Structural and solvent control over activation parameters for a pair of retro Diels-Alder reactions

Abstract

We report the temperature dependent NMR of two Diels-Alder adducts of furan: one formed with maleic anhydride and the other with N-methylmaleimide. These adducts are the products of so-called ‘click’ reactions, widely valued for providing simple, reliable, and robust reactivity. Under our experimental conditions, these adducts undergo a retro Diels-Alder reaction and we use our temperature dependent NMR to determine the rates of these reactions at multiple temperatures—ultimately providing estimates of the activation parameters for the reversion. We repeat these measurements in three solvents. We find that, in all solvents, the barrier to reversion is larger for the adduct formed with N-methylmaleimide. The barrier to reversion for this adduct is relatively insensitive to changes in solvent while the adduct formed with maleic anhydride responds more strongly to changes in solvent polarity. The differences in reaction barrier and solvent dependence arises because the adduct formed with N-methylmalemide is more stable—leading to a larger barrier to reversion—while the adduct formed with maleic anhydride experiences a larger change in dipole during the reaction—leading to a larger solvent dependence.

Using TOF-SIMS Spectrometry to Study the Kinetics of the Interfacial Retro Diels–Alder Reaction

“…The standard errors in the calculation of activation energy were obtained from the linear regressions. This value is very close to the value found in literature [28] for retro DA reaction between furan and methyl maleimide occurring in DMSO (134 ± 4 kJ•mol −1 ).…”

Application of New Efficient Hoveyda–Grubbs Catalysts Comprising an N→Ru Coordinate Bond in a Six-Membered Ring for the Synthesis of Natural Product-Like Cyclopenta[b]furo[2,3-c]pyrroles

“…Considering the fact that reversible Diels–Alder reactions are most influenced by the reaction temperature and the polarity of the solvent [ 35 , 36 , 37 , 38 ], we compared the isomeric composition of the most diverse acids 5a , b , g , i , m formed under the conditions indicated in Table 1 . The application of Lewis acids (10–25 mol % of AlEt 3 , BF 3 ·OEt 2 , TiCl 4 ) as catalysts in MeCN, PhH, PhMe, or CH 2 Cl 2 turned out to be ineffective, probably due to their fast binding by a free carboxyl group of the products and due to the difficulties associated with the purification of the resulting reaction mixtures.…”

“…The IMDAF reaction is highly stereoselective [33,34]; in the course of the tandem N-acylation/[4+2] cycloaddition sequence, only exo-adducts form as a mixture of two diastereomers (trans-5A and cis-5B) based on the orientation of the 3-allyl (or 3-methallyl) substituent relative to the 3a,6-epoxy-bridge (Figure 2). Considering the fact that reversible Diels-Alder reactions are most influenced by the reaction temperature and the polarity of the solvent [35][36][37][38], we compared the isomeric composition of the most diverse acids 5a,b,g,i,m formed under the conditions indicated in Table 1. The application of Lewis acids (10-25 mol % of AlEt 3 , BF 3 •OEt 2 , TiCl 4 ) as catalysts in MeCN, PhH, PhMe, or CH 2 Cl 2 turned out to be ineffective, probably due to their fast binding by a free carboxyl group of the products and due to the difficulties associated with the purification of the resulting reaction mixtures.…”

Closer Look at Inverse Electron Demand Diels–Alder and Nucleophilic Addition Reactions on s-Tetrazines Using Enhanced Sampling Methods

“…The RMSDs with different reference states were also computed to study the transformation of the iEDDA and azaphilic molecules via the reaction pathway. The crossing of RMSDs between reactant and product references shows that the reaction does not take place immediately but is delayed after (small) rearrangement of DCM solvent molecules [79].…”