N, N-Dimethylphenethyl amine is a scaffold present in many pharmacophores like Venlafaxine, isoquinolines-based anti-biotics and many oncological drugs. The lithiation-substitution reactions of these scaffolds played a vital role in the development of these drugs and helped synthetic organic chemists to design the process of development for many existing APIs. Hence the feasibility and regioselectivity of lithiation-substitution reaction on these scaffolds have been delineated under different reaction conditions.