Reaction of Nitrogen-Radicals with Organometallics Under Ni-Catalysis: N-Arylations and Amino-Functionalization Cascades

Article abstract of DOI:10.1002/anie.201900510

Herein, we report a strategy for the generation of nitrogen-radicals by ground-state single electron transfer with organyl–Ni^I species. Depending on the philicity of the N-radical, two types of processes have been developed. In the case of nucleophilic aminyl radicals direct N-arylation with aryl organozinc, organoboron, and organosilicon reagents was achieved. In the case of electrophilic amidyl radicals, cascade processes involving intramolecular cyclization, followed by reaction with both aryl and alkyl organometallics have been developed. The N-cyclization–alkylation cascade introduces a novel retrosynthetic disconnection for the assembly of substituted lactams and pyrrolidines with its potential demonstrated in the short total synthesis of four venom alkaloids.

Full text of DOI:10.1002/anie.201900510

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Reaction of Nitrogen-Radicals with Organometallics Under Ni-
Catalysis: N-Arylations and Amino-Functionalization Cascades
Authors: Lucrezia Angelini, Jacob Davies, Marco Simonetti, Laia Malet
Sanz, Nadeem S. Sheikh, and Daniele Leonori
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
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content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201900510
Angew. Chem. 10.1002/ange.201900510
Link to VoR: http://dx.doi.org/10.1002/anie.201900510
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10.1002/anie.201900510
Angewandte Chemie International Edition
COMMUNICATION
Reaction of Nitrogen-Radicals with Organometallics Under Ni-
Catalysis: N-Arylations and Amino-Functionalization Cascades
Lucrezia Angelini‡[a], Jacob Davies‡[a], Marco Simonetti[a], Laia Malet Sanz[b], Nadeem S. Sheikh[c], and
Daniele Leonori*[a]
A) Most exploited reactivity of N-radicals
Abstract: Here we report a strategy for the generation of nitrogen-
H
radicals by ground-state single electron transfer with organyl-Ni(I)
species. Depending on the philicity of the N-radical, two types of
processes have been developed. In the case of nucleophilic aminyl
radicals direct N-arylation with aryl organozinc, organoboron and
organosilicon reagents was achieved. In the case of electrophilic
amidyl radicals, cascade processes involving intramolecular
cyclization, followed by reaction with both aryl and alkyl
organometallics have been developed. The N-cyclization-alkylation
cascade introduces a novel retrosynthetic disconnection for the
assembly of substituted lactams and pyrrolidines with its potential
demonstrated in the short total synthesis of four venom alkaloids.
N
N
N
exo-trig cyclization
1,5-HAT
addition to π-systems
B) Radical transmetalations of C-radicals ([M] = Ni, Cu, Pd...)
[M]n+1
• arylation
• alkylation
• acylation
[M]n
+
C) Generation of N-radicals via SET reduction of N–OAr electrophores
NO2 NO2
• iminyl
Ar-O–
O
N
O
N
+ e–
SET
• amidyl
• aminyl
• aminium
NO2
NO2
N
Nitrogen-radicals are versatile synthetic intermediates that can
engage in a broad range of chemical reactions.[1] In general,
they are used in intramolecular cyclizations,[1] intramolecular 1,5-
H-atom abstractions (HATs)[2] and intermolecular additions onto
Scheme 1. A) Reactivity of N-radicals. B) SET transmetalation of C-radicals.
C) Generation of N-radicals by SET reduction of N–OAr hydroxylamines.
π-systems[3] (Scheme 1A).
A considerably underdeveloped
We were particularly interested by reports from the Vicic[9] and
Doyle[10] groups demonstrating how organyl-Ni(I) species can act
as competent reductant (Eox ≈ –1.1 V vs SCE), thus making a
ground-state SET with our derivatives potentially exergonic
(ΔGSET ≈ –4 kcal/mol–1). Specifically, we questioned if these
precursors could be used in Ni-catalyzed umpolung aminations
and amidations of aryl organometallic reagents.[11]
The preparation of tertiary anilines via umpolung strategies has
received considerable attention in the last few years.[12] However,
methods based on Ni-catalysis[13] have only been demonstrated
on aryl organozincs, thus a general strategy able to engage
easy to handle organometallics of boron and silicon has yet to
be reported.
Our proposed catalytic cycle would start with the transmetalation
of a Ni(I) species A with an aryl organometallic to give an aryl-
Ni(I) complex B (Scheme 2A). At this point, an energetically
favorable SET with the N-radical precursors C would deliver the
aryl-Ni(II) intermediate D and the N-radical E. Our mechanistic
picture hinged on the ability of E to intercept D and provide a N-
bound aryl-Ni(III) complex F. As related alkyl-Ni(III)-amides have
been shown by Hillhouse[14] to undergo facile reductive
elimination, we predicted the latter to generate the desired
product G and a Ni(I) species A thus closing the catalytic cycle.
In light of the wealth of organometallics utilized in Ni catalysis,[15]
we assessed the stability of our precursor (1) in the presence of
several potential coupling partners. We discovered 1 to be
stable in the presence of diarylzincs, aryl boronic acids and aryl
silanes up to high temperature (T ≈ 100 ºC) but to decompose
by addition of aryl Grignards. We thus considered the
development Ni-catalyzed umpolung aminations of N,N-dialkyl-
O-aryl-hydroxylamine derivatives as the redox active coupling
partners with aryl zincs, boronic acids and silanes.
reactivity stream is their engagement in transition metal-based
processes – an interplay heavily exploited with C-radicals
(Scheme 1B).[4] Indeed, the aptitude of N-radicals to undergo
SET transmetalation with organometallic complexes has been
scarcely adopted,[5] and its implementation has the capability to
unlock unique reactivity patterns. Given the relevance of
nitrogenated
molecules
as
therapeutic
agents
and
agrochemicals, methods facilitating their construction are of high
importance in both academia and industry.[6]
We have started a research program aimed at downstreaming
N-radicals using highly electron poor O-aryl hydroxylamine
derivatives (Scheme 1C).[7] These substrates can, under
photoredox conditions,[8] provide access to iminyl,[7d] amidyl[7c]
and aminium[7b] radicals for cyclization and aromatic C–H
amination. Central to the success of these processes is the high
reduction potential of these precursors (Ered ≈ –0.8 V vs SCE) as
this enables facile SET (single-electron transfer) reduction by
the excited state of many photoredox catalysts.
As part of an effort to expand the synthetic utility of these N-
radical precursors, we envisaged that their SET reduction could
be achieved using ground-state transition metal complexes.
[a]
L. Angelini, Dr J. Davies, Dr M. Simonetti and Dr Daniele Leonori
School of Chemistry
University of Manchester
Oxford Road, Manchester, M13 9PL, UK
E-mail: daniele.leonori@manchester.ac.uk
Website: https://leonoriresearchgroup.weebly.com
L. Malet Sanz
[b]
Eli Lilly and Company Limited
Erl Wood Manor
Windelesham, Surrey, GU20 6PH, UK
Prof. N. S. Sheikh
[c]
We started the optimization of the N-arylations reaction using
piperidine 1 (prepared on multi-gram scale in 1 step) (Scheme
2B).[16] By using Ph2Zn as the coupling partner, efficient
amination (1g2) could be achieved employing 5 mol% of
Department of Chemistry, College of Science
King Faisal University, P.O. Box 380, Al-Ahsa 31982, Saudi Arabia
These authors contributed equally to the work.
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.201900510
Angewandte Chemie International Edition
COMMUNICATION
NiCl2•6H2O and dtbbpy ligand in THF–DMF at room temperature. limited to the installment of secondary amines as efforts directed
Both the ligand and the DMF had a critical role in the success of
the reaction (entries 1–2). Replacing the catalytic system with
the preformed dttbpy•NiCl2 catalyst gave 2 in almost identical
yield. As organozinc reagents can be obtained by
transmetalation of Grignards with ZnCl2 we also evaluated the
use of PhZnCl, which gave 2 in high yield.[16]
towards the use of primary amines proved unsuccessful (16).
Pleasingly, we could access C-2 (17), C-3 (18) and C-4 (19)
aminated pyridines using both aryl organozincs and a boronic
acid (20) in good to moderate yields. C-2 (21) and C-3 (22)
amination of thiophene was also possible in high and moderate
yields, respectively. Two commercially available silanes were
also engaged in the reaction with 1 (23, 24). The successful
formation of product 18–21 is noteworthy as, to the best of our
knowledge, their preparation via umpolung or Chan-Lam
strategies on zincated/borylated pyridines and zincated 5-
membered ring heterocycles has not been reported before.[19]
Mechanistically we believe this umpolung amination strategy to
be distinct to known protocols based on N–Cl and N–OBz
reagents as pioneered by Johnson and Jarvo.[13] Indeed, the low
redox potentials of N–Cl and N–OBz piperidines (Ered≈ –1.9 V
and –1.8 vs SCE respectively) would result in endergonic SET
reductions. This suggests that a two-electron process [Niº/Ni(II)
cycle] is operating in processes based on those reagents while a
distinct radical reactivity characterizes our strategy with N–OAr
derivatives. To validate this mechanistic hypothesis, we tested
N-reagents 3, 4 and 5, which feature N–OAr, N–OBz and N–Cl
bonds, and can be used as radical-clock probes.[20] As shown in
Scheme 2D, although the N-arylation product 6 was obtained in
all cases, product 7, which would result from a radical 5-exo-trig
cyclisation, was exclusively obtained when using 3, regardless
Next, the amination was investigated with PhB(OH)2.[17] A similar
Ni-ligand system could be used, however the addition of Cs2CO3
was critical, likely by easing the transmetalation of the boronic
acid at the Ni(I) center (entries 3–4). Also in this case, the
solvent played an important role and optimum yields were
obtained in MTBE (entry 6).[16]
The implementation of aryl silanes proved more difficult and a
stoichiometric fluoride source was required to promote
reactivity.[18] Specifically, when PhSi(OEt)3 was used in
combination with CsF and TBAF, a complex mixture of products
was observed. Conversely, the use of TBAT provided 2 in high
yield (entry 5–6). Other trialkyl-phenyl silanes were evaluated,
but this reactivity could not be extended to other derivatives.[16]
With these set of optimized conditions, we evaluated the scope
of this umpolung aromatic amination strategy (Scheme 2C).
Using Ph2Zn we screened several aminyl precursors and found
the amination compatible with a functionalized piperidine (8),
morpholine (9), thiomorpholine (10), piperazines (11, 12), as well
as dialkyl-amines (13–15). At the moment this reactivity is
A) Proposed Ni-catalysed amination of organometallics
Ar [M]
B) Optimization of the amination of organometallics via aminyl radicals
(I)
[Ni], ligand, additive
Ar
[Ni]
X
+
Ph–[M]
N
1
OAr
N
Ph
N
solvent (0.1 M), T
[M]–X
A
G
2
Entry
[M]
[Ni] (mol%)
Ligand (mol%) Additive
Solvent
T (ºC) Yield (%)
(III)
(I)
N
[Ni] Ar
[Ni] Ar
B
1
2
3
4
5
6
ZnPh
ZnPh
NiCl2•6H2O (5)
NiCl2•6H2O (5)
–
–
–
–
THF
rt
rt
75
75
50
50
–
99
–
90
–
N
F
E
dtbpy (5)
dtbpy (5)
dtbpy (5)
dtbpy (5)
dtbpy (5)
THF–DMF
THF–DMF
MTBE
DMSO
DMSO
B(OH2) NiCl2•6H2O (5)
B(OH2) NiCl2•glyme (5)
Si(OEt)3 NiCl2•glyme (5)
Si(OEt)3 NiCl2•glyme (5)
OAr
SET
Cs2CO3
–
TBAT
N
C
(II)
[Ni] Ar
D
86
Ar = 2,4-(NO2)2-C6H3
ArO–
C) Scope of the process
Legend:
Ar–ZnAr
Ar–B(OH)2
Ar–Si(OEt)3
O
O
Cbz
N
F
F
O
S
N
Ph
N
N
Me Me
Ph Ph
N
S
Me
N
Me
H
S
N
8
N
N
N
N
N
N
N
N
N
OMe
N
Ar
Me
23
Cl
9
95%
10
85%
11
95%
12
83%
13
88%
14
15
88%
17
41%
18
19
29%
20
49%
21
83%
22
38%
24
16
–
83%
95%
37%
71%
83%
D) Probing the radical nature of process
E) Amination via amidyl radicals
Ph
Ph2Zn (1.5 equiv.)
NiCl2•6H2O (5 mol%)
dtbpy (5 mol%)
Ph
6 (%) 7 (%)
Me
OAr
Me
Ph
[M] = ZnPh : 12%
[M] = B(OH)2 : –
[M] = Si(OEt)3 : –
Me
Ph–[M]
Me
X
Me
Ph
N
N
N
Ph
N
Ph
N
vs
3: X = OAr
4: X = OBz
5: X = Cl
30
13
31
22
–
–
Ac
Ac
conditions
see part B
THF–DMF, rt, 16h
Ph
Ph
25
26
3–5
6
7
N-arylation
5-exo-trig
F) Computational studies (ΔG‡ and ΔGº values are in kcal mol–1
)
Me
(III)Ph
(III)Ph
I
Ph
L
Me
N
(II)
N
H + 2
(dtbpy)Ni
Br
N
(dtbpy)Ni
(dtbpy)Ni
N
H + 25
Ac
ΔG‡ = 2.1
ΔGº = –58.6
ΔG‡ = 6.7
ΔGº = 5.0
ΔG‡ = 11.7
ΔGº = –2.6
ΔG‡ = 10.3
ΔGº = –58.9
Br
Ac
I
L
Br
M
J
H
nucleophilic
electrophilic
Scheme 2. A) Proposed mechanism for a Ni-catalysed amination of organometallics via N-radicals. B) Reaction optimization using piperidine 1. C) Scope of the
process. D) Radical clock experiments. E) Amination of organometallics via amidyl radicals. F) DFT studies [UB3LYP/6-31G(d)-LANL2DZ][21]
.
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10.1002/anie.201900510
Angewandte Chemie International Edition
COMMUNICATION
from the nature of the organometallic partner (entries 1–6),
which supports our mechanistic framework.[22]
5-membered ring lactams (46–47), proving that cascades
centered on primary radicals are feasible.[27] The formation of
spirocyclic and bicyclic derivatives (48–49) was possible as well
as the extension of this methodology to strongly electrophilic
(thio)carbamoyl radicals (50–51). Next we prepared radical
precursor 52 with the aim of accessing α-benzyl-pyrrolidines, a
class of biologically active heterocycles. Gratifyingly, this
approach enabled the fast assembly of a small library in good to
moderate yields, spanning electron rich (48 and 54), electron
poor (55 and 56) and heteroaromatic derivatives (57–59).
Finally, we questioned if the presented cyclization-
functionalization strategy could be extended to alkyl
organometallic reagents (Scheme 3D).[28] Mechanistically, we
were intrigued by the possibility of accessing di-alkyl-Ni(III)
intermediate S, which would ultimately lead to a N-cyclization–
alkylation process. This strategy would deliver the concomitant
formation of vicinal sp3 C–N and sp3–sp3 C–C bonds, a
transformation that, to the best of our knowledge, has not been
possible by either ionic, transition metal-mediated or radical
pathways.
Having demonstrated the ability of aminyl radicals to participate
in the amination process, we evaluated the use of amidyl
radicals. However, despite attempting re-optimization, the use of
oxyamide 25 was not possible and the desired N-Ph-acetamide
26 was obtained in low yield only in combination with Ph2Zn
(Scheme 2E). We propose the different behavior of N-radical
precursors 1 and 25 to be related to the different philicity of their
respective N-radicals. In fact, while aminyls have a nucleophilic
character (calculated electrophilicity indexes,[23] ω+rc = +0.72 eV),
amidyls are electrophilic (ω+ = +1.2 eV).[16] This might thwart
rc
their SET transmetalation with aryl-Ni(II) species. In order to
support this mechanistic proposal, we performed DFT studies
evaluating the feasibility of N-radical transmetalation and
subsequent reductive elimination using (dtbpy)Ni(II)(Ph)Br H as
the model substrate. As shown in Scheme 2F, the reaction
profile associated with aminyl I revealed a low activation barrier
for the radical transmetalation (H + I g J), which is slightly
endothermic, and an almost barrier-less and highly exergonic
reductive elimination (J g H + 3). Conversely, both radical
transmetalation (H + L g M) and reductive elimination (M g H +
26) using amidyl L, have significantly higher barriers, which
might explain the low reactivity of 25.
After
a screening of alkyl organometallics and reaction
conditions using 28, we found that this cascade could be
unlocked using dialkyl-zinc reagents, and the preformed catalyst
NiBr2•dtbbpy.[16] The scope of the process was evaluated and
we were able to achieve lactamisation-methylation, ethylation
and i-butylation (60–62) cascades in good to high yields, as well
Given the unsuccessful development of umpolung aminations
via amidyl radicals, we wondered if this lack of reactivity could
be harnessed to develop radical cascade processes. Specifically, as introducing a 3,7-dimethyloctyl alkyl chain (63). Currently, the
we targeted the development of a multicomponent reaction
starting with the amidyl radical O generated via reductive SET of
the aryloxy amides N from B (Scheme 3A). At this point, as the
N-radical transmetalation is disfavored, a fast intramolecular 5-
use of more sterically hindered secondary organozincs (e.g. i-
Pr2Zn, 64) is a limitation with the exception of the sp2-like
cyclopropyl unit, which was introduced in high yield (65).
Finally, we extended this reactivity to 52 with the aim to build 2-
alkyl-pyrrolidines, a motif found in many highly biologically active
natural products.[29] Pleasingly, we successfully achieved
cyclization-alkylation cascades introducing methyl, ethyl and
cyclopropyl groups (66–68). By using ditridecyl zinc, we
accessed 69 that upon N-Boc reduction gave the Aracae
alkaloid (±)-bgugaine[30] 70 in just 2 steps. Substrates containing
di-substituted olefins are also amenable to this reactivity as
demonstrated by the successful formation of 71 where two
contiguous tertiary centres have been assembled by the radical
cascade.
exo-trig cyclization (k
≈
109 M–1)[24] would convert the
electrophilic amidyl O into the nucleophilic C-radical P. This
species should now possess the matched philicity to enter the
catalytic cycle by reacting with D. Reductive elimination from di-
organyl-Ni(III) species Q would generate the amido-arylated
product R. It is worth pointing out that, while Pdº-catalyzed
processes achieving related transformations using amides,
carbamates and their derivatives in conjunction with aryl halides
have been developed,[25] a radical umpolung counterpart has, to
best of our knowledge, not been reported yet.[26]
Having this mechanistic framework in mind, we prepared and
tested the norbornene precursor 28 (Scheme 3B). Pleasingly, by
using conditions similar to the ones developed for the N-
arylations, we successfully accessed arylated lactam 29 (exo
isomer) with all three organometallic reagents. In this case, as
the use of PhB(OH)2 proved optimum, we evaluated the
aromatic scope by taking advantage of the vast range of
commercially available boronic acids. As shown in Scheme 3C,
both electron-rich and electron-poor (30–33) partners were
successfully engaged, as well as substrates containing handles
for further functionalization at either para and meta positions
(34–35). ortho-Substituents were tolerated, albeit with
decreased efficiency (36). This reaction has also enabled the
installation of other (hetero)aromatics (37–38), including
substituted pyridines (39–41), quinoline (42), C2- and C3-
thiophenes (43–44), and N-Me-indole (45). The scope regarding
the amidyl radical substitution pattern was run in conjunction
with PhB(OH)2. The process allowed the construction of simple
As the N-radical precursors are easily assembled by Mitsunobu
reaction between the corresponding alcohol and the Boc-
NH(OAr) reagent,[16] we prepared 72 on gram scale. This
derivative was diversified by reaction with diethyl, di-n-propyl
and di-n-hexyl zinc reagents to give pyrrolidines 73–75 in good
yields but 1:1 syn:anti diasteroselectivity. This strategy allowed,
following N-Boc removal, the synthesis of the Myrmicaria
melanogaster ant venoms 76,[31] the Dendrobatib frog venoms
77[32] and the Solenopsis fugax ant venoms 78.
In conclusion, we have successfully developed cascade
reactions were N-radicals are generated by ground-state SET
with aryl- and alkyl-Ni(I) species. Based on the philicity of the N-
radical generated, direct transmetalation to organyl-Ni(II)
species or cyclization and then transmetalation could be
achieved. Overall this reactivity has enabled N-arylation, amino-
arylation and for the first time, amino-alkylation cascades using
readily available aryl and alkyl organometallic reagents.
This article is protected by copyright. All rights reserved.

10.1002/anie.201900510
Angewandte Chemie International Edition
COMMUNICATION
A) Proposed mechanism for the cyclization-arylation with amidyl radicals
B) Screaning of phenyl-organometallics
Ar
Ar [M]
(I)
Ph
[Ni]
X
N
[Ni], additive
solvent (0.1 M), T
[M]–X
A
+
Ph–[M]
O
ArO
R
N
N
O
Me
O
Me
28
29
(I)
(III)
[Ni] Ar
N
N
[Ni] Ar
B
O
N
O
O
P
O
Entry
[M]
[Ni] (mol%)
Additive Solvent T (˚C) Yield (%)
Q
r
OAr
N
SET
(II)
1
2
3
ZnPh NiBr2•dtbpy (20)Ni –Cs THF–DMFMT t7
76
83
45
[Ni] Ar
B(OH2) Cl2•dtbpy (20)NiCl 2CO3TB
BEDM
SO
55
0
O
D
ArO–
Si(OEt3)
2•dtbpy (20)
AT
Ar = 2,4-(NO2)2-C6H3
C) Scope of the cyclization-arylation cascade using Ar-B(OH)2
N
R1 R2 yield (%)
Me
R
F
Cl
N
30: OMe
H
H
H
H
52
78
73
74
26
84
43
R
N
OMe
Ar
31:
F
R1
R2
S
N
N
N
32: Cl
33: CN
H
H
S
O
H
H
N
34:
35:
36:
H
H
H
H
F
OMe
H
Me
O
37
65%
38
27%
39
60%
40
65%
41
32%
42
43
60%
44
45
23%
NO2
H
77%
64%
Me
Ph
N
Ph
Ph
R
H
R
H
yield (%)
X
R
Me
yield (%)
R
O
Me
Me
Boc
OAr
N
N
N
N
N
53:
73
61
75
73
46: CH2
47: CH2 CH2CH2Ph
73
76
50
48
S
N
54: OMe
55: Cl
56: CN
X
N
H
Ar
Boc
O
O
50:
51:
O
S
Cy
Me
52
Boc
48
74%, dr 2.5:1
49
96%, dr 4:1
59
30%
57
58
28%
55%
D) Cascades cyclization–alkylation of amidyl radicals with (alkyl)2Zn and their use in the synthesis of pyrrolidine alkaloids
Me
Me Me
alkyl
N
alkyl
(III)
alkyl–[M]
(alkyl)2Zn (1.0 equiv.)
NiBr2•dtbpy (20 mol%)T
H
Me
61
OAr
Me
[Ni] alkyl
N
Me
60
i-Pr
64
28
Ni
N
Me
O
N
O
F–DMF (1:1), r.t.
62
56%
63
57%
65
S
Me
O
O
88% 60%
–
83%
Me
( )12
Me
67
Boc
OAr
N
Me
66
N
LiAlH4
N
N
N
Me
Me
N
R
N
R
Me
R
( )4
Me
( )2
Me
( )11
Me
Me
alkyl
Boc
Boc
68
69
Me
Me
72
TFA
Me
71
53%
44% 58%
72% 57%
70: (±)-bgugaine
Araceae alkaloid
R = Boc
R = H
73, 68%, dr 1:1
74, 70% ,dr 1:1
75, 70%, dr 1:1
Me
76: Myrmicaria
77: Dendrobatid
78: Solenopsis
ant venoms
frog venom
ant venoms
Scheme 3. A) Proposed mechanism for cyliclization-arylation via N-radicals. B) Optimization of the process. C) Scope of the process. D) Cascade cyclization–
alkylation of amidyl radicals and applications in the synthesis of pyrrolidine alkaloids.
[5]
(a) M. S. Oderinde, N. J. Jones, A. Juneau, M. Frenette, B. Aquila, S.
Tentarelli, D. W. Robbins, J. W. Johannes, Angew. Chem. Int. Ed. 2016,
55, 13219; (b) X.-Y. Yu, Q.-Q. Zhao, J. Chen, J.-R. Chen, W.-J. Xiao
Angew. Chem. Int. Ed. 2018, 57, 15505.
Acknowledgements
D.L. thanks EPSRC for a Fellowship (EP/P004997/1), and the
European Research Council for a research grant (758427). L.A.
thanks Eli Lilly for a PhD CASE Award. N.S.S. thanks the
Deanship of Scientific Research, King Faisal University for the
research support through the Nasher Track (186021).
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Keywords: nitrogen radicals • single electron transfer • arylation
• radical cyclization • alkaloid
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Entry for the Table of Contents (Please choose one layout)
Layout 1:
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Text for Table of Contents
Lucrezia Angelin], Jacob Davies, Marco
Simonetti, Laia Malet Sanz, Nadeem S.
Sheikh], and Daniele Leonori*
Page No. – Page No.
Title
((Insert TOC Graphic here))
Layout 2:
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Cl
N
Author(s), Corresponding Author(s)*
[M]
[Ni]
N
N
H
N
OAr
Page No. – Page No.
N
N
Me
Me
OMe
Me
O
Reaction of Nitrogen-Radicals with
Organometallics Under Ni-Catalysis:
N-Arylations and Amino-
N-arylation
amino-arylation
cascade
amino-alkylation
cascade
[M] = Zn, B, Si
Functionalization Cascades
Nitrogen-radicals can be generated by ground-state SET with organo-Ni
complexes to achieve direct amination of aryl organometallics as well as amino-
arylation and, for the first time, amino-alkylation radical cascades.
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