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Can Grignard reagents add to amides? It appears from the synthetic pathway shown below that there has been some form of nucleophilic substitution at the carbonyl group.

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Source: 49th IChO Preparatory Problems, Task 29

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    $\begingroup$ I don't see why not...There's even a sort of electron sink - the benzyl ester - for the nitrogen... $\endgroup$ – Eashaan Godbole Aug 22 '17 at 11:40
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    $\begingroup$ I'm a bit more puzzled why the amide is cleaved and not the carbamate... $\endgroup$ – Martin - マーチン Aug 22 '17 at 12:56
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    $\begingroup$ Grignard can certainly react with tertiary amides (eg Weinreb amides) but I'm more than a little surprised than the ester isn't attacked first and that the chirality is retained. Is there any mention of an additional reagent? $\endgroup$ – Waylander Aug 22 '17 at 13:10
  • $\begingroup$ @Waylander looked it up (Org. Lett. 2004, 6, 1329) it's Grignard + TMEDA in THF $\endgroup$ – orthocresol Aug 22 '17 at 14:34
  • $\begingroup$ @Martin-マーチン the reference above also says that premixing TMEDA and the Grignard prior to reaction with the substrate minimises the extent to which cleavage of the Cbz group occurs $\endgroup$ – orthocresol Aug 22 '17 at 14:36

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