Multicomponent Domino Processes Based on the Organocatalytic Generation of Conjugated Acetylides: Efficient Synthetic Manifolds for Diversity‐Oriented Molecular Construction

Abstract

Abstract. 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 diversityoriented molecular construction. The domino process involves a nucleophile as catalyst and a terminal conjugated alkyne (H-C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 (non-degenerated chemical output).These properties convert the H-CC-Z unit into a privileged diversity 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 multi-substituted nitrogen-containing heterocycles.

Organocatalytic Asymmetric Synthesis of Organophosphorus Compounds

“…The immense progress in this field of organocatalysis has been recently reviewed. [55] In 2009 the development of a highly stereoselective, organocatalytic Michael-Knoevenagel domino reaction of 4-diethoxyphosphoryl-3-oxobutanoates 126 with a,b-unsaturated aldehydes 84 catalyzed by 86 b leading to enantiomerically enriched 6-substituted-3-diethoxyphosphoryl-2-oxocyclohex-3-enecarboxylates 127 was presented (Scheme 35). [56] This methodology proved to be general, since a wide range of a,b-unsaturated aldehydes 84 bearing either aromatic or aliphatic b-substituents could be easily reacted, affording the corresponding products 127 with high levels of stereocontrol.…”

Progress in Asymmetric Organocatalyzed Michael Addition/Hemi-aminoacetalization/Acylimminium-Cyclization Cascade Reactions

“…丙炔酸酯是构成 C 3 结构单元的重要化合物, 它可以 通过 Diels-Alder 反应、Michael 加成、卤原子的加成和各 种环化反应来实现杂环和芳香类化合物的合成 [20,21] . 其 结构非常活泼, 具有多个反应点(Scheme 7) [21] .…”

Synthesis, Characterization, and Anti‐inflammatory Activity of Novel Isoxazolyl‐4‐(2‐oxo‐2,3‐dihydro‐1H‐3‐indolyl)pyrrole‐3‐carboxylates

“…Multi‐component reactions can be defined as convergent chemical processes where three or more reagents are combined in such a way that the final product retains significant portions of all starting materials. Therefore, they lead to the connection of three or more starting materials in a single synthetic operation with high atom economy and bond‐forming efficiency, thereby increasing molecular diversity and complexity in a fast and often experimentally simple fashion .…”