A PM3 AND MNDO STUDY ON THE MECHANISM AND THE REGIOSELECTIVITY OF THE LITHIATION OF LITHIUM METHYL-1-NAPHTHYLCARBAMATE AND METHYL-2-NAPHTHYLCARBAMATE AND LITHIUM 1,2,3,4-TETRAHYDROISOQUINOLINECARBAMATE WITH TOLUENE

To assess the reliability of the MNDO and PM3 semiempirical methods in predicting the regioselectivity and mechanism of lithiation reactions, we calculated the reaction course of several lithium carbamates (4a, 4b, 8) with MeLi, the phenol/LiH complex, and the toluene (10)/LiMe system. For those carbamates in which H-atoms at two identically hybridized carbon centers compete for the incoming lithium cation (sp(2)-C in the case of lithium methyl-1-naphthylcarbamate (4a) and 4b, its 2-isomer; sp(3)-C in the case of lithium 1,2,3,4-tetrahydroisoquinolinecarbamate (8)), both methods describe the experimentally observed regioselectivity of the metalation steps correctly. Nevertheless, almost invariably erroneous results will be obtained by semiempirical methods for comparable reactions in which two differently hybridized carbon centers of the substrate might be involved. These findings follow from ab initio and semiempirical calculations for the toluene (10)-LiMe reaction. Here and in related cases of competing sp(2)- and sp(3)-centers, both semiempirical methods will predict the wrong regioselectivity. In the past, the feasibility of a H/Li exchange has been attributed to the ''agostic activation'', which results in an elongated C-H bond. In this paper we report that such an activation is an artifact of the semiempirical methods.