Development and Mechanistic Studies of Iron-Catalyzed Construction of Csp2-B Bonds via C-O Bond Activation

Article abstract of DOI:10.1021/acs.orglett.0c01937

Herein we describe an iron-catalyzed borylation of alkenyl and aryl carbamates through the activation of a C-O bond. This protocol exhibits high efficiency, a broad substrate scope, and the late-stage borylation of biorelevant compounds, thus providing potential applications in medicinal chemistry. Moreover, this method enables orthogonal transformations of phenol derivatives and also offers good opportunities for the synthesis of multisubstituted arenes. Preliminary mechanistic studies suggest that a FeII/FeIII catalytic cycle via a radical pathway might be involved in the reaction.

Full text of DOI:10.1021/acs.orglett.0c01937

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Letter
Development and Mechanistic Studies of Iron-Catalyzed
Construction of Csp2−B Bonds via C−O Bond Activation
Shasha Geng,§ Juan Zhang,§ Shuo Chen,§ Zhengli Liu, Xiaoqin Zeng, Yun He, and Zhang Feng*
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ABSTRACT: Herein we describe an iron-catalyzed borylation of
alkenyl and aryl carbamates through the activation of a C−O bond.
This protocol exhibits high efficiency, a broad substrate scope, and
the late-stage borylation of biorelevant compounds, thus providing
potential applications in medicinal chemistry. Moreover, this
method enables orthogonal transformations of phenol derivatives
and also offers good opportunities for the synthesis of multi-
substituted arenes. Preliminary mechanistic studies suggest that a
FeII/FeIII catalytic cycle via a radical pathway might be involved in
the reaction.
wing to their cheapness, abundance, and nontoxicity,
iron catalysts have been widely used to construct C−C
example of the iron-catalyzed borylation of alkenyl and aryl
carbamates, thus providing a facile and efficient route for the
synthesis of tri- and tetra-substituted alkenylboranes (Scheme
1).
Giving the important applications of carbamates in
orthogonal transformations and C−H bond functionalization
as the directing group,15 we have a great interest in the
exploration of the borylation of alkenyl and aryl carbamates.
O
bonds through classical cross-coupling reactions, such as
Kumada, Negishi, and Suzuki reactions, using organometallic
reagents or organoborons as substrates.1 However, the
formation of carbon−heteroatom bonds by iron catalysis has
rarely been explored.2 Moreover, organohalides are usually
used as substrates in iron-catalyzed cross-coupling reactions
due to their mild reactivity.3 Compared with organohalides,
oxygen-based electrophiles, such as enolate and phenol
derivatives, have become increasingly more attractive as
coupling partners because halide-containing waste can be
avoided, and ketones and phenols are commercially available
and easily produced.4 Iron-catalyzed C−C bond formation
reactions of oxygen-based electrophiles with organometallic
reagents were reported by the Nakamura, Garg, Shi, and Cook
groups in recent years.5 To the best of our knowledge, iron-
catalyzed carbon−heteroatom bond formation through un-
reactive C−O bonds has scarcely been developed, even though
unreactive C−O bonds have been well studied with nickel and
rhodium catalysts.6−9 This transformation is challenging
because it is difficult for the unreactive C−O bonds to
undergo oxidative addition with iron catalysts due to their
strong bond dissociation energy.10
Scheme 1. Iron-Catalyzed Construction of C−B Bonds
Organoboron compounds are very important and widely
employed in organic synthesis, materials science, as well as
applications in medicinal chemistry.11 To date, the transition-
metal-catalyzed formation of alkenylboranes has been less
reported.12,13 Thus the construction of Csp2−B bonds
catalyzed by base-metal catalysts using environmentally
friendly oxygen-based electrophiles as substrates in a green
and highly efficient way is very appealing. With our continuing
interest in transition-metal catalysis,14 herein we describe an
Received: June 10, 2020
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© XXXX American Chemical Society
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Consequently, we began our investigations by subjecting
alkenyl carbamate 1a to diborane 2a in the presence of various
bases and ligands. (For details, see the Supporting
Information.) To our delight, this reaction could proceed
when TMEDA was used as a ligand, albeit with poor efficiency
(Scheme 2, entries 1 and 2). The bases were crucial for this
tolerated. Thiophene carbamate could also react well,
providing the borylated product in 67% yield (16). Most
remarkably, the alkenyl carbamates without the π-extend
conjugated system were demonstrated as good substrates for
this borylation, providing the desired products in moderate
yields (19−26, 29, 32, 40−71%). Gratifyingly, unreactive
linear carbamate was also a suitable substrate, and the
corresponding product was isolated in an acceptable yield
(29, 40%). It should be mentioned that the tetra-substituted
alkenyl boronic esters are difficult to synthesize owing to their
steric hindrance and could be obtained in moderate yields
through our protocol (30−32, 40−70%). Encouraged by these
results, the borylation of aryl carbamates was evaluated as well.
When naphthyl carbamates were used as substrates, this
reaction proceeded smoothly, providing the borylated products
in moderate to excellent yields (33−41, 66−92%). Functional
groups, such as methoxy, trifluoromethyl, morpholyl, and
amine, were well-tolerated and afforded the corresponding
products in good yields (36, 38, 39, and 51). Polycyclic
aromatic substrates, such as phenanthryl carbamate, provided
42 in good yield (74%). Furthermore, N-heterocyclic ring
carbazole carbamate underwent this borylation reaction
smoothly as well, producing 44 in a good yield. Additionally,
biphenyl substrates also exhibited good reactivity, delivering
the borylated products in moderate to good yields (45−47,
57−71%). Substrates bearing an ortho bulky phenyl group also
reacted smoothly, producing 49 in reasonable yield.
Importantly, monophenyl carbamates are also applicable to
the reaction and provided the corresponding products in
moderate to excellent yields (50−60, 50−86%). This trans-
formation could be conducted on a 6 mmol scale, and a 58%
yield was obtained. To explore the scope of this trans-
formation, other oxygen-based electrophiles were evaluated.
Oxygen-based groups, such as OTs and OTf, produced the
borylated product in a <6% yield, and the OAc and
OPO(OPh)2 groups could not undergo this transformation
at all, in which a large amount of phenol and protonated
product were observed. The OPiv group could react with
diborane reagent 2a with low efficiency, providing the
corresponding product in 26% yield. (For details, see the
Supporting Information.) Other classical diborane reagents
were explored as well, and no transformation occurred. (For
details, see the Supporting Information.)
To further evaluate the application of this protocol, the late-
stage borylation of biorelevant compounds, such as estrone,
vitamin E, epiandrosterone, and stanolone carbamates, was
conducted (Scheme 3). The arylboranes and alkenylboranes
could be obtained in moderate to good yields (61−65, 46−
76%), which provided a facile access to the diversification of
phenol and ketone structures. Furthermore, the ortho- or
meta-arylation through C−H bond activation using carbamate
as the directing group was also carried out. The ortho-arylation
of monophenyl carbamates was conducted using Bedford’s
method.16 Furthermore, the ortho-arylated compounds under-
went a further transformation, affording the borylated
compounds in good yields (66−70, 55−67%). Similarly, the
meta-arylated and borylated compounds could also be
delivered in moderate to good yields (71 and 72, 50−
67%).17 These results demonstrate the inherent value of our
protocol, which provides an efficient method for obtaining the
valuable multisubstituted arenes.
Scheme 2. Representative Results for the Optimization of
a
the Iron-Catalyzed Borylation of 1a
a
Reaction conditions (unless otherwise specified): 1a (0.2 mmol, 1.0
equiv), dilborane 2a (0.4 mmol, 2.0 equiv), [Fe] (0.02 mmol, 0.1
equiv), ligand (0.03 mmol, 0.15 equiv), solvent (2.0 mL), base (0.8
b
1
mmol, 4.0 equiv), 100 °C, 15 h. Determined by H NMR using
mesitylene as an internal standard. The isolated yield is shown in
parentheses. MeOLi (5.0 equiv) was used.
c
reaction, and strong bases, such as t-BuOLi and MeOLi, could
promote the reaction. A 15% yield of the desired product could
be delivered using MeOLi as the base. Other bases, such as
K2CO3 and Cs2CO3, could not promote this transformation.
After testing other ligands, dinitrogen ligands stood out,
providing the borylated product in moderate yields (Scheme 2,
entries 3 and 4; for details, see the Supporting Information).
2,2-Bipyridine was demonstrated as the best choice, and the
desired product 3 was obtained in 50% yield (Scheme 2, entry
4). Then, other iron sources were evaluated. Fe(OTf)2 could
slightly improve the reaction efficiency, delivering 3 in 53%
yield (Scheme 2, entry 6). Switching the solvent from ethers to
toluene provided the borylated product in 86% yield (Scheme
2, entries 7 and 8). Control experiments were conducted,
which demonstrated the necessity of both an iron catalyst and
ligand. No desired product was observed in the absence of an
iron catalyst, and only a 20% yield of 3 was provided without
the use of a ligand. These results suggest that an electron-rich
ligand, 2,2-bipyridine, plays a crucial role in promoting this
transformation. To rule out the trace-metal effect in this
reaction, copper and nickel catalysts were tested, and no
desired product was observed, which suggested that this
reaction was indeed catalyzed by the iron catalysts.
After the optimal conditions were established, the scope of
this iron-catalyzed borylation reaction was explored. Alkenyl
carbamates could react smoothly, delivering the corresponding
products in moderate to good yields (3−32) (Table 1).
Moreover, this reaction exhibited good functional group
tolerance. Functional groups such as Cl, F, CF3, Tips, Opy
(2-pyridyloxy), and OBn (11, 12, 13, 14, 21, 22) were well-
To gain insight into the mechanism of this iron-catalyzed
borylation reaction, radical inhibition experiments were first
B
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a
Table 1. Scope of the Iron-Catalyzed Borylation of Alkenyl and Aryl Carbamates
a
Reaction conditions: Alkenyl carbamates (0.2 mmol, 1.0 equiv), diborane 2a (0.4 mmol, 2.0 equiv), Fe(OTf)2 (0.02 mmol, 0.1 equiv), bpy (0.03
b
mmol, 0.15 equiv), toluene (2.0 mL), MeOLi (1.0 mmol, 5.0 equiv), 100 °C, 15 h. Reaction conditions: Alkenyl carbamates (0.2 mmol, 1.0
equiv), Fe(OTf)2 (0.02 mmol, 0.1 equiv), t-BuDavephos (0.05 mmol, 0.25 equiv), PhCF3 (2.0 mL), MeOLi (1.0 mmol, 5.0 equiv), 100 °C, 15 h.
c
(For details, see the Supporting Information.) Reaction conditions: Aryl carbamates (0.3 mmol, 1.0 equiv), diborane 2a (0.6 mmol, 2.0 equiv),
d
Fe(OAc)2 (0.015 mmol, 0.05 equiv), TMEDA (0.03 mmol, 0.1 equiv), i-Pr2O (2.0 mL), t-BuONa (0.75 mmol, 2.5 equiv), 120 °C, 15 h. Reaction
conditions: Aryl carbamates (0.3 mmol, 1.0 equiv), diborane 2a (0.6 mmol, 2.0 equiv), Fe(OTf)2 (0.015 mmol, 0.05 equiv), MTBE (2.0 mL), t-
BuONa (0.75 mmol, 2.5 equiv), 120 °C, 15 h. Reaction conditions: Aryl carbamates (0.3 mmol, 1.0 equiv), diborane 2a (0.6 mmol, 2.0 equiv),
Fe(OTf)2 (0.03 mmol, 0.1 equiv), MTBE (2.0 mL), t-BuONa (0.75 mmol, 2.5 equiv), 120 °C, 15 h.
e
carried out. When a radical scavenger TEMPO or a radical
inhibitor BHT was used as the additive, only a small amount of
desired product was generated (Scheme 4A). Furthermore, the
radical intermediates were confirmed by EPR experiments.
(See the Supporting Information.) To further confirm whether
the boron radical or aryl radical participated in this reaction, a
radical clock experiment was conducted (Scheme 4B). Instead
of the radical ring-opening product 75, compound 76 was
obtained via a plausible β-carbon elimination pathway,18 which
revealed that the boron radical species could be ruled out.
Moreover, we also tried to verify the possibility of the aryl
radical in this reaction. However, the adduct of TEMPO with
aryl radical 73 was not observed by LC-MS. The deuterated
compound 77 was not obtained as well using d8-toluene as the
solvent. When a large amount of CD3OD as the additive was
added to the reaction to trap the reaction intermediates (see
the Supporting Information, Figure S2), only hydrodeoxy-
genated product 77 was generated, and no deuterated product
was observed, which suggested that the aryl-Fe species might
not be involved in this catalytic cycle. On the basis of these
deuterium experiments, there is the possibility that the aryl
radical could not be excluded, which might involve the cage
C
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Scheme 3. Late-Stage Functionalization of Biomolecules and Orthogonal Transformations of Phenols
Scheme 4. Mechanistic Studies
effect of the aryl radical. Second, to study how to initiate this
reaction, we conducted the sequential experiments. Without
the diboron reagent 2a, the substrate 33a was fully recovered,
and no protonated product was observed in the presence of 1
equiv of Fe(OAc)2, which revealed that the mixture of
Fe(OAc)2, TMEDA, and t-BuONa could not induce the
transformation of the C−O bond (Scheme 4, C1). Instead, 0.5
h later, when diboron reagent 2a was added to the mixture, the
borylated product could be obtained in 69% yield (Scheme 4,
C2), suggesting that this reaction might be triggered by the aid
of diboron reagent 2a, and the involvement of an iron−boron
intermediate was reasonable. Furthermore, the intermediate
was confirmed by 11B NMR. (See the Supporting Information,
Figure S4.) The iron−boron complex19 (11B NMR, δ 22) and
t-BuOBpin20 (11B NMR, δ 21) were observed after the mixture
of B2pin2, Fe(OAc)2, TMEDA, and t-BuONa reacted for 4 h.
When substrate 33a was added to the system, the iron−boron
complex gradually increased, and a large amount of t-BuOBpin
was generated. The iron−boron complex could react with aryl
carbamate 33a, providing the corresponding product in 60%
yield (Scheme 4, C3). On the basis of these results, we thought
that the iron-ate complex was in-situ-generated in the mixture
of B2pin2, Fe(OAc)2, TMEDA, and t-BuONa, which could
promote this transformation smoothly. Unfortunately, all of
the efforts to isolate the iron−boron complex have failed. At
the present, the exact structure of the iron−boron complex and
its coordination with t-BuONa could not be confirmed by
high-resolution mass spectrometry (HRMS).
D
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Next, to gain further insight into the nature of the iron-ate
complex in the reaction, the reaction mixture of Fe(OAc)2, t-
BuONa, and diboron was analyzed by X-ray photoelectron
spectroscopy (XPS). The XPS experiments suggest that a FeII/
FeIII catalytic cycle might be involved in the borylation
reaction. (See the Supporting Information, Figures S7−S10.)
Moreover, when 1 equiv of the boron−iron(I) complex was
used as the substrate (Scheme 4D),3b this reaction could not
proceed, and no borylated product was observed, which
suggested that the boron−iron(I) species might not be the
catalyst of this reaction. On the basis of these preliminary
results, a hypothesized mechanism is illustrated in Scheme 5.
Drug Research, Chemical Biology Research Center, School of
Pharmaceutical Sciences, Chongqing University, Chongqing
401331, P. R. China; orcid.org/0000-0001-7776-8200;
Email: fengzh@cqu.edu.cn
Authors
Shasha Geng − Sichuan Key Laboratory of Medical Imaging &
Department of Chemistry, School of Preclinical Medicine, North
Sichuan Medical College, Nanchong, Sichuan 637000, China;
Chongqing Key Laboratory of Natural Product Synthesis and
Drug Research, Chemical Biology Research Center, School of
Pharmaceutical Sciences, Chongqing University, Chongqing
401331, P. R. China
Juan Zhang − Chongqing Key Laboratory of Natural Product
Synthesis and Drug Research, Chemical Biology Research
Center, School of Pharmaceutical Sciences, Chongqing
University, Chongqing 401331, P. R. China
Scheme 5. Proposed Mechanism
Shuo Chen − Chongqing Key Laboratory of Natural Product
Synthesis and Drug Research, Chemical Biology Research
Center, School of Pharmaceutical Sciences, Chongqing
University, Chongqing 401331, P. R. China
Zhengli Liu − Chongqing Key Laboratory of Natural Product
Synthesis and Drug Research, Chemical Biology Research
Center, School of Pharmaceutical Sciences, Chongqing
University, Chongqing 401331, P. R. China
Xiaoqin Zeng − Chongqing Key Laboratory of Natural Product
Synthesis and Drug Research, Chemical Biology Research
Center, School of Pharmaceutical Sciences, Chongqing
University, Chongqing 401331, P. R. China
Yun He − Chongqing Key Laboratory of Natural Product
Synthesis and Drug Research, Chemical Biology Research
Center, School of Pharmaceutical Sciences, Chongqing
University, Chongqing 401331, P. R. China; orcid.org/
0000-0002-5322-7300
An iron-ate alkoxide complex I could be generated when the
ligand exchange occurs between t-BuONa and Fe(OAc)2.
Subsequently, the resulting iron species I transmetalates with
diboron to afford an ate complex II with a high reduction
potential,21 which would react with aryl carbamate through a
single electron-transfer pathway, delivering an iron(III)
intermediate III.22 Finally, as a consequence of reductive
elimination, the desired product would be afforded, along with
the regeneration of the iron(II) species IV as well. It should be
noted that the iron(IV) species could not be ruled out in this
catalytic cycle, even though the iron(IV) species was not
observed in the XPS experiments.
In conclusion, we have reported the first example of the iron-
catalyzed borylation of alkenyl and aryl carbamates via C−O
bond activation. This protocol features simple operation, high
efficiency, and a broad substrate scope. It also exhibits excellent
applications in the late-stage borylation of bioactive com-
pounds and the synthesis of ortho- or meta-substituted arenes,
offering a good platform in drug discovery and development.
Studies to further illustrate the mechanism and expand the
utilization of this novel transformation are in progress in our
lab.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c01937
Author Contributions
§S.G., J.Z., and S.C. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for the financial support from the NSFC (no.
21801029), the Graduate Scientific Research and Innovation
Foundation of Chongqing (no. CYS18046), Sichuan Key
Laboratory of Medical Imaging (North Sichuan Medical
College, no. SKLMI201901), the Strategic Cooperation of
Science and Technology between Nanchong City and North
Sichuan Medical College (no. 19SXHZ0441), the Chongqing
Postdoctoral Science Foundation (no. cstc2019jcyj-bshx0057),
the Fundamental Research Funds for the Central Universities
(no. 2020CDJQY-A043), and the Natural Science Foundation
of Chongqing (no. cstc2019jcyj-msxmX0048).
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01937.
Experimental data and copies of 1H NMR and 13C NMR
spectra for all new compounds (PDF)
REFERENCES
AUTHOR INFORMATION
Corresponding Author
■
■
(1) For reviews, see: (a) Czaplik, W. M.; Mayer, M.; Cvengros, J.;
von Wangelin, A. J. Coming of Age: Sustainable Iron-Catalyzed
Cross-Coupling Reactions. ChemSusChem 2009, 2, 396−417.
Zhang Feng − Sichuan Key Laboratory of Medical Imaging &
Department of Chemistry, School of Preclinical Medicine, North
Sichuan Medical College, Nanchong, Sichuan 637000, China;
Chongqing Key Laboratory of Natural Product Synthesis and
̈
(b) Bauer, I.; Knolker, H.-J. Iron Catalysis in Organic Synthesis.
Chem. Rev. 2015, 115, 3170−3387. (c) Piontek, A.; Bisz, E.; Szostak,
M. Iron-Catalyzed Cross-Coupling in the Synthesis of Pharmaceut-
E
https://dx.doi.org/10.1021/acs.orglett.0c01937
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
icals: In Pursuit of Sustainability. Angew. Chem., Int. Ed. 2018, 57,
11116−11128.
Catalyzed Silylation via C-OMe Cleavage. J. Am. Chem. Soc. 2017,
139, 1191−1197. (d) Somerville, R. J.; Hale, L. V. A.; Gomez-Bengoa,
2
(2) (a) Hatakeyama, T.; Imayoshi, R.; Yoshimoto, Y.; Ghorai, S. K.;
Jin, M.; Takaya, H.; Norisuye, K.; Sohrin, Y.; Nakamura, M. Iron-
Catalyzed Aromatic Amination for Nonsymmetrical Triarylamine
Synthesis. J. Am. Chem. Soc. 2012, 134, 20262−20265. (b) Matsubara,
T.; Asako, S.; Ilies, L.; Nakamura, E. Synthesis of Anthranilic Acid
Derivatives through Iron-Catalyzed ortho Amination of Aromatic
Carboxamides with N-Chloroamines. J. Am. Chem. Soc. 2014, 136,
646−649.
́
E.; Bures, J.; Martin, R. Intermediacy of Ni−Ni Species in sp C-O
Bond Cleavage of Aryl Esters: Relevance in Catalytic C-Si Bond
Formation. J. Am. Chem. Soc. 2018, 140, 8771−8780.
(9) (a) Mesganaw, T.; Fine Nathel, N. F.; Garg, N. K. Cine
Substitution of Arenes Using the Aryl Carbamate as a Removable
Directing Group. Org. Lett. 2012, 14, 2918−2921. (b) Hie, L.;
Ramgren, S. D.; Mesganaw, T.; Garg, N. K. Nickel-Catalyzed
Amination of Aryl Sulfamates and Carbamates Using an Air-Stable
Precatalyst. Org. Lett. 2012, 14, 4182−4185. (c) Mesganaw, T.; Garg,
N. K. Ni- and Fe-Catalyzed Cross-Coupling Reactions of Phenol
Derivatives. Org. Process Res. Dev. 2013, 17, 29−39.
(10) Blanksby, S. J.; Ellison, G. B. Bond dissociation energies of
organic molecules. Acc. Chem. Res. 2003, 36, 255−263.
(11) Entwistle, C. D.; Marder, T. B. Boron Chemistry Lights the
Way: Optical Properties of Molecular and Polymeric Systems. Angew.
Chem., Int. Ed. 2002, 41, 2927−2931.
(12) (a) Dombray, T.; Werncke, C. G.; Jiang, J.; Grellier, M.;
Vendier, L.; Bontemps, B.; Sortais, J.-B.; Sabo-Etienne, S.; Darcel, C.
Iron-Catalyzed C−H Borylation of Arenes. J. Am. Chem. Soc. 2015,
137, 4062−4065. (b) Yoshigoe, Y.; Kuninobu, Y. Iron-Catalyzed
ortho-Selective C−H Borylation of 2-Phenylpyridines and Their
Analogs. Org. Lett. 2017, 19, 3450−3453.
(13) For selected examples of Fe-catalyzed hydroborylation and
hydrosilylation, see: (a) Zhang, L.; Peng, D.; Leng, X.; Huang, Z.
Iron-Catalyzed, Atom-Economical, Chemo- and Regioselective
Alkene Hydroboration with Pinacolborane. Angew. Chem., Int. Ed.
2013, 52, 3676−3680. (b) Chen, J.; Cheng, B.; Cao, M.; Lu, Z. Iron-
Catalyzed Asymmetric Hydrosilylation of 1,1-Disubstituted Alkenes.
Angew. Chem., Int. Ed. 2015, 54, 4661−4664. (c) Du, X.; Zhang, Y.;
Peng, D.; Huang, Z. Base-Metal-Catalyzed Regiodivergent Alkene
Hydrosilylations. Angew. Chem., Int. Ed. 2016, 55, 6671−6675. (d) Jia,
X.; Huang, Z. Conversion of Alkanes to Linear Alkylsilanes Using An
Iridium-Iron-Catalysed Tandem Dehydrogenation-Isomerization-Hy-
drosilylation. Nat. Chem. 2016, 8, 157−161. (e) Wang, C.; Wu, C.-Z.;
Ge, S.-Z. Iron-Catalyzed E-Selective Dehydrogenative Borylation of
Vinylarenes with Pinacolborane. ACS Catal. 2016, 6, 7585−7589.
(f) Cheng, B.; Liu, W.-B.; Lu, Z. Iron-Catalyzed Highly
Enantioselective Hydrosilylation of Unactivated Terminal Alkenes. J.
Am. Chem. Soc. 2018, 140, 5014−5017. (g) Hu, M.-Y.; Lian, J.; Sun,
W.; Qiao, T.-Z.; Zhu, S.-F. Iron-Catalyzed Dihydrosilylation of
Alkynes: Efficient Access to Geminal Bis(silanes). J. Am. Chem. Soc.
2019, 141, 4579−4583.
(3) (a) Atack, T. C.; Lecker, R. M.; Cook, S. P. Iron-Catalyzed
Borylation of Alkyl Electrophiles. J. Am. Chem. Soc. 2014, 136, 9521−
9523. (b) Bedford, R. B.; Brenner, P. B.; Carter, E.; Gallagher, T.;
Murphy, D. M.; Pye, D. R. Iron-Catalyzed Borylation of Alkyl, Allyl,
and Aryl Halides: Isolation of an Iron(I) Boryl Complex. Organo-
metallics 2014, 33, 5940−5943. (c) Yoshida, T.; Ilies, L.; Nakamura,
E. Iron-Catalyzed Borylation of Aryl Chlorides in the Presence of
Potassium t-Butoxide. ACS Catal. 2017, 7, 3199−3203.
(4) Yu, D.-G.; Li, B.-J.; Shi, Z.-J. Exploration of New C−O
Electrophiles in Cross-Coupling Reactions. Acc. Chem. Res. 2010, 43,
1486−1495.
(5) For selected examples of Fe-catalyzed cross-coupling reactions
via the cleavage of the C−O bond, see: (a) Li, B.-J.; Xu, L.; Wu, Z.-H.;
Guan, B.-T.; Sun, C.-L.; Wang, B.-Q.; Shi, Z.-J. Cross-Coupling of
Alkenyl/Aryl Carboxylates with Grignard Reagent via Fe-Catalyzed C-
O Bond Activation. J. Am. Chem. Soc. 2009, 131, 14656−14657.
(b) Ito, S.; Fujiwara, Y.; Nakamura, E.; Nakamura, M. Iron-Catalyzed
Cross-Coupling of Alkyl Sulfonates with Arylzinc Reagents. Org. Lett.
2009, 11, 4306−4309. (c) Silberstein, A. L.; Ramgren, S. D.; Garg, N.
K. Iron-Catalyzed Alkylations of Aryl Sulfamates and Carbamates.
Org. Lett. 2012, 14, 3796−3799. (d) Agrawal, T.; Cook, S. P. Iron-
Catalyzed Cross-Coupling Reactions of Alkyl Grignards with Aryl
Sulfamates and Tosylates. Org. Lett. 2013, 15, 96−99. (e) Shi, W.-J.;
Zhao, H.-W.; Wang, Y.; Cao, Z.-C.; Zhang, L.-S.; Yu, D.-G.; Shi, Z.-J.
Nickel- or Iron-Catalyzed Cross-Coupling of Aryl Carbamates with
Arylsilanes. Adv. Synth. Catal. 2016, 358, 2410−2416. (f) Rivera, A. C.
P.; Still, R.; Frantz, D. E. Iron-Catalyzed Stereoselective Cross-
Coupling Reactions of Stereodefined Enol Carbamates with Grignard
Reagents. Angew. Chem., Int. Ed. 2016, 55, 6689−6693. (g) Wu, W.;
Teng, Q.; Chua, Y.-Y.; Huynh, H. V.; Duong, H. A. Iron-Catalyzed
Cross-Coupling Reactions of Arylmagnesium Reagents with Aryl
Chlorides and Tosylates: Influence of Ligand Structural Parameters
and Identification of A General N-Heterocyclic Carbene Ligand.
Organometallics 2017, 36, 2293−2297.
(6) (a) Kinuta, H.; Tobisu, M.; Chatani, N. Rhodium-Catalyzed
Borylation of Aryl 2-Pyridyl Ethers through Cleavage of the Carbon-
Oxygen Bond: Borylative Removal of the Directing Group. J. Am.
Chem. Soc. 2015, 137, 1593−1600. (b) Kinuta, H.; Hasegawa, J.;
Tobisu, M.; Chatani, N. Rhodium-Catalyzed Borylation of Aryl and
Alkenyl Pivalates through the Cleavage of Carbon−Oxygen Bonds.
Chem. Lett. 2015, 44, 366−368. (c) Tobisu, M.; Yasui, K.; Aihara, Y.;
Chatani, N. C-O Activation by A Rhodium Bis (N-Heterocyclic
Carbene) Catalyst: Aryl Carbamates as Arylating Reagents in
Directed C-H Arylation. Angew. Chem., Int. Ed. 2017, 56, 1877−1880.
(7) (a) Li, B.-J.; Li, Y.-Z.; Lu, X.-Y.; Liu, J.; Guan, B.-T.; Shi, Z.-J.
Cross-Coupling of Aryl/Alkenyl Pivalates with Organozinc Reagents
through Nickel-Catalyzed C-O Bond Activation under Mild Reaction
Conditions. Angew. Chem., Int. Ed. 2008, 47, 10124−10127.
(b) Huang, K.; Yu, D.-G.; Zheng, S.-F.; Wu, Z.-H.; Shi, Z.-J.
Borylation of Aryl and Alkenyl Carbamates through Ni-Catalyzed C-
O Activation. Chem. - Eur. J. 2011, 17, 786−791. (c) Su, B.; Cao, Z.-
C.; Shi, Z.-J. Exploration of Earth-Abundant Transition Metals (Fe,
Co, and Ni) as Catalysts in Unreactive Chemical Bond Activations.
Acc. Chem. Res. 2015, 48, 886−896.
(14) For selected examples of our previous contributions to the
palladium-catalyzed transformations, see: (a) Feng, Z.; Min, Q.-Q.;
Xiao, Y.-L.; Zhang, B.; Zhang, X. Palladium-Catalyzed Difluoroalky-
lation of Aryl Boronic Acids: A New Method for the Synthesis of
Aryldifluoromethylated Phosphonates and Carboxylic Acid Deriva-
tives. Angew. Chem., Int. Ed. 2014, 53, 1669−1673. (b) Feng, Z.; Min,
Q.-Q.; Zhao, H.-Y.; Gu, J.-W.; Zhang, X. A General Synthesis of
Fluoroalkylated Alkenes by Palladium-Catalyzed Heck-Type Reaction
of Fluoroalkyl Bromides. Angew. Chem., Int. Ed. 2015, 54, 1270−1274.
(c) Feng, Z.; Min, Q.-Q.; Zhang, X. Access to Difluoromethylated
Arenes by Pd-Catalyzed Reaction of Arylboronic Acids with
Bromodifluoroacetate. Org. Lett. 2016, 18, 44−47. (d) Feng, Z.;
Min, Q.-Q.; Fu, X.-P.; An, L.; Zhang, X. Chlorodifluoromethane-
Triggered Formation of Difluoromethylated Arenes Catalysed by
Palladium. Nat. Chem. 2017, 9, 918−923. (e) Feng, Z.; Xiao, Y.-L.;
Zhang, X. Transition-Metal (Cu, Pd, Ni)-Catalyzed Difluoroalkylation
via Cross-Coupling with Difluoroalkyl Halides. Acc. Chem. Res. 2018,
51, 2264−2278. For selected examples of our previous contributions
to the iron-catalyzed transformations, see: (f) Xiong, B.; Zeng, X.;
Geng, S.; Chen, S.; He, Y.; Feng, Z. Thiyl Radical Promoted Chemo-
and Regioselective Oxidation of C = C Bonds Using Molecular
Oxygen via Iron Catalysis. Green Chem. 2018, 20, 4521−4527.
(g) Geng, S.; Xiong, B.; Zhang, Y.; Zhang, J.; He, Y.; Feng, Z. Thiyl
Radical Promoted Iron-Catalyzed-Selective Oxidation of Benzylic sp3
(8) (a) Zarate, C.; Martin, R. A Mild Ni/Cu-Catalyzed Silylation via
C-O Cleavage. J. Am. Chem. Soc. 2014, 136, 2236−2239. (b) Zarate,
C.; Manzano, R.; Martin, R. Ipso-Borylation of Aryl Ethers via Ni-
catalyzed C-OMe Cleavage. J. Am. Chem. Soc. 2015, 137, 6754−6757.
(c) Zarate, C.; Nakajima, M.; Martin, R. A Mild and Ligand-Free Ni-
F
https://dx.doi.org/10.1021/acs.orglett.0c01937
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
C-H Bonds with Molecular Oxygen. Chem. Commun. 2019, 55,
12699−12702.
(15) (a) Sengupta, S.; Leite, M.; Raslan, D. S.; Quesnelle, C.;
Snieckus, V. Nickel(0)-Catalyzed Cross Coupling of Aryl O-
Carbamates and Aryl Triflates with Grignard Reagents. Directed
Ortho Metalation-Aligned Synthetic Methods for Polysubstituted
Aromatics via a 1,2-Dipole Equivalent. J. Org. Chem. 1992, 57, 4066−
4068. (b) Antoft-Finch, A.; Blackburn, T.; Snieckus, V. N,N-Diethyl
O-Carbamate: Directed Metalation Group and Orthogonal Suzuki−
Miyaura Cross-Coupling Partner. J. Am. Chem. Soc. 2009, 131,
17750−17752.
(16) Bedford, R. B.; Webster, R. L.; Mitchell, C. J. Palladium-
Catalysed ortho-Arylation of Carbamate-Protected Phenols. Org.
Biomol. Chem. 2009, 7, 4853−4857.
(17) Zhang, J.; Liu, Q.; Liu, X.; Zhang, S.; Jiang, P.; Wang, Y.; Luo,
S.; Li, Y.; Wang, Q. Palladium (II)-Catalyzed meta-Selective Direct
Arylation of O-β-Naphthyl Carbamate. Chem. Commun. 2015, 51,
1297−1300.
(18) Chen, C.; Shen, X.; Chen, J.; Hong, X.; Lu, Z. Iron-Catalyzed
Hydroboration of Vinylcyclopropanes. Org. Lett. 2017, 19, 5422−
5425.
(19) For an example of the copper−boron complex, see: Kleeberg,
C.; Dang, L.; Lin, Z.; Marder, T. B. A Facile Route to Aryl Boronates:
Room-Temperature, Copper-Catalyzed Borylation of Aryl Halides
with Alkoxy Diboron Reagents. Angew. Chem., Int. Ed. 2009, 48,
5350−5354.
(20) Romero, E. A.; Peltier, J. L.; Jazzar, R.; Bertrand, G. Catalyst-
free dehydrocoupling of amines, alcohols, and thiols with pinacol
borane and 9-borabicyclononane (9-BBN). Chem. Commun. 2016, 52,
10563−10565.
(21) Uchiyama, M.; Matsumoto, Y.; Nakamura, S.; Ohwada, T.;
Kobayashi, N.; Yamashita, N.; Matsumiya, A.; Sakamoto, T.
Development of A Catalytic Electron Transfer System Mediated by
Transition Metal Ate Complexes: Applicability and Tunability of
Electron-Releasing Potential for Organic Transformations. J. Am.
Chem. Soc. 2004, 126, 8755−8759.
(22) Noda, D.; Sunada, Y.; Hatakeyama, T.; Nakamura, M.;
Nagashima, H. Effect of TMEDA on Iron-Catalyzed Coupling
Reactions of ArMgX with Alkyl Halides. J. Am. Chem. Soc. 2009,
131, 6078−6079.
G
https://dx.doi.org/10.1021/acs.orglett.0c01937
Org. Lett. XXXX, XXX, XXX−XXX