In memory of Klaus HafnerThe 2-pyrone moiety can be found in a large number of natural products with a wide range of biological activities, including antibiotic, antifungal, cytotoxic, neurotoxic, phytotoxic, antiinflammatory and cardiotonic effects. With its heterocyclic structure encompassing the chemical nature of conjugated dienes, lactones, Michael acceptors and arenes, it can undergo a great variety of transformations such as cycloadditions, ringopening reactions, cross-couplings and lactamizations. Thus, 2-pyrones represent valuable synthetic precursors and worthwhile targets in organic, polymer, and medical chemistry. Owing to its exquisite chemical and physical properties, the synthesis and further transformations of 2-pyrones have attracted considerable attention over the past decade, showcasing transition metal and metal free strategies and using readily available starting materials, notably those stemming from renewable resources.

Reversing the regioselectivity of the renowned Diels–Alder reaction by overriding the usual thermodynamic and kinetic governing factors has always been a formidable challenge to synthetic organic chemists. Anthracenes are well-known to undergo [4 + 2]-cycloadditions with dienophiles at their 9,10-positions (central ring) over 1,4-positions (terminal ring) guided by the relative aromatic stabilization energy of the two possible products, and also by harboring the largest orbital coefficients of the highest occupied molecular orbital (HOMO) at the 9,10-positions. We, herein, report a 1,4-selective [4 + 2]-cycloaddition strategy of 9,10-unsubstituted anthracenes by installing electron-donating substituents on the terminal rings which is heretofore unprecedented to the best of our knowledge. The developed synthetic strategy does not require any premeditated engagement of the 9,10-positions either with any sterically bulky or electron-withdrawing substituents and allows delicate calibration of the regioselectivity by modulating the electron-donating strength of the substituents on the terminal rings. Likewise, the regioselective functionalization of the terminal anthracene ring in electrophilic substitution reactions is demonstrated. A mechanistic rationale is offered with the aid of detailed computational studies, and finally, synthetic applications are presented.

An atom economic reaction sequence in a multigram scale for the synthesis of 2-pyrone was developed starting from furfuryl alcohol, a renewable resource made from bran or bagasse, and cyclopentadiene as a recyclable auxiliary. Utilizing a thermal rearrangement of cyclopentadienone epoxide as the key step. Besides the synthesis of the parent compound, the synthetic route is amenable for substituted derivatives, giving rise to naturally occurring 2-pyrones.