Conformational Effects of Regioisomeric Substitution on the Catalytic Activity of Copper/Calix[8]arene C−S Coupling

Calix[8]arenes are tunable macrocycles amenable for the design of nanoreactors. Functionalization of its hydroxyl rim needs to be regioselective to create a cavity suitable for reagents to interact with the metal center, otherwise the catalytic process is affected. Here we present a 1,4-hydroxy-functionalized calix[8]arene-Cu(I) complex and show how regioisomer-induced conformational effects result in poor performance in catalytic C−S coupling relative to its 1,5-functionalized analogue.

Abstract

Functionalization of the phenolic rim of p-tert-butylcalix[8]arene with phenanthroline to create a cavity leads to formation of two regioisomers. Substitution of positions 1 and 5 produces the known C_2v -symmetric regioisomer 1,5-(2,9-dimethyl-1,10-phenanthroyl)-p-tert-butylcalix[8]arene (L^1,5 ), while substitution of positions 1 and 4 produces the C_s -symmetric regioisomer 1,4-(2,9-dimethyl-1,10-phenanthroyl)-p-tert-butylcalix[8]arene (L^1,4 ) described herein. [Cu(L^1,4)I] was synthesized from L^1,4 and CuI in good yield and characterized spectroscopically. To evaluate the effect of its cavity on catalysis, Ullmann-type C−S coupling was chosen as proof-of-concept. Selected aryl halides were used, and the results compared with the previously reported Cu(I)/L^1,5 system. Only highly activated aryl halides generate the C−S coupling product in moderate yields with the Cu(I)/L^1,4 system. To shed light on these observations, detailed computational investigations were carried out, revealing the influence of the calix[8]arene macrocyclic morphology on the accessible conformations. The L^1,4 regioisomer undergoes a deformation that does not occur with L^1,5 , resulting in an exposed catalytic center, presumably the cause of the low activity of the former system. The 1,4-connectivity was confirmed in the solid-state structure of the byproduct [Cu(L^1,4 −H)(CH₃CN)₂] that features Cu(I) coordinated inside a cleft defined by the macrocyclic framework.

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