Under the same strategy, a wide range of 6,7-disubstituted (-X2) pillar [4](1,4-epoxynapthalene) macrocycles , where X2 = Me2 (4b), (CH2)3 (4c), (CH2)4 (4d), (OMe)2 (4e) and F2 (4f), can be generated in very high yield (69-92% (Figure ). Analogous to 4a, reactions between 1 and 8b-f lead to the formation of a statistical mixture of various combination of exo/endo isomers. Attempts to grow high-quality single crystals of 4 for X-ray diffraction analysis failed, in all trials only amorphous powdery materials were obtained, presumably due to the existence of multiple conformations in the samples. As a result, mass spectrometry was predominantly used to characterize the degree of cycloaddition reaction between 1 and benzyne precursors 8. In all cases, molecular ions of the four-fold cycloaddition products are the only species detected in their corresponding ESI-MS spectra (see ESI). Deoxygenative aromatization of 4a with trimethylsilyl iodide (TMSI) in acetonitrile at 40 °C for 70 h would furnish the formation of pillar [4]naphthalene (2a) in 13% yield (Figure ). The 1 H NMR spectrum in chloroform-d1 of 2a revealed a C4v symmetry with four set of resonances assigned to naphthyl group (Ha-Hc) and methylene linker (Hd) in a 1:1:1:1 ratio (Figure ). ESI-MS spectrum revealed the mother ion peak at m/z 560.095 (Figure ). Numerous attempts to grow X-ray quality crystals (in different methods, concentrations, solvents and temperatures) resulted in the formation of an amorphous powder. As a result, DFT molecular modeling was employed for a spatial visualization of 2a (Figure and Table ). The lowest energy conformation (4u) of 2a has an inverse vase-shape structure with all four naphthyl groups tilting up, which is >3.3 kcal/mol more stable than the next preferred conformers (trans-2u2d and 3u1d) (Figure ). The tube-shaped conformer, with an alternate up-down-up-down geometry (cis-2u2d), is almost 5 kcal/mol higher in energy, resulting from steric clash between methylene CH and Np C-H. Variable-temperature (VT) NMR of 2a in CD2Cl2 from 298 K to 183 K showed that, upon cooling, only the resonances corresponding to the protons on the "upper" portion of naphthalene units (Hb and Hc, Figure ) are mostly affected (Figure ). The positionally-fixed methylene groups (Hd) are static. This provides strong evidences of a rapid exchange process in place between multiple conformers in solution. In a similar manner, dimethyl (2b), cyclopentyl (2c) and cyclohexyl (2d) analogues of 2 were produced in 6-7% yield, demonstrating the generality of our method to construct higher pillar [4]arenes from biorenewable calix [4]furan precursor 1. Notably, previous attempts to synthesize 2 using conventional approach from 2,3-dialkoxynaphthalene and 6a with Lewis acid catalysts failed, only a mixture of acyclic dimer, trimer and tetramer were obtained, further emphasizing the synthetic utility of our macrocyclic template approach with 1. The use of long reaction time and in low conversion to 2ad are in sharp contrast to analogous deoxygenative aromatization reactions with other epoxyarenes, which often take place at rt with satisfactory conversion. To examine if steric is the reason of poor conversion to 2a-d, we synthesized and obtained crystal structures of bis(epoxynapthyl)methane ( ), an acyclic model compound, as a pair of syn-(syn-9) and antiisomers (anti-9) (Figure ) from 1,1'-difurylmethane (5). 9 was then subjected to the deoxygenation condition. In this case, bis(napthyl)methane 10 was obtained in only 25% yield (Figure ). In the crystal structures of 9, the epoxy oxygens are shown to be slightly hidden by the neighboring olefinic C-H bonds (Figure ), which is expected to hinder the approach of electrophiles. Therefore, we attributed steric crowdedness in 4a-d prevent them from efficient deoxygenation.