6
$\begingroup$

I'm only interested in the first conversion: D to E.

I've been thinking about this for a little bit. My first thought was to use $\ce{TsCl}$ to make a good leaving group then a $\ce{Me}$ nucleophile. This didn't seem like it would work since $\ce{Li-Me/MeMgBr}$ would just displace the leaving group. My second thought was to convert the alcohol to a halide, make it a Grignard reagent, then react it with $\ce{MeBr}$. But that also wouldn't work. Any suggestions?

Question

$\endgroup$
  • 2
    $\begingroup$ Consider going via ketone. $\endgroup$ – permeakra May 15 '18 at 21:25
  • 2
    $\begingroup$ You might also consider an organocuprate as a nucleophile. Ordinarily, I wouldn't suggest a secondary electrophile for SN2, but this is also benzylic so... $\endgroup$ – Zhe May 15 '18 at 21:30
  • 1
    $\begingroup$ I considered ketone, that would add the methyl easily using Me-Li then an OH would be left. Add TsCl then a weak reducing agent, NaB(CN)H3, but would that work to remove the OH? $\endgroup$ – Malcolm Hall May 15 '18 at 21:48
  • 1
    $\begingroup$ Oxidise to ketone, Wittig, then hydrogenate $\endgroup$ – orthocresol May 15 '18 at 23:38
  • $\begingroup$ @MalcolmHall It should, but there is a more reliable way. The resulting alcohol should dehydrate really easy. In fact, it might dehydrate during acidic treatment of Grignard reagent adduct. $\endgroup$ – permeakra May 16 '18 at 4:15
-3
$\begingroup$

Steps:

  1. add $\ce{HBr}$
  2. add lithium dimethyl cuprate in ether (anhydrous)

This is the easiest approach.

enter image description here

$\endgroup$
  • $\begingroup$ Do you have a reference for the cuprate addition step? $\endgroup$ – Waylander May 16 '18 at 7:50
  • $\begingroup$ I though of this, but are you sure there is no difficulties with second step? Alkylcuprates are not very good with sterically loaded substrates and might have other weird behaviours? $\endgroup$ – permeakra May 16 '18 at 7:50
  • $\begingroup$ The 2nd step is a sn2 reacn n sn2 goes rapidly with benzylic halides.....as far as i know $\endgroup$ – user64227 May 16 '18 at 8:28
  • $\begingroup$ Cuprate chemistry is more complex than simple SN2 and I would like to see an example of such a reaction cited. $\endgroup$ – Waylander May 16 '18 at 10:20
  • $\begingroup$ A cuprate might work, it is a lot softer of a nucleophile than organolithiums/grignards, but ive only seen it used to attack the softer alkene end of an enone (ambidentate electrophile). Thanks for all the answers though $\endgroup$ – Malcolm Hall May 17 '18 at 9:39

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.