Benzocyclotrimers: from the Mills-Nixon effect to gas hosting

The formal annulation of three bicylic olefins yields a class of molecules termed benzocyclotrimers (BCTs), which have unusual electronic properties. The bonds in the central aromatic ring, for example, alternate in length: rather than resembling a substituted benzene, a BCT instead evokes comparison to a cyclohexatriene. Forty years have passed since the synthesis of heptiptycene, the first BCT, was reported. In the interim, many methods have been developed for preparing tris-bicycloannulated benzenes. More than thirty different BCTs have so far been reported, with a variety of morphological features and properties. Over the same period, yields have increased from just a few percent to almost quantitative conversion. This improvement in synthetic access has expanded interest beyond the original theoretical considerations (bond-length fixation in aromatics) to functional applications (supramolecular scaffolds). In this Account, we describe the evolution of synthetic approaches to BCTs and their derivatives, as well as the applications that are now being explored for these compounds. Early syntheses of BCTs involved chloroolefins treated with butyl lithium. A strained alkyne intermediate was postulated early on, and was indeed trapped in 1981. Subsequent efforts have focused on improving chemoselectivity by mitigating the drastic conditions required for the generation of the alkyne intermediate. Our introduction of Cu(I) to induce lithium-copper exchange was successful in this regard. Further improvement resulted from the use of bicylic bromo(trimethylstannyl)olefins. In an effort to avoid the toxicity of the tin reagents, the Heck reaction and Pd catalysis have been pursued for cyclotrimerizing bicylic bromo- and iodoolefins. Depending on the symmetry of the starting bicylic olefin, two diastereomers can be obtained in the preparation of a BCT: a syn compound with C(3) symmetry and an anti compound with C(s) symmetry. Studying the diastereomeric outcome in a variety of synthetic approaches has yielded valuable insight into the cyclotrimerization reaction. Moreover, highly symmetric compounds, such as a D(3)-symmetric trindane and C(3v)-symmetric sumanene, have been prepared as BCT derivatives. The structure of BCTs offers a versatile three-dimensional scaffold for studying molecular recognition. Like calixarenes, BCTs form complexes with a variety of guest molecules. Recent developments include the trapping of gases in a hydrogen-bonded dimer and the encapsulation of larger molecules within a covalently linked condensation derivative. Future innovations in this fertile research area will likely include highly functionalized curved aromatics, receptors, and sensors.