Carbon's Three-Center, Four-Electron Tetrel Bond, Treated Experimentally

Article abstract of DOI:10.1021/jacs.8b09367

Tetrel bonding is the noncovalent interaction of group IV elements with electron donors. It is a weak, directional interaction that resembles hydrogen and halogen bonding yet remains barely explored. Herein, we present an experimental investigation of the

Full text of DOI:10.1021/jacs.8b09367

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Article
Carbon’s Three-Center-Four-Electron Tetrel Bond, Treated Experimentally
Alavi Karim, Nils Schulz, Hanna Andersson, Bijan Nekoueishahraki, Anna-Carin C. Carlsson,
Daniel Sarabi, Arto Valkonen, Kari Rissanen, Jürgen Gräfenstein, Sandro Keller, and Máté Erdélyi
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Carbon’s Three-Center-Four-Electron Tetrel Bond, Treated Experimen-
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Alavi Karim,† Nils Schulz,‡ Hanna Andersson,†,║ Bijan Nekoueishahraki,† Anna-Carin C. Carlsson,†,
Daniel Sarabi,† Arto Valkonen, Kari Rissanen, Jürgen Gräfenstein,† Sandro Keller,¶ Máté Er-
délyi†,║,§,
*
† Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden
‡ Faculty of Chemistry and Biochemistry, Organic Chemistry I, Ruhr-Universitꢀt Bochum, Universitꢀtsstraße 150, 44801
Bochum, Germany
║ Department of Chemistry - BMC, Uppsala University, SE 751 20 Uppsala, Sweden
 University of Jyvaskyla, Department of Chemistry, P.O. Box. 35, FI-40014 University of Jyväskylä, Finland
¶ Molecular Biophysics, Technische Universität Kaiserslautern (TUK), 67663 Kaiserslautern, Germany
§ The Swedish NMR Centre, Medicinaregatan 5, SE-413 90 Gothenburg, Sweden
ABSTRACT: Tetrel bonding is the noncovalent interaction of Group IV elements with electron donors. It is a weak, directional
interaction that resembles hydrogen and halogen bonding, yet remains barely explored. Herein, we present an experimental investi-
gation of the carbon-centered, three-center four-electron tetrel bond, [NCN]+, formed by capturing a carbenium ion with a biden-
tate Lewis base. NMR-spectroscopic, titration-calorimetric- and reaction-kinetic evidence for the existence and structure of this
species is reported. The studied interaction is by far the strongest tetrel bond reported so far, and is discussed in comparison with
the analogous halogen bond. The necessity of the involvement of a bidentate Lewis base in its formation is demonstrated by provid-
ing spectroscopic and crystallographic evidence that a monodentate Lewis base induces a reaction rather than stabilizing the tetrel
bond complex. A vastly decreased Lewis basicity of the bidentate ligand or reduced Lewis acidity of the carbenium ion weakens –
or even prohibits – the formation of the tetrel bond complex, whereas synthetic modifications facilitating attractive orbital overlaps
promote it. As the geometry of the complex resembles the SN2 transition state, it provides a model system for the investigation of
fundamental reaction mechanisms and chemical bonding theories.
INTRODUCTION
both in solutions and in the solid state, and possesses a partial
covalent character.18-23 Whereas conventional halogen bonds,
RX…Y, are up to ~40 kJ/mol energy, the three-center four-
electron halogen bonds are significantly stronger, 120-150
kJ/mol.19,21 Due to its exceptional strength, the three-center N-
I-N halogen bond is applicable for stabilization of intricate
complex supramolecular complexes, for instance.24-26 The
noncovalent interactions in which tetrel elements, i.e. those
belonging to Group IV of the periodic system, act as electro-
philes are typically very weak, < 10 kJ/mol.27 Both computa-
tional and experimental evidence is available for the lightest
tetrel element, carbon, forming tetrel bonds.28-30 Complexes
possessing a three-center four electron tetrel bond with carbon
acting as the electrophilic center correspond to a pentacoordi-
nate configuration11 that is commonly referred to as an “acti-
vated complex” or “transition state”. This labile geometry31
involves a trigonal bipyramidal carbon with three of its sub-
stituents situated in one plane, whilst the incoming nucleophile
and leaving group are positioned apically in a linear three-
center four-electron tetrel bond. Among other reactions, the
classical bimolecular nucleophilic substitution (SN2) passes
through this high energy configuration, as discussed in virtual-
ly every undergraduate textbook. The carbon tetrel bond has
been suggested to play a critical role in directing SN2 reac-
tions.32 Because of its fundamental importance, the generation
of model compounds allowing the experimental investigation
Noncovalent interactions are receiving a vastly increasing
interest. Over the past decade, the hydrogen bond has been
redefined,1 and the analogous halogen,2 pnictogen,3 chalco-
gen,4,5 aearogen6 and coinage-metal7 bonds have been catego-
rized8,9 as either -hole10 or E-bond interactions.7 These inter-
actions, ZX…Y, are typically observed between a Lewis base,
Y, and a region of positive electrostatic potential on atom X,
being an electrophile connected to atom Z, along the extension
of the ZX bond. The stronger the interaction, the shorter and
more directional the XY and the longer the ZX bond is.
When the Lewis basicity of the atoms Z and Y are closely
matched (Z ≈ Y), the central electrophilic atom X is equally
shared between them, and accordingly the ZX and XY
bonds are equally strong and equally long. These interactions
were described as three-center four-electron bonds.11 With a
proton being the electrophilic atom (X = H), this special bond
(YXY) is commonly termed a “low-barrier”, a “short” or a
“strong” hydrogen bond.12 The low-barrier NHN and
OHO hydrogen bonds received great interest, as they were
proposed to be extra strong – up to ~125 kJ/mol – and accord-
ingly stabilize transition states and intermediates, for example
in enzyme-catalyzed reactions.13,14 Their true nature and ge-
ometry, however, remains the subject of intense debates.15-17
The analogous YXY halogen bond is static and symmetric
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of this carbon configuration has raised vast interest. All model
C+, of 1a-f (Figures 1 and 2) has an empty p-orbital capable of
simultaneously forming two NC bonds upon overlapping
with the nonbonding orbital of the two nitrogen donors that are
positioned at optimal distance and in an ideal orientation pro-
vided by 2a-c. This orbital overlap is expected to yield two
bonds possessing a partial covalent character,19,23,48 The result-
ing complex (3a-f, Figure 2) ought to have a three-center four-
electron [NCN]+ tetrel bond and a trigonal bipyramidal
geometry, analogous to that of the transition state of SN2.39
Here, we present the synthesis, solution NMR-spectroscopic,
calorimetric, and kinetic investigations of the intermolecular
tetrel bond complexes 3.
systems so far explored experimentally are intramolecular,33-40
and possess two intramolecular electron donor functionalities
geometrically forced into the apical positions of the electro-
philic carbon, trapping it in a (pseudo)pentacoordinate config-
uration.34-39,41,42
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By contrast, the investigation of intermolecular complexes
that require formation of a thermodynamically stable three-
center four-electron tetrel bond, allowing dissociation or
smooth adjustment of bond distances and angles for a stable
geometry, has so far lagged behind. Herein, we present the
first intermolecular three-center four-electron tetrel bond
complex possessing a carbon as the central electrophile, and
its investigation in solution.
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RESULTS AND DISCUSSION
Synthesis. 1,2-bis(pyridin-2-ylethynyl)benzenes 2a-c were
synthesized following a published procedure.21 Pyridine, 4-
picoline, 1a and 1f were commercially available, whereas 1d
and 1e were synthesized from their triaryl alcohol and triaryl
halide precursors, respectively (Supporting Information).50 To
generate complexes 3a-f (Figure 2, Table 1), 1a-f and ligands
2a-c (1:1) were mixed at room temperature under dry condi-
tions in an NMR tube, using dry CD2Cl2 as solvent. For the
generation of 5b-c (Figure 2, Table 1), two equivalents of dry
pyridine or picoline were added to the CD2Cl2 solution of
triphenylcarbenium tetrafluoroborate, 1a.
Structure elucidation. As 15N NMR has an inherently wide
chemical shift range of ~800 ppm, it is expected to provide
large, easy-to-detect chemical shift changes upon formation of
weak molecular complexes in which a nitrogen acts as a Lewis
base.22,48,51 Accordingly, ~100 ppm 15N NMR coordination
shifts, δ15Ncoord, have been reported for formation of
[NIN]+ halogen-bonded complexes.18,19,21,23 Following
literature conventions,21 coord is defined as the chemical shift
Figure 1. The three-center four-electron bond, [NCN]+, of a
hypercoordinate carbon (left) resembles the isoelectronic three-
center halogen bond, [NXN]+ (right). The empty p-orbital of
the central atom of both complexes possesses two electrophilic
regions (blue) that simultaneously receive electrons from two
Lewis bases (red), the nonbonding orbitals of two complexing
pyridines. The structures shown are [bis(pyridine)triphenyl-
carbenium]+ (left) and [bis(pyridine)iodine]+ (right) and are illus-
trated with their color-coded electrostatic potential mapped on the
electron isodensity surface at a contour value of 0.09 electron
Bohr-3. The color ramp indicates the most negative potential red
(0.3 a.u.) and the most positive potential blue (0.85 a.u.).
difference of the complex and the free ligand, that is coord
=
complex - ligand. Because of its proven applicability, 15N NMR
was applied here as the primary tool to detect analogous
[NCN]+ tetrel bond complexes (Table 1). The observation
of a single set of 15N NMR signals for 3a-f suggests the for-
mation of complexes in which the carbenium carbon is equally
bound to both Lewis basic nitrogens (Table 1, Figure 3). Ac-
cordingly, the 15N NMR chemical shift change observed on the
bidentate ligand is accompanied by a large 13C NMR chemical
shift change of the carbenium carbon (Table 1) of the interac-
tion partner, thus supporting the formation of a [N…C…N]+
three-center four-electron tetrel bond in 3a-d, whereas reveal-
ing the formation of no, or very weak, complexes for 3e-f. The
observed 15N complexation shifts, δ15Ncoord, are comparable
in magnitude, yet are somewhat smaller than those observed
for the isoelectronic halogen bonded compounds.19,21-23
Lately, the analogy of the three-center four-electron tetrel
bond of carbons38 to those of the isoelectronic halogen bond,
such as that of the central halogen of the triiodide ion, [III]-
42,43
,
and of [NXN]+ complexes,18,19,23 has been recog-
nized.11,44-47 The three-center halogen bond of [NXN]+
complexes is formed by the donation of two unshared elec-
trons of the nitrogens into the ‘p–holes’, that is the two lobes
of the vacant p–orbital of the halogen(I) (Figure 1).48 These ‘p-
holes’ are analogous to the electron depleted –hole that gives
rise to the formation of classical halogen, chalcogen, pnicto-
gen and tetrel bonds.49 Whereas the three-center four-electron
halogen bond complexes have been assessed experimentally,
the corresponding compounds encompassing three-center
four-electron tetrel bonds have so far been studied in silico,41,47
but rarely under standard laboratory conditions in solution.37,38
The molecular system studied here resembles the one we
previously applied for the assessment of the isoelectronic
halogen bond.18,19 Similar to the cationic halogen, X+, held in
position by two NX halogen bonds, the carbenium carbon,
Upon mixing 1a with 1,2-bis(phenylethynyl)benzene, an an-
alogue of 2c lacking any Lewis basic nitrogen, no 13C NMR
chemical shift alteration on 1a could be observed (Figure S1,
Supporting Information), corroborating that the interaction
seen for 3a-f involves the nitrogens. As an additional control
to confirm the involvement of the trityl carbon in the interac-
tion responsible for formation of 3a-f, the 15N NMR shift of 2c
was measured in the presence of tri-p-tolylmethanol. This
resulted in no nitrogen chemical shift alteration of 2c (Figure
S2, Supporting Information). The two control experiments
confirm that the large δ15Ncoord and δ13Ccoord observed for 3c
cannot be due to moisture-induced decomposition of 1a and
subsequent hydrogen bonding of triphenylmethanol to 2c.
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Figure 2. Synthesis of complexes 3a-f and 5b-c. For all compounds, R = H (a-c), Me (d), OMe (e), NMe2 (f), R’ = CF3 (a), Me (b), and H
(c-f). Hence, 3a (1a+2a), 3b (1a+2b), 3c (1a+2c), 3d (1d+2c), 3e (1e+2c), 3f (1f+2c), 5b (1a+4b), and 5c (1a+4c). Conditions: The com-
pounds were mixed in dry CD2Cl2 at room temperature in an NMR tube. The structure of 3a-f is not necessarily its preferred conformation.
Table 1. The 15N and 13C NMR Chemical Shiftsa and Coordination Shifts (ppm) of [NCN]+ Tetrel Bond Complexes.
15Nligand
-53.4
15Ncomplex 15Ncoord 13Cligand 13Ccomplex 13Ccoord
R, R’
H, CF3
H, Me
H, H
-81.5
-28.1
-82.0
-79.5
-45.5
-16.0
0.4
211.3
211.3
211.3
205.0
193.0
178.7
211.3
101.1
101.1
101.5
82
-110.2
-110.2
-109.8
-123.0
0.0
3a (1a+2a)
3b (1a+2b)
3c (1a+2c)
3d (1d+2c)
3e (1e+2c)
3f (1f+2c)
5b (1a+4b)
-69.2
-151.2
-144.0
-110.0
-80.5
-64.5
Me, H
OMe, H
-64.5
-64.5
193.0
178.7
89.2
NMe2, H -64.5
-64.9
0.0
H, Me
-73.8
-160.3
-115.5
-153.3
-75.8
-86.5
-41.7
-86.3
-8.8
-122.1
H, H
-67.0
211.3
90.3
-121.0
5c (1a+4c)
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a 15N NMR shifts were referenced to CH3NO2 (0 ppm) using a closed capillary.51
the electrophile. The15N -144.0 ppm of 3c indicates a strong
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2
NC bond, which is close in chemical shift to that of the cova-
lently functionalized pyridine of 5c (15N -153.3 ppm). Strong
complexation for 3c was supported by the comparable transla-
tional diffusion coefficients of 1a (11.5 × 10-10 m2s-1) and 2c
(13.8 × 10-10 m2s-1) of the complex. The diffusion coefficients
of 1a and one of the pyridines (δ15Ncoord -86.3 ppm) of com-
plex 5c are similar (9.8 × 10-10 m2s-1 and 9.4 × 10-10 m2s-1),
indicating that these are connected, whereas the second weak-
ly complexing pyridine (δ15Ncoord -8.8 ppm) has a diffusion
coefficient (25.6 × 10-10m2 s-1) that indicates that this pyridine
moves independently of 1a in solution.
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Dynamics. Compounds 3a-c might be involved in a bell–
clapper-type rearrangement;38 that is, instead of being present
as static and symmetric [NCN]+ tetrel bond complexes,
they might exist in solution as dynamic mixtures of rapidly
exchanging complexes possessing a covalent CN bond and a
pyridine weakly connected through a conventional CN tetrel
Figure 3. Superimposed 15N HMBC spectra of complexes 3c
(red) and 5c (green) acquired in CD2Cl2 solution at 25 °C. Where-
as 3c shows a single set of 15N NMR signals suggesting equally
strong coordination of the carbenium ion to both nitrogens, 5c has
an asymmetric structure with a strongly and a weakly coordinat-
ing nitrogen revealed by two sets of signals. Note that the struc-
ture drawn for 3c is not necessarily its most stable conformation.
bond, [NCN]+
[NCN]+. To differentiate between
the possibilities of a static and symmetric complex vs. a mix-
ture of rapidly interconverting, weakly coordinating ones, we
1
followed the standard procedures of the field,38 acquiring H
1
and 13C NMR and H,15N HMBC spectra for 3d at various
Whereas bidentate ligands 2a-c promote formation of a sym-
metric [NCN]+ complex, or possibly a rapidly equilibrating
temperatures. Both the static and the dynamic geometries are
expected to show a single sharp set of NMR signals at higher
temperatures. A single set of signals is expected to remain
detectable also at low temperature for a static [NCN]+
tetrel bond complex, whereas for a dynamic mixture of asym-
metric structures, two sets of signals, or at least significant
signal broadening, is expected.38 We observed a single sharp
set of 1H, 13C and 15N NMR signals at all temperatures, includ-
ing at -40°C (Figure S3-S5, Supporting Information). This
observation is best compatible with a static and symmetric
geometry, even if it cannot fully exclude a very low barrier
pair of asymmetric [NCN]+
[NCN]+ complexes,52
the monodentate Lewis bases pyridine and picoline form
asymmetric ion pairs with 1a as indicated by the observation
of two sets of 15N NMR chemical shifts for 5b-c (Table 1,
Figure 3). The coordination shifts, δ15Ncoord, of the latter
complexes suggests that one nitrogen forms a strong, presum-
ably covalent, bond to the carbenium carbon of 1a, whereas
the other nitrogen is involved in a weaker secondary interac-
tion. This hypothesis was corroborated by the identification by
single-crystal X-ray diffraction of 1-tritylpyridin-1-ium tetra-
fluoroborate crystals (CCDC 1581474), formed from the
CD2Cl2 solution of 5c (Figure 4). Hence, the bidentate Lewis
[NCN]+
[NCN]+ interconversion, with an energy
barrier G‡ << 38 kJ/mol and half-life of the possible inter-
converting states t1/2 << 6.4 μs, when estimated from the
chemical shift difference of pyridine (4c, (15N) -67 ppm) and
1-tritylpyridinium ion (5c, (15N) -153 ppm) as model com-
pounds for the equally populated, not exchanging free vs. N-
alkylated end states, the 15N NMR observation frequency
50.67 MHz and a coalescence temperature < -40°C.53 In order
to detect a possible low-barrier interconversion, we further
performed isotopic perturbation of equilibrium (IPE) NMR
measurements.54,55 Similar to earlier studies of related systems,
we compared the temperature dependence of the secondary
deuterium isotope effects of 3d to those of a static reference,
2c, and of its hydrogen bonded [NHN]+
[NHN]+
complex used as a dynamic reference, as described in detail
elsewhere.15,18-21,56 Selective deuterium labelling of 2c was
performed at the pyridine carbon closest to the nitrogen,19 and
isotope effects were collected in the temperature range 25 °C
to -40 °C, for all pyridine carbons. Signal overlaps prohibited
us from determining the temperature dependence of three- and
four-bond isotope effects, and hence from drawing a reliable
conclusion from the IPE NMR study (for details see page S46-
S48, in the Supporting Information). Overall, the variable
temperature study suggest that 3 is expectably present in solu-
tion as a static and symmetric [NCN]+ tetrel bond com-
plex, however we cannot fully exclude the possibility of
Figure 4. The molecular structure of 1-tritylpyridin-1-ium tetrafu-
loroborate. The thermal displacement parameters are shown at the
50% probability level.
base 2c stabilizes the reactive carbenium ion 1a, whereas its
monodentate analogue, pyridine, undergoes N-alkylation with
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Figure 5. Titration of the bidentate ligand 2c with 1a yields the strong 1:1 complex, 3c (top). Upon addition of an excess of 1a, the 1:2
complex of 1a:2c, 6c is formed, as revealed by the bimodal shape of the isotherm (bottom). Isothermal titration calorimetry was performed
at 25°C. Triphenylcarbenium tetrafluoroborate 1a at a concentration of 6.6 mM was titrated to the bidentate ligand 2c at a concentration of
0.5 mM. The main panel shows the isotherm depicting normalized heats of reaction, Q, as a function of the 1a/2c molar ratio in the calo-
rimeter cell (blue circles) along with uncertainties (blue horizontal lines) resulting from baseline assignment and peak integration.57 Non-
linear least-squares fits (red solid line) was based on the presumption of two interaction sites,58 as reflected in the bimodal shape of the
isotherm. Inset: The corresponding raw thermogram displaying differential heating power, p, versus time, t. Best-fit parameter values and
associated confidence intervals are summarized in the text, with the detailed analysis contained in the Supporting Information. Note that
the structure drawn for 3c is not necessarily its most stable conformation.
interconversion of analogous asymmetric [NCN]+
Despite repeated attempts, the crystallization of 3c and 3d
remained unsuccessful. It should, however, be noted that X-
ray crystallography would not necessarily be able to describe
[NCN]+ geometries encompassing conventional NC cova-
lent, and NC tetrel bonds.
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the geometry of three-center tetrel bond complexes in solution.
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The analogous [NHN]+ hydrogen bond complexes were
shown to be a rapidly interconverting mixture of asymmetric
geometries in solution whereas they are static, symmetric
complexes in the solid state.15 Preliminary DFT calculations of
5c and 3c were unable to reproduce the experimental observa-
tions (see Supporting Information S51–S66 for details). This
may indicate the need for higher-level computational ap-
proaches or that our structural interpretation of the NMR data
is not sufficiently accurate. DFT has previously correctly
predicted the geometry of an analogous asymmetric, intramo-
lecular three-center tetrel bond complex.37 Continued experi-
mental and computational investigations of the above and
closely related molecular systems are expected to be capable
of verifying or refuting the proposed structures of 3a–f.
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Binding affinity. Isothermal titration calorimetry was con-
ducted to determine the binding strength of complex 3c. Titra-
tion of the CH2Cl2 solution of 2c with triphenyl carbenium
tetrafluoroborate, 1a, dissolved in CH2Cl2, indicates the for-
mation of a strong 1:1 complex characterized by K1 = 1.9 nM,
G°1 = -49.8 kJ/mol, H°1 = -93.4 kJ/mol, and -TS°1 = 43.7
kJ/mol. Upon addition of an excess of 1a, a 1:2 (2c/1a) com-
plex 6c is generated in a second, weaker binding step with K2
= 237 nM, G°2 = -37.8 kJ/mol, H°2 = -53.1 kJ/mol, and -
TS°2 = 15.3 kJ/mol (Figure 5). Formation of the latter dial-
kylated 6c is in line with the smooth reaction of pyridine with
triphenylcarbenium tetrafluoroborate, 1a, to form 1-
tritylpyridin-1-ium tetrafluoroborate (5c). In the doubly posi-
tively charged complex 6c, the charge of the carbenium is
presumably distributed over the entire conjugated aromatic
system, akin to the analogous halogen bonded complexes.19,21
The formation of 6c upon addition of an excess of 1a to 2c
was also confirmed by NMR (15N -143.7 ppm, Supporting
Information, Figure S6). The free energy G°1 of the initial
complex formation results from a remarkable enthalpic contri-
bution, which is partly offset by a substantial loss of entropy;
for 6c, both contributions are largely reduced in magnitude,
but the reaction remains purely enthalpy driven. A reverse
titration, that is, addition of a CH2Cl2 solution of 2c into the
solution of 1a, supported the above binding model (Supporting
Information).
Figure 6. The progress of the Diels–Alder condensation, run
under literature conditions,59 of 1,3-cyclohexadiene (1.2 eq)
and acrolein (1 mmol) in CD2Cl2 in the presence of 0.5 mol%
1a or 3a was monitored by 1H NMR in an NMR tube at 25 °C
for 1 hour. The integral of the signals of the aldehyde proton
of the starting material and of the product was used to follow
the progress of the reaction. Whereas the reaction catalyzed by
1a (red) progresses with a second order rate, the addition of 2c
inhibits it (green) through masking the Lewis acidic 1a by
formation of the tetrel bond complex 3c.
were used, for example, to facilitate Diels–Alder reactions.59
Such reactions do not proceed in the absence of a catalyst,
whilst upon activation with 0.5 mol% triphenylcarbenium ion,
they give high conversion within 30 min. To provide addition-
al evidence for the participation of the carbenium p-orbital in a
tetrel bond, involving an orbital interaction, we ran the Diels–
Alder condensation of acrolein and cyclohexadiene (Figure 6)
in the presence of 1a, 3c and 7. Here, 7 denotes 2-((2-
(phenylethynyl)phenyl)ethynyl)-1-tritylpyridin-1-ium, formed
upon mixing 1a and 2-((2-(phenylethynyl)phenyl)-
ethynyl)pyridine (Supporting Information, page S8), a mono-
nitrogen analogue of 3c. We monitored the progress of each
Electron density. Upon complexation, a considerable
deshielding of the nitrogen of 2a-c and shielding of the carbe-
nium carbon of 1a-f were observed. The magnitude of the
observed chemical shift changes (Table 1) are expected to
reflect the electron density alteration of the studied complexes,
even if they do not necessarily correlate with bond strength.21
Upon decreasing the electron deficiency of the carbenium
carbon, 3c→f, smaller 15Ncoord and δ13Ccoord are detected
(Table 1). This may be due to a gradual weakening of the
[NCN]+ tetrel bond interaction upon decreasing the elec-
trophilicity of the carbenium carbon.
1
reaction by acquiring the H NMR integrals of the starting
material and the product using their well-separated aldehyde
protons as reporter nuclei. As shown in Figure 6, the Diels–
Alder reaction progresses with second order rate in the pres-
ence of 1a, whereas it does not give any conversion in the
presence of 3c and only low conversion in the presence of 7.
This is in excellent agreement with the observation of Fran-
zen, reporting that addition of the N-Lewis base 2,6-di-tert-
butylpyridine to 1a inhibits the Diels-Alder catalytic activity
of the latter.59 The lack of catalytic activity of 3c substantiates
strong complexation of 1a to 2c by the masking of the Lewis
acidic empty p-orbital of 1a without, however, providing
evidence specifically for formation of a three-center four-
electron bond. The observation is in agreement with the out-
come of the NMR and isothermal titration calorimetric studies,
and thus with formation of a stable intermolecular complex.
Increasing electron density of the Lewis basic nitrogen of
the bidentate ligand, 2a < 2c < 2b, is associated with an in-
crease of δ15Ncoord, in the order 3a < 3c < 3b. In contrast,
δ13Ccoord remains virtually unaltered. The weak electron
donating effect of a 4-Me substituent does not have a vast
influence on the coordination shifts as reflected by the compa-
rable δ15Ncoord and δ13Ccoord, of 3b and 3c as well as 5b and
5c.
CONCLUSIONS
The first experimental evidence of a stable, intermolecular
three-center four-electron tetrel bond complex is presented.
We demonstrate that a carbenium ion is converted into a tetrel
Masking Lewis acidity by tetrel bond formation. Tri-
phenyl carbenium ions are powerful Lewis acid catalysts that
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bond complex by simultaneous overlap of both lobes of the
tetrel bond complexes and their close analogues are expected
to be applicable to gain further insights into fundamental
reaction mechanisms and chemical bonding theories.
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empty p-orbital of the former species with the nonbonding
orbitals of two Lewis bases positioned to form a linear three-
center four-electron [NCN]+ bond. This bond resembles the
analogous three-center [NIN]+ halogen bond22 in geometry
and energy. Thus, formation of the [NCN]+ complex is
associated with ~50 kJ/mol change in free energy, as detected
by isothermal titration calorimetry. This complex possesses by
far the strongest tetrel bond so far reported.60,61 Its high stabil-
ity is corroborated by the inability of the complex to act as a
Lewis acid catalyst in a Diels–Alder reaction at room tempera-
ture. The observation of a single set of NMR signals even at
low temperatures suggests that the complex has a symmetric
three-center four electron bond, whose electron density can be
modulated by substitution. However, our observations cannot
fully exclude a very low barrier interconversion of asymmetric
species in solution. It should be noted that we were unable to
confirm the symmetric [NCN]+ geometry by computation
on the DFT level. Further computational studies of the com-
plexes studied herein may thus provide critical insights for
theoretical chemistry and, possibly, a more accurate structural
interpretation of the NMR and ITC data of 3a-f.
ASSOCIATED CONTENT
Supporting Information. Details on the synthesis, spectroscopic
data for compound identification, and details on the NMR, com-
putational, X-ray diffractometric, and kinetic investigations. This
material is available free of charge via the Internet at
http://pubs.acs.org.s.
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AUTHOR INFORMATION
Corresponding Author
* mate.erdelyi@kemi.uu.se.
Present Addresses
 Astra Zeneca R&D, Pepparedsleden 1, 431 83 Mölndal, Sweden
Funding Sources
The Swedish Research Council (2016-03602).
Notes
The authors declare no competing financial interest.
The formation of a stable three-center four-electron tetrel
bond complex requires the involvement of a bidentate Lewis
base whose donors are positioned at an optimal distance and
geometry to promote simultaneous overlaps with the unfilled
p-orbital of a carbenium ion. Upon use of two equivalents of
an analogous monodentate Lewis base, the carbenium does not
form a stable bidentate complex but rather N-alkylates the
electron donor. It should be noted that the isoelectronic
[bis(pyridine)iodine]+ and [bis(pyridine)bromine]+-type halo-
gen bonded model systems are stable in solution.19,20,22 Thus,
in contrast with the [NCN]+ complexes, the [NXN]+ ones
do not require the use of a bidentate ligand for thermodynamic
stability, highlighting an intriguing difference between halo-
gen and tetrel bonding. The difference in tetrel, halogen and
hydrogen bonding is further demonstrated by the fact that
[NCN]+ and [NIN]+ complexes are strong, static and
symmetric, whereas the analogous [NHN]+ complexes are
present in solution as mixtures of rapidly interconverting
ACKNOWLEDGMENT
We thank the Swedish Research Council (ME 2016:03602) for
financial support. N. Schulz thanks the Cluster of Excellence
RESOLV (EXC1069) by the Deutsche Forschungsgemeinschaft.
K. Rissanen and A Valkonen kindly acknowledge the Academy
of Finland (AV grant no. 314343) and the University of Jyväskylä
for financial support. J. Franzen and J. Bach of KTH, Sweden, are
gratefully acknowledged for instructive discussion on the Lewis
acidity of trityl cations. We also acknowledge M. Bedin (Uppsala
University) for helpful assistance in the early phase of the project.
This study made use of the NMR Uppsala infrastructure, which is
funded by the Department of Chemistry - BMC and the Discipli-
nary Domain of Medicine and Pharmacy at Uppsala University.
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ACS Paragon Plus Environment