Abstract: Verbenone is a natural monoterpenoid with pinene framework and plays an important role in the relationships between different species in some ecosystems. On the one hand, it is found in plants: large quantities of verbenone were observed in some rosemary oils (27.0–28.9%) [1] and it was found as major component in flowers of different chrysanthemum cultivars and their wild relatives [2]. On the other hand, verbenone is a purported anti-aggregation pheromone of several economically significant bark beetle species [3]. Moreover, the mycangial symbiotic fungus of Dendroctonus frontalis produces verbenone, thus, the development of fungus in the plant host may play a role in influencing the behavior of the beetle to a success fully colonized tree [4]. The most important way to obtain verbenone is the allylic oxidation of widespread—and available in large amounts—monoterpene α-pinene [5,6]. Verbenone as a component of essential oil can be used in aromatherapy [7]. Finally, one of the most important directions for the use of verbenone is fine chemistry. Verbenone, being a chiral compound, is used in the asymmetric synthesis of complex biologically active compounds, for example, a diol with a para-menthane skeleton with high antiparkinsonian activity [8] or the antitumor agent, taxol [9]. It is known that the extended enolate of verbenone can act as a d4-synthon, in particular, it reacts with aldehydes at the methyl group in the presence of a base [10,11,12]. At the same time, verbenone itself is a Michael acceptor, thus, is an a3-synthon. However, in the case of simple C-nucleophiles, this obvious approach does not work, and to obtain the corresponding products, the following detours are used: through cyclopropanation, followed by the opening of the cyclopropane ring [13]; or on the basis of nopinone, which temporarily introduces an additional SO2Ph acceptor into the α-positions, and is subsequently removed with Li/NH3 (liquid) [14]. However, verbenone can react with a strong delocalized conjugated C-nucleophile, such as a structurally similar dianion of crotonic acid. [15]. Moreover, the nucleophile, corresponding to an extended enolate, is attached at its γ-position. Therefore, verbenone can be potentially dimerized, and since in the case of verbenone dianion, it does not need to be created, the reaction should proceed under mild conditions. The resulting γ, β-dimer is promising for further modification, including the separate modification of each fragment with a pinane framework due to their structural difference. Importantly, to the best of our knowledge there are no data on the γ, β-dimerization of (−)-verbenone. Dimers of different structures obtained by the oxidation of the extended enolate of verbenone are described [16]. In particular, the γ, γ-attachment at methyl groups was observed when using CuCl2, but α, γ-joint occurred in the case of FeCl3.

Cite: Ardashov O.V. , Korchagina D.V. , Bagryanskaya I.Y. , Volcho K.P. , Salakhutdinov N.F.
(1S,5R)-6,6-Dimethyl-4-(((1S,2S,5S)-2,6,6-trimethyl-4-oxobicyclo[3.1.1]heptan-2-yl)methyl)bicyclo[3.1.1]hept-3-en-2-one
MolBank. 2022. V.2022. N4. P.M1465. DOI: 10.3390/m1465 WOS РИНЦ

Dates:

Submitted:	Sep 29, 2022
Accepted:	Oct 10, 2022
Published online:	Oct 13, 2022

Identifiers:

Web of science	WOS:000902978300001
Elibrary	56981788
OpenAlex	W4306153499

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