A Formal Synthesis of Himachalene Sesquiterpenes

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University of New Brunswick


Insect communications rely on chemical signalling, using chemical substances called pheromones. These chemicals are specific to individuals of the same species and are used for different purposes, such as gathering for food, mating, alerting other individuals to dangers, setting boundaries, or limiting the number of individuals in a certain space or on one host and to follow other individuals. The use of pheromones to disrupt insect behaviour, more specifically mating, became one of the most important and environmentally friendly pest control strategies as a core element of integrated pest management (IPM) programs. Pheromones are also used to monitor insect populations and in traps with other toxic substances to reduce the risks and losses caused by invasive species. In an endeavour to study the pheromonal activity of four himachalene sesquiterpenes as an insect pest management strategy for the control of the blueberry flea beetle Altica sylvia Malloch (a major insect pest of the blueberry plantations in North America), attempts to repeat literature synthetic routes were found to be low yielding. Where the nor-himachalene ketone was considered a convenient precursor to the rest of the target himachalenes, several strategies were investigated, of which two new routes to achieve the desired compound were found to be more efficient. The first furnished the 6,7-bicyclic core of the himachalenes via a sequence of allylic alkylation (AA), Cope rearrangement, and ring-closing metathesis (RCM). The second route relied on RCM to construct the required 2,2,6-trimethylcycloheptanone that could then be subjected to Robinson annulation to furnish the target precursor. These routes are easily amenable to result in an asymmetric version. Other routes examined included a formal [2+2] cycloaddition to construct a cyclobutane intermediate that can go in a ring opening-annulation sequence to form the six-membered ring, the use of Mukaiyama-Michael addition (MMA) to introduce the carbon sidechain required for the annulation of the 2,2,6-trimethylcycloheptanone and an intramolecular Diels-Alder (IMDA) cycloaddition to construct the fused 6,7-bicyclic system from an open chain. During the investigation of the MMA reaction, we developed new organocatalytic conditions using bis(trifluoromethane)sulfonimide (TFI) as the catalyst that was found to be effective at low catalyst loading.