Synthesis, Modification, and Characterization of a Family of Homologues of e xo-Calix[4]arene:  e xo-[n.m.n.m]Metacyclophanes, n,m ≥ 3

• Published in: Journal of organic chemistry 2000-08, Vol.65 (17), p.5185-5196
• Main Authors: Burns, Dennis H, Chan, Ho−Kit, Miller, Jeffrey D, Jayne, Charles L, Eichhorn, David M
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo0003044

A general strategy for the preparation of the family of exo-[n.m.n.m]metacyclophanes (n,m ≥ 3) in 6-steps (starting from 2-bromoanisole) that utilizes a [2 + 2] approach to furnish the exo-metacyclophane ring in good to moderate yield is described. The soluble copper catalyst [CuBr−LiSPh−LiBr−THF] is used to efficiently couple Grignard and alkyl or ether tosylate reagents in several of the synthetic steps, including the ring construction in the final step. The exo-[n.m.n.m]metacyclophane ring is conformationally mobile on the NMR time scale, and X-ray crystallography reveals that exo-[3.3.3.3]metacyclophane 2a assumes a cone conformation, and that exo-[6.6.6.6]metacyclophane 6a assumes a chair conformation. Molecular mechanics calculations show that both conformations for each exo-metacyclophane are very similar in energy. Regiocontrol over the alkylation and acylation of the phenolic oxygens of 2b is problematic, although the preparation of the tetraacetylated 18 and alkylation of 2b with CH2BrCl to furnish the methylene-linked mono- and bis-adducts 19 and 20 are straightforward.