[Guitarmaniac86]

Hi all.

I have a problem. My multistep synthesis towards a subclass of compounds is not working. I cannot go into details due to confidentialty. I will give you the jist though.

I started with a di-hydroxy ketone, protected with silyl groups and performed a Horner Wandsworth Emmons on it to get to the allyl  methyl ester I required. Subsequent reactions later I found the silyl groups too unstable to use so I switched to MEM groups due to their enhanced stability to reaction conditions later on. I chose silyl first because I thought they were more stable than MEM but I was wrong. I have now switched to MEM.

Problem: MEM groups are unstable to the HWE reaction conditions...

Protocol:

1.5 equivs NaH in THF and to it 1 equiv of methyl diethylphosophonoacetate is added dropwise and reacted for 1 hour at 25 C. 1 equiv of MEM protected ketone added dropwise react for 18 hours at 25C.

Work up: Quench water, add 5x reaction volume chloroform. Extract 3x with chloroform, wash combined chloroform layers brine, dry over mag sulfate. Column: gradient elution 100% Chloroform to 5% MeOH in chloroform.

Everything except the column is literature. I cannot fathom why the MEM group is unstable. I can wash out the phosphonate with water but I cannot purify the product and it looks like the MEM group is hydrolysing. MEM is supposedly stable to NaH and the phosphonate shouldnt interact with it... I dont think.

Any help is greatly appreciated.