Redox Neutral Radical-Relay Cobalt Catalysis toward C-H Fluorination and Amination

Article abstract of DOI:10.1021/acs.orglett.0c01072

A redox neutral radical-relay cobalt-catalyzed intramolecular C-H fluorination of N-fluoroamides featuring the in situ formed cobalt fluorides as the latent radical fluorinating agents is reported. Moreover, the reactivity of such a cobalt catalysis could be diverted from C-H fluorination to amination by engineering substrates' conformational flexibility. Preliminary mechanistic studies (UV-vis spectroscopy, cyclic voltammetry studies and DFT calculations, etc.) support the reaction proceeding a redox neutral radical-relay mechanism.

Full text of DOI:10.1021/acs.orglett.0c01072

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Letter
Redox Neutral Radical-Relay Cobalt Catalysis toward C−H
Fluorination and Amination
Peng Guo, Yuanyuan Li, Xiang-Gui Zhang, Jun-Fa Han, Yi Yu, Jun Zhu,* and Ke-Yin Ye*
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sı Supporting Information
ABSTRACT: A redox neutral radical-relay cobalt-catalyzed intramolecular C−H fluorination of N-fluoroamides featuring the in situ
formed cobalt fluorides as the latent radical fluorinating agents is reported. Moreover, the reactivity of such a cobalt catalysis could
be diverted from C−H fluorination to amination by engineering substrates’ conformational flexibility. Preliminary mechanistic
studies (UV−vis spectroscopy, cyclic voltammetry studies and DFT calculations, etc.) support the reaction proceeding a redox
neutral radical-relay mechanism.
he incorporation of fluorine atoms into organic molecules
is of great significance due to the unique properties of
Scheme 1. Organometallic Cobalt Fluorides in Catalysis
T
1
,2
fluorine element in life
agrochemicals) and material sciences. In this contest, recent
advances of selective fluorine incorporation including
(including pharmaceuticals and
3
4
5
6
nucleophilic fluorination, electrophilic fluorination, and
7
radical fluorination have dramatically enriched the synthetic
chemists’ tools for challenging carbon−fluorine bond for-
mation. Despite those advances, complementarily mild and
8
selective late-stage fluorination methods are still highly
demanding.
Among structurally diverse metal fluorides, organometallic
9
cobalt fluorides have drawn considerable attention of chemists
recently. Though bearing a fluorine atom, such complexes are
most frequently employed in the hydrofunctionalization of
1
0
olefins serving as nonfluorinating agents (Scheme 1A).
Typical synthetic route to those complexes requires a N-
fluoropyridinium salt as oxidant. Once formed, such species are
poised to undergo a facile reduction with silane generating
1
8
however, is elusive thus seldomly reported despite the
analogously rich precedents of organometallic fluorides
19
20
21
22
23
III
11
including Mn, Ag, Cu, Fe, and so on.
formal Co −H species, which are capable to facilitate the
Herein, we explore the organometallic cobalt fluorides as
latent radical fluorinating agents in the late-stage intra-
molecular fluorination (Scheme 1C, left). This protocol allows
highly selective fluorine-atom incorporation forming the
hydrogen atom addition across alkenes followed either by a
12
radical trapping, an oxidation to carbocation readily for
13
14
downstream nucleophilic addition or a cross-coupling to
their corresponding hydrofunctionalized products.
24
valuable functionalized benzylic fluorides under mild
The adoption of organometallic cobalt fluorides as the latent
conditions. Interestingly, engineering of substrate’s conforma-
9a
fluorinating agents is much less explored. Notable advances
of using cobalt fluorides as nucleophilic fluorinating agents
have been comprehensively investigated by Doyle and co-
workers in the enantioselective nucleophilic ring opening of
Received: March 24, 2020
1
5
16
epoxides and aziridines (Scheme 1B). Moreover, Baker and
co-workers have successfully employed the in situ generated
17
cobalt fluorides in the acyl chloride/fluoride metathesis. The
use of cobalt fluorides as the radical fluorinating source,
©
XXXX American Chemical Society
https://dx.doi.org/10.1021/acs.orglett.0c01072
A
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tional flexibility diverts the reaction pathway from C−H
fluorination to amination delivering another biologically
important pyrrolidine scaffold (Scheme 1C, right). Preliminary
mechanistic studies (including UV−vis spectroscopy, cyclic
voltammetry studies and DFT calculations) support the in situ
generated organometallic cobalt fluorides being key inter-
mediates in such a redox neutral radical-relay mechanism.
N-tert-Butyl fluoroamides, prepared and employed by Cook
and co-workers pioneeringly in the iron-catalyzed C−H
Scheme 2. Substrate Scope of the Co-catalyzed C−H
Fluorination
2
5
fluorination, exhibit much higher air, moisture, and thermal
26
stability compared with their haloamide analogues. Since
then, N-fluoroamides have been intensively investigated in the
27
Cu-catalyzed C−H functionalization. However, in those
transformations they only served as latent amidyl radicals
leaving the precious fluorine element to byproducts. We
anticipate the use of proper cobalt catalyst would take the
advantage of N-fluoroamides not only as amidyl radicals but
also fluorine surrogates in a redox neutral radical-relay manner.
Indeed, we found 10 mol % of Jacobsen Co(salen) complex
2
8
3
in 1,4-dioxane as solvent at 60 °C efficiently catalyzed the
intramolecular fluorine-relay of fluoroamide 1 forming C−H
fluorinated product 2 (92% NMR yield and 93% isolated yield,
entry 1, Table 1). A control experiment in the absence of
a
Reaction conditions: fluoroamide (0.2 mmol, 1 equiv), 3 (0.02
mmol, 10 mol %), 1,4-dioxane (c 0.05M), 60 °C, 10 h unless
b
Table 1. Reaction Conditions Optimization
otherwise noted. Yield of purified product. Gram-scale reaction, 48
c
d
e
h. 3 h. Dichloromethane as solvent. 20 mol % of 3 used.
with electron-donating (10, 11) or -withdrawing (12−15)
substituents all proceeded smoothly (57−86%). This reaction
could also be performed in a gram-scale manner in good yields
(81% for 2 and 80% for 13, respectively). Cyclopropane (16),
alkene (17) and alkyne (18, 19) functionalities were all well
tolerated. It is worthy of note that severe polymerization of the
styrene moiety in the preparation of 17, a significant side
b
entry
cat.
yield (%)
c
1
3
92 (93)
2
<5
78
21
60
75
<5
48
54
70
d
3
e
3
3
4
5
6
7
8
9
4
25
reaction in Fe-catalyzed C−H fluorination, was not observed
under current conditions. Besides primary C−H bonds,
secondary (20−22) and tertiary (23) C−H bonds could also
be efficiently fluorinated. Heterocycle incorporated substrates
including thiophene (24) and furan (25) were proved to be
good candidates for this fluorine-relay process, too. When
there were competing C−H bonds available, the 1,5-HAT
5
6
7
8
9
1
0
(
hydrogen-atom transfer) and sequential fluorination selec-
tively occurred at the activated benzylic C−H position (26).
To be noted, our protocol is capable to provide facile entries to
challenging fluorinated compounds (27−30) previously
25
unsuccessful in the iron catalysis (53−87%). It is worth
noting that though most substrates in Scheme 2 underwent the
desired transformation smoothly, an appreciable amount of the
defluorinated amide formation was observed for compounds
27−29. In addition, a multitude of functionalities (including
primary alcohol, epoxide, nitrile, aldehyde, ethyl cinnamate,
quinoline, etc.) were also highly compatible with this protocol
but not carboxylic acid, primary amine or indole as evaluated
by Glorius’ robustness screen method (see the Supporting
a
Reaction conditions: 1 (0.2 mmol, 1 equiv), 3 (0.02 mmol, 10 mol
b
19
%
), 1,4-dioxane (c 0.05M), 60 °C, 10 h. Yield determined by
F
NMR analysis using trifluoromethoxyl benzene as the internal
c
d
e
standard. Isolated yield. 5 mol % of 3. 1 mol % of 3.
cobalt showed no conversion (entry 2), while reducing catalyst
loading to 5 mol % (or 1 mol %) significantly depressed the
reaction yields to 78% (or 21%), suggesting a radical chain
29
Information for details).
To shed light on the mechanism of this Co-catalyzed
III
process is not likely (entries 3, 4). Co (salen)-Cl 4 was also
able to catalyze such a fluorine-relay event albeit in a
diminished yield (entry 5). Steric and electronic properties
of substituents at the salen scaffold were also evaluated
showing the Co(salen) complex 3 with highest catalytic
efficiency (entries 6−10).
fluorine-relay reaction, several mechanistic experiments were
II
then carried out. The facile redox character of Co (salen) 3
III/II
[E(Co ) = +125 mV vs Ag/AgCl] would allow it easily
being oxidized by fluoroamide 1 (E = −880 mV, N−F BDE ≈
p
−
1
30
63 kcal mol ), which is consistent with the observation of
color change from orange of Co(salen) 3 in MeCN to deep
brown rapidly upon addition of fluoroamide 1. Cyclic
With the optimal conditions in hand, we then evaluated the
scope and limitation of this protocol (Scheme 2). Substrates
B
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Letter
voltammetry studies indicated the mixture of Co(salen) 3 and
fluoroamide 1 generated a species (E1/2 = +80 mV, red trace)
Scheme 3. Proposed Mechanism
III
with similar cyclic voltammetry behavior of Co (salen)-Cl
31
(
E1/2 = +110 mV, purple trace, Figure 1A). The generation
Figure 1. (A) Cyclic voltammogram in DMF with nBu NBF (0.1 M)
4
4
as electrolyte: (a) fluoroamide 1 (12.5 mM), blue; (b) Co(salen) 3
2.5 mM), black; (c) mixture of Co(salen) 3 (2.5 mM) and
fluoroamide 1 (12.5 mM), red; (d) Co(salen)-Cl 4 (2.5 mM), purple.
Scan rate: 100 mV/s. (B) UV−vis absorbance of: (a) Co(salen) 3 (5
mM) in MeCN, blue; (b) mixture of Co(salen) 3 (5 mM) and
fluoroamide 1 (5.5 mM), black; (c) mixture of Co(salen) 3 (5 mM)
and fluoroamide 31 (5.5 mM), red.
mechanism was further substantiated by DFT calculations
(
(
vide infra).
DFT calculations were performed at the level of (U)B3LYP
theory and the relative Gibbs free energies for possible reaction
pathways of the cobalt-catalyzed C−H fluorination are
depicted in Figure 2. The two para t-Bu groups in Co(salen)
3
were simplified to H and only one enantiomer, i.e., (S,S)-3-
H, was used in the calculation. Accordingly, fluoroamide 1
initially interacts with Co(salen) 3-H to generate the cobalt
fluoride species A and an amidyl radical B via TS1 with a
of such a species was further evident by the UV−vis
spectroscopy studies as the characteristic absorption bands at
4
20 and 360 nm of Co(salen) 3 disappeared while new peaks
−
1
predicted energy barrier of 10.3 kcal mol . Subsequently, B
at 234 and 264 nm showed up upon addition of fluoroamide 1
or 31, which again is analogously to that of Co (salen)-Cl
−
1
III
undergoes 1,5-HAT reaction via TS2 (8.5 kcal mol ) to give a
benzyl radical C, from which C−H fluorinated product 2 can
be obtained in two possible pathways. In path A, C abstracts
the F atom from another equiv of 1 generating product 2 and a
3
2
(Figure 1B). Therefore, We tentatively assigned the new
III
15,16
species to be Co (salen)-F.
Additionally, radical rear-
rangement experiment of the ortho-cyclopropylmethyl fluo-
roamide 32 proceed smoothly delivering the unopened (33)
and opened (34) fluorides in 10:1 ratio (eq 1). The preference
of unopened fluoride versus opened one is surprising and it is
probably because benzyl stabilization increases the lifetime of
−
1
new amidyl B with an energy barrier of 14.9 kcal mol ,
whereas fluorine radical rebound from cobalt fluoride A to C is
−
1
almost barrier-free (1.7 kcal mol , path B). Though both
routes are principally feasible according to the calculations,
path B featuring cobalt fluoride A as the radical fluorinating
agent is more favorable. This conclusion is further supported
by the observation of much lower yield with 1 mol % of
catalyst and moderate asymmetric induction when using the
enantiomerically pure Co complex. Consistent with the
calculations, the kinetic-isotope-effect (KIE) analysis also
supports the 1,5-HAT or prior event being the rate-limiting-
25,27a
the short-live radical intermediate.
Radical inhibition test
using TEMPO completely shut down the reactivity and the
corresponding nitroxyl radical adduct 35 was isolated in 62%
yield (eq 2). Both experiments strongly support the existence
of radical intermediates in this cobalt catalyzed C−H
fluorination.
2
5,27a
step (see the Supporting Information for more details).
Unlike the unified Fe-catalyzed C−H fluorination,
2
5,34
this
redox neutral radical-relay cobalt catalysis was found to be
surprisingly sensitive to the conformational flexibility of
substrates. For instance, starting from the corresponding
conformationally flexible N-fluoroamide only intramolecular
27c,35
amination
product 36 could be obtained in 64% yield
other than the anticipated fluorinated one. Thus, diverse
biologically important pyrrolidines could be conveniently
prepared accordingly (Scheme 4). The intramolecular
amination of geminal disubstituted substrates generally
proceeded in good yields (37−42, 62−91%) consistent with
On the basis of the preliminary mechanistic information
gained, a redox neutral radical-relay mechanism is proposed
2
(
Scheme 3). The unpaired electron in the d orbital of the
z
II
36
square-planar Co (salen) 3 (spin density on Co ≈ 1.0) initially
interacts with the low-lying LUMO of the fluoroamide I
presumably via an inner-sphere SET (single-electron transfer)
mechanism generating the organometallic cobalt fluoride
species II and an amidyl radical III. Subsequent 1,5-HAT
transfers the spin density from nitrogen (III) to benzylic
Thorpe−Ingold effect. Besides substrates underwent benzylic
C−H amination, those without benzylic but with primary
(39−41) or secondary C−H (42, 43) bonds available for the
1,5-HAT also proceeded smoothly. In sharp contrast, the
analogous reaction using Cu catalysis was only limited to
27c
substrates at the benzylic positions. Distinct from the C−H
fluorination mentioned previously, N-fluorosulfonamide with
competing C−H bonds available for the 1,5-HAT preferred the
flexible primary C−H bond (44) other than the activated
33
carbon center (IV). Following the persistent radical effect,
fluorine radical rebound from the persistent cobalt fluoride II
(
at least comparable to the time scale of UV−vis spectroscopy
27d
and cyclic voltammetry) to the transient carbon-center radical
IV furnishes the fluorinated product V while regenerating the
Co(salen) 3 to close the catalytic cycle. This proposed
benzylic one. However, this protocol was not the choice of
piperidine preparation as both pyrrolidine (45) and piperidine
(46) were obtained unselectively. A more detailed mechanistic
C
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Letter
−
1
Figure 2. Relative Gibbs free energies (in kcal mol ) for possible reaction pathways of the Co-catalyzed C−H fluorination (see the Supporting
Information for more computational details).
Scheme 4. Substrate Scope of the Co-catalyzed C−H
Amination
ASSOCIATED CONTENT
sı Supporting Information
■
*
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01072.
Experimental procedures and characterization data for
all compounds and computational details (PDF)
AUTHOR INFORMATION
■
Corresponding Authors
Ke-Yin Ye − Key Laboratory of Molecule Synthesis and Function
Discovery (Fujian Province University), College of Chemistry,
Fuzhou University, Fuzhou 350108, China; orcid.org/
0
000-0003-3955-7079; Email: kyye@fzu.edu.cn
Jun Zhu − State Key Laboratory of Physical Chemistry of Solid
Surfaces and Collaborative Innovation Center of Chemistry for
Energy Materials (iChEM), Fujian Provincial Key Laboratory
of Theoretical and Computational Chemistry and Department
of Chemistry, College of Chemistry and Chemical Engineering,
Xiamen University, Xiamen 361005, China; orcid.org/
a
Reaction conditions: fluoroamide or fluorosulfonamide (0.2 mmol, 1
equiv), 3 (0.02 mmol, 10 mol %), 1,4-dioxane (c 0.05M), 60 °C, 10 h
unless otherwise noted. Yield of purified product. Dichloromethane
as solvent. Gram-scale reaction, 48 h. 20 mol % of 3 used.
b
c
d
0
000-0002-2099-3156; Email: jun.zhu@xmu.edu.cn
Authors
investigation is still needed to elucidate the origin of formation
of pyrrolidines.
3
7
Peng Guo − Key Laboratory of Molecule Synthesis and Function
Discovery (Fujian Province University), College of Chemistry,
Fuzhou University, Fuzhou 350108, China
In conclusion, we have shown that the redox neutral radical-
relay cobalt catalysis provides facile entries to biologically
important fluorinated compounds. Preliminary mechanistic
investigations revealed the in situ formed cobalt fluorides being
the key species in such a radical-relay fluorination. In addition,
it was found the conformational flexibility of substrates (N-
fluoroamides or N-fluorosulfonamides) diverts the reaction
pathway toward C−H fluorination or C−H amination
reaction, respectively. More detailed mechanism investigations
and applications of this protocol in the late-stage fluorination
Yuanyuan Li − State Key Laboratory of Physical Chemistry of
Solid Surfaces and Collaborative Innovation Center of
Chemistry for Energy Materials (iChEM), Fujian Provincial
Key Laboratory of Theoretical and Computational Chemistry
and Department of Chemistry, College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen 361005,
China
Xiang-Gui Zhang − Key Laboratory of Molecule Synthesis and
Function Discovery (Fujian Province University), College of
Chemistry, Fuzhou University, Fuzhou 350108, China
38
including asymmetric fluorine transfer are currently under-
way in our laboratory.
D
https://dx.doi.org/10.1021/acs.orglett.0c01072
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Organic Letters
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Letter
Jun-Fa Han − Key Laboratory of Molecule Synthesis and
Function Discovery (Fujian Province University), College of
Chemistry, Fuzhou University, Fuzhou 350108, China
Yi Yu − Key Laboratory of Molecule Synthesis and Function
Discovery (Fujian Province University), College of Chemistry,
Fuzhou University, Fuzhou 350108, China
(d) Leggans, E. K.; Barker, T. J.; Duncan, K. K.; Boger, D. L. Org. Lett.
2
012, 14, 1428−1431. (e) King, S. M.; Ma, X.; Herzon, S. B. J. Am.
Chem. Soc. 2014, 136, 6884−6887. (f) Crossley, S. W.; Obradors, C.;
Martinez, R. M.; Shenvi, R. A. Chem. Rev. 2016, 116, 8912−9000.
(
(
g) Ma, X.; Herzon, S. B. J. Am. Chem. Soc. 2016, 138, 8718−8721.
h) Ma, X.; Dang, H.; Rose, J. A.; Rablen, P.; Herzon, S. B. J. Am.
Chem. Soc. 2017, 139, 5998−6007.
Complete contact information is available at:
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(11) (a) Ding, K.; Dugan, T. R.; Brennessel, W. W.; Bill, E.; Holland,
P. L. Organometallics 2009, 28, 6650−6656. (b) Dugan, T. R.;
Goldberg, J. M.; Brennessel, W. W.; Holland, P. L. Organometallics
2
(
4
012, 31, 1349−1360.
12) (a) Waser, J.; Carreira, E. M. Angew. Chem., Int. Ed. 2004, 43,
099−4102. (b) Waser, J.; Gaspar, B.; Nambu, H.; Carreira, E. M. J.
Notes
The authors declare no competing financial interest.
Am. Chem. Soc. 2006, 128, 11693−11712. (c) Green, S. A.; Crossley,
S. W. M.; Matos, J. L. M.; Vasquez-Cespedes, S.; Shevick, S. L.;
Shenvi, R. A. Acc. Chem. Res. 2018, 51, 2628−2640. (d) Zhou, X. L.;
Yang, F.; Sun, H. L.; Yin, Y. N.; Ye, W. T.; Zhu, R. J. Am. Chem. Soc.
ACKNOWLEDGMENTS
■
Financial support from the National Natural Science
Foundation of China (No. 21901041) and the Top-Notch
Young Talents Program of China is gratefully acknowledged.
We thank Prof. Yi Li (Fuzhou University) and Prof. Chun-
Xiang Zhuo (Xiamen University) for helpful discussions.
2
(
019, 141, 7250−7255.
13) (a) Shigehisa, H.; Aoki, T.; Yamaguchi, S.; Shimizu, N.; Hiroya,
K. J. Am. Chem. Soc. 2013, 135, 10306−10309. (b) Shigehisa, H.;
Koseki, N.; Shimizu, N.; Fujisawa, M.; Niitsu, M.; Hiroya, K. J. Am.
Chem. Soc. 2014, 136, 13534−13537. (c) Shepard, S. M.; Diaconescu,
P. L. Organometallics 2016, 35, 2446−2453. (d) Shigehisa, H.;
Hayashi, M.; Ohkawa, H.; Suzuki, T.; Okayasu, H.; Mukai, M.;
Yamazaki, A.; Kawai, R.; Kikuchi, H.; Satoh, Y.; Fukuyama, A.;
Hiroya, K. J. Am. Chem. Soc. 2016, 138, 10597−10604. (e) Shigehisa,
H.; Kikuchi, H.; Hiroya, K. Chem. Pharm. Bull. 2016, 64, 371−374.
REFERENCES
■
(
1) (a) Reddy, V. P. Organofluorine Compounds in Biology and
Medicine; Elsevier, 2012. (b) Haufe, G., Leroux, F. R., Eds.; Fluorine in
life sciences: pharmaceuticals, medicinal diagnostics, and agrochemicals;
Elsevier, 2019.
(
f) Shigehisa, H. Chem. Pharm. Bull. 2018, 66, 339−346. (g) Touney,
E. E.; Foy, N. J.; Pronin, S. V. J. Am. Chem. Soc. 2018, 140, 16982−
6987. (h) Discolo, C. A.; Touney, E. E.; Pronin, S. V. J. Am. Chem.
(
2) (a) Jeschke, P. ChemBioChem 2004, 5, 570−589. (b) Fujiwara,
T.; O’Hagan, D. J. Fluorine Chem. 2014, 167, 16−29.
3) Berger, R.; Resnati, G.; Metrangolo, P.; Weber, E.; Hulliger, J.
Chem. Soc. Rev. 2011, 40, 3496−3508.
4) (a) Liang, T.; Neumann, C. N.; Ritter, T. Angew. Chem., Int. Ed.
013, 52, 8214−8264. (b) Landelle, G.; Panossian, A.; Pazenok, S.;
Vors, J. P.; Leroux, F. R. Beilstein J. Org. Chem. 2013, 9, 2476−536.
c) Champagne, P. A.; Desroches, J.; Hamel, J. D.; Vandamme, M.;
1
(
Soc. 2019, 141, 17527−17532. (i) Yahata, K.; Kaneko, Y.; Akai, S.
Org. Lett. 2020, 22, 598−603.
(
2
(14) (a) Green, S. A.; Matos, J. L.; Yagi, A.; Shenvi, R. A. J. Am.
Chem. Soc. 2016, 138, 12779−12782. (b) Shevick, S. L.; Obradors, C.;
Shenvi, R. A. J. Am. Chem. Soc. 2018, 140, 12056−12068. (c) Green,
S. A.; Huffman, T. R.; McCourt, R. O.; van der Puyl, V.; Shenvi, R. A.
J. Am. Chem. Soc. 2019, 141, 7709−7714. (d) Shevick, S. L.; Baker, M.
A.; Shenvi, R. A. Trends in Chem. 2019, 1, 540−541. (e) Lu, S.; Fu, N.
K.; Ernst, B. G.; Lee, W. H.; Frederick, M. O.; DiStasio, R. A., Jr; Lin,
S. ChemRxiv 2019, DOI: 10.26434/chemrxiv.9784625.v1.
(
Paquin, J. F. Chem. Rev. 2015, 115, 9073−174. (d) Chen, P.; Liu, G.
Eur. J. Org. Chem. 2015, 2015, 4295−4309. (e) Li, X.; Shi, X.; Li, X.;
Shi, D. Beilstein J. Org. Chem. 2019, 15, 2213−2270. (f) Szpera, R.;
Moseley, D. F. J.; Smith, L. B.; Sterling, A. J.; Gouverneur, V. Angew.
Chem., Int. Ed. 2019, 58, 14824−14848.
(15) (a) Kalow, J. A.; Doyle, A. G. J. Am. Chem. Soc. 2010, 132,
(
5) (a) Wu, J. Tetrahedron Lett. 2014, 55, 4289−4294. (b) Lee, J.
W.; Oliveira, M. T.; Jang, H. B.; Lee, S.; Chi, D. Y.; Kim, D. W.; Song,
3
1
268−3269. (b) Kalow, J. A.; Doyle, A. G. J. Am. Chem. Soc. 2011,
33, 16001−16012. (c) Shaw, T. W.; Kalow, J. A.; Doyle, A. G. Org.
C. E. Chem. Soc. Rev. 2016, 45, 4638−4650.
Synth. 2012, 89, 9−18. (d) Graham, T. J.; Lambert, R. F.; Ploessl, K.;
Kung, H. F.; Doyle, A. G. J. Am. Chem. Soc. 2014, 136, 5291−5294
For related reactions mediated by Cr(salen)-F complexes, see.
(
6
1
6) (a) Baudoux, J.; Cahard, D. Organic Reactions 2007, 69, 347−
72. (b) Lal, G. S.; Pez, G. P.; Syvret, R. G. Chem. Rev. 1996, 96,
737−1756. (c) Nyffeler, P. T.; Duron, S. G.; Burkart, M. D.;
(
e) Bruns, S.; Haufe, G. J. Fluorine Chem. 2000, 104, 247−254.
Vincent, S. P.; Wong, C. H. Angew. Chem., Int. Ed. 2005, 44, 192−212.
(f) Haufe, G.; Bruns, S. Adv. Synth. Catal. 2002, 344, 165−171.
(
7) (a) Rueda-Becerril, M.; Sazepin, C. C.; Leung, J. C.; Okbinoglu,
(16) Kalow, J. A.; Doyle, A. G. Tetrahedron 2013, 69, 5702−5709.
(17) (a) Leclerc, M. C.; Bayne, J. M.; Lee, G. M.; Gorelsky, S. I.;
T.; Kennepohl, P.; Paquin, J. F.; Sammis, G. M. J. Am. Chem. Soc.
2
012, 134, 4026−4029. (b) Chatalova-Sazepin, C.; Hemelaere, R.;
Paquin, J. F.; Sammis, G. M. Synthesis 2015, 47, 2554−2569. (c) Yan,
H.; Zhu, C. Sci. China: Chem. 2017, 60, 214−222.
Vasiliu, M.; Korobkov, I.; Harrison, D. J.; Dixon, D. A.; Baker, R. T. J.
Am. Chem. Soc. 2015, 137, 16064−73. (b) Lee, G. M.; Cle
Tom Baker, R. Catal. Sci. Technol. 2017, 7, 4996−5003.
ment, R.;
́
(
8) (a) Postigo, A. Late-Stage Fluorination of Bioactive Molecules and
Biologically-Relevant Substrates. Elsevier, 2018. (b) Campbell, M. G.;
Ritter, T. Chem. Rec. 2014, 14, 482−491. (c) Campbell, M. G.; Ritter,
T. Org. Process Res. Dev. 2014, 18, 474−480. (d) Neumann, C. N.;
Ritter, T. Angew. Chem., Int. Ed. 2015, 54, 3216−3221.
(18) Shigehisa, H.; Nishi, E.; Fujisawa, M.; Hiroya, K. Org. Lett.
2013, 15, 5158−5161. Though a radical mechanism was proposed in
this paper, the authors assumed fluorine element in the hydro-
fluorination products originated from N-fluoropyridinium salts
instead of cobalt fluorides.
(19) (a) Liu, W.; Huang, X.; Cheng, M.-J.; Nielsen, R. J.; Goddard,
W. A.; Groves, J. T. Science 2012, 337, 1322−1325. (b) Liu, W.;
Groves, J. T. Angew. Chem., Int. Ed. 2013, 52, 6024−6027.
(20) (a) Li, Z.; Song, L.; Li, C. J. Am. Chem. Soc. 2013, 135, 4640−
4643. (b) Zhu, L.; Chen, H.; Wang, Z.; Li, C. Org. Chem. Front. 2014,
1, 1299−1305. (c) Chen, H.; Zhu, L.; Li, C. Org. Chem. Front. 2017,
4, 565−568.
(
9) (a) Bennett, B. K.; Harrison, R. G.; Richmond, T. G. J. Am.
Chem. Soc. 1994, 116, 11165−11166. (b) Zheng, T.; Sun, H.; Chen,
Y.; Li, X.; Durr, S.; Radius, U.; Harms, K. Organometallics 2009, 28,
̈
5
771−5776. (c) Lian, Z.; Xu, X.; Sun, H.; Chen, Y.; Zheng, T.; Li, X.
Dalton Trans 2010, 39, 9523−9529. (d) Dugan, T. R.; Sun, X.;
Rybak-Akimova, E. V.; Olatunji-Ojo, O.; Cundari, T. R.; Holland, P.
L. J. Am. Chem. Soc. 2011, 133, 12418−12421.
(10) (a) Mukaiyama, T.; Isayama, S.; Inoki, S.; Kato, K.; Yamada, T.;
Takai, T. Chem. Lett. 1989, 18, 449−452. (b) Ishikawa, H.; Colby, D.
A.; Boger, D. L. J. Am. Chem. Soc. 2008, 130, 420−421. (c) Ishikawa,
H.; Colby, D. A.; Seto, S.; Va, P.; Tam, A.; Kakei, H.; Rayl, T. J.;
Hwang, I.; Boger, D. L. J. Am. Chem. Soc. 2009, 131, 4904−4916.
(21) (a) Bloom, S.; Pitts, C. R.; Miller, D. C.; Haselton, N.; Holl, M.
G.; Urheim, E.; Lectka, T. Angew. Chem., Int. Ed. 2012, 51, 10580−
10583. (b) Liu, Z.; Chen, H.; Lv, Y.; Tan, X.; Shen, H.; Yu, H. Z.; Li,
C. J. Am. Chem. Soc. 2018, 140, 6169−6175.
E
https://dx.doi.org/10.1021/acs.orglett.0c01072
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(
22) Bloom, S.; Pitts, C. R.; Woltornist, R.; Griswold, A.; Holl, M.
G.; Lectka, T. Org. Lett. 2013, 15, 1722−1724.
23) Kiplinger, J. L.; Richmond, T. G.; Osterberg, C. E. Chem. Rev.
994, 94, 373−431.
24) (a) Xia, J.-B.; Zhu, C.; Chen, C. J. Am. Chem. Soc. 2013, 135,
7494−17500. (b) Xu, P.; Guo, S.; Wang, L.; Tang, P. Angew. Chem.,
Int. Ed. 2014, 53, 5955−5958.
25) Groendyke, B. J.; AbuSalim, D. I.; Cook, S. P. J. Am. Chem. Soc.
016, 138, 12771−12774.
26) Bosnidou, A. E.; Duhamel, T.; Mun
019, DOI: 10.1002/ejoc.201900497.
27) (a) Li, Z.; Wang, Q.; Zhu, J. Angew. Chem., Int. Ed. 2018, 57,
3288−13292. (b) Li, J.; Zhang, Z.; Wu, L.; Zhang, W.; Chen, P.; Lin,
Z.; Liu, G. Nature 2019, 574, 516−521. (c) Bafaluy, D.; Munoz-
Molina, J. M.; Funes-Ardoiz, I.; Herold, S.; de Aguirre, A. J.; Zhang,
H.; Maseras, F.; Belderrain, T. R.; Perez, P. J.; Muniz, K. Angew.
(
1
(
1
(
2
(
2
̃
iz, K. Eur. J. Org. Chem.
(
1
̃
́
̃
Chem., Int. Ed. 2019, 58, 8912−8916. (d) Liu, Z.; Xiao, H.; Zhang, B.;
Shen, H.; Zhu, L.; Li, C. Angew. Chem., Int. Ed. 2019, 58, 2510−2513.
(
e) Modak, A.; Pinter, E. N.; Cook, S. P. J. Am. Chem. Soc. 2019, 141,
8405−18410. (f) Zeng, X.; Yan, W.; Paeth, M.; Zacate, S. B.; Hong,
1
P. H.; Wang, Y.; Yang, D.; Yang, K.; Yan, T.; Song, C.; Cao, Z.;
Cheng, M. J.; Liu, W. J. Am. Chem. Soc. 2019, 141, 19941−19949.
(
g) Zhang, H.; Zhou, Y.; Tian, P.; Jiang, C. Org. Lett. 2019, 21, 1921−
1
1
3
2
925. (h) Zhang, Z.; Stateman, L. M.; Nagib, D. A. Chem. Sci. 2019,
0, 1207−1211. (i) Zhang, Z.; Zhang, X.; Nagib, D. A. Chem. 2019, 5,
127−3134. (j) Yin, Z.; Zhang, Y.; Zhang, S.; Wu, X.-F. J. Catal.
019, 377, 507−510. (k) Qin, Y.; Han, Y.; Tang, Y.; Wei, J.; Yang, M.
Chem. Sci. 2020, 11, 1276−1282.
(28) Hansen, K. B.; Leighton, J. L.; Jacobsen, E. N. J. Am. Chem. Soc.
1
(
(
996, 118, 10924−10925.
29) Collins, K. D.; Glorius, F. Nat. Chem. 2013, 5, 597−601.
30) Meyer, D.; Jangra, H.; Walther, F.; Zipse, H.; Renaud, P. Nat.
Commun. 2018, 9, 4888.
31) Hanzlik, J.; Puxeddu, A.; Costa, G. J. Chem. Soc., Dalton Trans.
977, 542−546.
32) Shin, C.-K.; Kim, S.-J.; Kim, G.-J. Tetrahedron Lett. 2004, 45,
429−7433.
33) (a) Studer, A. Chem. - Eur. J. 2001, 7, 1159−1164. (b) Fischer,
H. Chem. Rev. 2001, 101, 3581−3610. (c) Studer, A. Chem. Soc. Rev.
004, 33, 267−273. (d) Yan, M.; Lo, J. C.; Edwards, J. T.; Baran, P. S.
J. Am. Chem. Soc. 2016, 138, 12692−12714.
34) Pinter, E. N.; Bingham, J. E.; AbuSalim, D. I.; Cook, S. P. Chem.
Sci. 2020, 11, 1102−1106.
35) A cobalt-catalyzed enantioselective intramolecular amination of
(
1
(
7
(
2
(
(
sulfonyl azides was reported recently: Hu, Y.; Lang, K.; Li, C.; Gill, J.
B.; Kim, I.; Lu, H.; Fields, K. B.; Marshall, M.; Cheng, Q.; Cui, X.;
Wojtas, L.; Zhang, X. P. J. Am. Chem. Soc. 2019, 141, 18160−18169.
(
(
36) Ingold, C. K.; Thorpe, J. F. J. Chem. Soc. 1928, 0, 1318−1321.
III
37) Preliminary DFT calculations suggest the Co -F might
facilitate the HAT step from the N-H bond during the amination
process, see Supporting Information for details.
(
38) (a) Lectard, S.; Hamashima, Y.; Sodeoka, M. Adv. Synth. Catal.
010, 352, 2708−2732. (b) Yang, X.; Wu, T.; Phipps, R. J.; Toste, F.
D. Chem. Rev. 2015, 115, 826−870.
2
F
https://dx.doi.org/10.1021/acs.orglett.0c01072
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