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 addendswere 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 Ac 2 O and a catalytic amount of strong acid, or in 79 % using only catalytic acid.

Recent Advances on Diels‐Alder‐Driven Preparation of Bio‐Based Aromatics

“…For once, hydrogenation stabilizes DA adducts, allowing for irreversible ligation and as a source of high‐value oxygenated bio‐based chemicals. Secondly, the aforementioned aromatization of 7‐ONBs generated from biomass‐derived furans represents one of the most important routes towards versatile aromatic renewable chemical commodities, allowing easy access to valuable scaffolds such as i) substituted benzenes, ii) phthalic anhydride derivates, iii) maleic anhydrides, and iv) phthalides [15] . Lastly, 7‐ONBs themselves can be used as modular linkers for controlled release of cargos by retro‐DA, [14c] as ligation handles in subsequent DA, as pharmacological scaffolds in drug discovery, [8] or even as a tunable platform to control copolymerization propagation rates [10] …”

Furoic acid and derivatives as atypical dienes in Diels–Alder reactions

“…Encouraged by this precedent and following our interest in the development of synthetic applications based on the Diels-Alder chemistry of readily available oxygenated bio-based furans, [33,34] we decided to investigate 2-furoic acids as underexplored class of dienes.…”

Hydrogen‐Binding‐Initiated Activation of O−H Bonds on a Nitrogen‐Doped Surface for the Catalytic Oxidation of Biomass Hydroxyl Compounds

“…[1] In the chemical transformation of most hydroxyl groups,how to realize the highly efficient activation of OÀHb onds becomes ac ritical point. [2] Generally,t he proton donating ability of hydroxyl groups contributes to hydrogen bonds (HBs) formed by themselves,w hich can usually lower their reactivity. [3] Interestingly,h owever,t his characteristic also endows HBs with the ability to facilitate activation of O À Hbonds,through forming strengthened HBs with other proton acceptors such as electric-rich heteroatoms and halogen ions.…”