[kriggy]

Hi guys, im trying to run Ru catalyzed metathesis of Fmoc-allylglycine-OMe and allylamine. I read that amine containing compounds are b$*%( for metathtesis but also that its been done with various protecting groups.

Anyway, I run the reaction with Trityl-allylamine with Grubbs 2nd gen in refluxing DCM and then with Hoveyda-Grubbs 2nd gen in relfuxing DCM but I have hardly any conversion and LCMS only shows some traces of isomerized allylglycine (same m/z and very close Rt to the starting material) but no product at all.

I was wondering if you have any tips for me? I think I could make the compound in a different way but metathesis is just one step from available materials. Also, Im not sure if my technique is good: I use dry DCM, mix everything, sparge with N2 and heat in oil bath but im not exactly sure how sensitive the reaction is. After adding HG catalyst, the reaction turns green and then light brown in few mins and darker brown-black overnight.

Thanks

[rolnor]

You should probably use Boc or similar Trit is very large and does not remove the basic caracter of the allylamine.

[rolnor]

Also, it seems like a pretty simple compound, can you make it without metathesis?

[kriggy]

Also, it seems like a pretty simple compound, can you make it without metathesis?

Enantiopure is difficult, metathesis is the fastest way IMO and the starting materials are cheap enough. But im willing to accept any ideas. I was considering some wittig approaches but they seem quite long in terms of steps. CH activation of alanin might be possible but does not seem reliable and require bunch of optimizations.

Anyway, thanks for the idea. I used Boc and I have some 40% isolated yield. Its good enough but I have terrible conversion of my starting material. I tried higher temperature which made it even worse. 10% HG-2nd gen catalyst which is already high loading.. Im wondering what is going on, maybe the catalyst is poisoned by the substrate anyway? Is there possible way around it? Add batchwise maybe? Or having bis-boc protected amine?

[rolnor]

You could try to add the catalyst in small portions? Exclude air.