References

Along the way, Dora found some helpful friends who taught her everything she needs to know about this reaction!

Reference found in article: Wadsworth, W. S.; Emmons, W. D. J. Am. Chem. Soc. 1961, 83, 1733-1738.
A key component of the transformation of molecule 3 to molecule 4 is the Horner-Wadsworth-Emmons reaction. This paper, written by Wadsworth and Emmons, details this mechanism in depth, in collaboration with ideas from a previous paper written by Emmons. In the first step of the reaction, a phosphonate anion adds to an aldehyde or ketone, forming an alkoxide intermediate. This intermediate is in equilibrium with a four-membered ring. The molecule then undergoes fragmentation yielding a phosphate anion and a newly formed double bond in the product. The paper discusses the benefits of using a phosphonate anion, because it reacts without reverse addition and can be used effectively with all ketones, even those that are sterically hindered. The phosphonate anion has three contributing resonance structures, giving the P=O bond some single bond character, which aid in its ability to react under mild conditions. The first step in the mechanism, where an aldehyde or ketone is added to the carbonyl group, yields an intermediate that is in equilibrium with a four-membered ring. These equilibrating structures then undergo fragmentation to yield the product and phosphate anion. Phosphonate anions can be used in conjunction with the Horner-Wadsworth-Emmons mechanism to yield a variety of different reaction products. For instance, they can react with alkyl halides to give α-substituted phosphonates, which will react with a hydride reagent and an aldehyde or ketone to give olefins, which is a type of synthetic fiber. Additionally, halogenation of a phosphonate anion with subsequent addition of an aldehyde or ketone will produce vinyl halides.

Reference citing our reference #1: Steinbach, T.; Wahlen, C.; Wurm, F. R. Polym. Chem. 2015, 6, 1192-1202.
This paper discusses the benefits of the Horner-Wadsworth-Emmons synthesis, which is a key part of our HTML mechanism. This mechanism allows for the introduction of stereochemically-controlled carbon-carbon double bonds. The HWE reaction is advantageous because of its increased nucleophilicity due to the phosphate carbanion intermediate. This intermediate allows for the use of milder reaction conditions. This is beneficial because a variety of functional groups along with less electrophilic aldehydes and ketones can be used experimentally.

Reference citing our reference #2: Moradei, O. M.; du Mortier, C. M.; Cirelli, A. F. Tetrahedron 1997, 22, 7397-7402.
This paper details the use of the Horner-Wadsworth-Emmons reaction through Olefin reactions to introduce a chain appendix to a cycle. The paper discusses how other conditions could have been used (Wittig conditions) but HWE was chosen because of the nucleophilicity of the phosphonates. As in our paper, HWE was used to obtain phosphorylated products which then undergo further reactions.

Reference citing our reference #3: Morin, M. S. T.; St-Cyr, D. J.; Arndtsten, B. A. Org. Lett. 2010, 12, 4916-4919.
The researchers involved with this paper were faced with a challenge where their original reagents could not be used due to the limited scope of dipoles available. The Horner-Wadsworth-Emmons reaction fixed this issue of alkene synthesis because of the stability of the phosphonate precursors used.