I2-Mediated Diversity Oriented Diastereoselective Synthesis of Amino Acid Derived trans-2,5-Disubstituted Morpholines, Piperazines, and Thiomorpholines

Saurav Bera, Gautam Panda

ACS Combinatorial Science · 2012 · 10.1021/co200129t

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– 1 rating
5 : Major extension (new functional group) –
4 : Minor extension (no new functional group) –
3 : Reproduced as published –
2 : Reproduced with deviation –
1 : Did not work –
– : Extension failed / Inconclusive ×1

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PhD student
13 Jul 2026 · edited
– : Extension failed / Inconclusive Extension failed

I have tried the iodoetherification as suggested in the paper, with R = H and NBn instead of NTs. Unfortunately I only saw a mixture of unidentified products.

06 Aug 2026

Hey Dan, I am thinking the Ts is key for these kinds of conditions. It's known to have amines (even tertiary) attack your oxidant first and funnel through an iminium intermediate, and they're often deactivated by Ts, Boc, as amides, etc. I think you'd have to use Ts first then swap to Bn if that's your end goal. Your alcohol could trap out your iminium intermediate and give you various cyclized products or trace water leading to acyclic. I've encountered this issue before, and I think you may be able to get away with making the ammonium adduct in situ with something like TFA and then submit it to the conditions.

06 Aug 2026

Hi Peter,
Thank you for the comment. Indeed, afterwards I have realised that potentially the oxidation was the issue, so then I used a different route to get to my desired compound.