P₄O₁₀/TfOH mediated domino condensation–cyclization of amines with diacids: a route to indolizidine alkaloids under catalyst- and solvent-free conditions

Abstract

A highly efficient and direct methodology for the construction of pyrrolo[2,1-a]isoquinoline, pyrido[2,1-a]isoquinoline, and 12b-H and 12b-OH isoindolo[2,1-a]isoquinolinone alkaloids from commercially available synthons is devised.

Pyrrolo[2,1-a]isoquinoline scaffolds for developing anti-cancer agents

“…Recently, it was reported the direct condensation–cyclization reaction of diverse primary amines 166 and dicarboxylic acids 167 for the construction of various indolizidine compounds like 168 and 169 . 78 The condensation was carried out in the presence of an 8.3 wt% mixture of phosphorus pentaoxide (P 4 O 10 ) and TfOH at 100 °C followed by reduction (sodium borohydride) of the subsequent iminium ion to produce the final products 168 and 169 (Scheme 12). The use of diverse aliphatic and aromatic dicarboxylic acids with various primary amines makes this method suitable also for synthesizing pyrrolo-, pyrido-, and isoindolo[2,1- a ]isoquinolines in excellent yields.…”

One-Pot Reaction Sequence: N-Acylation/Pictet–Spengler Reaction/Intramolecular [4 + 2] Cycloaddition/Aromatization in the Synthesis of β-Carboline Alkaloid Analogues

“…Such pathways often involve Bischler–Napieralski or Pictet–Spengler reactions as the central step of the whole sequence. Recent syntheses, which include the aza-Friedel–Crafts reaction as the main step, should be mentioned here as well. , Usually, the first two reactions mentioned above, crucial in the formation of the β-carboline fragment, demand elevated temperatures, and various acidic or organometallic catalysts . These methods, though effective, may pose challenges such as the synthesis and application of complex or difficult to access reagents, , multistage protocols, diastereoselectivity issues, , and a complex apparatus design.…”

Construction of indolizine scaffolds from α,ω-alkynoic acids and α,ω-vinylamines via sequential-relay catalysis in “one pot”

“…1), representing a class of fundamentally important scaffolds. 2 As useful precursors of indolizine scaffolds and versatile synthons, 3 aryl-fused indolizin-3-ones have aroused significant interest among organic and medicinal chemists. Thus, exploring novel methodologies, particularly those guided by the principles of green chemistry, 4 to construct these scaffolds is of prime importance.…”