They think it's all Overman... It is now! - Organic Chemistry Retrosynthesis

[@CasualChemistry]

It should be noted that the intention of this video is educational rather than the most practical possible, and also to build on the common undergraduate-level topics from previous videos on this channel. I figured the general strategy here might be new to people. I can't deny that there are other very good routes to this molecule - particularly those including Ellman chemistry using chiral auxiliaries on imines and Petasis boronate chemistry with chiral catalysts. I'd encourage people to look into these methods for the synthesis of chiral amines in high ee, and I'm sure these methods will come up in future videos on this channel.

[@shaunkelly7223]

nice video and far more complex chemistry involved for such a small and innocent looking target

[@CasualChemistry]

Thanks :) Fully asymmetric syntheses can be like that because you're having to worry about more factors than just yield I guess. In my experience, getting both the ee and the yield being good is a very frustrating part of this type of research - so you have a quite restricted toolkit for retrosynthesis.

[@Grak70]

Magical conversion of CF3 to CCl3 with KOH at the end there! :-) Thank you for continuing to post these. Retro synthesis was my favorite part of organic undergraduate. I learn so much chemistry I was never taught watching your videos. 💕

[@CasualChemistry]

D'Oh! Well spotted! I must of got carried away being on the home straight and annoying I didn't spot that in editing. I have my next few planned out but finding the time to make them has been tricky recently. It means a lot to me that people find these useful :)

[@nikitakarpov7534]

@@CasualChemistry and Arbuzov, not Arzubov ;) Enjoyed a lot, thanks!

[@CasualChemistry]

Oh dear - I do get that one muddled occasionally… whoops!

[@AlligatorKrokodil]

3:16 as far as i was concerned cross conjugated means you need to have 3 double bonds and here we only have two and an amine instead of an imine

[@CasualChemistry]

Hmm - I’d never heard of the definition of cross conjugation being restricted to double bonds, but to pi systems. So here the sp2 N atom being the third pi system. You certainly hear the phrasing a lot in heterocycle reactivity settings and in organic electronics for this sort of thing.

[@SavithaOrganicChemistry]

Excellent. From your each video I am learning new strategies. Amazed at your knowledge of organic chemistry.

[@CasualChemistry]

Glad you enjoyed the video 🙂 and happy that people are picking up new ideas from them

[@samuelluofficial]

bro your chair conformations are so nice looking! mine look like garbage every time I try to draw one...

[@CasualChemistry]

😊 Thanks. They’re from a lot of practice though

[@romanpolanski4928]

For the final part of the retrosynthesis I'm surprised you didn't suggest a classical crossed aldol reaction between 3-trifluoromethylbenzaldehyde and acetone - much simpler and cheaper than cuprate chemistry.

[@CasualChemistry]

There are certainly lots of ways of making the early intermediates and different routes to take. You'd need to add a hydrogenation step if you went in the aldol direction.

[@romanpolanski4928]

@@CasualChemistry Sorry, I forgot about the hydrogenation!

[@levtrot3041]

Why not just LDA+aldol the long ketone with CyCH2O ?Am i missing something ?

[@CasualChemistry]

Would also work fine. Would need to engineer the E1CB elimination as a second step. HWEs are just super easy in practice and could well be higher yielding.

[@levtrot3041]

@@CasualChemistry :DD

[@MultiDresse]

Nice video and good to see some named reactions🙂

[@CasualChemistry]

🙂 thanks. Those names reactions get everywhere

[@iliddle96]

Great video! Thanks for sharing

[@CasualChemistry]

🙂 Glad you enjoyed

[@redsuton8079]

Hi, can you please make a synthesis of aluminate coupling agent ???? there is basically no papers on it and it will be fun to have a look at it

[@CasualChemistry]

I'm assuming you mean in a polymer/materials sense here? I'm afraid that's a little outside my expertise if so. If you mean using aluminium organometallics, I do have a bit of a discussion of carboalumination chemistry in this video: kzbin.info/www/bejne/ZnixdYmBad9on5o

[@dlvivlviv]

Wittig would work perfectly, the reagent is well stabilized, and geometry can be predicted.

[@CasualChemistry]

Well yes, it would probably be absolutely fine, but the Wittig would likely be much more of a practical hassle in the lab than an HWE. I've always found that reaction to be a superior upgrade for C=C formation like this, particularly as HWE reactions are more likely to be fine with more complex setting than the one here. I guess by putting "enolate chemistry" I was using the broad term to describe the topic. The old school way of mono-bromination would be via the enol in acidic conditions. However, other controlled ways of doing this using NBS are possible using enolate equivalents (rather than reversible formation of the bare enolate with eg hydroxide ions)

[@ProfessorWaltherKotz]

Leopold Horner would be proud

[@CasualChemistry]

🙂

[@derenjoy3r]

Ayy