Abstract

Heterocycles, heteroaromatics and spirocyclic entities are ubiquitous components of a wide plethora of synthetic drugs, biologically active natural products, marketed pharmaceuticals and agrochemical targets. Recognizing their high proportion in drugs and rich pharmacological potential, these invaluable structural motifs have garnered significant interest, thus enabling the development of efficient catalytic methodologies providing access to architecturally complex and diverse molecules with high atom-economy and low cost. These chemical processes not only allow the formation of diverse heterocycles but also utilize a range of flexible and easily accessible building units in a single operation to discover diversity-oriented synthetic approaches. Alkynoates are significantly important, diverse and powerful building blocks in organic chemistry due to their unique and inherent properties such as the electronic bias on carbon–carbon triple bonds posed by electron-withdrawing groups or the metallic coordination site provided by carbonyl groups. The present review highlights the comprehensive picture of the utility of alkynoates (2007–2019) for the synthesis of various heterocycles (> 50 types) using transition-metal catalysts (Ru, Rh, Pd, Ir, Ag, Au, Pt, Cu, Mn, Fe) in various forms. The valuable function of versatile alkynoates (bearing multifunctional groups) as simple and useful starting materials is explored, thus cyclizing with an array of coupling partners to deliver a broad range of oxygen-, nitrogen-, sulfur-containing heterocycles alongside fused-, and spiro-heterocyclic compounds. In addition, these examples will also focus the scope and reaction limitations, as well as mechanistic investigations into the synthesis of these heterocycles. The biological significance will also be discussed, citing relevant examples of drug molecules highlighting each class of heterocycles.

Graphic Abstract

This review summarizes the recent developments in the synthetic methods for the synthesis of various heterocycles using alkynoates as readily available starting materials under transition-metal catalysis.

中文翻译：

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烷基酸作为过渡金属催化下快速组装各种杂环化合物的多功能和强大的化学工具：最近的发展和挑战

摘要

杂环，杂芳族和螺环实体是大量合成药物，具有生物活性的天然产物，市售药品和农用化学品靶标中无处不在的成分。认识到它们在药物中的高比例和丰富的药理潜力，这些宝贵的结构基序引起了人们的极大兴趣，从而使开发高效的催化方法学成为可能，从而使人们能够以高原子经济性和低成本获得结构复杂而多样的分子。这些化学过程不仅允许形成各种杂环，而且还可以在一次操作中利用一系列灵活且易于使用的建筑单元来发现面向多样性的合成方法。炔酸非常重要，有机化学的独特和固有特性，例如吸电子基团对碳-碳三键的电子偏压或羰基提供的金属配位点，是有机化学中多种多样而强大的构建基块。本综述着重介绍了使用过渡金属催化剂（Ru，Rh，Pd，Ir，Ag，Au，Pt，Cu，Al，Al 2）（2007-2019）用于合成各种杂环（> 50种）的实用情况的综合图景。 Mn，Fe）以各种形式存在。探究了多功能链烷酸酯（带有多功能基团）作为简单有用的原料的宝贵功能，从而与一系列偶合伙伴进行环化反应，以提供广泛的含氧，氮，硫的杂环以及稠合和螺环-杂环化合物。此外，这些实施例还将关注范围和反应限制，以及对这些杂环的合成的机理研究。生物学意义也将被讨论，列举了突出每一类杂环的药物分子的相关实例。

图形摘要

这篇综述总结了在过渡金属催化下使用炔酸作为容易获得的起始原料合成各种杂环的合成方法的最新进展。