Research Article
Iron-Catalyzed Triazole-Enabled C−H Activation with
ACCESS
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ABSTRACT: C−H/C−C functionalizations with oxymethylated
bicyclopropylidenes were accomplished with an iron catalyst under
external oxidant-free conditions. The combination of the unique
reactivity of bicyclopropylidenes with a robust iron(II) catalyst
enabled C−C cleavages in a chemoselective fashion, which allows
for the synthesis of isoquinolones, free isoquinolones, or bispiro-
fused isoquinolones. Mechanistic studies provided strong support
for the C−C cleavage via β-C elimination. A rare monoselective
C−F/C−H bond functionalization of trifluoromethylarene was also
observed.
KEYWORDS: iron, C−H/C−C activation, C−F/C−H activation, BCP, mechanism, Moßbauer study
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INTRODUCTION
functionalizations,
we now disclose the first C−H/C−
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−10
C activation with oxymethylated BCPs catalyzed by Earth-
abundant, nontoxic iron. Salient features of our findings
include (1) first iron-catalyzed C−H/C−C functionalization,
(2) exceedingly mild reaction conditions, and (3) leaving
group-enabled chemodivergency (Scheme 1).
Transition metal-catalyzed C−H activation
has emerged as
an increasingly powerful platform for efficient C−C and C−
Het formations, with transformative applications to material
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1,12
13,14
sciences,
natural product syntheses,
While most transformations have thus far been
accomplished with precious 4d and 5d metal catalysts,
and drug discov-
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5−18
ery.
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RESULTS AND DISCUSSION
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sustainable catalytic manifolds by 3d metal catalysis
especially iron-catalyzed C−H transformations
attracted significant attention because of their high Earth-
abundance, cost-efficiency, and low toxicity. However,
despite indisputable progress, iron-catalyzed C−H activations
continue to be severely limited.
and
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We initiated our studies by probing various reaction conditions
for the envisioned iron-catalyzed C−H/C−C activation of
benzamide 1a with BCP 2 (Tables 1 and S1 in the Supporting
Information). Preliminary studies indicated i-PrMgBr, tetrahy-
drofuran (THF), and 1,2-bis(diphenylphosphino)-ethane
have
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48−54
(
A significant stimulus in C−H activation chemistry was
respectively (Table S1, entries 5−15 and 33−45), while TAH
(triazolylmethyl) was the N-substituent of choice because of its
unique effectiveness as an orienting group in iron-catalyzed C−
recently gained by combining C−H activation with challenging
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5−79
C−C cleavages.
Despite considerable achievements,
catalytic C−H/C−C functionalizations remain underdevel-
39,40
H activation.
The unique reactivity of BCPs was reflected
oped, with the reported examples thus far being largely
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by the judicious choice of the leaving group governing the
chemoselectivity. Specifically, when alkyl ethers were employed
as leaving groups, bispiro-fused isoquinolone 4ac was obtained.
In sharp contrast, acyloxy-BCP 2f delivered isoquinolone 3af
restricted to precious metal catalysts,
activated vinyl-
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cyclopropanes,
and harsh oxidative conditions (Scheme
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4
1
a, b).
Bicyclopropylidenes (BCPs) have been recognized as
increasingly useful structural motifs in modern synthetic
(
entries 1−6). The C−H/C−C activation occurred efficiently
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chemistry.
However, despite being accessible via the
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Received: November 1, 2020
Revised: December 17, 2020
Published: January 7, 2021
Kulinkovich cyclopropanation reaction (Scheme 2) and in
strong contrast to alkylidenecyclopropanes, their applications
in C−H transformations continue to be scarce, with only two
ruthenium-catalyzed C−H hydroarylations being reported
where the cyclopropane rings were found to be con-
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served.
Within our program on sustainable C−C
©
2021 American Chemical Society
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ACS Catal. 2021, 11, 1053−1064