Intermolecular Allene Functionalization by Silver-Nitrene Catalysis

Article abstract of DOI:10.1021/jacs.0c04395

Under silver catalysis conditions, using [Tp*,BrAg]2 as the catalyst precursor, allenes react with PhI═NTs in the first example of efficient metal-mediated intermolecular nitrene transfer to such substrates. The nature of the substituent at the allene seems crucial for the reaction outcome since arylallenes are converted into azetidine derivatives, whereas methylene aziridines are the products resulting from alkylallenes. Mechanistic studies allow proposing that azetidines are formed through unstable cyclopropylimine intermediates, which further incorporate a second nitrene group, both processes being silver-mediated. Methylene aziridines from alkylallenes derive from catalytic nitrene addition to the allene double bonds. Both routes have resulted to be productive for further synthetic transformations affording aminocyclopropanes.

Full text of DOI:10.1021/jacs.0c04395

Subscriber access provided by the University of Exeter
Article
Intermolecular Allene Functionalization by Silver-Nitrene Catalysis
Manuel R. Rodríguez, Maria Besora, Francisco Molina,
Feliu Maseras, M. Mar Diaz-Requejo, and Pedro J. Pérez
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c04395 • Publication Date (Web): 26 Jun 2020
Downloaded from pubs.acs.org on June 27, 2020
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 12
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Intermolecular Allene Functionalization by Silver-Nitrene
Catalysis
Manuel R. Rodríguez,a María Besora,b,c Francisco Molina,a Feliu Maseras,b,d,* M. Mar Díaz-
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Requejo,a,* and Pedro J. Péreza,*
aLaboratorio de Catálisis Homogénea, Unidad Asociada al CSIC, CIQSO-Centro de Investigación en Química
Sostenible and Departamento de Química, Universidad de Huelva, 21007 Huelva, Spain
bInstitute of Chemical Research of Catalonia, ICIQ, Av. Països Catalans, 16, Barcelona Institut of Science and
Technology, 43007 Tarragona, Spain
cDepartament de Química Física i Inorgànica, Universitat Rovira i Virgili, 43007 Tarragona, Spain
dDepartament de Química, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain
KEYWORDS : allene aziridination, allene C-N bond formation, intermolecular nitrene transfer, silver
catalysis, azetidines, aminocyclopropanes, methylene aziridines
ABSTRACT: Under silver catalysis conditions, using [Tp*,BrAg]2 as the catalyst precursor, allenes react with
PhI=NTs in the first example of efficient metal-mediated intermolecular nitrene transfer to such substrates.
The nature of the substituent at the allene seems crucial for the reaction outcome since arylallenes are
converted into azetidine derivatives whereas methylene aziridines are the products resulting from
alkylallenes. Mechanistic studies allow proposing that azetidines are formed through unstable
cyclopropylimine intermediates which further incorporates a second nitrene group, both processes being
silver-mediated. Methylene aziridines from alkylallenes derive from catalytic nitrene addition to the allene
double bonds. Both routes have resulted productive for further synthetic transformations affording
aminocyclopropanes.
INTRODUCTION
Allenes have also been studied as substrates in this
context, albeit to date metal-catalyzed examples are
reduced to intramolecular processes.3 Intermolecular
transformations are only known for free nitrene
processes, lacking of any chemo- or regiocontrol.4 First
examples of the former appeared in 2010 when Blakey5
and Robertson6 independently reported the rhodium-
catalyzed amination of sulfamate-containing allenes
leading to aminocyclopropanes (Scheme 2a), using
PhI(OR)2 as the oxidant. The use of allenyl carbamates
instead of sulfamates provided, under similar reaction
conditions and rhodium catalysis, methylene aziridines
instead of aminocyclopropanes.7 From those initial
findings, the group of Schomaker8 has propelled this
allene functionalization chemistry, not only with rhodium
but also with silver-based catalysts, leading to methylene
aziridines en route to a number of derivatives (Scheme
2b). Inspired by these precedents, and the lack of
intermolecular examples for allene functionalization with
the nitrene transfer methodology, we have focused on
such goal. Our group has investigated over the years the
Among the catalytic methods developed in the last
decades for the generation of carbon-nitrogen bonds, the
metal-induced transfer of nitrene ligands to saturated or
unsaturated substrates has emerged as a powerful tool
toward that end.1 The transient metallonitrene
intermediates2 are frequently generated in situ upon
reaction of the metal catalyst with azide, iminoiodonane
or a mixture of amine and an oxidant. In this manner, a
number of compounds such as aziridines or amines,
among others, both in inter- or intramolecular
transformations, have been prepared (Scheme 1), as a
consequence of the addition or insertion of the nitrene
unit to C=C or C-H bonds, respectively.
Scheme 1. The metal-catalyzed nitrene transfer
reaction.
R
N
C
C
R-N3
R-N=IAr
C=C
C-H
LnM
[LnM=NR]
R
N
H
R-NH2 / Oxidant
C
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 12
development of copper- and silver-based catalysts for the employed) was stirred at room temperature for 2 h in
1
2
3
4
5
6
7
8
incorporation of nitrene units to organic substrates,
either the addition to double9 or triple10 carbon-carbon
bonds or the insertion into C-H bonds,11 among others.12
Herein we report the results obtained with allenes as the
substrates and PhI=NTs (Ts = p-toluensulfonyl) as the
nitrene source (Scheme 2), in the first effective catalytic
system for the functionalization of such unsaturated
CH2Cl2, a smooth reaction took place as inferred from the
gradual incorporation of insoluble PhI=NTs into the
solution. After that time the volatiles were removed and
the crude was investigated by NMR, showing deceptively
1
simple spectra. The H NMR spectrum contained (see SI),
in addition to two inequivalent sets of resonances typical
of the tosyl (toluensulfonyl) groups, an ABX spin system,
corresponding to a CH-CH2- unit, indicating a substantial
modification of the initial 3H pattern in the starting
allene substrate. Only when single crystals were grown
the structure of this new compound 1 was identified by X-
ray studies as that of (E)-4-methyl-N-(4-phenyl-1-
molecules
by
metal-induced
nitrene
addition.
Interestingly, we have found that the nature of the
substituents of the allenes exerts a decisive control in the
reaction outcome, leading to azetidines or methylene
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 2. Allene functionalization by metal-
catalyzed nitrene transfer reactions.
tosylazetidin-2-ylidene)benzenesulfonamide,
derived
from the incorporation of two NTs groups to the allene
molecule, which has undergone a shift of two H atoms
from their initial location (Scheme 3). To our knowledge,
there is no precedent of the formation of this type of
compounds from allenes in the context of nitrene
transfer.
After this finding, we performed a study toward
catalyst screening, with phenylallene and PhI=NTs,
employing several Cu-, Ag- and Au-complexes with Tpx
Previous work: Intramolecular nitrene addition
(a) Blakey, Robertson:
O
O
O
S
CH3
HN
O
SO2NH2
[Rh]
RO
oxidant
CH3
aminocyclopropanes
(b) Schomaker:
Figure 1. Catalyst screening for the nitrene transfer
reaction onto phenylallene.
X
N
O
[M]
R
R
( )n
O
X-NH2
( )n
H
oxidant
X = CO, SO2
IPrAuCl
M = Rh or Ag
methylene aziridines
Rh2(OAc)4
CuI
This work: Intermolecular nitrene transfer
IPrCuCl
R = Aryl
TpMsCu(THF)
AgOTf + Phen
[TpBr3Ag]2
Tp*Cu(MeCN)
R
NTs
[Ag]
PhI=NTs
N
R
Ts
azetidines
Ts
N
TpBr3Cu(MeCN)
[Tp*,BrAg]2
R = Alkyl
R
methylene aziridines
0
10
20
30
40
50
60
Yield (%)
aziridines from aryl- and alkyl-substituted allenes,
respectively. A mechanistic proposal is presented based
on experimental data and computational calculations.
(hydrotrispyrazolyborate) or NHC (N-heterocyclic
carbene) ligands, among others. Additionally, we also
selected Rh2(OAc)4 in view of the previously described
catalytic activity in the intramolecular nitrene transfer
reactions to allenes.5-8 The results are shown in Figure 1.
Regarding copper-based catalysts, CuI and IPrCuCl
revealed essentially no catalytic activity, with product
being either not observed or within the detection limit by
NMR. Similar behavior was observed with the
TpMsCu(THF) catalyst, which was largely surpassed by
complexes Tp*Cu(MeCN) and TpBr3Cu(MeCN), showing
the TpMs < Tp*< TpBr3 activity trend. Since the order of
electronic density at copper for the TpxCu cores is Tp* <
TpMs< TpBr3, we interpret that (a) the steric pressure of the
TpMs ligand does not favor this transformation and (b) the
more electron deficient metal centers favor the
transformation. Also, gold- and rhodium-based catalysts
turned out to be practically inactive for this
transformation, unlike the excellent results obtained with
the latter in the intramolecular transformations
RESULTS AND DISCUSSION
Functionalization of phenylallene: the probe
reaction. We first studied the reaction of phenylallene
with PhI=NTs in the presence of [Tp*,BrAg]2 as catalyst,
given the already described performance of this silver
complex in intermolecular nitrene transfer processes.9-11
When
a
1:40:400
mixture
of
[Tp*,BrAg]2:PhI=NTs:phenylallene (0.005 mmol of catalyst
Scheme 3. Azetidine formation from silver-
catalyzed nitrene transfer to phenylallene.
[Tp*,BrAg]2
NTs
2 PhI=NTs
N
Ts
DCM, rt
-PhI
1
Me
H
Me
Me
Br
B
N
N
N
N
Br
N
Br
Me
N
ACS Paragon Plus Environment
1
Me
Me
Tp*,Br

Page 3 of 12
Journal of the American Chemical Society
mentioned above. Finally, among the silver-based substituent in the phenyl group led to the corresponding
catalysts selected, the [Tp*,BrAg]2 complex revealed the
best activity. The structure of this complex is dinuclear,13
albeit in solution it equilibrates with mononuclear
Tp*,BrAg units available for catalysis. The perbromo
analog [TpBr3Ag]2 was at variance inactive, in line with the
behavior of both complexes in previous studies regarding
alkane amidation reactions.11c
azetidines 2-4 (Table 1, entries 2-4), with yields following
the trend para> meta>ortho, indicating some steric
hindrance of such group in the reaction outcome. In the
case of introducing an electron withdrawing substituent
in the aryl ring, such as Cl- or F-, the yields in azetidines 5
and 6 were 36% and 20%, respectively (Table 2, entries 5-
6). In line with this electronic effect, the OMe derivative
was highly reactive, giving rise to a mixture of products
where azetidine 7 was present only in 16% yield (Table 1,
entry 7). 1,1-Disubstituted allenes were also screened but
the expected azetidines were formed in very low yields. In
all cases, except for the OMe derivative, the mass balance
was completed with TsNH2 formed from initial
PhI=NTs.14
A second group of allenes investigated contains an
alkyl substituent instead an aryl one (Scheme 4). Under
the same reaction conditions, hexylallene showed a
completely distinct behavior compared with the previous
arylallenes. NMR studies of the reaction crude showed
two sets of resonances which have been identified as the
methylene aziridines 10a and 10b in 80:20 ratio
respectively, and with a yield of 40% (TsNH2 accounted
for 100% initial PhI=NTs). Both compounds 10a and 10b
1
2
3
4
5
6
7
8
The use of solvents previously described in rhodium
t
intramolecular allene functionalization such as BuCN or
9
isopropylacetate were not useful with our silver catalysts:
the nitrile blocked the transformation, very likely due to
coordination to the metal center, whereas the acetate
only led to 18% yield.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Scope of the reaction of PhI=NTs and aromatic
allenes using [Tp*,BrAg]2 as catalyst.a
R2
R3
[Tp*,BrAg]2
2 PhI=NTs
R1
R3
NTs
R1
R2
DCM, r.t.
-PhI
N
Ts
Ent.
1
R1
R2
H
R3
H
Product
Yieldb
45%c
55%
40%
30%
36%c
20%
Ph
NTs
1
2
3
4
5
6
N
Ts
2
3
4
5
6
p-Tol
m-Tol
o-Tol
H
H
H
H
H
H
H
H
H
H
NTs
NTs
NTs
NTs
NTs
Scheme 4. Scope of the reaction of PhI=NTs and
aliphatic allenes using [Tp*,BrAg]2 as catalyst.[a]
N
Ts
Ts
Ts
N
[Tp*,BrAg]2
R3
R1
N
Ts
R3
R1
N
R3
PhI=NTs
R2
R2
DCM, r.t.
-PhI
R2
R1
N
Ts
Ts
Ts
Ts
N
Ts
Ts
N
N
N
N
p-Cl-C6H4
o-F-C6H4
Cl
N
Ts
n-Pr
n-Hex
Bn
n-Hex
10b
80a:20b
n-Pr
Bn
10a
11
12a
12b
N
Ts
65%
70a:30b
30%
40%
F
Unreactive:
7
8
p-Anisyl
H
H
H
16%
5%d
MeO
NTs
NTs
7
8
Ts
N
N
Me
Ts
Me
Ph
Me
N
Ts
EtO2C
13
70% (61%)
13
6%d
9
Ph
Me
H
NTs
9
N
Ts
aReactions carried out at room temperature with 0.005 mmol of
catalyst, 40 equiv of PhI=NTs and 400 equiv of allene in 6 mL of
CH2Cl2. Reaction times: 2-4 h. Yields determined by NMR using
1,3,5-trimethoxybenzene as internal standard. TsNH2 accounted
for 100% of initial PhI=NTs not converted in methylene aziridine.
Isolated yield in brackets.
aReactions carried out at room temperature with 0.005 mmol of
catalyst, 40 equiv of PhI=NTs and 400 equiv of allene in 6 mL of
CH2Cl2. Reaction time: 2 h. bDetermined by NMR using 1,3,5-
trimethoxybenzene as internal standard. TsNH2 accounted for
100% of initial PhI=NTs not converted in azetidine. cStructure
confirmed by X-ray studies (see SI). dLow yield precluded full
characterization.
result from the respective metal-induced addition of the
nitrene unit NTs to the internal or terminal double bond,
respectively.
Scope of the reaction of allenes with PhI=NTs:
substrate control of the selectivity. Under the
optimized conditions (see SI for all variables studied), the
scope of the reaction has been extended to different
allenes, a first group bearing an aryl group located at C1.
The results are displayed in Table 1. The presence of a Me
The substrate scope of this latter transformation was
next examined with a series of aliphatic allenes (Scheme
4). Moderate to good yields (30-70%) were obtained for
the array of substrates selected. Using a symmetric allene
n
(R1 = R2 = Pr), the methylene aziridine 11 was obtained
with a yield of 65%. The benzyl derivative was less
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 12
reactive whereas the cyclic symmetrical cyclonone-1,2- for alkyl-substituted allenes, either mono or disubstituted
1
2
3
4
5
6
7
8
diene led to the cyclic methylene aziridine 13, for which
single crystal were grown allowing the determination of
the solid-state structure by X-ray studies (Scheme 4).
However, disubstitution at C1 or substitution with an
electron withdrawing group such as CO2Et inhibited this
transformation. These conversions of allenes into
(Scheme 4), but not with that observed for arylallenes
(Scheme 3), where azetidines have been generated.
However, we must recall independent work by Risler16
and Shipman17 on the stability of methylene aziridines.
Risler demonstrated that N-alkyl methylene aziridines
thermally convert into cyclopropylimines at high
temperatures (Scheme 5b). Also, isomerization of
methylene aziridines occurs under the reaction
conditions. Shipman later demonstrated that N-aryl
methylene aziridines undergo such conversion at lower
temperatures (Scheme 5c), but the presence of alkyl
groups in the alkenyl fragment blocks the formation of
the cyclopropylimine. The effect of the N-substituent and
the C-substituent can be explained by the stabilization
induced by R and R’ in the either diradical or zwiterionic
nature of the intermediate (Scheme 5d).
Scheme 5. Mechanistic considerations.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
PhI=NTs
1/2 [TpxAg]2
TpxAg
N
TpxAg
(a)
-PhI
R
Ts
- TpxAg
(b)
Risler
R1
Ts
N
Ts
N
N
R2
R
R
Scheme 6. Plausible mechanistic proposal.
R3
NR1
Ts
Ts
R2
150-190 ºC
N
N
+
R3
[Ag]
R1
N
R
R1 = alkyl
R2 = H, alkyl
R3 = H, alkyl
R2
R3
PhI=NTs
PhI
R
R = alkyl; 10-13
thermal
[Ag]-NTs
(c)
Shipman
R
Mes
N
NMes
NHMes
RO
ROH
88 ºC
NTs
R
R'OH
t1/2 = 9 min
NHTs
RO
NMes
R
Mes
N
R
NMes
N
PhI=NTs
[Ag]
110 ºC
110 ºC
R
N
R
R = H, Me
Mes = 2,4,6-Me3C6H2
PhI
NTs
R
R
NR
R
N
N
R = Ar ; 1-9

or
NTs
(d)
R
R'
R'
R'
R'
R = H, Me
Based on the pieces of information available, we
believe that Scheme 6 contains a reasonable initial, yet
incomplete explanation of the reaction of allenes and
PhI=NTs. In a first step, mixtures of methylene aziridines
are formed similarly to already described olefin
aziridination with this family of catalysts.9,15 Those formed
from alkylallenes should be stable at room temperature,
according with literature precedents. However, the
presence of aryl substituents, along with the Ts group
located at nitrogen could favor the formation of
azetidines and methylene aziridines are the first examples
of metal-catalyzed routes leading to such compounds in
an intermolecular fashion.
Mechanistic precedents and proposal. Previous work
from our group9,15 with the TpxAg core (from dinuclear
[TpxAg]2)13 in olefin aziridination reactions has shown that
the process starts with the formation of a triplet nitrene
TpxAg-NTs which further interacts with the olefin en
cyclopropylimines
in
this
case.
Thus,
such
route to the formation of the aziridine, in
a
cyclopropylimines should be available at room
temperature and trapping with nucleophiles such as
alcohols could be observable (vide infra). Finally, the
formation of the azetidines from arylallenes should be
explained along a pathway involving cyclopropylimine
intermediates and another NTs group transferred through
the silver center.
stereoretentive transformation. In view of these
precedents and the related work from the group of
Schomaker,3,8 it seems reasonable proposing the
formation of a mixture of methylene aziridines as the
result of the Ag-catalyzed transfer of the NTs group to
both inequivalent C=C bonds in the allenes (Scheme 5a).
These results are in agreement with the reaction outcome
ACS Paragon Plus Environment

Page 5 of 12
Journal of the American Chemical Society
Trapping of cyclopropylimines intermediates.
that the aryl and amide groups occupy mutually cis
positions in all cases except for the tetrasubstituted 17. 1H
NMR data show nearly identical chemical shifts for the
methylene protons of the cyclopropane rings, the only
distinct pattern being observed for compound 17.
1
2
3
4
5
6
7
8
Following the previous reasoning, we studied the reaction
of 1-arylallenes with PhI=NTs, under the same conditions
commented for the generation of azetidines (see Table 1)
but using one equiv of an alcohol relative to the allene.
Azetidines were no longer observed, but the series of
aminocyclopropanes 14-23 instead (Scheme 7).
Substitution at aryl group as well as several alcohols
such as methanol, ethanol or propargyl alcohol verified
this transformation. On the contrary, phenol or 2-
bromoethanol did not provide any conversion. The
molecular structures of several aminocyclopropanes were
determined by X-ray studies (Scheme 7), demonstrating
Scheme 8. Aminocyclopropanes from methylene
aziridine 13.a
OH
NHTs
9
28
85%
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
H2O
NTs
OAllyl
NHTs
OMe
NHTs
27 80%
24 83%
MeOH
Scheme 7. Direct Synthesis of Amino-
cyclopropanes from ArylAllenes.a
OH
13
Morpholine
R2
PhSH
O
[Tp*,BrAg]2
R3
R1
OR
PhI=NTs
SPh
NHTs
N
ROH
R1
NHTs
R2
R3
DCM, r.t.
-PhI
NHTs
26 95%
25 80%
OMe
OMe
NHTs
OMe
aReactions carried out at 75 C with 0.2 mmol of 13 and 10 equiv
of nucleophile (except morpholine, 1.5 equiv) in 2 mL of MeCN.
Reaction time: 2 h. Isolated yields.
NHTs
NHTs
Cl
14 50% (41%)
15 59%(45%)
16 40%
When moving to alkylallenes, we first employed 1-
hexylallene and cyclonone-1,2-diene as substrates,
operating under the same reaction conditions than those
leading to methylene aziridines, but in the presence of
additional MeOH. NMR studies of the reaction mixtures
carried out after PhI=NTs consumption revealed the
formation of the methylene aziridines. It seems that at
variance with the aryl system, the methylene aziridines
derived from alkylallenes do not suffer isomerization into
cyclopropylimines at room temperature. Taking advantage
of the availability of methylene aziridine 13 as an isolated
compound, we found that the corresponding
aminocyclopropane 20 could be formed upon heating at
75 °C in the presence of methanol. Several nucleophiles
(Scheme 8) such as alcohols, water, sulfides and amines
could be incorporated into the aminocyclopropanes 24-28
in very good yields (80-95%).
We interpret the formation of aminocyclopropanes 14-
28 as an evidence of the formation of cyclopropylimines
from the methylene aziridine precursors. Data collected
at this stage supports the proposal in Scheme 6 that the
methylene aziridines from arylallenes are not stable at
room temperature and convert into cyclopropylimines
whereas when using alkylallenes the methylene aziridines
are stable at room temperature and require heating to
induce cyclopropylimine formation.
NHTs
OMe
OMe
OMe
NHTs
NHTs
MeO
(55%)
19 66%
17 36%
18 40%
OMe
OMe
OEt
NHTs
NHTs
NHTs
F
20 60%
21 70%
22 46%
O
NHTs
23 30%
15
14
17
22
DFT studies. We first analyze computationally the
reaction of arylallene and alkylallene and PhI=NTs
induced by the silver catalyst Tp*,BrAg. Calculations
presented in this section are done with the B3LYP-D3
functional including dichloromethane solvent effects
through a continuum model. We have previously used a
similar methodology with this type of catalysts achieving
aReactions carried out at room temperature with 0.005 mmol of
catalyst, 40 equiv of PhI=NTs, 400 equiv of allene and 400 equiv
the alcohol in 6 mL of CH2Cl2. Reaction times: 2 h. Yields
determined by NMR using 1,3,5-trimethoxybenzene as internal
standard. TsNH2 accounted for 100% initial PhI=NTs not
converted into products. Isolated yields in brackets. ORTEP
plots (50% thermal ellipsoids) of the X-ray crystal structures of
14, 15, 17 and 22 are shown.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 12
good results.18 All reported energies correspond to Gibbs
intermediates with the new C-N bond formed (I2aT, I2bT
free energies in kcal mol-1. Further data on the method for
the calculations are supplied in the Computational
Details.
and I2cT) will cross to the singlet energy surface through
the corresponding MECPs (MECP1a, MECP1b and
MECP1c ) and form intermediates I2aS, I2bS and I2cS. I2aS
1
2
3
4
5
6
7
8
Scheme 9. Computationally postulated early steps for the reaction of phenylallene. Free energies in kcal mol-1.
[Ag]
(Ts)N
TS1aT
Ph
C
6.9
R1S+R2
5.9
[Ag]
Ph
6.7
[Ag]
(Ts)N
Ph
TS1bT
9
(Ts)N
C
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
I1aT
2.2
I1bT
-1.3
C
TS1cT
0.1
I2bT
MECP1b
-1.8
0.0
R1T+R2
[Ag]
-0.8
[Ag]
-1.3
I1cT
[Ag]+C
(Ts)N
Ph
[Ag]
C
(Ts)N
MECP1a
-5.8
(Ts)N
P2
Ph
C
Ph
N(Ts)
Ph
(Ts)N
Ph
C
I2aT
-9.4
Ph
[Ag]
[Ag]
Ph
(Ts)N
C
(Ts)N
(Ts)N
I1bT
[Ag]
N
C
I2cT
P1
[Ag]
(Ts)N
Ph
-38.0
MECP1c
-38.3
[Ag]
S
P2
Ph
O
-40.2
P1
N(Ts)
Ph
TS3S
-43.3
I2cS
(Ts)N
[Ag]
N
-42.8
Ph
-43.5
Ph
-44.8
TS2S
Ts
P3
Ph
TS4S
-48.9
P3
[Ag]
N
-48.7
I4S
H
[Ag]
N(Ts)
Ph
S
B
N
-51.6
O
Br
Br
N
N
N
N
I2bS
[Ag] = Br
[Ag]
N
N
Ph
-55.1
Ag
Ts
[Ag]
[Ag]
Ph
[Ag]
-57.0
I2aS
N
I3S
N(Ts)
N(Ts)
S
I5S
Ph
Ph
-60.6
O
-61.7
Ph
and I2bS present already a new C-C bond and correspond
to the metal-coordinated forms of products P1 and P2,
respectively. For I2cS, located in the lowest barrier favored
path, several steps must take place before product P3 is
reached. A very low energy transitions state leads to the
I3S intermediate, containing a 5-member ring which
involves the three carbons in the starting allene and the
Ts group attached to the nitrene center. The cleavage of
this ring leads to the formation of a new C-C bond and
ultimately to the P3 product. These are very exergonic
processes, thus completely irrerversible. At variance with
The silver fragment Tp*,BrAg is known to react with
PhI=NTs to form metallonitrenes.9
The ground state
a,b,19
of the metallonitrene complex R1 (Scheme 9) is a triplet,
located 5.9 kcal mol-1 below the corresponding singlet,
and 16.5 kcal mol-1 below Tp*,BrAg and NTs as separate
molecules.9
a,b
The initial reactivity of complex R1 is outlined in
Scheme 9. The nitrene center in R1 can attack the
phenylallene R2 at three different positions: a) at the less
substituted terminal carbon (=CH2), b) at the phenyl
substituted terminal carbon (=CHPh), and c) at the
phenylallene central carbon (=C=). We have computed
the transition states corresponding to each of the attacks:
TS1a, TS1b and TS1c, respectively. The barriers
corresponding to the attack to terminal carbons are quite
low (9.4 and 8.0 kcal mol-1 from adduct I1cT to TS1aT and
TS1bT) but cannot compete with the attack to the central
carbon of the allene, which is clearly the preferred
process. Transition state TS1cT has an associated barrier
of only 1.4 kcal mol-1.
the proposal shown in Scheme
6
where the
cyclopropylimine species would appear because of the
thermal rearrangement of the methylene aziridines,
calculations show that the presence of the silver catalyst
offers a reaction pathway favoring its formation without
the intermediacy of the three member rings.
Transition states TS1aT, TS1bT and TS1cT evolve
through multistep processes, see Scheme 9. The triplet
ACS Paragon Plus Environment

Page 7 of 12
Journal of the American Chemical Society
Products P1-P3 are not observed in the reaction
mechanism where the transition from the triplet to the
singlet spin state takes place through an MECP before the
formation of the first new nitrogen-carbon bond. We
label this alternative mechanism as “early spin-
transition”, to differentiate it from the previously reported
one where the transition took place after the bonds has
1
2
3
4
5
6
7
8
mixture of phenylallene and PhI=NTs. However,
cyclopropylimine P3 may evolve to the final product upon
reaction with a second metallonitrene complex R1, as
shown in Scheme 10. A new C-N bond is formed between
the nitrogen of the second silver-nitrene and the
cyclopropylimine P3 through TS6T with a barrier of only
11.3 kcal mol-1. As the N-C bond is formed, one of the C-C
bonds of the cyclopropane is broken, which results in
species I7T. Through MECP2 the system crosses to the
Scheme 11. The selectivity-determining step for
the two computed mechanisms for alkylallenes.
Free energies in kcal mol-1.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ag
[
]
Ag
[
]
Et
Ag
[
]
Scheme 10. Postulated computational mechanism
Et
C
(Ts)N
(Ts)N
for the formation of compound
1
from
C
(Ts)N
C
Et
cyclopropylimine. Free energies in kcal mol-1.
HMECP0c -3.2
HMECP0a -3.8
[Ag]
(Ts)N
N(Ts)
C
Ph
Late
spin-crossing
H
B
N
N
TS6T
-76.6
N
N
Br
N
N
[Ag] = Br
R1T+ P3
Br
-9.1 HTS1aT
-10.7 HTS1bT
HMECP0b -9.0
Ag
-81.8
[Ag]
I6T
Early
spin-crossing
-11.6 HTScT
-87.9
N(Ts)
+
MECP2
-125.3
[Ag]
I7T
O
S
N
N(Ts)
(Ts)N
-124.8
[Ag]
[Ag]
HI1T
-19.2
C
N(Ts)
(Ts)N
Ph
Ph
C
N(Ts)
C
P3
[
]
Ag
(Ts)N
N(Ts)
Ph
Et
C
TS7S
(Ts)N
(Ts)N
Ph
C
Ph
1
-139.5
I7S
-155.6
-149.8
[Ag]
been formed and the selectivity has been decided. Both
mechanisms could be characterized for ethyl-allene, the
corresponding selectivity-determining steps are shown in
Scheme 11. The two mechanisms differ in the associated
selectivity, the new mechanism reproducing the
experimental observation in which the major product is
methylene aziridine emerging from the blue pathway.
Remarkably, this alternative mechanism is absent in the
phenylallene system, which must then react through the
“late spin-transition” mechanism reported above, leading
to the azetidine through the black pathway in Scheme 9.
(Ts)N
N(Ts)
C
I8S
Ph
-164.7
[Ag]
N(Ts)
Ph
C
N(Ts)
singlet surface, that is 25 kcal mol-1 more stable than the
triplet. A second N-C bond is formed through TS7S,
generating the four membered cycle I8S. Product 1, which
is the only one experimentally observed, is delivered after
silver decoordination, an energetically disfavored step but
easily compensated by ulterior coordination of other
species to the silver center.
We next shifted our attention to the behavior of
alkylallenes, which have been experimentally shown to
produce methylene aziridines rather than azetidines. We
notice that the mechanism reported above in Scheme 11
may lead to aziridine products P1 and P2, though they are
kinetically disfavored with respect to the azetidine
emerging from P3. We computed a similar mechanism for
ethylallene as our model alkylallene system. To our initial
disappointment the resulting profile (fully described in
the SI, key step in Scheme 11) yielded the same selectivity,
which would favor the azetidine. Additional calculations
on the ulterior evolution of the azetidine products were
also unable to provide a satisfying explanation for the
different behavior of alkyl and arylallenes. The problem
was finally solved by the characterization of an alternative
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 12
1
2
Scheme 12. Mechanistic proposal for the different behavior of aryl- and alkylallenes.
3
4
5
6
NHTs
R
NTs
R
Nuc
Ts
Ts
Nuc-H
N

N
+
R
R
R = alkyl; 10-13
R = Alkyl ; 24-28
7
8
9
[Ag]
NTs
NTs
R = Aryl ; 1-9
NTs
PhI=NTs
PhI
[Ag]-NHTs
- [Ag]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
R
R
[Ag]-NTs
R
R'OH
H
NHTs
R
R'O
B
N
Br
Br
N
N
N
N
Br
[Ag] =
N
R = Aryl ; 14-23
Ag
We notice there is a minor problem in the computed
energetics, as the free energy for HMECP0b is still 2.6 kcal
mol-1 above that of HTScT. We view this as a minor
discrepancy as the reproduction of singlet/triplet energy
gaps has been shown to be particularly challenging for
DFT methods. More encouragingly, this alternative
mechanism provides satisfactory qualitative explanations
for the reactivity of alkylallenes. The “early spin-crossing”
path was absent in the arylallene system because of the
larger triplet/spin gap associated to the stabilization of
the triplet state associated to the spin delocalization to
the aryl ring. Additionally, the “early spin-crossing” path
favors the attack on the terminal substituted carbon since
it gives more weight to inductive effects than to the
delocalization effects that favor the central carbon in the
“late spin-crossing” mechanism. A detailed analysis of
spin densities in provided in the SI.
others.5,17 In their absence, cyclopropylimine reacts with a
second silver-nitrene intermediate en route to the
observed azetidine compounds.
At variance with the above, the methylene aziridines
generated from alkylallenes are stable under the reaction
conditions, and the presence of alcohol does not influence
the reaction outcome. Only when they are heated, in the
absence of any catalyst and with added nucleophiles, they
provide aminocyclopropanes because of the in situ
formation of a cyclopropylimine intermediate, which
traps the nucleophile.
CONCLUSIONS
We have discovered the catalytic capabilities of a silver
complex toward the intermolecular functionalization of
allenes toward azetidines or methylene aziridines,
depending of the nature (aryl or alkyl) of the substituents
in the allene reactant. The azetidines are formed by a
Global mechanistic proposal. From collected
experimental and computational data the global
mechanistic picture is shown in Scheme 12. A silver-
nitrene intermediate is formed from the TpxAg core and
PhI=NTs, which transfers the nitrene group to the allene
C=C bond leading to methylene aziridines for R = alkyl
and azetidines for R = aryl. The latter takes place through
the formation of a cyclopropylimine intermediate in a
silver-catalyzed route, which is kinetically more favorable
than the formation of the corresponding methylene
aziridines. For alkylallenes, a different selectivity has been
calculated due to an earlier transition from the triplet to
the singlet spin states.
sequential
process
involving
silver-mediated
by the
cyclopropylimine
formation
followed
incorporation of a second, also silver-mediated, nitrene
unit. At variance with that, alkylallenes are transformed
into methylene aziridines. Aminocyclopropanes can be
readily accessed from both alkyl- and arylallenes. This is
the first example of efficient modification of allenes by
metal-catalyzed nitrene transfer in an intermolecular
manner.
EXPERIMENTAL SUMMARY
General Procedure for the reaction of allenes and
PhI=NTs. The [Tp*,BrAg]2 complex13 (0.005 mmol) was
dissolved in deoxygenated DCM (6 mL) and the allene (2
mmol) was added before PhI=NTs (74.4 mg, 0.2 mmol) was
incorporated in one portion to the stirred solution. The flask
was covered with aluminum foil to protect the reaction
The presence of the cyclopropylimine intermediate
when employing arylallenes explains the formation of
aminocyclopropanes when the reaction is carried out in
the presence of alcohols, which add to the C=N bond as
previously described by Shipman or Blakey, among
ACS Paragon Plus Environment

Page 9 of 12
Journal of the American Chemical Society
mixture from light. After 4h, the solvent was removed under
reduced pressure and the crude was analyzed by NMR
1
spectroscopy and/or purified by column chromatography
(see SI). For aminocyclopropane synthesis the procedure was
identical also adding 2 mmol of the alcohol before addition
of PhI=NTs.
Derivatizations of the methylene aziridine 13. (E)-
10-tosyl-10-azabicyclo[7.1.0]dec-1-ene (58.2 mg, 0.2 mmol)
was dissolved in acetonitrile (2 mL) and the
corresponding nucleophile was added (2-10 mmol). The
reaction mixture was heated at 75 °C for 2 h, and then
solvent was removed under reduced pressure. The crude
was analyzed by NMR spectroscopy and/or purified by
column chromatography.
Computational Details. The presented computational
mechanistic study has been performed by optimization of
minima and transition states with the B3LYP-D3 functional20
including the D3 correction developed by Grimme and co-
workers21 and as implemented in Gaussian 09.22 The
6-31g(d)23 basis set was used for all atoms except for silver,
for which the Stuttgart-Dresden (SDD) basis set with
effective core potential (ECP) was used instead. 24 Frequency
calculations were carried out at the same level to obtain the
free energies and assure the nature of each stationary point.
Solvent effects were taken into account by using the SMD25
solvation model and default options for dichloromethane.
For the location of MECPs (Minimum Energy Crossing
Points) we used the code provided by Prof. Jeremy Harvey.26
The geometries of all species relevant for this study are
included in a data set collection of computational results
available in the ioChem-BD repository.27
2
3
4
5
6
7
8
9
2012, 51, 7384–7395. (b) Degennaro, L.; Trinchera, P.; Luisi,
R. Recent Advances in the stereoselective synthesis of
aziridines Chem. Rev. 2014, 114, 7881–7929. (c) Chang, J. W.
W.; Ton, T. M. U.; Chan, P. W. H. Transition-metal-
catalyzed aminations and aziridinations of C-H and C=C
bonds with iminoiodinanes. Chem. Rev. 2011, 11, 331–357.
(d) Díaz-Requejo, M. M.; Caballero A.; Fructos, M. R.;
Pérez, P. J. Alkane C-H Activation by Single-Site Metal
Catalysis, Springer, Amsterdam, 2012, Chap. 6. (e) Zalatan,
D. N.; Du Bois, J. Metal-catalyzed oxidations of C-H to C-N
bonds. Top. Curr. Chem. 2010, 292, 347−378.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(2) Carsch, K. M.; Dimucci, I. M.; Iovan, D. A.; Li, A.; Zheng,
S.-L.; Titus, C. J.; Lee, S. J.; Irwin, K. D.; Nordlund, D.;
Lancaster, K. M.; Betley. T. A. Synthesis of a copper-
supported triplet nitrene complex pertinent to copper-
catalyzed amination. Science 2019, 365, 1138-1143.
(3) Adams, C. S.; Weatherly, C. D.; Burke, E. G.; Schomaker, J.
M. The conversion of allenes to strained three-membered
heterocycles Chem. Soc. Rev. 2014, 43, 3136–316.
(4) (a) Bleiholder, R. F.; Shechter, H. Addition of
electronegatively substituted azides to allenes. J. Am.
Chem. Soc. 1968, 90, 2131–2137. (b) Bingham, E. M.; Gilbert,
J. C. Reaction of carbethoxynitrene with allenes. J. Org.
Chem. 1975, 40, 224–228. (c) Lwowski, W.; Maricich, T. J.
Carbethoxy nitrene by α-elimination. Reaction with
hydrocarbons. J. Am. Chem. Soc. 1965, 87, 3630–3637. (c)
McConaghy, J. S.; Lwowski, W. Singlet and triplet nitrenes.
I. Carbethoxynitrene generated by α-elimination. J. Am.
Chem. Soc. 1967, 89, 2357–2364. (d) Atkinson, R. S.;
Malpass, J. R. Nitrene addition to allenes: 1,4-
diazaspiro[2.2]pentanes. Tetrahedron Lett. 1975, 16, 4305–
4306.
(5) (a) Stoll, A. H.; Blakey, S. B. Rhodium-catalyzed allene
Supporting Information.
amination:
diastereoselective
synthesis
of
All procedures and characterization data for new
compounds, computational data and Cartesian coordinates
of the optimized structures. The Supporting Information is
available free of charge on the ACS Publications website.
aminocyclopropanes via a 2-amidoallylcation intermediate.
J. Am. Chem. Soc. 2009, 132, 2108–2109. (b) Stoll, A. H.;
Blakey, S. B. Rhodium-catalyzed allene amidation: A facile
entry into 2-amidoallylcations for unusual [3
+ 3]
annulation reactions. Chem. Sci. 2011, 2, 112–116.
(6) Feast, G. C.; Page, L. W.; Robertson, J. The intramolecular
amination of allenes. Chem. Commun. 2010, 46, 2835–2837.
(7) Robertson, J.; Feast, G. C.; White, L. V.; Steadman, V. A.;
Claridge, T. D. W. Structure and reactivity of bicyclic
methylene aziridines prepared by intramolecular
aziridination of allenes. Org. Biomol. Chem. 2010, 8, 3060–
3063.
(8) (a) Boralsky, L. A.; Grigg, R. D.; Marston, D.; Hershberger,
J. C.; Schomaker, J. M. Allene functionalization via bicyclic
methylene aziridines. Org. Lett. 2011, 13, 1924–1927. (b)
Adams, C. S.; Boralsky, L. A.; Guzei, I. A.; Schomaker, J. M.
Modular functionalization of allenes to aminated
stereotriads. J. Am. Chem. Soc. 2012, 134, 10807–10810. (c)
Burke, E. G.; Schomaker, J. M. Oxidative allene amination
for the synthesis of azetidin-3-ones. Angew. Chem. Int. Ed.
2015, 54, 12097–12101. (d) Schmid, S. C.; Guzei, I. A.;
Schomaker, J. M. A stereoselective [3+1] ring expansion for
the synthesis of highly substituted methylene azetidines.
Angew. Chem. Int. Ed. 2017, 56, 12229–12233. (e) Grigg, R.
AUTHOR INFORMATION
Corresponding Author
perez@dqcm.uhu.es
(PJP),
mmdiaz@dqcm.uhu.es
(MMDR), fmaseras@iciq.es (FM)
Funding Sources
No competing financial interests have been declared.
ACKNOWLEDGMENTS
Support for this work was provided by the MINECO
(CTQ2017-82893-C2-1-R, CTQ2017-87792-R and Red
Intecat CTQ2016-81923-REDC) and Universidad de
Huelva (PO FEDER 2014-2020-UHU-1254043). MR thanks
MINECO for a predoctoral fellowship.
REFERENCES
D.;
Schomaker,
J.
M.;
Timokhin,
V.
C-H
amination/cyclocarbonylation of allene carbamates:
A
versatile platform for the synthesis of α,β-unsaturated γ-
lactams. Tetrahedron 2011, 67, 4318–4326. (f) Weatherly, C.
D.; Rigoli, J. W.; Schomaker, J. M. Synthesis of 1,3-
(1) (a) Dequirez, G.; Pons, V.; Dauban, P. Nitrene chemistry in
organic synthesis: Still in its infancy? Angew. Chem Int. Ed.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 10 of 12
1
2
3
4
5
6
7
8
9
diaminated stereotriads via rearrangement of 1,4-
Vedernikov. A. N.; Caulton, K. G. Facile alkane
functionalization in copper-[2.1.1]-(2,6)-pyridinophane-
PhINTs systems. Chem. Commun. 2003, 162-163.
diazaspiro[2.2]pentanes. Org. Lett. 2012, 14, 1704–1707. (g)
Weatherly, C. D.; Guzei, I. A.; Schomaker, J. M.
Stereocontrolled synthesis of 1,3-diamino-2-ols by
aminohydroxylation of bicyclic methylene aziridines. Eur.
J. Org. Chem. 2013, 3667–3670. (h) Rigoli, J. W.; Weatherly,
C. D.; Vo, B. T.; Neale, S.; Meis, A. R.; Schomaker, J. M.
Chemoselective allene aziridination via Ag(I) catalysis.
Org. Lett. 2013, 15, 290–293. (i) Rigoli, J. W.; Weatherly, C.
D.; Alderson, J. M.; Vo, B. T.; Schomaker, J. M. Tunable,
chemoselective amination via silver catalysis. J. Am. Chem.
Soc. 2013, 135, 17238–17241. (j) Eshon, J.; Nicastri, K. A.;
Schmid, S. C.; Raskopf, W. T.; Guzei, I. A.; Fernández, I.;
Schomaker, J. M. Intermolecular [3+3] ring expansion of
(15) Maestre, L.; Sameera, W. M. C.; Díaz-Requejo, M. M.;
Maseras, F.; Pérez, P. J. A General Mechanism for the
Copper- and Silver-Catalyzed Olefin Aziridination
Reactions: Concomitant Involvement of the Singlet and
Triplet Pathways. J. Am. Chem. Soc. 2013, 135, 1338−1348.
(16) Quast,
H.;
Risler,
W.
Methyleneaziridine-
Cyclopropanimine Valence Isomerization. Angew. Chem.
Int. Ed. Engl. 1973, 12, 414-415.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(17) (a) Bayliffe, F. H.; Steven, A.; Ando, K.; Shipman, M.
Sodium Amide Induced Cyclization of 2-Iodoprop-2-
enylamines: Application to the Synthesis of 1-Aryl-2-
methyleneaziridines. Synlett 2015, 26, 1371–1374. (b) F.
Bayliffe, Ph. D. Thesis, Synthesis and Chemistry of
Methyleneaziridines Bearing Aryl Groups, Department of
Chemistry, University of Warwick, June 2013.
http://wrap.warwick.ac.uk/58188/1/WRAP_THESIS_Bayliff
e_2013.pdf.
(18) (a) Fructos, M. R.; Besora, M.; Braga, A. A. C.; Díaz-
Requejo, M. M.; Maseras, F.; Pérez, P.J. Mechanistic studies
on gold-catalyzed direct arene C–H bond functionalization
by carbene insertion: the coinage-metal effect.
Organometallics 2017, 36, 172-179 (b) Gava, R.; Fuentes, M.
A.; Besora, M.; Belderrain, T. R.; Jacob, K.; Maseras, F.;
Etienne, M.; Caballero, A.; Pérez, P. J. Silver-catalyzed
functionalization of esters by carbene transfer: the role of
ylide zwitterionic intermediates. ChemCatChem 2014, 6,
2206-2210.
(19) (a) Muñoz-Molina, J. M.; Belderrain, T. R.; Pérez, P. J.
Trispyrazolylborate coinage metals complexes: structural
features and catalytic transformations. Coord. Chem. Rev.,
2019, 390, 171-189. (b) Besora, M.; Braga, A. A. C.; Sameera,
W. M. C.; Urbano, J.; Fructos, M. R.; Pérez, P. J.; Maseras,
F. A computational view on the reactions of hydrocarbons
with coinage metal complexes. J. Organomet. Chem. 2015,
784, 2-12.
(20) (a) Becke, A. D. Density functional thermochemistry: III.
The role of exact exchange. J. Chem. Phys. 1993, 98, 5648–
5652. (b) Stephens, P. J.; Devlin, F. J.; Chabalowski, C.F.;
Frisch, M. J. Ab initio calculation of vibrational absorption
and circular dichroism spectra using density functional
force fields. J. Phys. Chem. 1994, 98, 11623-11627. (c) Lee, C.;
Yang, W. T.; Parr, R. G. Development of the Colle-Salvetti
Correlation-Energy Formula into a Functional of the
Electron Density. Phys. Rev. B 1988, 37, 785-789.
aziridines
to
dehydropiperi-dines
through
the
intermediacy of aziridinium ylides. Nat. Comm. 2020, 11,
1273.
(9) (a) Llavería, J.; Beltrán, A.; Díaz-Requejo, M. M.; Matheu,
M. I.; Castillón, S.; Pérez, P. J. Efficient silver-catalyzed
regio- and stereospecific aziridination of dienes. Angew.
Chem. Int. Ed. 2010, 49, 7092–7095. (b) Llavería, J.; Beltrán,
A.; Sameera, W. M. C.; Locati, A.; Díaz-Requejo, M. M.;
Matheu, M. I.; Castillón, S.; Maseras, F.; Pérez, P. J. Chemo,
regio, and stereoselective silver-catalyzed aziridination of
dienes: scope, mechanistic studies, and ring-opening
reactions. J. Am. Chem. Soc. 2014, 136, 5342–5350. (c)
Fructos, M. R.; Álvarez, E.; Díaz-Requejo, M. M.; Pérez, P. J.
Selective synthesis of N-substituted 1,2-dihydropyridines
from furans by copper-induced concurrent tandem
catalysis. J. Am. Chem. Soc. 2010, 132, 4600–4607.
(10) Rodríguez, M. R.; Beltrán, A.; Mudarra, A. L.; Alvarez, E.;
Maseras, F.; Díaz-Requejo, M. M; Pérez, P. J. Catalytic
nitrene transfer to alkynes: A novel and versatile route for
the synthesis of sulfinamides and isothiazoles. Angew.
Chem. Int. Ed. 2017, 56, 12842–12847.
(11) Díaz-Requejo, M. M.; Belderrain, T. R.; Nicasio, M. C.;
Trofimenko, S.; Pérez, P. J. Cyclohexane and benzene
amination by catalytic nitrene insertion into C-H bonds
with the copper-homoscorpionate catalyst TpBr3Cu(NCMe).
J. Am. Chem. Soc. 2003, 125, 12078–12079. (b) Fructos, M. R.;
Trofimenko, S.; Díaz-Requejo, M. M.; Pérez, P. J. Facile
amine formation by intermolecular catalytic amidation of
carbon-hydrogen bonds. J. Am. Chem. Soc. 2006, 128,
11784–11791 (c) Gómez-Emeterio, B. P.; Urbano, J.; Díaz-
Requejo, M. M.; Pérez, P. J. Easy alkane catalytic
functionalization. Organometallics 2008, 27, 4126–4130.
(12) Maestre, L.; Dorel, R.; Pablo, O.; Escofet, I.; Sameera W. M.
C.; Álvarez, E.; Maseras, F.; Díaz-Requejo, M. M.;
Echavarren, A. M.; Pérez, P. J. Functional-group-tolerant,
silver-catalyzed N-N bond formation by nitrene transfer to
amines. J. Am. Chem. Soc. 2017, 139, 2216–2223.
(13) Urbano, J.; Braga, A. A. C.; Maseras, F.; Álvarez, E.; Díaz-
Requejo, M. M.; Pérez, P. J. The Mechanism of the
Catalytic Functionalization of Haloalkanes by Carbene
Insertion: An Experimental and Theoretical Study.
Organometallics 2009, 28, 5968-5981.
(14) The formation of TsNH2 is usually explained as the result
of the presence of adventitious water. The use of molecular
sieves has been reported to eliminate this drawback.
However, in our case the addition of molecular sieves to
the reaction mixture did not alter the reaction outcome.
Vedernikov and Caulton have proposed the reaction with
solvent C-H bonds to account for such tosylamine. See:
(21) Grimme, S.; Antony, J.; Ehrlich S.; H. Krieg, A consistent
and accurate ab initio parameterization of density
functional dispersion correction (DFT-D) for the 94
elements H-Pu. J. Chem. Phys. 2010, 132, 154104.
(22) Gaussian 09, Revision D.01, Frisch, M. J.; Trucks, G. W.;
Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J.
R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.;
Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.;
Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.;
Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.;
Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.;
Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.;
Staroverov, V. N.; Kobayashi, R.; Normand, J.;
Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.;
Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.;
ACS Paragon Plus Environment

Page 11 of 12
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.;
Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.;
Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.;
Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J.
Gaussian 09, Revision B.01, Gaussian, Inc., Wallingford CT,
2009.
9
(23) (a) Ditchfield, R.; Hehre, W. J.; Pople, J. A. Self-consistent
molecular-orbital. An extended gaussian-type basis for
molecular-orbital studies of organic molecules. J. Chem.
Phys. 1971, 54, 724–728. (b) Hehre, W. J.; Ditchfield, R.;
Pople, J.A. Self—Consistent Molecular Orbital Methods.
XII. Further Extensions of Gaussian—Type Basis Sets for
Use in Molecular Orbital Studies of Organic Molecules. J.
Chem. Phys. 1972, 56, 2257–2261. (c) Hariharan, P.C.; Pople,
J.A. Influence of polarization functions on molecular-
orbital hydrogenation energies. Theor. Chim. Acta 1973, 28,
213–222.
(24) Andrae, D.; Haeussermann, U.; Dolg, M.; Stoll, H; Preuss,
H. Energy-adjusted ab initio pseudopotentials for the 2nd
and 3rd row transition-elements. Theor. Chem. Acc. 1990,
77, 123-141.
(25) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. Universal
solvation model based on solute electron density and on a
continuum model of the solvent defined by the bulk
dielectric constant and atomic surface tensions. J. Phys.
Chem. B, 2009, 113, 6378-6396.
(26) Harvey, J. N.; Aschi, M.; Schwarz, H.; Koch, W. The singlet
and triplet states of phenyl cation. A hybrid approach for
locating minimum energy crossing points between non-
interacting potential energy surfaces. Theor. Chem. Acc.
1998, 99, 95–99.
(27) Álvarez-Moreno, M.; de Graaf, C.; López, N.; Maseras, F.;
Poblet, J. M.; C. Bo. Managing the Computational
Chemistry Big Data Problem: The ioChem-BD Platform. J.
Chem. Inf. Model. 2015, 55, 95-103.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 12 of 12
1
R
PhINTs
2
3
4
5
Ts
N
6
7
8
R = Alkyl
R = Aryl
R
+
[Ag]
R
NTs
N
Ts
Ts
N
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
R
12
ACS Paragon Plus Environment