Isoprene-mediated lithiation of imidazole derivatives: mechanism considerations

The isoprene-mediated lithiation, with lithium metal, of different imidazole derivatives is an interesting methodology for their functionalization. Studies of different possible intermediates involved in the reaction employing density functional theory calculations, at the B3LYP/6-311++G(d,p) level are considered. A plausible mechanism is described, in which isoprene is reduced, to the corresponding radical anion, in the presence of Li(s), acting then as a base deprotonating N-methylimidazole (NMI) and producing the 1,1-dimethylallyl radical. This radical is further reduced by the excess of lithium proceeding once more as a base. This final step produces stable final products that compensate the previous equilibriums, making favourable the whole process.

Enantioselective catalytic lithiation using a chiral binaphthyl derivative as electron carrier

The lithiation, of the secondary chloride 2, catalyzed by binaphthyl derivatives, i.e. BINAM 4, BINOL 5, BINAP 6, H8-BINAP 7, Tol-BINAP 8, 2,2’-bis(pyrrolidin-1-yl)-1,1’-binaphthalene 9, and 2,2’-dimethyl-1,1’-binaphthalene 11, in the presence of different ketones has been studied, yielding the corresponding alcohol derivatives 3 and 12-16 in moderate to good yields. Binaphthyl derivative 11 has revealed to be very active as catalyst in the lithiation process at room temperature, and has allowed the preparation of the alcohol derivatives with enantioselectivities up to 50%.