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

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. (1)H 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 (1)H 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.

Synthesis, Structures and DFT Computational Studies of [3.1.1]Metacyclophanes Containing Benzofuran Rings

“…We previously reported the synthesis of calix[3]benzofurans which are unusual macrocycles bearing benzofuran units instead of only benzene rings. Recently, our group illustrated an efficient intramolecular cyclization synthetic route to produce macrocyclic [1.1.1]MCPs containing two and three benzofuran rings, using( p ‐tolylsulfonyl)methyl isocyanide (TosMIC) as the cross‐coupling cyclization reagent. In an analogous manner, the synthesis of 6,15,24‐tri‐ tert ‐butyl‐9,18,27‐trimethoxy[3.3.3]‐MCP‐2,11‐dione 5 was previously reported and is shown in Scheme .…”

“…The 1 H‐NMR signal patterns for 6 a shows that it is highly flexible in solution at room temperature and undergoes very fast conformational change. Previously, in the case of the symmetrical 1 5 ,3 5 ,5 5 ‐tri‐ tert ‐butyl‐1 2 ‐hydroxy‐1‐(1,3)‐benzena‐3,5(2,7)benzo‐furanacyclohexaphane, we had observed a calix[4]arene‐like cone conformation in both the solution and solid states . Dynamic ‘H‐NMR spectroscopy of 6 a showed that the protons of the Ar CH 2 Ar methylene group each appeared as a singlet, even down to –60 °C (CDCl 3 /CS 2 1:3) and thus its rate of conformational ring flipping is faster than the NMR time scale above this temperature.…”

Synthesis and conformational studies of calixarene analogue chiral [3.3.1]metacyclophanes

“…6,15,22-Tri-tert-butyl-9,18,25-trimethoxy[3.3.1]metacyclophane-2,11-dione 3 was synthesized by the coupling reaction of TosMIC adduct 1 with 2 according to the reported procedure [37]. , and triethylene glycol (5 mL) was heated at 120 C for 2 h and then at 200 C for 3 h. The cooled mixture was poured into water (50 mL), acidified with diluted HCl, and extracted with CH 2 Cl 2 (5 Â 30 mL), washed with water (2 Â 20 mL), dried over Na 2 SO 4 , and concentrated under reduced pressure.…”

Calix[3]arene-Analogous Metacyclophanes: Synthesis, Structures and Properties with Infinite Potential

“…The demethylation of [3.3.1]MCP-dione 19 in acetonitrile with in-situ-generated TMSI produced a mixture of benzofuran ring-containing products, the symmetrical 22a and unsymmetrical 23a and a new spirobisdihydro-furan 24 in 24 , 45 and 5% yields, respectively ( Figure 6 ) [ 39 ]. It is presumed that the trihydroxy-diketo intermediate 21 is first formed, and then undergoes intramolecular TMSI-mediated cyclizations to form the observed products [ 39 , 40 , 41 ]. Sawada and co-workers had previously reported that the treatment of tetramethoxy [2.1.2.1]MCPs with TMSI formed hemisphere-shaped calixarene analogues containing a dihydrobenzofuran ring [ 42 , 43 ].…”

“…All hydrogens except methoxy and phenolic hydrogens are omitted for clarity. Figure adapted and re-calculated from [ 39 ].…”