Improved simplicity and practicability in copper-catalyzed alkynylation of tetrahydroisoquinoline

Abstract

Alkynylation reactions of N-protected tetrahydroisoquinolines have been performed using several different protocols of cross dehydrogenative coupling. Initially, a CuCl-catalyzed method was investigated, which worked well with three different N-protecting groups, namely phenyl, PMP, and benzyl and t-BuOOH as oxidant in acetonitrile as solvent. The peroxide could then be replaced by simple air and acetonitrile for water, leading to an overall very environmentally friendly protocol. Finally, a decarboxylative alkynylation protocol starting from alkynoic acids was also developed using again air as oxidant. This avoids the use of gaseous alkynes in the introduction of short-chained alkyne substituents.Graphical abstract

Recent Advances in Cross‐Dehydrogenative Couplings (CDC) of C−H Bond in Aqueous Media

“…Schnürch and co-workers [42] reported a copper catalyzed alkynylation of N-protected tetrahydroisoquinolines in water under ambient air [Eq. (27)].…”

“…Xiao and co-workers [57] developed a new one-pot oxidative cross-coupling reaction between dithiolanes with alcohols [Eq. (42)]. Under very mild conditions, merging DDQ with cuprous iodide was quite effective for the reaction of an equimolar mixture of 2-aryl dithiolanes, alcohol, and water.…”

Copper(II) Oxide Nanoparticles Impregnated on Melamine‐Modified UiO‐66‐NH2 Metal–Organic Framework for C–N Cross‐Coupling Reaction and Synthesis of 2‐Substituted Benzimidazoles

“…The best reaction time was found to be 30 min. Using shorter time, the reaction was not completed, and using longer time, the reaction yield was almost constant ( Table 4, entries [6][7][8][9]. The effect of the catalyst amount on the reaction was also studied ( Table 4, entries 6 and 10-12), while the other parameters were kept constant.…”

“…Copper as an abundant and inexpensive element, compared with noble metals (e.g. Pd), has been widely used for catalyzing organic reactions such as photodecarboxylation, click azide‐alkyne cycloaddition , C–C cross‐coupling reaction of Suzuki–Miyaura and Stille and Sonogashira–Hagihara , alkynylation of tetrahydroisoquinoline , C–O cleavage/C–N formation for synthesis of indazolo[3,2‐ b ]quinazolinones , allylic C–H oxidation of cyclic olefins , aerobic oxidation of alcohols , oxidative amidation of methylarenes , and also synthesis of carbonyl dibenzofurans , â‐enamino esters , ynones , quinoxalines , polysubstituted pyridines , and indole‐2‐carboxylic esters .…”

Synthesis of Propargylamines by Cross-Dehydrogenative Coupling

“…Naryl THIQs are especially activated substrates towards CDC, that is why they have been widely studied as electrophilic partners in this reaction. Recently, Schnürch et al studied in detail the alkynylation of THIQs through CDC [28]: N-…”