Multicomponent domino processes based on the organocatalytic generation of conjugated acetylides: efficient synthetic manifolds for diversity-oriented molecular construction.
Multicomponent domino processes based on the organocatalytic generation of conjugated acetylides: efficient synthetic manifolds for diversity-oriented molecular construction.
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DOI：
10.1002/chem.200401267
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发表时间：
2005-06
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通讯作者：
D. Tejedor;David González-Cruz;Alicia Sántos-Expósito;J. J. Marrero-Tellado-J.;P. de Armas;F. García‐Tellado-F.-García
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作者：
D. Tejedor;David González-Cruz;Alicia Sántos-Expósito;J. J. Marrero-Tellado-J.;P. de Armas;F. García‐Tellado-F.-García
通过良好亲核试剂的作用有机催化生成强碱是在醛或活化酮存在下原位催化生成共轭乙炔的基础。该方法是负担得起的多组分，多米诺骨牌格式能够产生一组化学多样的多官能化的加合物，非常适合于多样性导向的分子结构。多米诺过程涉及亲核试剂作为催化剂和末端共轭炔（H-C [三重化学键] C-Z）和醛或活化酮作为结构单元。该过程的化学结果作为亲核试剂（叔胺或膦）、温度、化学计量和溶剂的函数而显著变化。这些多组分多米诺过程实现了具有良好原子经济性的分子结构，并且非常重要的是，具有将相同的起始单元精细地化学差异化并入产物中（非简并化学输出）。这些特性将H-C [三重化学键] C-Z单元转化为用于多样性导向分子构建的特定构建块。模块化和多样性为导向的相关杂环合成的应用进行了讨论。一个协议，涉及两个耦合的多米诺骨牌过程连接在一锅的方式将讨论作为一个有效的合成歧管的模块化和多样性为导向的建设多取代的含氮杂环。
The organocatalytic generation of a strong base by the action of a good nucleophile is the base for the in situ catalytic generation of conjugated acetylides in the presence of aldehydes or activated ketones. The method is affordable in a multicomponent, domino format able to generate a chemically diverse set of multifunctionalized adducts that are very well suited for diversity-oriented molecular construction. The domino process involves a nucleophile as catalyst and a terminal conjugated alkyne (H-C[triple chemical bond]C-Z) and an aldehyde or activated ketone as building blocks. The chemical outcome of this process changes dramatically as a function of the nucleophile (tertiary amine or phosphine), temperature, stoichiometry, and solvent. These multicomponent domino processes achieve molecular construction with good atom economy and, very importantly, with an exquisite chemo-differentiating incorporation of identical starting units into the products (nondegenerated chemical output). These properties convert the H-C[triple chemical bond]C-Z unit into a specific building block for diversity-oriented molecular construction. Applications to the modular and diversity-oriented synthesis of relevant heterocycles are discussed. A protocol involving two coupled domino processes linked in a one-pot manner will be discussed as an efficient synthetic manifold for the modular and diversity-oriented construction of multisubstituted nitrogen-containing heterocycles.