[ayee_mar]

For our O Chem 2 class we were assigned two individual problems to do on our own and I think I have them solved but with O chem there are always tons of limitations and restrictions that can trip you up so I'm just wondering if I can get a 2nd opinion on my work.

http://i.imgur.com/QOig2TN.jpg

http://i.imgur.com/2WHU5wx.jpg

[kriggy]

Few notes:
FC alkylations usualy lead into multi-substitued product so you need to adjust the ratios of reactans (I guess its fine since its OC2 course)
Im not sure about the last step in 1st synthesis. I cant see the whole picture but Im not sure. If you mean the raction as kumada coupling then you need to write a catalyst
In the secon reaction its again the FC alkylation. And I think you could do it in fewer stepes by using comercialy available compounds

[zsinger]

It MAY work, but there are FAR shorter ways to your target.  Do you have a starting material that is required?
           -Zack

[ayee_mar]

Few notes:
FC alkylations usualy lead into multi-substitued product so you need to adjust the ratios of reactans (I guess its fine since its OC2 course)
Im not sure about the last step in 1st synthesis. I cant see the whole picture but Im not sure. If you mean the raction as kumada coupling then you need to write a catalyst
In the secon reaction its again the FC alkylation. And I think you could do it in fewer stepes by using comercialy available compounds

I tend not to use alyklation for that reason but I see my professor use it in synthesis examples in the same manner, usually i'd write it in excess of reactant to prevent multi-substitution.

For the last step I turned the alcohol on the chain into a chlorine and then displaced it with a CH3 group. I just realized I made a mistake and used Mg in the reaction when I think it would just proceed as a regular Sn2 reaction using just CH3-I?

It MAY work, but there are FAR shorter ways to your target.  Do you have a starting material that is required?
           -Zack

I felt like there were far shorter ways as well, but I couldn't brainstorm any that were.  We were supposed to start with benzene for both reactions.

[zsinger]

I would look into cross coupling, unless that is out of the question.  Perhaps 4 synthons to your target.
     -Zac

[Mellitic]

This brings back such fond memories of O-Chem I + II!

Your first synthesis has some issues.  I don't think your SOCl₂ reaction will proceed cleanly, even if you use only one equivalent.  Also, your Grignard reaction is not going to be nice either with that ester, even if it is sterically hindered.  What if you installed that methyl group earlier, before you form the ester?  You could form the carboxylic acid later after you already have both methyls at the benzylic position.

In your second synthesis you are making a major mistake with your acylation reaction!  How is the electron poor nitrobenzene supposed to do that reaction?  You need a electron rich aromatic ring.  Find an electron donating group that will work for this reaction that will get you to your desired carboxylic acid intermediate.

[Mellitic]

I just realized I made a mistake and used Mg in the reaction when I think it would just proceed as a regular Sn2 reaction using just CH3-I?

You had it less wrong before.  To get that Sn2 reaction to work you need a nucleophile, however, the species you wanted to write was CH₃MgI, where CH₃^- is your attacking species into the carbon chlorine bond.  But as I mentioned in my last post, your ester is also a suitable electrophile and will also react under these conditions.

[ayee_mar]

I would look into cross coupling, unless that is out of the question.  Perhaps 4 synthons to your target.
     -Zac

Hmm the only cross coupling reaction we've been over has been the Gilman reaction and last semester we briefly touched on the Suzuki reaction, but i'll review both and see how they can fit!

This brings back such fond memories of O-Chem I + II!

Your first synthesis has some issues.  I don't think your SOCl2 reaction will proceed cleanly, even if you use only one equivalent.  Also, your Grignard reaction is not going to be nice either with that ester, even if it is sterically hindered.  What if you installed that methyl group earlier, before you form the ester?  You could form the carboxylic acid later after you already have both methyls at the benzylic position.

In your second synthesis you are making a major mistake with your acylation reaction!  How is the electron poor nitrobenzene supposed to do that reaction?  You need a electron rich aromatic ring.  Find an electron donating group that will work for this reaction that will get you to your desired carboxylic acid intermediate.

Really good points! I totally forgot about the esters reactivity. Also thank you for pointing out the NO2 substituent, i'll go back and review these synthesis's

[Mellitic]

Find an electron donating group that will work for this reaction that will get you to your desired carboxylic acid intermediate.

Actually, I should have said find a "less electron withdrawing group" since you still need a meta directing group.

[ayee_mar]

Ok so this is what I ended up doing with my finished assignment. Any opinions?

http://i.imgur.com/hZsalGi.jpg

http://i.imgur.com/wjSGTDH.jpg

[spirochete]

I didn't look at every step in detail, but one step that looks a little sketchy to me is the replacement of the tertiary tosylate with cyanide. Certainly if it worked you could hydrolyze the cyano group to an acid, but the actual replacement might not give entirely Sn1 as you're hoping.

There are two issues: 1, that tertiary tosylate may undergo some E2 reaction, rather than ionize. Typically E2 reactions "require" a strong base, but this is an extreme case where you're using a somewhat weak base with a tertiary leaving group. 2, if it does ionize significantly to form a carbocation, then you will probably get a mixture of E1 and Sn1. Maybe it would work but it would probably be quite solvent dependant, and you'd want to use a very polar solvent to encourage carbocation formation, while still being careful to not use a solvent that would react with the carbocation in undesirable ways.

[Mellitic]

Hopefully this comes before your assignment is due.  Both look much better!  I think the second synthesis is exactly what I would do.  For the first synthesis you can save a lot of steps by using acetyl chloride rather than formyl chloride (which is an unstable reagent that you would have to make, fyi).  From that ketone you can do the same Grignard reaction to get to your alcohol.

An Sn2 on that tertiary tosylate is going to be really poor (and watch your abbriviations, ~TsCl is not TsO~).  To get the carboxylic acid from the alcohol, you can brominate the alcohol with HBr.  Then use nBuLi and CO₂.

[zsinger]

Ask if you may cross couple...then we can chat over PM! .  Will be happy to help.  Your synth. doesn't work perfectly, but is MOSTLY correct.
      -Zack