[nottingham]

the intermediate alcohol is obtained by deprotection of the silic protecting group using TBAF. then I did the Swern oxidation in a small scale and I get the desired product in excellent yield. But when I scale up the reaction, no desired product was obtained. I am not sure what caused the failure of this normal reaction. Do you think the  residue of TBAF, which is difficult to remove during the workup or chromatography, will decompose the intermediate of Swern oxidation reaction.

[GSR]

Hi,

TBAF might play a role as a fluoride source and an electrophile (in E2 or SN2) type reaction. there is also a possibility of forming side products such as hydrogen, 1-butene, n-butane, and tributylamine, which I feel is difficult to isolate from the desided produt.

GSR

[DavidW]

Hmm if it works well in small scale, then perhaps TBAF may not be the (only) problem.  My experience with large scale Swern is that keeping the internal temperature at -78C is pretty important.  If I remember the original literature correctly, the activated complex can decompose above -40C.  A large scale reaction would take a longer time to cool to -78C.  Also, is your product stable?

You may also consider the Parikh-Doering oxidation with SO3-pyridine.  I find that to be very effective in large scale oxidation and gives comparable yields as the Swern oxidation without the temperature issue.   

[movies]

You might also look for formation of the MTM (methyl thio methylene) ether of your alcohol.  It's a common side product in Swern reactions.