In summary, we have developed a new atom-economical, domino synthesis of nitrogen heterocycles. It was shown that both sulfonamides and carbamates are compatible with the overall process and participate in the domino reaction to form heterocycles via exo and endo type cyclizations. Given the inherent availability of propargyl alcohols through classical alkynylation chemistry, this catalytic domino reaction remarkably disconnects the α-position of a substituted nitrogen heterocycle to a triple bond (of a propargyl alcohol) in a retrosynthetic manner, further increasing the arsenal of possible chemical approaches to the synthesis of alkaloids. Further investigations on this process are underway and will be reported in due course.
Nitrogen-containing heterocycles are ubiquitous subunits of a variety of biologically active substances. Although this has spurred the development of a considerable body of synthetic methods aimed at their efficient preparation, there is a continuous need for new processes which can produce functionalized azacyclic substructures which maximize atom economy.
The Ruthenium catalyzed, atom-economical domino redox isomerisation/cyclization of tethered aminopropargyl alcohols is reported. This process displays a broad scope and functional group tolerance. Furthermore, it presents a novel retrosynthetic disconnection linking simple and easily available, linear propargyl alcohols with added-value nitrogen heterocycles in a single catalytic step.
The computational study is extended to additional substrates, namely, 1-naphthylmethyl-, 2-methylallyl-, and 2-thiophenemethylamines.AB - The oxidative coupling of primary amines with internal alkynes catalyzed by Ru complexes is presented as a general atom-economy methodology with a broad scope of applications in the synthesis of N-heterocycles.