Inter‐ and intramolecular hetero diels‐alder reactions, 40. Effect of high pressure on the stereoselectivity of intermolecular hetero diels‐alder reactions

Abstract

The hetero Diels-Alder reaction of enamino ketone 1 with the vinyl ethers 7-11 leading to the dihydropyrans 12a-e and 13ae is studied in dichloromethane under high pressures up to 7 kbar. The kinetics is measured by on-line FT-IR spectroscopy up to 3 kbar. For the first time individual rate coefficients kci, and k,,,,, have been determined. Pressure-averaged activation volumes, m, for the overall reaction leading to the formation of the two diastereomers in dichloromethane solution between -(19.1 i 1.7) and -(25.4 & 1.6) cm3 mol-' are measured. The corresponding activation enthalpies, AH*, are between (62.2 i 1.6) and (76.3 f 3.6) k J mol-l. The cycloaddition shows a remarkable increase in diastereoselectivity in favour of the cis adducts 12ae toward higher pressure. The pressure-averaged differences in activation volume, -AAV*, for the two reaction pathways leading to cis and trans diastereomers are found to be between -(4.5 i 0.3) and -(6.9 i 0.7) cm3 mol-l. The corresponding differences in activation enthalpy, AAH*, are between -(4.7 f 1.4) and -(9.9 i 1.6) kJ mol-'. Combination of the overall rate coefficient k = kCi, + k, , , for the reaction leading to the two diastereomers with the measured product ratio, cCis/ctrans, which is identified with the ratio of the rate coefficients kCi,/kt,,,,, yields the individual coefficients k,, and k,,,,.The rate coefficient k,, is strongly influenced by the steric demand of the substituents on both diene and dienophile whereas ktrans varies to a smaller extent, and the observed changes appear to be mainly due to the electronic properties of the substituents.

Influence of Non-Covalent Interactions in the Exo- and Regioselectivity of Aza-Diels–Alder Reactions: Experimental and DFT Calculations

“…To our delight, 3a was obtained as the only product in 55% yield. Considering that Aza-Diels–Alder reactions are normally conducted in apolar solvents such as benzene or xylene in order to facilitate the solubility and compatibility of the required reagents and catalysts, this is a great achievement to the use of more environmentally friendly processes (Scheme ). Moreover, considering that one of the most interesting features of 7-azaindoles is the variability of their biological properties with regard to the substitution pattern, the use of the aldimine 1a allows the introduction of two versatile groups in the final product, namely, the nitrile group that can be converted to other functional groups and the phenyl group derived from benzaldehyde that can be substituted by other aldehyde derivatives.…”

Regioselectivity Switch Towards the Development of Innovative Diels‐Alder Cycloaddition and Productive Applications in Organic Synthesis

“…In terms of selectivity, DA cycloaddition is a well‐known phenomenon that contributes to the expansion of a wide range of compounds with intricate capabilities and controlled stereochemistry [37–39] . Numerous synthetic accomplishments have been established so far with exceptional efficacy based on various selectivity characteristics in order to create top‐notch organic frameworks [40–45] .…”

“…In terms of selectivity, DA cycloaddition is a well-known phenomenon that contributes to the expansion of a wide range of compounds with intricate capabilities and controlled stereochemistry. [37][38][39] Numerous synthetic accomplishments have been established so far with exceptional efficacy based on various selectivity characteristics in order to create top-notch organic frameworks. [40][41][42][43][44][45] This review aims to compile the work based on selectivity in cycloaddition protocols to generate a systematic, synthetically valuable composition in organic synthesis, inspired by the distinct results accumulated by the DA reaction.…”

Correlation between pressure and steric interactions in organic reactions

“…[38][39][40][41] Changes in diastereoselectivity due to steric hindrance may be expected with an increase in pressure. Large DDV* values (up to K11 cm 3 mol K1 ) were determined in these cycloadditions.…”