10.1002/anie.201704948
Angewandte Chemie International Edition
COMMUNICATION
We acknowledge support by start-up funds from Colorado State
University and from the ACS Petroleum Research Fund (ACS
PRF56878-DNI1). We thank Professor Matthew J. Gaunt for his
help with preparing this manuscript.
for heterobiaryl 2g and requires increased catalyst loading
and temperature for ester 2k. This short survey indicates
that NiCl2.glyme can be used in a glove box-free protocol
but is less reactive than Ni(COD)2.
As phosphonium ions are uncommon functional groups
for cross-coupling reactions, we questioned whether they
could be used orthogonally to halides and enable iterative
coupling sequences.[18] Negishi and Suzuki reactions are
possible where the palladium catalyst reacts exclusively
with the C–Br bond in 1ac leaving the phosphonium ion
for further transformation (1n & 1ad, Schemes 2a & 2b).
Palladium catalysis must be used to achieve orthogonality
as our Ni-catalysis protocol results in mixtures of mono
and diarylated products.[19] Chemoselective reactions with
arylboronic esters are also feasible; palladium-catalyzed
esterification, conducted at 10% loading to drive the
reaction to completion, formed 1af with the phosphonium
salt intact. Subsequent nickel-catalyzed arylation formed a
trisubstituted pyridine 2bc (Scheme 2c).
Keywords: pyridines • cross-coupling • phosphonium salt •
nickel-catalysis • late-stage
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Scheme 2. Chemoselective cross-coupling reactions.
[13] Control experimets show the boronic acid is rapidly converted to the
boroxine, see Supporting Information for details.
In summary, nickel catalysis enables heterocyclic
phosphonium salts to function as generic alternatives to
heteroaryl halides in nickel-catalyzed Suzuki reactions. A
broad range of pyridines and diazines can be converted
into heterobiaryls using this protocol, including complex
substrates. We expect this chemistry to be relevant to
medicinal chemists.
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a minor decomposition pathway of the salt to the C-H compound.
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[19] 1H NMR Yields: 40% 1ad and 8% diarylation, see Supporting Information.
Acknowledgements
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