Disconnecting Dactylol - Retrosynthesis

[@Humakhatunskitchen]

Could you bring up more such videos on natural product molecules

[@CasualChemistry]

Will do - they’re in my plan. I’m back on the video making now as my dissertation is finished 🙂

[@crabcrab2024]

Supercool! Metathesis for the formation of the 8 membered ring is a hit. I wonder why I didn’t find it ? Dummy me. But at least I guessed all the other steps right. :) Thank you for yet another great video!

[@CasualChemistry]

🙂 Many thanks. There's definitely other ways of making the ring with perhaps some ylid chemistry but you do run this risk of doing intermolecular reactions instead.

[@viteta5506]

Great video. However I wonder how much of a problem would be the SN2 reaction on the neopentyl center, as someone else noted in the comments. I though about having an aldehyde in the place of the bromine, so we would have an aldol reaction instead. Then apply some non-ionic deoxygenation, or protected the carbonyl, oxidate the alcohol to a ketone, eliminate it, and finally deprotect the ketone to follow through the Grignard step. Just some thoughts.

[@CasualChemistry]

Thanks 🙂 I’ll admit that I agree that the route you suggest would likely be less hassle. I made a bit of an aside comment to acknowledge the non-trivial substitution, but I didn’t want to distract the discussion into that area (might have been a bad call on my part). There are options for additional reagents that can tweak things away from a strictly classical SN2 mechanism I suppose as a starting point for lab-based exploration

[@palamalama]

Loved that 8 membered ring synthesis!

[@CasualChemistry]

🙂 Glad you enjoyed!

[@dlvivlviv]

Great work!

[@CasualChemistry]

Thanks! 🙂

[@Felixkeeg]

On a side note: Methyl isobutyrate smells actually quite pleasantly

[@CasualChemistry]

Nice. I really don’t like the 4-carbon acids and aldehydes, but I guess that ester is more of the traditional fruity smells for esters.

[@jipdendrip17]

Classic neopentyl-effect. That SN2 will go really slow. I like claisen rearrangement for these kind of dissconnections but not sure that will help here.

[@CasualChemistry]

Indeed - they can be troublesome for sure for SN2. It is indeed a classic Claisen motif - I think I even drew the gamma, delta unsaturated carbonyl curled round subconsciously at some point as it was lurking in my head. But I agree there's not an awful lot of advantage here.

[@vlad4512]

Could one do this with a Diels Alder reaction?

[@CasualChemistry]

Not directly to make that 8 membered ring. The Diels-Alder is for cyclohexenes and usually work best if you have an electron deficient dienophile.