Applications of the Horner–Wadsworth–Emmons Olefination in Modern Natural Product Synthesis

Abstract

Here, we have summarized more than 30 representative natural product syntheses published in 2015 to 2020 that employ one or more Horner-Wadsworth-Emmons (HWE) reactions. We comprehensively describe the applied phosphonate reagents, HWE reaction conditions and key steps of the total synthetic approaches. Our comprehensive review will support future synthetic approaches and serve as guideline to find the best HWE conditions for the most complicated natural products known

Wadsworth–Emmons Reaction by Using the Fluorapatite Catalyst: Kinetic Studies

“…Wadsworth–Emmons (WE) reaction has now become the most explored and common reaction for selective double bond formation . The reaction has a wide range of utilization in the synthesis of intermediates required for fine chemicals such as analgesics, perfumes, insecticides, fragrances, pheromones, carotenoids, prostaglandins, and pharmaceuticals and is classically carried out using bases under homogenous conditions. − The advantage of the WE reaction is the use of cheaper triethylphosphite, and water-soluble phosphates are easy to separate at the end of the reaction, and phosphonates result in a high rate of reaction than phosphine .…”

“…27 The enormous possibilities of HWE reaction with the compatibility and selectivity of the functional group for wide synthetic routes for natural products are discussed by Roman et al in their review paper. 1 Chavan et al 28 reported an intramolecular HWE reaction for the synthesis of a six-member scaffold of Tamiflu. Tamiflu is the medicine to prevent influenza A and B, which resulted in deadly mutation in the COVID-19 pandemic.…”

“…New chiral bicyclic amines, enamines, and imines were synthesized from the HWE reaction of hexahydroquinoxalin-2­( 1H )-one derived-phosphonate as the phosphonate carbanion source and carbonyl substrates . The enormous possibilities of HWE reaction with the compatibility and selectivity of the functional group for wide synthetic routes for natural products are discussed by Roman et al in their review paper . Chavan et al reported an intramolecular HWE reaction for the synthesis of a six-member scaffold of Tamiflu.…”

Synthesis of cyclopent-1-enecarbonitriles via a tandem Giese/HWE reaction initiated by visible light

“…Therefore, it is postulated that the base plays a dual role in the tandem reaction acting as an electron donor in the radical reaction and as a base in the subsequent Horner–Wadsworth–Emmons olefination. 17 In the first stage, substrate 1 undergoes SET ( E 1/2 = −1.23 V vs . SCE) that generates anion radical 5 .…”

Visible light-enabled synthesis of phosphorylated indolizine and pyridoindole derivatives via HAT-mediated radical cascade cyclization

“…Phosphonates are of great significance in organic synthesis, [1][2][3] medicinal chemistry, 4 and agrochemistry. A series of phosphonates and their derivatives have been approved as antivirus agents, [5][6][7] antibiotics, 8 anti-osteoporosis agents, 9 vasodilators, 10 and insecticides 11 (Fig.…”