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Sulfamidophosphonate synthesis via n-butyllithium: ratio of starting materials

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rolnor:
Great! Maybe there is a cool explanation why the LiHMDS is better to use

Babcock_Hall:
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.

rolnor:

--- Quote from: Babcock_Hall on May 17, 2024, 09:42:36 AM ---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.

--- End quote ---

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

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