This Surprising Synthesis Will Teach You Organic Chemistry (Rauvomine B)
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- Опубликовано: 26 июл 2024
- 🤯 "Protecting groups protect" - Makes sense, right? Well, until it doesn't. In this video, we will learn more about this, and explore interesting organic chemistry reactions by studying the total synthesis of rauvomine B (note: not peer reviewed yet so it could be all made up).
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00:00 Surprises with protecting groups
00:38 Rauvolfia natural products
02:16 Retrosynthesis of rauvomine B
03:42 Forward synthesis: CBS reduction/ kinetic resolution, allylation
05:57 Allylation deep dive
08:21 Pictet-Spengler, selenoxide elimination, ring closing metathesis (RCM)
10:39 Pivotal step: Cycloaddition, Rhodium-catalyzed cyclopropanation, hydrolysis
11:42 The effect of the Boc protecting group
14:50 Conclusion and outlook
Key references:
- 10.26434/chemrxiv-2024-jp63v-v2 | Total Synthesis of (-)-Rauvomine B via a Strain-Promoted Intramolecular Cyclopropanation (Preprint)
- Org Lett 2017, 19, 3998 | Rauvomines A and B, Two Monoterpenoid Indole Alkaloids from Rauvolfia vomitoria
- JACS 1992, 114, 6858 | Isomerization of (pi-allyl)palladium complexes via nucleophilic displacement by palladium(0). A common mechanism in palladium(0)-catalyzed allylic substitution
- Org. Lett. 2019, 21, 8473 | Divergent Access to Histone Deacetylase Inhibitory Cyclopeptides via a Late-Stage Cyclopropane Ring Cleavage Strategy. Short Synthesis of Chlamydocin 
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We're back with a more chemistry-focused video. Is it too challenging, easy or just right?
Thanks for watching and a special shoutout to the channel members!
www.patreon.com/totalsynthesis; instagram.com/totalsynthesis_official/
The effort put in the visuals for this video is admirable. Amazing work!
@@yin-fire3263 Thank you! Appreciate it :)
TOTAL SYNTHESIS DROPPED
Babe wake up
@@totalsynthesis😏
@@totalsynthesis whats that babe?
Damn, with these videos I always notice I really dont know a lot about organic chemistry after all and start asking myself whether I should have studied more OC during my Biochemistry degree lol
great video btw
Thank you! You can always live out your alternate you with these videos haha
I m having the same thoughts... however im about to start my phd in oc after my master in biochem lol
Good luck!
bro just casually explained complex total synthesis like it's his everyday problem. Great video btw
😂😂 thanks man, appreciate it
Thank you for yet another interesting video about total synthesis. This one is quite full of undergrad organic chemical reactions, but still has a nice twist in the end. About the isomerization in allylic substitution, the Pd-allyl complex is able to undergo several isomerization reactions known as SAE (syn-anti exchange) and AAR (apparent allylic rotation), and these isomerization reactions can be inhibited or promoted by judicious choice of solvent and ligands. So the Tsuji-Trost reaction has some good intricacies in it!
Thanks for your comment and the insights!
"Triangles are my favorite shape, three points where two lines meet." - Alt J clearly is describing his love of cyclopropane containing molecules 😊
Thank you for these. Your quality is very recognized and appreciated.
Thanks so much!!
Incredible video, I love your immense detail and explanation of the mechanisms!
Thanks so much!!
Beautiful chemistry mate, syntheses like this one are a true art.
Fully agreed! Thanks for the comment :)
this could be a perfect class for undergraduates.
Shoot I already saw it 😭
Also that other comment where I said I was tired of doing CBD I meant looking at synthetic sequences not doing cannabidiol lmao
That cis-trans tertiary amine fused 6 membered thing was quite cool though in order to trigger the cyclopropanation, along with avoiding Diazo compounds
Wake up babe Total Synthesis just posted 🙂↕️🙂↕️
I love this channel
The channel loves you 🔥
My maaan 🔥
This just reinforces my decision to major in physics and not OC
Hahaha, to each their own
I love you total synthesis le sigh
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Nice video as always! But seeing an equilibrium being depicted with a resonance arrow did hurt my eyes
Ahahah I sometimes miss small stuff like this in my video creation frenzy
1st minute: vomitoria hahahaaaaa
the rest of the video: ok brah i'll be back just lemme watch the whole course of organic synthesis ...
God this channel is relaxing
Chemistry rambling ASMR 😂
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Sweet
Just like you
i love your videos ahah #keephandling
Thanks!
Lots of learning right from the start. The racemization due to tetrakis Pd was a pleasant Aha ! as this was briefly mentioned in Hegedus' book. The last part regarding BOC and the 3d structures were over my head, I will have to take another look at it. Do you suggest any reading material for developing intuition for this kind of result? One more thing after the click chem- : is the equilibrium of the triazole ring with this open chain isomer only for electron deficient triazoles as this is a much sought out design feature in Med chem and one would not want the ring opening up in vivo?
Great question. My guess is it's only significant for electron-deficient triazoles and at elevated temperatures (in this case at 80-100 °C). Due to fast and highly favored subsequent reactions, any ring-opened triazoles react away, shifting the equilibrium towards that side. But I haven't gone into literature to understand more about this ring opening (I was pretty surprised myself). So that might answer your first question as well haha - seeing many random examples always helps, but we will all get surprised at some point! This is one of these things you can't really predict unless you know about it.
@@totalsynthesis Thanks, I wonder if a triazole (not electron poor) opened up (at high T) in one of my projects and hence the activity of the "molecule" went to nothing !
Any suggestions for developing retrosynthetic skills? The first disconnection itself was informative to me - that's the level I am at !
@@GG-fd31 One of the OG books for retrosynthesis is 'Logic of Chemical Synthesis' by Corey. This one really goes into strategy and efficiency. Obviously this requires some 'baseline' understanding of e.g., what are the, let's say, top 5 reactions to make cyclopropanes (or cyclobutanes). Not sure if there is a book that spells out all of this in an exhaustive manner (I'm actually working on one myself at the moment that could help some students).
@@totalsynthesis I look forward to your book. When do you expect it to be published?
@@GG-fd31 Thanks! I really don't know, I already started with the idea more than a year ago but have now said I might want to get it through by around end of this year. I'm aiming to create: summary/ overview of key topics (so starting kinda high school level almost), organic reaction toolkit incl. protecting groups, high level retrosynthesis strategy, and some case studies (total synthesis + pharmaceuticals)
aaand a couple of "mock exams" (all with solutions and explanations). Overall it will have like 200+ individual problems to solve (some smaller questions, some more complex)
8:52 According to the Clayden textbook the spiro intermediate followed by migration is actually the more likely and common path (chapter 29 page 746) because the carbon at the 3-position is always the stronger nucleophile.
I just opened my book and in that example, it's important that they have a csp3-OH(BF3) as the electrophile. This means the spirocyclization is a 5-exo-tet closure (so no issues). However, in our example, it would be 5-endo-trig which is disfavored kinetically. So the Clayden example can't be compared 1 to 1. As far as I understood, the general mechanism is not understood, and likely depends on the starting materials (see Angew. Chem. Int. Ed. 2011, 50, 8538 and references therein).
@@totalsynthesis Fair enaugh. Guess I need to take a closer look at it. But not at 11pm after a few glasses of Whiskey :D
😂😂 cheers brah
Imma be real as a organic chem grad i have no clue what the hell just happened
Wow. Organic Chemistry: 70% vocabulary 30% field practice
The use of strange lingo is surely off the charts in organic chemistry
Synthesis is the most fun you can have with your clothes on. The power, the *POWER_!_*
Never seen a allylic cation complexed to transition metal before
Palladium baby!
Anion!
@@totalsynthesis - love the channel. Could I recommend the process development of sildenafil as a future topic? The full story is in Org. Process Res & Dev.
It’s simple chemistry but the choice of reaction conditions and optimisation are really fascinating - the product crystallises straight from the final reaction step in finished purity. They won an award for green chemistry for the development of it.
Thanks for your comment and the suggestion! You mean Green Chem., 2004 ,6, 43?
@@totalsynthesis - the ref I read is:
Org. Proc. Res. Dev. 2000, 4, 1, 17-22 Dale et al
It’s an interesting bit of chemical work in the secretive world of process scale up.
like always the best chemistry content out there but the downside is you will always make me feel extremely dumb and like i know absolutely nothing
😂😂 thanks croc, I appreciate it!
first !
Chad subscriber 🎩
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