Mechanistic Insights into Copper-Catalyzed Carboxylations

Article abstract of DOI:10.1021/acs.organomet.9b00710

The copper-NHC-catalyzed carboxylation of organoboranes with CO₂ was investigated using computational and experimental methods. The DFT and DLPNO-CCSD(T) results indicate that nonbenzylic substrates are converted via an inner-sphere carboxylation of an organocopper intermediate, whereas benzylic substrates may simultaneously proceed along both inner-and outer-sphere CO₂ insertion pathways. Interestingly, the computations predict that two conceptually different carboxylation mechanisms are possible for benzylic organoboranes, one being copper-catalyzed and one being mediated by the reaction additive CsF. Our experimental evaluation of the computed reactions confirms that carboxylation of nonbenzylic substrates requires copper catalysis, whereas benzylic substrates can be carboxylated with and without copper.

Full text of DOI:10.1021/acs.organomet.9b00710

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Mechanistic Insights into Copper-Catalyzed
Carboxylations
Marc F. Obst, Ashot Gevorgyan, Annette Bayer,* and Kathrin H. Hopmann*,†
†
‡
,‡
†Hylleraas Center for Quantum Molecular Sciences, Department of Chemistry, UiT The Arctic University of Norway, N-9037
Tromsø, Norway
‡
Department of Chemistry, UiT The Arctic University of Norway, N-9037 Tromsø, Norway
*
S Supporting Information
ABSTRACT: The copper-NHC-catalyzed carboxylation of organo-
boranes with CO2 was investigated using computational and
experimental methods. The DFT and DLPNO-CCSD(T) results
indicate that nonbenzylic substrates are converted via an inner-sphere
carboxylation of an organocopper intermediate, whereas benzylic
substrates may simultaneously proceed along both inner- and outer-
sphere CO insertion pathways. Interestingly, the computations predict
2
that two conceptually different carboxylation mechanisms are possible
for benzylic organoboranes, one being copper-catalyzed and one being
mediated by the reaction additive CsF. Our experimental evaluation of
the computed reactions confirms that carboxylation of nonbenzylic
substrates requires copper catalysis, whereas benzylic substrates can be carboxylated with and without copper.
INTRODUCTION
Scheme 1. Cu-Catalyzed Carboxylations Reported by Hou
X = 70, Y = 24, Cu = CuCl, L = IPr, B = MeOLi, R″ = H),
Sawamura (X = 100, Y = 12, Cu = CuOAc, L = 1,10-phen, B
■
(
Carbon dioxide has significant potential as a carbon source for
chemical synthesis, because it is plentiful, readily available, and
t
=
KO Bu, R″ = H), and Skrydstrup (X = 120, Y = 16, Cu =
1−7
cheap.
In this function, CO could help replace fossil
9−11
2
CuI, L = IPr, B = CsF, R″ = Alkyl)
carbon sources, such as crude oil or natural gas, thus reducing
the dependence on these finite resources. A challenge in this
approach is the relatively high chemical inertness of CO2,
resulting in the necessity for catalysts or reactive cosubstrates
for many reactions involving CO . Nevertheless, CO -based
2
2
synthesis pathways for a variety of products have been
developed, which can be classified into three categories: (i)
reactions selectively reducing CO2 to formic acid, CO,
We here set out to investigate the mechanistic details of the
Cu-NHC-catalyzed carboxylation of in situ formed organo-
boranes. To achieve this goal, we employed computational
methods, namely density functional theory (DFT) and
domain-based local pair natural orbital coupled cluster
11
methanol, or lower alkanes, (ii) reactions fixating CO through
2
carbon−carbon (C−C) bond formation to form e.g. carboxylic
acids, and (iii) reactions fixating CO2 through carbon−
heteroatom (C−X) bond formation, leading to cyclic
(
DLPNO-CCSD(T)). We were particularly interested to
6
−8
establish if the CO molecule experiences activation from the
carbonates or carbamates.
2
copper center during C−C bond formation (implying an
inner-sphere mechanism) or if an outer-sphere path with a free
A Cu(I)-based system able to fixate CO through C−C
2
9
bond formation was published independently by Hou and
Sawamura in 2011 and improved upon by Skrydstrup,
Nielsen, and co-workers in 2017 (Scheme 1). The reaction
1
0
CO molecule is preferred, as recently proposed by us for Rh-
2
12
11
catalyzed hydrocarboxylation. Further, it can be noted that
the Cu-catalyzed reaction reported by Skrydstrup, Nielsen, and
co-workers occurs in the presence of 3 equivalents of CsF,
protocol involves two steps: first, a hydroboration with the 9-
11
borabicyclo[3.3.1]nonane dimer (9-BBN) , and second, a
2
and we thus paid particular attention to the role of CsF in the
reaction mechanism, because we recently showed that it may
(
1,10-phenanthroline)Cu(I)- or IPrCu(I)-catalyzed (IPr = 1,3-
bis(2,6-diisopropylphenyl)imidazol-2-ylidene) carboxylation of
the in situ formed organoborane with CO in the presence of a
2
Special Issue: Organometallic Chemistry for Enabling Carbon
Dioxide Utilization
base. Skrydstrup and co-workers employed the milder base
CsF instead of the strong alkoxides used by Sawamura or Hou,
expanding the scope of substrates to cyclic olefins, stilbenes, β-
Received: October 22, 2019
9
−11
substituted styrenes, and terminal acetylenes.
©
XXXX American Chemical Society
A
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Figure 1. The two investigated organoboranes sub1 (derived from cyclohexene R1) and sub2 (derived from trans-β-methylstyrene R2) as well as
the NHC ligand used, IPr.
13
promote carboxylations. Different types of substrates were
investigated, involving both a benzylic and a nonbenzylic
organoborane, which here are shown to have different
mechanistic preferences. Our experiments support the
computational predictions.
ΔGCCSD(T) = ΔGωB97XD,PCM,BS1 − ΔEωB97XD,Vac,BS1
+
ΔECCSD(T),Vac,BS3
(1)
Final DFT standard state Gibbs free energies were obtained similarly
by applying the BS1 thermal and entropic corrections (393.15 K) to
the SP DFT energies calculated at the BS2 level:
COMPUTATIONAL AND EXPERIMENTAL DETAILS
■
ΔGDFT = ΔGDFT,PCM,BS1 − ΔEDFT,PCM,BS1 + ΔEDFT,PCM,BS2
Computational Model. All calculations were performed on the
full molecular systems without any truncations or symmetry
constraints. The two in situ formed organoboranes sub1 and sub2
Figure 1) derived from cyclohexene R1 and trans-β-methylstyrene
R2, respectively, were used to investigate the reaction mechanism.
(
2)
All energies correspond to a 1 atm standard state.
Experimental Methods. Commercially available starting materi-
als, reagents, catalysts, and anhydrous and degassed solvents were
used without further purification. Thin-layer chromatography was
carried out using Merck TLC silica gel 60 F254 and visualized by short-
wavelength ultraviolet light or by treatment with potassium
(
These substrates were chosen because they previously showed high
11
yields in experiments (R1, 94%; R2, 89%) while having different
electronic properties. For steps where CsF enters or leaves, the
reference structure for CsF was modeled as a dimer, Cs F . However,
1
13
permanganate (KMnO ) stain. H and C NMR spectra were
4
2
2
1
recorded on a Bruker Avance 400 MHz spectrometer at 20 °C. All H
NMR spectra are reported in parts per million (ppm) downfield of
as the exact nature of the CsF reference state under experimental
conditions (dioxane solvent, 120 °C) is not known, we also computed
the overall barriers with an alternative tetrameric reference state
TMS and were measured relative to the signals for CHCl (7.26
3
13
ppm). All C NMR spectra were reported in ppm relative to residual
CDCl (77.20 ppm) and were obtained with H decoupling. Coupling
(
Cs F ) for comparison (Table S1 and Scheme S1).
1
4
4
3
Computational Methods. Geometries were optimized using the
constants, J, are reported in hertz (Hz). High-resolution mass spectra
HRMS) were recorded from methanol solutions on an LTQ
Orbitrap XL instrument (Thermo Scientific) in negative electrospray
ionization (ESI) mode. Melting points were measured using a Stuart
SMP50 automatic melting point detector.
14
long-range corrected ωB97XD functional. This functional was
(
1
5,16
chosen on the basis of good results in recent benchmarks.
17,18
Additional DFT calculations were performed using the PBE
and
19
20
B3LYP functionals with the GD3BJ dispersion correction to assess
the robustness of the computed results (details are given in the
Supporting Information). The employed software was Gaussian16
B.01 for all DFT calculations. For optimizations, the basis set BS1
was used, which consists of the SDD basis for Cu and Cs as well as the
General Procedure for Cu-Catalyzed/Cu-Free Hydrocarbox-
ylation. Inside a glovebox, a 45 mL pressure tube was charged with
21
the corresponding olefin (1.7 mmol), (9-BBN) (1 equiv), and dry
2
dioxane (4 mL (Cu-catalyzed), 6 mL (Cu-free)). The flask was closed
with a suitable cap, removed from the glovebox, and heated to 65 °C
for 16 h. Afterward, the pressure tube was transferred back to the
glovebox. To the reaction mixture at 20 °C was added CsF (3 equiv)
and, in the case of Cu-catalyzed reactions, a solution of the catalyst (a
mixture of CuI (5 mol %), IPrHCl (6 mol %), and NaOtBu (6 mol
6
-31+G* basis for all other elements. DFT single-point (SP) energies
were calculated at the BS2 level, using the same DFT functional as
used in optimizations. BS2 comprises the SDD basis for Cu and the
def2-TZVP basis for all other elements. Both BS1 and BS2 employed
the SDD ECPs for Cu and Cs. Solvation effects were included in
optimizations and SP calculations through the use of an IEFPCM
model of 1,4-dioxane.
%
) in dry dioxane (3 mL) stirred at 20 °C for 30 min before use). The
pressure tube was closed with a cap and removed from the glovebox.
Afterward, CO2 (120 mL) was added via a syringe, followed by
stirring the reaction mixture at 120 °C for 16 h. Next, the reaction
In order to obtain accurate electronic energies beyond DFT, we
22,23
employed DLPNO-CCSD(T).
This method is reported to have
mixture was diluted with 30 mL of Et O and transferred into a 500
2
an accuracy comparable to that of CCSD(T), while scaling
considerably better, allowing the treatment of large molecules with
mL separating funnel. The resulting mixture was extracted with 30 mL
of saturated basic (NaHCO ) solution (three times). The resulting
3
2
4−26
high accuracy.
The DLPNO-CCSD(T) SP energies were
basic solution was washed with 15 mL of Et O (once), acidified (50−
2
calculated using the ωB97XD-based geometries obtained as described
above. The DLPNO-CCSD(T) method was used with the scalar-
relativistic ZORA operator and basis set BS3, consisting of the SARC-
ZORA-TZVPP basis for Cs and the minimally augmented ma-ZORA-
def2-TZVPP basis for all other elements. These calculations were
55 mL 6 M HCl), and extracted with 30 mL of Et O (three times).
2
The resulting solution of Et O was distilled to dryness to give the
2
corresponding acid.
RESULTS AND DISCUSSION
27
■
accelerated by using the RIJCOSX approximation employing the
auxiliary basis sets def2-TZVP/C and SARC/J. The employed
Cu(I)-Catalyzed Conversion of sub1. We initiated our
investigation of the copper-catalyzed carboxylation of organo-
boranes from the mechanism proposed by Skrydstrup, Nielsen,
2
8
software for these calculations was ORCA 4.1.2. The final
DLPNO-CCSD(T) standard state Gibbs free energies (ΔGCCSD(T))
were obtained by applying the ωB97XD-based thermal, entropic, and
solvation corrections at 393.15 K (120 °C) and the BS1 level to the
SP DLPNO-CCSD(T) electronic energies. Unless explicitly stated
otherwise, the ΔGCCSD(T) energies are used for the discussion.
1
1
and co-workers. Their schematic proposal suggests a
transmetalation of I-Cu-IPr with CsF to form the active
species F-Cu-IPr, which reacts with the organoborane to give a
Cu-alkyl intermediate, followed by insertion of CO . Our
2
B
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Scheme 2. Computed Catalytic Cycle for the Copper-NHC-
Catalyzed Carboxylation of Organoboranes, Based on Our
Work Here and the Proposed Mechanism by Skrydstrup,
,
a 11
Nielsen, and Co-workers
Figure 3. Optimized geometry of TS2a‑3a for sub1. Distances are in Å.
The NHC ligand (IPr) is transparent for clarity. Color code for this
and subsequent figures: C, gray; H, white; N, blue; B, pink; F, green;
O, red.
intermediate 3a, concomitant with release of (9-BBN)-F.
This step has a barrier of 22.8 kcal/mol and can be viewed as a
transmetalation, with the cyclic TS (TS2a‑3a, Figure 3)
composed of copper, boron, and the reactive carbon. When
this TS is reached, the fluoride is already fully transferred to
boron. A separate TS for fluoride transfer could not be
identified. The formed Cu-alkyl intermediate 3a has a relative
energy of 0.4 kcal/mol, making it relatively stable. 3a can then
a
insert a CO molecule via TS3a‑4a. Several TSs were identified
The “B” in a blue circle denotes 9-BBN.
2
for this step, which can be classified as inner or outer-sphere,
depending on the presence of Cu−CO interactions at the
2
computational results indicate that such a mechanism is
feasible for the cyclohexene-derived organoborane sub1,
although our data suggest some modifications to the original
proposal, with the obtained mechanism shown in Scheme 2.
We will refer to this mechanism as A, with the computed Gibbs
free energy profile for sub1 shown in Figure 2.
The computed pathway A starts with a nucleophilic attack of
the fluoride ligand of the active species (F-Cu-IPr) at the
boron atom of the substrate. The corresponding transition
transition state. With a computed barrier of 31.9 kcal/mol, the
inner-sphere TS is clearly preferred for sub1, in comparison to
the outer-sphere TS with a barrier of 39.6 kcal/mol (Figure 4).
The energies obtained with different DFT functionals
(ωB97XD, PBE-D3BJ, B3LYP-D3BJ) provide the same clear
preference for an inner-sphere attack (Table S2 in the
Supporting Information). This result is in line with the
inner-sphere mechanism predicted for carboxylation of non-
30−32
3
benzylic Csp carbons with Rh complexes,
but it is in
state (TS1 ) has a barrier of 16.8 kcal/mol relative to 1 and is
contrast to computational work on Ni- and Pd-mediated
carboxylations, supporting outer-sphere pathways for non-
‑2a
characterized by a partial transfer of the fluoride from copper
to boron. At the intermediate 2a, the fluoride is bridging
between boron and the metal center. The energy of this
intermediate is 7.2 kcal/mol. In the following step, a concerted
rearrangement leads to the formation of the Cu-alkyl
32−34
3
benzylic Csp carbons.
In our computations, the CO2
insertion step is rate-limiting. The formed intermediate 4a has
a relative energy of −11.3 kcal/mol. The final step of the
catalytic cycle is the transmetalation of 4a with CsF to
Figure 2. Computed Gibbs free energy profile (kcal/mol) of the Cu(I)-catalyzed path A for sub1 (red) and sub2 (blue). The “B” in a blue circle
denotes 9-BBN, and L denotes IPr.
C
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Figure 4. Optimized geometries of the inner- and outer-sphere TS for CO insertion (TS3a‑4a) with the nonbenzylic substrate sub1. Distances are
2
in Å. The IPr ligand is transparent for clarity. Color code as in Figure 3.
Figure 5. Optimized geometries for the inner- and outer-sphere TS for CO insertion (TS3a‑4a) with the benzylic substrate sub2. Distances are in Å,
2
and energies are relative to 1. The IPr ligand is transparent for clarity. Color code as in Figure 3.
Table 1. Computed Overall Standard State Gibbs Free Energy Barriers (kcal/mol, 323 K) for the Cu-Catalyzed Pathway A and
CsF-Mediated Pathway B Obtained at Different Levels of Theory
substrate
method
solvation model
path A
path B
ΔΔG(A−B)
sub1
sub1
sub1
sub1
sub1
sub1
sub2
sub2
sub2
sub2
sub2
sub2
DLPNO-CCSD(T)
DLPNO-CCSD(T)
ωB97XD
ωB97XD
PBE-GD3BJ
B3LYP-GD3BJ
DLPNO-CCSD(T)
DLPNO-CCSD(T)
ωB97XD
ωB97XD
PBE-GD3BJ
PCM
PCM+Explicit
PCM
PCM+Explicit
PCM
PCM
PCM
PCM+Explicit
PCM
PCM+Explicit
PCM
PCM
31.9
31.9
33.6
33.6
26.4
29.9
36.2
39.2
40.4
40.6
25.6
29.8
53.3
47.7
53.9
48.6
−21.4
−15.5
−20.3
−15.0
−23.2
−20.6
−0.8
0.6
4.0
5.0
−4.0
0.9
a
49.6
50.5
a
37.0
38.6
36.4
35.6
a
29.6
a
B3LYP-GD3BJ
28.9
a
Energies based on SP calculations on the ωB97XD structures (TS3 ), as reoptimization at the given level was unsuccessful.
b‑5
Scheme 3. Our Proposed Mechanism for the CsF-Mediated
Carboxylation of Benzylic Organoboranes
transmetalation could be located. The overall barrier of 31.9
kcal/mol for the Cu(I)-IPr-catalyzed carboxylation of sub1 via
path A is feasible at the experimental temperature of 393 K (on
35
the basis of the discussion by Baik and co-workers, a barrier
of up to ∼33.2 kcal/mol should be viable). It can be noted that
3
path A for Csp carboxylation of the nonbenzylic organoborane
sub1 is similar to the reported mechanism for Cu-NHC-
3
6
catalyzed Csp2 carboxylation of arylboronate esters, although
regenerate the active species F-Cu-IPr and form the product 5
t
(
relative energy of −15.0 kcal/mol). No TS for this
the involvement of CsF here, instead of KO Bu, provides some
D
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Figure 6. Computed Gibbs free energy profile (kcal/mol) of the CsF-mediated pathway B for the two substrates sub1 (red) and sub2 (blue). The
B” in a blue circle denotes 9-BBN.
“
state is employed in calculations. If the reference state is Cs4F4
instead of Cs F , the barrier for TS is reduced from 36.2 to
2
2
3a‑4a
3
3.5 kcal/mol (see Table S1 in the Supporting Information).
Thus, there is an uncertainty in the carboxylation barrier for
sub2 with mechanism A, which is further discussed below
(
Table 1). For sub1, a similar CsF−substrate adduct 2b can
also be optimized (Figure 2), but it is not lower in energy than
and therefore does not influence the rate-limiting barrier for
sub1.
We proceeded to explore if a variant of pathway A, with a
1
transmetalation of the alkyl to copper occurring directly from
the CsF−sub2 adduct 2b, may provide lower barriers.
However, this pathway showed unfeasible barriers of at least
47 kcal/mol for sub2 (Table S4 in the Supporting
Information). The adduct 2b is thus not expected to be
reactive, and it needs to dissociate prior to Cu-catalyzed
transmetalation of sub2.
Figure 7. CO insertion TS (TS ) for sub2 via path B in the
presence of a 1,4-dioxane molecule. Color code as in Figure 3.
2
3b‑5
differences with respect to the formed intermediates and
products.
CsF-Mediated Carboxylation. We recently showed that
13
Cu(I)-Catalyzed Conversion of sub2. The computed
steps for the Cu-IPr-catalyzed carboxylation of the trans-β-
methylstyrene-derived borane sub2 are essentially as for sub1,
with the Gibbs free energy profile shown in Figure 2. However,
CsF can mediate the carboxylation of benzylic boranes. As
the reaction conditions (Scheme 1) of the copper system
involves addition of 3 equiv of CsF, we proceeded to explore if
the additive could be the carboxylating agent. Setting out from
the low-lying 2b adduct, a possible carboxylation pathway
involving a organocaesium species 3b may exist, as shown in
there are two major differences. First, for the CO insertion
2
TS, the inner- and outer-sphere conformers are only 0.3 kcal/
mol apart (TS3a-4a, Figure 5). This indicates that, for benzylic
carbons, a Cu-NHC-catalyzed carboxylation may operate via
both inner- and outer-sphere pathways. The DFT-based
energies also support this conclusion (Tables S2 and S3 in
the Supporting Information). It can be noted that a recent
study on Cu-NHC-mediated boracarboxylation of alkenes
reported an inner-sphere TS for carboxylation of a benzylic
13
our previous work. This pathway will be referred to as path B
and is shown in Scheme 3, while the corresponding computed
Gibbs free energy profile is shown in Figure 6. This pathway is
of no importance for sub1, for which we compute a rate-
limiting barrier of 53.3 kcal/mol (Figure 6). However, for sub2
the rate-limiting barrier computed for the CsF-mediated
carboxylation path B is 37.0 kcal/mol (Figure 6), indicating
that it is equally likely to occur as the copper-catalyzed
pathway A (36.2 kcal/mol, Figure 2). It needs to be mentioned
here that the TS for the rate-limiting step of path B (TS2b‑3b)
3
7
3
Csp carbon; however, it is unclear if the outer-sphere path
was evaluated. For Rh-mediated carboxylations, we have earlier
observed a very strong preference for outer-sphere pathways
12
−1
for benzylic substrates. Second, sub2 features a different
resting state in comparison to sub1, which is greatly
influencing the rate-limiting barrier. Our calculations predict
that the complexation of sub2 with the reaction additive CsF
leads to an energetically low-lying species (2b), −9.3 kcal/mol
shows only a small imaginary frequency of 16i to 35i cm with
the different DFT functionals, making both its optimization
38
and its interpretation challenging. However, a displacement
of the TS geometry along the intrinsic reaction coordinate
(IRC) supports that TS2b‑3b indeed is linking 2b and 3b,
implying that the small imaginary frequency may be an
inherent feature of this TS.
below 1. This raises the rate-limiting barrier for CO insertion
2
from 29.5 kcal/mol to 36.2 kcal/mol for sub2, which appears
slightly above a feasible barrier limit at the experimental
temperature (∼33.2 kcal/mol, vide supra). It can be noted that
the barrier of this step is dependent on which CsF reference
Explicit Solvation Effect. All calculations presented above
(Figures 2 and 6) were performed with an implicit IEFPCM
model to obtain an approximate estimate of the effect of the
E
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Scheme 4. Experimental Conditions and Yields for Cu-Catalyzed and CsF-Mediated Carboxylation of Cyclohexene and trans-
β-Methylstyrene
solvent (1,4-dioxane) on the reaction geometries and energies.
This is a standard approach in computational chemistry;
however, it does not take into account the effect that explicit
solvent may have. We here recomputed paths A and B with
one explicit 1,4-dioxane molecule added as a ligand to the Cs-
containing species (Figure 7). For the different computational
protocols, the computed barriers (Tables S5 and S6 in the
Supporting Information) are either identical or change by a
maximum of 3 kcal/mol relative to the energies obtained with
the implicit solvent model. In particular, we find that the
involvement of explicit solvent does not change the proposed
mechanistic preferences of sub1 (preferably path A) or sub2
different methods. This state is not involved in the reactivity of
sub1, where smaller energetic variations between the computa-
tional protocols are observed. The results for sub2 show a
trend, where the computed barriers for both path A and B are
consistently below 33 kcal/mol with B3LYP-D3BJ or PBE-
D3BJ but consistently above 33 kcal/mol with DLPNO-
CCSD(T) or ωB97XD. Although the results indicate that both
paths A and B may be equally likely to occur for sub2, a clear
conclusion regarding their feasibility cannot be made. An
important point in this analysis is the expected accuracy of the
computed values. Absolute barriers obtained with DFT may
29
have an error of more than 5 kcal/mol, and also for DLPNO-
CCSD(T), a recent benchmark showed an average deviation of
more than 7 kcal/mol between experimental and computed
(
paths A and B equally likely with DLPNO-CCSD(T)).
Discussion of the Computed Barriers. Table 1 shows
39
the computed overall barriers at 323 K for the Cu-catalyzed
pathway A and the CsF-mediated pathway B for sub1 and
sub2 obtained with different levels of theory.
dissociation energies, with the origin of the error being
unknown. A conclusion on the feasibility of paths A and B for
sub2 thus cannot be made from computations alone. We
therefore proceeded to perform experimental tests.
For sub1, it can be seen that the different computational
protocols predict barriers that vary by up to 7.2 kcal/mol.
However, all methods predict that the preferred pathway is A,
which has a feasible barrier close to the discussed threshold of
Experimental Evaluation. A possible prediction derived
from our computational work is that sub1 will only work under
Cu-catalysis (path A), whereas sub2 may be converted either
with Cu-catalysis (path A) or via a CsF-mediated path (path
B). We tested this hypothesis by redoing the experiment in
Scheme 1 with the two alkenes cyclohexene (R1; the precursor
of organoborane sub1) and trans-β-methylstyrene (R2; the
precursor of organoborane sub2), with or without Cu-IPr
added to the reaction mixture (Scheme 4). For cyclohexene,
the reaction gives 0% yield in the absence of copper but 73%
yield in the presence of copper. This is in excellent agreement
with the computed barriers, predicting that Cu-catalysis is
essential for sub1 (Table 1). For this substrate, the results for
path A indicate that the CsF additive only seems to be
important for the transmetalation step allowing reformation of
35
3
3.2 kcal/mol at 323 K for all electronic structure methods
(
DLPNO-CCSD(T), ωB97XD, PBE-D3BJ, B3LYP-D3BJ) and
molecular models (with/without 1,4-dioxane) tested here.
Instead, for path B, all methods and models predict a barrier
above 47 kcal/mol for sub1. This strongly indicates that Cu
catalysis via path A is viable for sub1, whereas the CsF-
mediated path B is excluded.
For sub2, the different protocols predict barriers that vary by
up to 15 kcal/mol (Table 1). This large variation cannot be
explained definitely, but one possibility is that the stability of
the predicted resting state of sub2 (the low-lying CsF−
substrate adduct 2b) may be described rather differently by the
F
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the active IPr-Cu-F species but it should not be involved in the
*E-mail for K.H.H.: kathrin.hopmann@uit.no.
ORCID
Annette Bayer: 0000-0003-3481-200X
Kathrin H. Hopmann: 0000-0003-2798-716X
Notes
CO insertion.
2
In contrast, the sub2 precursor trans-β-methylstyrene is
converted to the carboxylic acid with and without copper
added to the reaction mixture, providing 84% and 91% yields,
respectively (Scheme 4). The higher yield in the absence of
copper may be attributed to a decarboxylation reaction
The authors declare no competing financial interest.
13
mediated by the copper complex. The experimental results
support the prediction that conversion of sub2 can occur in the
absence of copper, indicating that path B may be operative. In
the presence of both copper and CsF, it cannot be determined
which pathway occurs for sub2, but on the basis of our
computations indicating similar barriers for the copper-
catalyzed path A and the CsF-mediated path B (Table 1),
we predict that both occur simultaneously.
ACKNOWLEDGMENTS
■
This work has been supported by the Research Council of
Norway through a Centre of Excellence Grant (No. 262695),
by the Tromsø Research Foundation (No. TFS2016KHH), by
Notur-The Norwegian Metacenter for Computational Science
through grants of computer time (Nos. nn9330k and
nn4654k), and by NordForsk (No. 85378) and the members
of the Nordic Consortium for CO Conversion (NordCO ).
2
2
CONCLUSIONS
■
We have investigated the Cu-NHC-catalyzed carboxylation of
cyclohexene and trans-β-methylstyrene using DFT and
DLPNO-CCSD(T). Several interesting conclusions can be
drawn. First, a main conclusion is that nonbenzylic organo-
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge at
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Corresponding Authors
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Organometallics XXXX, XXX, XXX−XXX