Site-selective C–H functionalization in a cyclodextrin metal-organic framework

Abstract

Confinement is a unifying element in selective enzymatic reactions but has rarely been used to control site selectivity of carbon–hydrogen (C–H) bond functionalization in artificial receptors. Herein, we demonstrate the selective functionalization of one of seven C(sp3)–H bonds on a D-glucopyranosyl residue of γ-cyclodextrin (γ-CD) by irradiating 2-benzoylbenzoate in a γ-cyclodextrin-containing metal-organic framework (CD-MOF-1). Both 1H NMR spectroscopy and X-ray crystallography of the products confirm that functionalization occurs selectively at one of the two C(sp3)–H bonds on the C6 position of a D-glucopyranosyl residue. The alignment of 2-benzoylbenzoate inside (γ-CD)2 tunnels in CD-MOF-1, as revealed by X-ray crystallography, precludes C–H functionalization on the outer surface of the γ-CD tori. Theoretical calculations indicate less steric hindrance associated with C6-functionalized (γ-CD)2 tunnels in CD-MOF-1 compared with C3 and C5, leading to the observed site selectivity.