I don't know why this isn't one of the main chemistry channel here around. The perfection of the explanations, the simplicity of the format and the passion behind it tells me that you need to be more recognized ahahsh
😀 thanks for the feedback - very much appreciated and keeps me motivated to make more videos. Please feel free to share my channel with your Chemistry friends 🙂
😀 thanks for the feedback - very much appreciated and keeps me motivated to make more videos. Please feel free to share my channel with your Chemistry friends 🙂
Criminally underrated channel for how clearly and succinctly you explain the logic behind the synthesis! Have you considered covering Noyori’s Ru-BINAP hydrogenation catalyst before? I think the mechanism is pretty interesting
Thanks for the feedback 😀 Very much appreciated! I certainly have the Noyari hydrog on my to-do list. I need to work out a way that can deal with explaining that mechanism in as simple terms as possible - it certainly is a bit fiddlier to explain than others!
I'm at the middle of my Chemical Engineering career and I'm taking Organic Chemistry, this video is so exciting and helpful to understand this topic as it is revolutionary. I love this.
Thanks for the feedback 🙂 very much appreciated. I have some similar styled videos on my channel if you fancy checking them out on a variety of molecules - this one’s quite a complex one. Definitely more on the way as I like making this type of video.
This was really eye opening! I just finished OC I in University and there occasionally was some talk about retrosynthesis, but having a concrete example of the highest quality really made it click (pun intended) for me. Even though I barely knew any of the reactions you used I could generally follow your explanation, even as a "beginner" in organic chemistry, and was delighted when I heard reagents/reactions I knew from my class. If you wanted to make these videos more interesting for a less educated audience however, I would suggest reading out more of the abbreviations like mCPBA, KHMDS and LDA. (
Thanks for the feedback 🙂 Glad you enjoyed the video. I’ve been trying to keep an eye out for abbreviations and improve my videos with the proper full reagents instead. I have a bit of a blind spot sometimes when I’m talking to myself into the microphone so a few have slipped through here. I remembered to do triflate and KHMDS actively. I’ll work on being more careful on this as it’s a good point. I’ll admit I made this video in a bit of a hurry last night to try and capitalise on Click Chemistry fever given the announcement on Wednesday 🙂
I have a retrosynthesis playlist too on my channel if you liked the approach. It’s been something I wanted as a focus for my channel as there wasn’t much out there when I looked. It’s my favourite topic to teach I think.
Wow, thank you very much for this video, very interesting as always! Could you make a video about the olefin metathesis and the catalysts used? Also everything with asymmetric catalysis is very much appreciated :)
🙂 thanks for the feedback! Metathesis already on my to-do list when I’ve worked out how to pitch it in an interesting way - will almost certainly use some sort of cascade synthesis as a way to demonstrate the different catalysts’ behaviour. Also with asymmetric catalysis - I’ve got a few more videos in the planning stages. I’m trying to build some resources that I can refer back to in fiddlier retrosynthesis targets.
Serious question. like many UA-cam presentations on Click Chemistry, this is very interesting and informative. What’s missing in all is what is truly unique and defining of Click Chemistry. Is it that azines and some alkynes only react significantly with each other and therefore stable with respect to competing reactions? Is that it? There are lots of high specificity cross-linking reactions in the world, especially if you allow catalysts.
Well, if you want me to be completely honest even defining "Click Chemistry" isn't so totally clear - I see the Nobel Prize awarding this year as much more a recognition of the fast and wide-ranging applicability of the AAC chemistry over the last 20 or so years (the type of cycloaddition itself of course was already known before that - cf. Huisgen). In organic chemistry, this chemistry has permeated loads of disparate branches of chemistry, biology, physics and materials science - way more so than say the organocatalysis chemistry that won the 2021 prize which largely hasn't found a significant footing in applicable science beyond some neat stuff in some parts of academia. I'd direct you to my other Click Chemistry video (ua-cam.com/video/RqA4xQ4ujWI/v-deo.html) for the other part of why this is useful - and it's really on the lego approach that the chemistry brings. Triazoles are pretty innocent when built into molecules reactivity-wise and so using them as connectors allows the very, very rapid assembly of libraries of compounds for testing in pharmaceutical, materials, etc. contexts to discover new technology faster. It's really the ultimate Lego approach that genuinely works reliably and in high yield and specificity without the hyperbole of research papers. The chemistry is tolerant of loads of functional groups too allowing an even more diverse library of compounds to be synthesised for exploration. The strained alkyne chemistry in this video specifically is one of the earliest examples of chemistry that can even work reliably in cellular environments - though there have been more developed since that would also fall under the umbrella term of "Click Chemistry" (e.g. tetrazines come to mind as the next step in the development of these ideas). From all of evolution to get to our current natural world, azides and alkynes are not found in biological systems. The presence of some S or N atoms in many key biological molecules can really screw over a lot of in vitro organic chemistry catalysts in vivo, and so make a lot of otherwise reliable chemistry not work, even beyond the fact of any toxicity factors in living systems. Hope this is a helpful expansion on my thoughts and understanding for you :)
Yes. Thanks. It is good to see a Nobel that is enjoyable if a little screwy. Good antidote to some of the weirdnesses and scandals. I learned about 1,3-dipolar additions in graduate school. Teaching biochemistry to medical and graduate students I emphasized the variations on what they learned in sophomore organic. I gave the cyclooxygenase reaction as an example of 1,3-dipolar additions but now I am not sure. Does it really fit the requirement? In the end, I emphasize how most of what we study biochemistry are only three types redox, acyl and phosphoryl transfer and nucleophilic addition to carbonyls and the reverse which is better received message. Anyway, thanks for excellent presentation and you answer.
Such a great video! ❤eThank you for this! But what is your opinion on using ozonolysis for the 8-members ring formation? Would the dangling alkene mess with ozonolysis?
Thanks 🙂 I’d imagine the ozonolysis was tried at some point but the dangling C=C would definitely be cleaved too, probably first in fact. The mild but importantly electrophilic oxidation is a nice solution that you don’t see so often.
Watching this channel, I noticed that I'm super rusty in basic organic reactions and by extension organic retrosynthesis. I did my MSc in an organometallic lab where my focus was on developing a methodology for the heterogenization of gold(I) catalysed hydroamination if 2-alkynylanilines and I didn’t get much time to revise these fundamentals. What textbook would you recommend for doing so? In my bachelors we used the Clayden one but it seems some people have a few bones to pick with this book.
One that’s quite good at doing the application of the Chemistry in Clayden (I don’t have any major problems with it as an early undergrad text btw) is the extended by Warren on more modern techniques and also the versions of “The Disconnection Approach” from the 2000s onwards are also more application focussed that might be what you’re looking for. To be honest, I’m a big fan of the Oxford Chemistry Primers - many are available on ebook subscriptions at unis as they’re out of print. But you can often find them for quite cheap on eBay too. They tend to summarise ideas very concisely if you’ve vaguely come across them in the past.
@@CasualChemistry Interesting, I was just sent The Disconnection Approach yesterday by a friend, so that's two ticks for this book. Thanks for the recommendations, I'll have a browse on b-ok ;)
Ah - yes you’re right! That was careless and never spotted that! No idea how that happened - I must have been distracted by highlighting the indole. The synthesis and discussion is correct though.
Probably just a bit easier on scale the way they did it. I’d imagine NaH was tried at some point - perhaps they got alkylation regioisomers, but I agree it would usually be safe on an indole if you wanted N alkylation
Great video and wonderful channel! I wanted to ask about using CsF for TMS removal. I would understand that it can be used for a TMS group as it is quite labile. But can it be used for deprotection of silyl ethers like TBDMS and such? Have never encountered it, so I am very curious to know
Thanks! 🙂 you tend to see CsF more commonly for cleaving a C-Si bond rather than O-Si ones. I guess it’s just a bit more niche, and probably more expensive than other common sources of fluoride. It’s a basic deprotection system I guess, and sometimes for deprotection of silyl ethers and acidic option might well work in higher yield.
Thanks! 🙂 you tend to see CsF more commonly for cleaving a C-Si bond rather than O-Si ones. I guess it’s just a bit more niche, and probably more expensive than other common sources of fluoride. It’s a basic deprotection system I guess, and sometimes for deprotection of silyl ethers and acidic option might well work in higher yield.
🙂 thanks. I use Microsoft whiteboards and OneNote, the record with any sort of screen capturing (they’ve all been similar). The pen setting is one thicker than the default for most of my videos when I realised it made things hopefully a bit clearer.
It’s normally referred to as a BARAC type compound. There’s a link to the original paper in the video description that I based the discussion on. Lots of variants also exist - I picked one that’s mainly just the core structure.
Sure - I have some in the preparation stage 🙂 I have some asymmetric synthesis videos on my channel already on some retrosyntheses and explanations of key reactions. In fact, I’m making those explainer videos specifically to make it easier for me to talk about more complex molecules in the future (and then I can refer back to them for details).
I don't know why this isn't one of the main chemistry channel here around. The perfection of the explanations, the simplicity of the format and the passion behind it tells me that you need to be more recognized ahahsh
😀 thanks for the feedback - very much appreciated and keeps me motivated to make more videos. Please feel free to share my channel with your Chemistry friends 🙂
😀 thanks for the feedback - very much appreciated and keeps me motivated to make more videos. Please feel free to share my channel with your Chemistry friends 🙂
Criminally underrated channel for how clearly and succinctly you explain the logic behind the synthesis! Have you considered covering Noyori’s Ru-BINAP hydrogenation catalyst before? I think the mechanism is pretty interesting
Thanks for the feedback 😀 Very much appreciated! I certainly have the Noyari hydrog on my to-do list. I need to work out a way that can deal with explaining that mechanism in as simple terms as possible - it certainly is a bit fiddlier to explain than others!
This is honestly such a fantastic video! Really glad it appeared in my recommendations. Cheers!
🙂 Thanks for the feedback - very much appreciated!
I'm at the middle of my Chemical Engineering career and I'm taking Organic Chemistry, this video is so exciting and helpful to understand this topic as it is revolutionary. I love this.
😀 Glad you enjoyed the video - the feedback is very much appreciated!
There are many steps which I would never have figured out on my own. This is some great mechanistical analysis and I'm glad you covered this topic.
Thanks for the feedback 🙂 very much appreciated. I have some similar styled videos on my channel if you fancy checking them out on a variety of molecules - this one’s quite a complex one. Definitely more on the way as I like making this type of video.
This was really eye opening! I just finished OC I in University and there occasionally was some talk about retrosynthesis, but having a concrete example of the highest quality really made it click (pun intended) for me.
Even though I barely knew any of the reactions you used I could generally follow your explanation, even as a "beginner" in organic chemistry, and was delighted when I heard reagents/reactions I knew from my class. If you wanted to make these videos more interesting for a less educated audience however, I would suggest reading out more of the abbreviations like mCPBA, KHMDS and LDA. (
Thanks for the feedback 🙂 Glad you enjoyed the video. I’ve been trying to keep an eye out for abbreviations and improve my videos with the proper full reagents instead. I have a bit of a blind spot sometimes when I’m talking to myself into the microphone so a few have slipped through here. I remembered to do triflate and KHMDS actively. I’ll work on being more careful on this as it’s a good point. I’ll admit I made this video in a bit of a hurry last night to try and capitalise on Click Chemistry fever given the announcement on Wednesday 🙂
I have a retrosynthesis playlist too on my channel if you liked the approach. It’s been something I wanted as a focus for my channel as there wasn’t much out there when I looked. It’s my favourite topic to teach I think.
Wow, thank you very much for this video, very interesting as always! Could you make a video about the olefin metathesis and the catalysts used? Also everything with asymmetric catalysis is very much appreciated :)
🙂 thanks for the feedback! Metathesis already on my to-do list when I’ve worked out how to pitch it in an interesting way - will almost certainly use some sort of cascade synthesis as a way to demonstrate the different catalysts’ behaviour. Also with asymmetric catalysis - I’ve got a few more videos in the planning stages. I’m trying to build some resources that I can refer back to in fiddlier retrosynthesis targets.
Serious question. like many UA-cam presentations on Click Chemistry, this is very interesting and informative. What’s missing in all is what is truly unique and defining of Click Chemistry. Is it that azines and some alkynes only react significantly with each other and therefore stable with respect to competing reactions? Is that it? There are lots of high specificity cross-linking reactions in the world, especially if you allow catalysts.
Well, if you want me to be completely honest even defining "Click Chemistry" isn't so totally clear - I see the Nobel Prize awarding this year as much more a recognition of the fast and wide-ranging applicability of the AAC chemistry over the last 20 or so years (the type of cycloaddition itself of course was already known before that - cf. Huisgen). In organic chemistry, this chemistry has permeated loads of disparate branches of chemistry, biology, physics and materials science - way more so than say the organocatalysis chemistry that won the 2021 prize which largely hasn't found a significant footing in applicable science beyond some neat stuff in some parts of academia.
I'd direct you to my other Click Chemistry video (ua-cam.com/video/RqA4xQ4ujWI/v-deo.html) for the other part of why this is useful - and it's really on the lego approach that the chemistry brings. Triazoles are pretty innocent when built into molecules reactivity-wise and so using them as connectors allows the very, very rapid assembly of libraries of compounds for testing in pharmaceutical, materials, etc. contexts to discover new technology faster. It's really the ultimate Lego approach that genuinely works reliably and in high yield and specificity without the hyperbole of research papers. The chemistry is tolerant of loads of functional groups too allowing an even more diverse library of compounds to be synthesised for exploration.
The strained alkyne chemistry in this video specifically is one of the earliest examples of chemistry that can even work reliably in cellular environments - though there have been more developed since that would also fall under the umbrella term of "Click Chemistry" (e.g. tetrazines come to mind as the next step in the development of these ideas). From all of evolution to get to our current natural world, azides and alkynes are not found in biological systems. The presence of some S or N atoms in many key biological molecules can really screw over a lot of in vitro organic chemistry catalysts in vivo, and so make a lot of otherwise reliable chemistry not work, even beyond the fact of any toxicity factors in living systems.
Hope this is a helpful expansion on my thoughts and understanding for you :)
Yes. Thanks. It is good to see a Nobel that is enjoyable if a little screwy. Good antidote to some of the weirdnesses and scandals. I learned about 1,3-dipolar additions in graduate school. Teaching biochemistry to medical and graduate students I emphasized the variations on what they learned in sophomore organic. I gave the cyclooxygenase reaction as an example of 1,3-dipolar additions but now I am not sure. Does it really fit the requirement? In the end, I emphasize how most of what we study biochemistry are only three types redox, acyl and phosphoryl transfer and nucleophilic addition to carbonyls and the reverse which is better received message. Anyway, thanks for excellent presentation and you answer.
Thank you very for your clear explanation
🙂 Thanks! Glad you enjoyed the video
I hope, I'll get the chance to do some click chemistry myself in the future. It sounds awesome.
🙂 Well it’s definitely on trend now if it wasn’t before. It’s always pleasing when something so simple in lots of ways can be so widely used.
Such a great video! ❤eThank you for this! But what is your opinion on using ozonolysis for the 8-members ring formation? Would the dangling alkene mess with ozonolysis?
Thanks 🙂 I’d imagine the ozonolysis was tried at some point but the dangling C=C would definitely be cleaved too, probably first in fact. The mild but importantly electrophilic oxidation is a nice solution that you don’t see so often.
Watching this channel, I noticed that I'm super rusty in basic organic reactions and by extension organic retrosynthesis. I did my MSc in an organometallic lab where my focus was on developing a methodology for the heterogenization of gold(I) catalysed hydroamination if 2-alkynylanilines and I didn’t get much time to revise these fundamentals. What textbook would you recommend for doing so? In my bachelors we used the Clayden one but it seems some people have a few bones to pick with this book.
One that’s quite good at doing the application of the Chemistry in Clayden (I don’t have any major problems with it as an early undergrad text btw) is the extended by Warren on more modern techniques and also the versions of “The Disconnection Approach” from the 2000s onwards are also more application focussed that might be what you’re looking for.
To be honest, I’m a big fan of the Oxford Chemistry Primers - many are available on ebook subscriptions at unis as they’re out of print. But you can often find them for quite cheap on eBay too. They tend to summarise ideas very concisely if you’ve vaguely come across them in the past.
@@CasualChemistry Interesting, I was just sent The Disconnection Approach yesterday by a friend, so that's two ticks for this book. Thanks for the recommendations, I'll have a browse on b-ok ;)
8:39 the bond cleavage lines are wrong arent they?
Ah - yes you’re right! That was careless and never spotted that! No idea how that happened - I must have been distracted by highlighting the indole. The synthesis and discussion is correct though.
I wonder why simply NaH wasn't chosen to deprotonate the indole N-H in this case. NaH wouldn't touch the C-H.
Probably just a bit easier on scale the way they did it. I’d imagine NaH was tried at some point - perhaps they got alkylation regioisomers, but I agree it would usually be safe on an indole if you wanted N alkylation
Great video and wonderful channel!
I wanted to ask about using CsF for TMS removal. I would understand that it can be used for a TMS group as it is quite labile. But can it be used for deprotection of silyl ethers like TBDMS and such? Have never encountered it, so I am very curious to know
Thanks! 🙂 you tend to see CsF more commonly for cleaving a C-Si bond rather than O-Si ones. I guess it’s just a bit more niche, and probably more expensive than other common sources of fluoride. It’s a basic deprotection system I guess, and sometimes for deprotection of silyl ethers and acidic option might well work in higher yield.
Thanks! 🙂 you tend to see CsF more commonly for cleaving a C-Si bond rather than O-Si ones. I guess it’s just a bit more niche, and probably more expensive than other common sources of fluoride. It’s a basic deprotection system I guess, and sometimes for deprotection of silyl ethers and acidic option might well work in higher yield.
@@CasualChemistry Thank you! keep doing what you are doing, its great!
What do you use to make these videos? And what pen settings? Thank you for the videos :)
🙂 thanks. I use Microsoft whiteboards and OneNote, the record with any sort of screen capturing (they’ve all been similar). The pen setting is one thicker than the default for most of my videos when I realised it made things hopefully a bit clearer.
@@CasualChemistry thank you, do you use a drawing tablet to write?
Yes - iPad with an Apple Pencil
What is the name of this compound
It’s normally referred to as a BARAC type compound. There’s a link to the original paper in the video description that I based the discussion on. Lots of variants also exist - I picked one that’s mainly just the core structure.
Sir plz make vedio on asymmetric synthesis
Sure - I have some in the preparation stage 🙂 I have some asymmetric synthesis videos on my channel already on some retrosyntheses and explanations of key reactions. In fact, I’m making those explainer videos specifically to make it easier for me to talk about more complex molecules in the future (and then I can refer back to them for details).
Great! Thanks.
😀 Glad you enjoyed the video!
Wow, just wow
🙂 Thanks for the feedback - much appreciated!
Seria excelente si pusieran subtítulos en español, saludos desde PERÚ.
I think they take a little bit of time to process on UA-cam but I think subtitles get translated over time.