Synthesis of Medicinally Important Heterocycles

描述（由申请人提供）：绝大多数具有重要药用价值的药物含有杂环或碳环。功能取代的炔的亲电环化反应研究很少，尽管它似乎是一个非常有前途的路线，以一个非凡的范围内的医学上有趣的，功能取代的杂环和碳环。Larock小组已经进行了初步的工作，表明在非常温和的反应条件下，官能取代的炔的亲电环化很容易得到非常高产率的各种卤素、硫和硒取代的苯并噻吩、异喹啉、苯并呋喃和异香豆素。这项工作将继续并扩展到各种各样的其他环化，包括香豆素，呋喃香豆素，呋喃黄酮，吲哚，苯并硒吩，苯并内酰胺，二氢嘧啶，2-呋喃酮，2-吡咯啉酮，苯并吡喃，色酮和杂原子类似物，呋喃，噻吩，吡咯，恶唑，异恶唑，吡唑，吡啶，喹啉，香豆素，茚，茚酮，萘酚和苯酚。碘环化、Sonogashira偶联和进一步亲电环化是合成稠合多环杂环化合物的有效途径。功能取代的联烯的类似环化反应也很有希望。亲电试剂的范围，这可能是在这些环化，包括有机钯化合物，也将进行探讨。随后通过钯催化的方法对所得含卤素杂环和碳环的精细加工提供了用于构建药学上感兴趣的化合物的高度有效的方法，其合成将被追求。

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.