Extreme Diels-Alder Reactions Your Chemistry Teacher Warned You About
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- Опубліковано 10 чер 2024
- 🧠 Remember your chemistry introduction to Diels-Alder reactions? At that time, these extreme reactions would have been beyond your wildest imagination. If you want to learn some unique aspects to one of the most versatile and robust reactions known to chemists, check out this video! We will focus on two natural product total syntheses, covering basic organic chemistry and advanced synthesis.
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00:00 Exotic reactions hidden within complex structures
01:02 Natural product isolation basics | Biosynthetic origins of lissodendoric acid A and manzamine
04:58 Retrosynthesis of lissodendoric acid A | Allenes and Diels-Alder cycloaddition
08:37 Forward synthesis of lissodendoric acid A
12:06 ♡ Thank you for your support ♡
12:27 Context and retrosynthetic analysis of pedrolide
14:26 Caveat on cyclopentadienes in synthesis
16:27 Forward synthesis of pedrolide
Key references:
- Lissodendoric Acids A and B, Manzamine-Related Alkaloids from the Far Eastern Sponge Lissodendoryx florida | Org. Lett. 2017, 19, 5320
- Revisiting the manzamine biosynthetic hypothesis | Nat. Prod. Rep. 2023, 40, 964
- Mercuric ion catalyzed rearrangements of ten-membered-ring allenes | J. Org. Chem. 1975, 40, 585
- Total synthesis of lissodendoric acid A via stereospecific trapping of a strained cyclic allene | Science 2023, 379, 261
- Diels-Alder cycloadditions of strained azacyclic allenes | Nat. Chem. 2018, 10, 953
- Pedrolane, a Polycyclic Diterpene Scaffold Containing a Bicyclo[2.2.1]heptane System, from Euphorbia pedroi | Org. Lett. 2021, 23, 274
- Enantioselective Total Synthesis of (+)-Pedrolide | J. Am. Chem. Soc. 2023, 145, 8332
Some recommended books on organic synthesis:
- Clayden, Greeves, Warren; Organic Chemistry (basic organic chemistry knowledge)
- Wyatt, Warren; Organic Synthesis: The Disconnection Approach (excellent introduction to retrosynthesis)
- Kurti, Czako; Strategic Applications of Named Reactions in Organic Synthesis (extensive toolkit of functional group reactions and applications thereof with common conditions)
- Nicolaou; Classics in Total Synthesis 1-3 (the ultimate total synthesis trilogy)
- Nicolaou; Molecules That Changed the World (the world's most important molecules and their impact on everyday life)
- Carreira, Kvaerno; Classics in Stereoselective Synthesis (compilation of the groundbreaking methods of stereoselective synthesis and application to synthesis of stereochemically complex structures) - Наука та технологія
💘 Big thanks again to all channel supporters and followers! Let me know any feedback and recommendations for future videos.
www.patreon.com/totalsynthesis; instagram.com/totalsynthesis_official/
Regarding pedrolide, I've just realized Synthesis Workshop has a video ua-cam.com/video/wy5IFF5U8c8/v-deo.html that you should check out for direct commentary of the lead chemist, including in-depth information (e.g., optimization studies).
Man I'm still absolutely mesmerized by the Petrolide synthesis by Marlene Fadel and Carreira, I am fortunate enough to take a course by Prof. Carreira and Ms. Fadel was my Lab TA, which is quite surreal honestly!
The time between first isolation and completed synthesis, particularly considering the structural complexity, is pretty insane!
@@totalsynthesis Absolutely, I was talking to Carreira and he was really proud of their timely achievement. Are you also around at ETH?
I love that this is all way over my head (undergrad and only been up through ochem1) watching your vids on crazy shit like this stokes my thirst to understand every minute detail you're talking about even though I can generally follow along. Thank you and wish I was in a position to be a patron ❤
Thanks a lot!
Wow that cyclopentadiene unmasking was one of the most beautiful reactions I have ever seen. Thanks for the video.
That was straight up 🔥
Thanks!
Phytochemistry alkaloid chem fan vs Marine chemistry enjoyer.
Both known for decimating half the population of a species trying to isolate a single active compound that have utterly deranged scaffolds 😂
😂😂
This is the good shit. Nice vid
Thanks mate
Amazing videos, Im mostly overwhelmed by the end, but thats how it should be.
Thanks!
You included the wrong reference for the eel paper. Though the one you cited also deals with massacring eels.
"J. Am. Chem. Soc. 1990, 112, 11, 4380-4386" is the one you quote from in the video.
Oh snap, thanks! I mixed up my massacres
I thought I was ready but maybe a few more months of digesting data🎉
I would have synthesized those compouds much earlier, but there was an easier way to get a Nobel prize🎉
Your Diels Alder mechanism proposed in 1942 proved to be a bit sus though: pubs.acs.org/doi/10.1021/ja01264a521
At 9:53 you mention that they use Bu4NBr as a phase transfer catalyst for CsF. Why not just use TBAF (Bu4NF) instead? I think I'm missing something obvious, but I'm confused!
Great work, keep it up! I much prefer the serious takes with only a few jokes, so I really like this video. You're awesome!
Thanks! Not sure if they document it anywhere but maybe that system simply proved experimentally to be superior
@@totalsynthesis thanks! I reply if I find anything. Again, really great work. Thank you so much for creating high-quality synthesis content that is both entertaining and educational
@@totalsynthesis Now that I think of it, I wonder if using TBABr and CsF instead of TBAF alone was chosen because this allows you to control two variables--the stoichiometry of fluoride and the amount of phase transfer catalyst. The only other thing I can think of is the resulting salt formation/counterion size might in some way be related
@@AlphaNumeric123 Good points!
In general, CsF is poorly soluble in ACN so the F is slowly released allowing the hugely reactive Allene to remain in low concentrations throughout the reaction. When TBAF is used, even under slow addition w a syringe pump, the Allene is generated too quickly and can lead to dimerization via 2+2 or other unwanted reactivity. This is true of benzyne formation as well. This is a funny case where the CsF need a little help at colder temperature so it acts as a way to increase available F while not flooding the reaction w F. Hope this helps 😊
Pufferfish and friends
omg I found my brother