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

Abstract

International audienceTrihydroxy[3.3.1]metacyclophane, which can be regarded as an unsymmetrical or incomplete “homocalix[3]arene”, has been prepared from trimethoxy[3.3.1]metacyclophane by demethylation with trimethylsilyl iodide in MeCN. Di-O-methylation at the lower rim of trihydroxy[3.3.1]metacyclophane in the presence of K2CO3 in acetone afforded a novel, inherently chiral calixarene–analogue, namely a macrocyclic [3.3.1]metacyclophane, 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 [(S)-(+)-1-(9-anthryl)-2,2,2-trifluoroethanol], which caused a splitting of the OMe group and AB patterns corresponding to the methylene protons

Synthesis and Structure of 1,2‐Dimethylene[2.10]metacyclophane and Its Conversion into Chiral [10]Benzenometacyclophanes

“…Very recently, we reported a synthesis and conformational study of [2. n ]MCP‐1‐enes and the reaction with BBr 3 to afford tetrahydrobenzofuranophane . We also reported inherent chirality in the MCP structure . As part of our continued interest in the synthesis of inherently chiral MCPs, we undertook a systematic investigation of the starting compound 5,21‐di‐ tert ‐butyl‐8,24‐dimethoxy‐1,2‐dimethyl[2.10]MCP‐1‐ene ( 1 ), containing both decane and ethylene bridges, which were synthesized from 1,10‐bis(5‐ tert ‐butyl‐2‐methoxyphenyl)decane in four steps by using the tert ‐butyl group as a positional protective group on the aromatic ring .…”

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

“…The demethylation of 20a using tetramethylsilyl iodide (TMSI) in acetonitrile produced the corresponding trihydroxy[3.3.1]MCP, 20b, as expected, but when BBr 3 in dichloromethane was used, the partial demethylation of 20a resulted, forming only the dihydroxy[3.3.1]MCP, 20c . Upon further treatment with TMSI/MeCN, however, 20c afforded the trihydroxy[3.3.1]MCP 20b [ 38 ]. Its 1 H-NMR spectrum (in CDCl 3 ) exhibits the signals for the hydroxyl groups at ~ δ 3.33 and 6.25 ppm, which is evidence for the formation of intramolecular hydrogen bonding and a cone conformation [ 38 ].…”

“…Upon further treatment with TMSI/MeCN, however, 20c afforded the trihydroxy[3.3.1]MCP 20b [ 38 ]. Its 1 H-NMR spectrum (in CDCl 3 ) exhibits the signals for the hydroxyl groups at ~ δ 3.33 and 6.25 ppm, which is evidence for the formation of intramolecular hydrogen bonding and a cone conformation [ 38 ]. In contrast, both the 1 H-NMR spectrum and a single crystal analysis confirmed the 2-partial-cone conformation of macrocycle 20c .…”

“…The efficient syntheses of larger macrocyclic MCPs in which the aromatic groups are linked by varying larger numbers of −CH 2 − groups can also be effectively accomplished using two other non-sulfur extrusion processes, namely the low-valent zinc McMurry coupling reaction, or the TosMIC (p-tolylsulfonylmethyl isocyanide) [30,31] methodology that was used to great advantage by Vogtle's group, for the synthesis of [3 n ]MCPs [32]. The synthesis, conformations and properties of several types of the larger homocalix [3]arene-analogue MCPs [33][34][35][36][37][38], using TosMIC has been reported by our group. For example, the synthesis of the symmetrical all-trimethylene-bridged hexahomocalix [3]arene analogue MCP, namely tri-tert-butyl-trimethoxy[3.3.3]MCP 13a, was achieved via the TosMIC-NaH mediated cyclotrimerization reaction of 2,6-bis(bromomethyl)-4-tert-butylanisole 14, followed by acid hydrolysis, to form trione 15 along with dione 16 in 22% and 10% yields, respectively (Scheme 3) [33], although better yields of 15 (68%) could be obtained using the 1 + 1 coupling reaction of bis-TosMIC adduct 17 with 14, instead, as shown in Scheme 3.…”

Synthesis and Structures of [2.n]Metacyclophan‐1‐enes and their Conversion to Highly Strained [2.n]Metacyclophane‐1‐ynes

“…The bromine adduct of [2.10]metacyclophan‐1‐ene on the other hand, gave the [2.10]metacyclophane‐1‐yne as the major product, along with a monodehydrobrominated product 1‐bromo[2.10]metacyclophan‐1‐ene as a by‐product . We also recently reported the synthesis, structures and DFT (Density Functional Theory) computational studies of several [2. n ]metacyclophanes and [3.3]metacyclophanes as well as ring‐expanded metacyclophanes containing three aromatic rings …”