CHEMISTRY OF CHIRAL PHOSPHORUS-STABILIZED CARBANIONS

这个应用程序由四个主要部分组成，每个部分都有自己的特定 目的但统一于共同的目标，以理解和利用 手性、磷稳定的碳负离子的化学。 第一部分的目标是为项目奠定基础 涉及结构、连接、配置和 三种重要的磷稳定碳负离子的构象 种类：1)膦酸，2)膦酸和3)膦氧化物。 这些研究将使用广泛的物理方法，包括 变温，多核核磁共振，弛豫测量，冷冻 和X射线结晶学。此外，还将使用计算方法 为了阐明碳负离子的理论结构和详细的 凝聚力。需要解决的主要问题是杂交状态， 择优构象、旋转势垒和稳定机制 碳负离子。 第二部分的主要目标是合理设计 手性助剂用于修饰环氧乙烷的反应性和局部环境 负离子。基于从研究中获得的结构信息 在第一节中，对尺寸、形状和尺寸的具体要求 电子性质将被结合到各种氨基醇和 二胺佐剂。最佳辅助剂的主要标准是：1) 光学活性形式的现成可获得性，2)高选择性反应 碳负离子衍生物和3)温和去除和易于回收。 第三部分的目标是最多样化的，所有这些目标都涉及 磷稳定剂的化学反应活性/选择性 碳负离子。一系列简单的亲电取代反应 烯丙基阴离子计划包括烷基化、Michael加成、环氧化物 开环、羰基加成、胺化、氧化和阴离子 重新安排。此外，精选的非碳离子反应 手性修饰的磷化合物将被检查。 具有重要生物意义的膦酸和膦酸的数量 近年来，衍生品增长迅速。在几乎每一起案件中， 分子的绝对构型对于 生物活性。在这个项目中开发的反应将提供 有效地获取许多类别的这些化合物，特别是 α-氨基膦酸类。作为α-氨基甲酸的类似物 这些化合物已被用作酶抑制剂、抗生素、 杀虫剂和镇痛剂。 手性碳负离子在一般合成中的应用 要求能够清洁地去除含磷量高的附属物 立体选择性。本部分第四部分的主要目标是 建议是开发能够分解碳的新反应- 磷键，用碳-氮，-氧和- 保持构型不变的碳键。

This application consists of four major sections each with its own specific aims but unified in the common objective to understand and utilize the chemistry of chiral, phosphorus-stabilized carbanions. The goal of the first section is to establish the foundation of the project involving the fundamental issues of structure, bonding, configuration and conformation of phosphorus-stabilized carbanions in three important families: 1) phosphonic acids, 2) phosphinic acids and 3) phosphine oxides. These studies will employ a wide range of physical methods including variable temperature, multinuclear NMR, relaxation measurements, cryoscopy and X-ray crystallography. In addition, computational methods will be used to elucidate the theoretical structures of carbanions and details of bonding. The major issues to be addressed are the hybridization state, preferred conformation, rotational barrier and mechanism of stabilization of the carbanions. The principal objective of the second section is the rational design of chiral auxiliaries used to modify the reactivity and local environment of the anion. Based ont he structural information available from the studies in the first section, the specific requirements for size, shape and electronic properties will be incorporated into various amino alcohol and diamine adjuvants. The major criteria for an optimal auxiliary are: 1) ready availability in optically active form, 2) highly selective reactions of carbanion derivatives and 3) mild removal and easy recovery. The third section is the most diverse in its goals, all of which involve the chemical reactivity/selectivity of the phosphorus-stabilized carbanions. A myriad of electrophilic substitution reactions of the simple and allyl anions is planned including alkylation, Michael addition, epoxide opening, carbonyl addition, amination, oxidation and anionic rearrangements. In addition, a selection of non-carbanionic reactions of the chirally-modified phosphorus compounds will be examined. The number of biologically important phosphonic and phosphinic acid derivatives has increased rapidly in recent years. In nearly every case, the absolute configuration of the molecules has been critical for biological activity. The reactions developed in this project will provide efficient access to many classes of these compounds, in particular, the alpha-aminophosphonic acids. As analogs of alpha-aminocarboxylic acids these compounds have found application as enzyme inhibitors, antibiotics, insecticides and analgesics. The utility of the chiral carbanions for general synthetic applications requires the ability to remove the phosphorus appendage cleanly with high stereoselectivity. The principal objective of the fourth section of this proposal is the development of new reactions capable of cleaving carbon- phosphorus bonds and replacing them with carbon-nitrogen,-oxygen and - carbon bonds with preservation of configuration.