Asymmetric Synthesis of Three Alkenyl Epoxides: Crafting the Sex Pheromones of the Elm Spanworm and the Painted Apple Moth

A concise synthesis of the sex pheromones of elm spanworm as well as painted apple moth has been achieved. The key steps were the alkylation of acetylide ion, Sharpless asymmetric epoxidation and Brown’s P2-Ni reduction. This approach provided the sex pheromone of the elm spanworm (1) in 31% total yield and those of the painted apple moth (2, 3) in 26% and 32% total yields. The ee values of three final products were up to 99%. The synthesized pheromones hold promising potential for use in the management and control of these pests.


Introduction
The elm spanworm and the painted apple moth, as lepidopteran pests, have inflicted considerable economic damage upon both forestry and horticulture [1].The elm spanworm, Ennomos subsignaria (Hübner, Kassel, Germany), is distributed in Canada, the eastern region of the United States and Newfoundland and mainly damages deciduous tree species, such as hickory (Caryra), ash (Franxinus), oak (Quercus), red maple (Acer rubrum), elm (Ulmus), basswood (Tilia), beech (Fagus), horse chestnut (Aesculus) and so on [2][3][4].The painted apple moth, Teia anartoides (Walker), is a pestilential species prevalent in Australia and New Zealand, whose larvae feed on a variety of plants [5,6].It is a severe threat to forested areas as well as to agricultural, horticultural and silvicultural crops.Presently, the management of these two pest species mainly relies on the application of chemical pesticides [7,8].As conflicts between agricultural production and environmental matters become more acute, developing green and efficient solutions to pest management gains more importance.

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Scheme 1. Retrosynthetic analysis of the sex pheromone 1.

Synthesis of Target Compounds
Scheme 1. Retrosynthetic analysis of the sex pheromone 1.

Synthesis of Target Compounds
With chiral epoxy alcohols in hand, we focused on the synthesis of the target pheromones 1-3, as outlined in Scheme 3. The hydroxyl group in 14 was activated by treating with trifluoromethanesulfonic anhydride to afford a corresponding triflate.Then, the alkynylation coupling reaction between the in situ-generated triflate and 17 was undertaken, offering the desired epoxy alkyne 18 in 80% yield [22].Following a similar proce-Scheme 2. Synthesis of chiral epoxy alcohols 14-16.

Synthesis of Target Compounds
With chiral epoxy alcohols in hand, we focused on the synthesis of the target pheromones 1-3, as outlined in Scheme 3. The hydroxyl group in 14 was activated by treating with trifluoromethanesulfonic anhydride to afford a corresponding triflate.
Molecules 2024, 29, x FOR PEER REVIEW synthesize compounds 14-16 into target pheromones 1-3, achieving conversio yields ranging from 69% to 75% in two steps.This approach has demonstrated h ciency and straightforward execution.The structures of these three sex pheromon characterized by 1 HNMR, 13 CNMR, HRMS and specific rotation ( 1 HNMR and 1 spectras are available in the supplementary materials), which were consistent w references [4,5].

General Information
All reactions were carried out within a Schlenk line system under an inert phere of argon.Commercially available reagents were utilized as received, witho tional purification.In contrast, solvents underwent distillation following standard dures prior to use.Column chromatography was generally performed on a silica g 300 mesh), and elution was performed with petroleum ether and ethyl acetate. 1 H NMR spectra were recorded on a Bruker DP-X500 MHz spectrometer (Bruker Corp Beijing, China).Chemical shifts were reported in ppm relative to internal tetrameth for 1 H NMR and CDCl3 (77.16 ppm) for 13 C NMR. High-resolution mass spectra ( were collected on Waters LCT Premier™ with an ESI mass spectrometer (Waters ration, Beijing, China).Optical rotations were determined by a Rudolph Research ical AUTOPOL-IV.Melting points were measured on a STUART-SMP3 Melt-Tem ratus without correction (Stuart Equipment, Beijing, China).

General Information
All reactions were carried out within a Schlenk line system under an inert atmosphere of argon.Commercially available reagents were utilized as received, without additional purification.In contrast, solvents underwent distillation following standard procedures prior to use.Column chromatography was generally performed on a silica gel (200-300 mesh), and elution was performed with petroleum ether and ethyl acetate. 1 H and 13 C NMR spectra were recorded on a Bruker DP-X500 MHz spectrometer (Bruker Corporation, Beijing, China).Chemical shifts were reported in ppm relative to internal tetramethylsilane for 1 H NMR and CDCl 3 (77.16ppm) for 13 C NMR. High-resolution mass spectra (HRMS) were collected on Waters LCT Premier™ with an ESI mass spectrometer (Waters Corporation, Beijing, China).Optical rotations were determined by a Rudolph Research Analytical AUTOPOL-IV.Melting points were measured on a STUART-SMP3 Melt-Temp apparatus without correction (Stuart Equipment, Beijing, China).

Conclusions
In summary, we have developed an efficient and novel asymmetric synthesis of the sex pheromone of the elm spanworm (1) and the painted apple moth (2 and 3).The central components of our strategy involved the alkylation of acetylide ion to connect chiral epoxy triflate with alkyne, Sharpless asymmetric epoxidation to construct the stereocenters, and Brown's P2-Ni reduction to provide a cis alkene.Compared to the reported procedures, this approach has the advantages of cheaper starting materials, a shorter synthetic route, higher total yield and higher enantiopurity.Our research would be beneficial for the control of Ennomus subsignaria (Hübner) and Teia anartoides (Walker).

Figure 1 .
Figure 1.The sex pheromones of the elm spanworm and the paint

Figure 1 .
Figure 1.The sex pheromones of the elm spanworm and the painted apple moth.