You need to reduce the alkyne to the cis alkene and add 1-bromo isopropanol to the terminal side , as well as an esterification of the acid.
Any idea how to do any of those?
Not a bad idea! I think your professor is looking for a 2-step addition of the alkyl chain, but doing it directly with your suggested reagent should work.
One caveat: how will you deprotonate the alkyne (pKa ā 25) without deprotonating the carboxylic acid (pKa ā 5)? Your carboxylate will alkylate as well, and you'll likely end with some dimerization products.
Hmm having the carbocylic acid there already is kinda annoying cuz then you cant do lithium alkyne in to epoxide directly. So you might have to protect the carboxylic acid in to an oxazoline then you can perform the organolithium addition on to the epoxide, hydrogenate with lindlars and then finally deprotect and turn it in to the methyl ester.
Edit i forgot about the terminal bromide that makes it tricky aswell
Edit 2 copied my responce from the ochem subreddit cuz it got removed there
Paper chemistry bc it's gonna be a mess practically:
1. Esterification of acid
2. Reduction of double bond
3. Cross metathesis
Or
1. Esterification
2. Hydroboration / hydrostannylation of double bond.
3. Stille/Suzuki sp3 cross coupling OR epoxide opening
Or
1. Esterification
2. Ozonolysis
2. Wittig reaction (e.g. with acetonide protected 1,2 butanediol)
3. Acetonide deprotection
4. Selective bromination of primary alcohol (might be problematic with the double bond)
Or if you wanna go full "might be theoretically possible but prolly won't work":
1. Esterification
2. Cross alkyne metathesis
3. Reduction
https://preview.redd.it/f25yn5vzu46d1.png?width=916&format=png&auto=webp&s=b7bacd5b6eb57fc1c578dde83f84cb2922c6a896
Alright, what do you all think of this?
And what about your ideas?ššš
Iām working on it. In de mean time I could use some help haha
You need to reduce the alkyne to the cis alkene and add 1-bromo isopropanol to the terminal side , as well as an esterification of the acid. Any idea how to do any of those?
What if you deprotonate the alkyne to an acetylide ion. Let it react with 1,3-dibromo-2-propanol. Then just do lindlar to get the cis alkene.
Not a bad idea! I think your professor is looking for a 2-step addition of the alkyl chain, but doing it directly with your suggested reagent should work. One caveat: how will you deprotonate the alkyne (pKa ā 25) without deprotonating the carboxylic acid (pKa ā 5)? Your carboxylate will alkylate as well, and you'll likely end with some dimerization products.
Hmm having the carbocylic acid there already is kinda annoying cuz then you cant do lithium alkyne in to epoxide directly. So you might have to protect the carboxylic acid in to an oxazoline then you can perform the organolithium addition on to the epoxide, hydrogenate with lindlars and then finally deprotect and turn it in to the methyl ester. Edit i forgot about the terminal bromide that makes it tricky aswell Edit 2 copied my responce from the ochem subreddit cuz it got removed there
With more simple ideas: 1 > 2: MeOH, H+ 2 > 3: NaNH2 3 > 4: 3-bromopropene 4 > 5: mCPBA 5 > 6: 1. NaBr, DMSO, 2. H2O
Paper chemistry bc it's gonna be a mess practically: 1. Esterification of acid 2. Reduction of double bond 3. Cross metathesis Or 1. Esterification 2. Hydroboration / hydrostannylation of double bond. 3. Stille/Suzuki sp3 cross coupling OR epoxide opening Or 1. Esterification 2. Ozonolysis 2. Wittig reaction (e.g. with acetonide protected 1,2 butanediol) 3. Acetonide deprotection 4. Selective bromination of primary alcohol (might be problematic with the double bond) Or if you wanna go full "might be theoretically possible but prolly won't work": 1. Esterification 2. Cross alkyne metathesis 3. Reduction
The TRUE answer
https://preview.redd.it/f25yn5vzu46d1.png?width=916&format=png&auto=webp&s=b7bacd5b6eb57fc1c578dde83f84cb2922c6a896 Alright, what do you all think of this?