COMMUNICATIONS
DOI: 10.1002/adsc.202001515
Use of Imidazo[1,5-a]pyridin-3-ylidene as a Platform for Metal-
Imidazole Cooperative Catalysis: Silver-Catalyzed Cyclization of
Alkyne-Tethered Carboxylic Acids
a
Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
E-mail: sawamura@sci.hokudai.ac.jp; higashida@icredd.hokudai.ac.jp
Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo 001-0021, Japan
b
Manuscript received: December 4, 2020; Revised manuscript received: January 20, 2021;
Version of record online: Februar 1, 2021
on the nature of the catalyst not only through steric
effect but also through a coordinative interaction. In
fact, imidazo[1,5-a]pyridin-3-ylidene ligands have
Abstract: Silver complexes with 5-(4-(tert-butyl)-
1H-imidazol-1-yl)-imidazo[1,5-a]pyridin-3-ylidene
ligands were synthesized as metal-imidazole acid-
base cooperative catalysts. Single crystal XRD
analysis revealed that the silver atom was located in
the vicinity of the imidazole ring and that cationic
silver complexes formed dimers through coordina-
tion between the silver metal and the imidazole
been modified at the C5 position with sterically bulky
aromatic rings,[4] coordinative substituents,[5] chiral
auxiliaries,[6] and other substituents.[7]
Therefore, we envisioned that imidazo[1,5-a]
pyridin-3-ylidene could be used as a robust template
for producing acid-base cooperative catalysts[8] by
pendant. These cationic silver complexes served as
locating a Lewis acidic transition metal center and a
catalysts for cyclization of alkyne-tethered carbox-
basic functional group such as imidazole at the C3
ylic acids. NMR experiments indicated that the
carbene carbon and the C5 position, respectively
dimeric cationic silver complex dissociated to a
(Figure 1b). More specifically, we chose the 4-(tert-
monomer upon protonation of the imidazole moiety,
resulting in coordination of an acetonitrile to the
silver atom. DFT calculations supported the acid-
butyl)-1H-imidazol-1-yl group as the rigid basic
substituent at the C5 position so as to spatially separate
the Lewis acidic center and the basic center in the
base cooperative action of the silver-imidazole for
catalytic region. Here, we report the synthesis of
the efficient alkyne-carboxylic acid cyclization.
protonated precursors for such imidazo[1,5-a]pyridin-
3-ylidene ligands, their conversion to the correspond-
ing silver(I) complexes, and their application to the
Keywords: Silver catalyst; Cooperative catalysis; N-
silver-catalyzed cyclization of alkyne-tethered carbox-
Heterocyclic carbene; Cyclization
ylic acids (Figure 1c).[9,10]
The synthesis of 5-(4-(tert-butyl)-1H-imidazol-1-
yl)-imidazo[1,5-a]pyridinium salt as an NHC precursor
N-Heterocyclic carbenes (NHCs) are strong σ-donating is outlined in Scheme 1. Acetal protection of commer-
ligands, and their transition metal complexes have cially available 6-bromo-2-pyridinecarboxaldehyde (1)
been widely investigated as catalysts for reaction gave 2-bromo-6-(diethoxymethyl)pyridine (2) in 96%
development due to their robustness and tunability.[1] yield. The 4-(tert-butyl)-1H-imidazolyl substituent was
To date, a broad spectrum of NHC ligands with introduced through copper-catalyzed coupling between
different electronic and steric properties have been 2 and 4-(tert-butyl)-1H-imidazole to give 2-(4-(tert-
synthesized and evaluated. Imidazo[1,5-a]pyridin-3- butyl)-1H-imidazol-1-yl)-6-(diethoxymethyl)pyridine
ylidene (Figure 1a) is an NHC scaffold with a rigid (3) in 79% yield. In this coupling, using
bicyclic framework, introduced independently by benzotriazole[11] as a ligand for the copper catalyst was
Lassaletta[2] and Glorius.[3] Since the substituent at the crucial for obtaining 3 in a reasonable yield. After
C5 position of the imidazo[1,5-a]pyridin-3-ylidene removing the acetal protection under acidic conditions,
projects into the catalytic environment around the reductive amination with 2,4,6-trimethylphenylmeth-
NHC-bound metal center, it is expected that ligand ylamine or 2,6-diisopropylphenylmethylamine fol-
modification at this position would have great impact lowed by N-formylation[12] produced the corresponding
Adv. Synth. Catal. 2021, 363, 1631–1637
1631
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