AN ANNULATION METHOD FOR THE SYNTHESIS OF HIGHLY SUBSTITUTED POLYCYCLIC AROMATIC AND HETEROAROMATIC-COMPOUNDS
AN ANNULATION METHOD FOR THE SYNTHESIS OF HIGHLY SUBSTITUTED POLYCYCLIC AROMATIC AND HETEROAROMATIC-COMPOUNDS
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DOI：
10.1021/ja00164a033
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发表时间：
1990-04-11
影响因子：
15
通讯作者：
MILLER, RF
中科院分区：
文献类型：
--
作者：
DANHEISER, RL;BRISBOIS, RG;MILLER, RF
已经开发了合成高度取代的多环芳香族和杂芳香族化合物的一般策略。这种新的芳香环化反应是用乙炔衍生物和乙烯基或芳基重氮酮的二氯乙烷溶液辐照而简单地完成的。从机理上讲，反应通过重氮酮的光化学沃尔夫重排进行，生成芳基或乙烯基烯酮，然后进行三个周环反应的级联。利用该方法可以制备多种取代苯酚、萘、苯并呋喃、苯并噻吩、吲哚和咔唑。芳香环化反应在海洋生物碱海拉唑全合成中的应用表明了该方法的合成实用性，自19世纪世纪最早的有机合成研究以来，合成取代芳香化合物的有效方法的发明一直引起化学家的兴趣。芳香族化合物的经典方法利用容易获得的苯衍生物，并且严重依赖于亲电和亲核取代反应。近年来，定向金属化反应已经加入了经典的取代方法，作为另一种载体引入取代基到预先存在的芳环上。高度取代的芳香族化合物的第二种方法涉及成环方法的应用：收敛策略，其中芳香族系统在单个步骤中由无环前体组装，所有（或大多数）取代基已经就位。环化策略比经典的线性取代策略具有几个优点，特别是当应用于制备高度取代的靶分子时。例如，环化路线经常避免与芳族取代反应相关的区域化学不确定性，并提供通过更常规的路线不能获得的取代模式。成环策略的固有收敛性质促进了高度取代的芳香族化合物的有效组装，这将需要使用经典取代方法的长的多步骤路线。
A general strategy for thesynthesis of highly substituted polycyclic aromatic and heteroaromatic compounds has been developed. The new aromatic annulation is achievedsimply by the irradiationof a dichloroethane solution of an acetylene derivative and a vinyl or aryl-diazo ketone. Mechanistically, the reaction proceeds via the photochemical Wolff rearrangement of the diazo ketone to generate an aryl-or vinylketene, followed by a cascade of three pericyclic reactions. A variety of substituted phenols, naphthalenes, benzofurans, benzothiophenes, indoles, and carbazoles can beprepared by using the method. The application of the aromatic annulation to the total synthesis of the marine alkaloid hyellazole demonstrates the synthetic utility of the method.The invention of efficient methods for the synthesis of sub-stituted aromatic compounds has commandedthe interest of chemists since the time of the earliest synthetic organic investigations in the 19th century. Classical approaches to aromatic compounds exploited readily available benzene derivatives and relied heavily on electrophilic and nucleophilic substitution re-actions. In recent years, directed metalation reactions have joined the classical substitution methods as another vehicle for the in-troduction of substituents onto preexisting aromatic rings. A second approach to highly substituted aromatic compounds involves the applicationof annulation methods: convergent strategies in which the aromatic system is assembled from acyclic precursors in a single step, with all (ormost) substituents already in place. Annulation strategies enjoy several advantages over classical linear substitution strategies, especially when applied to the preparation of highly substituted target molecules. For ex-ample, annulation routes frequently avoid the regiochemical am-biguities associated with aromatic substitution reactions and provide access to substitution patterns that cannot be obtained via the more conventional routes. The intrinsic convergent nature of annulation strategies facilitates the efficient assembly of highly substituted aromatics that would require long, multistep routes using classical substitution methodology.