Cascade Intermolecular Michael Addition–Intramolecular Azide/Internal Alkyne 1,3-Dipolar Cycloaddition Reaction in One Pot

Abstract

A rapid one-pot protocol for the synthesis of indole-based polyheterocycles via a sequential Lewis acid catalyzed intermolecular Michael addition and an intramolecular azide/internal alkyne 1,3-dipolar cycloaddition reaction has been described. The generality of the method has been demonstrated by treating a series of aromatic/aliphatic 2-alkynyl indoles with substituted (E)-1-azido-2-(2-nitrovinyl)benzenes to furnish annulated tetracyclic indolo[2,3-c][1,2,3]triazolo[1,5-a][1]benzazepines in good yields.

Palladium(II)-Catalyzed Intramolecular Oxidative C–H/C–H Cross-Coupling Reaction of C3,N-Linked Biheterocycles: Rapid Access to Polycyclic Nitrogen Heterocycles

“…In particular, we achieved the synthesis of pentacyclic indole-fused indolizine derivative 2m , which is structurally related to that of the marine alkaloids such as fascaplysin and homofascaplysin C . Although these latter polycyclic heterocycles occupy an important place in medicinal chemistry and life science, their construction often requires multistep approaches and harsh reaction conditions and suffers from disadvantages of a limited substrate scope. , To the best of our knowledge, our findings represent also the first examples of intramolecular C–H/C–H cross-coupling of indoles with pyrrole and 1,2,3-triazole partners.…”

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

“…The varying acetonitrile/water ratio demonstrated no impact on the product yield (Table 1, entries 18 and 19). The reaction was found to proceed well in pure acetonitrile as well (Table 1, entries [20][21][22] and even led to a better yield at 140 °C than in the acetonitrile/water mixture. Finally, we tested NMP as a green solvent that is also one of the safest choices for per-forming high-temperature MW-assisted syntheses (high boiling point, nonvolatile).…”

“…In the next step of our study, the Ugi products 6 were involved in IAAC. Compounds such as 6aab, 6abb and 6aeb with terminal alkyne fragment can be easily cyclized under thermal uncatalyzed conditions in various solvents -from nonpolar benzene to polar protic solvents, and even in water, depending on substrate solubility [20]. Firstly, we used a procedure similar to described by I. Akritopoulou-Zanze et al [13] for cyclization: compound 6aab was refluxed in benzene for 8 hours until TLC monitoring demonstrated the full transformation of starting material into a new compound.…”

Progress in the Synthesis of Fused 1,2,3‐Triazoles

“…Metals other than copper and palladium that have potential to catalyse fused triazole formation. Kundu and his group afforded lewis acid [Yb(OTf) 3 ] mediated intermolecular Michael addition of 2‐alkynyl indoles 242 with ( E )‐1‐azido‐2‐(2‐nitrovinyl)benzenes 243 and further intramolecular internal alkyne‐azide cycloaddition to construct fused triazoles 245 [79] . They generated indolo[1,3‐ c ][1,2,3]triazolo[1,5‐ a ][1]benzazepine derivatives 245 from a variety of aliphatic and aromatic 2‐alkynyl indoles and ( E )‐1‐azido‐2‐(2‐nitrovinyl)benzenes in good yields (Scheme 75).…”