Synthesis and Applications of Hajos-Parrish Ketone Isomers

Numerous natural products possess ring systems and functionality for which Hajos-Parrish ketone isomers with a transposed methyl group (termed "iso-Hajos-Parrish ketones") would be of value. However, such building blocks have not been exploited to the same degree as the more typical Hajos-Parrish hydrindane. An efficient three-step synthesis of such materials was fueled by a simple method for the rapid preparation of highly functionalized cyclopentenones, several of which are new chemical entities that would be challenging to access through other approaches. Furthermore, one iso-Hajos-Parrish ketone was converted into two distinct natural product analogues and one natural product. As one indication of the value of these new building blocks, that latter target was obtained in 10 steps, having previously been accessed in 18 steps using the Hajos-Parrish ketone. Moving methyl groups: Hajos-Parrish ketone isomers with a transposed methyl group, termed "iso-Hajos-Parrish ketones", are useful building blocks for diverse targets. A new synthetic method to cyclopentenones is used in a three-step approach to several of these compounds. Furthermore, a natural product that was previously accessed in 18 steps was now synthesized in 10 steps using an iso-Hajos-Parrish ketone.