SYNTHETIC APPLICATIONS OF CONJUGATED KETENE DITHIOACETAL

本次调查的具体目的是探索和发展 α-氧代酮二硫代缩醛的化学。目前正在进行两个程序 为有效利用该官能团而开发的 选择性(即化学选择性、区域选择性和立体选择性) 碳-碳键结构和官能团操纵。这个 第一种方法涉及化学选择性和立体选择性的偶联物 将有机铜加成到α-氧代乙烯酮二硫代缩醛和 生成的乙烯基硫代酯。第二种方法涉及 酮甲酰的1，2-亲核加成，然后是酸 催化重排，构成一种用途广泛的1，3-羰基 允许区域选择性序列的转位方法学 碳-碳键结构。具体目标有两个。第一, 这两种方法的范围、局限性和反应参数 将被非常仔细地检查。二、综合应用 与α-亚烷基酮的合成有关， α-吡喃，以及简单和环状苯衍生物 检查过了。这些方法论的发展将提供一般路线 到几类化合物，并将为 构建特定的替代模式。每一种合成纤维 应用将需要研究以优化反应条件和 确定合成路线的范围和限制。这个 顺序区域、立体声和声音方法的发展 利用化学选择性构筑新的碳-碳键 α-氧代酮烯二硫缩醛级联将提供多种用途的合成 机遇。在前期工作中，这些综合方法的威力 肌地黄酮的全合成证明了这一点。直接进入 进入区域和立体特定取代的丰富化学 烯丙醇是另一个例子。 杂环化合物的合成方法的发展(例如 α-吡喃)和苯类芳香族化合物将有助于 搜索活性药用化合物。本方法论适用于 生物活性天然产物的合成及人工合成 梅迪纳尔。

The specific aim of this investigation is to explore and develop the chemistry of Alpha-oxoketene dithioacetals. Two procedures are being developed for the efficient exploitation of this functional group for selective (i.e. chemoselective, regioselective and stereoselective) carbon-carbon bond constructions and functional group manipulations. The first method involves the chemoselective and stereoselective conjugate addition of organocuprates to Alpha-oxoketene dithioacetals and to the resultant vinylogous thioesters. The second method involves 1,2-nucleophilic additions to the ketone carbonyl followed by acid catalyzed rearrangement and constitutes a versatile 1,3-carbonyl transposition methodology that permits regioselective sequential carbon-carbon bond constructions. The specific goals are two-fold. First, the scope, limitations, and reaction parameters of these two procedures will be examined in very careful detail. Second, the synthetic application of this chemistry to the synthesis of Alpha-alkylidene ketones, Alpha-pyrones, and simple and annulated benzene derivatives will be examined. Development of these methodologies will provide general routes to several classes of compounds and will provide versatility for the construction of specific substitution patterns. Each of the synthetic applications will require studies to optimize reaction conditions and determine the scope and limitations of the synthetic routes. The development of methods for the sequential regio-, stereo-, and chemoselective construction of new carbon-carbon bonds utilizing the Alpha-oxoketene dithioacetal cascade will provide versatile synthetic opportunities. In preliminary work the power of these synethetic methods has been illustrated by a total synthesis of Myodesmone. The direct entry into the rich chemistry of regio- and stereospecifically substituted allylic alcohols provides another example. The development of methods for the synthesis of heterocycles (e.g. Alpha-pyrones) and benzenoid aromatic compounds will contribute to the search for active medicinal compounds. The methodologies are applicable to the synthesis of biologically active natural products and synthetic medicinals.