A Dinickel Catalyzed Cyclopropanation without the Formation of a Metal Carbene Intermediate

Article abstract of DOI:10.1002/anie.202011602

(NDI)Ni₂ catalysts (NDI=naphthyridine-diimine) promote cyclopropanation reactions of 1,3-dienes using (Me₃Si)CHN₂. Mechanistic studies reveal that a metal carbene intermediate is not part of the catalytic cycle. The (NDI)Ni₂(CHSiMe₃) complex was independently synthesized and found to be unreactive toward dienes. Based on DFT models, we propose an alternative mechanism that begins with a Ni₂-mediated coupling of (Me₃Si)CHN₂ and the diene. N₂ extrusion followed by radical C?C bond formation generates the cyclopropane product. This model reproduces the experimentally observed regioselectivity and diastereoselectivity of the reaction.

Full text of DOI:10.1002/anie.202011602

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: A Dinickel Catalyzed Cyclopropanation without the Formation of a
Metal Carbene Intermediate
Authors: Arnab K. Maity, Annah E. Kalb, Matthias Zeller, and
Christopher Uyeda
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202011602
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10.1002/anie.202011602
Angewandte Chemie International Edition
RESEARCH ARTICLE
A Dinickel Catalyzed Cyclopropanation without the Formation of
a Metal Carbene Intermediate
Arnab K. Maity, Annah E. Kalb, Matthias Zeller, and Christopher Uyeda*[a]
[a]
A. K. Maity, A. E. Kalb, M. Zeller, C. Uyeda
Department of Chemistry
Purdue University
560 Oval Dr., West Lafayette, IN 47907 (USA)
E-mail: cuyeda@purdue.edu
Supporting information for this article is given via a link at the end of the document.
Abstract: (NDI)Ni2 catalysts (NDI = naphthyridine–diimine) promote
cyclopropanation reactions of 1,3-dienes using (Me3Si)CHN2.
Mechanistic studies reveal that a metal carbene intermediate is not
part of the catalytic cycle. The (NDI)Ni2(CHSiMe3) complex was
independently synthesized and found to be unreactive toward dienes.
Based on DFT models, we propose an alternative mechanism that
begins with a Ni2-mediated coupling of (Me3Si)CHN2 and the diene.
N2 extrusion followed by radical C–C bond formation generates the
cyclopropane product. This model reproduces the experimentally
observed regioselectivity and diastereoselectivity of the reaction.
made for nitrene transfer reactions using organoazides and
iminoiodinanes.[8]
General Catalytic Mechanism for
DiazoalkaneBased Cyclopropanations
Examples of Isolable Metal
Carbene Complexes
N2
CO2Me
O
R
O
O
O
O
Rh
Rh
O
R
N
R
R
R
R
R
R
O
O
N
[M]
[M]
Me
Me
Ar
Ph
Ph
N
Cu
R
N
R
R
Introduction
Ar
[M]
N2
R
R
Most transition metal catalyzed cyclopropanation reactions
use diazoalkanes as carbene precursors.[1] Mechanistic
proposals for these reactions generally invoke the formation of a
metal carbene complex by catalyst-induced N2 extrusion (Figure
1). It should be noted however that for a majority of catalysts, the
key M=CR2 intermediate cannot be directly observed, let alone
R
Regioselective Dinickel-Catalyzed Cyclopropanation of 1,3-Dienes
i-Pr
Me
N
N
N
Ni
structurally
characterized.[2]
Therefore,
alternative
Me
i-Pr
Ni
i-Pr
N
cyclopropanation pathways that do not involve M=CR2 species
warrant consideration. Additionally, identifying such pathways
may provide new avenues to develop cyclopropanation reactions
with substrate scopes or selectivity properties that are
complementary to existing methods.
i-Pr
SiR3
H
1
(5 mol%)
R3Si
N2
+
22 °C, 6 h, C6H6
i-Pr
Me
i-Pr
Me
N
N
N
N
Catalytic cyclopropanations are mechanistically related to
oxygen-atom transfer reactions. For example, the active oxidant
in a cytochrome P450 catalyzed oxidation is a ferryl porphyrin
radical cation (compound I), generated from the activation of O2.[3]
Abiological variants of this process have also been developed,
often using iodosylarenes or peroxycarboxylic acids as O-atom
sources.[4] Collman and Brauman demonstrated that the
selectivites observed in (TPP)Mn catalyzed alkane C–H
hydroxylations are dependent on the identity of the oxidant.[5] This
observation indicates that the O-atom donor is present in the
selectivity-determining step, effectively ruling out a common M=O
intermediate. In related work, Nam investigated a (TMC)Fe
catalyzed epoxidation and observed that chiral peroxycarboxylic
acid and iodosylarene reagents can induce high levels of
enantioselectivity.[6] Taken together, these and several other
studies[7] show that high-valent M=O species may not always be
true catalytic intermediates, even in cases where they have been
synthesized and characterized. Similar observations have been
N
N
Ni
Ni
Me
i-Pr
Ni
i-Pr
Me
i-Pr
Ni
i-Pr
vs.
H
N
N
N
N
Diazoalkane–diene
coupling pathway
i-Pr
i-Pr
SiMe3
SiMe3
H
Isolable but not
kinetically competent
Figure 1. Metal carbenes are key intermediates in several catalytic
cyclopropanation reactions using diazoalkanes. Dinickel complexes catalyze
regioselective cyclopropanations of 1,3-dienes without generating a Ni2(μ-CR2)
intermediate.
Here, we present a diazoalkane-based cyclopropanation
reaction that does not involve the formation of a metal-bound
carbene intermediate (Figure 1). The reaction being investigated
is
a
(NDI)Ni2 catalyzed (NDI
=
naphthyridine–diimine)
cyclopropanation of 1,3-dienes using (Me3Si)CHN2. The putative
(NDI)Ni2(CHSiMe3) intermediate in this reaction is an isolable
molecule but is unreactive toward 1,3-dienes. On the basis of DFT
1
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10.1002/anie.202011602
Angewandte Chemie International Edition
RESEARCH ARTICLE
modeling studies, we instead propose a mechanism in which the
Ni2(diazoalkane) adduct reacts with the 1,3-diene to generate a
metallacycle. Subsequent N2 elimination and diradical cyclization
yields the cyclopropane product.
could be determined by XRD analysis. Isolated alkenes are
unreactive
using
catalyst
1,
allowing
for
the
monocyclopropanation of a triene to form product 11 in 80% yield.
2,3-Disubstituted dienes and terminally substituted dienes do not
undergo cyclopropanation. Finally, the vinylcyclopropane
products of this reaction are viable substrates for Ni-catalyzed
1,3-rearrangements to form trimethylsilylcyclopentenes.[11] The
rearrangement of 8 exhibits a modest selectivity for activation of
the C–C bond bearing the TMS group, consistent with an α-silicon
effect.[12] An inspection of the crystal structure of 14 reveals that
the C–C(TMS) bond is 0.04 Å longer than the C–C bond that leads
to the minor regioisomer.
Results and Discussion
Catalytic Regioselective Cyclopropanation of 1,3-Dienes
Transition metal catalyzed cyclopropanation reactions of
unsymmetrical 1,3-dienes have previously been investigated, but
they have limited synthetic utility because of their poor
regioselectivity.[9] For example, additions of ethyl diazoacetate to
myrcene (2) yield mixtures of monocyclopropane regioisomers
(ranging from 1.2:1 to 3.1:1) using common cyclopropanation
catalysts such as Rh2(OAc)4, Cu(OTf)2, and Pd(OAc)2.[10]
Presumably, this lack of selectivity reflects the inability of the
metal carbene intermediate to adequately discriminate between
the two double bonds on the basis of subtle differences in their
steric and electronic properties.
SiR3
1
(5 mol%)
R3Si
N2
+
22 °C, 6 h
C6H6
H
SiMe3
SiMe3
SiMe3
O
Me
Me
In light of this precedent, we were surprised to find that (i-
PrNDI)Ni2(C6H6) (1) catalyzes the cyclopropropanation of myrcene
(2) using (Me3Si)CHN2 (3) to afford 4 as a single regioisomer
9
10
8, 88% Yield
(6:1 dr)
, 87% Yield
(5:1 dr)
, 86% Yield
(7:1 dr)
1
within the limits of H NMR detection (Figure 2). After a reaction
SiMe3
SiMe3
SiMe3
O
time of 6 h at 22 °C, product 4 is obtained in 92% yield as a 10:1
ratio of diastereomers. The (NDI)Ni2 catalyst appears to be
uniquely active in this transformation relative to other nickel
catalysts. For example, complexes bearing structurally related
nitrogen-based chelating ligands (5–7) provided no yield of
cyclopropanes under the same set of reaction conditions.
N
N
O
Ts
O
11, 80% Yield
(>20:1 dr)
12, 98% Yield
(1.5:1 dr)
13, 85% Yield
(7:1 dr)
SiMe3
SiPhMe2
O
O
Me
Me
Me
N
N
O
Me
Me
Me
SiMe3
H
1
(5 mol%)
O
+
N2
+
22 °C, 12 h
C6D6
14, 92% Yield
15, 79% Yield
(>20:1 dr)
(>20:1 dr)
92% Yield
10:1 trans/cis
2
3
4 (trans)
SiMe3 4 (cis)
SiMe3
Catalytic Vinylcyclopropane Rearrangement
SiMe3
SiMe3
(Ar = 2,6-diisopropylphenyl)
SiMe3
Ni(COD)2 (5 mol%)
Me
N
IPr (10 mol%)
22 °C, 12 h, pentane
86% Yield
4
< 1% Yield of with:
+
Ar
N
Ar
N
Ar
N
N
Ni
N
Me
Ni
N
Ar
N
Ni
N
Ni
8
16:17
16
17
(4:1
)
N
Ni
COD Ar
COD
COD
(
i-PrNDI)Ni2(C6H6) (1)
Figure 3. Substrate scope studies. Reaction conditions: 1,3-diene (0.2 mmol),
(Me3Si)CHN2 (0.22 mmol), 1 (5 mol%), 22 °C, 6 h, C6H6. For 15, (PhMe2Si)CHN2
was used instead of (Me3Si)CHN2. Isolated yields and dr values were
determined following purification by column chromatography.
i-PrIP)Ni(COD) (5)
(
i-PrDAD)Ni(COD) (6)
(bpy)Ni(COD) (7)
(
Figure 2. Ni2-catalyzed cyclopropanation of myrcene (2) using (Me3Si)CHN2 (3).
Reaction conditions: 2 (0.05 mmol), 3 (0.06 mmol), catalyst (5 mol%), 22 °C, 12
h, C6D6. Yields and trans/cis ratios were determined by 1H NMR integration.
Synthesis of Ni2 Diazoalkane, Carbene, and Diene Complexes
The scope of 2-substituted 1,3-dienes is summarized in
Figure 3. Common polar and non-polar functional groups are
tolerated. The regioselectivity is uniformly high regardless of the
substituent at the 2-position. On the other hand, the
diastereoselectivity is variable and does not display any
straightforward correlation to the steric or electronic properties of
the substituent. Larger silyl groups lead to improvements in
diastereoselectivity (15 vs. 13). The relative stereochemistry of
the major diastereomer was assigned using NOESY experiments,
and product 14 proved to be a crystalline solid whose structure
In order to gain insight into the cyclopropanation mechanism
and the origin of the regioselectivity, we targeted the synthesis of
plausible catalytic intermediates. (Me3Si)CHN2 (3) reacts
stoichiometrically with (i-PrNDI)Ni2(C6H6) (1) to yield a dark brown
crystalline solid that was determined to be the µ-η2:η1 diazoalkane
adduct (18) by XRD analysis (Figure 4b). The N1–N2 distance of
the bound diazo ligand is elongated (1.29(2) Å) relative to the
expected distance for a free diazoalkane (e.g., 1.146(2) Å for
bis(4-dibromophenyl)diazomethane).[13] The C1–N2–N1 angle is
also bent (133(1)°), indicating a reduction in the N1–N2 bond
2
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10.1002/anie.202011602
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RESEARCH ARTICLE
order. The 1H NMR spectrum for 18 displays a well-defined set of
paramagnetically shifted signals spanning a broad chemical shift
window of –79 to +120 ppm. The effective magnetic moment was
calculated to be 2.80µB, consistent with an S = 1 ground state
(Evans method, THF-d8, 298 K).
We next examined the interaction between the Ni2 catalyst
and the 1,3-diene component of the reaction. Upon heating a 1:1
mixture of (i-PrNDI)Ni2(C6H6) (1) and phthalimide-substituted diene
21 at 60 °C in THF for 12 h, quantitative ligand substitution was
observed to form the green diamagnetic diene adduct 20. In the
solid state, the bound diene resides in an s-cis geometry and
binds in a µ-η2:η2 fashion across the two Ni centers (Figure 4d).
The C1–C2 and C3–C4 distances are elongated (1.384(4) Å and
1.368(4) Å, respectively), indicating a significant degree of back-
A
i-Pr
Me
i-Pr
Me
N
N
N
N
N
N
Ni
Ni
C
60 °C
1
bonding from the Ni–Ni bond. In solution, the H NMR spectrum
Me
i-Pr
i-Pr
Me
i-Pr
Ni
i-Pr
Ni
N
N
H
N
N
THF
-N2
for 20 shows no evidence of line broadening, and the number of
signals corresponds to a C1-symmetric species, suggesting that
there are no fluxional processes that interconvert other possible
binding modes of the diene.
i-Pr
H
i-Pr
C
SiMe3
S = 1
18
S = 1
19
Me3Si
B
C
Mechanistic Studies of Cyclopropanation
Ni2
Ni2
Ni1
Ni1
The successful isolation of Ni2 diazoalkane, carbene, and
diene complexes provided us with a unique opportunity to assess
their relevance to the mechanism of the catalytic
cyclopropanation. To determine the primary catalyst resting
states under standard turnover conditions, a reaction between 2
N2
C1
N1
C1
D
and
3
was monitored by 1H NMR spectroscopy. At 73%
conversion of the diene, (i-PrNDI)Ni2(N2CHSiMe3) (18) accounted
for 40% of the total catalyst loading. Isolated complexes 18 and
20 could be used as catalysts in the place of (i-PrNDI)Ni2(C6H6) (1)
and provided 4 in similar yields and diastereoselectivities,
verifying that they are both catalytically competent (Table 1,
entries 1 and 2).
i-Pr
i-Pr
Me
Ni2
N
N
Ni1
C1
N
Ni
C4
C3
Me
i-Pr
Ni
N
C2
i-Pr
S = 0
20
O
N
O
Table 1. Evaluating the catalytic activity of (NDI)Ni2 complexes.[a]
Me
Me
Me
Me
Me
Me
SiMe3
H
catalyst (5 mol%)
+
N2
+
22 °C, 6 h,
C6D6
i-
Figure 4. (a) Conversion of
( (
i-PrNDI)Ni2(N2CHSiMe3) complex (18) to
PrNDI)Ni2(CHSiMe3) (19). (b) Solid-state structure of 18. Selected bond
distances and angles: Ni1–Ni2, 2.627(1) Å; Ni1–N1, 1.74(2) Å; Ni2–N2, 1.80(1)
Å; Ni2–N1 1.90(3) Å; N1–N2, 1.29(2) Å; C1–N2, 1.30(1) Å; C1–N2–N1 133(1)°.
(c) Solid-state structure of 19. Selected bond distances: Ni1–Ni2 2.354(4) Å;
Ni1–C1 1.897(4) Å; Ni2–C1 1.901(5) Å. (d) Solid-state structure of 20. Selected
bond distances: Ni1–Ni2 2.5778(5) Å; Ni1–C1 1.970(2) Å; Ni1–C2 2.062(2) Å;
Ni2–C3 1.982(2) Å; Ni2–C4 1.992(2) Å; C1–C2 1.384(4) Å; C2–C3 1.456(3) Å;
C3–C4 1.368(4) Å.
2
3
4
4
(cis)
SiMe3
(trans)
SiMe3
entry
catalyst
trans:cis
10:1
10:1
–
Yield 4
92%
87%
0%
1
2
3
(
(
(
i-PrNDI)Ni2(N2CHSiMe3) (18)
i-PrNDI)Ni2(diene) (20)
i-PrNDI)Ni2(CHSiMe3) (19)
The diazoalkane adduct 18 is stable in THF solution for >24
h at room temperature. However, upon warming to 60 °C, it
[a] Reaction conditions: 2 (0.05 mmol), 3 (0.06 mmol), catalyst (5 mol%), 22 °C,
6 h, C6D6. Yields and trans/cis ratios were determined by 1H NMR integration.
i-
undergoes N2 extrusion to yield the dark purple
(
PrNDI)Ni2(CHSiMe3) complex (19) (Figure 4a).[14] We[15] and
Hillhouse[16] previously characterized Ni2(μ-CPh2) complexes that
display unsymmetrical structures due to a π-interaction between
one Ni and the Ph substituent. By comparison, 19 lacks this
feature and is pseudo-Cs symmetric in the solid state (Figure 4c).
The number of 1H NMR signals in THF-d8 suggests that this
symmetry is maintained in solution. Like the diazo precursor 18,
19 exhibits an S = 1 ground state, assigned on the basis of its
effective magnetic moment (2.79µB; Evans method, 298 K). DFT
models corroborate this spin state assignment and show one
unpaired electron residing in the NDI π-system and the other in a
Ni2-based orbital.
i-
A
stoichiometric reaction between the isolated
(
PrNDI)Ni2(N2CHSiMe3) complex (18) and diene 21 (1.0 equiv)
yielded cyclopropane 13 in 60% yield (7:1 dr) after 12 h at room
temperature (Figure 5a). As the reaction progresses, the
unreacted diene coordinates to the free (NDI)Ni2 that is being
generated, preventing full conversion from being reached.
Similarly, (i-PrNDI)Ni2(diene) (20) also reacts with (Me3Si)CHN2 (3)
(1.0 equiv) to form a mixture of cyclopropane 13 (30% yield),
unreacted 20 (70% yield), and the (i-PrNDI)Ni2(C6D6) (1) (30%
yield) (Figure 5b). Nearly quantitative yield of cyclopropane 13
was achieved, when the equivalency of (Me3Si)CHN2 (3) was
increased to 3.0 equiv. Thus, experiments under both catalytic
3
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10.1002/anie.202011602
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RESEARCH ARTICLE
and stoichiometric conditions are consistent with 18 and 20 either
lying on the catalytic cycle or being in an off-cycle equilibrium.
We reasoned that (i-PrNDI)Ni2(CHSiMe3) (19) was unlikely to
be an intermediate in the catalytic cyclopropanation, because it is
only generated from the diazoalkane precursor 18 at elevated
temperatures. The catalytic cyclopropanation, by contrast,
reaches full conversion within hours at room temperature. As
further evidence that 19 is not a catalytic intermediate, it does not
react stoichiometrically with diene 21 even after heating at 80 °C
for 12 h (Figure 5c). (i-PrNDI)Ni2(CHSiMe3) (19) is also not
competent as a catalyst for the reaction between 3 and 2 (Table
1, entry 3). Interestingly, when 19 was treated with a less hindered
diene (22), there was still no formation of cyclopropanated
products, but the [4 + 1]-cycloaddition product 16 was obtained in
20% yield. Notably, there are no detectable [4 + 1]-cycloaddition
products formed in any of the catalytic reactions shown in Figure
3.
carbene complex. To identify such a mechanism, DFT
calculations were carried out with the constraint that any
reasonable model would need to rationalize the unusual
regioselectivity observed in the reaction. First, the diazoalkane
and diene adducts were calculated at the BP86/6-311G(d,p) level
of theory (Figure 6). The optimized structures (S1 and S2) were
found to closely reproduce the structures observed
experimentally by XRD (18 and 20). Additionally, the calculations
accurately determined an S = 1 ground state for the diazoalkane
complex and an S = 0 ground state for the diene complex.
A (NDI)Ni2 complex containing both the diazoalkane and
the diene bound to the active site was located (S3). The
diazoalkane lies in the (NDI)Ni2 plane and maintains its µ-η2:η1
coordination mode. The diene binds in an η2-fashion through the
less hindered double bond. The Ni–Ni distance is significantly
elongated to 3.103 Å, suggesting the absence of a direct metal-
to-metal covalent bond. The 1-position of the diene is located in
close proximity to the diazoalkane carbon, and a transition state
(S4) for the coupling could be successfully optimized with an
activation barrier of +16.3 kcal/mol. [17] The resulting metallacycle
(S5) is nearly isoenergetic with S3.
O
A
N
O
21
O
N
From here, we explored several possible concerted
pathways for cyclopropanation where C–C bond-formation occurs
in concert with N2 expulsion. While several such transition states
could be located, they were all found to be prohibitively high in
energy. Instead, an energetically viable stepwise mechanism was
identified. Homolytic cleavage of the C–N bond (S6) has a
calculated activation barrier of +18.0 kcal/mol. The resulting
diradical intermediate (S7) was modeled as an open-shell singlet
with a C-centered α-TMS radical. The other unpaired electron
(anti-parallel spin) is delocalized in the π-system of the NDI ligand.
The triplet spin state for S7 was also considered and found to be
0.6 kcal/mol lower in energy. Given this small energy difference,
any barrier to spin flipping would likely make the open-shell singlet
pathway more favorable. From S7, the final cyclopropane product
is generated from a low-barrier attack of the C-centered radical
on the Ni-bound allyl ligand (+1.0 kcal/mol).
(1.0 equiv)
O
22 °C, 12 h
6D6
i-PrNDI)Ni2(diene)
(
i-PrNDI)Ni2(N2CHSiMe3)
(
+
C
18
20
13
SiMe3
(1.0 equiv)
30% yield
60% yield (7:1 dr)
O
B
SiMe3
N
N2
3
H
O
22 °C, 6 h
-PrNDI)Ni2(diene)
i
-PrNDI)Ni2(diene)
i
(
(
+
C
6D6
20
13
20
SiMe3
(1.0 equiv)
with 1.0 equiv
with 3.0 equiv
70% yield
0% yield
30% yield (7:1 dr)
>99% yield (7:1 dr)
R
C
(1.0 equiv)
In the calculated reaction pathway, the initial coupling step
(S4) is reversible, and the N2 expulsion step (S6) is rate-
determining and irreversible. Therefore, the regioselectivity of the
cyclopropanation is determined by the relative energies of the S6
transition states. Gratifyingly, the transition state leading to the
alternative regioisomer (S6’) is 5.9 kcal/mol higher in energy. In
S6’, the metallacycle is rotated in order to alleviate an unfavorable
steric interaction between the benzyl group and an i-Pr substituent
of the catalyst (Figure 6).
SiMe3
R
80 °C, 12 h
6D6
-PrNDI)Ni2(CHSiMe3
i
)
+
(
C
19
SiMe3
R
(1.0 equiv)
O
13
R =
R =
, 0% Yield
0% Yield
N
O
8, 0% Yield
16, 20% Yield
Because C–N bond cleavage in S6 forms of a planar radical
intermediate, the diastereoselectivity of the cyclopropanation is
not determined in this step but rather in the later recombination
step S8. From S7, single bond rotation would allow for the C–C
bond formation to occur on either face of the radical. The
transition state leading to the alternative diastereomer was
calculated to be 1.1 kcal/mol higher in energy, which is consistent
with the dr determined experimentally for this substrate
combination (6:1 dr; ΔΔG‡ = +1.1 kcal/mol).
Figure 5. Stoichiometric cyclopropanation reactions with (a) 18, (b) 20, and (c)
19. Yields and dr values were determined by 1H NMR integration.
DFT Models for the Ni2-Catalyzed Cyclopropanation
The experimental results described above indicate that
there is a viable cyclopropanation mechanism that proceeds from
the diazoalkane and does not involve the formation of a Ni2
4
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10.1002/anie.202011602
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RESEARCH ARTICLE
N
N
Bn
N
Bn
N
H
SiMe3
Bn
N
Ni
N
N
Ni
N
N
Ni
N
Me3Si
H
N
Ni
N
Ni
N
Bn
Ni
N
N
N
N
Bn
SiMe3
N
N
N
Ni
N
SiMe3
N
N
N
+ 25.4
+ 19.5
S6'
Ni
H
H
S4
N
N
S6
S8'
Ni
N
H
SiMe3
N
Ni
N
S8
N
+ 14.0
regioselectivity
determining step
+ 16.3
N
N
N
Ni
+ 12.9
Ni
+ 11.9
N
N
diastereoselectivity
determining step
N
S1
N
N
N
Bn
Ni
Ni
N
+ 4.1
(S = 1)
H
SiMe3
N
+ 1.5
N
[0 kcal/mol]
S7
H
N
N
Me3Si
N
N
N
N
N
Ni
– 5.5
N
– 5.9
(S = 0)
N
Bn Ni
Ni
Bn Ni
Ni
N
Ni
N
H
N
Me3Si
N
N
N
Bn
N
S2
N
S5
Bn
S3
SiMe3
H
SiMe3
N
N
N
H
Ni
N
Ni
N
S9
metallacycle is rotated to avoid a
Bnꞏꞏꞏi-Pr steric interaction
Origin of regioselectivity:
Major Regioisomer (S6)
Minor Regioisomer (S6')
(+5.9 kcal/mol)
Figure 6. Calculated reaction pathway for the (i-PrNDI)Ni2 catalyzed cyclopropanation to form 8 (BP86/6-311g(d,p) level of DFT). Relative free energies are shown
in kcal/mol. Unless otherwise indicated, all structures correspond to S = 0 spin states. S7, S8, and S8’ were modelled as open-shell singlets with a C-centered α-
TMS radical and the other unpaired electron delocalized in the NDI π-system. Transition states leading to the alternative regioisomer and diastereomer are shown.
catalyzed reaction arise from avoiding
cycloaddition of a M=CR2 and an alkene, the most common
mechanism proposed for other classes of catalysts.
a direct [2 + 1]-
Conclusion
In summary, (NDI)Ni2 catalysts promote cyclopropanation
reactions of 1,3-dienes using (Me3Si)CHN2. Mechanistic studies
rule out (NDI)Ni2(CHSiMe3) (19) as a catalytic intermediate.
Complex 19 is only generated from the diazoalkane adduct 18
when heated for an extended period of time at 60 °C. By contrast,
the catalytic cyclopropanation reaches full conversion within
hours at room temperature. Furthermore, isolated 19 does not
react stoichiometrically with dienes nor does it function as a
cyclopropanation catalyst.
Acknowledgements
This work was supported by the NIH (R35 GM124791). XRD data
were collected using instruments funded by the NSF (CHE-
1625543). C.U. acknowledges support from a Camille Dreyfus
Teacher–Scholar award.
An alternative mechanism was identified using DFT models.
An initial coupling of the bound diazoalkane and the 1,3-diene
forms a metallacyclic intermediate. Homolytic C–N bond cleavage
expels N2 and generates a diradical intermediate that undergoes
rapid recombination to form the cyclopropane product. Notably,
this calculated pathway reproduces the experimentally observed
regioselectivity and diastereoselectivity of the reaction. It also
provides a rationale for the observation that monoalkenes, unlike
1,3-dienes, do not undergo cyclopropanation. Together, these
results show that diazoalkanes can participate in catalytic
cyclopropanation reactions without the generation of a metal
carbene intermediate. The unusual selectivity properties of the Ni2
Keywords: nickel • carbenes • metal-metal interactions •
cyclopropane • homogeneous catalysis
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RESEARCH ARTICLE
Entry for the Table of Contents
Me
Me
Me
SiMe3
H
Ni2 Catalyst
Me
+
single
regioisomer
N2
10:1 dr
SiMe3
i-Pr
Me
N
N
R
N
a diazoalkane–diene
coupling mechanism
Ni
Me
N
Ni
i-Pr
N
N
i-Pr
i-Pr
SiMe3
H
Dinickel complexes catalyze regioselective cyclopropanations of unsymmetrical 1,3-dienes using TMSCHN2. Mechanistic studies
suggest that the reaction proceeds by a diazoalkane–diene coupling mechanism and does not require the formation of a dinickel
carbene intermediate.
Institute and/or researcher Twitter usernames: @UyedaLab, @PurdueChemistry
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