Catalytic Radical Process for Enantioselective Amination of C(sp3)?H Bonds

Article abstract of DOI:10.1002/anie.201808923

A new catalytic radical system involving Co^II-based metalloradical catalysis is effective in activating sulfamoyl azides for enantioselective radical 1,6-amination of C(sp³)?H bonds, affording six-membered chiral heterocyclic sulfami

Full text of DOI:10.1002/anie.201808923

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Catalytic Radical Process for Enantioselective Amination of
C(sp3)-H Bonds
Authors: Chaoqun Li, Kai Lang, Hongjian Lu, Yang Hu, Xin Cui, Lukasz
Wojtas, and X. Peter Zhang
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.201808923
Angew. Chem. 10.1002/ange.201808923
Link to VoR: http://dx.doi.org/10.1002/anie.201808923
http://dx.doi.org/10.1002/ange.201808923

10.1002/anie.201808923
Angewandte Chemie International Edition
COMMUNICATION
Catalytic Radical Process for Enantioselective Amination of
C(sp3)–H Bonds
Chaoqun Li,[b] Kai Lang,[a] Hongjian Lu,[b] Yang Hu,[b] Xin Cui,[b] Lukasz Wojtas,[b] and X. Peter Zhang*[a]
Abstract:
A
new catalytic radical system via Co(II)-based
intramolecular radical substitution, the C-centered radical
intermediates II could be converted to six-membered cyclic
sulfamides through C–N bond formation while regenerating the
Co(II)-metalloradical catalyst (Scheme 1).[11a,11d-e,11g] Although
substrate control of diastereoselectivity was previously
demonstrated, whether the Co(II)-catalyzed radical amination
could be rendered highly enantioselective is an unanswered
important question that was not entirely clear due to the lack of
information on the key C–N bond formation step. Does the
metalloradical catalysis is effective in activating sulfamoyl azides for
enantioselective radical 1,6-amination of broad types of C(sp3)–H
bonds, affording six-membered chiral heterocyclic sulfamides in high
yields with excellent enantioselectivities. The Co(II)-catalyzed C–H
amination features an unusual degree of functional group tolerance
and chemoselectivity. The unique profile of reactivity and
stereoselectivity is attributed to the underlying stepwise radical
pathway. The resulting optically active cyclic sulfamides can be
readily converted to synthetically useful chiral 1,3-diamine derivatives
with retention of the original enantiopurity.
intramolecular homolytic radical substitution proceed in
a
concerted fashion (SH2 type) or a stepwise manner (SH1 type)
with first homolytic cleavage of the Co–N bond? Obviously, the
former mechanism is the essential prerequisite for achieve
asymmetric induction. Even under the operation of SH2-type
mechanism, realization of high enantiocontrol would entail the
judicious identification of a D2-symmetric chiral amidoporphyrin
with a proper chiral environment that could effectively differentiate
the two prochiral faces of the ζ-Co(III)-alkyl radicals II for the
succeeding C–N bond formation (Scheme 1). If realized, it would
establish the first asymmetric catalytic system for enantioselective
intramolecular radical C(sp3)–H amination of sulfamoyl azides to
form six-membered chiral heterocyclic sulfamides, which are
interesting heterocycles in their own right, but also serve as useful
synthetic intermediates for preparation of valuable chiral 1,3-
diamines (see Figure S1 in Supporting Information).[12]
Radical chemistry has the potential to offer new synthetic tools
for construction of organic molecules with a unique profile of
reactivity and selectivity that is complementary to ionic
chemistry.[1,2] Despite significant progress in the field, the control
of stereoselectivity, particularly enantioselectivity, presents a
formidable task and has been largely unaddressed for many types
of radical reactions. Among considerable efforts in surmounting
this challenge,[3] metalloradical catalysis (MRC) represents a
conceptually new approach in that metal-centered radicals are
explored as open-shell catalysts for activating organic
compounds to generate metal-supported radical species as well
as for controlling their following homolytic radical reactions in a
catalytic manner.[4,5] In this respect, Co(II) complexes of
porphyrins, as stable 15e metalloradicals, have recently been
demonstrated as efficient catalysts that homolytically activate
diazo compounds and organic azides to generate a-Co(III)-alkyl
radicals[6] and a-Co(III)-aminyl radicals,[7] respectively. These
metal-stabilized organic radicals can serve as key intermediates
to undergo subsequent radical reactions, such as radical addition
to C=C bonds and H-atom abstraction of C–H bonds as well as
radical substitution for C–C/C–N bond formation, leading to the
development of new catalytic radical processes. Representative
examples include radical olefin cyclopropanation,[8] radical olefin
aziridination,[9] radical C–H alkylation,[10] and radical C–H
amination.[11]
O
O
O
O
2R
S
2R
S
N3
N
NH
N
[Co(Por*)]
H
H
N2
+
R1
ꢀ
R1
H
O
O
O
O
2R
S
2R
S
N
N
N
N
N3
N
NH
N
Co
H
H
R1
H
ꢀ
R1
[Co(Por*)]
Enantioselective
C–N Bond
Formation?
radical
substitution
radical
activation
N2
R2
R2
MRC
N
N
O
H
O
S
S
H
1R
H
1R
O
N
O
N
H
ζ-Co(III)-
α-Co(III)-
Aminyl
Radicals
Alkyl
Radicals
N
N
N
N
N
N
N
N
Co
Co
H-atom
abstraction
II
I
In addition to attaining controllable reactivity, the Co(II)-based
metalloradical catalysis (Co(II)-MRC) enables the control of
stereoselectivity through the use of D2-symmetric chiral
amidoporphyrins as the supporting ligands.[8,9b,9e,10] In particular,
Co(II)-MRC was previously applied for homolytic activation of
sulfamoyl azides to generate corresponding a-Co(III)-aminyl
radicals I that could undergo 1,6-H-atom abstraction from C(sp3)–
H bonds to give ζ-Co(III)-alkyl radicals II (Scheme 1). Following
Scheme 1. Working proposal for control of enantioselectivity of intramolecular
1,6-C(sp3)–H radical amination of sulfamoyl azides via Co(II)-based MRC.
Catalytic intramolecular C–H amination provides an attractive
approach for the construction of N-heterocycles.[4d,4e,13] Despite
advancements, enantioselective variant of intramolecular C–H
amination remains largely underdeveloped.[13e,f] We wish to report
herein the development of the first asymmetric catalytic system
for enantioselective 1,6-C(sp3)–H amination of sulfamoyl azides
via Co(II)-MRC. Under neutral and non-oxidative conditions, the
Co(II) complex of a structure-optimized D2-symmetric chiral
amidoporphyrin allows for effective activation of sulfamoyl azides
even at room temperature for intramolecular radical amination,
forming the six-membered heterocyclic sulfamides in high yields
with excellent enantioselectivities. In addition to benzylic C–H
bonds, the Co(II)-based radical amination is also suitable for
allylic, propargylic, non-activated, and even electron-deficient C–
[a]
[b]
Dr. K. Lang, Prof. Dr. X. P. Zhang
Department of Chemistry, Merkert Chemistry Center, Boston
College, Chestnut Hill, Massachusetts 02467, United States
E-mail: peter.zhang@bc.edu
Dr. C. Q. Li, Dr. H. J. Lu, Dr. Y. Hu, Dr. X. Cui, Dr. L. Wojtas,
Department of Chemistry, University of South Florida, Tampa, FL
33620, United States.
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.201808923
Angewandte Chemie International Edition
COMMUNICATION
H bonds. Additional features of the C–H amination system include
a remarkable degree of functional group tolerance, which is
attributed to its underlying stepwise radical mechanism.
were suitable substrates for the amination (Table 1; entries 4 and
5). Additionally, sulfamoyl azide 1f derived from indole could be
aminated to form the heterocycle-containing cyclic sulfamide 2f in
94% yield with 96% ee (Table 1; entry 6). Furthermore, this Co(II)-
MRC could be extended for chemoselective amination of allylic
and propargylic C–H bonds as demonstrated with sulfamoyl azide
1g–1j. The corresponding cyclic sulfamides 2g–2j were
generated in high yields with excellent enantioselectivities without
affecting the C=C and CºC functionalities (Table 1; entries 7–10).
Moreover, the amination worked equally well with non-activated
C–H bonds. For example, the regioselective 1,6-amination of
homobenzylic C–H bonds (1k) as well as of b-C–H bonds to
functional groups such as hydroxyl (1l), Weinreb amide (1m),
allylic amide (1n), and oxazolidinone imide (1o) could be achieved
without reacting with the weaker benzylic or a-C–H bonds (Table
1; entries 11–15). This remarkable regioselectivity indicated that
the corresponding a-Co(III)-aminyl radicals I (Scheme 1) had a
strong preference for 1,6- over 1,7- or 1,5-H-atom abstraction. It
O
O
O
O
Bn
S
H
Bn
S
N3
H
[Co(D2-Por*)] (2 mol %)
N
N
NH
N2
+
Ph
H
Ph
1a
2a
Me
Me
Me
Me
Me
Me
Me
Me
H
H
H
H
(S)
(S)
(S)
(S)
O
O
O
O
O
H
N
N
H
H
N
N
H
O
N
N
N
N
N
N
N
N
Co
Co
O
H
N
N
H
H
N
N
H
O
O
O
O
O
(S)
(S)
(S)
(S)
H
H
H
H
Me
Me
Me
Me
Me
Me
Me
Me
[Co(P1)]: 93% yield; −40% ee
(P1 = 3,5-DitBu-ChenPhyrin)
[Co(P2)]: 21% yield; −31% ee
(P2 = 2,6-DiMeO-ChenPhyrin)
Me
Me
Me
Me
(R)
(R)
(R)
(R)
H
H
H
H
is noteworthy that the metalloradical process features
a
(R)
(R)
(R)
(R)
O
O
O
O
remarkable level of functional group tolerance, encompassing a
broad spectrum of functionalities such as alkene, alkyne, alcohol,
indole, oxazolidinone, amide and other groups. This and the other
unique attributes are in consistence with the underlying stepwise
radical mechanism.
O
H
N
H N
N
H
N H
O
N
N
N
N
N
N
N
N
Co
Co
O
H
N
H N
N
H
N H
O
O
O
O
O
(R)
(R)
Me
(R)
(R)
Me
(R)
(R)
Me
(R)
(R)
Me
H
H
H
H
Table 1. [Co(P4)]-catalyzed 1,6-C–H amination of different sulfamoyl azides[a],[b]
O
O
O O
[Co(P3)]: 90% yield; 50% ee
(P3 = 3,5-DitBu-QingPhyrin)
2R
S
2R
S
[Co(P4)]: 93% yield; 90% ee
(P4 = 2,6-DiMeO-QingPhyrin)
N3
[Co(P4)] (2 mol %)
N
NH
N
H
H
N2
+
R1
H
R1
Scheme 2. Ligand effect on Co(II)-catalyzed enantioselective intramolecular C–
H amination. [a] Carried out in MTBE at RT for 48 h on 0.10 mmol scale under
N2 in the presence of 4 Å MS; [azide 1a] = 0.1 M. Isolated yields.
1
2
O
O
O
O
O
O
Bn
S
Et
S
iPr
S
N
NH
N
NH
N
NH
At the outset, sulfamoyl azide 1a was selected as the model
substrate for intramolecular 1,6-C(sp3)–H radical amination via
Co(II)-MRC (Scheme 2). After testing of different solvents, MTBE
(methyl tert-butyl ether) was identified as the optimal reaction
medium. The first-generation metalloradical catalyst [Co(P1)] (P1
= 3,5-DitBu-ChenPhyrin)[8a] was effective in catalyzing this
reaction even at room temperature, affording the six-membered
cyclic sulfamide 2a in high yield with a low but significant level of
enantioselectivity. Switching to the bulkier metalloradical catalyst
[Co(P2)] (P2 = 2,6-DiMeO-ChenPhyrin)],[8e] however, resulted in
significant decrease in yield without improving enantioselectivity.
When the second-generation catalyst [Co(P3)] (P3 = 3,5-DitBu-
QingPhyrin)[8g,9e]was used, enhancement of asymmetric induction
was observed with restoration of the high catalytic reactivity.
Significant further increase in enantioselectivity was obtained with
the employment of the more sterically hindered catalyst [Co(P4)]
(P4 = 2,6-DiMeO-QingPhyrin)], affording 2a in 93% yield with 90%
ee.
H
H
H
entry 1: (⎯)-2a
93% yield; 90% ee
entry 3: (⎯)-2c
89% yield; 93% ee
entry 2: (⎯)-2b
92% yield; 92% ee
O
O
O
O
O
O
Bn
S
Bn
S
Bn
S
N
NH
N
NH
N
NH
Cl
OMe
NBoc
entry 6: (⎯)-2f
94% yield; 96% ee
H
H
H
entry 4: (⎯)-2d
93% yield; 84% ee
entry 5: (⎯)-2e
91% yield; 92% ee
O
O
O
O
O
O
Br
NH
Bn
S
Bn
S
Bn
S
N
NH
N
NH
N
Br
C6H13
TBS
H
H
H
entry 7: (+)-2g
72% yield; 94% ee
entry 8: (⎯)-2h
88% yield; 89% ee
OMe
entry 9: (⎯)-2i
88% yield; 93% ee
O
O
O
O
O
O
Bn
S
Bn
S
Bn
S
N
NH
N
NH
N
NH
OH
TIPS
H
H
H
entry 12: (+)-2l
88% yield; 64% ee
entry 10: (⎯)-2j
88% yield; 94% ee
entry 11: (⎯)-2k
92% yield; 73% ee
O
O
O
O
Under the optimized conditions, the [Co(P4)]-catalyzed
system proved to be generally effective for intramolecular
amination of various sulfamoyl azides with different types of
C(sp3)–H bonds (Table 1). In addition to N-benzyl sulfamoyl azide
1a (Table 1; entry 1), this Co(II)-based C–H amination could
tolerate sulfamoyl azides with varied N-substituents as shown for
N-ethyl and N-isopropyl sulfamoyl azides 1b and 1c (Table 1;
entries 2 and 3). Similarly, benzyl C–H bonds next to arenes with
both electron-donating (1d) and -withdrawing (1e) substituents
O
O
Bn
S
Bn
S
Bn
S
N
NH
N
NH
N
NH
O
Me
O
H
O
N
H
O
H
O
N
N
OMe
entry 13:c (+)-2m
93% yield; 88% ee
entry 14:c (⎯)-2n
91% yield; 89% ee
entry 15:c (⎯)-2o
93% yield; 86% ee
[a] See footnote a of Scheme 2. [b] Isolated yields. [c] Performed in benzene.
This article is protected by copyright. All rights reserved.

10.1002/anie.201808923
Angewandte Chemie International Edition
COMMUNICATION
Table 2. [Co(P4)]-catalyzed amination of electron-deficient C–H bonds[a],[b]
convenient chiral synthons for further transformations to prepare
optically active a,g-diamino acid derivatives.[12]
O
O
O O
Bn
S
H
Bn
S
N3
H
N
[Co(P4)] (2 mol %)
N
NH
N2
+
A set of experiments was conducted to probe the underlying
mechanism (Scheme 4). First, the amination of mono-deuterated
azide 1a-D by the achiral catalyst [Co(P5)] (P5 = 3,5-DitBu-
IbuPhyrin;[9a] see SI) was performed to determine the
intramolecular kinetic isotope effect (KIE), obtaining a value of 6.6
(Scheme 4A). This large KIE agrees well with the proposed C–H
bond cleavage via hydrogen-atom abstraction (Scheme 1).
Second, as detailed in the Supporting Information, the a-Co(III)-
aminyl radical I from the reaction of 1a with [Co(P5)] could be
directly detected by both EPR spectroscopy (Figure S2) and
HRMS (Figure S3). Third, to trap the radical intermediate II,
amination of 1a by [Co(P5)] was carried out in the presence of
TEMPO (Scheme 4B). While the yield of the amination product
(±)-2a was significantly reduced, it concurrently generated
TEMPO-containing sulfamide (±)-3a as a major product, which
was ascribed to the trapping of the C-centered radical II by
TEMPO. When the reaction was catalyzed by chiral catalyst
[Co(P4)] under the standard conditions, the amination product (–)-
2a was still formed as the major product with the same
enantioselectivity (90% ee), albeit in a relatively lower yield than
in the absence of TEMPO (from 93% to 82%). Meanwhile the
TEMPO trapping product 3a was obtained as a minor product in
14% yield with 16% ee. The difference in activity between
[Co(P4)] and [Co(P5)] indicates that the more sterically hindered
ligand environment of P4 facilitated the radical substitution of
intermediate II (Scheme 1). Collectively, these results support the
proposed stepwise radical mechanism (Scheme 1).
R1
H
R1
1
2
Me
OMe
O
O
O
O
O
O
Bn
S
Bn
S
N
NH
(s)
Bn
S
N
NH
N
NH
H
O
(X-ray)c
H
O
H
O
entry 1: (⎯)-2p
94% yield; 95% ee
F
entry 2: (⎯)-2q
93% yield; 92% ee
entry 3: (⎯)-2r
93% yield; 95% ee
O
O
O
O
O
O
Me
NH
Bn
S
Bn
S
Bn
S
OtBu
O
N
NH
N
N
NH
N
OMe
H
H
H
O
O
entry 4: (⎯)-2s
92% yield; 98% ee
entry 5: (+)-2t
95% yield; 96% ee
entry 6: (⎯)-2u
92% yield; 91% ee
MeO
O
O
O
O
O
O
Bn
S
OMe
Bn
S
N
NH
(s)
Bn
S
N
NH
N
O
N
NH
N
O
CN
H
(X-ray)c
H
H
entry 7: (⎯)-2v
93% yield; 90% ee
entry 8: (⎯)-2w
93% yield; 92% ee
entry 9: (+)-2x
88% yield; 83% ee
[a] See footnote a of Scheme 2; performed in benzene. [b] Isolated yields. [c]
[S] Absolute configuration.
The [Co(P4)]-based system could also enable the
enantioselective amination of various types of electron-deficient
C–H bonds (Table 2). For instance, a-C–H amination of ketone
azides 1p–1s were efficiently achieved, affording optically active
a,g-diamino ketone derivatives 2p–2s in high yields with excellent
enantioselectivities (Table 2; entries 1–4). The absolute
configuration of 2p was established as (S). The electron-deficient
C–H bond a to the ester in azide 1t was also aminated smoothly,
forming a,g-diamino ester 2t (Table 2; entry 5). Furthermore, this
system could be applied to C–H bonds a to amides with varied N-
substituents, producing a,g-diamino amides 2u–2w (Table 2;
entries 6–8). Moreover, the C–H bonds a to cyano group could be
enantioselectively aminated as shown with the formation of a,g-
diamino nitrile 2x (Table 2; entry 9). The same (S) absolute
configuration as 2p was established for 2x.
A. Kinetic Isotope Effect
O
O
O O
O
O
Bn
S
Bn
S
Bn
S
H
N
NH
N
ND
N3
[Co(P5)] (4 mol %)
N
+
D
Ph
D
Ph
H
Benzene; 4 Å MS; 40 ºC; 48 h
82% yield; kH/kD = 6.6
Ph
1a-D
(±)-2a-D
(±)-2a-H
B. Radical Intermediate Trapping
O
S
O
O
O
O
O
TEMP
H
Bn
Bn
S
Bn
S
H
[Co(P5)] (4 mol %)
TEMPO (5 equiv)
N
NH
H2N
NBn
O
N3
H
N
Ph
H
+
Ph
Benzene; 4 Å MS; 40 ºC; 48 h
(±)-2a
29% yield
(±)-3a
Ph
1a
41% yield
O
O
O
O
O
O
S
TEMP
H
O
O
O O
S
Bn
S
H
[Co(P4)] (2 mol %)
TEMPO (5 equiv)
N3
H
H2N
+
NBn
O
N
NH
N
Bn
S
Bn
S
Boc
1) 10% Pd/C; HCO2NH4
MeOH; THF
2) pyridine; H2O; 80 o
N
NH
N
N
Ph
H
(Boc)2O; DMAP
DCM
Ph
MTBE; 4 Å MS; rt; 48 h
Ph
CO2tBu
CO2tBu
H
(⎯)-2a
82% yield; 90% ee
3a
1a
C
14% yield; 16% ee
H
3t
95% yield
2t
96% ee
Scheme 4. Mechanistic studies on Co(II)-catalyzed C–H amination.
Cbz
optically active
NH2 NHBoc
CO2tBu
NH NHBoc
CO2tBu
CbzCl
α,!-diaminobutyric
acid ester as valuable
pharmacophores
In summary, metalloradical catalysis (MRC) has been
successfully applied for the development of the first highly
asymmetric catalytic system for intramolecular 1,6-C(sp3)–H
amination of sulfamoyl azides. Supported by the D2-symmetric
chiral amidoporphyrin, the Co(II)-based metalloradical system
can effectively activate various sulfamoyl azides to aminate a
broad range of C(sp3)–H bonds. At room temperature under
neutral and non-oxidative conditions, the six-membered cyclic
sulfamides were produced in high yields with excellent
enantioselectivities. The Co(II)-catalyzed amination exhibits a
high degree of functional group tolerance and unusual level of
chemoselectivity, which are attributed to the unique stepwise
radical mechanism. The resulting optically active sulfamides can
NaHCO3
H
H
4t
90% yield; 96% ee
5t
97% yield; 96% ee
Scheme 3. Desulfonylation for formation of chiral 1,3-diamines.
To demonstrate the synthetic utility, the enantioenriched 2t
was selected as a model substrate to access chiral 1,3-diamine
derivatives by desulfonylation and differential protection (Scheme
3). After Boc-protection, the resulting bis-protected cyclic
sulfamide 3t could proceed with selective debenzylation, followed
by smooth desulfonylation, to afford the N-Boc-protected a,g-
diamino ester 4t in high yield with full retention of the original
enantiopurity. The primary amine in 4t could be readily converted
to the differentially N,N'-protected 1,3-diamine 5t without erosion
of the optical purity. Both 1,3-diamines 4t and 5t may serve as
This article is protected by copyright. All rights reserved.

10.1002/anie.201808923
Angewandte Chemie International Edition
COMMUNICATION
Lu, J. V. Ruppel, X. Cui, S. Lopez de Mesa, L. Wojtas, X. P. Zhang, J.
Am. Chem. Soc. 2011, 133, 15292; h) X. Xu, S. Zhu, X. Cui, L. Wojtas,
X. P. Zhang, Angew. Chem. Int. Ed. 2013, 52, 11857; Angew. Chem.
2013, 125, 12073; i) A. R. Reddy, F. Hao, K. Wu, C.-Y. Zhou, C. M. Che,
Angew. Chem. Int. Ed. 2016, 55, 1810; Angew. Chem. 2016, 128, 1842;
j) Y. Wang, X. Wen, X. Cui, L. Wojtas, X. P. Zhang, J. Am. Chem. Soc.
2017, 139, 1049; k) A. Chirila, B. G. Das, N. D. Paul, B. de Bruin,
ChemcatChem 2017, 9, 1413; l) X. Xu, Y. Wang, H. X., Cui. Wojtas, X.
P. Zhang, Chem. Sci. 2017, 8, 4347; m) S. Roy, S. K. Das, B.
Chattopadhyay, Angew. Chem. Int. Ed. 2018, 57, 2238; Angew. Chem.
2018, 130, 2260.
be easily converted to synthetically useful 1,3-diamines with full
retention of the original enantiopurity.
Acknowledgements
We are grateful for financial support by NIH (R01-GM098777)
and in part by NSF (CHE-1624216).
Keywords: amination • cobalt • heterocycles • metalloradical
catalysis • radicals
[9]
a) J. V. Ruppel, J. E.Jones, C. A. Huff, R. M. Kamble, Y. Chen, X. P.
Zhang, Org. Lett. 2008, 10, 1995; b) V. Subbarayan, J. V. Ruppel, S. Zhu,
J. A. Perman, X. P. Zhang, Chem. Commun. 2009, 4266; c) L.-M. Jin, X.
Xu, H. Lu, X. Cui, L. Wojtas, X. P. Zhang, Angew. Chem. Int. Ed. 2013,
52, 5309; Angew. Chem. 2013, 125, 5417; d) H. Jiang, K. Lang, H. Lu,
L. Wojtas, X. P. Zhang, Angew. Chem. Int. Ed. 2016, 55, 11604; Angew.
Chem. 2016, 128, 11776; e) H. Jiang, K. Lang, H. Lu, L. Wojtas, X. P.
Zhang, J. Am. Chem. Soc. 2017, 139, 9164.
[1]
a) Chatgilialoglu, C.; Studer, A. Encyclopedia of Radicals in Chemistry,
Biology and Materials; John Wiley & Sons: Chichester, U.K., 2012. b)
Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry of Radical
Reactions: Concepts, Guidelines, and Synthetic Applications; Wiley-
VCH: Weinheim, Germany, 2008.
[2]
[3]
a) M. P. Sibi, S. Manyem, J. Zimmerman, Chem. Rev. 2003, 103, 3263;
b) N. Kern, M. P. Plesniak, J. J. W. McDouall, D. J. Procter, Nat. Chem.
2017, 9, 1198.
[10] a) X. Cui, X. Xu, L.-M. Jin, L. Wojtas, X. P. Zhang, Chem. Sci. 2015, 6,
1219; b) Y. Wang, X. Wen, X. Cui, X. P. Zhang, J. Am. Chem. Soc. 2018,
140, 4792; c) A. S. Karns, M. Goswami, B. de Bruin, Chem. Eur. J. 2018,
24, 5253; d) X. Wen, Y. Wang, X. P. Zhang, Chem. Sci. 2018, 9, 5082.
[11] a) H. Lu, H. Jiang, L. Wojtas,; X. P. Zhang, Angew. Chem. Int. Ed. 2010,
49, 10192; Angew. Chem. 2010, 122, 10390; b) H. Lu, V. Subbarayan,
J. Tao, X. P. Zhang, Organometallics 2010, 29, 389; c) H. Lu, J. Tao, J.
E. Jones, L. Wojtas, X. P. Zhang, Org. Lett. 2010, 12, 1248; d) H. Lu, H.
Jiang, Y. Hu, L. Wojtas, X. P. Zhang, Chem. Sci. 2011, 2, 2361; e) H. Lu,
Y. Hu, H. Jiang, L. Wojtas, X. P. Zhang, Org. Lett. 2012, 14, 5158; f) L.-
M. Jin, H. Lu, Y. Cui, C. L. Lizardi, T. N. Arzua, L. Wojtas, X. Cui, X. P.
Zhang, Chem. Sci. 2014, 5, 2422; g) H. Lu, C. Li, H. Jiang, C. L. Lizardi,
X. P. Zhang, Angew. Chem. Int. Ed. 2014, 53, 7028; Angew. Chem. 2014,
126, 7148; h) O. Villanueva, N. M. Weldy, S. B. Blakey, C. E. MacBeth,
Chem. Sci. 2015, 6, 6672; i) H. Lu, K. Lang, H. Jiang, L. Wojtas, X. P.
Zhang, Chem. Sci. 2016, 7, 6934; j) P. F. Kuijpers, M. J. Tiekink, W. B.
Breukelaar, D. L. J. Broere, N. P. van Leest, J. I. van der Vlugt, J. N. H.
Reek, B. de Bruin, Chem. Eur. J. 2017, 23, 7945; k) Z.-Y. Gu, Y. Liu, F.
Wang, X. Bao, S.-Y. Wang, S.-J. Ji, ACS Catal. 2017, 7, 3893.
a) J. S. Lin, X. Y. Dong, T. T. Li, N. C. Jiang, B. Tan, X. Y. Liu, J. Am.
Chem. Soc. 2016, 138, 9357; b) W. Zhang, F. Wang, S. D. McCann, D.
Wang, P. Chen, S. S. Stahl, G. Liu, Science 2016, 353, 1014. c) J. S. Lin,
F. L. Wang, X. Y. Dong, W. W. He, Y. Yuan, S. Chen, X. Y. Liu, Nat.
Commun. 2017, 8, 14841.d) C. Morrill, C. Jensen, X. Just-Baringo, G.
Grogan, N. J. Turner, D. J. Procter, Angew. Chem. Int. Ed. 2018, 57,
3692.
[4]
[5]
a) H. Miyabe, A. Kawashima, E. Yoshioka, S. Kohtani, Chem. Eur. J.
2017, 23, 6225; b) A. Studer, D. P. Curran, Angew. Chem. Int. Ed. 2016,
55, 58; Angew. Chem. 2016, 128, 58; c) H. Pellissier; H. Clavier, Chem.
Rev. 2014, 114, 2775; d) H. Lu, X. P. Zhang, Chem. Soc. Rev. 2011, 40,
1899; e) T. G. Driver, Org. Biomol. Chem. 2010, 8, 3831; f) M. P. Doyle,
Angew. Chem. Int. Ed. 2009, 48, 850; Angew. Chem. 2009, 121, 864.
a) A. Gansäuer, T. Lauterbach, H. Bluhm, M. Noltemeyer, Angew. Chem.
Int. Ed. 1999, 38, 2909; Angew. Chem. 1999, 111, 3112; b) A. Gansäuer,
C.-A. Fan, F. Keller, J. Keil, J. Am. Chem. Soc. 2007, 129, 3484; c) A.
Gansäuer, L. Shi, M. Otte, J. Am. Chem. Soc. 2010,132,11858; d) S.
Hildebrandt, A. Gansäuer, Angew. Chem. Int. Ed. 2016, 55, 9719; Angew.
Chem. 2016, 128, 9871; e) N. Funken, F. Mühlhaus, A. Gansäuer,
Angew. Chem. Int. Ed. 2016, 55, 12030; Angew. Chem. 2016, 128,
12209; f) W. Hao, X. Wu, J. Z. Sun, J. C. Siu, S. N. MacMillan, S. Lin, J.
Am. Chem. Soc. 2017, 139, 12141; g) Y.-Q. Zhang, E. Vogelsang, Z.-W.
Qu, S. Grimme,; A. Gansäuer, Angew. Chem. Int. Ed. 2017, 56, 12654;
Angew. Chem. 2017, 129, 12828; h) W. Hao, J. H. Harenberg, X. Wu, S.
N. MacMillan, S. Lin, J. Am. Chem. Soc. 2018, 140, 3514.
[12] a) J.-C. Kizirian, Chem. Rev. 2008, 108, 140; b) X. Ji, H. Huang, Org.
Biomol. Chem. 2016, 14, 10557; c) G. Ronquist, R. Hugosson, B. J.
Westermark, Cancer Res. Clin. Oncol. 1980, 96, 259.
[13] a) J. M. Alderson, J. R. Corbin, J. M. Schomaker, Acc, Chem. Res. 2017,
50, 2147; b) F. Collet, C. Lescot, P. Dauban, Chem. Soc. Rev. 2011, 40,
1926; c) Y. Liu, X. Guan, E. L.-M. Wong, P. Liu, J.-S. Huang, C.-M. Che,
J. Am. Chem. Soc. 2013, 135, 7194; d) J. M. Alderson, A. M. Phelps, R.
J. Scamp, N. S. Dolan, J. M. Schomaker, J. Am. Chem. Soc. 2014, 136,
16720; e) J.-L. Liang, S.-X. Yuan, J.-S. Huang, W.-Y. Yu, C.-M. Che,
Angew. Chem. Int. Ed. 2002, 41, 3465; Angew. Chem. 2002, 114, 3615;
f) E. Milczek, N. Boudet, S. Blakey, Angew. Chem. Int. Ed. 2008, 47,
6825; Angew. Chem. 2008, 120, 6931.
[6]
[7]
a) W. I. Dzik, X. Xu, X. P. Zhang, J. N. H. Reek, B. de Bruin, J. Am. Chem.
Soc. 2010, 132, 10891; b) J. L. Belof, C. R. Cioce, X. Xu, X. P. Zhang, B.
Space, H. L. Woodcock, Organometallics 2011, 30, 2739; c) H. Lu, W. I.
Dzik, X. Xu, L. Wojtas, B. de Bruin, X. P. Zhang, J. Am. Chem. Soc. 2011,
133, 8518.
a) V. Lyaskovskyy, A. I. Olivos Suarez, H. Lu, H. Jiang, X. P. Zhang, B.
de Bruin, J. Am. Chem. Soc. 2011, 133, 12264; b) A. I. Olivos Suarez, H.
Jiang, X. P. Zhang, B. de Bruin, Dalton Trans. 2011, 40, 5697; c) K. H.
Hopmann, A. Ghosh, ACS Catal. 2011, 1, 597; d) M. Goswami, V.
Lyaskovskyy, S. R. Domingos, W. J. Buma, S. Woutersen, O. Troeppner,
I. Ivanović-Burmazović, H. Lu, X. Cui, X. P. Zhang, E. J. Reijerse, S.
DeBeer, M. M. van Schooneveld, F. F. Pfaff, K. Ray, B. de Bruin, J. Am.
Chem. Soc. 2015, 137, 5468.
[8]
a) Y. Chen, K. B. Fields, X. P. Zhang, J. Am. Chem. Soc. 2004, 126,
14718; b) Y. Chen, J. V. Ruppel, X. P. Zhang, J. Am. Chem. Soc. 2007,
129, 12074; c) S. Zhu, J. A. Perman, X. P. Zhang, Angew. Chem. Int. Ed.
2008, 47, 8460; Angew. Chem. 2008, 120, 8588; d) S. Fantauzzi, E.
Gallo, E. Rose, N. Raoul, A. Caselli, S. Issa, F. Ragaini, S. Cenini,
Organometallics 2008, 27, 6143; e) S. Zhu, J. V. Ruppel, H. Lu, L. Wojtas,
X. P. Zhang, J. Am. Chem. Soc. 2008, 130, 5042; f) S. Zhu, X. Xu, J. A.
Perman, X. P. Zhang, J. Am. Chem. Soc. 2010, 132, 12796; g) X. Xu, H.
This article is protected by copyright. All rights reserved.

10.1002/anie.201808923
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
R2
N
Chaoqun Li, Kai Lang, Hongjian Lu, Yang
Hu, Xin Cui, Lukasz Wojtas, and X. Peter
Zhang*
O
O
O
O
O
H
S
2R
S
2R
S
1R
N3
O
Co(II)-MRC
H N
N
N
NH
H
H
N
N
R1
H
-N2
N
R1
Co
ꢀ
N
Page No. – Page No.
Alkylsulfamoyl
Azides
up to 95% yield
up to 98% ee
α-Alkylaminosulfonyl-
α-Co(III)-Aminyl Radical
Catalytic
Radical
Process
for
Enantioselective Amination of C(sp3)–
H Bonds
An enantioselective radical process has been established via cobalt(II)-based
metalloradical catalysis for stereoselective amination of aliphatic C–H bonds at room
temperature to form chiral 1,3-diamines under neutral and non-oxidative conditions.
This article is protected by copyright. All rights reserved.