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.

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.

Explorations into a series of different approaches for 9-membered carbocycle formation have afforded the first reported example of a 9-exo-dig ring closure via a Au^III-promoted reaction between an alkyne and an aryl ring as well as several additional, unique Friedel–Crafts-type cyclizations. Analyses of the factors leading to the success of these transformations are provided, with the application of one of the developed 9-membered ring closures affording an efficient and scalable synthesis of the bioactive resveratrol trimer caraphenol A. That synthesis proceeded with an average yield of 89 % per step (7.8 % overall yield) and has provided access to more than 600 mg of the target molecule.

Although quinone methides are often postulated as intermediates in the biosynthesis of many polyphenolic natural products, deploying their power in a laboratory setting to achieve similar bond constructions has sometimes proven challenging. Herein, a total synthesis of the resveratrol trimer vaticanol A has been achieved through three instances of quinone methide chemistry. These operations, one of which succeeded only under very specific conditions, expediently generated its [7,5]-carbocyclic core, afforded a unique sequence for dihydrobenzofuran formation, and concurrently generated, in addition to the target molecule, a series of diastereomers reflective of many other isolates.

Although quinone methides are often postulated as intermediates in the biosynthesis of many polyphenolic natural products, deploying their power in a laboratory setting to achieve similar bond constructions has sometimes proven challenging. Herein, a total synthesis of the resveratrol trimer vaticanol A has been achieved through three instances of quinone methide chemistry. These operations, one of which succeeded only under very specific conditions, expediently generated its [7,5]-carbocyclic core, afforded a unique sequence for dihydrobenzofuran formation, and concurrently generated, in addition to the target molecule, a series of diastereomers reflective of many other isolates.

Explorations into a series of different approaches for 9-membered carbocycle formation have afforded the first reported example of a 9-exo-dig ring closure via a Au^III-promoted reaction between an alkyne and an aryl ring as well as several additional, unique Friedel–Crafts-type cyclizations. Analyses of the factors leading to the success of these transformations are provided, with the application of one of the developed 9-membered ring closures affording an efficient and scalable synthesis of the bioactive resveratrol trimer caraphenol A. That synthesis proceeded with an average yield of 89 % per step (7.8 % overall yield) and has provided access to more than 600 mg of the target molecule.