Enantiomeric Recognition of Amino Acid Salts by Macrocyclic Crown Ethers Derived from Enantiomerically Pure 1,8,9,16-Tetrahydroxytetraphenylenes

Abstract

Asymmetric synthesis of (R,R)- and (S,S)-1,8,9,16-tetrahydroxytetraphenylenes was achieved from starting material (2R,3R)-butane-2,3-diol and (2S,3S)-butane-2,3-diol respectively by utilizing a center-to-axis strategy. A series of crown ether compounds 20, 24, and 25 and their corresponding enantiomers derived from chiral tetrahydroxytetraphenylene were synthesized in enantiomerically pure forms. Enantiomeric recognition properties of these hosts toward l- and d-amino acid methyl ester hydrochloride were studied by the UV spectroscopy titration. The tetramer hosts (S,S,S,S,S,S,S,S)-20 and (R,R,R,R,R,R,R,R)-20 exhibited the best enantioselectivities toward L- and D-alanine methyl ester hydrochloride salt with K(L)/K(D) = 4.1 and KD/KL = 3.9, respectively. The new chiral macrocyclic hosts would further enrich the host-guest chemistry.

The Application of Molecular Tethers in Controlling Axial Chirality

“…[23] Diol 12 was initially converted to its bis-tosylate derivate and then coupled to the phenoxide salt of 19 to give aryl iodide 20 in a moderate yield. An intramolecular Ullmann reaction on 20 led to the installation of the requisite biaryl bond and formation of 21 as a single diastereomer in 70% yield.…”

Our Expedition in Eight‐Membered Ring Compounds: From Planar Dehydrocyclooctenes to Tub‐Shaped Chiral Tetraphenylenes

“…The enantiomeric recognition properties of these hosts towards l-and d-amino acid methyl ester hydrochlorides were studied by UV spectroscopic titration. [45] The tetramer hosts (S,S,S,S,S,S,S,S)-185a and the corresponding (R,R,R,R,R,R,R,R)-185a featuring four tetraphenylene units exhibited the best enantioselectivities towards l-and d-alanine methyl ester hydrochloride salt with KL/KD = 4.10 and KD/KL = 3.90, respectively. The larger cavity sizes of the pentamer (S,S,S,S,S,S,S,S,S,S)-185b and hexamer (S,S,S,S,S,S,S,S,S,S,S,S)-185c are believed to be responsible for the weaker host-guest enantioselectivities, leading to a much lower degree of differentiation.…”

“…Very recently, a center-to-axis chirality transfer strategy toward the enantiomeric construction of the biaryl axis was developed. [45] As shown in Scheme 23, an intramolecular Ullmann coupling reaction using chiral butane-2,3-diols as chiral auxiliaries is the pivotal step for the realization of diiodide 151; the structure of 151 was confirmed by NMR spectroscopy and its absolute configuration was fully established by a crystallographic analysis. Then, a copper-mediated oxidative coupling reaction of 151 afforded optically pure 152.…”

Synthesis of tetraphenylene derivatives and their recent advances

“…Recently, Wong and co-workers developed an efficient process towards chiral tetrahydroxytetraphenylenes based on the strategy of 'center-to-axis chirality transfer' [47]. As depicted in Scheme 22, employing chiral butane-2,3-diol as chiral auxiliaries, diiodide (70) was prepared and allowed to undergo a CuCl 2 -mediated coupling reaction to afford the optically pure tetraphenylene (71).…”

“…Furthermore, Wong and co-workers developed a series of crown ether compounds (149) and their corresponding enantiomers were derived from chiral tetrahydroxytetraphenylene 58 in enantiomerically pure forms (Scheme 46) [47]. Enantiomeric recognition properties of these hosts towards Land D-amino acid methyl ester hydrochloride were studied by UV spectroscopic titration.…”