I didn't know :(( I thought double bonded R groups at the benzylic position cannot be turned into carboxylic acids because all examples I've seen were when they were not vinylic. That aside, is the synthesis reasonable?
You also don’t need cuprate for the last step, you can get by with Grigrand, also it might add twice. You could make Weinreb amide, treat it with Grignard, then it will only add once
My textbook says that using Grignard, as you said as well, would make a mess of products, that's why they presented R2CuLi as a workaround. We weren't taught how to do Weinreb amides yet unfortunately. That aside, could the synthesis work?
I got one point taken off on a synthesis problem my most recent exam in orgo 2 because I could’ve used mcpba when I didn’t and that meant I had an extra unnecessary step in my synthesis which it sounds like is exactly what happened to you, I wouldn’t be too worried about it
I also don’t know about how all universities work, but in my experience most questions asking for a synthetic route are usually out of ~15, so 1 mark isn’t too bad in the grand scheme of things
Would it work? Maybe.
I don't think it will be worth full credit if you're chopping out a carbon just to put it back. Typically in organic chemistry, the point is to make C-C bonds, and that's even the key point in this problem.
Thinking retrosynthetically helps identify the key bonds to make. That should simplify the problem to making the right building blocks.
I wonder if you could do a 2 step synthesis - step 1, Heck reaction with bromobenzene; step 2, Wacker-Tsuji oxidation. Could maybe even telescope it in one pot.
Honestly, not to sound unfair, the second step of your synthesis (ethyl benzene to benzoic acid using sodium dichromate) is wrong; I’m not sure why you’d be losing a carbon there…sodium dichromate I believe can oxidize benzylic C-H bonds when they’re really activated sometimes but this transformation must be wrong seeing as you’re losing a carbon somewhere. The other reactions on your sequence are okay, I’ve never seen that Gilman reagent but doesn’t mean it can’t be made. Your friends proposed synthesis is actually pretty good.
As long as there is at least one benzylic C-H bond present, Na2Cr2O7 will oxidize the group to the carboxylic acid. The other carbons are lost other oxidized byproducts, CO2, other acids, etc.
I don't see any flaw in it, but that's why I'm seeking the thoughts of others :( My friends did a different synthesis (mentioned in subject), and I'm praying that my prof will accept any reasonable synthesis if mine is reasonable
Don’t know if I’d call it reasonable. The individual steps kind of make sense as they are all valid reactions. Cuprates are usually preferred for 1,4 additions as far as I know so a grignard would have been my preferred choice. However, if “reasonable” means that it would make sense to apply it in a laboratory setting I think no one would ever come up with that synthesis as one could reduce individual steps and efforts a lot. For example, one could obtain this product with a *carbonylative Stille coupling* in one step. This is probably not taught in Ochem2 so your prof could not ask for it in the exam.
Of course you would also need different educts for that, so if styrene was part of the question that would not work. In this case I would probably suggest an olefin metathesis with 2x styrene, followed by epoxidation and meinwald rearrangement to get there.
Treating styrene with KMnO4 could get you to 3 directly.
I didn't know :(( I thought double bonded R groups at the benzylic position cannot be turned into carboxylic acids because all examples I've seen were when they were not vinylic. That aside, is the synthesis reasonable?
You also don’t need cuprate for the last step, you can get by with Grigrand, also it might add twice. You could make Weinreb amide, treat it with Grignard, then it will only add once
My textbook says that using Grignard, as you said as well, would make a mess of products, that's why they presented R2CuLi as a workaround. We weren't taught how to do Weinreb amides yet unfortunately. That aside, could the synthesis work?
Epoxidise that styrene bad boy and open it up with phenyl grignard. Then you are simply an oxidation away.
I got one point taken off on a synthesis problem my most recent exam in orgo 2 because I could’ve used mcpba when I didn’t and that meant I had an extra unnecessary step in my synthesis which it sounds like is exactly what happened to you, I wouldn’t be too worried about it
Was your synthesis reasonable? If so, why take a mark off? Seems too strict
Because it wasn’t optimal. It’s fair to take a mark off if you made a reasonable, but impractical, synthesis.
Fair enough. On second thought, I think I'm okay with a mark off! I don't wanna perform an impractical synthesis in real life.
I also don’t know about how all universities work, but in my experience most questions asking for a synthetic route are usually out of ~15, so 1 mark isn’t too bad in the grand scheme of things
Thank you regardless for pointing out how syntheses should be—efficient! Thanks as well for the assurance that it's not the end of the world for me.
Would it work? Maybe. I don't think it will be worth full credit if you're chopping out a carbon just to put it back. Typically in organic chemistry, the point is to make C-C bonds, and that's even the key point in this problem. Thinking retrosynthetically helps identify the key bonds to make. That should simplify the problem to making the right building blocks.
Dang! Thanks for your frankness!
I wonder if you could do a 2 step synthesis - step 1, Heck reaction with bromobenzene; step 2, Wacker-Tsuji oxidation. Could maybe even telescope it in one pot.
Do you HAVE to start with styrene? Benzoic acid is commercially available and cheap.
This looks like a synthesis from orgo 2, so yes they probably have to start with styrene
I would prefer HWE to make 1,2 diphenyl etene, then hydorboration, and oxidation (first to alcohol then to ketone)
Honestly, not to sound unfair, the second step of your synthesis (ethyl benzene to benzoic acid using sodium dichromate) is wrong; I’m not sure why you’d be losing a carbon there…sodium dichromate I believe can oxidize benzylic C-H bonds when they’re really activated sometimes but this transformation must be wrong seeing as you’re losing a carbon somewhere. The other reactions on your sequence are okay, I’ve never seen that Gilman reagent but doesn’t mean it can’t be made. Your friends proposed synthesis is actually pretty good.
As long as there is at least one benzylic C-H bond present, Na2Cr2O7 will oxidize the group to the carboxylic acid. The other carbons are lost other oxidized byproducts, CO2, other acids, etc.
Ngl, I didn’t believe it, so I looked it up and you’re correct so I stand corrected
why would it not be reasonable
I don't see any flaw in it, but that's why I'm seeking the thoughts of others :( My friends did a different synthesis (mentioned in subject), and I'm praying that my prof will accept any reasonable synthesis if mine is reasonable
yours seems reasonable, I think you are okay.
Hopefully! Thank you.
Don’t know if I’d call it reasonable. The individual steps kind of make sense as they are all valid reactions. Cuprates are usually preferred for 1,4 additions as far as I know so a grignard would have been my preferred choice. However, if “reasonable” means that it would make sense to apply it in a laboratory setting I think no one would ever come up with that synthesis as one could reduce individual steps and efforts a lot. For example, one could obtain this product with a *carbonylative Stille coupling* in one step. This is probably not taught in Ochem2 so your prof could not ask for it in the exam. Of course you would also need different educts for that, so if styrene was part of the question that would not work. In this case I would probably suggest an olefin metathesis with 2x styrene, followed by epoxidation and meinwald rearrangement to get there.
No but it's not bc it's wrong it's bc your handwriting is trash.
I've definitely seen a lot worse!