Abstract 2016 An Efficient, Metal-Free Route to 2-Naphthols

In an attempt to design a novel non-metal synthetic pathway for (+)-Brazilin via an acid-catalyzed rearrangement-cyclization reaction, we recently discovered an unprecedented reaction mode of 2,3-epoxy alcohols derived from 2-benzylidene-1-indanones. Treatment of these epoxy alcohols with trifluoroacetic acid triggers a skeletal rearrangement/aromatization reaction which affords substituted 2-naphthols in high yield. Overall, we have identified a high-yielding, 4-step synthetic route to 2-naphthols which does not require chromatographic purification until the final step. We are currently using various analogs of 1-indanone as precursors in the synthesis of 2-naphthols to further expand the scope of this reaction. These 2-naphthol products are a common structural feature of many biologically active compounds, including 2-arylpyrrolidines and TPY-β. Given the operational simplicity and low cost of this synthesis route, we will easily be able to prepare libraries of TPY-β analogues for biological evaluation.