Functionalization of 1,3-Phenylene-16-crown-5 via Direct Lithiation

Abstract

1,3-Phenylene-16-crown-5 (1) was selectively and quantitatively lithiated at the intraannular 2-position with n-butyllithium, making functionalization of this system easier than that of the 1,3-xylylene crown ethers. The lithiation yielded the corresponding (2-lithio-1,3-phenylene)-16-crown-5 (2) without cleavage of the polyether ring. Subsequent reaction with deuterium oxide, dimethyl disulfide, iodine, carbon dioxide, dimethyltin dichloride (0.5 molar equiv), mercury dibromide (0.5 molar equiv), benzyl bromide, and magnesium dibromide yielded (2-deuterio-1,3-phenylene)-16-crown-5 (3), [2-(methylthio)-1,3-phenylene]-16-crown-5 (4), (2-iodo-1,3-phenylene)-16-crown-5 (5), (2-carboxy-1,3-phenylene)-16-crown-5 (6), dimethylbis[(1,3-phenylene-16-crown-5)-2-yl]stannane (7), bis[(1,3-phenylene-16-crown-5)-2-yl]mercury (8), 2-benzyl-1,3-phenylene-16-crown-5 (9), and [2-(bromomagnesio)-1,3-phenylene]-16-crown-5 (10), respectively. Functionalized analogues of this crown ether have not been reported previously. X-ray crystal structures of 6, 7, and 10 were determined. According to the crystal structure of 6, the carboxylic substituent takes part in intramolecular hydrogen bonding with a transannular crown ether oxygen (O(8)). The crystal structure of 7 is the first one for a bis(crown ether)tin(IV) compound and reveals close proximity between tin and four of the ten crown ether oxygens. In the Grignard reagent 10 the magnesium is hexacoordinated in a distorted-octahedral fashion with the bromine and a THF oxygen in the apical positions and three of the five crown ether oxygens plus carbon C(1) in planar positions. It is the first example of a crown ether Grignard reagent in which the metal center is not completely intramolecularly coordinated.