Synthetic and Mechanistic Studies on the Solvent-Dependent Copper-Catalyzed Formation of Indolizines and Chalcones

Abstract

Copper nanoparticles supported on activated carbon have been found to catalyze the multicomponent synthesis of indolizines from pyridine-2-carbaldehyde derivatives, secondary amines and terminal alkynes in dichloromethane; in the absence of solvent, however, heterocyclic chalcones are formed. We provide compelling evidence that both processes take place through aldehyde-amine-alkyne coupling intermediates. In contrast to other well-known mechanisms for chalcone formation from aldehydes and alkynes, a new reaction pathway is presented involving propargyl amines as intermediates which do not undergo rearrangement. The formation of indolizines or chalcones is driven by inductive and solvent effects, with a wide array of both being reported. In both reactions, the nanoparticulate catalyst has been shown to be

Substrate‐Controlled Divergent Synthesis of Enaminones and Pyrroles from Indolizines and Nitroso Compounds

“…The indolizines 1 were prepared from pyridine‐2‐carbaldehydes, secondary amines and terminal alkynes using two methods: the aldehyde (2 mmol), amine (2 mmol) and alkyne (2 mmol) were added to a reactor tube containing (a) CuNPs/C (80 mg, ca. 0.5 mol%) and dichloromethane (2.0 mL) for the indolizines 1 a – 1 g , or (b) CuI (38 mg, 10 mol%) under solvent‐free conditions for the indolizines 1 i – 1 s . The reaction mixture was warmed to 70 °C without the exclusion of air and monitored by TLC and/or GLC until total or steady conversion of the starting materials.…”

“…In view on these antecedents, there is a certain upsurge of interest in designing novel synthetic strategies that impart functionalization and substitution patterns to enaminones and pyrroles unreachable by other routes. By virtue of our current interest in the application of copper nanoparticles to multicomponent reactions, we published the solvent‐controlled three‐component synthesis of amino‐substituted indolizines and the synthesis of heterocyclic chalcones from pyridine‐2‐carbaldehyde derivatives, secondary amines and terminal alkynes catalyzed by copper nanoparticles on activated carbon (CuNPs/C) (Scheme ) . The reactivity of the aforementioned indolizines has been explored only recently: their heterogeneous catalytic hydrogenation led to indolizidines in a chemo‐ and diastereoselective manner, whereas an acid‐base treatment furnished a new family of solvatochromic dyes through a metal‐free C−H site‐selective alkenylation…”

Tailoring of the Frontier Orbital Character in Co2+/3+ Complexes with Triarylamine Substituted Terpyridine Ligands

“…Toluene was taken from a solvent purification system SPS‐800 by MBraun. ( E )‐1‐(6‐Bromopyridin‐2‐yl)‐3‐phenylprop‐2‐en‐1‐one and 1‐[2‐oxo‐2‐(2‐pyridinyl)ethyl]pyridinium iodide were synthesised as reported in the literature. All other chemicals were purchased from commercial suppliers and were used without further purification.…”

One‐Pot Alkynylation of Azaaryl Aldehydes and Spontaneous Base‐Free Rearrangement into Enone Esters: an Autoinductive Mechanism

“…[29][30][31][32][33] All these methods require first forming and isolating the propargylic alcohol and then submitting it to the rearrangement conditions. [35,36] We have recently reported on the use of the Soai's autocatalyst in the asymmetric alkynylation of azaaryl aldehydes with various zinc acetylinides. [34] The reaction was promoted by KOtBu and provided a rapid access to (E)-1-en-4-yn-3-ol and (Z)-2-en-4-yn-1-ol compounds.…”

“…Moreover, the synthesis of heterocyclic chalcones has been accomplished from pyridine-2-carbaldehyde derivatives, secondary amines and alkynes with CuNPs/C as catalyst. [35,36] We have recently reported on the use of the Soai's autocatalyst in the asymmetric alkynylation of azaaryl aldehydes with various zinc acetylinides. [37][38][39] During our investigations, an interesting rearrangement was observed with electron-deficient alkynes under the same reaction conditions, which gave rise to heteroaromatic enone.…”