Organometallic Synthesis of 2,3,6,7-Tetrasubstituted 1,8-Bis(dimethylamino)naphthalenes for Investigation of the Double Buttressing Effect in Proton Sponges

Abstract

The lithiation of 2,7-disubstituted derivatives of 1,8-bis(dimethylamino)naphthalene (DMAN, proton sponge) bearing potentially ortho-directing OMe, NMe2, and SMe groups was studied. It has been shown that OMe groups facilitate selective dual β-lithiation of the naphthalene moiety while the 2(7)-NMe2 groups allow only monolithiation presumably due to the decreased acidity of the ring C–H bonds and conformational immobilization after coordination to the lithium atom. In contrast, the SMe groups provided no ring lithiation and underwent deprotonation of their methyl fragment. The first representatives of previously unknown 2,3,6,7-tetrasubstituted DMANs have been synthesized in good yield after treatment of 2,7-dimethoxy-3,6-dilithio DMAN with the appropriate electrophiles (MeI, Me2S2, Me3SiCl, DMF, etc.). Because the exceedingly high basicity of 2,7-dimethoxy DMAN is commonly attributed to the so-called “buttressing effect” (BE), the availability of 2,3,6,7-tetrasubstituted species provided the first opportunity to study the double BE version. Using X-ray diffraction and basicity measurements, we showed that due to the high conformational mobility of the methoxy groups, the most striking manifestations of double BE are the strong planarization of peri-NMe2 groups and a significant decrease in basicity, while the length and the other properties of the intramolecular NHN hydrogen bond in the corresponding protonated species undergo minor changes.