Benzocyclobutenes (BCBs) are valuable precursors for the synthesis of bioactive molecules such as steroids, alkaloids, and terpenoids. However, both the ring-opening temperature (ROT) of BCBs and the precise electronic nature of the resulting reactive intermediate, ortho-quinodimethane (o-QDM) with varying degrees of diradical character, is crucial for controlling reaction outcomes. In this study, we prepared and investigated the ring-opening behavior of a series of 1-substituted BCBs bearing ether, amine, amide, or carbamate groups. ROT values, determined by differential scanning calorimetry (DSC), were found to be significantly influenced by the electronic nature of the substituent. The natural bond orbital (NBO) method was employed to assess the orbital contribution of the substituent lone pair, confirming its strong impact on ROT. Thermal activation of these compounds in the presence of either a dienophile or a spin trap (TEMPO) led to the formation of the corresponding Diels-Alder adducts or dialkoxyamines, respectively, consistent with the involvement of a reactive o-QDM intermediate exhibiting partial diradical character. Furthermore, the diradical character of the ring-opened species was estimated to be 15%-19% using the Natural Orbital Occupation Number (NOON) computational method. The combination of experimental and computational data provides significant insight into the electronic structure governing the ring-opening process.
Dallegre et al. (Tue,) studied this question.