Synthesis of enantiomerically pure inherently chiral calix[4]arenes using the meta-substitution strategy

• Published in: Tetrahedron letters Vol. 60; no. 3; pp. 260 - 263
• Main Authors: Tlustý, Martin, Spálovská, Dita, Babor, Martin, Lhoták, Pavel
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 17-01-2019
• Subjects: Absolute configuration; Bischler-Napieralski; Calixarene; Enantiomers; Inherent chirality; Mercuration; Mercuration; Bischler-Napieralski; Calixarene; Inherent chirality; Enantiomers; Absolute configuration
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2018.12.026

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•meta-Substituted aminocalix[4]arene was acylated by amino acids derivatives (Phe, Ala).•The combination of inherent chirality with chiral AAs led to diastereomers separable by preparative TLC.•Cyclization with Tf2O/2-ClPyr yielded the corresponding enantiomerically pure oxazoles.•Straightforward and scalable approach towards enantiomerically pure inherently chiral calix[4]arenes.
A meta-substituted aminocalix[4]arene 4 immobilized in the cone conformation was prepared via mercuration of the starting tetra-propoxy derivative, followed by nitrosation and reduction reactions. Acylation of the amino group by chiral amino acid residues ((S)-N-trifluoroacetyl-Ala or (S)-N-trifluoroacetyl-Phe) allowed for the preparation of diastereomeric amides that were separated by preparative TLC on silica gel. Subsequent cyclization under Bischler-Napieralski reaction conditions yielded calixarenes 7b and 7c bearing an oxazole moiety in the meta position instead of the expected upper rim-bridged compounds. The reaction sequence represents a straightforward approach towards enantiomerically pure inherently chiral calix[4]arene derivatives (without HPLC separation steps). The absolute configuration of the enantiomers were confirmed by single crystal structure determination (X-ray).