An efficient one-pot sequential hydrogen isotope exchange (HIE)/ reductive deuteration approach was developed for the preparation of α,β-deuterated alcohols using ketones as the precursors. The HIE step can also be used for the synthesis of α-deuterated ketones. This method has been applied in the synthesis of four deuterated drug and MS internal standards.Letter pubs.acs.org/OrgLett
We report the first
highly chemoselective synthesis of α,α-dideuterio
alcohols with exquisite incorporation of deuterium (>98% [D2]) using pentafluorophenyl esters as ketyl radical precursors,
SmI2 as a mild reducing agent, and D2O as the
deuterium
source. This system tolerates a variety of functional groups, offering
rapid entry to valuable α,α-dideuterated alcohol building
blocks. More generally, this report introduces pentafluorophenyl esters
as the most reactive O-ketyl precursors reported
to date.
Selective introduction of the deuterium
atom into the α-position
of amines is important for the development of all types of novel deuterated
drugs and agrochemicals due to the pervasive presence of amines. In
this study, we report the first general single-electron-transfer reductive
deuteration of both ketoximes and aldoximes using SmI2 as
an electron donor and D2O as a deuterium source for the
synthesis of α-deuterated primary amines with excellent levels
of deuterium incorporations (>95% [D]). This protocol exhibits
excellent
chemoselectivity and tolerates a variety of functional groups. The
potential application of this new method was showcased in the synthesis
of deuterated drugs, such as rimantadine-d
4, the tebufenpyrad analogue, derivatives of nabumetone and pregnenolone,
and a series of building blocks for the rapid and general assembly
of deuterated drugs and pesticides.
A highly chemoselective reductive deuteration of acyl fluorides to provide α,α-dideuterio alcohols with exquisite levels of deuterium incorporation was developped using SmI2 and D2O as deuterium source. This method introduces...
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