We
introduce an organocatalytic approach for oxaziridinium-mediated
C–H hydroxylation that employs secondary amines as catalysts.
We also demonstrate the advantages of this operationally simple catalytic
strategy for achieving high yielding and highly selective remote hydroxylation
of compounds bearing oxidation-sensitive functional groups such as
alcohols, ethers, carbamates, and amides. By employing hexafluoroisopropanol
as the solvent in the absence of water, a proposed hydrogen-bonding
effect leads to, among other advantages, as high as ≥99:1 chemoselectivity
for remote aliphatic hydroxylation of 2° alcohols, an otherwise
unsolved synthetic challenge normally complicated by substantial amounts
of alcohol oxidation. Initial studies of the reaction mechanism indicate
the formation of an oxaziridinium salt as the active oxidant and a
C–H oxidation step that proceeds in a stereospecific manner
via concerted insertion or hydrogen atom-transfer/radical rebound.
Furthermore, preliminary results indicate that site selectivity can
be affected by amine catalyst structure.
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