Thioamide-Directed Cobalt(III)-Catalyzed Selective Amidation of C(sp3)?H Bonds

Article abstract of DOI:10.1002/anie.201709273

A mild, oxidant-free, and selective Cp*Co^III-catalyzed amidation of thioamides with robust dioxazolone amidating agents via C(sp³)?H bond activation to generate the desired amidated products is reported. The method is efficient and allows for the C?H amidation of a wide range of functionalized thioamides with aryl-, heteroaryl-, and alkyl-substituted dioxazolones under the Cp*Co^III-catalyzed conditions. The observed regioselectivity towards primary C(sp³)?H activation is supported by computational studies and the cyclometalation is proposed to proceed by means of an external carboxylate-assisted concerted metalation/deprotonation mechanism. The reported method is a rare example of the use of a directing group other than the commonly used pyridine and quinolone classes for Cp*Co^III-catalyzed C(sp³)?H functionalization and the first to exploit thioamides.

Full text of DOI:10.1002/anie.201709273

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Thioamide Directed Co(III) Catalyzed Selective Amidation of
C(sp3)-H Bonds
Authors: Peng Wen Tan, Adrian M. Mak, Michael B. Sullivan, Darren
James Dixon, and Jayasree Seayad
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201709273
Angew. Chem. 10.1002/ange.201709273
Link to VoR: http://dx.doi.org/10.1002/anie.201709273
http://dx.doi.org/10.1002/ange.201709273

10.1002/anie.201709273
Angewandte Chemie International Edition
COMMUNICATION
Thioamide Directed Co(III) Catalyzed Selective Amidation of
C(sp3)-H Bonds
Peng Wen Tan, Adrian M. Mak, Michael B. Sullivan, Darren J. Dixon* and Jayasree Seayad*
Abstract: A mild, oxidant-free and selective Cp*CoIII-catalyzed
amidation of thioamides with robust dioxazolone amidating agents
via C(sp3)-H bond activation to generate the desired amidated
products is reported. The method is efficient and allows for the C-H
amidation of a wide range of functionalized thioamides with aryl-,
heteroaryl- and alkyl- substituted dioxazolones under the Cp*CoIII
catalyzed conditions. The observed regioselectivity towards primary
C(sp3)-H activation is supported by computational studies and the
cyclometalation is proposed to proceed via an external carboxylate
assisted concerted metalation/ deprotonation mechanism. The
reported method is a rare example of the use of a directing group
other than the commonly used pyridine/quinolone classes for
Cp*CoIII catalyzed C(sp3)-H functionalization and the first to exploit
thioamides.
activation, studies on the C(sp3)-H activation/functionalization by
Cp*CoIII catalysts remain limited.[8,9] This scarcity of reports
prompted us to explore possible transformations that could
uncover and advance the potential of cobalt catalysis for C(sp3)-
H bond activation, a process that is often beset by the poor
reactivity of C(sp3)-H bonds.[12]
Thioamides, a versatile class of building blocks derived from
carboxylic acids, are known for their convenient synthetic
applicability to furnish heterocyclic compounds.[13] Thioamide
motifs are also used as biologically active compounds in
pharmaceuticals and agrochemicals.[14] Consequently, new
synthetic methods for their efficient and direct modification via C-
H functionalization strategies are attractive. In 2015, Miura and
co-workers demonstrated that tertiary thioamide derivatives
could serve as effective directing groups (DGs) to effect Cp*RhIII
catalyzed
ortho
C(sp2)-H
activation/alkenylation
of
The arena of C-H functionalization has witnessed
benzothioamides (Figure 1a).[15] Furthermore, Yu et al. disclosed
the thioamide directed PdII-catalyzed α-C(sp3)-H cross-coupling
of cyclic amines with aryl- and heteroarylboronic acids (Figure
1b).[16] Inspired by these recent studies we envisaged that the
thioamide moiety could likely serve as an efficient directing
group to facilitate C(sp3)-H activation for further transformations
under Cp*CoIII catalyzed conditions. To this end, herein we
disclose the discovery and development of a direct, selective,
tremendous
growth
over
the
past
decade.[1]
The
activation/functionalization of ubiquitous C-H bonds in place of
traditional pre-activated functional groups is particularly
attractive in terms of its directness, resource efficiency and atom
economy for carbon-carbon / carbon-heteroatom bond formation.
In the majority of cases, C-H bond activation/functionalization
reactions employ precious metal catalyst complexes of
palladium, rhodium, iridium or ruthenium, owing to their
phenomenal reactivity and ease of handling and a plethora of
important studies have been published.[1] However, it is not until
only recently that the field has witnessed a substantial shift
towards using earth-abundant first-row transition-metal catalysts
as alternatives due to, among other reasons, their lower cost
and toxicity.[2] Of the first row transition metals, cobalt complexes
have revealed exemplary reactivity in this regard, ranging from
transformations catalyzed by low-valent cobalt complexes to
high-valent cobalt catalyzed C-H functionalization reactions.[3-9]
Notably, high-valent Cp*CoIII catalysts have received significant
mild
and
oxidant-free
Cp*CoIII
catalyzed
C(sp3)-H
activation/amidation of thioamides using readily prepared and
easy-to-handle dioxazolones as amidating reagents (Figure 1c).
To our knowledge this is the first example of a Cp*CoIII catalyzed
C(sp3)-H functionalization reaction using a thioamide as an
alternative directing group to the commonly used
pyridine/quinoline classes.
a. (T. Satoh & M. Miura): Cp*RhIII-catalyzed ortho C(sp2)-H alkenylation
R1 NPri2
R1 NPri2
attention due to their great stability yet outstanding reactivity[3-8]
,
R2
R3
2
C(s
p
)
-H
R2
R3
S
S
RhIII
analogous to that of their RhIII and IrIII counterparts.[10-11] Despite
the substantial amount of preceding work that has demonstrated
transformations pivoting on Cp*CoIII catalyzed C(sp2)-H bond
+
R4
R4
functionalization
H
b. Yu: PdII-catalyzed C(sp3)-H arylation
sp3)-
C(
R1
S
H
H
S
B(OH)2
Me
+
PdII
Me
Me
N
R1
N
Me
[*]
P. W. Tan and Dr. J. Seayad
functionalization
Me
Me
n
Organic Chemistry, Institute of Chemical and Engineering Sciences,
8 Biomedical Grove, Neuros, #07-01, Singapore 138665, Singapore
E-mail: jayasree_seayad@ices.a-star.edu.sg
n
c. This work: Cp*CoIII-catalyzed C(sp3)-H amidation
O
O
S
HN
R2
R3
S
H
Prof. Dr. D. J. Dixon
3 )-H
C(
sp
O
N
Department of Chemistry, Chemistry Research Laboratory,
University of Oxford, 12 Mansfield Road, Oxford, UK
E-mail: darren.dixon@chem.ox.ac.uk
O
CoIII
functionalization
N
R2
+
N
R1
R3
R1
Mild conditions
Redox neutral / oxidant-free
Good functional group tolerance
R3 = alkyl, aryl
Dr. Adrian M. Mak and Dr. Michael B. Sullivan
Institute of High Performance Computing
1 Fusionopolis Way #16-16 Singapore 138632
E-mail: makwk@ihpc.a-star-.edu.sg
Figure 1. Thioamide directed transition metal catalyzed C(sp3/sp2)-H
functionalization reactions.
To assess the potential of the Cp*CoIII catalysis for any
desired C(sp3)-H functionalization, we began a preliminary
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201709273
Angewandte Chemie International Edition
COMMUNICATION
investigation using model substrates thioamide 1a and
dioxazolone 2a (Table 1) in the presence of catalytic
[Cp*Co(MeCN)3][SbF6]2 in dichloroethane (DCE) at 40 °C for
24h (entry 1). Encouragingly, the reaction proceeded smoothly
to furnish the amidated product 3a in 56% yield (determined by
1H NMR by integration against an internal standard). It was
noteworthy that exclusive mono amidation with selective C(sp3)-
H activation at one of the primary methyl groups of the thioamide
1a instead of the -methylene protons in the piperidine ring was
observed. To optimize the yield of the reaction further, different
carboxylic acids and their salts were evaluated as additives.
Importantly, addition of 20 mol% sodium benzoate resulted in a
significant increase in yield (89%, entry 4). While DCE proved to
be the optimal solvent, other solvents such as trifluoroethanol,
dioxane and toluene (entries 5, 6 & 7), completely suppressed
reactivity and the reactions yielded trace or no product.
Switching [Cp*Co(MeCN)3][SbF6]2 for Cp*Co(CO)I2 (entry 8) or
[Cp*Rh(MeCN)3][SbF6]2 (entry 9) or no transition metal catalyst
at all (entry 10) led to diminished or no reactivity. While the
reaction worked at room temperature with slightly lower yield
(entry 12), a higher catalyst loading (entry 11) did not result in an
improvement to the yield relative to entry 4. A control reaction
using 2,2-dimethyl-1-(piperidin-1-yl)propan-1-one, the amide
precursor of 1a, as the substrate instead of 1a showed no
reactivity confirming the role of the thioamide as directing group
for this intriguing primary C(sp3)-H activation.
11
[Cp*Co(MeCN)3][SbF6]2
(10)
DCE
DCE
PhCO2Na
(40)
85
71
12[b]
[Cp*Co(MeCN)3][SbF6]2
(5)
PhCO2Na
(20)
[a] Reaction condition: 1a (0.3 mmol), 2b (0.36 mmol), catalyst, additive,
solvent (3 mL), T= 40 °C, 24 h. [b] Reaction was carried out at RT. [c] 1H NMR
yield using CH2Br2 as internal standard; isolated yield in parentheses.
Having identified the optimal reaction conditions for the
synthesis of 3a, various substituted dioxazolones were then
evaluated to determine their influence on the overall reactivity
and to establish the reaction scope with respect to the amidating
reagent (Table 2). In general, this C(sp3)-H functionalization
methodology was amenable to a range of aryl-substituted
dioxazolones bearing various electron-withdrawing and electron-
donating substituents, furnishing the corresponding amidated
products in typically good to excellent yields. Whereas a low
yield was obtained in the case of reaction with para-CF3-
substituted 3-phenyldioxazolones (3h), Cl- (3b) and Br- (3c)
substituents in the para-position were well-tolerated delivering
products that are synthetically useful for downstream
transformations. Furthermore, reactions with heteroaryl-
containing dioxazolone substrates proceeded smoothly under
the optimized conditions to afford 3k and 3l in 83% and 75%
yield respectively. Considering the difficulty of installing alkyl N-
acyl amide moiety using other amidating reagents such as alkyl
acyl azides,[17] it was gratifying to note that alkyl-substituted
dioxazolone substrates performed well to afford 3m and 3n in
good yields.
Table 1. Optimization studies on C(sp3)- H activation/ amidation reactions of
1a & 2a
Catalyst
Additive
O
S
O
S
Table 2. C(sp3)-H activation/amidation of thioamide 1 with various substituted
dioxazolones
Me
Me
º
O
N
N
Ph
N
+
O
H
Me Me
N
Me
R
Ph
Solvent
40 oC, 24 h
[Cp*Co(MeCN)3][SbF6]2
(5 mol%)
O
S
H
S HN
O
PhCO2Na
(10 mol%)
2a
1a
3a
O
+
N
N
O
Me
Me
Me
DCE (3 mL)
40- 60 oC, 24 h
N
Me
R
Entry [a]
Catalyst
(mol%)
Solvent
Additive
(mol%)
Yield[c]
(%)
1a, 0.3 mmol
2, 0.36 mmol
3, isolated yield
R
Me
1
2
[Cp*Co(MeCN)3][SbF6]2
(5)
DCE
DCE
-
56
3b, R= Cl, 85%
3c, R= Br, 84%
3d, R=F, 86%
3e, R=Me, 74%
3f, R= t-Bu, 71%
3g, R= OMe, 78%
3h, R= CF3, 32%
S
HN
O
S
N
HN
[Cp*Co(MeCN)3][SbF6]2
(5)
PivOH
(20)
79
O
N
Me
Me
Me
Me
3i, 64%
3
[Cp*Co(MeCN)3][SbF6]2
(5)
DCE
PhCO2H
(20)
85
F
F
O
O
S
4
[Cp*Co(MeCN)3][SbF6]2
(5)
DCE
PhCO2Na
(20)
89 (86)
S
HN
S
HN
S
HN
O
O
5
[Cp*Co(MeCN)3][SbF6]2
(5)
TFE
PhCO2Na
(20)
-
5
-
N
N
N
Me
Me
Me
Me
Me
Me
3k, 83%
3l, 75%
3j, 60%
6
[Cp*Co(MeCN)3][SbF6]2
(5)
Dioxane
Toluene
DCE
PhCO2Na
(20)
Ph
O
tBu
S
N
HN
S
HN
O
7
[Cp*Co(MeCN)3][SbF6]2
(5)
PhCO2Na
(20)
N
Me
Me
Me
Me
3n, 74%
3m, 66%
8
Cp*Co(CO)I2
(5)
PhCO2Na
(20)
-
9
[Cp*Rh(MeCN)3][SbF6]2
(5)
DCE
PhCO2Na
(20)
71
-
Subsequently, the scope of our protocol was broadened to
include various thioamides derived from different cyclic or
acyclic amines and carboxylic acids. As presented in Table 3,
10
-
DCE
PhCO2Na
(20)
This article is protected by copyright. All rights reserved.

10.1002/anie.201709273
Angewandte Chemie International Edition
COMMUNICATION
thioamide substrates containing piperazine (4a and 4b) and
morpholine (4c) scaffolds worked well to afford the desired
amidated products in synthetically useful yields of 60-77%.
While simple acyclic thioamide substrate (4d) displayed good
reactivity, reactions with thioamides containing different ring
sizes of azacycles (4e and 4f) were also shown to be successful.
4-Substituted piperidinyl thioamides proceeded well in this
transformation to generate products 4h and 4i in moderate to
good yields. Remarkably, primary C(sp3)-H activation was
favored even in the presence of benzylic methylene protons – as
showcased by reaction products 4g, 4h and 4l – thus pointing
towards steric factors as overriding determinants of reactivity.[18]
Furthermore, isopropyl piperidinylthioamide 1k also reacted well
under these conditions to furnish 4j in 57% yield. Unfortunately,
cyclopropanethioamide 1n, cyclohexanethioamide 1o and
propionthioamide 1p were unreactive under the standard
conditions.
thioamide using nickel boride afforded amine 6a in 60% yield
(Scheme 1c).[20]
Ph
a)
O
S
H
S HN
O
Standard condition
O
+
N
N
O
Me
Me
Me
N
Me
Ph
3a, 83%
1a, 0.9 mmol
2a, 1.08 mmol
Ph
Ph
O
b)
O
HN
O
S
HN
Ag2CO3
N
DCM. rt. 18 h
Me
Me
N
Me
Me
5a, 84%
3a
Ph
O
Ph
c)
NiCl2.6H2O,
NaBH4
S
HN
HN
O
N
N
MeOH/THF (1:1)
Me
Me
Me
Me
0 o
C
Table 3: C(sp3)-H activation/amidation of various thioamides with 3-
phenyldioxazolones 2a
3a
6a, 60%
Scheme 1. a) Three-fold scale-up reaction. b) Oxidative desulfurization of
thioamide 3a. c) Reduction of thioamide 3a.
In line with prior art[5,6] and our preliminary computational
studies using ab initio and DFT methods implemented in Q-
Chem 5.0,[21] a redox-neutral Cp*CoIII catalytic cycle for the
C(sp3)-H activation/amidation of 1a and 2a is postulated to be in
operation in this chemistry as depicted in Scheme 2. Firstly, we
presumed that the first benzoate anion coordinates with
[Cp*Co]2+ to form the intermediate, A in a 2 coordination mode.
Subsequent binding of 1a to A to form B was found to be
exergonic (G298 = -117.0 kJmol-1). Approach of a second
external benzoate anion (ext) promotes the internal coordinated
benzoate (int) converting from a 2 to a 1 ligand forming C,
facilitated by an agostic interaction of Ha with Co. The
regioselectivity of C(sp3)-H activation in 1a was then analyzed.
Thus the interatomic distances of Hb—Ob (3.913 Å) and Cb—Co
(4.959 Å) in intermediate C were calculated to be much larger
than that of Ha—Oa (2.365 Å) and Ca—Co (2.396 Å) at the local
minimum (see supporting information, Table S1), rendering Cb—
Hb unlikely to be activated by Co. This supports the observed
selective C-H amidation at the primary methyl group of the
thioamide. The cyclometalation in complex C then leads to the
intermediate D potentially by an external carboxylate assisted
concerted metalation/ deprotonation (CMD-ext) mechanism[8a, 22]
The activation barrier for CMD-ext was determined to be lower
(G‡ 4.5 kJmol-1) than the traditional intramolecular
concerted metalation/deprotonation (CMD-int) (G‡
= 40.9
.
[a] Reaction was carried out at 60 °C.
=
298
To investigate the efficiency and further practicality of this
transformation, a three-fold scale-up of the reaction using the
standard substrates 1a and 2a was performed (Scheme 1a).
Pleasingly, negligible deviation in the obtained yield of 3a was
observed. Additionally, diversification of the amidated product to
access other important functionalities was achieved through
simple chemical modifications. For example conversion of
thioamide 3a to amide 5a was efficiently carried out with Ag(I)
carbonate (Scheme 1b),[19] whilst selective reduction of the
298
kJmol-1) thus favoring the former.
Subsequently, the
coordination of intermediate D with dioxazolone 2a followed by
migratory insertion of the amido group results in a synchronous
CO2 extrusion to afford the amido complex F. Proto-
demetalation of F would release product 3a and concurrently
regenerate active species A ready for further catalytic turnovers.
The absence of reactivity observed in compound 1n and 1o
were further examined and based on our preliminary
This article is protected by copyright. All rights reserved.

10.1002/anie.201709273
Angewandte Chemie International Edition
COMMUNICATION
calculations, their most stable conformations have CH3 groups
oriented away from the metal center (a dihedral of ~120° to the
C=S) when coordinated to A (see supporting information, Figure
S3). Therefore, an effective cyclo-cobaltation is less likely to
occur. Further investigations on the mechanism will be
discussed in detail in our subsequent work.
Experimental Section
General procedure for the synthesis of 3: In a N2-filled glovebox,
a 8 mL reaction vial was charged with thioamide 1a (0.30 mmol,
1 equiv), dioxazolone 2 (0.36 mmol, 1.2 equiv), PhCOONa (0.03
mmol, 4.32 mg), [Cp*Co(MeCN)3][SbF6]2 (0.015 mmol, 11.8 mg)
in DCE (3 mL). The sealed reaction vial was then brought out of
the glovebox and reaction was run under inert atmosphere at
40-60 °C. After 24 hours, the reaction mixture was cooled to
room temperature and solvent was removed in vacuo. The crude
reaction mixture was then purified and products were isolated by
flash column chromatography (EtOAc/ PE = 1/9 to 2/3).
[Cp*Co]2+
PhCOO-
N
S
H
Me
Me
N
Ph
S
N
Cp*
Co
3a
O
Me
Me
proto-demetalation
Me
H+
O
O
1a
X-
*Cp
Co
Ph
O
*Cp
Co
Oa
OCOPh
S
Ph
N
A
Ob
Ha
Ca
Me
Me
H
H
X = SbF6 or OCOPh
S
Ph
N
Hb
Acknowledgements
Me
Me
F
Cb
N
3)-H
C(s
p
CO2
X-
The authors acknowledge the University of Oxford and the
Agency for Science, Technology and Research (A*STAR)
Singapore for a predoctoral fellowship. This work was also
supported by the A*STAR Computational Resource Centre
(A*CRC) through the use of its high-performance computing
facilities.
migratory
Insertion
B
CoIII
Ph
N
O
*Cp
functionalization
PhCOO-
Cp*
OCOPh
S
Co
O
O
(ext)
Me
Me
Co
PhCOO-
Ha
N
Oa
(int)
Hb
Ob
Cb
H
Ca
E
OCOPh
S
*Cp
Co
H
S
Ph
O
Me
Me
Me
Me
N
coordination
PhCOOH
O
O
N
Keywords: cobalt Cp* • C(sp3)-H activation • amidation •
thioamide • selective
N
cyclo-cobaltation
C
Ph
D
2a
[1]
For selected reviews on C-H functionalization, see: a) R.-Y. Zhu, M. E.
Farmer, Y.-Q. Chen, J.-Q. Yu, Angew. Chem. Int. Ed. 2016, 55, 10578;
Angew. Chem. 2016, 128, 10734; b) O. Daugulis, J. Roane, L. D. Tran,
Acc. Chem. Res. 2015, 48, 1053; c) K. Shin, H. Kim, S. Chang, Acc.
Chem. Res. 2015, 48, 1040; d) Z. Chen, B. Wang, J. Zhang, W. Yu, Z.
Liu, Y. Zhang, Org. Chem. Front. 2015, 2, 1107; e) J. Wencel-Delord, F.
Glorius, Nat. Chem. 2013, 5, 369; f) J. Yamaguchi, A. D. Yamaguchi, K.
Itami, Angew. Chem. Int. Ed. 2012, 51, 8960; Angew. Chem. 124,
9092; g) S. R. Neufeldt, M. S. Sanford, Acc. Chem. Res. 2012, 45, 936;
h) K. M. Engle, T.-S. Mei, M. Wasa, J.-Q. Yu, Acc. Chem. Res. 2012,
45, 788; i) T. W. Lyons, M. S. Sanford, Chem. Rev. 2010, 110, 1147; j)
D. A. Colby, R. G. Bergman, J. A. Ellman, Chem. Rev. 2010, 110, 624;
k) C-H Bond Activation in Organic Synthesis (Ed.: J. J. Li), CRC Press,
Boca Raton, FL, J. J. Li, 2015, pp. 1-327.
TSCMD-ext
C
Scheme 2: Postulated mechanism for C(sp3)-H activation/amidation of
thioamide 1a with dioxazolone 2a. All bond lengths are in Ångstroms and
relative free energies are in kJmol-1 for density functional theory (DFT)-
optimized structures of intermediate C and TSCMD-ext
.
In conclusion, we have discovered and developed a mild,
efficient and selective method for C(sp3)-H bond activation /
amidation employing thioamides as the directing group, with
aryl-, heteroaryl- and alkyl- substituted dioxazolones under
CoIIICp* catalytic conditions. Additionally, a wide range of
thioamides with piperazine, morpholine, tetrahydroisoquinoline
and other substituted N-containing heterocycles were well-
tolerated. This work stands as a rare example of Cp*CoIII
catalyzed C(sp3)-H functionalization using an alternative
directing group to the commonly used pyridine/quinoline classes
and the first using a thioamide. Computational studies support
the observed regioselectivity towards primary C(sp3)-H activation
and suggest that the cyclometalation proceeds via an external
carboxylate assisted concerted metalation/ deprotonation
mechanism. Investigations into other synthetically relevant
CoIIICp* catalyzed C(sp3)-H bond functionalization reactions
directed by thioamide moieties – from ubiquitous amides, amino
acids and peptides – are currently ongoing and the results will
be disclosed in due course.
[2]
[3]
[4]
For selected reviews on first-row transition-metals catalyzed C-H
functionalization, see: a) W. Liu, L. Ackermann, ACS Catal. 2016, 6,
3743; b) B. Su, Z.-C. Cao, Z.-J. Shi, Acc. Chem. Res. 2015, 48, 886; c)
J. Miao, H. Ge, Eur. J. Org. Chem. 2015, 7859; d) L. Ackermann, J. Org.
Chem. 2014, 79, 8948; e) K. Gao, N. Yoshikai, Acc. Chem. Res. 2014,
47, 1208; f) E. Nakamura, N. Yoshikai, J. Org. Chem. 2010, 75, 6061;
g) A. A. Kulkarni, O. Daugulis, Synthesis 2009, 4087.
For recent reviews on cobalt catalyzed C-H functionalization, see: a) T.
Yoshino, S. Matsunaga, Adv. Synth. Catal. 2017, 359, 1245; b) S.
Wang, S.-Y. Chen, X.-Q. Yu, Chem. Commun. 2017, 53, 3165; c) P. G.
Chirila, C. J. Whiteoak, Dalton Trans, 2017, 46, 9721; d) M. Moselage,
J. Li, L. Ackermann, ACS Catal. 2016, 6, 498; e) D. Wei, X. Zhu, J.-L.
Niu, M.-P. Song, ChemCatChem 2016, 8, 1242; f) T.K. Hyster, Catal.
Lett. 2015, 145, 458.
For pioneering contributions on CoIIICp* catalyzed C(sp2)-H activation
reactions, see: a) H. Ikemoto, T. Yoshino, K. Sakata, S. Matsunaga, M.
Kanai, J. Am. Chem. Soc. 2014, 136, 5424; b) T. Yoshino, H. Ikemoto,
S. Matsunaga, M. Kanai, Angew. Chem. Int. Ed. 2013, 52, 2207;
Angew. Chem. 2013, 125, 2263; c) T. Yoshino, H. Ikemoto, S.
Matsunaga, M. Kanai, Chem. Eur. J. 2013, 19, 9142.
This article is protected by copyright. All rights reserved.

10.1002/anie.201709273
Angewandte Chemie International Edition
COMMUNICATION
[5]
For pioneering works on CoIIICp* catalyzed C(sp2)-H and C(sp3)-H
activation/ amidation reactions using dioxazolones, see: a) J. Park, S.
Chang, Angew. Chem. Int. Ed. 2015, 54, 14103; Angew. Chem. 2015,
127, 14309; b) N. Barsu, M. A. Rahman, M. Sen, B. Sundararaju, Chem.
Eur. J. 2016, 22, 9135.
[11] For selected reviews and examples of RhIII catalyzed reactions, see: a)
X. Wang, A. Lerchen, T. Gensch, T. Knecht, C. G. Daniliuc, F. Glorius,
Angew. Chem. Int. Ed. 2017, 56, 1381; Angew. Chem. 2017, 129,
1401; b) N. Semakul, K. E. Jackson, R. S. Paton, T. Rovis, Chem. Sci.
2017, 8, 1015; c) F. Lied, A. Lerchen, T. Knecht, C. Muck-Lichtenfeld, F.
Glorius, ACS Catal. 2016, 6, 7839; d) B. Ye, N. Cramer, Acc. Chem.
Res. 2015, 48, 1308; e) G. Song, X. Li, Acc. Chem. Res. 2015, 48,
1007; f) A. Archambeau, T. Rovis, Angew. Chem. Int. Ed. 2015, 54,
13337; Angew. Chem. 2015, 127, 13535; g) S. Yu, S. Liu, Y. Lan, B.
Wan, X. Li, J. Am. Chem. Soc. 2015, 137, 1623; h) X. Wang, D.-G. Yu,
F. Glorius, Angew. Chem. Int. Ed. 2015, 54, 10280; Angew. Chem.
2015, 127, 10419; i) T. A. Davis, C. Wang, T. Rovis, Synlett, 2015, 26,
1520; j) T. K. Hyster, D. M. Dalton, T. Rovis, Chem. Sci. 2015, 6, 254;
k) N. Kuhl, N. Schroder, F. Glorius, Adv. Synth. Catal. 2014, 356, 1443;
l) T. Piou, T. Rovis, J. Am. Chem. Soc. 2014, 136, 11292; m) P. W. Tan,
N. A. B. Juwaini, J.Seayad, Org. Lett. 2013, 15, 5166. n) D. A. Colby, A.
S. Tsai, R. G. Bergman, J. A. Ellman, Acc. Chem. Res. 2012, 45, 814.
[12] a) J. F. Hartwig, J. Am. Chem. Soc. 2016, 138, 2; b) H. Li, B.-J. Li, Z.-J.
Shi, Catal. Sci. Technol. 2011, 1, 191; c) R. Jazzar, J. Hitce, A.
Renaudat, J. Sofack-Kreutzer, O. Baudoin, Chem. Eur. J. 2010, 16,
2654.
[6]
For other CoIIICp* catalyzed activation / amidation reactions, see: a) Y.
Park, Y. Kim, S. Chang, Chem. Rev. 2017, 117, 9247; b) J. Huang, Y.
Huang, T. Wang, Q. Huang, Z. Wang, Z. Chen, Org. Lett. 2017, 19,
1128; c) F. Wang, L. Jin, L. Kong, X. Li, Org. Lett. 2017, 19, 1812; d) R.
Mei, J. Loup, L. Ackermann, ACS Catal. 2016, 6, 793; e) H. Wang, M.
M. Lorion, L. Ackermann, Angew. Chem. Int. Ed. 2016, 55, 10386;
Angew. Chem. 2016, 128, 10542; f) F. Wang, H. Wang, Q. Wang, S.
Yu, X. Li, Org. Lett, 2016, 18, 1306; g) X. Wang, A. Lerchen, F. Glorius,
Org. Lett. 2016, 18, 2090; h) B. Sun, T. Yoshino, S. Matsunaga, M.
Kanai, Chem. Commun. 2015, 51, 4659; i) P. Patel, S. Chang, ACS
Catal. 2015, 5, 853; j) Y. Liang, Y.-F. Liang, C. Tang, Y. Yuan, N. Jiao,
Chem. Eur. J. 2015, 21, 16395; k) J. R. Hummel, J. A. Ellman, Org. Lett.
2015, 17, 2400; l) B. Sun, T. Yoshino, S. Matsunaga, M. Kanai, Adv.
Synth. Catal. 2014, 356, 1491.
For relevant examples of CoIIICp* catalyzed C(sp2)-H activation
reactions, see: a) R. Mandal, B. Sundararaju, Org. Lett. 2017, 19, 2544;
b) L. N. Chavan, K. K. Gollapelli, R. Chegondi, A. B. Pawar, Org. Lett.
2017, 19, 2186; c) S. Nakanowatari, R. Mei, M. Feldt, L. Ackermann,
ACS Catal. 2017, 7, 2511; d) J. A. Boerth, J. A. Ellman, Angew. Chem.
Int. Ed. 2017, 56, 9976; Angew. Chem. 2017, 129, 10108; e) D. Zell, Q.
Bu, M. Feldt, L. Ackermann, Angew. Chem. Int. Ed. 2016, 55, 7408;
Angew. Chem. 2016, 128, 7534; f) H. Wang, M. Moselage, M. J.
Gonzalez, L. Ackermann, ACS Catal. 2016, 6, 2705; g) A. Lerchen, S.
Vasquez-Cespedes, F. Glorius, Angew. Chem. Int. Ed. 2016, 55, 3208;
Angew. Chem. 2016, 128, 3261; h) T. Gensch, F. J. R. Klauck, F.
Glorius, Angew. Chem. Int. Ed. 2016, 55, 11287; Angew. Chem. 2016,
128, 11457; i) A. Lerchen, T. Knecht, C. G. Daniliuc, F. Glorius, Angew.
Chem. Int. Ed. 2016, 55, 15166; Angew. Chem. 2016, 128, 15391; j)
J.A. Boerth, J. R. Hummel, J. A. Ellman, Angew. Chem. Int. Ed. 2016,
55, 12650; Angew. Chem. 2016, 128, 12840; k) J. R. Hummel, J. A.
Ellman J. Am. Chem. Soc. 2015, 137, 490; l) J. Li, L. Ackermann,
Angew. Chem. Int. Ed. 2015, 54, 3635; Angew. Chem. 2015, 127,
3706; m) A. B. Pawar, S. Chang, Org. Lett. 2015, 17, 660; n) T. Gensch,
S. Vasquez-Cespedes, D.-G. Yu, F. Glorius, Org. Lett. 2015, 17, 3714;
o) M. Moselage, N. Sauermann, J. Koeller, W. Liu, D. Gelman, L.
Ackermann, Synlett 2015, 26, 1596; p) Y. Suzuki, B. Sun, K. Sakata, T.
Yoshino, S. Matsunaga, M. Kanai, Angew. Chem. Int. Ed. 2015, 54,
9944; Angew. Chem. 2015, 127, 10082; q) Z.-Z. Zhang, B. Liu, C.-Y.
Wang, B.-F. Shi, Org. Lett. 2015, 17, 4094; r) M. Sen, D. Kalsi, B.
Sundararaju, Chem. Eur. J. 2015, 21, 15529; s) D. G. Yu, T. Gensch, F.
de Azambuja, S. Vasquez-Cespedes, F. Glorius, J. Am. Chem. Soc.
2014, 136, 17722.
[7]
[13] For selected reviews, see: a) M. Koketsu, H. Ishihara, Curr. Org. Synth.
2007, 4, 15; b) G. Purrello, Heterocycles 2005, 65, 411; c) T. S.
Jagodzinski, Chem. Rev. 2003, 103, 197; d) R. N. Hurd, G. DeLaMater,
Chem. Rev. 1961, 61, 45.
[14] a) T. Lincke, S. Behnken, K. Ishida, M. Roth, C. Hertweck, Angew.
Chem. Int. Ed. 2010, 49, 2011; Angew. Chem. 2010, 122, 2055; b) P.
Angehrn, E. Goetschi, H. Gmuender, P. Hebeisen, M. Hennig, B. Kuhn,
T. Luebbers, P. Reindl, F. Ricklin, A. Schmitt-Hoffmann, J. Med. Chem.
2011, 54, 2207; c) A. Bach, J. N. N. Eildal, N. Stuhr-Hansen, R.
Deeskamp, M. Gottschalk, S. W. Pedersen, A. S. Kristensen, K.
Stromgaard, J. Med. Chem. 2011, 54, 1333; d) K. L. Dunbar, D. H.
Scharf, A. Litomska, C. Hertweck, Chem. Rev. 2017, 117, 5521.
[15] Y. Yokoyama, Y. Unoh, R. A. Bohmann, T. Satoh, K. Hirano, C. Bolm,
M. Miura, Chem. Lett. 2015, 44, 1104.
[16] J. E. Spangler, Y. Kobayashi, P. Verma, D.-H. Wang, J.-Q. Yu, J. Am.
Chem. Soc. 2015, 137, 11876.
[17] Y. Park, K. T. Park, J. G. Kim, S. Chang, J. Am. Chem. Soc. 2015, 137,
4534.
[18] a) L. V. Desai, K. L. Hull, M. S. Sanford, J. Am. Chem. Soc. 2004, 126,
9542; b) V. V. Dunina, O. A. Zalevskaya, V. M. Potapov, Russ. Chem.
Rev. 1988,57, 250.
[19]
M. Avalos, R. Babiano, C. J. Duran, J. L. Jimenez, J. C. Palacios,
Tetrahedron Lett. 1994, 35, 477.
[20] M. L. Bennasar, E. Zulaica, J. M. Jimenez, J. Bosch, J.Org. Chem. 1993,
58, 7756.
[21] Y. Shao, et al., Mol. Phys. 2015, 113, 184.
[22] J. Jiang, R. Ramozzi, K. Morokuma, Chem. Eur. J. 2015, 21, 11158.
[8]
[9]
For CoIIICp* catalyzed C(sp3)-H activation reactions, see: a) M. Sen, B.
Emayavaramban, N. Barsu, J. R. Premkumar, B. Sundararaju, ACS
Catal. 2016, 6, 2792; Also see ref. 5b.
For other cobalt catalyzed C(sp3)-H functionalization examples, see: a)
N. Barsu, S. K. Bolli, B. Sundararaju, Chem. Sci. 2017, 8, 2431; b) W.
N. Palmer, J. V. Obligacion, I. Pappas, P. J. Chirik, J. Am. Chem. Soc.,
2016, 138, 766; c) X. Wu, K. Yang, Y. Zhao, H. Sun, G. Li, H. Ge, Nat.
Commun. 2015, 6, 6462; d) J. Zhang, H. Chen, C. Lin, Z. Liu, C. Wang,
Y. Zhang, J. Am. Chem. Soc., 2015, 137, 12990; e) A. D. Bolig, M.
Brookhart, J. Am. Chem. Soc., 2007, 129, 14544.
[10] For IrIIICp*
& / amidation
RhIIICp* catalyzed C(sp3)-H activation
reactions, see: a) H. Wang, G. Tang, X. Li, Angew. Chem. Int. Ed. 2015,
54, 13049; Angew. Chem. 2015, 127, 13241; b) X. Huang, Y. Wang, J.
Lan, J. You, Angew. Chem. Int. Ed. 2015, 54, 9404; Angew. Chem.
2015, 127, 9536; c) T. Kang, Y. Kim, D. Lee, Z. Wang, S. Chang, J. Am.
Chem. Soc. 2014, 136, 4141; d) N. Wang, R. Li, L. Li, S. Xu, H. Song,
B. Wang, J. Org. Chem. 2014, 79, 5379; e) T. Kang, H. Kim, J. G. Kim,
S. Chang, Chem. Commun. 2014, 50, 12073.
This article is protected by copyright. All rights reserved.

10.1002/anie.201709273
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
O
A mild, efficient and selective
method for C(sp3)-H bond
P. W. Tan, A. M. Mak, M. B.
Sullivan, D. J. Dixon* and J.
Seayad*
O
CO2
O
N
O
R3
activation / amidation employing
thioamides as the directing group,
with aryl-, heteroaryl- and alkyl-
substituted dioxazolones under
CoIIICp* catalytic conditions, is
described.
R3 = alkyl, aryl
3)-H
S
HN
R2
R3
C
(sp
N
Page No. – Page No.
CoIII
R1
functionalization
Thioamide Directed Co(III)
Catalyzed Selective Amidation of
C(sp3)-H Bonds
S
H
Mild conditions
Redox neutral / oxidant-free
Good functional group tolerance
N
R2
R1
This article is protected by copyright. All rights reserved.