Three-component cycloaddition, acetylene

In the presence of octacarbonyldicobalt, three-component cycloaddition of acetylenes occurs with alkenes and carbon monoxide, affording cyclopentenones. Although thermal activation of the organometallic was the original method of effecting this transformation, a variety of reaction additives have since been explored, resulting in procedures that permit the... 

Bora and co-workers44 have developed a microwave-assisted three-component synthesis of indolizines. The reaction involves a 1,3-dipolar cycloaddition reaction between the in situ generated dipole (from the bromoacetophenone and pyridine) and acetylene, Scheme 5.26. The developed method provides fast access to cycloadducts, which otherwise are accessible only through multi-step synthesis. 

The benzannulation reaction is a versatile method for the formation of polysubstituted aromatic compounds such as naphthoquinones. This three-component coupling involves the reaction between an a. unsaturated Fischer carbene, an acetylene, and a CO ligand, and initially proceeds by cycloaddition of the alkyne with the carbene complex. The regioselectivity of this step is highly dependent on the substituents on the acetylene moiety and is usually low in the case of internal acetylenes. 

The alkynyl functionality of alkynones 1 is perfectly suited for subsequent copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) in the sense of an MCR (2015ASC(357)617). A microwave-assisted three-component reaction of aroyl chlorides 4, TMS-substituted acetylene (5a), and benzyl azide (10a) consisting of modified Sonogashira cross-coupling I, desilylation, and CuAAC furnishes 4-disubstituted 1,2,3-triazoles 11 in moderate to excellent yields (Scheme 5) (201 OOL(12)4936). 

A number of 3-triazolyl-2-iminochromenes were synthesized with Cul catalyst through three-component condensation. Initially, a Cul-catalyzed cycloaddition between 2-azidoacetonitrile and an acetylene could lead to a triazole intermediate. 

Vinyl- and acetylenic tricarbonyl compounds are reactive dienophilic components in Diels-Alder reactions. Cycloadditions of these compounds with substituted butadienes were recently used to develop a new synthetic approach to indole derivatives [14] (Scheme 2.9) by a three-step procedure including (i) condensation with primary amines, (ii) dehydration and (iii) DDQ oxidation. 

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