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In the above reaction, I know that I have to use either $\ce{HBr}$ or $\ce{PBr3}$ and then $\ce{NaCN}$, DMF, $\ce{H+}$ and $\ce{H2O}$. However, I'm just confused on when to use $\ce{HBr}$ or $\ce{PBr3}$. How is the stereochemistry controlled?

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  • $\begingroup$ Try to think in terms of desirable configuration. It seems to me that neither would work as desired. $\endgroup$ – permeakra Mar 5 '18 at 6:31
  • $\begingroup$ Who says you have to use PBr3? $\endgroup$ – Waylander Mar 5 '18 at 10:11
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As @permeakra has said neither reagent will get you the stereochemistry you want in the product. The HBr route goes through a carbocation which scrambles the stereochemistry completely.

PBr3 will invert the stereochemistry, then SN2 -CN addition will invert it again, giving you the wrong product.

You need something that turns the -OH group into a leaving group while preserving the stereochemistry, so that the CN can displace it by a SN2 process. This will invert the stereochemistry giving you the product, after hydrolysis, you want.

I suggest forming a sulfonate, either tosylate, triflate or (my choice) mesylate. This should be displaced smoothly by cyanide under the DMF conditions you refer to.

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  • $\begingroup$ What if we use a Lewis acid like AlCl3 or FeBr3 at the beginning? Will that work? $\endgroup$ – dr.drizzy Mar 5 '18 at 12:10
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    $\begingroup$ No. That is still going to go by a carbocation $\endgroup$ – Waylander Mar 5 '18 at 14:00

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