Staudinger Reactions - Bioothogonal before Click Chemistry

The original bioorthogonal chemistry using azides and their reaction phosphines to form aza-ylids, which can do bioconjugation reactions and other useful transformations in organic synthesis.
The aza-ylid (aminophosphorane) generated can react directly with water in a hydrolysis reaction to give an amine product. The reduction of the azide to the amine under these conditions is mild and tolerant of many other functional groups, whereas a hydrogenation or borohydride reduction might not be. The only by-product it triphenylphosphine oxide which is inert, separable and provides a strong enthalpy driving force.
The aza-ylid can also react with carbonyl functional groups. If it reacts with a ketone or an aldehyde, you make the imine product, that can be useful in general synthesis of nitrogen containing molecules, including heterocycles.
#chemistry #organicchemistry #science

[@liammccreary2941]

I really appreciate your work here! These videos are some of the most beneficial on TH-cam for me. I’m a medicinal chemist and reminding myself of some of the less commonly used or older reactions really helps with creative drug design! Thank you and keep up the excellent work

[@CasualChemistry]

:) Thanks - that's really cool to hear and I'm glad the videos have been helpful.

[@campbeja001]

Good job

[@CasualChemistry]

🙂 Thanks

[@dlvivlviv]

Great!
You also forgot traceless Staudinger ligation. It is quite useful too

[@CasualChemistry]

🙂 Thanks. Definitely not an exhaustive list of what you can do with the chemistry. But hopefully a useful summary I can use to refer back to in future videos

[@palamalama]

Awesome video! How stable are those nitrogen ylides? Can they be isolated or is it always done in one pot?

[@CasualChemistry]

You don’t normally see them isolated but perhaps there are examples if you have say a well conjugating R group. The formation in situ though is pretty mild and selective which is nice.

[@chemistry-experiments78]

Isn't Staudinger that guy that exploded Na and CCl4?

[@CasualChemistry]

Maybe - I don't know I'm afraid. He's certainly more associated with this phosphines and azides reactions in the synthetic chemistry world.

[@liammccreary2941]

Btw what’s your chosen way of separating out the TPPO byproduct?

[@CasualChemistry]

Hmm, depends on the circumstances. In the past, a switch to diethylether as the polar solvent component in columns has been pretty successfully, particularly after removing most of it by trituration beforehand. There was a cool procedure published recently (can't quite remember when but in the last year or so) showing an effective removal method using Zn2+ salts. I haven't tried it myself though.