Reaction of furan with maleic anhydride: Solventless chemistry reveals the first solid form of the elusive endo-isomer of archetypal Diels-Alder product

The Diels-Alder reaction of dienes and dienophiles is a central transformation in organic chemistry. It also had a central position in the development of pericyclic reactions and the frontier molecular orbital theory approach to understanding organic reactivity. The reaction between furan and maleic anhydride is one of the earliest examples of a Diels-Alder reaction^[1] yet, despite many kinetic and thermodynamic studies, isolation of the endo-isomer has remained elusive. We report here the first single crystal X-ray diffraction structure of this important endo-cycloaddition product, and its co-crystal with the commonly obtained exo-isomer. These structural determinations have been supported by theoretical modelling and crystal structure prediction approaches, providing experimental insight into relative stabilities of the endo- and exo-isomers in the solid-state. This first observation of the solid form of the endo-isomer of the furan-maleic anhydride Diels-Alder adduct previously had been observed only as a short-lived intermediate hydride. This was enabled via a "greener" solvent-free synthesis, and represents an important contribution to Diels-Alder chemistry.