Viable route and DFT study for the synthesis of optically active limonaketone: A barely available natural feedstock in Cedrus atlantica

Herein, we report a novel, easy and efficient synthesis pathway of optically active limonaketone, a high added value monoterpene, starting from limonene, natural and low-cost feedstock. The strategy was de-veloped in an excellent three-step total synthesis of limonaketone, potentially important intermediate in limonene ozonolysis and barely available in Cedrus atlantica essential oil (0.1% yield). The first step was the epoxidation of limonene which proceed in 91% yield. The ozonolysis of the prepared limonene ox-ide leads to the formation of the characteristic ketone function of limonaketone in 92% yield. The last step was performed by a deoxygenation in the presence of Zn and gave limonaketone in quantitative yield. The optically pure limonaketone has been efficiently synthesized from limonene and the overall yield was 84%. A molecular electron density theory (MEDT) analysis was carried out by using density functional theory (DFT) calculations at the M06-2X/6-311G(d,p) (LANL2DZ for Zn) level to understand the observed chemoselectivity in the Zn-deoxygenation reaction as well as its corresponding mechanistic pathway. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

A novel, efficient synthesis pathway for optically active limonaketone was developed, starting from limonene, with an overall yield of 84%. The strategy involved a three-step total synthesis of limonaketone, a potentially important intermediate in limonene ozonolysis. By utilizing density functional theory calculations, the chemoselectivity in the Zn-deoxygenation reaction and its mechanistic pathway were elucidated.