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Organic Chemistry Forum for Graduate Students and Professionals / Re: Sulfamidophosphonate synthesis via n-butyllithium: ratio of starting materials
« Last post by rolnor on Today at 05:37:15 PM »https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b01523
Granberg KL, J. Med Chem. 2019, 62, 3, 1385-1406.
One thing that attracted me to this method is that the ratio of the methyl sulfonamide to base to the chlorophosphate is 1:2:1; in other words, there is not the approximate twofold of excess of the methyl sulfonamide over the phosphorylating agent that I found in most other protocols. As to what is different, my speculation is that the steric bulk of this base prevents it from removing a proton from the product, which is more acidic than the starting material.
Or maybe the product becomes a TMS enol? I know that ethyl acetate is best lithiated by LiHMDS it gives better yields, better than LDA. Its interesting. I dont know if steric bulk stops deprotonation, maybe it does