性。 以（i）高立体选择性羟醛为中心的研究 反应（酸和碱介导）， α-酰基膦酸二酯，（ii）立体化学控制 Mukaiyama-Michael反应，和（iii）立体选择性 手性亚磷酰胺高烯醇阴离子的烷基化反应 描述的是。 这三部分的核心特征是 研究计划是建立一个高度 立体选择性构建碳-碳方法 非环状分子中的键。 高非对映异构体和 对映选择性预测的基础上， 助剂的立体化学和空间体积以及 分子内金属离子络合能力。 具体地， α-酰基-1，3，2-二氧磷酯用于控制烯醇化物 烷基化时的几何形状和非对映体偏好。 手性引入1，3，2-二氧磷酰基 骨骼产生了从骨骼的不对称转移的可能性， 手性助剂 过渡态模型的检验 深入了解可能控制 非对映选择性 最后，手性的缩合 衍生自（1 S，2 R）-（+）-麻黄碱的磷酰胺， （E）-3-苯基丙烯醛或巴豆醛提供底物 适用于螯合控制对映选择性烷基化 的前手性有机金属中间体。