A Convergent Radical Cascade for the Synthesis of Azaindanes

The azaindane motif is present in a number of drug candidates and combines the benefits of both a high sp³-fraction and an heteroaromatic ring. However, only a limited number of efficient approaches for the elaboration of this motif have been reported, and very few are flexible enough to enable the fast generation of analogues. Here we report the exploration of a convergent process for the construction of a variety of azaindanes and related semi-saturated fused heterocycles from an heteroaromatic triphenylpyridinium (Katritzky Salt) and an alkene coupling partner. In this process, two new C─C bonds are formed in a single step involving the activation of a pyridine-containing Katritzky salt under visible light irradiation in acidic conditions without the use of additional reductant/oxidant or photocatalyst. Under these operationally simple conditions, a variety of functional groups are tolerated, but the outcome of the reaction is dependent on the electronic nature of the pendant heterocycle and the alkene reaction partner. To help the exploration of future substrates, guidelines are established to predict the outcome of the reaction. Additionally, mechanistic studies shed light on the role played by the acid additive as well as the triphenylpyridine by-product in this process.