10.1002/chem.201804077
Chemistry - A European Journal
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the amine nucleophile with thiols, provided the 13C-labeled thioe-
sters 13C-2a and 13C-2b in satisfactory yields. Furthermore, when
N-hydroxysuccinimide (NHS) was used, the corresponding NHS-
ester 13C-3 could be produced in an unoptimized yield.
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A recent paper reported the use of Ni0-mediated aminocarbonylation for
the preparation of six structurally simple 11C-labeled carboxamides. Be-
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In summary, a novel protocol has been developed for the ac-
ylation of amines applying a new class of NiII-pincer complexes,
carbon monoxide and alkylzinc reagents. Particularly noteworthy
with this method is its adaptability to carbon-isotope labeling by
the use of isotope labeled CO. We believe this method will find
suitable applications for carbon-14 labeling of pharmaceutically
relevant molecules, and considering the fast reaction times as il-
lustrated in one of the examples, it could also find uses for iso-
tope-labeling with the short-lived carbon-11.
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Acknowledgments
We are deeply appreciative of generous financial support from the
Danish National Research Foundation (grant no. DNRF118), the
Lundbeck Foundation and Aarhus University.
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Keywords: • aminocarbonylation • nickel • pincer complexes •
alkylzinc reagents • isotope-labeling
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[15] All zinc reagents with the exception of pentadecanylzinc bromide, were
obtained commercially as a 0.5 M solution in THF. For the latter reagent,
this was prepared in DMA from pentadecanyl bromide and zinc (see
Supporting Information section). All carbonylation reactions were
performed under strictly dry conditions to avoid protonation of the
alkylzinc reagents.
[16] The formation of acetone could originate either from the anionic NiII-
species, [(NN2-pincer)NiII(C(O)CH3)(CH3)–, generated from the reaction
of [(NN2-pincer)NiII(C(O)CH3) with methylzinc chloride, or from the direct
acyl substitution of the acyl-NiII complex with the methylzinc reagent.
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[7]
Odell and Eriksson have demonstrated the possibility on the use of free
radical chemistry for the synthesis of simple 11C-labeled amides though
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