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?


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    $\begingroup$ Consider going via ketone. $\endgroup$ – permeakra May 15 '18 at 21:25
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    $\begingroup$ 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
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    $\begingroup$ 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
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    $\begingroup$ 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


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

This is the easiest approach.

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  • $\begingroup$ 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

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