Carbodiimide Synthesis via Ti-Catalyzed Nitrene Transfer from Diazenes to Isocyanides

Article abstract of DOI:10.1021/acscatal.9b04107

Simple Ti imido halide complexes such as [Br₂Ti(N^tBu)py₂]₂ are competent catalysts for the synthesis of unsymmetrical carbodiimides via Ti-catalyzed nitrene transfer from diazenes or azides to isocyanides. Both alkyl and aryl isocyanides are compatible with the reaction conditions, although product inhibition with sterically unencumbered substrates sometimes limits the yield when diazenes are employed as the oxidant. The reaction mechanism has been investigated both experimentally and computationally, wherein a key feature is that the product release is triggered by electron transfer from an η²-carbodiimide to a Ti-bound azobenzene. This ligand-to-ligand redox buffering obviates the need for high-energy formally Ti^II intermediates and provides further evidence that substrate and product "redox noninnocence" can promote unusual Ti redox catalytic transformations.

Full text of DOI:10.1021/acscatal.9b04107

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Article
Carbodiimide Synthesis via Ti-Catalyzed
Nitrene Transfer from Diazenes to Isocyanides
Evan P. Beaumier, Meghan E. McGreal, Adam R Pancoast, Ryan Hunter Wilson,
James T Moore, Brendan Joseph Graziano, Jason D. Goodpaster, and Ian A. Tonks
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b04107 • Publication Date (Web): 11 Nov 2019
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Page 1 of 14
ACS Catalysis
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Carbodiimide Synthesis via Ti-Catalyzed Nitrene Transfer from
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Evan P. Beaumier, Meghan E. McGreal, Adam R. Pancoast, R. Hunter Wilson, James T. Moore,
Brendan J. Graziano, Jason D. Goodpaster,* Ian A. Tonks*
Department of Chemistry, University of Minnesota - Twin Cities, 207 Pleasant Street SE, Minneapolis, Minnesota
5455, United States
5
t
2 2 2
ABSTRACT: Simple Ti imido halide complexes such as [Br Ti(N Bu)py ] are competent catalysts for the synthesis of
unsymmetrical carbodiimides via Ti-catalyzed nitrene transfer from diazenes or azides to isocyanides. This is the only
example of catalytic nitrene transfer to isocyanides where diazenes have been employed as the nitrene source. Both
alkyl and aryl isocyanides are compatible with the reaction conditions, although product inhibition with sterically
unencumbered substrates sometimes limits the yield when diazenes are employed as the oxidant. The reaction
mechanism has been investigated both experimentally and computationally, wherein a key feature is that product
2
release is triggered by electron transfer from an η -carbodiimide to a Ti-bound azobenzene. This ligand-to-ligand redox
II
buffering obviates the need for high-energy formally Ti intermediates, and provides further evidence that substrate
and product “redox noninnocence” can promote unusual Ti redox catalytic transformations.
Keywords: Titanium, Nitrene Transfer, Isocyanide, Carbodiimide, Redox Catalysis, Redox Non-Innocence
thioureas.36,37 However, nitrene transfer to isocyanides is an
INTRODUCTION
attractive alternative as it provides a potentially more
3
8-52
direct and atom economical alernative.
Transition metal-catalyzed nitrene transfer
reactions are efficient and highly atom economical routes
1
–4
for the synthesis of nitrogen-containing molecules. There
are many examples of transition metal-catalyzed nitrene
5
–8
1
9
transfer using Rh,
Ag, and late transition metal
0–12
porphyrin complexes.
However, there are significantly
fewer examples of catalytic nitrene transfer reactions with
early transition metals. This is partly because the reactivity
of high-valent early transition metal imido (M≡NR)
complexes is dominated by redox-neutral reactions such as
13–16
[
2+2]-cycloaddition and 1,2-addition.
Recently, we
have demonstrated that azobenzene can be used as an
oxidant in formal nitrene transfer reactions that stem from
1
7–24
initial Ti≡NR and alkyne [2+2]-cycloaddition.
In an
effort to expand the use of azobenzene as a nitrene source
in catalytic reactions beyond [2+2] cycloadditions, we
sought to use isocyanides as migratory insertion partners
with Ti≡NR fragments en route to catalytic carbodiimide
formation.
Carbodiimides are used as dehydration reagents in
2
5–27
28,29
30–
chemical synthesis,
polymer materials,
and dyes.
3
3
Unsymmetrical carbodiimides are often synthesized via
3
4,35
dehydration of ureas
or dehydrosulfurization of
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a in PhCF
Page 2 of 14
3
at 115 °C for 24 hours afforded 1-tert-butyl-3-
1
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
10% (NNN)ZrCl
C6D6, 55 oC, 2 h
phenylcarbodiimide (2a) in 59% yield (Table 1, entry 1).
The more electron-deficient catalysts 1b, 1c, and 1d, which
we previously found to be more active for Ti redox
RN3
+
tBuNC
RN=C=N Bu + N2
t
t
quantitative
R = Ad, Bu
2
0
catalysis, gave yields of 77%, 85%, and 69%, respectively
Table 1, entries 2-4). Given that the yields of reactions with
(NNN)ZrCl
via:
(
MeO
MeO
iPr
iPr
1b-1d were comparable, further reactions were carried out
using 1d because it is cheaper and more stable than 1c, and
easier to synthesize and more soluble than 1b. Increasing
t
N
N
C
N Bu
N
Zr
N
N
Zr
NR
t
the concentration of BuNC from 0.724 M to 0.988 M and
Cl
Cl
using 5 mol % 1d generated 2a in 85% yield (entry 5). In
each entry where tert-butylisocyanide was used, small
amounts of BuNCN Bu (3) were generated, with yields
ranging from 8-13%. The formation of this side product will
be discussed later.
N
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
iPr
(NNN)3-
iPr
(NNN)1-
t
t
MeO
MeO
excess
tBuN3
6
% (BDI)Nb(N Bu)2
t
tBuN=C=NR
+ N2
+
RNC
C6D6, 80 oC, 20 h
R = Cy, Bn, nBu
TON up to 17
Both 2,6-xylylisocyanide and cyclohexylisocyanide gave
poor yields of 2a’ and 2a”, respectively, even after
prolonged reaction times (entries 6-9). These low yields
could be a result of the formation of stable tris(RNC)
adducts (vide infra) or from product inhibition. Reactions of
t
(BDI)Nb(N Bu)2
via:
tBu
Ar
t
Ar N
N Bu
N
N
C
NR
Nb
Nb
t
N
N
PhNNPh with BuNC catalyzed by 1d in the presence of
t
t
N Bu
Ar
N Bu
Ar
approx. 10% of either 2a’ or 2a” resulted in severe rate
inhibition (SI, Figure S55), indicating that the low yields in
entries 6-9 may partially be a result of product inhibition. In
contrast, bulkier 2a exhibits weaker product inhibition (SI,
Figure S54), leading to productive catalysis.
i
Ar = 2,6- Pr2Ph
Figure 1. Examples of catalytic carbodiimide formation
using early transition metals. Top: Redox-active ligands
enable oxidation with a Zr catalyst. Bottom: π-overloading
yields Nb (bis)imidos that are active toward isocyanide
Table 1. Exploration of catalyst and isocyanide scope.a
2
insertion. Both proceed through key  -carbodiimide
10% Ti catalyst
adducts.
PhN=NPh
+
RNC
2
PhN=C=NR
+
RN=C=NR
PhCF3, 115 o
24 h
C
X equiv.
R =
3
Although there are several examples of isocyanide
migratory insertions into high-valent early transition metal
there are only two examples of catalytic
carbodiimide formation (Figure 1). In one case, Heyduk
used a redox-active (tris)amide ligand capable of reversible
reduction from an NNN “quinonate” to an NNN
catecholate on Zr (NNN = bis(2-isopropylamido-4-
methoxyphenyl)amide). A similar approach for catalytic
nitrene carbonylation has been demonstrated by
t
2
a: Bu
Ti catalysts:
2a’: 2,6-Me2Ph
t
5
3–57
1a: py TiCl (N Bu)
imidos,
3
2
2a”: Cy
1
b: py3TiBr2(NPh)
1c: (THF)3TiI2(NPh)
t
1d: [py2TiBr2(N Bu)]2
-
1
3-
3
-
Entr
y
Equiv.
RNC
Ti
cat.
%
%
R
4
7
yield 2 yield 3
tBu
tBu
tBu
1
2
3
2.2
2.2
2.2
2.2
3
1a
1b
1c
1d
1d
59
77
85
69
85
13
8
2
-
Wolczanski using a redox-active diamide-diimine (dadi )
ligand capable of reversible reduction to an ene-tetraamide
4-
2-
i
dadi
ligand (dadi
=
{-CH=N(1,2-C
). In the second case, Arnold and Bergman have
accomplished catalytic carbodiimide formation using a π-
6 4 2
H )N(2,6- Pr -
9
58
6 3 2
C H )}
4b
tBu
10
12
t
loading strategy with (BDI)Nb(N Bu)
2
(BDI
=
2,6-
5b
tBu
4
6
diisopropylphenyl-β-diketiminate), where the two imido
ligands competitively π-donate into the Nb center,
providing a more reactive imido. Both examples of catalytic
carbodiimide formation use azides as the terminal oxidant
2,6-
6b
3
1d
<1d
-
Me
2
Ph
2
,6-
2
7b,c
8b
3
3
3
1d
1d
1d
3d
-
-
-
(
Figure 1). Herein, we report that catalytic nitrene transfer
Me Ph
from diazenes to isocyanides can be achieved with simple Ti
imido halide complexes, demonstrating that the redox-
noninnocence of the substrates and products are enough to
stabilize otherwise high-energy low-valent intermediates.
Cy
Cy
<1d
<1d
9b,c
RESULTS AND DISCUSSION
a: Reaction conditions: 0.165 mmol PhNNPh, 0.362 mmol RNC (entries
1-4) or 0.495 mmol RNC (entries 5-9), 0.0165 mmol Ti catalyst (10 mol
t
We first explored the reaction of BuNC with PhNNPh under
1
%
). Yields were determined via No-D H NMR with respect to 1,3,5-
catalytic conditions similar to those in our previous Ti-
trimethoxybenzene as an internal standard. b:
5
mol
%
19
t
catalyzed nitrene transfer reactions (Table 1). Reaction of
[py TiBr (N Bu)] (10 mol% [Ti]). c: Reaction time = 144 h. d: Yields
2 2 2
2
.2 equiv. tert-butylisocyanide with PhNNPh and 10 mol %
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ACS Catalysis
were determined via GC-FID with respect to 1,3,5-trimethoxybenzene
as an internal standard.
adamantyl group, the stronger coordinating ability of AdN3
compared to PhNNPh may also promote productive
catalysis through outcompeting product inhibition or
isocyanide coordination.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
6 5
Next, the azoarene scope was investigated in C D Br, which
gave a slightly lower NMR yield of 2a than when using
PhCF . Table 2, entry 1). A variety of electronically donating
and withdrawing diazenes were examined, most of which
provided the corresponding 1-tert-butyl-3-
arylcarbodiimides 2a-2f in good yields (Table 2, entries 1-
,). 4,4’-bis(trifluoromethyl)-azobenzene provided 2f
3
t
Table 3. [py
synthesis from AdN .
3
2
TiBr
2
(N Bu)]
2
(1d)-catalyzed carbodiimide
a
N3
6
5% 1d
successfully, albeit only in 43% yield (Table 2, entry 6).
Notably, this same diazene is completely unreactive in Ti-
catalyzed nitrene transfer to alkynes for pyrrole
+
1.5 RNC
AdN=C=NR + N2
PhCF3, 115 o
C
4a - 4c
24 h
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
19
formation. Several ortho-substituted derivatives were
explored as well, yielding the corresponding 1-tert-butyl-3-
arylcarbodiimides in good yields for o-Me (2g) and o-Et
(2h) (Table 2, entries 7-8), though the yield decreased
Entry
R
Product
4a
% yield
63
1
2
3
tBu
Cy
i
notably with bulkier o- Pr substitution (2i, Table 2, entry 9).
4b
55
t
t
Again, BuNCN Bu (3) was generated in all reactions, with
2
2,6-Me Ph
4c
86
yields ranging from 6-11%. These reactions can also be
t
easily scaled: a 1 g scale reaction of azobenzene with BuNC
a: Reaction conditions: 0.280 mmol AdN
3
, 0.420 mmol RNC, 0.0140
mmol 1d (5 mol %) in 1 mL PhCF . Isolated yields.
3
resulted in 72% isolated yield of 2a (Table 2, entry 1).
Although 1,1-insertion of early metal imidos into
t
53–57
Table 2. Diazene scope for [py
catalyzed carbodiimide formation.
2
TiBr
2
(N Bu)]
2
(1d)-
isocyanides has been demonstrated previously,
we next
a
wanted to explore the mechanism of this reaction in more
detail to understand how ligands, substrates, and products
could synergistically affect the Ti redox process. Compared
to previous catalytic examples where overt redox-
t
2
ArN=C=N Bu
N
Y
Ar
2a - 2i
5
% 1d
N
tBuNC
+
3
+
C D Br, 115 oC
47
6
5
t
t
noninnocent ligands were used to promote catalysis, here
X
BuN=C=N Bu
2
4 h
3
the critical factors promoting redox catalysis are less clear.
Same excess kinetic measurements indicated both product
inhibition and catalyst decomposition over the course of the
reaction, precluding a full kinetic investigation (SI, Figures
S53 and S54). Further preliminary kinetic studies indicated
very complex and intractable reaction orders. Thus, we
turned to DFT calculations to give further insight into the
potential speciation and energetics of catalysis.
Entr
y
Product
% yield
X
Y
% yield 3
2
2a
79
72%)
1
H
H
9 (3%)c
c
(
2
3
Me
F
H
H
2b
2c
2d
2e
2f
75
11
8
70
4
Cl
H
70
8
5
OCF
3
H
71
7
6b
7
CF
H
H
44
7
3
Me
Et
iPr
2g
2h
2i
69
8
8
H
70
6
9
H
42
6
t
a: Reactions conditions: 0.165 mmol PhNNPh, 0.495 mmol BuNC,
t
0
2 2 2 6 5
.00825 mmol [py TiBr (N Bu)] (5 mol %) in 0.5 mL C D Br. Yields
1
were determined via H NMR with respect to 1,3,5-trimethoxybenzene
as an internal standard. b: 8 h reaction time; significant product
decomposition occurs between 8 and 24 h. c: Isolated yield, reaction
t
conditions: 5.49 mmol PhNNPh, 16.5 mmol BuNC, 0.275 mmol
Figure 2. Proposed mechanism for carbodiimide formation
using isocyanides and diazenes catalyzed by 1d.
t
[py
2
TiBr
2
(N Bu)]
2
(5 mol %) in 20 mL PhCF
3
at 115 °C for t = 40 h.
Given the product inhibition seen with less bulky
isocyanides, we envisioned that increasing the steric bulk of
the nitrene source would allow for productive catalysis.
The results of reactions of adamantyl azide (AdN ) with
3
various isocyanides catalyzed by 1d are shown in Table 3.
Combined experimental and DFT results are consistent with
the mechanism of 1-tert-butyl-3-phenylcarbodiimide (2a)
formation proposed in Figure 2. First, an isocyanide
coordinates to the Ti imido, which then undergoes a 1,1-
migratory insertion into the Ti-imido bond, generating an
η -carbodiimide. Next, substitution of the carbodiimide
ligand with PhNNPh occurs via either an associative or
Here, the less sterically encumbered CyNC and 2,6-xylylNC
(
Table 3, entries 2-3) also give satisfactory yields of the
2
unsymmetric carbodiimide products 4b and 4c,
respectively. In addition to the steric encumberance of the
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dissociative manner to give the product carbodiimide and
Page 4 of 14
1
py
-3.7
0.0
-5.5
19.8
6.7
--
44.5
25.8
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
an η -hydrazido, which disproportionates
2
19,59–62
to
regenerate the Ti imido and 0.5 equiv. PhNNPh. The
formation of BuNCN Bu via retro-1,1 insertion will be
discussed later (vide infra).
2 py
-1.6
23.2
12.8
30.1
t
t
1
py
and
-2.6
1.7
24.5
13.9
26.2
22.1
A significant challenge in studying these simple Ti halide
catalytic systems is the potential for speciation. Previous
DFT analysis of Ti-catalyzed nitrene transfer in the [2+2+1]
synthesis of pyrroles showed large energetic changes based
t
1 BuNC
1 tBuNC 7.8 -0.08
29.3
29.3
11.0
15.6
26.8
23.8
38.4
21.4
2 tBuNC 2.3
6.1
2
0
on ligand speciation.
Here, pyridine, isocyanide,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
azobenzene, or carbodiimide could potentially act as a
spectator ligand in some (or all) steps of catalysis. As a
result, we undertook a study of the effect of various ligand
combinations across the entirety of the reaction profile for
the synthesis of 2a from BuNC and PhNNPh (Figure 3). The
6 spectator ligand combinations investigated were a single
-
PhNNPh
4.6
0.03
20.7
4.0
6.6
-11.4
t
The ancillary ligand combination significantly impacts the
energetics of catalysis (Table 4). A key observation is that
many possible ligand combinations are close in energy, and
thus multiple species may be participating in catalysis. Most
importantly, however, is that coordination of azobenzene
(Figure 4, orange) significantly lowers the barrier for all
steps of catalysis—in particular, there is a strong effect on
product release. As will be discussed below, this is due to
two factors: (1) azobenzene is not a strong -donor ligand,
resulting in an electron-deficient Ti that facilitates 1,1-
migratory insertion in TS1; and (2) azobenzene is a strongly
-accepting ligand and can directly accept the pair of
electrons in TS2 that were formerly backbonding into the
C=N * of the η -carbodiimide ligand, cirvumenting the
formation of a discrete Ti species proceeding from TS2 to
IM3. This -acceptor character can be observed in the
computed azobenzene N-N bond lengths: from IM0 through
TS2, the N-N bond length of 1.25 Å is consistent with an N=N
double bond, but upon carbodiimide dissociation it is
lengthened to 1.40 Å in IM3.
pyridine (red), two pyridines (blue), pyridine/isocyanide
(
green), 1 isocyanide (grey), two isocyanides (black), and
azobenzene (orange). In all possible ligand combinations,
pathways matching the steps shown in Figure 2 were found
to be lowest energy.
C-Nbond
formation
product
release
L=
pyridine
pyridine
IM3
1
2
Ph
N
1pyridine
BuNC
BuNC
t
2
N Bu
1
L
C
Ti
1
II
Br
Br
2 BuNC
azobenzene
TS2
TS1
Ph
N
20.7
Ph
N
IM2
L
Ti
t
N Bu
C
Br
Br
L
Ti
Br
Br
IM0
IM1
6.6
4
Ph
.0
0.03
N
t
N Bu
L
C
Ti
-4.6
Br
Br
-
11.4
Ph
N
t
[TiII]
N Bu
L
C
Ti
Br
Br
Figure 3. Free energy (kcal/mol) reaction profiles for
various ligand combinations for isocyanide amination
t
catalysis leading to 2a from BuNC and PhNNPh. Free
energy values listed are for L = azobenzene. All intermediate
and transition state energies are relative to the IM0
intermediate bearing two pyridine ancillary ligands. For all
other free energy values, see Table 4.
Table 4. Free energies (kcal/mol) for intermediates and
transition states of various ligand combinations shown in
Figure 3. The lowest-energy species for each
intermediate/transition state is bolded and italicized.
IM0 IM1
TS1
IM2
TS2
IM3
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A:C-Nbondformation
B:productrelease
Natural Bond Order (NBO)65,66 analysis further supports the
importance of the azobenzene -acceptor character.
1
2
3
4
5
6
7
8
9
IM1
IM2
Ti-N
σ-bond
Previously, we have benchmarked formal Ti oxidation
Ti-N
π-bond
2
states by examining the occupancy of the Ti 3dz orbital
through NBO analysis, where occupancies closer to 0.4
IV
correlate well to formal Ti , and occupancies closer to 0.6
II 20
2
correlate well to formal Ti . The 3dz occupancies of all
intermediate ligand combinations, as well as for the 1,1-
insertion and product dissociation transition states TS1 and
TS2, is presented in Table 5. Here, structures with weaker
delocalized
N lone pair/
Ti-N π-bond
Ti-C
σ-bond
C-N
π-bond
2
TS1
TS2
donors (pyridine, azobenzene) have lower 3dz occupancy
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
in TS1 (correlating to a more oxidized Ti metal center) and
thus undergo more facile 1,1-insertion with isocyanide.
Additionally, structures with -accepting ligands
2
(
isocyanide, azobenzene) have lower 3dz occupancy in
TS2, making ligand loss more facile as the building charge
II
on the Ti fragment can be simultaneously buffered by the
-accepting ligands. Importantly, Ti remains significantly
more oxidized when azobenzene is a ligand because the
weak N=N  bond is an excellent -acceptor—in fact, by
IM2
IM3
new N
lone pair
new N-C
σ-bond
new N
lone pair
2
NBO analysis of the 3dz occupancy, Ti remains close to the
+
4 oxidation state throughout catalysis when azobenzene is
C-N
π-bond
bound.
new
delocalized
Ti-N π-bond
Azobenzene’s synergistic “redox-neutral” buffering of
electron density serves the same purpose as an ancillary
redox noninnocent ligand, and was previously proposed by
67,68
Wang for several other Ti redox catalytic reactions.
Figure 4. (A) IBOs of the reactant (IM1), transition state
TS1), and product (IM2) in the first step of BuNC
t
Interestingly, previous computations for pyrrole product
(
II
release from Ti in the related catalytic formal [2+2+1]
amination with PhNNPh. The IBOs show the Ti-N -bond
forming a new N-C  bond (blue orbital) and the C-N -bond
forming a new N lone pair (red orbital). (B) IBOs from the
intermediate (IM2), transition state (TS2), and final
dissociated product (IM3). The IBOs show the Ti-N  bond
breaking to form a new N lone pair (purple orbital), the Ti-
C  bond breaking to form a new C=N -bond (orange
orbital), and a delocalized N lone pair/Ti-N -bond
transferring through the titanium to form a new Ti-N -
bond with azobenzene (green orbital).
synthesis of pyrroles does not require this type of
2
0
buffering. While the reasons for this difference are
currently unclear, a contributing factor could be the
stability of the released product: in the case of pyrrole
release, reformation of the aromatic ring (loss of Ti-pyrrole
II
backbonding) could be enough of a driving force to eject Ti
even in the absence of azobenzene as a redox buffer; on the
contrary, in carbodiimide synthesis (and the related
68
carboamination reactions calculated by Wang ), formation
of a single C=N  bond is likely not enough of a driving force
II
to eject free Ti . Nonetheless, it is also important to note that
Next, intrinsic bond orbital (IBO) analysis was carried out
on the reaction pathway with ligated azobenzene (Figure 4).
IBOs provide a connection between DFT calculations and
the curved arrow formalism
electron flow during a reaction. For the 1,1-insertion step
Figure 4a, IM1 proceeding through TS1 to IM2) an
electron pair on one of the Ti≡NR -bonding orbitals (blue)
attacks the isocyanide C=N * orbital, forming the new C=N
bond and pushing an electron pair on to N (red). This type
of Ti≡N  to C-N  bond-forming event is reminiscent of our
the other (non-azobenzene bound) pathways are low
enough in energy (~25 kcal/mol, Table 4) that they also
may contribute to the overall reaction rate to some extent,
and that azobenzene is not absolutely critical for catalysis.
6
3,64
, and give a simple view of
(
2
Table 5. NBO-derived Ti 3dz occupancies of calculated
intermediates and transition states from Figure 3. Values
IV
closer to 0.4 are assigned as formally Ti while closer to 0.6
II
(
bold, italics) are assigned as formally Ti .
20
recent report on [2+2+1] pyrrole formation, where C-N
IM0
IM1
TS1
IM2
TS2
IM3
bond formation occurs through
electrocyclization event. For the product release step
Figure 4b, IM2 proceeding through TS2 to IM3), the
azobenzene -acceptor character is very important. Here
TS2 involves 3 critical orbital changes: (1) breaking of the
 orbitals in an
1 py
py
0.32 0.31
0.31 0.31
0.36
0.35
0.45
0.44
--
0.76
0.63
(
2
0.65
t
1 py
and
BuNC-Ti  bond to form the product carbodiimide C=N 
bond (orange), (2) breaking of the Ti=NPh  bond to form a
new  backbond with azobenzene (orange), and (3)
breaking of the Ti-NPh σ-bond to form the carbodiimide N
lone pair (purple).
0.30 0.32
0.36
0.39
0.46
0.45
0.56
0.58
0.62
0.67
1 tBuNC
1 tBuNC 0.32 0.31
ACS Paragon Plus Environment

ACS Catalysis
Page 6 of 14
2 tBuNC 0.31 0.32
PhNNPh 0.31 0.31
0.37
0.35
0.47
0.44
0.57
0.62
0.39
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0.40
Next, we investigated the formation of the “nitrene
t
t
scrambled” BuNCN Bu byproduct 3 that is observed in all
t
reactions with BuNC. Notably, when using catalysts 1b and
t
t
1c (Table 1, entries 2 and 3; Figure 5), BuNCN Bu was still
formed in 8% and 9% yield, respectively. These results
t
t
demonstrate that BuNCN Bu formation is not solely
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
t
generated from stoichiometric reaction of the Bu imido
group of the precatalyst.
t
PhN=C=N Bu
1
0% py3TiBr2(NPh) (1b)
or-
0% (THF)3TiI2(NPh) (1c)
2
a
-
7
7-85%
1
Figure 6. Possible mechanisms leading to formation of Ti
tert-butyl imido moieties responsible for catalytic
production of BuNCN Bu (3).
PhN=NPh
+
1.5 tBuNC
+
PhCF3, 115 o
C
2
4 h
t
t
t
t
BuN=C=N Bu
t
3
no Bu imido from
precatalyst
8-9%
Figure 7 shows the DFT-calculated free energy profiles of
isocyanide metathesis (blue) and carbodiimide metathesis
t
t
Figure 5. Formation of BuNCN Bu (3) using catalytic 1b or
1c demonstrates that this sideproduct is not solely formed
t
(
red) catalyzed by py
2
TiBr
2
(N Bu). In the isocyanide
metathesis pathway (Figure 7, blue), the first steps of the
t
from Ti(N Bu) precatalyst activation.
reaction are identical to productive carbodiimide formation
t
(
Figure 3, IM0 through IM2), where BuNC first coordinates
A process in which the nitrene fragments are formally
scrambled could reasonably occur through either an
isocyanide metathesis or carbodiimide metathesis pathway
Figure 6). In an isocyanide metathesis, a Ti≡NPh imido
undergoes a 1,1-insertion with BuNC to form an  -
carbodiimide. Instead of undergoing ligand dissociation to
liberate the carbodiimide product, the  -carbodiimide
to the Ti≡NPh imido followed by 1,1-insertion of isocyanide
2
into the Ti-imido bond, yielding an  -carbodiimide (IM2).
2
From here, the  -carbodiimide Ti complex rearranges to
(
t
2
the adjacent C=N Bu -bond, resulting in an isomeric  -
carbodiimide structure (IM3-ICM) of almost equal energy
to IM2. IM3-ICM next undergoes rate-determining (27.2
t
2
2
t
kcal/mol) retro-1,1 insertion, yielding a Ti≡N Bu imido with
undergoes retro-1,1 insertion to liberate PhNC and a
a bound PhNC ligand (IM4-ICM), which can dissociate to
t
t
Ti≡N Bu imido, which can react further with BuNC to yield
t
yield the free Ti≡N Bu imido IM5-ICM. In the carbodiimide
t
t
BuNCN Bu (Figure 6, top). In a carbodiimide metathesis
metathesis pathway (Figure 7, red), the starting Ti≡NPh
t
pathway, an equivalent of BuNCNPh product undergoes
[2+2] cycloaddition with a Ti≡NPh imido, ultimately
t
imido IM0 undergoes [2+2] cycloaddition with PhNCN Bu,
yielding the guanadinate IM2-CM. IM2-CM then undergoes
rate-determining (34.7 kcal/mol) retro-[2+2] cycloaddition
t
liberating PhNCNPh and the Ti≡N Bu imido necessary to
t
t
yield BuNCN Bu (Figure 6, bottom). There is only a single
t
in the opposite manner, yielding the Ti≡N Bu imido IM3-CM
0
46
report of d metal imido promoted isocyanide metathesis.
with the expulsion of PhNCNPh.
6
9–71
On the contrary, there are both stoichiometric
and
7
2–75
0
catalytic
examples of carbodiimide metathesis with d
metal imidos, although dihalide Ti imidos have been shown
to be poor catalysts for this transformation.
Experimentally, we have not observed either of the
expected byproducts of these pathways, PhNC or PhNCNPh,
in significant quantities under catalytic conditions, although
control experiments indicate that both pathways may be
operable (SI, Figure S52).
7
4
ACS Paragon Plus Environment

Page 7 of 14
ACS Catalysis
environment around Ti is somewhat ambiguous, showing
isocyanidemetathesis
carbodiimidemetathesis
Ph
NPh
1
2
3
4
5
6
7
8
9
similar barriers for several possible ligand combinations.
Alternatively, the carbodiimide dissociation step likely
proceeds while Ti is bound to a diazene ligand in an overall
associative ligand exchange process, given that the barrier
for carbodiimide dissociation is significantly lower with this
combination than all other possibilities probed. The low
N
C
N
[Ti]
t
Bu
[Ti] = TiBr2py2
TS2-CM
4.7
3
PhN
C
t
N Bu
[Ti]
Ph
NPh
C
N
TS3-ICM
27.2
TS1
23.2
[Ti]
N
t
Bu
2
barrier for azobenzene-bound Ti to dissociate an  -
TS1-CM
2.6
carbodiimide is a result of the azobenzene acting as a redox
buffer, immediately accepting a pair of electrons upon
2
2
dissociation of the  -carbodiimide and circumventing a
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
II
IM2
2.8
Bu
discrete Ti intermediate. In addition, the unanticipated
1
N
t
t
formation of the symmetrical carbodiimide BuNCN Bu, a
byproduct observed during catalysis, was proposed to form
via a rare isocyanide metathesis mechanism evidenced
through both experiment and DFT analysis. This is only the
second report of an isocyanide metathesis in the literature.
Importantly, this study indicates that certain substrates can
participate in synergistic backbonding/redox buffering to
significantly reduce the barrier for overall redox processes,
which may provide further avenues for exploring early
transition metal redox catalysis outside of more classical
redox noninnocent ligand designs.
[Ti]
IM3-ICM
13.0
+
PhNCNPh
PhN
Ph
IM3-CM
5.0
C
N
N Bu
t
[Ti]
IM4-ICM
[
Ti]
6
.7
IM2-CM
.2
Ph
IM0
4
N
C
Ph
NPh
IM5-ICM
0.42
Bu
0.0
N
C
IM1
-1.6
[
Ti] N Bu
t
[Ti]
N
Bu
N
[
Ti]
+
PhNC
EXPERIMENTAL SECTION
Figure 7. Free energy profiles of possible mechanisms
leading to formation of Ti tert-butyl imido moieties
responsible for catalytic production of BuNCN Bu (3). Blue:
isocyanide metathesis with BuNC. Red: carbodiimide
metathesis with PhNCN Bu (2a). All intermediate and
transition state energies are relative to the IM0
intermediate bearing two pyridine and two bromide
ancillary ligands.
General Considerations. All chemical manipulations were
carried out in a glovebox under a nitrogen atmosphere.
Azobenzene (TCI America) was purified via flash
t
t
t
t
chromatography (hexanes), finely ground, and dried in
19,20
vacuo prior to use. Substituted azobenzenes,
tert-
2,6-
76
77
butylisocyanide,
dimethylphenylisocyanide,
cyclohexylisocyanide,
78
1-tert-butyl-3-
1-(2,6-dimethylphenyl)-3-
1-cyclohexyl-3-
and 1,3-diphenylcarbodiimide
7
8
8
9
0
0
phenylcarbodiimide,
phenylcarbodiimide,
phenylcarbodiimide,
Comparing the scrambling pathways, the rate-determining
barrier for isocyanide metathesis (TS3-ICM, 27.2 kcal/mol)
is significantly lower than for carbodiimide metathesis
(TS2-CM, 34.7 kcal/mol), indicating that isocyanide
metathesis is the likely major pathway of scrambling. The
80
were prepared following literature procedures. 2,6-
Dimethylphenylisocyanide and 1-azidoadamantane
(Millipore-Sigma) were dried in vacuo overnight prior to
use, and stored at -35 °C in the glovebox. Liquid isocyanides
and carbodiimides were freeze-pump-thaw degassed three
times, brought into the glovebox, passed through activated
computed
unsymmetrical carbodiimide formation (Table 4, TS2, 2 py,
0.1 kcal/mol) is slightly higher than TS3-ICM for
rate-determing
step
for
productive
3
t
81
isocyanide metathesis. However, these calculations were
performed with 2 ancillary pyridine ligands, and upon
ligand exchange to azobenzene the productive redox
pathway to unsymmetrical product is much lower in energy
basic alumina, and stored at -35 °C. py
3
TiCl
were prepared following literature
Br was prepared according to literature
, vacuum
transferred, and then filtered through activated basic
alumina. CH Cl , hexanes, pentane, THF, C CH , and PhCF
2
(N Bu) and
1
7
(THF)
procedures. C
3 2
TiI (NPh)
6
D
5
82
procedure. NMR solvents were dried over CaH
2
(
Table 2, TS2, 1 azobenzene 6.6 kcal/mol) Since isocyanide
and carbodiimide metatheses are redox neutral pathways,
coordination of azobenzene will not significantly change the
barrier for TS3-ICM or TS2-CM (by analogy, as seen in
Figure 3, and Table 4, the barrier for TS1 changes < 5
kcal/mol moving from py ligation to azobenzene ligation).
2
Thus, productive catalysis will in most cases kinetically
outcompete isocyanide metathesis if azobenzene is present,
2
2
6
H
5
3
3
were dried on a Pure Process Technology solvent
purification system.
1H, 13C, and 19F NMR spectra were recorded on Bruker
Avance 400 MHz, Bruker Avance III 500 MHz, or Bruker
Avance III HD 500 MHz spectrometers. Chemical shifts are
t
t
reported with respect to residual protio-solvent impurity
accounting for the low yields of the symmetrical BuNCN Bu
byproduct.
1
for H (s, 7.26 ppm for CHCl
3
; s, 7.16 ppm for C
HBr), solvent carbons for
; t 128.08 ppm for C ) and
COOH for F (s, -76.6 ppm in CDCl ). No-D reactions in
PhCF were referenced to 1,3,5-(OMe) (s, 6.13 ppm for
). For quantification of product yields with respect to
1,3,5-(OMe) , spectra were collected at a delay time =
30, acquisition time = 5, and number of scans = 4. GC
6 5
D H; s 7.30
6 4
for most deshielded shift for C D
13
In conclusion, we have demonstrated that catalytic nitrene
transfer to isocyanides using diazenes or azides can be
accomplished with the simple Ti imido halide complex
. DFT analysis of the reaction profile
suggests that during the initial steps of isocyanide
coordination to Ti and 1,1 migratory insertion, the ligand
C (t, 77.16 ppm for CDCl
3
6 6
D
19
CF
3
3
3
3 6 3
C H
t
[Br
2
Ti(N Bu)py
2
]
2
6 3
C H
3 6 3
C H
ACS Paragon Plus Environment

ACS Catalysis
chromatographs were collected on Agilent 7890B GC MHz, CDCl
Page 8 of 14
, 25 °C, δ, ppm): 9.13 (br s, 4H, py-H), 8.89 (br s,
3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
system equipped with the HP-5 column (30 m, 0.32 mm,
0.25 µm, 7 inch cage), an oxidation-methanation reactor
(Polyarc® System, Activated Research Company) and a FID
2H, py-H), 7.83 (t, J = 7.2 Hz, 2H, py-H), 7.72 (br s, 1H, py-H),
7.36 (t, 4H, J = 6.2 Hz, py-H), 7.29 (br s, 2H, py-H), 7.07-7.08
(m, 4H, Ar-H), 6.82 (m, 1H, Ar-H). C NMR (101 MHz, CDCl ,
3
1
3
8
3,84
detector for quantitative carbon detection.
X-ray data
25 °C, δ, ppm): 152.1, 151.4, 138.9, 137.5, 124.2, 124.0,
were collected using Bruker Photon II CMOS
a
122.7.
diffractometer for data collection at 100(2) K using Mo Kα
t
radiation (normal parabolic mirrors). The data intensity
Synthesis of [py
2
TiBr
2
(N Bu)]
2
(1d). TiBr (3.00 g, 8.16
4
8
5
was corrected for absorption and decay (SADABS). Final
cell constants were obtained from least-squares fits of all
measured reflections and the structure was solved and
2 2
mmol, 1 equiv.) and 60 mL CH Cl were added to a 200 mL
round bottom flask containing a Teflon stir bar in an N2
glove box. The flask was sealed with a rubber septum and
cooled to -35 °C. Then, tert-butylamine (3.76 g, 51.4 mmol,
6.3 equiv.) was added slowly. The reaction was sealed with
a rubber septum and allowed to stir at room temperature
for 4 h. The reaction mixture was filtered over Celite to
remove the resulting precipitate and rinsed with CH Cl
until the filtrate became colorless (approximately 50 mL).
The filtrate was transferred to a clean 200 mL round bottom
flask containing a Teflon stir-bar. Pyridine (2.65 g, 33.5
mmol, 4.1 equiv.) was then added, and the flask was sealed
with a rubber septum and allowed to stir at room
temperature overnight. Volatiles were removed in vacuo,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
8
6
refined using SHELXL-2014/7.39.
All non-hydrogen
atoms were refined with anisotropic displacement
parameters. Details regarding refined data and cell
parameters are available in Table S1. CCDC entry 1923119
contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge via http://
2
2
www.ccdc.cam.ac.uk/conts/retrieving.html,
Cambridge
Crystallographic Data Center, 12 Union Road, Cambridge
CB2 1EZ, United Kingdom, fax: (+44) 1223-336-033, or e-
mail:deposit@ccdc.cam.ac.uk.
Computational Details. Geometry optimizations were
and the reaction mixture was suspended in hot PhCH
approximately 150 mL), filtered over Celite, and rinsed
with additional hot PhCH until the filtrate grew clear in
3
color (approximately 150 mL). Volatiles were removed in
vacuo, and the resulting solid was dissolved in minimal hot
3
performed using the Gaussian09 program version e01.8
7
(
8
8
Calculations were run using the restricted M06 functional
89
at the 6-311G(d,p) basis set with a superfine grid, and the
90
SMD solvation model for PhCF
3
with ε
= 9.18.
Thermodynamic corrections were calculated with
frequency analysis to be either minima (with no imaginary
frequencies) or transition states (with one imaginary
frequency) with temperature corrections at 388.15 K, and
2 2
CH Cl , cooled to room temperature, then layered with an
equal volume of hexane and allowed to cool to -35 °C for
several days to afford 2.78 g of 1d as an orange crystalline
solid (78%). X-ray quality crystals were grown via vapor
-1
the removal of frequencies smaller than 50 cm . The NBO
diffusion of pentane into a CH
2
Cl
temperature overnight. H NMR (400 MHz, CDCl
ppm): 9.31 (d, 4H, J = 4.9 Hz, py-H), 7.86 (t, 2H, J = 7.5 Hz,
2
solution of 1d at room
6
5,66
calculations utilized the NBO 5.G
program. The
1
3
, 25 °C, δ,
procedure used in this study for generating the d orbital
9
1
occupation numbers is outlined in Webster et. Al. The
13
py-H), 7.43 (t, 4H, J = 6.5 Hz, py-H), 1.04 (s, 9H, -C(CH
NMR (101 MHz, CDCl , 25 °C, δ, ppm): 152.1, 138.8, 124.1,
4.6, 30.6.
3 3
) ). C
9
2
IBOs were generated in MOLPRO using the the restricted
3
8
8
89
M06 functional at the 6-311G(d,p) basis set and where
7
9
3
visualized using VMD 1.9.3.
General Procedure for Reaction Optimization: 0.5 mL of
a stock solution of PhCF containing 0.330 M azobenzene
(30.1 mg, 0.165 mmol), 0.729 M tert-butyl isocyanide (30.3
mg, 0.365 mmol), and 0.0326 M 1,3,5-(OMe) (2.74 mg,
.0163 mmol) as an internal standard was prepared and
Synthesis of py
prepared in similar fashion to py
1.09 g, 2.97 mmol, 1 equiv.) and 10 mL CH
to a 20 mL scintillation vial containing a Teflon stirbar in an
glovebox. (TMS) NPh (0.704 g, 2.97 mmol, 1 equiv.) in 8
3 2
TiBr (NPh) (1b). The title compound was
3
94
3
TiBr
2
(N-p-tolyl). TiBr4
(
2
Cl were added
2
3 6 3
C H
0
N
2
2
used for NMR tube reactions related to the reaction
2
mL CH Cl
2
was then slowly added to the mixture. The
optimization reactions. In an N glovebox, the requisite Ti
2
reaction was sealed with a Teflon screw cap and stirred for
0.5 h at 60 °C, then at room temperature for 1.5 h. The
reaction mixture precipitated at this point and was filtered
on a sintered glass frit. The precipitate was rinsed with 20
mL hexanes and dried in vacuo. The solid was then dissolved
catalyst (10 mol % in Ti, 0.0165 mmol in Ti) was added to
an NMR tube and was dissolved with 0.5 mL of the stock
solution. The NMR tube was sealed, then wrapped with
electric tape and parafilm, and an initial t = 0 No-D NMR
spectrum was taken. The reaction was then heated in an oil
bath for 24 h at 115 °C. After 24 h, a final No-D NMR
spectrum was taken. Yields were determined by referencing
to the internal standard, 1,3,5-(OMe) C H .
using approximately 10 mL CH
stirred at room temperature for 0.5 h. Next, the resulting
solution was filtered through Celite and rinsed with CH Cl
2 2
Cl and 5 mL pyridine and
2
2
3
6
3
until the filtrate became colorless (approximately 50 mL).
The filtrate was then layered with 40 mL hexanes and
cooled to -35 °C overnight to afford 1b as dark brown
crystals. Upon rinsing the resulting complex with hexanes,
a yellow-brown powder was obtained. The resulting
powder was dried in vacuo at 40 °C for 2 days, affording 825
mg of 1b (52%). Elemental analysis was not attempted, as
complex decomposition through pyridine loss would occur
General Procedure for Diazene Scope: 0.5 mL of a stock
t
6 5 2 2 2
solution of C D Br containing 0.0165 M [py TiBr (N Bu)]
(1d, 7.2 mg, 0.00824 mmol, 10 mol % in Ti), 0.986 M tert-
butyl isocyanide (41.0 mg, 0.493 mmol), and 0.0359 M
1,3,5-(OMe)
standard was prepared and used for NMR tube reactions
related to the diazene scope. In an N glovebox, the requisite
diazene (0.165 mmol) was added to an NMR tube and was
3 6 3
C H (3.02 mg, 0.0180 mmol) as an internal
2
1
under prolonged drying on the vacuum line. H NMR (400
ACS Paragon Plus Environment

Page 9 of 14
ACS Catalysis
dissolved with 0.5 mL of the stock solution. The NMR tube
Chem. 2014, 58, 225–302.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
was sealed, then wrapped with electric tape and parafilm,
1
and an initial t = 0 H NMR spectrum was taken. The reaction
(6)
(7)
Roizen, J. L.; Harvey, M. E.; Du Bois, J. Metal-
Catalyzed Nitrogen-Atom Transfer Methods for the
Oxidation of Aliphatic C-H Bonds. Acc. Chem. Res.
2012, 45, 911–922.
was then heated in an oil bath for 24 h at 115 °C. After 24 h,
1
a final H NMR spectrum was taken. Yields were determined
3 6 3
by referencing to the internal standard, 1,3,5-(OMe) C H .
ASSOCIATED CONTENT
Supporting Information
Davies, H. M. L.; Manning, J. R. Catalytic C-H
Functionalization by Metal Carbenoid and Nitrenoid
Insertion. Nature 2008, 451, 417–424.
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The Supporting Information is available free of charge on the
ACS Publications website.
(8)
Du Bois, J. Rhodium-Catalyzed C-H Amination. an
Enabling Method for Chemical Synthesis. Org.
Process Res. Dev. 2011, 15, 758–762.
Full experimental, kinetic, and computational details are
provided in the supporting information (PDF).
(9)
Alderson, J. M.; Corbin, J. R.; Schomaker, J. M.
Tunable, Chemo- and Site-Selective Nitrene
Transfer Reactions through the Rational Design of
Silver(I) Catalysts. Acc. Chem. Res. 2017, 50, 2147–
2158.
AUTHOR INFORMATION
Corresponding Author
*
(I.A.T.) E-mail: itonks@umn.edu
*
(J.D.G.) E-mail: jgoodpas@umn.edu
(10)
Lu, H.; Zhang, X. P. Catalytic C-H
Functionalization by Metalloporphyrins: Recent
Developments and Future Directions. Chem. Soc.
Rev. 2011, 40, 1899–1909.
ACKNOWLEDGMENT
Financial support was provided by the National Institutes of
Health (1R35GM119457), and the Alfred P. Sloan Foundation
(11)
Che, C.-M.; Lo, V. K.-Y.; Zhou, C.-Y.; Huang, J.-S.
Selective Functionalisation of Saturated C-H Bonds
with Metalloporphyrin Catalysts. Chem. Soc. Rev.
2011, 40, 1950–1975.
(
I.A.T. is a 2017 Sloan Fellow). Instrumentation for the
University of Minnesota Chemistry NMR facility was supported
from a grant through the National Institutes of Health
(
S10OD011952). X-ray diffraction experiments were
performed with a diffractometer purchased through a grant
from NSF/MRI (1229400) and the University of Minnesota. We
acknowledge the Minnesota Supercomputing Institute (MSI) at
the University of Minnesota and the National Energy Research
Scientific Computing Center (NERSC), a DOE Office of Science
User Facility supported by the Office of Science of the U.S.
Department of Energy under Contract No. DE-AC02-
(12)
Fantauzzi, S.; Caselli, A.; Gallo, E. Nitrene Transfer
Reactions
Mediated
by
Metallo-Porphyrin
Complexes. Dalt. Trans. 2009, 0, 5434–5443.
(13)
Wolczanski, P. T. Activation of Carbon-Hydrogen
Bonds via 1,2-RH-Addition/-Elimination to Early
Transition Metal Imides. Organometallics 2018, 37,
0
5CH11231, for providing resources that contributed to the
results reported within this paper.
5
05–516.
(
14)
15)
Hazari, N.; Mountford, P. Reactions and
Applications of Titanium Imido Complexes. Acc.
Chem. Res. 2005, 38, 839–849.
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