The reaction of aryl phosphonates with carbonyls in the presence of t-BuOK in THF yields exclusively (E-)olefins. Can the use of LiCl further improve the (E)-isomer up to 100%?
There are some references related that using LiCl improve the E selectivity. You can also improved the E selectivity by performing same reaction using NaH in non polar aprotic solvent like toluene.
In general, if we use LiCl then which one will be better solvent, THF or DMF. The base is same, t-BuOK.
The HWE reaction is obviously really sensitive to water - be it from the lithium chloride or as KOH as a fine crust on the outside of clumps of KOtBu. When I did this chemistry on t-butyl diethylphosphonlyacetate with straight-chain aldehydes for a stereocontrolled conjugate addition later, the reaction worked best with freshly sublimed KOtBu, LiCl freshly crystallised from dry 1,4-dioxane, and all the other reagents (THF, the aldehyde and the phosphonate) all as dry as possible - distilled and kept under nitrogen or argon being best. The procedure followed for the HWE is that of Stephen Davies - too many to number at the moment!
Sorry, forgot to mention that all the selectivities were >99% E. To get Z, you had to tinker with the esters involved in this case.
Using LiCl as an additive, the reaction can proceed with a weaker base such as DBU and Hünig’s base (the Roush-Masamune conditions). This is useful when the reactants are unstable under strongly basic conditions involving NaH or LDA. LiCl is considered to act as a Lewis acid to increase the acidity of the activated proton.
Dear Carlos Vivar
The substrate is not sensitive towards base, but the R-CH2-phosphonate is not highly stabilized (R= simple aromatic, not ester), in such condition if we can use BuOK in THF, then addition of LICl may produce 100% E? Similar to that of Schlosser modification for simple wittig.
I used several time this reaction. My condition have always been 0°C, acetonitrile as solvent, LiCl and DBU as a base using aldehdes as substrates. When I used tiethyl phosphonoproprionate I got a mixture E:Z around 3:1 but with simple ethyl phosphonoacetate th selectivity was increased to >90:1. The problem here are sterics in the "coupling" partners. LiCl seem to help to increase the selectivity toward the E isomer but the stereochemical outcome is very dependent on the particular substrates you are using.
The selectivity of the HWE reaction is dependent on the Curtin Hammett principle. The stabilised anion addition to the ketone/aldehyde results in an open chain intermediate which collapses via a 4 membered oxaphosphetane. This addition is reversible and the open chain intermediate interconverts between the threo and erythro isomers potentially also by epimerisation. Addition of LiCl lowers the energy of the open chain intermediate, facilitating the interconversion between the isomers.
It will only increase your selectivity if the rate determining oxaphosphetane intermediate for the E - product is significantly higher than that for the Z - product. As your R group is a phenyl then it should help.
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