Herein we describe a general, mild and scalable method for deuterium incorporation by potassium methoxide/hexamethyldisilane-mediated dehalogenation of arylhalides. With CDCN as a deuterium source, a wide array of heteroarenes prevalent in pharmaceuticals and bearing diverse functional groups are labeled with excellent deuterium incorporation (>60 examples). The ipso-selectivity of this method provides precise access to libraries of deuterated indoles and quinolines. The synthetic utility of our method has been demonstrated by the incorporation of deuterium into complex natural and drug-like compounds.
It is challenging to develop simple and low cost catalytic systems while maintaining high reactivity and selectivity. An iron-catalyzed intramolecular C−H amination of sulfamate esters using simple and cheap ligands is reported with general substrate scope (31 examples, up to 95% yield). The addition of second ligand, bipyridine, is able to accelerate the reaction and increase the yield. The ready availability of these iron catalysts provides a promising approach to selective introduction of nitrogen into hydrocarbon feedstock.
Cyclic
sulfonamides (sultams) play a unique role in drug discovery
and synthetic chemistry. A direct synthesis of sultams by an intramolecular
C(sp3)–H amidation reaction using an iron complex
in situ derived from Fe(ClO4)2 and aminopyridine
ligand is reported. This strategy features a readily available catalyst
and tolerates a broad variety of substrates as demonstrated by 22
examples (up to 89% yield). A one-pot iron-catalyzed amidation/oxidation
procedure for the synthesis of cyclic N-sulfonyl
ketimines is also realized with up to 92% yield (eight examples).
The synthetic utility of the method is validated by a gram-scale reaction
and derivatization of the products to ring-fused sultams.
An
efficient strategy for N/O-(deutero)alkylation of indoles and
phenols with alkoxides/alcohols as the alkylation reagents is described.
The consecutive detosylation/alkylation transformations feature mild
reaction conditions, high ipso-selectivity, and good
functional group tolerance (>50 examples). A one-pot selective
N-alkylation
of unprotected indoles with alcohols and TsCl is also realized. The
application of this method is demonstrated by the introduction of
isotope-labeled (CD3 and 13CH3) groups
using the readily accessible labeled alcohols and the synthesis of
pharmaceuticals.
A two-component and metal-free azidotrifluoromethylation of alkenes is realized using readily synthesized trifluoromethanesulfonyl azide (N3SO2CF3) as a bifunctional reagent for both CF3 and N3 groups.
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