Metal-Free, Adjustable, and Recyclable Catalytic Systems for the Construction of C–C Bonds by Activating Propargylic Alcohols

Abstract

Pyrano[3,coumarin derivatives and C3-substituted 4-hydroxycoumarins as important skeletal structures of active natural products and pharmaceutically relevant molecules have received increasing attention. However, developing an adjustable system for selectively synthesizing them is still a challenging task. Herein, sulfonic acid-functionalized ionic liquid was successfully used as the catalyst for the alkylation of 4-hydroxycoumarin derivatives with secondary aromatic propargylic alcohols using dimethyl carbonate as the green solvent, giving up to 98% yield. On the other hand, protonated imidazole-based ionic liquidcatalyzed cyclization was also selectively achieved with a nearly quantitative yield. Developed metal-free catalytic systems exhibited well adjustable and recyclable properties, avoiding the contamination of metal and halogen, reducing the neutralization after the reaction, and benefiting the separation between the catalyst and the product. New strategies were applied for performing the gramscale reaction smoothly. The adjustable systems might occur through two different mechanisms involving propargylic or allenic carbocation and hydrogen bonding effects between the catalysts and the substrates.

Ionic liquids revolutionizing biomedicine: recent advances and emerging opportunities

“…199 Sulfonic acid-functionalized ILs were utilized for catalytic synthesis of pyrano[3,2- c ]coumarin derivatives and C3-substituted 4-hydroxycoumarins. 200 IL cations had a strong influence on the catalytic activity in the synthesis of quinazoline-2,4(1 H ,3 H )-diones, in which the H-bonds formed by the cations and the alkalinity of the cations affected the reaction. 201 Wang et al proposed IL catalytic mechanisms for the reactions of pyrano[3,2- c ]coumarin derivatives and C3-substituted 4-hydroxycoumarins.…”

Recent Progress in Application of Propargylic Alcohols in Organic Syntheses

“…In 2022, two types of ionic liquids, namely sulfonic acid‐functionalized ionic liquid, and protonated imidazole‐based ionic liquid employed for the alkylation and cyclization of 4‐hydroxycoumarins 75 with secondary and tertiary aryl propargyl alcohols 1 , respectively (Scheme 36). [40] Using these green and sustainable catalytic systems, a broad range of C3‐substituted 4‐hydroxycoumarins 76 , as well as pyrano[3,2‐ c ]coumarins 77 were obtained in moderate to excellent yields. The screening of various ionic liquids in these transformations was successful and with the ability to reuse the catalysts, the desired products were obtained in different percentages of efficiency.…”

The Synthesis of Nitrogen- and Oxygen-Containing Heterocyclic Scaffolds Assisted by Ionic Liquids: A 2022 Literature Survey

“…Miao and co-workers reported a metal- free, adjustable, and recyclable approach using 1-butylpyridine-1-ium triflate [BsPy][OTf] and 1-methyl-1-imidazol-3-ium triflate [HMim][OTf] as catalysts (Scheme 54 ). 124 The alkylation of 4-hydroxycoumarins 160 using secondary propargylic alcohols 161 was achieved by employing [BsPy][OTf] to yield products 162 in 64–98% yields, whereas cyclization of 160 using tertiary propargylic alcohols 163 in the presence of [HMim][OTf] produced products 164 in 35–97% yields. Both catalysts were reused without any significant change in activity after several runs.…”

“…ILs for the catalysis of Groebke-Blackburn-Bienayme reaction in synthesis of imidazo[1,2-a]pyridines (125) using substituted aminopyridine (122), tert-butyl isocyanide (123) and substituted aldehydes (124, Scheme 40). 100 The reaction in a sealed tube in ethanol/methanol under microwave irradiation was performed for 1-4 h at 150 o C. The key ILs were prepared using 1-methylimidazole and 1,4-butanesultone yielding zwitterions, which was further reacted with different acids.…”

“…Miao and co-workers reported the metal free, adjustable, and recyclable catalytic approach using 1-butyl pyridine-1-mum triflate [BsPy][OTf] and 1-methyl-1-imidazol-3-ium triflate [HMim][OTf] (Scheme 54). 123 The alkylation of 4-hydroxycoumarin (160) using secondary propargylic alcohol (161) was achieved using For the first time, Xu and co-workers reported the catalytic activity of 1-hexyl-3methyl-imidazolium chloride hexafluorophosphate [HMIM][PF 6 ] and tryptophan for the piperidine-free synthesis of caulerpin and its derivatives (166) via Knoevenagel condensation of methyl 2-(3-formyl-1H-indol-2-yl) acetate (165) in 23-31% yields (Scheme 55). 124 The yield of 166 was found to be reduced when 165 was substituted at the C-6 position on benzenoid nucleus of indole.…”