Synthesis of Versatile 1-Indanones and their Conversion to 1,2-Naphthoquinones, Key Precursors for the Construction of Perylenequinone Core

4,9-Dihyroxy-3,10-perylenequinones are natural pigments produced by a wide variety of molds, which act as photodynamic phototoxins to their hosts. Due to their unique photosensitizing properties, considerable attention has been paid to the application of these perylenequinones in photodynamic therapy (PDT) as anticancer, antiviral, and antifungal agents, particularly in developing efficient methodologies for the synthesis of naturally occurring perylenequinones and their analogues. However, the reported synthetic routes are pretty lengthy (over about 20 reaction steps) to the final bioactive perylenequinones, and the introduction of diverse substituents into perylenequinone core is likely to be difficult in one specific route. Consequently, perylenequinone derivatives with diverse structural features have not prepared in sufficient quantity to allow investigation of their structure-activity relationships. In addition, our literature analysis on the structural features of perylenequinones indicated that the successful formation of perylenequinones and the variation in the yields is likely to be dependent on the diversity of substitution at the 3-position of 1,2-naphthoquinone, a key precursor for the construction of peryleneqinone core in the dimerization step (Scheme 1). In our previous work, we prepared the novel perylenequinone core through a dimerization of 1,2-naphthoqinone (Scheme 1). While this synthetic route was pretty efficient in terms of relatively short reaction steps to the perylenequinone core (11 steps) and the satisfactory overall yield, it also is limited in the introduction of diverse substituents into the 1and 12positions of the perylenequinone core. We endeavored to develop a novel pathway to construct the perylenequinone core with the goal of the easy introduction of diverse substituents at the 1and 12-positions. To this end, we designed 1-indanones 4-6 as precursors, which would bear diverse substituents at the 2-position (6, Scheme 2) and which, in turn, could be readily converted by ring expansion to 3-substituted-1,2-naphthoquinones 7, the key precursor to perylenequinone (Scheme 2). We also hoped that this synthetic route could shorten the reaction pathway by at least several reaction steps. We focused on the efficient synthesis of versatile 1-indanones bearing diverse substituents at the 2-position of the molecule, and their conversion to the corresponding naphthoquinones. Presently, we report the efficient synthetic methodology of versatile 2-substituted1-indanone 6 and demonstrate that these 1-indanones are useful precursors for the efficient preparation of 1,2naphthoquinone 7, as we expected. On the basis of our literature survey for the preparation of multi-functionalizable 1-indanones 4-6 in mild and economic conditions, and in acceptable yields, we investigated the Hauben-Hoesch condensation reaction, a kind of FriedelCraft acylation with nitriles, which involves the electrophilic substitution of aromatic C-H bonds with intramolecular