Dehydrogenative C-H phenochalcogenazination

Article abstract of DOI:10.1021/acs.orglett.1c00573

Heavy-atom-modified chalcogen-fused triarylamine organic materials are becoming increasingly important in the photochemical sciences. In this context, the general and direct dehydrogenative C-H phenochalcogenazination of phenols with the heavier chalcogen

Full text of DOI:10.1021/acs.orglett.1c00573

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Letter
Dehydrogenative C−H Phenochalcogenazination
Christopher Cremer, M. Alexander Eltester, Hicham Bourakhouadar, Iuliana L. Atodiresei,
and Frederic W. Patureau*
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ABSTRACT: Heavy-atom-modified chalcogen-fused triarylamine organic materials are becoming increasingly important in the
photochemical sciences. In this context, the general and direct dehydrogenative C−H phenochalcogenazination of phenols with the
heavier chalcogens selenium and tellurium is herein described. The latter dehydrogenative C−N bond-forming processes operate
under simple reaction conditions with highly sustainable O2 serving as the terminal oxidant.
“I shall not decide whether that smell belongs to both, or
whether tellurium is often associated with the new substance.
Nevertheless, as a reminder of the affinity of the latter with
tellurium, I have named it selenium.”1 Upon the discovery of
the latter element in 1818, Berzelius had already noted the
chemical similarity of newly found selenium with already
known sulfur and tellurium. He also noted some important
redox differences. Another essential difference within the
chalcogen group lies with the variation of covalent radius,
which approximatively doubles from oxygen to tellurium.2
Vast numbers of organic heterocyclic structures are known
with oxygen and sulfur, yet considerably fewer with selenium
and almost none with metalloid tellurium. However, the
chemistry of selenium and tellurium is becoming increasingly
important in the field of heterocyclic chemistry, associated to
the emergence of novel properties.2 The latter are becoming a
research priority in the field of bioactive compounds3 and, in
particular, organic materials and catalysts (Figure 1).4−8
Meanwhile, the cross-dehydrogenative phenothiazination
reaction has grown into a straightforward synthetic tool for
Figure 1. Recent selected Se- and Te-containing heterocyclic
materials and catalysts.
the direct access to important triarylamine structures (Scheme
1).9 Its most important conceptual feature is that it represents
a rare case of intermolecular dehydrogenative amination
reaction, wherein no catalyst nor additive is required, apart
from a mild oxidant.10 Importantly, even trivial O2 can serve as
Received: February 17, 2021
Published: April 13, 2021
an efficient oxidant in this reaction, conferring on it a highly
sustainable character.11 Its specificity is moreover excellent, in
particular for phenothiazines as N−H substrates (PSZH, X =
S) and phenols and related electron-rich arenes as C−H
substrates.9 Until now, however, this reaction has been mostly
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Scheme 1. Dehydrogenative Phenothiazination Reaction
Scheme 3. Dehydrogenative C−H Phenochalcogenazination
with Selenium and Tellurium: Isolated Yields
Scheme 2. PXZH Synthesis, Isolated Yields
limited to phenothiazines as the N−H coupling partners. The
reason for this high specificity is well-understood: PSZHs
combine a low N−H bond dissociation energy (BDE)12 and
low oxidation potential with N-centered radical persistency.13
These features facilitate their oxidative interception with
phenols or/and phenol radicals into a C−N bond-forming
cross-dehydrogenative coupling process. But how exactly
limited are the PSZHs backbones as coupling partners? Can
the bridging chalcogen atom X be varied? Some authors have
already noted in earlier works that phenoxazine POZH (X =
O) is also a competent N−H substrate in the dehydrogenative
C−H chalcogenazination reaction.9 This finding, along with
the rising interest for heavy-atom-modified chalcogen-fused
triarylamine organic materials (Figure 1),3−8 encouraged us to
investigate the larger chalcogens. Thus, the aim of the present
work is to explore whether or not phenoselenazines (PSeZHs,
a
b
c
Two mmol scale. K2HPO4 was utilized instead of K2CO3. 150 °C,
18 h.
X = Se) and phenotellurazines (PTeZHs, X = Te) can also act
as efficient N−H substrates.
After investigating several synthetic routes from the
literature, we selected a simple 2,2′-diododiarylamine pathway
under basic conditions with elemental selenium or tellurium to
furnish the desired PXZH azines in high yields.7 This approach
is inexpensive, easy, mild, versatile in terms of functional group
tolerance, and importantly, scalable. The synthetic results are
summarized in Scheme 2 (see also the Supporting Information
(SI)). Generally, the yields are excellent for the selenium
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analogues and encouraging for the tellurium ones, which is
presumably due to the larger and more-strained heterocyclic
structure of the latter. Typical functional groups such as chloro,
methoxy, methyl, and CF3 were otherwise well-tolerated.
These new PSeZHs and PTeZHs were then evaluated as
N−H coupling partners in the O2-mediated cross-dehydrogen-
ative phenochalcogenazination of some characteristic phenols.
For this, we utilized a basic aerobic method recently developed
for phenothiazines (PSZH).7 To our satisfaction, the method
afforded high yields with almost identical conditions than
required for PSZHs and POZH (X = S and O, respectively),
moreover with excellent functional group tolerance (Scheme 3;
see also the SI). Indeed, electron-donating (methyl, methoxy)
and electron-withdrawing groups (chloro, bromo, CF3) were
well-accommodated. Even a tyrosine derivative14 could be
obtained (PSeZ_23), albeit in low yield. The method is
moreover easily scalable. For instance, PSeZ_12 was obtained
in 84% yield on a 2 mmol scale.
Se), and the considerably shorter C−X−C angles, from
117.24(10)° for X = O (quasi-regular and flat hexagonal
heterocycle) to 94.61(7)° for X = Se (heavily distorted
heterocyclic ring). While no X-ray structure of a tellurium
congener could be obtained at this stage, the heterocyclic
distortion therein is expected to be even greater, with a C−
Te−C angle expected at ca. 91°, and a C−Te distance
expected at ca. 2.1 Å.15
Based on literature precedents with X = S,13 the
dehydrogenative C−H phenochalcogenazination reaction is
expected to run along a radical mechanism, as depicted in
Scheme 5. The phenochalcogenazine PXZH undergoes
Scheme 5. Proposed Mechanism
We were then able to obtain an X-ray structure of one of
these heavy-chalcogen-fused triarylamine structures, that of
PSeZ_7 (Figure 2, Scheme 4). Very similar to that observed in
hydrogen atom abstraction (HAT) upon reaction with O2
under basic conditions to generate a persistent PXZ• mostly
nitrogen centered neutral radical. The latter key species can
accumulate, eventually triggering HAT from the phenol. The
phenol radical generated in this manner is then intercepted by
PXZ• to form the cross-dehydrogenative C−N coupling
product. In support of this mechanism, a recently published
study demonstrated that all phenochalcogenazines (X = O, S,
Se, Te) have a similarly low oxidation potential (determined by
cyclic voltammetry), associated with a mostly N-centered
neutral radical persistency (determined by EPR spectroscopy
after O2 exposure).7 Although some small differences were
observed in the case of the larger PTeZH congener, which
seems, according to its EPR profile, to accommodate a mostly
protonated radical cation intermediate PTeZH• +, these altered
features do not seem to forbid the C−N cross-dehydrogenative
coupling reactivity, as illustrated in Scheme 3.
Figure 2. X-ray structure of PSeZ_7, 50% probability level, side and
front view. Compound PSeZ_7 crystallized with one diisopropyl
ether molecule. The solvent molecule has been omitted for clarity
(see the SI).
a
Scheme 4. Characteristic Differences from X = O to Te
In summary, we demonstrated that the dehydrogenative C−
H phenochalcogenazination reaction is a general concept,
which can be extended to include selenium and tellurium. The
latter afford the corresponding heavy-atom chalcogen-fused
triarylamine materials in good yields, while utilizing only O2 as
a most sustainable terminal oxidant. This new synthetic tool
should facilitate the development of heavy-atom-based fused
organic materials.
a
Characteristic 1H NMR signals in DMSO-d6. X-ray structure of
POZ_7 and PSZ_7: see ref 13. X-ray structure of most resembling
PTeZH: see ref 15.
the known cases of oxygen and sulfur, the PSeZ moiety sits
mostly perpendicular to the plane of the phenol moiety.
Surprisingly, however, the potential and characteristic intra-
molecular OH···N hydrogen bond does not seem to take place
within this crystal. Indeed, the pyramidal-shaped triarylamine
moiety is pointing in the opposite direction, with respect to the
OH group, which itself is pointing toward a solvent molecule.
Other characteristic features are the expected longer C−X
bonds (from 1.3865(15) Å for X = O to 1.8971(16) Å for X =
ASSOCIATED CONTENT
* Supporting Information
■
sı
CCDC 2063310 contains the supplementary crystallographic
data for this paper (compound PSeZ_7). These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/
cif, or by emailing data_request@ccdc.cam.ac.uk, or by
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contacting The Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; fax: + 44 1223
336033. The Supporting Information is available free of charge
at https://pubs.acs.org/doi/10.1021/acs.orglett.1c00573.
Experimental procedures and characterization of new
compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Frederic W. Patureau − Institute of Organic Chemistry,
RWTH Aachen University, 52074 Aachen, Germany;
orcid.org/0000-0002-4693-7240;
Email: Frederic.Patureau@rwth-aachen.de.
Authors
Christopher Cremer − Institute of Organic Chemistry,
RWTH Aachen University, 52074 Aachen, Germany;
orcid.org/0000-0002-3484-0505
M. Alexander Eltester − Institute of Organic Chemistry,
RWTH Aachen University, 52074 Aachen, Germany;
orcid.org/0000-0002-0564-3588
Hicham Bourakhouadar − Institute of Organic Chemistry,
RWTH Aachen University, 52074 Aachen, Germany
Iuliana L. Atodiresei − Institute of Organic Chemistry,
RWTH Aachen University, 52074 Aachen, Germany
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c00573
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
ERC Project No. 716136: “2O2ACTIVATION,” is acknowl-
edged for financial support.
■
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