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.
An environmentally friendly electrochemical approach for iodoamination of various indole derivatives with a series of unactivated amines, amino acid derivatives, and benzotriazoles (more than 80 examples) has been developed. This strategy was further applied in late-stage functionalization of natural products and pharmaceuticals and gram-scale synthesis and radiosynthesis of 131 I-labeled compounds. Fundamental insights into the mechanism of the reaction based on control experiments, density functional theory calculation, and cyclic voltammetry are provided.
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.
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