Synthesis of a Ketone Challenge

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[triple_gem_shining]

This was a good one. I tried to ox the alcol first then protect with ethylene glycol and hit a wall when i couldnt reduce just the cyclo ketone. I almsot forgot about tms and tbaf! Thank you for the reminder!!!

[Supercatzs]

great video, i love synthesis problems, was able to get it fairly quickly!

[diveshsandhu]

Thank you sir. Some of your videos have helped me to make my concept strong.

[SIILCT]

trying to refresh my knowledge from organic chemistry 3 😅

[Hydrogenatomtransfermybeloved]

I would immediately use weinreb amide for that, the oxidation doesn't seem necessary
and just in case, use a PG for the alcohol, preferably TBS since TMS just falls off if the alcohol isn't tertiary and sterically encumbered

I think you could elaborate on how to make the SM that is the halohydrin because that IS the challenge. If I specifically had to make the halohydrin intermediate I think I would go for the appel type reaction with an iodide or bromide on a monoprotected cyclopenta 1, 3-diol
If it were only synthesising the TM, I think some conjugate addition stetter reaction followed by a reduction could do the trick since barbier type additions aren't always the most favourable imo but ig it seems better

[iolandatesta]

I think your synthesis is the most efficient one but an alternative could be stork enamination that you explained some days ago? We can avoid protecting the alcol too, i guess, if the enamine it's more reactive then the alcol. Idk if it is

[essenceofdark]

You made a little mistake at 2:32. You said that "we turn our OH into an alcohol" but it should be a ketone 😄

Another possible way to accomplish this synthesis would be:

1) Protection of OH in the Starting Material with TMSCl/Pyridine

2) Kolbe-Nitrile-Synthesis with (Na/K)CN on the Halide to form a Nitrile (Electrophile)

3) Bring on a Isopropyl-Grignard-Reagent (Nucleophile) and add this on our Nitrile to form an Imine

4) Acidic Work-Up from the Imine to build our Keton without Oxidation Step

5) Deprotection of our OH with TBAF

[nicoceraudo]

Isn't there still a chance that the chloride leaving group acts as a nucleophile, substituting the bromine-group after the OH-protection? :o
I think p-Toluenesulfonic anhydride would be better for protection.

[swaradarajadhyaksha]

U have done phd in organic? Btw nice video