Intramolecular redox-active ligand-to-substrate single-electron transfer: Radical reactivity with a palladium(II) complex

Article abstract of DOI:10.1021/ja502164f

Coordination of the redox-active tridentate NNO ligand L^H2 to Pd^II yields the paramagnetic iminobenzosemiquinonato complex 3. Single-electron reduction of 3 yields diamagnetic amidophenolato complex 4, capable of activating aliphatic azide 5. Experimental and computational studies suggest a redox-noninnocent pathway wherein the redox-active ligand facilitates intramolecular ligand-to-substrate single-electron transfer to generate an open-shell singlet nitrene-substrate radical, ligand radical , enabling subsequent radical-type C-H amination reactivity with Pd^II.

Full text of DOI:10.1021/ja502164f

Communication
pubs.acs.org/JACS
Intramolecular Redox-Active Ligand-to-Substrate Single-Electron
Transfer: Radical Reactivity with a Palladium(II) Complex
Daniel L. J. Broere,† Bas de Bruin,† Joost N. H. Reek,† Martin Lutz,‡ Sebastian Dechert,§
̈
and Jarl Ivar van der Vlugt*,†
†Homogeneous, Bioinspired & Supramolecular Catalysis, van ’t Hoff Institute for Molecular Sciences, University of Amsterdam,
Science Park 904, 1098 XH Amsterdam, The Netherlands
‡Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH Utrecht, The Netherlands
§Institut fur Anorganische Chemie, Georg-August-Universitat Gottingen, 37077 Gottingen, Germany
̈
̈
̈
̈
S
* Supporting Information
ABSTRACT: Coordination of the redox-active tridentate
NNO ligand LH2 to PdII yields the paramagnetic
iminobenzosemiquinonato complex 3. Single-electron
reduction of 3 yields diamagnetic amidophenolato
complex 4, capable of activating aliphatic azide 5.
Experimental and computational studies suggest a redox-
noninnocent pathway wherein the redox-active ligand
facilitates intramolecular ligand-to-substrate single-electron
transfer to generate an open-shell singlet “nitrene-substrate
radical, ligand radical”, enabling subsequent radical-type
C−H amination reactivity with PdII.
edox-active ligands are highly relevant for many metal-
Rloenzymatic transformations, supplying electrons and
facilitating selective atom transfer reactivity.1 Synthetic
analogues have recently also shown remarkable potential in
enabling two-electron redox processes for bond activation and
formation processes, either acting as an electron reservoir or
directing radical-type reactivity when combined with transition
metals.2 Single-electron transfer (SET) from a redox-active
ligand to a substrate without metal oxidation state change is
very rare.3 Transformations mediated by palladium are
dominated by two-electron processes,4 whereas ligand-to-
substrate SET might allow selective substrate activation via a
controlled radical-type mechanism while benefiting from
favorable Pd-substrate coordination.
In order to induce and control this ligand-to-substrate
electron transfer reactivity on a suitable stable Pd platform and
to avoid ligand dissociation during the redox-state shuttling
events, we integrated the redox-active 2-aminophenol5 (NHOH)
unit within a tridentate NNHOH pincer6 scaffold. Upon double
deprotonation, this ligand may coordinate to PdII as a 2-
amidophenolato dianion (NNOAP), iminobenzosemiquinonato
radical monoanion (NNOISQ), or a neutral iminobenzoquinone
(NNOIBQ, Figure 1), without formal redox changes occurring at
Pd.7 Single-electron transfer reactivity from such an NO-
fragment to exogenous electron acceptors is not described to
date for any of its redox states. We envisioned that the
(NNOAP) state might be ideally suited to establish intra-
molecular ligand-to-substrate electron shuttling and to perform
radical-type reactions with PdII.
Figure 1. (A) Redox states of PdII-coordinated NNO ligand. (B)
Concept of ligand-to-substrate single-electron transfer demonstrated
for an azide substrate, generating a “nitrene-substrate radical, ligand
radical” on PdII.
We herein report the synthesis of this new redox-active
NNHOH pincer ligand, bearing an additional pyridine donor to
impart coordinative stability, the resulting air- and moisture-
stable paramagnetic PdII complex (S = 1/2) 3, and its one-
electron reduced diamagnetic derivative 4. The ligand-centered
redox behavior of this one-electron reduced species was probed
experimentally and computationally (DFT). The combined
data indicate that single-electron transfer from the redox-active
ligand to an organic azide occurs under thermal activation to
produce a “nitrene-substrate radical, ligand-radical” PdII
intermediate with an open-shell singlet (singlet diradical)
ground state. As proof-of-principle reactivity with this ligand-
based electron transfer concept, this unusual intermediate
undergoes intramolecular sp3 C−H amination to generate a
pyrrolidine species.
The two-step synthesis of NNHOH ligand LH2 involves
double addition of MeCeCl2 on 2-cyanopyridine8 to form
amine 1 (Scheme 1), followed by condensation with 1,3-di(tert-
Received: March 3, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ja502164f | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
a
Scheme 1. Synthesis of LH2, 2, 3, and 4
correlate well with the experimental data. The giso value of
2.0055 supports an NNOISQ ligand radical coordinated to PdII.
The calculated spin-density plot for 3 (93% total spin density,
34% on the iminosemiquinonato nitrogen) is in agreement with
EPR data (Figure 2, right).
The molecular structure of 3 (Figure 3) shows metric
parameters that are characteristic for the (N)NOISQ ligand
a
Reagents: (i) DTBQ, DTBC, neat; (ii) PdCl2(NCMe)2; (iii) NEt3,
air; (iv) CoCp2.
butyl)quinone to produce an iminoquinone intermediate that is
reduced in situ by 1,3-di(tert-butyl)catechol.9 The geminal
methyl and tert-butyl groups are incorporated in the framework
to prevent β-H elimination and to stabilize the NNOISQ
oxidation state upon coordination, respectively. Colorless
solid LH2 is bench-stable for months but susceptible to
oxidation in solution under air, concomitant with a color
change to green and broadening of the NMR signals. For
Figure 3. Top left: Displacement ellipsoid plot (50% probability level)
of 3. H atoms and solvent omitted for clarity.11 Top right: Cyclic
voltammogram of 3 in CH2Cl2 (10−3 M); scan rate 200 mV s−1;
referenced to Fc/Fc+. Bottom: Relevant XRD metric parameters of 3
(left) and 4 (right).
H2
reference, we also synthesized L′ bearing no gem-dimethyl
groups.10
oxidation state.12 DFT (b3-lyp/def2-TZVP) calculated opti-
mized geometric parameters for the doublet NNOISQ ground
state matched well with the experimentally found values.10
Cyclic voltammetry of 3 in CH2Cl2 solution revealed fully
reversible one-electron oxidation and reduction events at +0.04
V and −1.11 V vs Fc/Fc+, respectively (Figure 3, right).
Chemical reduction of 3 with CoCp2 in CH2Cl2 furnished
[CoCp2][PdCl(NNOAP)] as soluble, air-sensitive diamagnetic
species 4. Single crystals were obtained by reactive diffusion of a
CoCp2 solution into a solution of 3 in benzene. The anionic
portion of this complex is almost isostructural to 3 (Figure 3),
showing an elongated Pd−Cl bond and characteristic bond
lengths for the (N)NOAP oxidation state that matched well with
DFT calculated metric parameters. Synthesis of the neutral
analogue 4PPh3 was achieved by addition of 1 equiv of PPh3 to
either the in situ reduction of 3 or preformed 4.10
Ligand LH2 reacts as a neutral ligand with PdCl2(MeCN)2 to
give orange PdCl2(LH2) (2) in high yield. NMR analysis
suggests pyridine and −NH coordination to Pd (diastereotopic
−CH3 groups; δ 6.58 (NH)), with no interaction of the −OH
group (δ 6.53).10 Addition of NEt3 in MeOH under aerobic
conditions resulted in brown paramagnetic compound 3,
characterized as PdCl(L•) (L• = NNOISQ). Magnetic
susceptibility measurement of 3 at 298 K using Evans’
method11 gave an effective magnetic moment (μeff) of 1.78
μB, indicating an S = 1/2 ground state. X-band EPR
spectroscopy in toluene at 298 K (Figure 2, left) revealed
1
hyperfine couplings with 105Pd, 15N, and two H nuclei. The
simulated spectrum and calculated hyperfine couplings
We anticipated that the reduced nature of the NNOAP
scaffold in species 4 could be utilized to generate an unpaired
electron at a coordinated substrate by unprecedented intra-
molecular ligand-to-substrate SET on PdII. To support this
hypothesis, we performed DFT calculations on 4 with model
azide N3Et. MO plot analysis showed that loss of N2
concomitant with SET from the NNOAP ligand to the nitrene
substrate is indeed accessible, generating a rare “nitrene-
substrate radical,13,14 ligand-radical” PdII species 5NR with an
open-shell singlet (singlet diradical) ground state. 5NR bears
87% α-spin density at the nitrene N-atom (Figure 4; left:
Figure 2. Left: Experimental and simulated EPR spectrum of 3.
Microwave frequency = 9.382892 GHz. Power = 2 mW. Modulation
amplitude = 0.1 G. Simulated (DFT) g value and hyperfine couplings
A (MHz): giso 2.0055 (2.0059); APd +12.8 (+10.7); AN +22.8
R
HOMO for 4N3 , right: spin density distribution for 5NR).
To exploit this concept of ligand-based single-electron
transfer to generate a substrate radical, we investigated the
reactivity of these Pd(NNO) complexes in radical-type sp3 C−
H amination.15 These reactions often proceed via a radical-type
mechanism involving C−H abstraction followed by a radical-
iso
iso
(+17.1); AH1 −10.6 (−7.9); AH2 −2.8 (−2.4). DFT parameters:
iso
iso
ORCA (b3-lyp/def2-TZVP). Right: DFT (b3-lyp/def2-TZVP)
calculated spin-density plot for 3.
B
dx.doi.org/10.1021/ja502164f | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
NNOAP ligand. Loss of N2 generates Pd-nitrene intermediate B
that can exist in three plausible electronic states. The open-shell
singlet diradical (OSS) is more stable than the CSS and triplet
states by 10.6 and 5.8 kcal/mol, respectively. Furthermore, the
OSS nitrene diradical B is most effectively generated from A
(lowest barrier of 11.5 kcal mol−1) via electron transfer from
the NNO-ligand, with no redox chemistry occurring at Pd.
Subsequent intramolecular H-atom abstraction forms inter-
mediate C for the OSS and triplet states with barriers of 20.3
and 19.4 kcal mol−1, respectively. A subsequent low barrier
transition state for the radical rebound step (1.3 kcal mol−1) to
form D was found on the OSS surface. For the CSS species,
direct C−H insertion of the nitrene fragment in B to form D
has a higher absolute barrier than the stepwise radical process
on the OSS surface (Figure 5). Reaction of intermediate D with
Figure 4. DFT (b3-lyp/def2-TZVP) calculated HOMO plot for model
R
complex 4N3 (left) and spin-density plot for model diradical 5NR
(right) with blue: positive (α) and red: negative (β) spin density. R =
ethyl.
rebound step, or alternatively via direct insertion of the radical
nitrene fragment in the C−H bond. The Fe-mediated C−H
amination of unactivated alkyl azides occurs via a radical
pathway involving metal-based redox chemistry,16 but a ligand-
induced radical pathway for this reaction has never been
disclosed. Upon reduction of 3 to 4 with cobaltocene in the
presence of unactivated azide 5 and Boc2O, pyrrolidine 6 (∼1
equiv with respect to 4), and the reduced Boc-protected amine
7 were observed (Scheme 2). Use of 4PPh3, Pd0 (dba)3,
2
Scheme 2. Conversion of Azide 5 into Pyrrolidine 6
Figure 5. DFT (b3-lyp/def2-TZVP) calculated free energy profile
ΔG°298 K (in kcal mol−1) for C−H amination of azide complex A
derived from 4 for the three possible spin states.
PdIICl2(NCMe)2, complex 2 (with and without CoCp2),
complex 3 (with and without AgPF6 or TlPF6), CoCp2, or
Boc2O gives 6 and an unidentified paramagnetic Pd complex.
Reaction of independently prepared D, by addition of
pyrrolidine to 4, with Boc2O also generated product 6. Using
an isotopically labeled analogue of azide 5, selectively
monodeuterated at the benzylic position,10 we established a
kinetic isotope effect (KIE) of 3.35 0.1 for formation of 6,
which is reproduced very well by DFT calculations (KIE of
3.65). Attempts to trap a rare Pd(organo-azide) complex or a
hitherto elusive (quasi)stable Pd-nitrene analogue of B using
e.g. PhINNs, AdN3, or C6F5N3 did not provide a clear
indication for the formation of such species.10
CoCp2 did not result in the formation of product 6.17 The
+
H2
analogous PdCl-complex of L′ was inactive, likely due to
H
formation of iminopyridyl ligand L′ via facile β-H elimination,
which prohibits redox activity of the NO-fragment. Notably, in
the presence of TEMPO-H, reaction of in situ generated 4 with
azide 5 did not lead to any pyrrolidine formation, and the
detection of TEMPO• by EPR spectroscopy10 supports the
trapping of an active radical intermediate.
Based on these data and supported by DFT calculations, we
propose the following mechanism for the intramolecular
cyclization using 4 (Scheme 3). Initial chloride substitution
by azide 5 gives closed-shell singlet (CSS) species A with an
In conclusion, a new redox-active NNO pincer ligand LH2 has
been synthesized and coordinated to PdII, affording para-
magnetic (S = 1/2) complex 3 bearing the ligand-centered
radical NNOISQ (L•), as supported by spectroscopic, X-ray
crystallographic, and computational data. Reduction of 3
generates diamagnetic complex 4, [CoCp2][PdCl(NNOAP)],
which is able to activate azide 5 for intramolecular C−H bond
amination to produce pyrrolidine 6. DFT calculations, isotopic
labeling, and trapping experiments support a process that
involves intramolecular single-electron transfer from the redox-
active ligand to the substrate upon thermal activation of the
organic azide, thus producing an unusual ‘nitrene-substrate
radical, ligand-radical’ PdII intermediate B with an open-shell
singlet (singlet diradical) ground state. The noninnocent NNO
ligand is proposed to dictate single-electron reactivity onto PdII,
enabling radical-type pathways using a metal that is normally
involved in two-electron processes. This concept is likely more
broadly applicable with group 8−10 metals, including for
cooperative bond activation processes and catalysis.
Scheme 3. OSS Pathway from Azide 5 into 6 via Radical-
Type sp3 C−H Amination with 4; calculated free energies
ΔG for species A−D and transition states (red) and relative
barriers ΔΔG (blue) in kcal mol−1
C
dx.doi.org/10.1021/ja502164f | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
(9) Adapted from: Bang, Z. N.; Komissarov, V. N.; Sayapin, Y. A.;
Tkachev, V. V.; Shilov, G. V.; Aldoshin, S. M.; Minkin, V. I. Russ. J.
Org. Chem. 2009, 45, 442.
ASSOCIATED CONTENT
■
S
* Supporting Information
General methods, experimental data for new compounds, NMR
spectra, crystallographic details and cif files for 3 and 4,
computational data. This material is available free of charge via
the Internet at http://pubs.acs.org.
(10) See Supporting Information for details.
(11) Sur, S. K. J. Magn. Reson. 1989, 82, 169.
(12) (a) Lippert, C.; Hardcastle, K. I.; Soper, J. D. Inorg. Chem. 2011,
50, 9864. (b) Sun, X.; Chun, H.; Hildenbrand, K.; Bothe, E.;
Weyhermuller, T.; Neese, F.; Wieghardt, K. Inorg. Chem. 2002, 41,
̈
4295. (c) Chaudhuri, P.; Verani, C. N.; Bill, E.; Bothe, E.;
AUTHOR INFORMATION
Weyhermuller, T.; Wieghardt, K. J. Am. Chem. Soc. 2001, 123, 2213.
̈
■
(13) Review, N-centered ligand radicals in catalysis: (a) Olivos
Corresponding Author
Suar
Bruin, B. Angew. Chem., Int. Ed. 2013, 52, 12510. See also:
(b) Lyaskovskyy, V.; Olivos Suarez, A. I.; Lu, H.; Jiang, H.; Zhang, X.
́
ez, A. I.; Lyaskovskyy, V.; Reek, J. N. H.; van der Vlugt, J. I.; de
j.i.vandervlugt@uva.nl
́
Notes
P.; de Bruin, B. J. Am. Chem. Soc. 2011, 133, 12264. Proposed Pd-
nitrene or −imido species: (c) Mooibroek, T. J.; Schoon, L.;
Bouwman, E.; Drent, E. Chem.Eur. J. 2011, 17, 13318. (d) Berry,
J. F. Comm. Inorg. Chem. 2009, 30, 28.
(14) Pd(organo-azide) complexes are very rare: (a) Barz, M.;
Herdtweck, E.; Thiel, W. Angew. Chem., Int. Ed. 1998, 37, 2262.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Research funded by the European Research Council (ERC
Starting Grant 279097 to J.I.v.d.V.). NWO is thanked for
financing the X-ray diffractometer at UU. We thank Prof. Franc
(b) Besenyei, G.; Par
Int. Ed. 2000, 39, 956.
́ ́ ́
kanyi, L.; Foch, I.; Simandi, L. I. Angew. Chem.,
Meyer (Gottingen) for access to his XRD equipment.
̈
(15) Reviews: (a) Jeffrey, J. L.; Sarpong, R. Chem. Sci. 2013, 4, 4092.
(b) Roizen, J. L.; Harvey, M. E.; Du Bois, J. Acc. Chem. Res. 2012, 45,
911. (c) Gephart, R. T.; Warren, T. H. Organometallics 2012, 31, 7727.
(16) Hennessy, E. T.; Betley, T. A. Science 2013, 340, 591.
(17) Pd2dba3 did lead to full conversion, but only to 7. Pd-black is
observed after reaction; we propose that a decomposition product of 4
is responsible for the formation of 7.
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