Fe-Catalyzed Cascade Reaction: C-H Activation and Cyclization in Efficiently Coumarin Synthesis

EasyChair Preprint 15510

Abstract

In general, the C-H bonds are omnipresent in organic/medicinal compounds in pharmaceutical fields, but the direct C-H functionalization is challenging due to its low reactivity and very large bond dissociation energy: 105 and 110 kcal/mol in CH₄ and C₆H₆. In the conventional strategy, it requires pre-functionalization using halogenated compounds, giving halogenated byproducts. However, the systems of precious metals: Pd, Pt, Au, Ru, Ag etc. and La-series metals, which are high cost and toxic for the contamination with products, are used for direct C-H activation and cyclization. Still now, little attention has been paid to the nontoxic, environmentally benign, cheaper Fe-systems as a catalyst in such fields. On the other hand, coumarins and its derivatives show biological activities: antioxidant, analgesic, anti-inflammatory and antimutagenic and so play a great role in the medicine fields. Contrast to transition-metal catalyst uses, here we disclosed a greener, nontoxic and cheaper methodology for coumarin synthesis by developing a Fe-catalytic system, in-situ Fe(OTf)₃ (OTf: triflate), revealing C-H activation and cyclization between propynoic acid: R-C≡-CO₂H (R = H, alkyl) and different phenols at a time, affording 33-95% coumarins (~20 scopes). In comparison with previous palladium- and platinum-catalyzed methods, this Fe-catalyzed process explored better yields. Substituent screening explored that terminal methyl substituted propynoic acid, H₃C-C≡C-CO₂H (acidic H absence) showed lower activity, while, electronic and inductive effects for phenols, governed the significant role in such cascade reactions. In summary, this methodology of Fe(III)-catalyzed coumarin synthesis is an efficient and economically nontoxic process, playing a great role in different fields of pharmaceuticals, catalysis and chemistry.

Keyphrases: C-H activation, Catalysis, Coumarin, Fe-Catalyst, cascade reaction

@booklet{EasyChair:15510,
  author    = {Md. Shahajahan Kutubi and Tsugio Kitamura},
  title     = {Fe-Catalyzed Cascade Reaction: C-H Activation and Cyclization in Efficiently Coumarin Synthesis},
  howpublished = {EasyChair Preprint 15510},
  year      = {EasyChair, 2024}}