CHEMISTRY OF CHIRAL PHOSPHORUS-STABILIZED CARBANIONS

此应用程序由四个主要部分组成，每个部分都有其特定的 目的，但统一在共同的目标，以了解和利用 手性磷稳定碳负离子化学。 第一部分的目标是建立项目的基础 涉及结构、键合、构型和 磷稳定的碳负离子的构象在三个重要的 家族：1）膦酸，2）次膦酸和3）氧化膦。 这些研究将采用广泛的物理方法，包括 变温，多核核磁共振，弛豫测量，冰点下降 和X射线晶体学 此外，还将使用计算方法 阐明碳负离子的理论结构， 前将芯片 要解决的主要问题是杂交状态， 优选构象、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 手性助剂用于改变反应性和局部环境， 阴离子 根据研究中获得的结构信息， 在第一节中，对尺寸、形状和 电子性质将被并入各种氨基醇中， 二胺助剂 最佳辅助的主要标准是：1） 以光学活性形式容易获得，2）高度选择性反应 碳负离子衍生物的去除温和，易于回收。 第三部分是其目标最多样化的，所有这些都涉及到 磷稳定的化学反应性/选择性 碳负离子。 无数的亲电取代反应， 和烯丙基阴离子，包括烷基化，迈克尔加成，环氧化 开环、羰基加成、胺化、氧化和阴离子 重新安排 此外，选择的非碳负离子反应， 将检验手性改性的磷化合物。 生物学上重要的膦酸和次膦酸的数量 近年来，衍生品迅速增加。 几乎在每一个案例中， 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 有效地获得许多类别的这些化合物，特别是， α-氨基膦酸 作为α-氨基羧酸的类似物 这些化合物已发现作为酶抑制剂，抗生素， 杀虫剂和止痛剂。 手性碳负离子在一般合成中的应用 要求能够以高效率干净地除去磷附属物， 立体选择性 第四节的主要目的 该提议是开发能够裂解碳的新反应， 磷键，并用碳氮，氧和- 保持构型的碳键。

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.