Synthesis and conformational studies of chiral macrocyclic [1.1.1]metacyclophanes containing benzofuran rings

Islam, Md Monarul; Tomiyasu, Hirotsugu; Matsumoto, Taisuke; Tanaka, Junji; Rahman, Shofiur; Georghiou, Paris E.; Redshaw, Carl; Yamato, Takehiko

Abstract

Macrocyclic [1.1.1]metacyclophanes (MCPs) containing benzene and benzofuran rings linked by methylene bridges and which can be viewed as calixarene analogues, have been synthesized by demethylation of [3.3.1]MCP-diones with trimethylsilyl iodide (TMSI) in MeCN. The [3.3.1]MCP-diones are synthesized by using (p-tolylsulfonyl)methyl isocyanide (TosMIC) as the cyclization reagent in N,N-dimethylformamide (DMF) with an excess of sodium hydride. ¹H NMR spectroscopy revealed that the remaining hydroxyl group on the phenyl ring is involved in intramolecular hydrogen bonding with the oxygen of one of the benzofuran rings. O-Methylation at the lower rim of monohydroxy[1.1.1]MCP in the presence of K₂CO₃ in acetone afforded a novel and inherently chiral calixarene analogue, namely the macrocyclic [1.1.1]MCP, possessing C₁ symmetry. The inherent chirality of the two conformers was characterized by ¹H NMR spectroscopy by addition of an excess of Pirkle's chiral shift reagent, which caused a splitting of the corresponding methylene protons to AB patterns. Single crystal X-ray analysis revealed the adoptation of a hemisphere-shaped cone isomer. DFT calculations were carried out to investigate the energy-minimized structures and the hydrogen bonds of the synthesized MCPs.

Citation

Islam, M. M., Tomiyasu, H., Matsumoto, T., Tanaka, J., Rahman, S., Georghiou, P. E., Redshaw, C., & Yamato, T. (2015). Synthesis and conformational studies of chiral macrocyclic [1.1.1]metacyclophanes containing benzofuran rings. Organic & biomolecular chemistry, 13(34), 9055-9064. https://doi.org/10.1039/c5ob01002k

• Journal Article Type: Article
• Acceptance Date: Jul 17, 2015
• Online Publication Date: Jul 20, 2015
• Publication Date: Jul 20, 2015
• Deposit Date: Jul 22, 2015
• Publicly Available Date: Nov 23, 2017
• Journal: Organic and biomolecular chemistry
• Print ISSN: 1477-0520
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 34
• Pages: 9055-9064
• DOI: https://doi.org/10.1039/c5ob01002k
• Keywords: Benzofuran rings , Macrocyclic [1.1.1]metacyclophanes , MCPs
• Public URL: https://hull-repository.worktribe.com/output/376712
• Publisher URL: http://pubs.rsc.org/en/Content/ArticleLanding/2015/OB/C5OB01002K#!divAbstract
• Additional Information: Authors' accepted manuscript of article published in: Organic and biomolecular chemistry, 2015 at http://pubs.rsc.org/en/Content/ArticleLanding/2015/OB/C5OB01002K#!divAbstract
• Contract Date: Nov 23, 2017