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Access to chiral calix[4]arenes can unlock novel supramolecular architectures for enantioselective catalysis and molecular recognition. However, accessibility to these structures has been significantly hindered so far. We report herein the synthesis and characterization of di- and trifunctionalized cone-calix[4]arenes featuring a lactone moiety spanning the distal positions at the upper rim. The lactones force the whole skeleton to assume pinched- cone conformations. The ring-closure is favored by the high conformational flexibility of the calixarene scaffold.
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The new lactones are remarkably stable in the solid state, while a quick hydrolysis to restore the parent carboxylic acids occurs in solution under acidic/basic conditions. Slow aminolyses of lactones 2–3 yield inherently chiral products featuring three different functionalities at the upper rim, at room temperature. The subsequent ring-closing/opening methodology presented here highlights the versatility of these lactones as powerful synthons for the preparation of a variety of threefold upper rim functionalized, inherently chiral calix[4]arenes fixed in the cone structure.
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