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Chemistry Forums for Students => Organic Chemistry Forum => Organic Chemistry Forum for Graduate Students and Professionals => Topic started by: Babcock_Hall on February 01, 2024, 12:52:03 PM

Title: Phenolic hydroxyl in Horner Wadsworth Emmons reaction
Post by: Babcock_Hall on February 01, 2024, 12:52:03 PM
https://www.cell.com/cell-chemical-biology/pdf/S1074-5521(98)90169-7.pdf
Bogyo and collaborators (Chemistry & Biology June 1998, 5:307-320) used a diethyl sulfonylphosphonate which had a phenol group on sulfur in a Horner reaction.  The phenolic -OH was not protected.  The substrate was a peptide aldehyde, and the base was NaH.  This paper cites a 1997 paper for the reaction conditions, but the 1997 paper does not provide a detailed protocol.  I am thinking about trying a reaction in which the aldehyde would have an unprotected hydroxypyridine group, and I am wondering whether the reaction above is a relevant precedent.  Both the ideal choice of the base and the number of equivalents are of interest.
Title: Re: Phenolic hydroxyl in Horner Wadsworth Emmons reaction
Post by: Babcock_Hall on February 02, 2024, 05:58:27 PM
I neglected to explain a few things in my previous comment.  The hydroxyl group was para with respect to the sulfonyl group in the paper I cited in my previous comment.  We are attempting to synthesize a vinyl sulfone from 3-hydroxyisonicotinaldehyde.  Although we were able to get a low but acceptable yield using an isomeric aldehyde in a Knoevenagel reaction, we have only obtained a few milligrams of the product with this aldehyde, which is not enough for our collaborators to use.  That is why we are considering using a Horner Wadsworth Emmons reaction.
Title: Re: Phenolic hydroxyl in Horner Wadsworth Emmons reaction
Post by: amorapotter on December 25, 2024, 10:42:57 PM
The Bogyo study is a good starting point, as it shows the feasibility of using unprotected phenols in a similar reaction. However, given the added complexity of your substrate (hydroxypyridine), conducting systematic trials with both NaH and milder bases like DBU is advised to identify the optimal conditions.slope (https://slopeio.org)

Would you like assistance in designing a detailed experimental plan for your trials?
Title: Re: Phenolic hydroxyl in Horner Wadsworth Emmons reaction
Post by: Babcock_Hall on January 12, 2025, 10:15:47 PM
We are moving in a different direction right now, but if that changes, I will return to this thread.