Rapid progress in the research of metal-free transformations has been observed in the past decades; however, there’s still plenty of room there to be solved. In this talk, some of my past research experience in this field will be shared with you, especially for the young graduate students in order you may make one-step-further research in your related projects/research. First part: This talk starts from the Brønsted acid catalyzed Friedel-Crafts reaction for the conversion of cheap chemicals to value-added products. Unsymmetrical di-and triarylmethanes are generally synthesized through metal-catalyzed cross-coupling or Friedel– Crafts arylation using multistep harsh reaction conditions with pre-functionalized starting materials. These reaction protocols use pyrophoric materials such as Grignard reagents, metal hydrides, and toxic, hazardous, and problematic solvents like benzene, DMF, and THF. As an alternative, we will use a cheap, commercially available Brønsted acid-catalytic system, I will describe a one-pot three-component approach for the synthesis of unsymmetrical polyarylated alkanes from renewable feedstock chemicals. The developed method could also be scaled up and will be applied for a short and efficient synthesis of a phenanthrene-based anti-breast cancer agent, which reduced the conventional six-step cross-coupling approach to the one step Friedel–Crafts approach. Also, the method will apply for the late-stage functionalization of various natural products such as thymol, menthol, and eugenol etc. Second part: Reversing the conventional site-selectivity of C−H activation provides efficient retrosynthetic disconnections to otherwise unreactive bonds. In this part, I will focus on the Brønsted acid catalyzed reaction that selectively performs meta-amination/arylation of anisidines with amines/arenes in a one-pot procedure. I will also focus on the scalability and functional group tolerance, including late-stage functionalization of pharmaceutical compounds and natural products. The control experiments and detailed computational analysis will be discussed for the better understanding of mechanism and the origin of metaselectivity. Also, the synthesis of challenging drugs will be highlighted. Thirst part: Some ongoing projects will be discussed if time permits. Moreover, the largescale synthesis of pharmaceutically active ingredients (APIs) through metal-free protocol will be discussed briefly.