The Horner-Wadsworth-Emmons reaction has evolved in the last years as one of the most powerful and reliable method for stereocontrolled olefin synthesis. The reaction has become a widespread standard tool in natural products total syntheses, providing access to relatively simple as well as highly complex synthetic targets. In this work we present the most representative applications within the field of natural product synthesis from 2000 to the present year. The examples comprise the synthesis of macrocycles, 5 to 7 membered rings, lipids and related compounds, alkaloids and cyclic ethers. They were chosen from a large amount of literature reports and illustrate the use of the HWE reaction in the synthesis and elaboration of key intermediates and in the crucial assembly of highly functionalized synthetic precursors.

The first general procedure for the synthesis of 5- to 7-membered cyclic iminoethers by microwave-assisted cyclization of ω-amido alcohols promoted by polyphosphoric acid (PPA) esters is presented. 2-Aryl-2-oxazolines and 5,6-dihydro-4H-1,3-oxazines were efficiently prepared using ethyl polyphosphate/CHCl. Trimethylsilyl polyphosphate in solvent-free conditions allowed for the synthesis of hitherto-unreported 4,5,6,7-tetrahydro-1,3-oxazepines. The method involves good to excellent yields and short reaction times.The reaction mechanism and the role of PPA esters were investigated in a chiral substrate.

A novel type of spin traps 1 derived from the pyrimidoquinoxaline N-oxide heterocyclic core is reported.EPR technique was used to evaluate their ability to trap methyl radicals generated in a Fenton reaction in the presence of DMSO. All the synthesized nitrones showed spin trapping properties and the corresponding nitroxides 2 were characterized by EPR. The novel spin traps showed remarkably persistent signals, as confirmed in a competition experiment with DMPO. The addition rate constants leading to the spin adducts (k add ) were determined, and very good correlations were found with steric and electronic parameters of the parent nitrones. The spin adducts decomposition rate constants (k dec ) and the corresponding half-life times (t 1/2 ) were also determined. DFT and MP2 calculations were used in order to rationalize the adducts hfcc and the structural factors influencing their addition and decomposition rates.