[pharmkid]

Hey guys,

My professor decided to give three retro-synthesis problems that will be on our final exam to us early to try to figure out. We were instructed to go to anyone for help except for other professors and grad students at my university so I was just looking to find some help. I believe the easiest way to show is to upload these problems in picture form.

Problem A:


Problem B:


Problem C:


All the problems have to be worked from right to left, showing reagents and intermediates (mechanisms are not-important for these problems).

In problem A  I have gotten to what I believe is the second to last step by first using DiBAl-H @ -78deg. C. along with acid and water to remove the ester and replace it with a hydrogen. After that I attacked it with a grignard reagent to add the propene group. The next step was a three part process attacking first with NH₃, followed by strong acid and a dean-stark apparatus, and then reduction with NaBH₄ to give a hepta-1,6-diene(?) with an NH₂ attached to the fourth carbon in the chain. I am confused about how to turn this chain into the di-hetero-cycle seen as the answer. Do the two double bonds simply attack the NH₂ in some sort of spontaneous add/elim. reaction or do they need to be made to attack?

In problem B I also feel confident that I am close to the answer. I am very strong in EAS and can get to the middle structure with no problem and know that to change the NO₂ to NH₂ reduction with H₂ and a nickle catalyst must take place. From here, however, I am confused. How is the carbonyl group added to the NH₂ making a secondary amide, and how is the Br added to the other carbonyl attached to the benzene ring?

Problem C has me completely lost. It seems to maybe start with aldol or claisen chemistry but every way I look at it I come to a dead end.

Any help with any of these problems would be GREATLY appreciated as I will be able to receive partial credit on any correct steps for these problems. Anyway thanks for taking the time to look over my question and please help if you can!

[aldoxime_amine]

I am confused about how to turn this chain into the di-hetero-cycle seen as the answer. Do the two double bonds simply attack the NH₂ in some sort of spontaneous add/elim. reaction or do they need to be made to attack?

Can you get halo groups at the 2 extremes of the carbon chain? Do you think that will sove the problem or is something else needed?

[aldoxime_amine]

b) Are you aware of acetylation reactions/ acetylating agents?

[aldoxime_amine]

c) That cyclic structure indicates something like an intramolecular reaction.

What sort of a group would be preferred at positions 1 or 2 so that an intramolecular cyclization with the given cyclic structure is possible?

How do we protect aldehydes and ketones in general?

[James Newby]

slightly off topic, are you at Uni of Nottingham in UK?? Saw a seminar from a prof a couple of weeks ago with a few of these questions

[pharmkid]

Can you get halo groups at the 2 extremes of the carbon chain? Do you think that will sove the problem or is something else needed?

You could by adding X₂ I believe but I'm unsure how that would help the problem. The last carbon on each side of the chain needs to be attached to the nitrogen to make the ring structure.

[pharmkid]

slightly off topic, are you at Uni of Nottingham in UK?? Saw a seminar from a prof a couple of weeks ago with a few of these questions

No, University of South Carolina. Thought if he gave answers to these questions, please post 'em!

[pharmkid]

b) Are you aware of acetylation reactions/ acetylating agents?

Yes but I know how to attach substitutes to the benzene it is getting the ketone attached to the amine, and the bromine attached to the other ketone that is giving me problems. Though I have an idea about how to attach the ketone to the amine. Mostly I'm confused about attaching the Bromine. Would a radical reaction work? Like reacting the ketone with Br₂ and ultraviolet light?

[nj_bartel]

think enolate

[pharmkid]

I've got problem B figured out, and most of the steps for A and C. Seeing as how these will just be a small part of the final I'm trying not to kill myself over them too badly as I'll get most of the points for these through partial credit. Horay for finishing the last hard organic chem. I'll ever have to do!

[third.beyond]

pharmkid, please post results.

I'm in your class, and am really scared. X'D

I am just wanting to pass the class at this moment, and I have A figured out, about 2/3 of B, but none of C. Please help me. (I know the test is in 2 hrs.. just figured you might get online before the test.

[nj_bartel]

aldol, oxidation, hydroboration, acetal