An NHC-Stabilised Phosphinidene for Catalytic Formylation: A DFT-Guided Approach

Article abstract of DOI:10.1002/chem.202101202

In recent years, the applications of low-valent main group compounds have gained momentum in the field of catalysis. Owing to the accessibility of two lone pairs of electrons, NHC-stabilised phosphinidenes have been found to be excellent Lewis bases; however, they cannot yet be used as catalysts. Herein, an NHC-stabilised phosphinidene, 1,3-dimethyl-2-(phenylphosphanylidene)-2,3-dihydro-1H imidazole (1), for the activation of CO₂ is reported.A closer inspection of the CO₂ activation process by DFT calculations along with intrinsic bond orbital analysis shows that phosphinidene is associated with phenylsilane through a noncovalent π-π interaction between two phenyl rings which activates the Si?H bond facilitating hydride transfer to the CO₂ molecule. Detailed DFT studies along with spectroscopic experiments were combined to understand the mechanism of CO₂ activation and its catalytic reductive functionalisation leading to the formylation of a range of chemically inert primary amides under mild reaction conditions.

Full text of DOI:10.1002/chem.202101202

Accepted Article
Accepted Article
Title: An NHC-stabilized phosphinidene for catalytic formylation: A DFT
guided approach
Authors: Swadhin Kumar Mandal
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An NHC-stabilized Phosphinidene for Catalytic Formylation: A
DFT Guided Approach
Sreejyothi P.a, Kalishankar Bhattacharyyab, Shiv Kumara, Pradip Kumar Hotaa, Ayan Dattab* and
Swadhin K. Mandala*
[a]
[b]
Sreejyothi P, S.Kumar, Dr. P.K. Hota, Prof. S.K. Mandal
Department of Chemical Sciences
Indian Institute of Science Education and Research-Kolkata
Mohanpur-741246, India.
E-mail: swadhin.mandal@iiserkol.ac.in
Dr. K. Bhattacharyya, Prof. A. Datta
Department of Spectroscopy
Indian Association for the Cultivation of Science
Jadavpur-700032, West Bengal (India)
E-mail: spad@iacs.res.in
Supporting information for this article is given via a link at the end of the document.((Please delete this text if not appropriate))
Abstract: In recent years, applications of low-valent main group
compounds in the field of catalysis are gaining momentum. NHC-
stabilized phosphinidenes owing to the access of two lone pairs of
electrons, have been found as excellent Lewis bases; however, they
are yet to be used as catalysts. Herein, we report an NHC stabilized
phosphinidene 1,3-dimethyl-2-(phenylphosphanylidene)-2,3-dihydro-
1H-imidazole (1) for the activation of CO2. A closer inspection of the
CO2 activation process by DFT calculations along with intrinsic bond
orbital analysis unravels that phosphinidene is associated with
phenylsilane through a non-covalent π-π interaction between two
phenyl rings which activates the Si-H facilitating its transfer to the CO2
molecule. Detailed DFT studies along with spectroscopic experiments
were combined to understand the mechanism of CO2 activation and
its catalytic reductive functionalization leading to the formylation of a
range of chemically inert primary amides under mild reaction
conditions.
NHC stabilized phosphinidenes can best be presented by the two
extreme canonical structures A and B (Scheme 1a). Form A refers
to a carbon-phosphorus single bond with two lone pairs of
electrons available on phosphorus whereas the form B represents
a
conventional phosphaalkene with a P-C double bond.
Depending on the electronic property of carbene, the major
valence bond form may switch from one extreme to another. In
2013, Bertrand and co-workers synthesized a series of NHC-
phosphinidene adducts by introducing a range of electronically
diverse NHCs and analysed them by 31P NMR spectroscopic
shifts.9 It was observed that the NHC stabilized phosphinidenes
displayed a high field chemical shift in 31P NMR spectra in
comparison to that observed for typical phosphalkenes (δ = 230-
420 ppm),[20] which may be considered as an indication of a high
electron density around phosphorus nucleus in these carbene
stabilized phosphinidenes. On the other hand, the higher π
acceptance property of NHC triggers the back donation from
phosphorus to NHC, resulting in the relative downfield chemical
shift in 31P NMR spectroscopy.[9] Such an electronic influence
suggests that the phosphinidenes can be made ambiphilic
depending on the nature of stabilizing ligand.[21] The polarisation
of P-C bond depends on the electronic properties of N-
heterocyclic carbene as well as on the substituent on phosphorus
center.[2] In 1997, Arduengo, Cowley and co-workers
demonstrated that NHC stabilized phosphinidene ((IMes)PPh)
Introduction
Phosphinidenes belong to neutral monovalent Group 15
analogues of carbenes possessing phosphorus in +1 oxidation
state having access to two lone pairs of electrons.[1-4] Similar to
the parent carbene (:CH2), the parent phosphinidene exists in a
triplet ground state with ETS = 22 kcal/mol.[5] Nevertheless, the
ground state of phosphinidenes can be tuned into a stable singlet
state by introducing appropriate substituents.[6] For example, in
1997, Arduengo and co-workers demonstrated that a singlet
phosphinidene could be realized by N-heterocyclic carbene
coordination to the phosphinidene moiety.[7] In following years, a
number of singlet phosphinidenes have been synthetically
accomplished by the groups of Robinson,[8] Bertrand,[9-10]
[IMes
=
(1,3-dimesitylimidazolin-2-ylidene)] can form
a
bis(borane) adduct [{(IMes)PPh}(BH3)2] upon treatment with
BH3.THF[22] (Scheme 1b). The formation of such bis borane adduct
clearly suggests the availability of two lone pairs of electrons and
strong nucleophilicity of phosphorus center. This result prompted
many to consider NHC stabilized phosphinidene as a potential
ligand for coordination to various metals.[12-13,17,23-28] Recently, IPr
(1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)
stabilized
Driess,[11] Tamm,[12-13] Roesky,[14-15] Grützmacher,[16]
others[17-18] stabilized by various carbenes. Recently, Bertrand
and co-workers isolated singlet phosphinidene at room
temperature using a bulky N-heterocyclic phosphane.[19] The
and
phosphinidene Au(I) complexes were used as catalysts in
cycloisomerization of the 1,6-enynes to five- or six-membered
1,3-dienes (Scheme 1b).[13] Furthermore, NHC stabilized
phosphinidenes were exploited for the activation of small
a
1
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molecules. Ragogna et al. illustrated the efficiency of
phosphinidenes in the ring-opening of THF in presence of a strong
Lewis acid B(C6F5)3 (Scheme 1b).[29] In 2013, Robinson et al.
reported the activation of O2 by an NHC stabilized phosphinidene
dimer to form diphosphorus tetroxide (Scheme 1b).[30] However,
beyond such small molecules’ activation, the free phosphinidenes
have not been explored in catalysis. In this regard, we strategized
the possibility of utilizing phosphinidene as a metal-free catalyst.
In 2017, Slootweg and Grützmacher reported an NHC stabilized
phosphinidene adduct 1,3-dimethyl-2-(phenylphosphanylidene)-
2,3-dihydro-1H-imidazole (1).
compound could fix CO2, leading to its catalytic activation.[36] In
this regard, low-valent phosphorus compounds also showed
promise towards CO2 activation, for example, Driess and co-
workers demonstrated
a silylene-stabilized zero-valent P2
complex to activate CO2 molecules in stoichiometric fashion.[37]
However, low-valent phosphorus compounds such as
phosphinidenes are yet to be realized as catalysts in CO2
activation or in any organic transformation. Herein we report an
NHC-stabilized phosphinidene 1 as a catalyst for CO2 activation
and formylation of chemically inert primary amides under ambient
conditions. It may be noted that in literature, metal-free catalytic
formylation of amines is quite well-studied.[38-41] Such formylation
of amines using CO2 has been accomplished with various low-
valent metal-free main group compounds in recent time.[42-43] For
example, reports by So and co-workers demonstrated the use of
NHC-stabilized silylene[44] and N-phosphinoamidinato N-
heterocyclic carbene-diborene[45] for catalytic formylation of
amines using CO2. On the contrary, the formylation of primary
amides by metal-free catalyst has rarely been explored except in
a recent report.[46] The catalytic formylation of primary amides
using CO2 is a challenging transformation as they are inert
compared to amines toward such formylation. In this work, the
NHC stabilized phosphinidene 1 was used as a catalyst for
formylation of a range of primary amides at room temperature
using CO2 and silane under mild conditions. The nucleophilicity of
1 activates silane to incorporate CO2 into Si-H bond leading to
formyl transfer to the primary amides.
Results and Discussion
The NHC stabilized phosphinidene 1 was chosen for this study as
the 31P NMR data indicates that it has highly shielded phosphorus
(δ = -57.2 ppm in CD3CN) and it was prepared following the
reported procedure.[28] At first, to get insight into the bonding
scenario of the phosphinidene 1, we have carried out density
functional theory (DFT) calculations at the M06-2X/Def2-TZVP
level of theory. Geometry optimization of 1 using the same level
of theory suggests a closed-shell singlet ground state with a large
EST = 48.7 kcal/mol (Figure 1a).
Scheme 1. a.Two extreme canonical structures of NHC stabilized
phosphinidene. b. NHC-stabilized phosphinidenes used for various organic
transformations. c. This work highlights the first catalytic application of
phosphinidene resulting in activation of CO2 to formylate a range of chemically
inert primary amides under mild reaction conditions.
A preliminary DFT calculation on its bonding revealed the Wiberg
bond index (WBI) of C(carbene)-P as 1.23 with C-P π bonded
electron density mostly polarized towards the phosphorous centre
(vide infra). This finding from DFT calculation along with its
upfield 31P NMR chemical shift, indicates a strong nucleophilic
character of phosphorus in 1. Thus encouraged, we attempted to
explore this phosphinidene 1 towards the development of a metal-
free catalyst. As a proof of concept, we have chosen catalytic
formylation of primary amides, which proceeds through the
activation of CO2 by phosphinidene 1. It is now established that
CO2 can be activated and functionalized by various nucleophilic
metal-free catalysts such as N-bases, phosphanes, ionic liquids
and various carbenes.[31] The area of metal-free catalytic
activation of CO2 is gaining tremendous attention due to its
efficacy under mild reaction conditions as it avoids rare and heavy
transition metals.[32-35] Recently, various low-valent main group
compounds have been tested for their ability towards catalytic
CO2 activation with only limited success. For example, Inoue and
Figure 1. a) Optimized structure of 1 in singlet ground states at M06-2X/Def2-
TZVP level of theory and the highest occupied and lowest unoccupied molecular
orbitals (isosurface = 0.03 au). Hydrogen atoms are omitted for the sake of
clarity. Color code: C, gray; N, blue; and P, orange. b) NBO orbitals of 1
(isosurface = 0.02 au) displaying electron density distribution of the lone pair of
electrons on phosphorus, C-P σ bond and C-P π bond.
co-workers demonstrated
a
neutral Al-Al double-bonded
2
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The bonding analysis reveals that the highest occupied molecular
orbital (HOMO) of 1 corresponds to the π orbitals formed between
the carbene carbon and phosphorus with a significant contribution
coming from the phosphorus. On the other hand, LUMO has
mostly π* orbital characteristics located on the carbene center of
1 (Figure 1a). The longer bond distance of Ccarbene-P in 1 (1.78Å)
in comparison to the classical phosphaalkenes (Ccarbene-P ≈ 1.65-
1.67Å) validates the phosphinidene character of 1.[2] Further,
Natural bond orbital (NBO) analyses demonstrate that Ccarbene-P
bond in 1 exhibits a partial double-bond character which is
indicative from the Wiberg bond index (WBI) of Ccarbene-P bond
(1.23). Furthermore, NBO analysis reveals that electron density
of the C-P σ bond in 1 is mainly polarized towards the carbene
carbon (Ccarbene(1): 67.7%), whereas C-P π bonded electron
density is mostly polarized towards the phosphorous centre
(70.1%, See Table S1). Such unsymmetrical π electronic
distribution around the C-P bond of 1 supports its upfield chemical
shift in 31P NMR spectroscopy and is indicative of its nucleophilic
nature. Next, we explored whether such nucleophilicity of 1 can
be exploited in CO2 activation. First, we performed a control
reaction by mixing 1 (5 mol%) with phenylsilane (1 equiv) in
acetonitrile in an argon-filled glovebox. Subsequently, it was
taken to undergo two cycles of freeze pump and thaw which was
then exposed to 1 atm CO2 while warming up the frozen reaction
mixture to room temperature. After 12 h, NMR spectroscopic
analysis of the reaction mixture was performed and a peak at δ
transfer to CO2 with a free-energy of activation of 15.8 kcal/mol
through the TS1 as shown in Figure 2d. Such Si-H activation
mode for CO2 reduction also was reported in the literature
previously.[51] Further, the WBI calculations reveal that C-P bond
of phosphinidene attains a significantly reduced value of 0.99 in
TS1 from its original value 1.23 calculated for free 1, which
strongly supports the flow of π- electron density from P center
during activation of CO2 molecule (vide infra).
1
8.4 ppm was observed in H NMR spectrum, whereas 13C NMR
spectrum displayed a peak at δ 161.2 ppm in CD3CN.[47] This
observation suggests activation of CO2 by 1 in presence of silane
resulting in the formation of phenylsilane formate (5) in which CO2
got inserted into the Si-H bond of phenylsilane. Our efforts to
isolate the phenylsilane formate (5) failed, as it decomposed
during isolation. However, this initial finding prompted us to take
up further detailed investigation to understand such CO2
activation in presence of 1 and phenylsilane. DFT studies
proposed the formation of a π- π stacked phosphinidene-
phenylsilane adduct 1a (Figure 2a) with favourable binding
energy -8.3 kcal/mol, while such non-negligible interaction
weakens the Si-H bond (~1.49 Å) as compared to the Si-H bond
length calculated in free silane (1.45 Å). In order to understand
such interaction between 1 and phenylsilane, DFT calculation
was undertaken and it revealed that upon interaction of
phenylsilane with 1, they associate as 1a through a π-stacking
interaction between two adjacent phenyl rings with a separation
of 3.69 Å. Optimized structure of 1-silane adduct (1a) is displayed
in Figure 2a where P and Si are separated by a distance of 3.63
Ao indicating a very weak interaction. Dispersion interaction
density plot of the 1a shows that non-covalent π-stacking
interactions are mainly arising from the rather strong London
dispersion forces (Figure 2b). stabilizing the π-stacked complex
by -8.3 kcal/mol. Note that the M06-2X DFT functional has been
shown to be successful in describing middle-range dispersion
interactions like π-stacking.[48] We further evaluated the non-
covalent interactions using open source NCI code.[49-50] As shown
in Figure 2c, non-covalent electron density (shown in green)
between the phenyl rings of the adduct is attributed to the strong
π-π interactions between them. The large separation between P
and Si centers (3.63 Å) in 1a supports almost negligible direct
interaction between them; however, on addition of CO2, the P and
Si distance reduce to 2.56 Å (TS1). Further, it significantly
weakens the Si-H bond (~1.72 Å) and favours the hydride
Figure 2. a) Optimized structure of phosphinidene-silane adduct 1a. b)
Dispersion interaction density plot of 1a. c) Non-covalent interaction plot (NCI)
of the 1-phenylsilane adduct showing the non-covalent electron density. d) The
relative Gibbs free energies for 298
K (in kcal/mol) at M06-2X/6-
311++G(d,p)(SMD:acetonitrile) level of theory. Optimized structures of selected
intermediate and transition state structures are also represented. Distances are
in Å.
In order to check the stability of catalyst during the activation of
CO2, we have performed a low temperature 31P{1H} NMR analysis
of the catalytic reaction mixture in presence of CO2. In such
experiment, an equimolar amount of 1 and phenylsilane were
loaded in a J Young NMR tube in CD3CN, subjected to two cycles
of freeze, pump and thaw, and exposed to CO2 at low temperature
(~-40 °C). 31P{1H} NMR analysis of the reaction mixture, in a
precooled NMR probe at -35°C confirmed the presence of 1 in the
reaction medium (see SI Fig S45). For deeper understanding of
CO2 activation by 1a, we have carried out the intrinsic bond orbital
(IBO) analysis scheme developed by Knizia et al.[52] This
procedure is extensively applied to understand the bond
breaking/bond making process along the reaction coordinate.[53-
54]
Here, the evolution of IBO along the intrinsic reaction
coordinates of the transition states as shown in Figure 3. have
been assessed to analyse the relevant electron density flow from
1 to phenylsilane during the CO2 activation. As shown in Figure 3,
three IBOs corresponding to the π(CNHC-P), σ (P-Si), and σ (Si-
H) bond have revealed significant charge flux along the intrinsic
3
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reaction coordinate (IRC). Figure 3. demonstrates the IBO
(purple lobe) of the C-P bond of 1 being transformed into the P-Si
bond while IBO (light blue lobe) evolves from a Si-H bond in silane
to a C-H bond on the CO2. Upon closer inspection to the orbital
distribution along the reaction coordinate, it reveals that π bond
of the C-P in 1 is transforming into the
standard substrate. It was found that 10 mol% 1 can perform
catalytic formylation of primary amides in 24 h using CO2 and
PhSiH3 under ambient temperature with 37% NMR conversion
(Table 1, entry 1). Under such conditions, various solvents such
as acetonitrile, toluene, chlorobenzene, dioxane, hexane were
screened (Table 1, entries 2-6) and it was observed that
acetonitrile delivers the best conversion (75%). It may be noted
that polar solvents such as THF, acetonitrile and dioxane provided
better reactivity as compared to the other non-polar solvents such
as hexane and toluene. Such an observation may be accounted
for the better solubility of CO2 in polar solvents as also reported in
a recent study.[57] Next, we screened other silanes such as Et3SiH,
Ph2SiH2 and PMHS (Table 1, entries 7-9), however, the reaction
did not yield the desired product. From this optimization study, it
may be concluded that under 1 atm CO2, 10 mol% catalyst
delivered the best yield of formylated product (Table 1, entry 3).
With this optimized condition in hand, we explored various amide
substrates for reductive formylation to establish efficacy of 1 as a
catalyst. The formylation reaction with benzamide resulted in 75%
isolated yield upon purification using silica gel chromatography
(Table 3, 3b). Electron donating methyl-substituted benzamides
Table 1. Optimization of reaction conditions for formylation of primary amides
using 1 as a catalyst.
Figure 3. Intrinsic bond orbital analysis of the selected geometries along
Intrinsic reaction coordinate (IRC) of transition-state during CO2 activation by 1.
Intrinsic bond orbital (IBO) transformations along the P-Si bond are shown in
purple lobe and dissociation of Si-H towards electrophilic C centers of CO2 are
shown in blue. Transformations of Si-H to C-H bonds are shown as blue lobe
and intrinsic bond orbital (green lobe) corresponding to lone pair of electrons on
phosphorus center remains unaltered along the reaction coordinates. a, b, c, d,
e, and f correspond to the selected geometries from the IRC.
Sl No.
Silane
Solvent
Conversion
(%)
1
2
3
4
5
6
7
8
9
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
PhSiH3
Et3SiH
Ph2SiH2
PMHS
THF
37
NR
75
-bond between the P-Si bond. However, IBO (green lobe)
corresponding to the lone-pair of electrons on the phosphorus
atom in 1 remains preserved along the reaction coordinates as
shown in Figure 3. Since electronic redistribution occurs from the
π bond of the C-P towards the P-Si bond during the CO2 activation,
therefore 1 acts as a strong nucleophile to complete the CO2
activation via silane activation through the formation of 1-silane
adduct 1a. Calculated WBI ~1.20 of C-P bond in 1a also explains
the electronic redistribution for the activation mechanism of CO2
as it reduced significantly to 0.99 in the TS1 (Figure 2d, vide
supra). These findings on CO2 activation by the NHC stabilized
phosphinidene 1 in the presence of a silane prompted us towards
the development of a catalytic process. We have chosen the
formylation of primary amides by CO2 as a model transformation
since amide formylation has been considered extremely
challenging because of their inertness towards chemical
functionalization. Until 2018, the catalytic formylation of amide
was not known and till date only one study has been reported for
catalytic formylation of primary amides under metal-free
conditions.[46] N-formyl amides have widespread applications in
pharmaceutical industry in which they represent the synthetic
intermediates of many natural products.[55] Further they belong to
important class of reagents in several reactions as well as act as
amino protecting groups in peptide synthesis.[56] In our
optimization study, 2-methyl benzamide (2a) was used as a
Toluene
Acetonitrile
Chlorobenzene 12
Hexane
NR
20
Dioxane
Acetonitrile
Acetonitrile
Acetonitrile
NR
NR
NR
[a] Reaction conditions: Amide (0.3 mmol), silane (0.6 mmol), 1 (0.03 mmol,
10 mol%), and solvent (1 mL), NR stands for “No Reaction”
delivered corresponding formylated products 3a (68%), 3d (74%),
3e (61%) in good to very good isolated yields whereas electron-
withdrawing substrates afforded 3l (56%), 3n (57%) in moderate
yield. However, substrates possessing both electron-donating
and withdrawing substituents delivered 56% yield (3j). In
presence of chloride substitution, primary amides displayed low
reactivity towards formylation resulting in 3r (43%), 3m (40%) and
4
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3q (53%). In addition, the catalyst was efficient in performing the
formylation of heteroatom containing amides in good to moderate
yield of 3i (71%) and 3s (49%). Substrates bearing the nitro group
afforded 3p in 45% and 3o in 43% yield. Biphenylamide displayed
low reactivity yielding 33% (3t) whereas cinnamamide tolerated
the reaction conditions resulting in a yield of 48% (3g). However,
the reaction proceeded smoothly in presence of 2-/3-/4-methoxy
substituted benzamide in 72%, 76%, 82% (3c, 3k, 3h),
respectively while 2-ethoxy substituted benzamide led to 69% (3f)
yield. We were delighted to observe that 1 acts as an effective
catalyst in promoting the formylation of various aliphatic primary
amides (linear and cyclic) with an NMR conversion ranging from
27-77% (3u-3y).
Scheme 2 Plausible mechanistic cycle for formylation of primary amides using
NHC-stabilized phosphinidene 1.
At first, 1 interacts with PhSiH3 through π-π interaction between
two adjacent phenyl rings which initiates activation of the Si-H
bond (Figure 2a). Upon interaction of the CO2 molecule with such
π-π stacked adduct 1a, the C-P π bonded electron density flows
to further activate the Si-H bond resulting in its facile transfer to
the CO2 molecule (Figures 2d and 3), leading to the formation of
phenylsilyl formate which has been characterized by NMR
spectroscopy.[50] It may be noted that the activation of CO2
proceeds by a concerted pathway as depicted in Figure 3, and
this step is exergonic by -16.7 kcal/mol and therefore, it drives the
formylation reaction (Figure 4).
Table 2. Formylation of primary amides using the NHC stabilized phosphinidene
1 as a catalyst.
Figure. 4 Computed Gibbs free energy profile at 298 K using NHC stabilized
phosphinidene catalyst for formylation of benzamide using CO2.
Simultaneously in presence of 1, phenylsilane undergoes
dehydrogenation reaction with amide to form N-silylated amide (4)
on liberation of H2 molecule which was identified by 1H NMR
spectroscopic analysis (δ 4.58 ppm in CD3CN)[58] as well as GC-
MS analysis (Figure S50, SI) in a control reaction. Similar
activation of primary amides upon liberation of hydrogen molecule
by 9-BBN via N-borylation of primary amide has been reported in
recent literature.[59] Upon the formation of the N-silylated amide, it
reacts with the phenylsilyl formate. Subsequently, the formyl
transfer takes place from 5 to 4 and the reaction proceeds through
various transition states as depicted in Figure 4 leading to the
formation of desired product 3 along with siloxanes as the by-
product, also reported previously.[44] Furthermore, in a control
experiment, triphenylsiloxane Ph3Si-O-SiPh3 was identified as the
by-product by 1H and 29Si NMR spectroscopy when Ph3SiH was
used as the reducing agent.[46]
Reaction conditions. Amide (0.3 mmol), PhSiH3 (0.6 mmol), 1 (0.03 mmol, 10
mol%), and ACN (1 mL), Isolated yield in the parenthesis. [a] NMR conversion
using hexamethylbenzene as an internal standard.
This result establishes that NHC stabilized phosphinidene 1 can
act as an efficient catalyst for formylation of a range of primary
amides using CO2 under mild conditions. Based on the above
findings from control experiments and DFT calculations, a
plausible catalytic cycle is proposed in Scheme 2.
5
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recomputed along the each points of IRCs using ORCA, to generate the
IBO plots using the IboView program with iboexp=2.[65]
Conclusion
In conclusion, an NHC stabilized phosphinidene 1 was used as
the first metal-free catalyst in any organic transformation. Catalyst
1 effectively performed the formylation of a range of primary
amides using CO2 as a reagent under ambient temperature. The
CO2 activation is facilitated by a proposed weakly bound
phosphinidene-silane intermediate. Detailed DFT studies and
control experiments helped us to understand the underlying
mechanism involved in this transformation. London dispersion
force between the π-stacked aromatic rings along with the
nucleophilicity of 1 plays a crucial role in structural reorganization
of the catalyst. This result paves the way towards designing
strategy to use phosphinidenes as catalysts towards various
organic transformations.
General procedure for the formylation of primary amides.
Under an argon atmosphere, a 25 mL Schlenk tube equipped with a stir
bar and a J. Young valve was charged with amide (0.3 mmol), 1 (10 mol%),
phenylsilane (0.6 mmol) and acetonitrile (1 mL). For substrate having Br
or Cl or NO2 substituent, 100 µL DMSO was added for the solubility. The
mixture was degassed by two successive freeze-pump-thaw cycles and
was exposed with carbon dioxide in the frozen state. The reaction mixture
was allowed slowly to warm to room temperature and stirred for 24 h. Next,
the solvent was evaporated under reduced pressure and the product was
purified by column chromatography on silica gel (Merck, 100-200 mesh).
The N-formyl amide was collected as an analytically pure solid using
hexane-ethyl acetate mixture as the eluent. The corresponding formamide
was identified by 1H and 13C NMR spectroscopy in CDCl3 or DMSO-d6 or
CDCl3 and DMSO-d6 mixture.
Experimental Section
Materials and Methods
o
All reactions were performed in oven dried glassware (130 C) under dry
Acknowledgements
and oxygen free atmosphere (Argon) using standard Schlenk line
technique or inside Ar filled MBraun glovebox which is maintained at <0.1
ppm level of O2 and H2O. The solvents used for the reaction were dried
using Na/benzophenone mixture or CaH2 before use. All chemicals were
purchased from Sigma-Aldrich, Alfa Aesar, Merck, or Spectrochem and
used as received. 1 was prepared following the reported procedure.28
Thin-layer chromatography (TLC) was performed on a Merck 60 F254
silica gel plate (0.25 mm thickness). Column chromatography was
performed on a Merck 60 silica gel (100−200 mesh).GC-MS analysis was
carried out using Clarus 590 GC-MS instrument (Perkin Elmer). The
1H,13C,31P and 29Si NMR spectra were recorded on JEOL ECS 400 MHz
spectrometer and on Bruker Avance III 500 MHz spectrometer with
residual proton resonances (for CDCl3:1H at δ = 7.26, 13C{1H} at δ = 77.16,
CD3CN:1H at δ = 1.94, 13C{1H} at δ = 1.32, for DMSO: 1H at δ = 2.5, 13C{1H}
at δ = 39.5. Carbon dioxide was purchased from Praxair in a 5.5 purity gas
cylinder with 99.995% purity.
We acknowledge financial support from the MHRD-STARS
project, (STARS/APR2019/CS/473/FS). S.P thanks DST Inspire
for research fellowship. A.D thanks SERB project,
CRG/2020/000301 Intrinsic bond orbital analysis for support. K.B
acknowledges IACS for a research fellowship. We thank Dr.
Rangeet Bhattacharya for the help in VT NMR experiments.
Keywords: Phosphinidene • DFT • Intrinsic bond orbital analysis
• CO2 activation • Amide formylation
[1] F. Mathey, Angew. Chem., Int. Ed. 1987, 26, 275-286; Angew. Chem. 1987,
99, 285-296.
[2] T. Krachko, J. C. Slootweg, Eur. J. Inorg. Chem. 2018, 2734-2754.
[3] A. Doddi, M. Peters, M. Tamm, Chem. Rev. 2019, 119, 6994-7112.
[4] K. Lammertsma, Top. Curr. Chem. 2003, 229, 95-119.
[5] F. Zittel, W. C. Lineberger, J. Chem. Phys. 1976, 65, 1236-1243.
[6] T. Nguyen, A. Van Keer, L. G. Vanquickenborne, J. Org. Chem. 1996,
61, 7077-7084.
Computational Methods
All geometry optimization, singlet point calculations, vibrational frequency
and reaction free energies were carried out using density functional theory
through the Gaussian 16 suite of programs.[60] To determine spin
multiplicity of ground state of the complexes, both restricted and
unrestricted calculations were performed in the gas phase using hybrid
meta-GGA M06-2X functional[61] in conjunction with Def2-TZVP basis set
of theory using ORCA.[62] Natural bond orbital analysis (NBO) and Wiberg
bond indices (WBI) were performed at the M06-2X/Def2-TZVP level of
theory using the NBO6 version.[63] For main group element, M06-2X is
highly recommended for the thermochemical calculations, henceforth
M06-2X/6-31+G(d) level of theory was conducted to describe the reaction
energy of reductive functionalization of CO2. Harmonic vibrational
frequencies were calculated at same level of theory to ensure the absence
of saddle point of intermediate geometries and only one imaginary
frequency in transition state structures. IRC calculation was further
performed to confirm that the TS structure connected with reactants and
products. To account the solvation energies in acetonitrile, self-consistent
reaction field (SCRF) approach using SMD continuum solvation model has
been utilized.[64] Furthermore, to improve the accuracy of the reaction
energies obtained from the M06-2X/6-31+G(d,p) level of theory, single-
point calculations were carried out using triple-ζ valance shell with
additional diffuse and polarization basis set (6-311++G(d,p)) on the top of
the optimized geometries. All the free energies are obtained from the M06-
2X/6-311++G(d,p)(SMD)//M06-2X/6-31+G(d,p) level of theory at 298 K. To
investigate the intrinsic bond orbitals (IBO), single point calculations were
[7] A. J. Arduengo III, H. V. R. Dias, J. C. Calabrese, Chem. Lett. 1997, 26, 143-
144.
[8] Y. Wang, Y. Xie, M.Y. Abraham, R.J. Gilliard Jr., P. Wei, H.F. Schaefer III,
P.v.R. Schleyer,G.H. Robinson, Organometallics 2010, 29, 4778-4780.
[9] O. Back, M. Henry-Ellinger, C.D. Martin, D. Martin, G. Bertrand, Angew.
Chem. Int. Ed. 2013, 52, 2939–2943; Angew.Chem. 2013,125, 3011–3015.
[10] L. Liu, D. A. Ruiz, F. Dahcheh, G. Bertrand, Chem. Commun. 2015, 51,
12732–12735.
[11] K. Hansen, T. Szilvási, B. Blom, S. Inoue, J. Epping, M. Driess, J. Am.
Chem. Soc. 2013, 135, 11795-11798.
[12] A. Doddi, D. Bockfeld, T. Bannenberg, P. G. Jones, M. Tamm, Angew.
Chem. Int. Ed. 2014, 53, 13568-13572; Angew.Chem. 2014, 126,13786-13790.
[13] A. Doddi, D. Bockfeld, A. Nasr, T. Bannenberg, P. G. Jones, M. Tamm,
Chem. Eur. J. 2015, 21, 16178–16189.
[14] S. Roy, K. C. Mondal, S. Kundu, B. Li, C. J. Schürmann, S. Dutta, D. Koley,
R. Herbst-Irmer, D. Stalke, H. W. Roesky, Chem. Eur. J. 2017, 23, 12153–
12157.
[15] S. Kundu, S. Sinhababu, A. V. Luebben, T. Mondal, D. Koley, B. Dittrich, H.
W. Roesky, J. Am. Chem. Soc. 2018, 140, 151–154.
[16] A.M. Tondreau, Z. Benkö, J.R. Harmer, H. Grützmacher, Chem. Sci. 2014,
5, 1545–1554.
6
This article is protected by copyright. All rights reserved.

10.1002/chem.202101202
Chemistry - A European Journal
FULL PAPER
[17] V. A. K. Adiraju, M. Yousufuddin, H. V. R. Dias, Dalton Trans. 2015, 44,
4449-4454.
[54] M. Mandal, C. E. Elwell, C. J. Bouchey, T. J. Zerk, W. B. Tolman, C. J.
Cramer, J. Am. Chem. Soc. 2019, 141, 17236-17244.
[18] H. Schneider, D. Schmidt, U. Radius, Chem. Commun. 2015, 51, 10138-
10141.
[55] J. E. Mathieson, J. J. Crawford, M. Schmidtmann, R. Marquez, Org. Biomol.
Chem. 2009, 7, 2170–2175.
[19] L. Liu, D. A. Ruiz, D. Munz, G. Bertrand, Chem 2016, 1, 147-153.
[20] M. Regitz and O. J. Scherer, Multiple Bonds and Low Coordination
Phosphorus Chemistry, Georg Thieme, Stuttgart and NewYork, 1990, p.157.
[21] M. M. Hansmann, R. Jazzar, G. Bertrand, J. Am. Chem. Soc. 2016, 138,
8356-8359.
[56] P. V. S. Ramya, S. Angapelly, B. N. Babu, C. S. Digwal, A. Nagarsenkar,
S. Gannoju, B. Prasanth, M. Arifuddin, K. Kanneboina, K. Rangan, A. Kamal,
Asian J. Org. Chem. 2017, 6, 1008-1013.
[57] A. Cerveri, R. Giovanelli, D. Sella, R. Pedrazzani, M. Monari, O. N. Faza,
C. S. López, M. Bandini, Chem. Eur. J. 2021, DOI: 10.1002/chem.202101082.
[58] G. R. Fulmer, A. J. M. Miller, N. H. Sherden, H. E. Gottl
10.1002/chem.202101082ieb, A. Nudelman, B. M. Stoltz, J. E. Bercaw, K. I.
Goldberg, Organometallics 2010, 29, 2176-2179.
[22] A. J. Arduengo III, C. J. Carmalt, J. A. C. Clyburne, A. H. Cowley, R. Pyati,
Chem. Commun. 1997, 981–982.
[23] T. G. Larocque, G. G. Lavoie, New J. Chem. 2014, 38, 499-502.
[24] L. Liu, D. A. Ruiz, F. Dahcheh, G. Bertrand, Chem. Commun. 2015,
51,12732–12735.
[59] M. Bhunia, S. R. Sahoo, A. Das, J. Ahmed, P. Sreejyothi, S. K.
Mandal, Chem. Sci. 2020, 11, 1848-1854.
[60] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J.
R. Cheeseman, G. Scalmani, V. Barone, G. A. Petersson, H. Nakatsuji, X. Li,
M. Caricato, A. V. Marenich, J. Bloino, B. G. Janesko, R. Gomperts, B.
Mennucci, H. P. Hratchian, J. V. Ortiz, A. F. Izmaylov, J. L. Sonnenberg, D.
Williams-Young, F. Ding, F. Lipparini, F. Egidi, J. Goings, B. Peng, A. Petrone,
T. Henderson, D. Ranasinghe, V. G. Zakrzewski, J. Gao, N. Rega, G. Zheng,
W. Liang, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T.
Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, K. Throssell, J. A.
Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. J. Bearpark, J. J. Heyd, E. N.
Brothers, K. N. Kudin, V. N. Staroverov, T. A. Keith, R. Kobayashi, J. Normand,
K. Raghavachari, A. P. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi,
J. M. Millam, M. Klene, C. Adamo, R. Cammi, J. W. Ochterski, R. L. Martin, K.
Morokuma, O. Farkas, J. B. Foresman, D. J. Fox, Gaussian 16, Revision A.03,
Gaussian, Inc., Wallingford CT, 2016.
[61] Y. Zhao,D. G. Truhlar, Theor. Chem. Acc. 2008, 120, 215-241.
[62] F. Neese, The ORCA program system. Wiley Interdiscip. Rev. Comput.
Mol. Sci. 2012, 2, 73-78.
[63] F. Weinhold, C. R. Landis, Cambridge University Press: Cambridge, UK,
2005
[64] A. V. Marenich, C. J. Cramer, D. G Truhlar, J. Phys. Chem. B. 2009, 113,
6378−6396.
[65] E. R. Hoffman, Magn. Reson. Chem. 2006, 44, 606-616.
[25] D. Bockfeld, A. Doddi, P. G. Jones, M. Tamm, Eur. J. Inorg. Chem. 2016,
3704–3712.
[26] M. Klein, G. Schnakenburg, A. Espinosa Ferao, N. Tokitoh, R. Streubel,
Eur.J. Inorg. Chem. 2016, 685–690.
[27] M. Peters, A. Doddi, T. Bannenberg, M. Freytag, P. G. Jones, M. Tamm,
Inorg. Chem. 2017, 56, 10785–10793.
[28] T. Krachko, M. Bispinghoff, A. M. Tondreau, D. Stein, M. Baker, A. W.
Ehlers, J. C. Slootweg, H. Grützmacher, Angew. Chem. Int. Ed. 2017, 56, 7948–
7951; Angew. Chem. 2017, 129, 8056-8059.
[29] C. M. E. Graham, C. R. P. Millet, A. N. Price, J. Valijus, M. J. Cowley, H. M.
Tuononen, P. J. Ragogna, Chem. Eur. J. 2018, 24, 672–680.
[30] Y. Wang, Y. Xie, P. Wei, H. F. Schaefer III, P. V. R. Schleyer, G. H.
Robinson, J. Am. Chem. Soc. 2013, 135, 19139-19142.
[31] P. Sreejyothi, S. K. Mandal, Chem. Sci. 2020, 11, 10571–10593.
[32] F.-G. Fontaine, M.-A. Courtemanche, M.-A. Légaŕe, Chem. Eur.J. 2014, 20,
2990-2996.
[33] G. Fiorani, W. Guo, A. W. Kleij, Green Chem. 2015, 17, 1375-1389.
[34] A. Tlili, E. Blondiaux, X. Frogneux, T. Cantat, Green Chem. 2015, 17, 157-
168.
[35] M. Hulla, P. J. Dyson, Angew. Chem. Int. Ed. 2020, 59, 1002-1017; Angew.
Chem. 2020, 132, 1014-1029.
[36] P. Bag, C. Weetman, S. Inoue, Angew. Chem. Int. Ed. 2018, 57, 14394-
14413; Angew. Chem. 2018, 130, 14594-14613.
[37] Y. Wang, T.Szilvasi, S. Yao, M. Driess, Nat. Chem. 2020, 12, 801−807.
[38] C. Das Neves Gomes, O. Jacquet, C. Villiers, P. Thuéry, M. Ephritikhine, T.
Cantat, Angew. Chem. Int. Ed. 2012, 51, 187-190; Angew. Chem. 2012, 124,
191-194.
[39] O. Jacquet, C. Das Neves Gomes, M. Ephritikhine, T. Cantat, J. Am. Chem.
Soc. 2012, 134, 2934-2937.
[40] L.-D. Hao, Y.-F. Zhao, B. Yu, Z.-Z. Yang, H.-Y. Zhang, B.-X. Han, X.
Gao, Z.-M. Liu, ACS Catal. 2015, 5, 4989-4993.
[41] M. Hulla, F. D. Bobbink, S. Das, P. J. Dyson, ChemCatChem 2016, 8,
3338-3342.
[42] C. C. Chong, R. Kinjo, Angew. Chem. Int. Ed. 2015, 54, 12116-12120;
Angew. Chem. 2015, 127, 12284-12288.
[43] D. Sarkar, C. Weetman, C. Dutta, E. Schubert, C. Jandl, D. Koley, S.
Inoue, J. Am. Chem. Soc. 2020, 142, 15403-15411.
[44] B.-X. Leong, Y.-C. Teo, C. Condamines, M.-C. Yang, M.-D. Su, C.-W. So,
ACS Catal. 2020, 10, 14824-14833.
[45] J. Fan, J.-Q. Mah, M.-C. Yang, M.-D. Su, C.-W. So, J. Am. Chem. Soc.
2021, 143, 4993-5002.
[46] P. K. Hota, S. C. Sau, S. K. Mandal, ACS Catal. 2018, 8, 11999-12003.
[47] A. Gopakumar, L. Lombardo, Z. Fei, S. Shyshkanov, D. Vasilyev, A.
Chidambaram, K. Stylianou, A. Züttel and P. J. Dyson, J. CO2 Util. 2020, 41,
101240.
[48] A. Nijamudheen, D. Jose, A. Shine, A. Datta, J. Phys. Chem. Lett. 2012, 3,
1493-1496.
[49] J. Contreras-García, E. R. Johnson, S. Keinan, R. Chaudret, J.-P. Piquemal,
D. N. Beratan, W. Yang, J. Chem. Theory Comput. 2011, 7, 625–632.
[50] E. R. Johnson, S. Keinan, P. Mori-Sánchez, J. Contreras-García, A. J.
Cohen, W. Yangm, J. Am. Chem. Soc. 2010, 132, 6498-6506.
[51] Q. H. Zhou and Y. X. Li, J. Am. Chem. Soc. 2015, 137, 10182-10189.
[52] G. Knizia, J. Chem. Theory Comput. 2013, 9, 4834-4843.
[53] W.-M. Ching, A. Zhou, J. E. M. N. Klein, R. Fan, G. Knizia, C. J. Cramer, Y.
Guo and L. Que, Jr., Inorg. Chem. 2017, 56 , 11129-11140 .
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Entry for the Table of Contents
This work highlights introduction of a low-valent phosphorus compund in the arena of catalysis in which N-heterocyclic carbene
stabilized phosphinidene (1) was utlized for the activation of CO2. The DFT calculations unravel that nucleophilicilty of the phosphorus
center and a non-colvant π-π interaction between the phenyl rings of phenylsilane and the catalyst syngersticaly drives the formylation
of primary amides by CO2 under mild conditions.
8
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