Evans Auxiliaries and a Friend for Aldol Reactions
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- Опубликовано: 7 сен 2024
- Using chiral auxiliaries for asymmetric synthesis - diastereoselective aldol reactions with chelating enolates and cyclic transition states. The transition states can be constructed using the Zimmerman-Traxler model.
Motivation in my previous video:
• Making a Synthesis Ste...
Following selective enolisation, either by hard enolisation with strong bases such as LDA or by soft enolisation methods using a Lewis acid and a weak base, a stereodefined enolate can react with aldehydes in an aldol reaction. Both the nucleophile and electrophile are prochiral and so we form two new stereocentres from this reaction. The reaction is diastereoselective. The diastereoselectivity can be increased by using chelation into a six-membered ring transition state, in which big groups prefer to go equatorial.
A chiral auxiliary can be used to select further for a particular combination of stereocentres that can be formed in this reaction. The chiral auxiliary adds another level of diastereoselectivity and the Evans auxiliary can lead to very high d.r. (diastereomeric ratio). When the aldol reaction is complete, the chiral auxiliary can be cleaved carefully, separate by chromatograhpy, and recycled.
Another type of chiral auxiliary is the lactate auxiliary which uses a stereocentre derived from lactic acid. Both enantiomers of lactic acid are available in the chiral pool. There are similar types of diastereoselectivity observed with these chiral auxiliaries and this topic will be expanded upon in my next video.
REFERENCES
Evans Aldol Reaction:
J. Am. Chem. Soc. 1981, 103, 8, 2127-2129
doi.org/10.102...
Lactate Aldol Auxiliaries:
Tet.Letters Vol. 35. No. 48, pp. 9083-9086. 1994
doi.org/10.101...
FURTHER DETAIL
Felkin-Anh Model:
• Ultimate Guide to the ...
Boron aldol reaction:
• Boron Aldol Reaction -...
Another example of use of chiral auxiliaries:
• Retrosynthesis 2 - Org...
#chemistry #organicchemistry #education
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Love how your videos are always easy to follow yet detailed, keep it up mate
Thanks 🙂 More in the pipeline including an extension on this one.
I agree. The way Mr. CasualChemistry builds it up is impressive, and it is clear that he really understands and sees organic chemistry. The collection of Paterson aldol methodology is powerful and especially suited for polyketide products. The syn/anti-switch with Bn/Bz, respectively, is something that I had forgotten about. I only remembered the Bz/anti (probably due to the formyl hydrogen bond). Thank you for your efforts and I look forward to the next video!@@CasualChemistry
Sounds like you might have an idea where the next video will pick up from. Got some other stuff I want to touch on. The next video will hopefully wrap up a loose trilogy of connected topics
Thank you for providing such a well-visualised explanation!!
🙂 Thanks
Thank you from France ! I really appreciate the clearity of the message
Thanks 🙂 Took a bit of time to work out what I wanted to say on this topic and this feedback is very much appreciated
Was waiting for your video. Thanks
You’re welcome 🙂 I’ve re-recorded this a few times to get the message I wanted to send across. Ended up being longer than expected (!)
This is by far the best explanation of this material I’ve ever seen! Thank you for making this video, this’ll help so much with my syntheses!
🙂 Thanks. It’s been bugging me for a while that this topic can get confusing if lecturers try to rush explanations. I’ve been meaning to make this particular video for ages
Very informative, excellent!
🙂 Glad you enjoyed
Nice to see that you draw what Stuart Warren called atom-specific curly arrows - as seen for the aldol reaction at 0:44.
I might have unconsciously picked that up from him in lectures back in the day 🙂 Very useful in complex molecules for sure so very much a habit
Wonderful!
Extraodinary!
You really understand chemistry!
Too often people thinks it's Always " by Heart"
🙂 Thanks. Definitely one of my motivations for starting this channel is to play around with techniques and models to show memorisation isn’t the best approach to the subject. Unfortunately a lot of teachers encourage by-heart learning for organic chemistry but it hinders getting to the underlying principles.
@@CasualChemistry if i had a chemist professor as you... On France WE have the same issues. Some awsome teacher teaches us how tro thinks and proceed ans other feeds us with hundred of reactions and expects students to know everything
@geff9115 probably how they learnt it themselves and just assuming that’s the best method. That’s a shame. Organic chem is more like maths I think - learn the methods well and you can solve more things
Something that I never touched on
Thanks man, I really did need that, although I don’t know if I have much motivation to get through it but I will try I suppose
🙂 A topic I wanted to make sure was out there on RUclips for people as I see it getting muddled a fair bit when teaching
this is the good shit that i needed so badly, thx man
No worries 🙂 Mean meaning to get something out there on this topic for a while
Love the thumbnail
Seemed appropriate for the 1980s-themed chemistry 🙂
you guys are not good content creator, but GREAT content creator
🙂 Thanks!
Doesn't the oxygen of the carbonyl on the oxazolidinone also co-ordinate to the metal centre making the dipole moments the same for the enolate and the carbonyl of the oxazolidinone? Why does the opposition of dipole moments outweigh the potential for additional co-ordination to the metal centre?
I guess it depends on the metal...
Absolutely the right idea - it does depend on the metal. I’m going to revisit this in my next video. In this case Li is too small to do the 3-way chelation you mention. Boron with two alkyl ligands has no space left to do it either. But when you start branching into using transition metals or later p block elements, there’s a few other things that you can do including this 3-way chelation.
Hello, I have a question at 3:18 , how do you visualise and draw the bonds the way you do? I try so hard to do it and i cant understand which bond should be a wedged bond or a hashed bond. Another example is 7:50. Do you have any advice?
Sorry for slow reply - I was busy finishing my dissertation. Back on to the videos now 🙂 I’m afraid there’s not an easy answer here other than a lot of practice on my part. I find it easiest to try and get as much of the molecule as possible in the plane of the paper - and definitely keep all the reaction arrows in the plane too else the 3D gets messy.
Playing with a tetrahedron model can be a good idea too so you can visualise that important shape in several ways. Eg both like a pyramid but also like a triangle with a pointy out bit from one perspective. And from another perspective like two lines joining two atoms, one behind the other, at right angles.
Anyone got a 3D animation of this to help me connect the 2D diagram to the 3D shape?
I’m not aware of a specific one but I could have a go at making one as a Short video - though my animating skills aren’t great but I could add some extra steps showing rotations/other models to help? Do you have a timestamp for a bit that you found particularly tricky for me to focus on?
@@CasualChemistry all those curvy arrows this coming from this way, or get that from that and I'm only seeing a 2d plane... But I know pi bonds are sticking up and downish , right, or are they coming out of the page from the plane you wrote the arrows on?
There's a lot of new stuff, 45 years since I was in school.
My college level is high school stuff now ....
For me I usually see carbon skeleton structures and usually use that to rationalise diastereoselectivity and enantioselectivity, such as on cyclopentenone conjugate additions maybe, but yes you do need to understand 3d structures to be able to rationalise diastereoselectivity on some other reactions, particularly pericyclic reactions. An example would be the claisen reaction, which could pass through a chair or boat like transition state depending on the substrate which the chair and boat TS lead to different diastereoners
Use a modelling kit to visualise I guess, I’ve never got the time to use my own one
me, a high school student, watching this: :0
🙂 Spoilers for quite a way after high school