C-H Amination Mediated by Cobalt Organoazide Adducts and the Corresponding Cobalt Nitrenoid Intermediates

Article abstract of DOI:10.1021/jacs.0c04252

Treatment of (ArL)CoBr (ArL = 5-mesityl-1,9-(2,4,6-Ph3C6H2)dipyrrin) with a stoichiometric amount of 1-azido-4-(tert-butyl)benzene N3(C6H4-p-tBu) furnished the corresponding four-coordinate organoazide-bound complex (ArL)CoBr(N3(C6H4-p-tBu)). Spectroscopi

Full text of DOI:10.1021/jacs.0c04252

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Article
C–H Amination Mediated by Cobalt Organoazide Adducts
and the Cor-responding Cobalt Nitrenoid Intermediates
Yunjung Baek, Anuvab Das, Shao-Liang Zheng, Joseph
H. Reibenspies, David C. Powers, and Theodore A. Betley
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c04252 • Publication Date (Web): 26 May 2020
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C–H Amination Mediated by Cobalt Organoazide Adducts and the
Corresponding Cobalt Nitrenoid Intermediates
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Yunjung Baek,† Anuvab Das,‡ Shao-Liang Zheng,† Joseph H. Reibenspies,‡ David C. Powers,‡ and
Theodore A. Betley†*
†Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts
02138, United States.
‡Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States.
ABSTRACT: Treatment of (ArL)CoBr (ArL = 5-mesityl-1,9-(2,4,6-Ph3C6H2)dipyrrin) with a stoichiometric amount of 1-azido-
4-(tert-butyl)benzene N3(C6H4-p-tBu) furnished the corresponding four-coordinate organoazide-bound complex
(ArL)CoBr(N3(C6H4-p-tBu)). Spectroscopic and structural characterization of the complex indicated redox innocent ligation
of the organoazide. Slow expulsion of dinitrogen (N2) was observed at room temperature to afford a ligand functionalized
product via a [3+2] annulation, which can be mediated by a high-valent nitrene intermediate such as a CoIII iminyl
(ArL)CoBr(·N(C6H4-p-tBu)) or CoIV imido (ArL)CoBr(N(C6H4-p-tBu)) complex. The presence of the proposed intermediate and
its viability as a nitrene group transfer reagent are supported by intermolecular C−H amination and aziridination
reactivities. Unlike (ArL)CoBr(N3(C6H4-p-tBu)), a series of alkyl azide-bound CoII analogues expel N2 only above 60 °C,
affording paramagnetic intermediates that convert to the corresponding Co-imine complexes via α−H–atom abstraction.
The corresponding N2-released structures were observed via single-crystal-to-crystal transformation, suggesting
formation of a Co-nitrenoid intermediate in solid-state. Alternatively, the alkyl azide-bound congeners supported by a
more sterically accessible dipyrrinato scaffold tBuL (tBuL = 5-mesityl-(1,9-di-tert-butyl)dipyrrin) facilitate intramolecular 1,3-
dipolar cycloaddition as well as C–H amination to furnish 1,2,3-dihydrotriazole and substituted pyrrolidine products,
respectively. For the C–H amination, we observe that the temperature required for azide activation varies depending on
the presence of weak C–H bonds, suggesting that the alkyl azide adducts serve as viable species for C–H amination when
the C–H bonds are (1) proximal to the azide moiety and (2) sufficiently weak to be activated.
1. INTRODUCTION
metals have been observed. For example, organoazides
bound to an early transition metal such as tantalum,26-27
vanadium,28-29 or tungsten30 display a significantly bent N–
N–N moiety along with a relatively short M–Nγ distance
due to a π–back bonding interaction. This binding mode
is most commonly observed when the organoazide
behaves as a dianionic ligand in the form of a diazenimido
(Figure 1a). In contrast, organoazides prefer to bind in a
neutral (redox-innocent) fashion to late transition metals
(e.g., palladium,24 iridium,31 copper,32 silver,32 ruthenium,33
and cobalt34) and exhibit a relatively linear N–N–N moiety
(Figure 1b-c). Interestingly, an iron-based organoazide
adduct reported by the Peters group manifests
intermediate binding properties of the aforementioned
two extremes by displaying a partially oxidized iron center
along with a bent N–N–N moiety owing to a spin
delocalization through the azide moiety (Figure 1d).35 In
addition to these η1-type interactions, an η2-coordination
has been observed by Hillhouse using a 1,2-bis(di-tert-
butylphosphino)ethane nickel complex (Figure 1e).36
Transition-metal-mediated C–H amination is an
appealing synthetic route for direct incorporation of N-
functionality into unactivated C–H bonds.1-6 For such
transformations, metal nitrene complexes (e.g., imido,
M(NR2–);7-9 iminyl, M(2NR–);10-19 nitrene adducts, M(3NR)20-
21) have been invoked as viable N-group transfer reagents,
attracting great interest for synthesizing these
complexes.22 Toward this end, N2 extrusion from
organoazides (N3R) represents one of the most common
approaches to generate metal nitrene complexes.23 As
such, while many metal nitrene compounds have been
isolated,
the
corresponding
precursors,
metal-
organoazide adduct complexes are relatively rare due to
rapid N2 expulsion.24
Despite the transient nature of metal-organoazide
adduct complexes, a few examples have been structurally
characterized.25 Owing to the possible resonance
structures and the dipolar character of the azide moiety,
several binding modes of organoazides towards transition
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Moreover, μ2-coordination has been observed with a
heterobinuclear complex composed of zirconium and
iridium (Figure 1f).37
Indeed, using alkyl azide adducts, we were able to directly
observe the proposed high-valent Co-nitrene
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8
intermediate within a crystal lattice following either
thermolysis or X-ray irradiation of single crystals of the
azide adducts. Alternatively, a more sterically accessible
ligand tBuL (tBuL = 5-mesityl-(1,9-di-tert-butyl)dipyrrin)
offers greater flexibility to analogous alkyl azide adducts
enabling facile intramolecular C–H amination to afford
substituted pyrrolidines. Detailed mechanistic studies on
the C–H amination processes establish the competency of
the azide adduct itself to undergo C–H amination without
necessitating a high-valent metal nitrene intermediate.
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Figure 1. Observed binding modes of organoazides to a
metal center(s).
2. RESULTS AND DISCUSSION
2.1. Synthesis of Cobalt Organoazide Adducts. Our
group has previously reported the preparation of both
four- and three-coordinate dipyrrinato CoII complexes,
(ArL)CoCl(py) (ArL = 5-mesityl-1,9-(2,4,6-Ph3C6H2)dipyrrin)
(1)45 and (ArL)CoBr (2),46 respectively. We envisioned that
treatment of such CoII complexes with an organoazide
would furnish either the corresponding organoazide-
bound complexes or cobalt nitrene species. Heating a
Each binding mode can dictate
a
discrete
decomposition pathway for conversion to the
29, 36-37
corresponding metal nitrene compounds.26-27,
Moreover, in a few cases, metal-organoazide adducts, and
not the corresponding metal nitrene complexes, are
proposed as viable nitrene group transfer reagents as
elucidated by kinetic analysis.25, 38-40 Thus, studying the
nature of the binding interaction and the electronic
structure of organoazide-bound metal complexes
becomes critical for investigating subsequent nitrene
group transfer reactions.
solution of
1 in benzene-d6 with 1-azido-4-(tert-
butyl)benzene N3(C6H4-p-tBu) at 60 °C, however, affords
no reaction. In contrast, the coordinatively unsaturated
complex
2 rapidly consumes the azide at room
temperature to generate a new paramagnetic species as
Our group has previously demonstrated both intra- and
intermolecular C–H amination mediated by FeIII iminyl
species generated from dipyrrinato FeII complexes and
various organoazides.11-13, 41 In the synthesis of these ferric
iminyl complexes, the corresponding organoazide-bound
iron complexes have been invoked as intermediate
species. However, no such intermediate was detected due
to extremely fast N2 extrusion. Similarly, organoazide
adducts have been often proposed as relevant precursors
verified by 1H NMR spectroscopy.
Crystals of this product were obtained from
a
toluene/pentane mixture at –35 °C. X-ray diffraction
analysis revealed formation of the corresponding four-
coordinate aryl azide-bound complex (ArL)CoBr(N3(C6H4-
p-tBu)) (3) (Scheme 1, Figure 2). The solid-state structure
of
3 exhibits a distorted trigonal monopyramidal
geometry (τ4 = 0.80),47 featuring an axially coordinated aryl
azide with a Co–N distance of 2.111(5) Å, and a nearly
linear N–N–N angle of 174.8(7) °. Additionally, an
intramolecular π–π stacking between the aryl unit of the
parent organoazide and one of the phenyl rings from the
2,4,6-triphenylphenyl substituents was observed (Figure
S-1).48-49
in other late, first-row transition metal-catalyzed C–H
42-44
amination processes,15,
those species is absent.
yet structural evidence for
In order to unveil the presence and structural identity of
transient organoazide-bound metal complexes, we chose
to investigate analogous dipyrrinato cobalt complexes as
cobalt is typically harder to oxidize given its higher
electronegativity relative to iron. With this approach, we
report herein the synthesis and spectroscopic
Scheme 1. Synthesis of 3
characterization of
a series of organoazide-bound
dipyrrinato CoII complexes. By utilizing a sterically
encumbered dipyrrin scaffold ArL (ArL = 5-mesityl-1,9-
(2,4,6-Ph3C6H2)dipyrrin),
we
were
able
to
crystallographically characterize both aryl and alkyl azide-
bound Co complexes. From those adduct species, we
demonstrate a range of intra- and intermolecular C–H
activation processes as well as N-group transfer reactivity,
which is proposed to be mediated by a high-valent nitrene
intermediate such as a CoIV imido or CoIII iminyl species.
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coordinates to the N as opposed to terminal N ligation.
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To date, only a few complexes feature this binding motif,
most of which feature a second- or third-row transition
metal such as Rh,50 Pd,24 Ag,32 Ir,31 or Au.51 Among first-
row transition metals, a bis(pyrrolyl)pyridine pincer
cobalt(II) complex is the only example reported to exhibit
a similar interaction with 1-azidoadamantane.34 We note
that neither mono nor bis ortho-substituted aryl azides
exhibits observable binding to 2, highlighting the
preferred Co–N interaction over the more sterically
accessible N.
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2.2. Electronic Structure of 3. As mentioned above,
the binding mode of the organoazide observed for 3 is
rare, especially for first-row transition metals. In addition,
given that the steric profile of organoazides is not the
dominating factor that dictates the binding mode, we
Figure 2. Solid-state structure of 3 at 100 K with thermal
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hypothesized that
3 may favor certain electronic
ellipsoids set to the 50% probability level (hydrogen atoms
and solvent molecules are omitted for clarity; Co aquamarine,
C gray, N blue, Br, maroon). Selected bond lengths (Å) and
angles (deg) for 3: Co–N 2.111(5); N–N 1.282(7); N–N
1.125(7); N–N–N 174.8(7).
configurations. As such, we sought to investigate the
electronic structure of 3 by characterizing the binding
properties of the organoazide. First, as the bond length of
Co–Nα (2.111(5) Å) is within the range of a Co–N single
bond, we speculated that 3 can be best described as a
We note that complex 3 displays a relatively rare
binding mode of the organoazide, where the cobalt center
Figure 3. (a) Solution IR spectra of free 1-azido-4-(tert-butyl)benzene (above, blue) and 3 (below, red) in benzene. (b) EPR
spectrum of 3 in frozen toluene at 4 K (above, black) and its simulation (below, red); simulation parameters: S = 3/2, g1 = 2.4, g2
= 2.4, g3 = 2.4; A1(Co) = 0 MHz, A2(Co) = 600 MHz, A3(Co) = 200 MHz. (c) Mulliken spin-density plot calculated for 3.52
Scheme 2. Intra- and Intermolecular Nitrene Group Transfer Reactivity of 3
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3
Lewis acid-base pair. Moreover, we observed that aryl
density (S = /2) is mostly localized on the cobalt center
azides such as 2-azido-1,3,5-trifluorobenzene or 1-azido-
2,3,4,5,6-pentafluorobenzene display no binding affinity
towards 2, suggesting that the relatively electron deficient
aryl azides are not sufficiently donating. These results are
in line with the lack of reactivity between 1 and 1-azido-
4-(tert-butyl)benzene as pyridine is more Lewis basic than
the aryl azide, suggesting a simple dative interaction
between the cobalt and the organoazide.
(Figure 3c). Thus, we believe that the bonding between the
cobalt and the aryl azide can be best depicted as a redox-
neutral, Lewis acid-base interaction. This electronic
structure assignment is in accord with the previous report
by Marynick which showed that in the absence of π-
backbonding, coordination through Nα is favored as the
substituted nitrogen atom (Nα) is more basic than the
terminal N.32
The solution IR spectrum of 3 in benzene revealed a
distinct blue-shifted ν(N3) stretch at room temperature,
indicating the absence of π-backbonding (Figure 3a).
Additionally, the frozen toluene solution EPR spectrum of
3 at 4 K displays a typical hyperfine structure of a high-
2.3. N-group Transfer Reactivity of 3. With a
comprehensive understanding of the electronic
properties of 3, we sought to investigate its N2 extrusion
reactivity and subsequent N-group transfer chemistry.
While 3 is relatively stable at low temperatures, slow decay
to a new paramagnetic species was observed over 3 days
at room temperature. The same transformation was
completed in 20 hours at 50 °C accompanied by a color
change from maroon to purple.
3
spin (S = /2) CoII center, validating the redox-innocent
ligation of the azide moiety (Figure 3b). These
spectroscopic data are further corroborated with single-
point DFT calculations using the crystallographic
coordinates of 3 to illustrate that the unpaired spin
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Figure 4. (a) Solid-state structure for 4 at 100 K with the thermal ellipsoids set at the 50% probability level (hydrogen atom
except for N–H and solvent molecules are omitted for clarity; Co aquamarine, C gray, N blue, Br maroon, H white). (b) UV/vis
traces for the conversion of 3 to 4 in benzene at 50 °C with spectra recorded every 30 min for 20 h. (c) Solid-state structure for
5 at 100 K with the thermal ellipsoids set at the 50% probability level (hydrogen atoms except for aniline N–H and solvent
molecules are omitted for clarity; Co aquamarine, C gray, N blue, Br maroon, H white).
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Single crystals of the purple product were grown from
a hexane/benzene mixture (2:1) stored at – 35 °C.
Interestingly, the solid-state structure of the species
revealed a N2-released product (4), which is formed upon
ligand functionalization. The central phenyl ring of one of
the 2,4,6-triphenylphenyl substituents from ArL is
dearomatized following a [3+2] annulation with the
parent aryl azide fragment. The aryl moiety of the parent
azide restores its aromaticity upon a subsequent H–atom
transfer (HAT). Additionally, the solid-state structure
highlights the syn-addition of the nitrene moiety into the
phenyl group (Scheme 2, Figure 4a).
For this unique annulation process, either a CoIII iminyl
(ArL)CoBr(·N(C6H4-p-tBu)) or a CoIV imido (ArL)CoBr(N(C6H4-
p-tBu)) species could serve as a potential intermediate.
Given that the aryl moiety of the parent azide is engaged
in the transformation, we propose that the CoIII iminyl
complex would be the more relevant intermediate, as
significant radical delocalization throughout the aryl unit
was observed for the iron analogue (ArL)FeCl(·N(C6H4-p-
tBu)).11
Figure 4c). Furthermore, at room temperature, exposure
of 3 to either 200 equiv of styrene in benzene or neat
cyclohexene afforded the corresponding aziridine product
(1-(4-(tert-butyl)phenyl)-2-phenylaziridine) or amination
product (4-(tert-butyl)-N-(cyclohex-2-en-1-yl)aniline) in
34% and 21% yield, respectively (Scheme 2). Along with
the desired products, in both cases, formation of the
corresponding diazene and aniline was also detected.
Similar diazene generation has been observed in several
other N-group transfer reactions mediated by the
33, 35
corresponding metal-nitrene complexes.13,
These
results corroborate the presence of a transient Co-nitrene
equivalent and demonstrate its viability as a nitrene-
group delivery reagent.14-15, 53-59
2.4. Reactivity of Dipyrrinato CoII Alkyl Azide
Adducts. Encouraged by the N-group transfer reactivity
of 3, we attempted to expand the C–H amination reactivity
by modifying the bound organoazide. Particularly, we
were inspired by our previously reported Fe-catalyzed
intramolecular C–H amination which is mediated by a
high-spin ferric alkyl iminyl complex.12, 60 Given that we
propose
3
furnishes an analogous high-valent
The conversion from 3 to 4 exhibits no accumulation of
intermediate species by H NMR spectroscopy and clean
intermediate, we envisioned that the similar
transformation affording N-heterocyclic compounds
might be feasible by replacing the aryl azide of 3 with an
alkyl azide.
1
isosbestic points (at λ = 340, 460, and 575 nm) are
observed via UV/vis spectroscopy (Figure 4b), presumably
due to a fast [3+2] annulation process following loss of
N2. Nevertheless, in the presence of excess 1,4-
cyclohexadiene, a benzene-d6 solution of 3 exclusively
furnished the corresponding aniline-bound CoII complex
(ArL)CoBr(NH2(C6H4-p-tBu)) (5) at 50 °C, likely following
two sequential H−atom abstraction (HAA) steps mediated
by the proposed Co-nitrene intermediates (Scheme 2,
Akin to the synthesis of 3, we were able to prepare a
series of alkyl azide-bound cobalt complexes by treating
2 with a stoichiometric amount of organoazides such as
benzyl azide, (4-azidobutyl)benzene, or 1-azido-4-
methylpentane (Scheme 3, complexes 6, 7, and 8,
respectively). α-Gem-dimethyl substituted alkyl azides,
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however, do not bind to 2 likely owing to the steric relative to the free azide (Figure S-2). The frozen toluene
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hindrance around the Nα atom, suggesting that the innate
binding preference for Nα over Nγ is retained. Indeed, the
solid-state structures of 7 and 8 revealed that each azide
binds through the Nα with a Co–Nα distance 2.041(3) Å
and 2.053(4) Å, respectively (Figure 5a and 5b). Similar to
EPR spectrum of 8 features a hyperfine structure for high-
spin CoII, indicating a similar dative interaction of the alkyl
azide as observed for the aryl congener 3 (Figure S-6).
Given that adducts of linear alkyl azides are often
proposed as intermediates for the transition-metal-
mediated ring-closing catalysis to generate N-
heterocycles, it is noteworthy that no such adduct has
been structurally characterized prior to this study.12, 42, 44, 61
3, both
7
and
8
exhibit
a
distorted trigonal
monopyramidal geometry with τ4 = 0.84 and 0.81,
respectively. Additionally, solution IR spectrum of 8
displays a distinct blue-shifted azide stretch by 46 cm−1
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Scheme 3. Synthesis and Reactivity of Dipyrrinato CoII Alkyl Azide Adduct Complexes
Figure 5. Solid-state structures for (a) 7, (b) 8 and (c) 9 at 100 K with thermal ellipsoids at the 50% probability level (hydrogen
atoms except for imine moiety of 9 and solvent molecules are omitted for clarity; Co aquamarine, C gray, N blue, Br maroon, H
white).
Interestingly, these alkyl azide-bound CoII complexes
display distinct kinetic profiles from 3. First, unlike 3, none
of these complexes (6-8) expels N2 at room temperature.
Instead, upon heating to 60 °C in benzene-d6, quantitative
formation of the corresponding imine adduct was
observed (Scheme 3). In the case of 6, the corresponding
benzyl imine bound complex (9) was crystallographically
characterized with a Co–Nα distance of 2.029(2) Å (Figure
5c). A similar transformation has been observed in our
previous studies on C–H amination catalysis mediated by
either a ferric iminyl10, 12 or a cobalt imido46 species via
rapid intramolecular α–H–atom abstraction.57 Thus, the
reactivity of 6-8 is in line with our proposed generation of
a CoIII iminyl or CoIV imido intermediate (Scheme 3).
Moreover, unlike the conversion process of 3 to 4 showing
intermediate was observed by 1H NMR spectroscopy while
heating a benzene-d6 solution of 8 at 60 °C to afford the
corresponding imine adduct (Figure S-7). We speculated
that the observed transient intermediate could be the
proposed cobalt nitrene complex. However, our attempts
to isolate the intermediate were unsuccessful due to the
rapid subsequent α–HAA.
2.5.1. In Crystallo Thermal Extrusion of N2 from 8.
We envisioned that observation of the N2-released
intermediate (e.g., 7−N2 and 8−N2 in Scheme 3) may be
accomplished in a crystal lattice upon thermolysis.62-63
Given that 8 reacts above 60 °C in solution, a single crystal
of 8 was heated to 345 K on an X-ray diffractometer for 5-
10 min followed by cooling back to 100 K for full data
collection. The thermolysis was repeated four times on the
no accumulation of intermediates,
a paramagnetic
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same single crystal of 8 until the crystal decomposed and
of the crystal inhibits observation of higher conversions.65-
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8
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each data set was compared to the initial 100 K X-ray
structure to monitor relative changes in occupancy of the
nitrogen atoms (Nα, Nβ, and Nγ) and the bond distance
between Co and the bound nitrogen atom (Nα).
The results suggest that loss of N2 occurred upon
cleavage of the Nα –Nβ bond as indicated in a reaction-
difference map (Table S-2 and Figure S-26). The reaction
difference map indicates the difference between the two
data sets obtained before and after the four iterations of
heating of the same single crystal of 8. While almost no
change has been detected for the ancillary ligand (ArL), a
Indeed, noticeable changes in occupancy of the Nβ and
Nγ were observed while the space group of the crystal
(monoclinic P21/c) did not change. Specifically, the
occupancies of Nβ and Nγ decreased by 16% (relative
conversion) upon the first heating and by an additional
4% (relative conversion) over the subsequent three
heating iterations to afford an overall 20% conversion.
Based on the relatively subtle changes in the occupancies
of nitrogen atoms over the last three heating iterations,
we propose that the solid-state reaction reached
significantly shorter Co–Nα distance 1.82(3)
Å as
9
compared to the initial distance of 2.053(4) Å was
observed from the final model of 8−N2 which is refined
based on the changes in the reaction-difference map
(Figures 6a). We do not refine electron density for the
extruded N2, which is likely lost from the crystal at the
elevated temperatures used to promoted N−N cleavage.67
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few minutes.64
Given that one of our previously reported four-
maximum conversion within
a
coordinate CoIII complexes,
a
metallacycloindoline
Nevertheless, because the quality of the single crystal
sample decays upon N2 escape from the crystal lattice, we
cannot fully exclude the possibility that the lower quality
(ArL)Co(κ2-NHC6H2-2,4-Me2-6-CH2) exhibits a Co−N bond
length of 1.845(3) Å,45 the observed
Figure 6. Solid-state structures for (a) 8–N2 collected at 100 K following heating to 345 K, (b) 8–N2, and (c) 7–N2 collected at
100 K upon X-ray irradiation with thermal ellipsoids at the 50% probability level (hydrogen atoms and solvent molecules are
omitted for clarity; Co aquamarine, C gray, N blue, Br maroon).
Co−Nα bond length (1.82(3) Å) suggests that 8−N2 is likely
a CoIII iminyl rather than a CoIV imido complex.
Furthermore, computational analysis on 8–N2 reveals
significant spin density localized on the Nα, suggesting
that the nitrene (NR) unit is more likely an open-shell
iminyl (2NR1–) as opposed to a closed-shell imido (NR2–),
proposing that 8–N2 can be best described as a Co(III)
iminyl rather than a Co(IV) imido (Table S-4 and S-5).
National Laboratory (ANL). Prolonged irradiation of each
of 7 and 8 with a high-flux synchrotron source led to the
X-ray induced conversion to 7−N2 (69% conversion) and
8−N2 (65% conversion), respectively. Conversion was
calculated based on occupancy changes of the Nβ and Nγ
(Figures S-28, S-29). Both 7−N2 and 8−N2 exhibit
significantly contracted Co–Nα distances of 1.840(7) Å and
1.787(8) Å, respectively, which is in agreement with the
preliminary result observed upon thermolysis (Figure 6b-
c). In contrast to the result from thermolysis and
presumably due to the lower temperature at which it was
generated, the extruded N2 moiety was observed along
with the proposed iminyl complex. Based on the
observation that evolved N2 is not observed in 8-heat(1-
4) (presumably due to diffusion out of the crystalline
sample), we allowed the N2 occupancy to refine
independent of the occupancy of the iminyl fragment. X-
ray induced elimination of N2 from 7 or 8 was not
2.5.2. In Crystallo X-ray Induced N2–Extrusion from
7 and 8. In order to gain further evidence for the
proposed intermediate and minimize the heat-induced
crystal decay, we have performed the similar experiments
at a significantly lower temperature (100 K) upon
irradiation with a high-flux X-ray source.68-69 Indeed, in
crystallo N2 loss was also observed when crystallographic
data was collected using a synchrotron source (0.41328 Å,
30 keV) at the Advanced Photon Source (APS), Argonne
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observed using rotating anode sources, and thus these that the observed N2-released structures (7−N2 and 8−N2)
1
2
3
4
5
6
7
8
could be either the corresponding CoIII amide (NHR) or
CoII imine (NH=CHR’) complexes. Our assignment is
supported by the observation that both 7 and 8 are stable
at room temperature (as indicated by 1H NMR
spectroscopy (Figure S-16)) and their chemical
composition has been corroborated by CHN elemental
analysis, which excludes co-crystallization of 7 or 8 along
with their corresponding CoIII amide or CoII imine complex.
Moreover, neither 7 nor 8 exhibits intermolecular HAA
reactivity as mentioned in section 2.4, suggesting that
formation of a CoIII amide complex is highly unlikely,
especially in the solid-state. Lastly, as mentioned above,
7−N2 and 8−N2 display significantly different Co−Nα
distances with respect to the one from the authentic imine
adduct 9 (2.029(2) Å). However, we emphasize that further
studies and spectroscopic characterization will be
necessary to better assign these compounds’ identity and
understand their electronic structure.
observations indicate that N3 activation is induced by
sufficiently high-flux X-ray irradiation. Similar flux-
induced chemical reactions have been observed in
disulfide cleavage reactions during prolonged X-ray
irradiation of protein samples and has been suggested to
arise as a mechanism to dissipate absorbed X-ray
energy.70,71-72
These results closely parallel recent observations of
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photochemical and X-ray induced loss of N2 from Ru2
50, 73
azide 63 and Rh2 adamantyl azide
complexes, which
resulted in nitride and nitrene intermediates, respectively.
Combined with the present example of N2 loss from a
cobalt complex featuring organic azide ligands, this suite
of reports highlights the potential from in crystallo
chemical transformations to provide access to crystalline
samples of reactive intermediates that are insufficiently
stable to be handled by more classical methods. Further,
while in the Ru2 and Rh2 examples, significant conversion
was obtained in the solid state, the current case highlights
the potential to derive chemically meaningful structural
information even from incompletely converted crystalline
samples.
2.6. Ligand Modification for a Sterically Accessible
CoII Synthon. With a better understanding of the
structures and reactivity of Co-organoazide adducts and
the resulting Co-nitrene complexes, we hypothesized that
the steric hindrance of ArL limits the flexibility of the alkyl
chain of 7 and 8, thus precluding the desired cyclization.
As such, we attempted to synthesize a sterically more
accessible dipyrrinato CoII synthon. Metalation of (tBuL)Li
The significantly contracted Co−Nα distances lead us to
formulate 7−N2 and 8−N2 as the corresponding Co-iminyl
complexes. Given high errors in our X-ray studies as a
result of rapid crystal decomposition during data
collection and the fact that detecting the presence of
H−atoms is often limited by single crystal X-ray diffraction
techniques, we cannot completely exclude the possibility
Scheme 4. Synthesis of 10, 11, and 12
(
tBuL
=
5-mesityl-(1,9-di-tert-butyl)dipyrrin)
with
anhydrous CoCl2 or CoBr2 in diethyl ether followed by
refluxing in toluene afforded the dimeric
Scheme 5. 1,3-Dipolar Cycloaddition Reactivity
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11
Figure 7. (a) Solid-state structures for (a) 11, (b) 12, and (c) 14-Br at 100 K with thermal ellipsoids at the 50% probability level
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(hydrogen atoms and solvent molecules are omitted for clarity; Co aquamarine, C gray, N blue, O red, Br maroon).
species [(tBuL)CoCl]2 (10) and [(tBuL)CoBr]2 (11), respectively
(Scheme 4, Figure 7a). Complexes 10 and 11 are suitable
synthons to explore further reactivity with organoazides
as they do not feature exogenous solvent molecules
which can potentially hamper the desired binding of
organoazide substrates. Moreover, such dimers can
readily dissociate into the corresponding solvent-bound
monomeric species, when exposed to Lewis basic
molecules, as exemplified by the thf-adduct 12 (Scheme
4, Figure 7b). This result suggests a similar dissociation
may be possible in the presence of organoazides to
generate the corresponding monomeric organoazide-
bound complex.
substituted Nα. It is noteworthy that the reaction occurs at
room temperature, since in the absence of metal
complexes, a similar transformation occurs only upon
refluxing with an activated olefin moiety.74 Furthermore,
as 1,3-dipolar cycloadditions are generally facilitated by
Lewis-acids,75-78 the observation is in line with our
assignment that the cobalt center is Lewis acidic. The
observed cycloaddition transformation supports our
initial hypothesis that smaller substituents on the dipyrrin
platform enhance the flexibility of the alkyl chain.
Encouraged by this result, we next subjected a series of
alkyl azides lacking internal olefins such as (4-
azidobutyl)benzene, 1-azido-4-methylpentane, or 1-
azidobutane to a benzene-d6 solution of 10. In all cases,
the corresponding alkyl azide-bound complexes were
generated immediately at room temperature as judged by
1H NMR spectroscopy (Scheme 6, complexes 15, 17, and
19). Akin to 2, neither 10 nor 11 binds α-gem-dimethyl
substituted alkyl azides suggesting the binding propensity
towards the Nα–atom is maintained. Furthermore, solution
IR spectra of these adducts in benzene exhibit a blue-
shifted azide stretch validating that the azide coordination
is redox innocent (Figures S-3, S-4, and S-5).
Indeed, upon treatment of either 10 or 11 with a
stoichiometric amount of 6-azidohex-1-ene, the
immediate formation of the corresponding azide adduct
(13) was confirmed by 1H NMR spectroscopy (Scheme 5).
Interestingly, a benzene-d6 solution of 13 readily converts
into a new paramagnetic species at room temperature,
identified as the corresponding 1,2,3-dihydrotriazole-
bound cobalt complex (14) via X-ray diffraction studies
(Scheme 5, Figure 7c). The solid-state structure of 14-Br
displays the product bound through the Nγ instead of Nα,
presumably due to the steric encumbrance around the tri-
Scheme 6. Intramolecular C–H Amination or Activation
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Figure 8. Solid-state structures for (a) 16-Br, (b) 18, and (c) 20 at 100 K with thermal ellipsoids at the 50 % probability level
(hydrogen atoms except for N–H or imine C–H and solvent molecules are omitted for clarity; Co aquamarine, C gray, N blue, Br
maroon, Cl green, H white.)
In contrast to 7 or 8, however, our attempts to isolate
any of these azide-bound species were unsuccessful due
to a greater driving force to regenerate the initial dimeric
species (10 or 11) during crystallization, emphasizing the
reversible binding of the organoazide. Nonetheless, the
maximum value in the Job plot between 11 and 1-azido-
4-methylpentane appeared at 0.5 mole fraction of a total
concentration of CoII center ([CoII]total = 2[11]) suggesting
a 1:1 complexation of a single CoII center and each of the
organoazides as a monomeric species (e.g., 17) (Figure S-
corresponding pyrrolidine-bound complexes (16) and
(18), respectively (Scheme 6a, Figure 8a-b). It is notable
that loss of N2 from 15 and 17 occurs at a lower
temperature compared to the reactivity observed from 7
and 8 and proceeds without any imine formation.
Surprisingly, at the same temperature (40 °C), no reaction
was observed for 19, which possesses a stronger, primary
C–H bond at the C4 position of the alkyl chain. Instead, 19
expels N2 upon heating to 80 °C to afford the
corresponding imine adduct (20) via α−H–atom
abstraction (Scheme 6b, Figure 8c). Given that N2
elimination is irreversible, these observations suggest the
following: (1) the temperature required for N2 expulsion
and subsequent cyclization depends on the C–H bond
strength on the fourth carbon (C4) of the linear alkyl azide
and (2) there is no formation of an N2-released
intermediate (such as a CoIV imido or CoIII iminyl species)
at relatively low temperatures as the azide moiety of 19
remains intact at 40 °C.
1
9). Moreover, the changes in H NMR chemical shifts of
11 as a function of concentration of organoazides to the
corresponding monomeric organoazide adducts are
almost identical regardless of the identity of the aliphatic
group of the azide substrates, suggesting the nearly same
binding affinities of the azides to a CoII center (Figure S-
10).
Gratifyingly, upon heating a benzene-d6 solution of 15
and 17 at 40 °C, we observed clean formation of the
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Scheme 7. Intermolecular H–Atom Abstraction from
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2
3
4
5
6
7
8
9
19
Scheme 8. Proposed Pathways for Intramolecular C–H Amination or Activation
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Thus, we hypothesize that activation of the azide moiety
can be induced by the interaction with C–H bonds when
those bonds are weak enough to be activated, suggesting
that the azide adducts themselves are viable species for
C–H amination. To further support this hypothesis, we
heated a benzene-d6 solution of 19 in the presence of
excess 1,4-cyclohexadiene to investigate whether an
external weak C–H bond can promote loss of N2 at a lower
temperature. Indeed, under these conditions, slow
conversion to the corresponding amine adduct (21) was
observed at 40 °C (Scheme 7, Figure S-11). Recalling that
19 expels N2 only above 80 °C in the absence of 1,4-
cyclohexadiene, this result supports the idea that the
interaction of the azide moiety with a weak C–H bond is a
key step towards N2 release and subsequent C–H
amination.
complexes. For example, benzylic C–H bond amination
and olefin aziridination catalyzed by Co38 and Ru40
porphyrin complexes, respectively, are proposed to be
mediated by azide adduct species as opposed to the
corresponding metal nitrene complexes. Likewise, C–H
activation or group transfer reactions promoted by a
simple oxidant adduct is not only limited to organoazide-
bound complexes but also observed for iodoimine
(ArI=NTs),79 iodosylarene (ArIO) or iodoxyarene (ArIO2)
adducts,80-81 suggesting that metal-ligand multiply
bonded species are not always the active group transfer
reagents. While we cannot fully exclude the presence of a
high-energy intermediate complex such as a reorganized
form of the azide adducts for this specific route (pathway
I), we propose that these cobalt-organoazide adducts
serve as active group transfer reagents. Furthermore, we
believe that a key feature enabling pathway I is the
sterically accessible dipyrrin scaffold tBuL facilitates the
positioning of the weak C–H bonds at C4 proximal to the
azide moiety for concomitant C–H activation and C–N
bond formation; whereas proximal orientation of the
substrate C–H bonds is not possible for the more sterically
encumbered ArL. Secondly, in the absence of proximal
weak C–H bonds, C–H activation (i.e., α−H–atom
abstraction) may be mediated by the corresponding CoIV
imido or CoIII iminyl intermediates, which can be
Taken together, we propose two distinct pathways for
activation of the azide moiety followed by intramolecular
C–H amination or C–H activation. First, in the presence of
relatively weak C–H bonds (e.g., benzylic or tertiary C–H
bonds), we believe that formation of pyrrolidines is
directly mediated by the azide adducts, rather than a
high-valent intermediate such as a CoIV imido or CoIII
iminyl species (Scheme 8, pathway I). Such direct nitrene
group transfer reactivity has been previously reported
from
a
few proposed metal-organoazide adduct
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generated at relatively high temperatures via thermal N2 towards understanding the nature and reactivity of
1
2
3
4
5
6
7
8
extrusion (Scheme 8, pathway II). We propose that such
intermediates generated at high temperatures would
structurally resemble the Co-nitrene complexes described
in Sections 2.5.1. and 2.5.2.
commonly not isolable organoazide-bound metal
complexes for C–H amination processes.
ASSOCIATED CONTENT
Supporting Information.
This material is available free of charge via the Internet at
http://pubs.acs.org.
3. CONCLUSIONS
In this report, we demonstrated the synthesis of a series
of organoazide-bound dipyrrinato CoII complexes and
highlighted that their nitrene group transfer reactivity can
be tuned by the (1) identity of the bound organoazide
(aryl azide versus alkyl azide) and (2) steric properties of
the substituents on the dipyrrin scaffold (2,4,6-
triphenylphenyl versus tert-butyl). First, by utilizing a
sterically encumbered ligand ArL, the binding mode of the
organoazides was characterized by single-crystal X-ray
diffraction, solution IR spectroscopy, and EPR
spectroscopy (at 4 K) to identify a redox neutral
coordination through the N preferentially over Nγ.
Although such binding mode is consistent among varying
the R substituents (aryl versus alkyl) of the organoazides,
we observed notably different kinetics for N2 extrusion as
well as scope of N-group transfer reactivity. For instance,
the aryl azide-bound complex 3 eliminates N2 at room
temperature to undergo either intra- or intermolecular C–
H amination. We propose that such transformations are
mediated by a CoIV imido or CoIII iminyl species, yet no
accumulation of intermediates was spectroscopically
detected. In contrast, the analogous complex 8 featuring
an aliphatic azide expels N2 only above 60 °C, and an
intermediate species was observed during the conversion
into the corresponding imine compound. Although
isolation of the intermediate was not feasible in solution
due to the facile subsequent α−H−atom abstraction, we
were able to cleave the N−N bond within a crystal lattice
to observe the corresponding N2-released structure,
which we have assigned as the corresponding Co-
nitrenoid (i.e., CoIII(2NR), CoIV(NR)) complex. Future work
will focus on studying the electronic structure of the Co-
9
General experimental considerations and procedures,
multinuclear NMR data, IR spectra, EPR spectra,
computational details (PDF)
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Crystallographic data (CIF)
AUTHOR INFORMATION
Corresponding Author
*betley@chemistry.harvard.edu
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
T.A.B. acknowledges this work was supported by a grant from
the NIH (GM-115815), the Dreyfus Foundation (Teacher-
Scholar Award), and Harvard University. Y.B. gratefully
acknowledges a Kwanjeong Graduate Student Fellowship.
D.C.P. thanks the Welch Foundation (A-1907) and the U.S.
Department of Energy (DE-SC0018977) for financial support.
The authors thank Yu-Sheng Chen for helpful discussion.
Crystal structures of 7−N2 and 8−N2 in section 2.5.2 were
determined at ChemMatCARS Sector 15, which is housed at
the APS, which is principally supported by the NSF (Grant
NSF/ CHE-1346572). Use of the PILATUS3 X CdTe 1M
detector is supported by the NSF (Grant NSF/DMR-1531283).
Use of the APS was supported by the U.S. DOE under
Contract No. DE-AC02-06CH11357.
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