Iridium(III)-Catalyzed Intermolecular C(sp3)?H Insertion Reaction of Quinoid Carbene: A Radical Mechanism

Article abstract of DOI:10.1002/anie.201911138

Described herein is an Ir^III/porphyrin-catalyzed intermolecular C(sp³)?H insertion reaction of a quinoid carbene (QC). The reaction was designed by harnessing the hydrogen-atom transfer (HAT) reactivity of a metal-QC species with aliphatic substrates followed by a radical rebound process to afford C?H arylation products. This methodology is efficient for the arylation of activated hydrocarbons such as 1,4-cyclohexadienes (down to 40 min reaction time, up to 99 % yield, up to 1.0 g scale). It features unique regioselectivity, which is mainly governed by steric effects, as the insertion into primary C?H bonds is favored over secondary and/or tertiary C?H bonds in the substituted cyclohexene substrates. Mechanistic studies revealed a radical mechanism for the reaction.

Full text of DOI:10.1002/anie.201911138

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Accepted Article
Title: Iridium(III)-Catalyzed Intermolecular C(sp³)–H Insertion Reaction
of Quinoid Carbene through a Radical Mechanism
Authors: Hai-Xu Wang, Yann Richard, Qingyun Wan, Cong-Ying Zhou,
and Chi-Ming Che
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201911138
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10.1002/anie.201911138
Angewandte Chemie International Edition
RESEARCH ARTICLE
Iridium(III)-Catalyzed Intermolecular C(sp3)–H Insertion Reaction
of Quinoid Carbene through a Radical Mechanism
Hai-Xu Wang, Yann Richard, Qingyun Wan, Cong-Ying Zhou, and Chi-Ming Che*
Abstract: Herein is described an Ir(III) porphyrin-catalyzed
intermolecular C(sp3)–H insertion reaction of quinoid carbene (QC).
The reaction was designed by harnessing the hydrogen atom transfer
(HAT) reactivity of metal-QC species with aliphatic substrates
followed by a radical rebound process to afford C–H arylation
products. This methodology is efficient for the arylation of activated
hydrocarbons such as 1,4-cyclohexadienes (down to 40 min reaction
time, up to 99% yield, up to 1.0 g scale); it features unique
regioselectivity which is mainly governed by steric effect, as the
insertion into primary C–H bonds is favored over secondary and/or
tertiary C–H bonds in substituted cyclohexene substrates.
Mechanistic studies revealed a radical mechanism for the reaction.
have demonstrated that, in addition to carbene transfer reactivity,
isolated Ru(II)-QC complexes could undergo stoichiometric
hydrogen atom transfer (HAT) reactions with activated C(sp3)–H
bonds,[4] thereby displaying their metallaquinone feature;[8] this
has inspired us to develop a stepwise radical-based C(sp3)–H
insertion pathway analogous to those involving metal-oxo
species.[2c] Although catalytic carbene C–H insertion reactions are
dominated by concerted mechanism,[2b,c,e] radical pathway has
been reported for several intramolecular reactions[9] which are
mostly initiated by open-shell carbene radical species;[10] great
challenge still lies in the development of intermolecular reactions.
The closed-shell Ru-QC complexes could undergo intermolecular
HAT with aliphatic C–H substrates, yet no subsequent radical
rebound process was observed presumably due to reductive
quenching of ligand radical by the electron-rich Ru(II) center
(Figure 1b);[4] we envisioned that changing the metal center to a
less reducing Ir(III)[11] might increase the lifetime of the ligand
radical and thus facilitate the rebound step. Herein is described a
protocol of Ir(III) porphyrin-catalyzed intermolecular QC insertion
reactions into C(sp3)–H bonds via a radical mechanism.
Introduction
Transition metal-catalyzed carbene transfer and insertion
reactions constitute powerful synthetic tools in modern organic
chemistry.[1] In particular, catalytic carbene C–H insertion
reactions with -diazocarbonyl compounds allow direct
functionalization of sp3 and/or sp2 C–H bonds (Figure 1a).[2]
Alternatively, metal-carbene intermediates serving as aryl
synthons have been demonstrated with quinone diazides as
carbene sources;[3] the thus formed metal-quinoid carbene (QC)
species is electrophilic[4] and termed as “umpoled phenol” by
Baran and co-worker.[5] Although several examples of C(sp2)–H
QC insertion reactions into simple arenes and directing group-
containing substrates have been reported in the literature,[6]
catalytic activation/functionalization of C(sp3)–H bonds by metal-
QC intermediates remains rarely explored.[7] Very recently we
[*]
Dr. H.-X. Wang, Dr. Q. Wan, Prof. Dr. C.-Y. Zhou, and Prof. Dr. C.-
M. Che
State Key Laboratory of Synthetic Chemistry
Department of Chemistry
The University of Hong Kong
Pokfulam Road, Hong Kong (China)
E-mail: cmche@hku.hk
Prof. Dr. C.-M. Che
HKU Shenzhen Institute of Research & Innovation
Shenzhen (China)
Figure 1. Intermolecular metal-carbene C(sp3)–H insertion catalysis. (a)
Conventional approach with -diazocarbonyl compounds. (b) Ir(III) porphyrin-
catalyzed QC insertion reaction (this work) based on the stoichiometric HAT
reactivity of Ru(II)-QC complexes reported in ref 4. Por = porphyrinato dianion.
Prof. Dr. C.-Y. Zhou
College of Chemistry and Materials Science
Jinan University
Guangzhou (China)
Results and Discussion
Y. Richard
Faculté des Sciences
Université catholique de Louvain
Place des Sciences 2, 1348 Louvain-la-Neuve (Belgium)
We initiated our trial with 1,4-cyclohexadiene (CHD) as the
aliphatic C–H substrate (5 equiv) and [Ir(TTP)Me] (2 mol%) as the
catalyst, and the C(sp3)–H arylated product 1a was obtained in
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201911138
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RESEARCH ARTICLE
48% yield (Table 1, entry 1). The reaction was significantly
retarded by a bulkier porphyrin ligand such as TMP or TDCPP
(entry 2–3), and gratifyingly, by using OEP ligand that is free of
porphyrin meso-substituents, an increase in yield of 1a to 62%
was observed (entry 4); these findings suggest that spatial
environment of the catalyst might play an important role in this
reaction. Other common catalysts for carbene transfer reactions
showed no to low activity under the reaction conditions (entry 5–
7; see also Table S1). The product yield was subsequently
improved to 88% by adding 10 equiv of CHD (entry 8).
Table 1. Optimization of reaction conditions.[a]
Entry
Catalyst
x (equiv of CHD)
Yield of 1a [%][b]
1
2
3
4
5
6
7
8
[Ir(TTP)Me]
5
48
14
9
[Ir(TMP)Me]
[Ir(TDCPP)Me]
[Ir(OEP)Me]
[Rh2(esp)2][c]
[Cu(CH3CN)4(BF4)]
[Co(TTP)]
5
5
5
62
5
5
5
<1
<1
88
5
[Ir(OEP)Me]
10
[a] Reaction condition: quinone diazide (0.2 mmol),
catalyst (0.004 mmol), CHD (x equiv), and 4 Å molecular
sieves (M.S., 60 mg) in dichloromethane (DCM, 1 mL) at RT.
[b] Yields were determined by 1H NMR with PhTMS
(phenyltrimethylsilane) as internal standard. [c] H2esp =
α,α,α′,α′-tetramethyl-1,3-benzenedipropionic acid.
With the optimized catalyst and reaction conditions (condition
A) in hand, we next investigated the substrate scope of this
methodology. Various p-quinone diazides, including those with
electron-withdrawing ester and halogen groups (1a–d,h) as well
as electron-donating alkyl and alkoxy groups (1f,g), could be
converted to the corresponding substituted phenol products in
high to quantitative yields with CHD as substrate (Scheme 1).
Steric encumbrance around the carbonyl oxygen atoms of the QC
moieties (1a–f) showed minor influence on the reaction
outcomes; on the other hand, installation of substituents ortho to
the carbene carbon (1g,h) led to much longer reaction time and
slightly decreased product yields. Arylation products derived from
benzo-fused p-quinone diazide or o-quinone diazide could hardly
be detected (1i,j).
Scheme 1. Substrate scope. Isolated yields are reported. [a] Condition A:
quinone diazide (0.2 mmol), [Ir(OEP)Me] (0.004 mmol), aliphatic substrate (2
mmol), and 4 Å M.S. (60 mg) in DCM (1 mL) at RT. Condition B: quinone diazide
(0.2 mmol), [Ir(OEP)Me] (0.004 mmol), aliphatic substrate (1 mL), and 4 Å M.S.
(60 mg) at 50 oC. [b] Major regioisomer is shown. [c] Overall yield of all
regioisomers. Yields and regioselectivity were determined by 1H NMR. [d] 1-
Methylcyclohexene as substrate. Inset: Primary C(sp3)–H insertion product
(13a) as major product with 3-methylcyclohexene as substrate.
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10.1002/anie.201911138
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Scope of the aliphatic substrates was then studied. Arylation
was readily achieved onto substituted CHDs, terpinolene, and
2,5-dihydrofuran, all of which contain doubly activated C(sp3)–H
bonds (allylic and/or  to oxygen), with moderate to high product
yields under condition A (Scheme 1, 2–8a); less activated
substrate such as tetrahydrofuran (THF) resulted in markedly
lower yield (9a). Under a harsher condition (condition B), our
methodology was further extended to substrates bearing C–H
bonds that are allylic, benzylic, and/or  to nitrogen (10–16a),
including those which could not be activated by Ru-QC species
(e.g., cyclohexenes).[4] Compared to the oxygen-containing
heterocycles (8–9a), the nitrogen analogues (11a, 16a) exhibited
lower reactivity, which is likely due to the bulkiness of the N-Boc
(Boc = tert-butyloxycarbonyl) groups. Except for indane (15a), QC
transfer onto benzylic C–H bonds was unsuccessful, which is
attributable to the steric hindrance exerted by the phenyl rings.
The unactivated aliphatic hydrocarbons (n-hexane, cyclooctane)
were not activated by the Ir-QC intermediate.
in markedly lower yields of 1a and 12a, together with the formation
of TEMPO-trapped products 1a’ and 12a’, respectively (1a’ is
likely derived from oxidation of the initially trapped product); this
serves as a strong proof for the intermediacy of alkyl radical in the
catalytic cycle. The low overall yields of C–H arylation product
(1a/12a) and TEMPO-trapped product (1a’/12a’) are attributable
to the formation of side products and some insoluble black
precipitate (see the Supporting Information for details).
Further investigations were conducted on the HAT step
(Scheme 3). A KIE (kinetic isotope effect) value of 3.2 ± 0.3 was
obtained with THF/THF-d8 as substrates (Scheme 3a). Although
the quinoid oxygen atom of the Ir-QC intermediate is likely
responsible for the HAT step,[4] it has been suggested
computationally that electrophilic carbene carbon might also
mediate such a process.[13] Steric control experiments were
designed to address this issue (Scheme 3b): for 9,10-
dihydroanthracene (DHA) substrate, HAT reactivity of Ir-QC
maintained yet the rebound step was not observed; even by
shielding the carbene carbon with two ortho substituents, the HAT
reaction could still take place. These results indicate that
changing the steric environment around the carbene carbon has
little effect on the HAT step which is in disfavor of the HAT
mechanism occurring at the carbene carbon.
Steric effect was found to play an essential role in dictating
the regioselectivity. Installation of a simple methyl or methoxy
group  to the reactive methylene position of CHD could induce a
relatively high regioselectivity ratio (r.r., 8:1 to 11:1) in the product
mixture (2–3a, Scheme 1). For substituted cyclohexenes, the
steric factor was found to override the stability order of alkyl
radicals: (i) for 1-methylcyclohexene, primary C–H insertion
reaction to give 13a dominated over insertion into secondary C–
H bonds (Scheme 1); (ii) for 3-methylcyclohexene, 13a was again
the major product with other regioisomers only detected in trace
amount (inset of Scheme 1). We propose the HAT-initiated radical
isomerization[12] of 3-methylcyclohexene to 1-methylcyclohexene
(Scheme S1) to follow a mechanism similar to that proposed
by Norton and coworkers in related studies; the 1-
methylcyclohexene then acts as a substrate for the Ir catalysis to
afford 13a, as has been investigated in Scheme 1. These findings
infer that the radical rebound process is relatively slow and
sterically demanding, which is accountable for the fact that less
hindered porphyrin ligands and substrates generally gave better
reaction outcomes (vide supra).
Scheme 3. Mechanistic studies on the HAT step. (a) Kinetic isotope effect. (b)
Control experiments.
Detection of Ir-QC intermediate was subsequently carried out.
Addition of N2QCtBu into a CDCl3 solution of [Ir(TTP)Me] at –50 oC
led to the formation of a new species with a downfield shift of Ir-
CH3 at –4.51 ppm (Scheme 4a and Figure S1), which is
comparable to that observed for [Ir(TTP)(Me)(C(Ph)CO2Me)] (–
4.80 ppm)[14] and is tentatively assigned to [Ir(TTP)(Me)(QCtBu)];
however, it could only be formed in ~10% yield, and further
addition of diazo precursor caused its decomposition to the azine
product (Scheme 4a).[15] This intermediate was also detected by
MALDI-HRMS (matrix-assisted laser desorption/ionization-high
resolution mass spectrometry) in which both the experimental m/z
values and isotopic pattern are consistent with its formulation
Scheme 2. Radical trapping experiments.
The proposed radical mechanism of this methodology is
substantiated by trapping experiments (Scheme 2). With CHD
(condition A) and cyclohexene (condition B) as substrates,
addition of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) resulted
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10.1002/anie.201911138
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RESEARCH ARTICLE
(Scheme 4b). We envision that the HAT reactivity of the
diamagnetic Ir-QC intermediate[16] is similar to those of organic
quinones[17] and Ru-QC complexes.[4] Density functional theory
(DFT) calculations on [Ir(OEP)(Me)(QCtBu)] revealed that its
LUMO (lowest unoccupied molecular orbital) is mainly QC * in
character (Scheme 4c), which is similar to Ru-QC complexes.[4]
was calculated to be mainly localized around the carbene unit
(75% out of the whole QC moiety), consistent with the reaction
outcome that radical rebound takes place at the carbene carbon.
X-band EPR (electron paramagnetic resonance) spectrum (100
K) of the reaction mixture containing [Ir(OEP)Me], N2QCtBu, and
DHA revealed signals with gꞱ = 2.055 and g‖ = 1.961 (Figure 2b).
Although the EPR pattern and gx, gy values could be suggestive
of an Ir(IV)[18] formulation (B in Figure 2c),[19] the EPR signals are
much sharper (Figure S3) and the gz value is significantly deviated
from those obtained for the geometrically similar Ir(IV) salen
complexes (gx, gy = 2.10–2.17 and gz = 1.51–1.55).[18c] We
suggest that the proposed ligand-centered radical form (A in
Figure 2c) to have significant contribution to the electronic
structure of the Ir-QC-H· intermediate.
1081.4344
Experimental
1081.4368
Simulated
Scheme 4. Detection of Ir-QC intermediate [Ir(TTP)(Me)(QCtBu)] by 1H NMR (a)
and MALDI-HRMS (b), and calculated QCtBu * orbital (LUMO) for
[Ir(OEP)(Me)(QCtBu)] (c).
Experimental
Simulated
Scheme 5. Summary of mechanistic studies for the proposed catalytic cycle.
g = 2.055
g = 1.961
g = 2.003
3200
3300
3400
3500
3600
Field (G)
The catalytic reaction affording 1a could be scaled up to 1.0 g
with negligible influence on the product yield by using only 0.2
mol% of catalyst; a total turnover number (TON) of 430 could be
calculated accordingly (Scheme 6a). These arylated 1,4-
cyclohexadiene products, such as 1a, could be readily
functionalized to more complex and useful structures; the crude
mixture of 1a was directly subjected to the following reactions
thanks to the high purity. The cyclohexadienyl moiety could be
aromatized (1aa), epoxidized (1ab), and hydrogenated (1ac) in
71–88% overall yields starting from the quinone diazide (Scheme
6b). Functionalization of the phenol group could also be
performed with 1ac as a model substrate (also using its crude
mixture). Ullman coupling and Sonogashira coupling to afford 1ad
and 1ae were realized in 79 and 81% overall yields, respectively;
alkylation to give 1af and subsequent Claisen rearrangement to
give 1ag were also achieved in high yields.
Figure 2. Calculated spin density (a) and EPR study (b) for Ir-QC-H·
intermediate [Ir(OEP)(Me)(QCtBu-H·)]. In the EPR spectrum, signals at g = 2.003
are attributable to alkyl radical and/or ligand radical. (c) Proposed resonance
forms (A and B) for Ir-QC-H· intermediate.
We further performed DFT calculations on the Ir-QC-H·
intermediate [Ir(OEP)(Me)(QCtBu-H·)]. The QC ligand was found
to be more aromatized in the Ir-QC-H· intermediate (Figure S4).
The spin density is mainly distributed on the QC moiety (40%) and
lesser on the Ir ion (20%, Figure 2a), which supports our proposal
that an Ir(III) center could help preserve the radical character of
the QC ligand (Scheme 5). For the QC moiety, the spin density
Conclusion
In summary, we have developed a direct C(sp3)–H arylation
protocol based on Ir(III) porphyrin-catalyzed quinoid carbene
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10.1002/anie.201911138
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RESEARCH ARTICLE
(QC) insertion reaction. This method tolerates various
substituents on the carbene precursors, affording functionalized
phenol moieties anchored onto 1,4-cyclohexadienes; several
other types of C(sp3)–H bonds (allylic, benzylic, and/or  to
heteroatoms) can also be activated and arylated. This
methodology is enabled by the HAT reactivity of metal-QC
intermediate, which represents a rare example of radical
mechanism in intermolecular carbene C–H insertion catalysis.
Such a reaction pathway, together with the steric demand of
porphyrin ligand, also gives rise to the unique regioselectivity of
this reaction.
Chemical Science. Y.R. thanks the FAME/Mercator scholarship.
We thank Drs. Jie-Sheng Huang, Ka-Pan Shing, and Zhou Tang
for helpful discussions.
Keywords: carbenes • diazo compounds • homogeneous
catalysis • iridium • radical reactions
[1]
[2]
M. P. Doyle, M. A. McKervey, T. Ye, Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds, Wiley, 1998.
a) H. M. L. Davies, R. E. J. Beckwith, Chem. Rev. 2003, 103, 2861; b) M.
P. Doyle, R. Duffy, M. Ratnikov, L. Zhou, Chem. Rev. 2010, 110, 704; c)
C.-M. Che, V. K.-Y. Lo, C.-Y. Zhou, J.-S. Huang, Chem. Soc. Rev. 2011,
40, 1950; d) H. Lu, X. P. Zhang, Chem. Soc. Rev. 2011, 40, 1899; e) A.
Caballero, M. M. Díaz-Requejo, M. R. Fructos, A. Olmos, J. Urbano, P.
J. Pérez, Dalton Trans. 2015, 44, 20295.
[3]
a) A. G. Griesbeck, E. Zimmermann in Science of Synthesis (Ed.: A. G.
Griesbeck), Thieme, 2006, pp. 807; b) D. I. A. Othman, M. Kitamura,
Heterocycles 2016, 92, 1761.
[4]
[5]
[6]
H.-X. Wang, Q. Wan, K. Wu, K.-H. Low, C. Yang, C.-Y. Zhou, J.-S.
Huang, C.-M. Che, J. Am. Chem. Soc. 2019, 141, 9027.
H. T. Dao, P. S. Baran, Angew. Chem. Int. Ed. 2014, 53, 14382; Angew.
Chem. 2014, 126, 14610.
a) E. R. Baral, Y. R. Lee, S. H. Kim, Adv. Synth. Catal. 2015, 357, 2883;
b) S.-S. Zhang, C.-Y. Jiang, J.-Q. Wu, X.-G. Liu, Q. Li, Z.-S. Huang, D.
Li, H. Wang, Chem. Commun. 2015, 51, 10240; c) D. Das, P. Poddar, S.
Maity, R. Samanta, J. Org. Chem. 2017, 82, 3612; d) Z. Liu, J.-Q. Wu,
S.-D. Yang, Org. Lett. 2017, 19, 5434; e) R. Chen, S. Cui, Org. Lett. 2017,
19, 4002; f) K. B. S. Magar, T. N. J. I. Edison, Y. R. Lee, Eur. J. Org.
Chem. 2017, 2017, 7046; g) K. Wu, B. Cao, C.-Y. Zhou, C.-M. Che,
Chem. Eur. J. 2018, 24, 4815; h) Y.-S. Jang, Ł. Woźniak, J. Pedroni, N.
Cramer, Angew. Chem. Int. Ed. 2018, 57, 12901; Angew. Chem. 2018,
130, 13083; i) B. Ghosh, A. Biswas, S. Chakraborty, R. Samanta, Chem.
Asian J. 2018, 13, 2388.
[7]
[8]
[9]
a) M. Kitamura, K. Otsuka, S. Takahashi, T. Okauchi, Tetrahedron Lett.
2017, 58, 3508; b) D. I. A. Othman, K. Otsuka, S. Takahashi, K. B. Selim,
M. A. El-Sayed, A. S. Tantawy, T. Okauchi, M. Kitamura, Synlett 2018,
29, 457; c) B. Ghosh, R. Samanta, Chem. Commun. 2019, 55, 6886.
a) N. Ashkenazi, A. Vigalok, S. Parthiban, Y. Ben-David, L. J. W. Shimon,
J. M. L. Martin, D. Milstein, J. Am. Chem. Soc. 2000, 122, 8797; b) A.
Dauth, U. Gellrich, Y. Diskin-Posner, Y. Ben-David, D. Milstein, J. Am.
Chem. Soc. 2017, 139, 2799.
a) N. P. van Leest, R. F. J. Epping, K. M. van Vliet, M. Lankelma, E. J.
van den Heuvel, N. Heijtbrink, R. Broersen, B. de Bruin, in Advances in
Organometallic Chemistry, Vol. 70 (Eds.: P. J. Pérez, F. G. A. Stone, R.
West), Academic Press, 2018, pp. 71; b) X. Cui, X. Xu, L.-M. Jin, L.
Wojtas, X. P. Zhang, Chem. Sci. 2015, 6, 1219; c) B. G. Das, A. Chirila,
M. Tromp, J. N. H. Reek, B. de Bruin, J. Am. Chem. Soc. 2016, 138,
8968; d) C. te Grotenhuis, B. G. Das, P. F. Kuijpers, W. Hageman, M.
Trouwborst, B. de Bruin, Chem. Sci. 2017, 8, 8221; e) Y. Wang, X. Wen,
X. Cui, X. P. Zhang, J. Am. Chem. Soc. 2018, 140, 4792; f) X. Wen, Y.
Wang, X. P. Zhang, Chem. Sci. 2018, 9, 5082; g) C. te Grotenhuis, N.
van den Heuvel, J. I. van der Vlugt, B. de Bruin, Angew. Chem. Int. Ed.
2018, 57, 140; Angew. Chem. 2018, 130, 146; h) A. S. Karns, M.
Goswami, B. de Bruin, Chem. Eur. J. 2018, 24, 5253; i) M. Lankelma, A.
M. Olivares, B. de Bruin, Chem. Eur. J. 2019, 25, 5658.
Scheme 6. (a) Gram-scale synthesis of 1a and determination of TON. (b)
Product transformation of 1a using crude reaction mixture. DDQ = 2,3-dichloro-
5,6-dicyano-p-benzoquinone; mCPBA
= 3-chloroperbenzoic acid; d.r. =
diastereomeric ratio; Tf = triflate; Cy = cyclohexyl.
[10] a) W. I. Dzik, X. P. Zhang, B. de Bruin, Inorg. Chem. 2011, 50, 9896; b)
H. Lu, W. I. Dzik, X. Xu, L. Wojtas, B. de Bruin, X. P. Zhang, J. Am. Chem.
Soc. 2011, 133, 8518.
Acknowledgements
This work is supported by Hong Kong Research Grants Council
(HKU 17303815) and Basic Research Program-Shenzhen Fund
(JCYJ20170412140251576, JCYJ20170818141858021, and
JCYJ20180508162429786). We thank UGC funding administered
by The University of Hong Kong for supporting the MALDI-TOF-
MS Facilities under the Support for Interdisciplinary Research in
[11] Ir(IV) porphyrinoids have only been observed spectroscopically. a) K. M.
Kadish, Y. J. Deng, C.-L. Yao, J. E. Anderson, Organometallics 1988, 7,
1979; b) J. H. Palmer, M. W. Day, A. D. Wilson, L. M. Henling, Z. Gross,
H. B. Gray, J. Am. Chem. Soc. 2008, 130, 7786; c) T.-L. Lam, K.-C. Tong,
C. Yang, W.-L. Kwong, X. Guan, M.-D. Li, V. K.-Y. Lo, S. L.-F. Chan, D.
L. Phillips, C.-N. Lok, C.-M. Che, Chem. Sci. 2019, 10, 293.
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[12] a) G. Li, J. L. Kuo, A. Han, J. M. Abuyuan, L. C. Young, J. R. Norton, J.
H. Palmer, J. Am. Chem. Soc. 2016, 138, 7698; b) S. A. Green, S. W. M.
Crossley, J. L. M. Matos, S. Vásquez-Céspedes, S. L. Shevick, R. A.
Shenvi, Acc. Chem. Res. 2018, 51, 2628.
[13] K. Chen, S.-Q. Zhang, O. F. Brandenberg, X. Hong, F. H. Arnold, J. Am.
Chem. Soc. 2018, 140, 16402.
[14] B. J. Anding, J. Brgoch, G. J. Miller, L. K. Woo, Organometallics 2012,
31, 5586.
[15] Azine formation is a common decomposition pathway for reactive metal-
carbene intermediates. K. P. Kornecki, J. F. Briones, V. Boyarskikh, F.
Fullilove, J. Autschbach, K. E. Schrote, K. M. Lancaster, H. M. L. Davies,
J. F. Berry, Science 2013, 342, 351.
[16] Hydrogen atom abstraction by diamagnetic species is not unusual. J. M.
Mayer, Acc. Chem. Res. 2011, 44, 36.
[17] F. Wurche, W. Sicking, R. Sustmann, F. G. Klärner, C. Rüchardt, Chem.
Eur. J. 2004, 10, 2707.
[18] Previously, gx, gy = 2.10–2.48 and gz = 1.51–1.96 have been observed
for Ir(IV) complexes. a) T. P. Brewster, J. D. Blakemore, N. D. Schley, C.
D. Incarvito, N. Hazari, G. W. Brudvig, R. H. Crabtree, Organometallics
2011, 30, 965; b) K. Shin, Y. Park, M.-H. Baik, S. Chang, Nat. Chem.
2017, 10, 218; c) C. L. Lee, L. Wu, J.-S. Huang, C.-M. Che, Chem.
Commun. 2019, 55, 3606.
[19] Ir(II) porphyrin species can be precluded due to their weak EPR signals.
H. Zhai, A. Bunn, B. Wayland, Chem. Commun. 2001, 1294.
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10.1002/anie.201911138
Angewandte Chemie International Edition
RESEARCH ARTICLE
RESEARCH ARTICLE
Hai-Xu Wang, Yann Richard, Qingyun
Wan, Cong-Ying Zhou, and Chi-Ming
Che*
Page No. – Page No.
Iridium(III)-Catalyzed Intermolecular
C(sp3)–H Insertion Reaction of
Quinoid Carbene through a Radical
Mechanism
Direct intermolecular C(sp3)–H arylation is achieved by an Ir(III) porphyrin-catalyzed
formal quinoid carbene (QC) insertion reaction through a stepwise radical
mechanism. This reaction is enabled by the hydrogen atom transfer (HAT) reactivity
of metal-QC intermediate, and the subsequent radical rebound step is facilitated by
an electrophilic Ir(III) center that preserves the radical character of the QC ligand.
This article is protected by copyright. All rights reserved.