Synthesis of 1,3,6-Trisubstituted Azulenes

We have developed a short, general synthetic route to 1,3,6-trisubstituted azulenes. The key intermediate, 6-methylazulene, was synthesized from readily available and inexpensive starting materials in 63% yield over two steps. The methyl group of 6-methylazulene was then used as a synthetic handle to introduce different substituents at the 6-position via two different methods. Subsequently, the 1- and 3-positions were substituted with additional functional handles, such as formyl, chloromethylketone, and iodide. The efficiency of the synthetic route was demonstrated by preparing a collection of three different products with the best demonstrated yield 33% over seven steps.