ORIGIN OF THE REGIOSELECTIVE LITHIATION OF 1,3-DISUBSTITUTED HETEROATOM AROMATICS - MNDO EVIDENCE FOR BIDENTATE COMPLEXATION

The regioselective lithiation of several prototype 1,3-disubstituted heteroatom aromatics, such as 1,3-dimethoxybenzene (DMB), 1,3-difluorobenzene (DFB), and 3-fluoroanisole (FA), has been studied by means of the semiempirical MNDO method. Calculations show clear-cut evidence for the intermediate formation of chelated species 6, which formally derives from the bidentate coordination of the coordinatively unsaturated lithium base by the educt working as a "pair of tweezers". A very strong agostic interaction on C2-H exists at this stage of the reaction coordinate, even though lithium atoms are formally pentacoordinated. In all cases studied the energy barriers corresponding to lithiation at C2 by the bidentate coordination mode of approach are lower than those of the monodentate coordination mode leading either to lithiation at C2 or C6. Both the experimentally observed rate enhancement and regioselectivity are thus fully supported by the bidentate coordination mode of approach. These results can be satisfactorily explained by examining the "neighbor" and "non-neighbor" interactions being developed in reaching the alternative transition states. Thus, by partitioning the MNDO-calculated transition state total energy it can be recognized that five large, overall attractive, neighbor interactions (two O-Li, one C-H, and two C2-Li) are being established in reaching the transition structure (TS6-c2) by the bidentate coordination mode, but only three major interactions (one O-Li, one C-H, and one C2-Li) develop throughout the monodentate coordination mode.