[darkdevil]

Hi there,
DO you think I can Lithiate the N-atom in indigo? and then adding an alkyl halide to alkylate the two N positions?
This is a related paper.. but they did not start with a vinylogous amide like I do. But I guess they should be similar?

https://www.google.com.hk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&ved=0CDoQFjAB&url=http%3A%2F%2Fjournal.kcsnet.or.kr%2Fmain%2Fj_search%2Fj_download.htm%3Fcode%3DB070120&ei=LbI5UqOyCobYige8oICQDw&usg=AFQjCNGNOjL_20BLTJ3l3dawkstBKvtELw&sig2=ak_Bl04LqnBZXcYFODJEXg

[opsomath]

A few thoughts.

1. THF is likely a poor solvent for this system, you want a strongly chelating solvent that can expose the nucleophile. I see that you are going with DMF, which may be a good one.

2. I'd seriously think about PTC, especially with that known to be a method that's worked before. Try fluorene alkylation conditions (conc. aqueous KOH, toluene, alkyl halide, phase transfer catalyst, 100°C) first. The PTC I used was Aliquat 336 mostly, but CTAB or various others, or even Lysol, should work.

[clarkstill]

I agree with opsomath; PTC is excellent for giving the reactivity of the naked, unsolvated anion.  I've always used NBu4Br and NBu4I with conc KOH and toluene at room temperature for alkylations, but they were probably not as challenging as the one you're attempting so heat might help too.

[darkdevil]

Thank you very much for the suggestions. Hope the PTC method would work in toluene.
I will try it in the coming weekend! Frustrated... but I believe it will work some times! THank you again..and I will keep this updated  =)

[opsomath]

If the PTC works, you will never go back. Workup and purification is dramatically easier for everything, if the reaction works at all.

[clarkstill]

And no need for dry glassware