Synthesis of Medicinally Important Heterocycles

说明书(申请人提供)：绝大多数重要的医学药物都含有杂环或碳环。人们对功能取代的炔烃的亲电环化反应的研究很少，尽管这似乎是一条非常有前途的路线，可以得到一系列非常有药用价值的功能取代的杂环和碳环。LaRock小组开展的初步工作表明，在非常温和的反应条件下，官能化取代的炔烃的亲电环化很容易产生各种卤代、硫代和硒取代的苯并噻吩类、异喹啉类、苯并呋喃类和异香豆素类化合物。这项工作将继续并扩展到广泛的其他环化反应，包括香豆素、呋喃香豆素、呋喃黄酮、吲哚、苯并硒、苯并内酰胺、二氢嘧啶、2-呋喃酮、2-吡咯烷酮、苯并吡喃、色酮和杂原子类似物、呋喃、噻吩类、吡咯、恶唑、异恶唑、吡唑、吡啶、喹啉、香豆素、吲哚、吲哚、萘酚和酚。顺序的碘环化、Sonogashira偶联和进一步的亲电环化是合成多环杂环化合物的有效途径。类似的官能化取代的联烯的环化反应似乎也很有希望。还将探索在这些环化反应中可能使用的亲电试剂的范围，包括有机钯化合物。随后通过钯催化过程精制得到的含卤素的杂环和碳环，为构建具有药用价值的化合物提供了高效的方法，这些化合物的合成将被继续进行。

DESCRIPTION (provided by applicant): The vast majority of medicinally important drugs contain a heterocyclic or carbocyclic ring. The electrophilic cyclization of functionally-substituted alkynes has been little studied, although it would appear to be a very promising route to an extraordinary range of medicinally interesting, functionally-substituted heterocycles and carbocycles. The Larock group has carried out preliminary work suggesting that the electrophilic cyclization of functionally-substituted alkynes readily affords very high yields of a wide variety of halogen-, sulfur- and selenium-substituted benzothiophenes, isoquinolines, benzofurans, and isocoumarins under exceptionally mild reaction conditions. This work will be continued and extended to a wide variety of additional cyclizations including coumestans, furocoumarins, furoflavones, indoles, benzoselenophenes, benzolactams, dihydropyrimidines, 2-furanones, 2-pyrrolinones, benzopyrans, chromones and heteroatom analogues, furans, thiophenes, pyrroles, oxazoles, isoxazoles, pyrazoles, pyridines, quinolines, coumarins, indenes, indenones, naphthols, and phenols. Sequential iodocyclization, Sonogashira coupling and further electrophilic cyclization appears promising as an efficient route to fused polycyclic heterocycles. Analogous cyclizations of functionally-substituted allenes also appear quite promising. The range of electrophiles, which might be employed in these cyclizations, including organopalladium compounds, will also be explored. Subsequent elaboration of the resulting halogen-containing hetero- and carbocycles via palladium-catalyzed processes provides highly, efficient methodology for the construction of pharmaceutically interesting compounds, whose synthesis will be pursued.