This video was excellent!! It's my second day of advanced organic chemistry in undergrad and we are covering a David MacMillan paper exactly on this topic. This video helped me understand MUCH better. Keep up the good work!
Many thanks for the feedback and glad you enjoyed the video. I'll be getting on to more when my in-person teaching load decreases a bit in the next few weeks. I have lots of ideas on related topics/ideas.
Having gotten a chance to meet him I feel like the most shocking thing wasn’t even how incredibly smart and well he explains things. The shocking thing to me was how normal he felt and how thankful he was for all of the people who’ve helped him get to where he is. He’s the most incredible person i’ve ever met in my life and I’ll remember that forever.
Great video! Thank you very much! I'm still in High School and doing a presentation on asymmetric Organocatalysis and your videos already helped me a lot! I'd be very thankful if you could explain the Hydrolysis at the end (Minute 12:00) to me in more detail (please also tell me where the OHC group is coming from)? I hope you see this and can find the time to answer me. Have a great day!
Many thanks - glad the video has been helpful :) For the hydrolysis of the iminium ion to the aldehyde, I'll try and explain the steps in text below. You might find my video on Acetals useful as it's essentially the same mechanism with a N swapped in for a O. (R)(H)C=N(R)(R)+ gets attacked by water at the carbon (like a carbonyl) to give (R)(H)C(OH2)+(NR2) A proton is transferred to make the amine a leaving groups to (R)(H)C(OH)(NHR2)+ Then the oxygen lone pair comes down and kicks out NHR2 an an amine and forms the C=O double bond.
These videos are great! Very clear and concise explanations of some difficult concepts. After watching this, all of my confusion has vanished...fantastic!😃👍
Sure. I have some plans on my to-do list that will lean into these ideas quite heavily. I’m planning a variety of discussions on alkene formations with defined geometries etc
Many thanks for the feedback🙂 If you have a racemic mixture of enantiomers, on standard TLC they will be exactly the same Rf. If you had some special silica which has been functionalised with a chiral organic (for example certain sugars are common for this) you would see some separation of spots. This is how enantiomers can be separated on scale without too much effort by chiral HPLC, though that often requires optimisation for specific molecules. On normal TLCs, you would expect to see separation between spots for diastereoisomers with sensible solvent systems as these are chemically distinct isomers.
Fantastic video, I'm definitely going to watch some of the others on your channel and I'm looking forward to more content from you in the future :). I'm actually in the process of writing my third year literature project on MacMillan's catalysts and their applications in the synthesis of biologically active products. With regard to the extra pi stacking from the Ph due to the CH2, I think you've even went beyond what MacMillan explained in his papers.
Thanks :) Glad you enjoyed the video and I definitely have a list of new videos I want to make as soon as I can. Some of the rationalisation of these mechanisms can come much later after other research groups have played around with similar ideas, and then you can start inferring why certain other catalysts have e.g. decreased enantioselectivity over other.
@@CasualChemistry Glad to hear it! Yeah I suppose that makes sense, I'd guess computational studies would also need to be done to verify that those stabilising interactions actually do exist as well.
Thanks for your excellent explanation. In the minute 11.03, if the imminium does not have phenyl group, it will give two types of endo products... So it will give the final product with phenyl in the backward and CHO in the forward, and phenyl in the forward and CHO in the backward,,, is that what you mean?
Many thanks for the feedback - much appreciated 🙂 With your question: yes that is the point I’m trying to make there. If you don’t have the stereocentre on the organocatalyst, you get a mixture of the two enantiomers of the 1,2-syn diastereomer (as you’ve described) in a 50:50 mixture - a racemic product, rather than a preference for one enantiomer as intended
what about if we have the Z dienophile??... How the transition state will look like... I am kind of thinking exo product will be formed but confused about the transition state.\
Well I think it's not so clear so that's a recipe for just getting poor selectivity. I'm assuming that you mean a Z-geometry for the C=C bond (not the C=N bond): in which case there are a few things to think about. When a Z- alpha,beta unsaturated aldehyde is in the the presence of these catalysts, they might isomerise to E anyway by conjugate addition and subsequent rotation and E1CB-type mechanism. If you've locked in a Z-geometry (e.g. using a ring) I agree things are less likely to be so selective for endo:exo. There will be a fight over the electronic preference for pi-stacking and the steric constraints, which you could only work out by doing the experimental work and finding out. Often, if there is any fighting for selectivity ("mismatched" reactivity) the most likely outcome is just poor selectivity, which in this case would be low ee. Though I'm sure people have found ways to make particularly large steric effects that totally override the pi-stacking effect and favour an exo product - but arguably those situations aren't particularly general and so less useful as a methodology.
🙂 Many thanks for the feedback - glad you enjoyed the video. I have a few ideas for future videos on metal catalysis in a more general sense so I'll see if that reaction can fit nicely in one of those discussions.
I have a few videos pitched at different levels mainly through different undergrad stages, particularly some of the things in the retro synthesis playlist explain some key ideas. More of these videos are on the way. I hope you find them useful 🙂
Thanks for the feedback :) I assume you mean pKa here which I would estimate at about 15. You might find the Evans tables useful for this sort of thing: ccc.chem.pitt.edu/wipf/MechOMs/evans_pKa_table.pdf
![[Dome Refraction] Mark and David's work remains vital.](http://i.ytimg.com/vi/ihsezWvJzfY/mqdefault.jpg)
This video was excellent!! It's my second day of advanced organic chemistry in undergrad and we are covering a David MacMillan paper exactly on this topic. This video helped me understand MUCH better. Keep up the good work!
Many thanks for the feedback and glad you enjoyed the video. I'll be getting on to more when my in-person teaching load decreases a bit in the next few weeks. I have lots of ideas on related topics/ideas.
Having gotten a chance to meet him I feel like the most shocking thing wasn’t even how incredibly smart and well he explains things.
The shocking thing to me was how normal he felt and how thankful he was for all of the people who’ve helped him get to where he is.
He’s the most incredible person i’ve ever met in my life and I’ll remember that forever.
Your videos are by far the best I have seen in balancing detail with easy comprehension. Nice job!
🙂 thanks for the feedback - glad you enjoyed the videos!
Great video! Thank you very much! I'm still in High School and doing a presentation on asymmetric Organocatalysis and your videos already helped me a lot! I'd be very thankful if you could explain the Hydrolysis at the end (Minute 12:00) to me in more detail (please also tell me where the OHC group is coming from)? I hope you see this and can find the time to answer me. Have a great day!
Many thanks - glad the video has been helpful :)
For the hydrolysis of the iminium ion to the aldehyde, I'll try and explain the steps in text below. You might find my video on Acetals useful as it's essentially the same mechanism with a N swapped in for a O.
(R)(H)C=N(R)(R)+ gets attacked by water at the carbon (like a carbonyl) to give (R)(H)C(OH2)+(NR2)
A proton is transferred to make the amine a leaving groups to (R)(H)C(OH)(NHR2)+
Then the oxygen lone pair comes down and kicks out NHR2 an an amine and forms the C=O double bond.
These videos are great! Very clear and concise explanations of some difficult concepts.
After watching this, all of my confusion has vanished...fantastic!😃👍
Many thanks for the feedback - much appreciated 🙂
Great video! Please at some point can you show kinetic versus thermodynamic control in synthetic applications?
Sure. I have some plans on my to-do list that will lean into these ideas quite heavily. I’m planning a variety of discussions on alkene formations with defined geometries etc
good explanation sir, am curious about racemic mixture.
would you tell how the isomers in tlc?
does the spot closed to each other?
Many thanks for the feedback🙂 If you have a racemic mixture of enantiomers, on standard TLC they will be exactly the same Rf. If you had some special silica which has been functionalised with a chiral organic (for example certain sugars are common for this) you would see some separation of spots. This is how enantiomers can be separated on scale without too much effort by chiral HPLC, though that often requires optimisation for specific molecules.
On normal TLCs, you would expect to see separation between spots for diastereoisomers with sensible solvent systems as these are chemically distinct isomers.
Fantastic video, I'm definitely going to watch some of the others on your channel and I'm looking forward to more content from you in the future :).
I'm actually in the process of writing my third year literature project on MacMillan's catalysts and their applications in the synthesis of biologically active products. With regard to the extra pi stacking from the Ph due to the CH2, I think you've even went beyond what MacMillan explained in his papers.
Thanks :) Glad you enjoyed the video and I definitely have a list of new videos I want to make as soon as I can. Some of the rationalisation of these mechanisms can come much later after other research groups have played around with similar ideas, and then you can start inferring why certain other catalysts have e.g. decreased enantioselectivity over other.
@@CasualChemistry Glad to hear it! Yeah I suppose that makes sense, I'd guess computational studies would also need to be done to verify that those stabilising interactions actually do exist as well.
Great video, thanks!
You’re welcome 🙂
Thanks for your excellent explanation. In the minute 11.03, if the imminium does not have phenyl group, it will give two types of endo products... So it will give the final product with phenyl in the backward and CHO in the forward, and phenyl in the forward and CHO in the backward,,, is that what you mean?
Many thanks for the feedback - much appreciated 🙂 With your question: yes that is the point I’m trying to make there. If you don’t have the stereocentre on the organocatalyst, you get a mixture of the two enantiomers of the 1,2-syn diastereomer (as you’ve described) in a 50:50 mixture - a racemic product, rather than a preference for one enantiomer as intended
Perfect videos, much appreciated!
Many thanks 🙂 Glad you’ve enjoyed them
what about if we have the Z dienophile??... How the transition state will look like... I am kind of thinking exo product will be formed but confused about the transition state.\
Well I think it's not so clear so that's a recipe for just getting poor selectivity. I'm assuming that you mean a Z-geometry for the C=C bond (not the C=N bond): in which case there are a few things to think about. When a Z- alpha,beta unsaturated aldehyde is in the the presence of these catalysts, they might isomerise to E anyway by conjugate addition and subsequent rotation and E1CB-type mechanism. If you've locked in a Z-geometry (e.g. using a ring) I agree things are less likely to be so selective for endo:exo. There will be a fight over the electronic preference for pi-stacking and the steric constraints, which you could only work out by doing the experimental work and finding out. Often, if there is any fighting for selectivity ("mismatched" reactivity) the most likely outcome is just poor selectivity, which in this case would be low ee. Though I'm sure people have found ways to make particularly large steric effects that totally override the pi-stacking effect and favour an exo product - but arguably those situations aren't particularly general and so less useful as a methodology.
Very nice, very helpful.
🙂 Thanks
excellent💖💖
Such a brief And Nice explanation! Thank you sir 🤗. Please make a video on fukuyama coupling 🙏
🙂 Many thanks for the feedback - glad you enjoyed the video. I have a few ideas for future videos on metal catalysis in a more general sense so I'll see if that reaction can fit nicely in one of those discussions.
Sir , please make a video basic organic chemistry level in undergraduate degree student.
I have a few videos pitched at different levels mainly through different undergrad stages, particularly some of the things in the retro synthesis playlist explain some key ideas. More of these videos are on the way. I hope you find them useful 🙂
@@CasualChemistry thank you
Thanks alot💕💕
You’re welcome 🙂 glad you enjoyed the video
Hey I’m a big fan, please help me find the PH of Phenacetin 😭 please!
Thanks for the feedback :) I assume you mean pKa here which I would estimate at about 15. You might find the Evans tables useful for this sort of thing: ccc.chem.pitt.edu/wipf/MechOMs/evans_pKa_table.pdf
Nice
Many thanks 😊 glad you enjoyed the video