Total synthesis 2-epi-alpha-cedren-3-one via a cobalt-catalysed Pauson-Khand reaction

Kerr, William J. and McLaughlin, Mark and Paterson, Laura C. and Pearson, Colin M. (2018) Total synthesis 2-epi-alpha-cedren-3-one via a cobalt-catalysed Pauson-Khand reaction. Tetrahedron, 74 (38). pp. 5062-5068. ISSN 0040-4020

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    Abstract

    Herein we target the total synthesis of 2-epi-alpha-cedren-3-one, a natural compound isolated from the essential oil of Juniperus thurifera. Overall, our synthetic sequence presents an optimised and robust series of chemical transformations, with prominent features including a low temperature and highly (Z)-selective Wittig olefination reaction, which is vital for the establishment of the relative stereochemistry within the final natural product, and a microwave-assisted, catalytic, intramolecular Pauson-Khand cyclisation reaction, which is used to construct the intriguing tricyclic core of the target molecule. Our optimum cyclisation protocol utilises only 20 mol% of transition metal, and delivers the complex tricyclic structure in just 10 minutes. Further manipulations of the annulation product culminate in the first total synthesis of the described natural target.