Dynamic Trapping as a Selective Route to Renewable Phthalide from Biomass‐Derived Furfuryl Alcohol

Abstract

A novel route for the production of the versatile chemical building block phthalide from biorenewable furfuryl alcohol and acrylate esters is presented. Two challenges that limit sustainable aromatics production via Diels–Alder (DA) aromatisation—an unfavourable equilibrium position and undesired regioselectivity when using asymmetric addends—were addressed using a dynamic kinetic trapping strategy. Activated acrylates were used to speed up the forward and reverse DA reactions, allowing for one of the four DA adducts to undergo a selective intramolecular lactonisation reaction in the presence of a weak base. The adduct is removed from the equilibrium pool, pulling the system completely to the product with a fixed, desired regiochemistry. A single 1,2‐regioisomeric lactone product was formed in up to 86 % yield and the acrylate activating agent liberated for reuse. The lactone was aromatised to give phthalide in almost quantitative yield in the presence of Ac2O and a catalytic amount of strong acid, or in 79 % using only catalytic acid.

The Interplay between Kinetics and Thermodynamics in Furan Diels–Alder Chemistry for Sustainable Chemicals Production

“…This was recently evidenced in a study targeting phthalide 184 (Scheme 27 A). [122] Lactone 183 (see Section 7 for its formation) was shown to exhibit significantly improved thermal stability compared to the related intermolecular adducts 186 and 187 : the energy barrier for its cycloreversion was calculated to be at least 5 kcal mol −1 higher in the former case (Scheme 27 B). Thus, the aromatization of 183 could be performed with high selectivity in a variety of acidic conditions.…”

“…Another clear manifestation of sterics is the superior stability of the exo adduct over the endo diastereoisomer: in the former, the oxanorbornene substituents are oriented anti to the bulkier bridge of the bicycle, which leads to a thermodynamic benefit of 2–3 kcal mol −1 [48, 121] . In reactions between 2‐monosubstituted furans and nonsymmetrical dienes, distal ( meta ) regioisomers generally prevail at equilibrium over the proximal ( ortho ) isomers, for similar reasons [122, 118] . Finally, the absence of steric repulsions in the adduct between furan and ethylene presumably contributes significantly to its high stability relative to other typical furan DA adducts (e.g.…”

“…The lactonization strategy was also recently successfully applied in DA reactions between furfuryl alcohol and acrylate esters [122, 142] . Nonactivated ester groups are not electrophilic enough to undergo lactonization: in such cases, the DA equilibrium conversion was low and a mixture of all four isomeric adducts was formed.…”

Selective Hydrogenation of Furfural: Pure Silica Supported Metal Catalysts

“…[13] Furfuryl alcohol can be used as raw material for the electrocatalytic synthesis of heterocycles, [14] synthesis of high-performance thermosetting plastics, [15] and production of phthalate esters. [16] Tetrahydrofurfuryl alcohol is a valuable biomass-derived chemical, which is an important precursor for the production of linear diol and biodegradable solvents. [17] Tetrahydrofurfuryl alcohol can be used as raw materials for the production of γ-butyrolactone, [18] the synthesis of dihydropyran-hydroxyvaleraldehyde, and 1,5-pentanediol.…”