Multicomponent domino processes based on the organocatalytic generation of conjugated acetylides: efficient synthetic manifolds for diversity-oriented molecular construction.
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.
Tejedor
David
D
Instituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas, Astrofísico Francisco Sánchez 3, La Laguna, Canary Islands, Spain.
González-Cruz
David
D
Santos-Expósito
Alicia
A
Marrero-Tellado
Jose Juan
JJ
de Armas
Pedro
P
García-Tellado
Fernando
F
D000447:Aldehydes / Q000737:chemistry; D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D007659:Ketones / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction
D000447:Aldehydes; D000480:Alkynes; D007659:Ketones