Multi-Component Methodologies in Solid-Phase Organic Synthesis

Abstract

Solid-phase organic synthesis, particularly when used in conjunction with combinatorial techniques, is emerging as a revolutionary technology in chemistry. Multi­ component reaction systems are particularly valued because several elements of diversity can be introduced in a single transformation thereby expanding the diversity of compound libraries. A variety of multi-component reactions have been successfully adapted for solid-phase technology as described in this review.

Automated Library Generation Using Sequential Microwave-Assisted Chemistry. Application toward the Biginelli Multicomponent Condensation

“…14 In times where a premium is put on speed, diversity, and efficiency in the drug discovery process, MCR strategies offer significant advantages over conventional linear-type syntheses. 15 The Biginelli protocol is particularly attractive because the resulting dihydropyrimidine (DHPM) scaffold displays a wide range of biological activities, which has led to the development of a number of lead compounds based on that structural core. 16 In recent years a variety of different combinatorial protocols based on the classical Biginelli MCR have been advanced.…”

Ammonium Chloride-Promoted Four-Component Synthesis of Pyrrolo[3,4-b]pyridin-5-one

“…However, the number game of the high-throughput synthesis has gradually been transformed into a quality and strategy game such that synthetic libraries were more and more oriented from oligomeric compounds to nonoligomeric heterocyclic structures . Within this context, we initiated a research program aimed at the development of highly efficient synthesis of heterocyclic and macrocyclic compounds by combined use of multicomponent reaction (MCR) and domino processes . The guiding principle is to devise a novel multicomponent synthesis of a heterocycle 13 that is appropriately functionalized, allowing it to be engaged in the subsequent domino process.…”

Facile access to regio- and stereoselective synthesis of highly functionalized spiro[indoline-3,2′-pyrrolidines] incorporating a pyrene moiety: experimental, photophysical and theoretical approach

“…However, higher efficiency, higher reaction yields, lower cost, shorter reaction duration, and improved selectivity can be achieved by designing multicomponent reactions (MCRs), which provide access to synthesis of a massive number of compounds that have interesting biological properties using readily available starting materials. 1 Multicomponent [3 + 2] cycloaddition reactions, also known as Huisgen reactions, provide a direct and straightforward entry for the construction of many five-membered heterocyclic ring systems. 2 In the past few decades, [3 + 2] cycloaddition of azomethine ylides, which represent one of the most reactive and versatile classes of 1,3-dipoles, has been used to trap a range of dipolarophiles to construct pyrrolidine, pyrrolizine and pyrrolothiazole derivatives in a regio and stereo controlled fashion.…”