Ionic liquid promoted Diels-Alder Reaction between anthrone and maleimides

Pentafulvene–Maleimide Cycloaddition for Bioorthogonal Ligation

“…This increase in k 2 was attributed to neighboring group participation of the carboxylic acid group activating the maleimide through hydrogen-bonding with the imide carbonyls. 46 For the reaction of fulvene 1a with the dichloromaleimide 2d, k 2 was determined via HPLC and 1 H NMR spectroscopy due to the significantly slower kinetics, which were nearly 2 orders of magnitude lower (k 2 ≈ 0.01 M s −1 at 37 °C), which may result from steric hindrance at the maleimide alkene group due to the presence of the bulky chloride groups (Figures S82−S87). Importantly, the cycloadducts 3a−3c showed no degradation post-storage in PBS at 23 °C for >10 months (Figures S88−S94), demonstrating the high stability of the alkylidene norbornene cycloadducts, which is an important consideration for bioconjugates.…”

“…Surprisingly, we observed a marked increase in the k 2 of fulvene 1a with maleimide derivatives 2b and 2c as compared to 2a (Figures S70–S81 and Table ), with values of ∼0.7 M –1 s –1 at 37 °C. This increase in k 2 was attributed to neighboring group participation of the carboxylic acid group activating the maleimide through hydrogen-bonding with the imide carbonyls . For the reaction of fulvene 1a with the dichloromaleimide 2d , k 2 was determined via HPLC and 1 H NMR spectroscopy due to the significantly slower kinetics, which were nearly 2 orders of magnitude lower ( k 2 ≈ 0.01 M –1 s –1 at 37 °C), which may result from steric hindrance at the maleimide alkene group due to the presence of the bulky chloride groups (Figures S82–S87).…”

“…Complete conversion of 2e and the formation of the cycloadduct 3e (endo/exo 25:1) was demonstrated by 1 H NMR spectroscopy and liquid chromatography mass spectrometry (LC-MS) (Figures S97 and S98). Conceivably, the faster rate observed for the formation of 3e as compared to those of 3a and 3b may result from neighboring group participation of the peptide functional groups coordinating to the maleimide and reducing the activation energy for the cycloaddition, although further studies are underway to confirm these hypotheses.…”

1,3-Disulfonic acid imidazolium hydrogen sulfate: a reusable and efficient ionic liquid for the one-pot multi-component synthesis of pyrimido[4,5-b]quinoline derivatives

“…16 Ionic liquids are dened as salts that are in a liquid form at or below 100 C. 17 They have several unique properties like high chemical and thermal stability, negligible vapor pressure, non-volatility, environmental compatibility, reusability, greater selectivity and ease of isolation. 18,19 ILs have been successfully employed as dual solvent-catalyst for several organic transformations such as esterication, 20 Diels-Alder, 21 and Wittig, 22 synthesis.…”