A Doubly Biomimetic Synthetic Transformation: Catalytic Decarbonylation and Halogenation at Room Temperature by Vanadium Pentoxide

Article abstract of DOI:10.1002/cctc.201600843

The halogenation of the C?H bond by metal-oxo-peroxo species and the decarbonylation of aldehydes by metal-peroxo species are performed routinely in biological systems. However, metal-mediated decarbonylative halogenation is unknown in nature. In this work, we have shown that widely available V₂O₅ and VO(acac)₂ (acac=acetylacetonate) can catalyze decarbonylative halogenation through the generation of an intermediate vanadium-oxo-peroxo species, which was characterized by using ⁵¹ V NMR, UV/Vis, and resonance Raman spectroscopy. Further detection of formic acid from the reaction mixture confirmed the biomimetic aspects of decarbonylative halogenation. A detailed experimental and DFT study indicated a concerted mechanism for this decarbonylative halogenation performed under simple and mild reaction conditions.

Full text of DOI:10.1002/cctc.201600843

Accepted Article
Title: A Doubly Biomimetic Synthetic Transformation: Catalytic
Decarbonylation and Halogenation at RT by Vanadium Pentoxide
Authors: Debabrata Maiti, SUJOY RANA, Bhawana Pandey, Aniruddha
Dey, Rameezul Haque, and Gopalan Rajaraman
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ChemCatChem
A Doubly Biomimetic Synthetic Transformation: Catalytic Decarbonylation and
Halogenation at RT by Vanadium Pentoxide
Sujoy Rana, Bhawana Pandey, Aniruddha Dey, Rameezul Haque, Gopalan Rajaraman* and Debabrata Maiti*
Abstract: Halogenation of C–H bond by metal-oxo-peroxo
and decarbonylation of aldehyde by metal-peroxo species
are routinely done in biological systems. However, metal
mediated decarbonylative halogenation is unknown in Nature.
In this work, we have shown that widely available vanadium
pentoxide (V2O5) and VO(acac)2 can carry out the
decarbonylative halogenation via generating an intermediate
vanadium-oxo-peroxo species, which was characterized by
51V NMR, UV-Vis and Resonance Raman study. Further
detection of formic acid from the reaction mixture confirmed
the biomimetic aspects of decarbonylative halogenation. A
detailed experimental and DFT study indicated a concerted
mechanism for this decarbonylative halogenation performed
under simple and mild reaction conditions.
strategies.
Scheme 1. Mechanistic action followed by V-HPO
Scheme 2. Decarbonylation and halogenation reaction
Scheme 3. Decarbonylative halogenation byV2O5
Introduction:
Vanadium haloperoxidases (V-HPO) are involved in the
halogenation of more than 4500 natural products. Reaction
of hydrogen peroxide with vanadium center in V-HPO results
in vanadium-oxo-peroxo species formation.[1] A subsequent
halide attack forms vanadium oxyhalide intermediate, which
is primarily responsible for the halogenation of several
natural products as evident from literature (Scheme 1).[1c, 2]
The vanadium ion is oxidatively inert during the process and
maintains its V(5+) oxidation state throughout the catalytic
cycle. Several synthetic complexes including an array of
ligands coordinated to vanadium centers have been reported
to serve as functional mimics of V-HPO.[1a] In Nature
We started the present investigation with decarbonylative
chlorination of 2-methoxynaphthaldehyde by V2O5 (1) in
presence of KCl and H2O2. The desired 1-chloro-2-
methoxynaphthalene was obtained in good yield (Table 1,
entry 1). In absence of V2O5 and keeping all other reagents
deformylation is a common phenomenon. Cytochrome-P450, (e.g. KCl, H2O2) constant reaction was performed with 2-
14α-demethylase
and
cyanobacterial
aldehyde
methoxy-1-naphthaldehyde. Expectedly no trace of 1-chloro-
2-methoxynaphthalene was obtained. Further, exploration
with 2-hydroxynaphthaldehyde also produced the expected
1-chloronaphthalen-2-ol (50%) (Table 1, entry 2) by
successful decarbonylation and chlorination.
decarbonylase dependent enzymes carry out deformylation
reactions via eliminating formate.[3] In these cases both
mono and dinuclear heme-iron(III)-peroxo species has been
proposed as the plausible intermediates. Synthetic mono-
nuclear non-heme [FeIII(TMC)(2-O2)]+ (side-on peroxo) can
promote deformylation of aldehydes via elimination of
formate (HCO2-).[4] However, the coalescence of both the
phenomenon of decarbonylation and halogenation into a
single-step decarbonylative halogenation can be envisaged
by the vanadium-oxo-peroxo species (Scheme 2).[5]
Table 1. Decarbonylative halogenation by using V2O5 as
catalyst
Results and Discussion:
We envisioned that vanadium pentoxide, V2O5 (1) can
produce vanadium-oxo-peroxo, upon addition of acid and
hydrogen peroxide, which will carry out the decarbonylative
halogenations in presence of halide and hydrogen peroxide
(Scheme 3).
In addition to realizing this double-biomimetic reaction with
V2O5, a detailed experimental studies have been performed
to elucidate the mechanism of this decarbonylative
halogenation reaction. The commercial accessibility as well
as the cost-effectiveness of V2O5 is expected to attract
synthetic chemists to realize the full potential of these novel
[*] Sujoy Rana, Bhawana Pandey, Aniruddha Dey, Rameezul
Haque, Gopalan Rajaraman* and DebabrataMaiti*
Department of Chemistry, Indian Institute of Technology Bombay,
V2O5 (0.09 mmol), substrate (0.5 mmol), KCl (0.55 g, 7.5 mmol),
H2O2 (330 L, 3.25 mmol), acidic solution (prepared by HCl addition
to w ater) 2 mL and citrate-phosphate buffer (2 mL), acetone (1 mL).
Powai,
Mumbai-400076,
India.
E-mail:
gopalan.rajaraman@gmail.com (GR); dmaiti@chem.iitb.ac.in (DM)
[**] This activity is supported by SERB-India (EMR/2015/000164).
Financial support has been received from CSIR-India/UGC-India
(fellowship to S.R. and B.P.).
DM sincerely thanks Dr. Jyotishman Dasgupta (TIFR), and his
group member, Ms. Ankita Das for helping to conduct Resonance
Raman in hisLaboratory.
The relatively electron deficient substrate 6-bromo-2-
methoxy-1-naphthaldehyde
decarbonylative halogenated product
provided
corresponding
6-bromo-1-chloro-
2-methoxynaphthalene (30%) (Table 1, entry 4). The
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10.1002/cctc.201600843
ChemCatChem
decrease in yield of halogenated product is due to the
presence of electron withdrawing group bromo (-Br) at 6
completion of the reaction in presence of organic substrate
the yellowish-green color aqueous part which is likely to be
the VO2+.
position.
The
α,β-unsaturated
aldehyde
3,3-
diphenylacrylaldehyde,
provided
corresponding
UV-vis spectra recorded in absence of the exogenous
-1
substrate showed a band at 452 nm (ϵ = 391 M cm-1, Figure
decarbonylative halogenated product, (2-chloroethene-1,1-
diyl)dibenzene (10%) and benzophenone (15%) as a by-
product. Interestingly when more electron rich substrate was
used corresponding aromatic ring halogenation was
observed. The electron-rich 2-aminobezaldehyde provided
2,4,6-tricloroanline (20%) (Table 1, entry 5). In this case
aromatic ring gets chlorinated after formation of
decarbonylative halogenation product, 2-chloroaniline due to
the presence of electron rich amino group (-NH2). Scope of
the V2O5 catalyzed bromination reaction was explored with
2-methoxy-1-naphthaldehyde and 6-bromo-2-methoxy-1-
naphthaldehyde in presence of potassium bromide (KBr) and
H2O2 under standard reaction protocol. The decarbonylative
bromination reaction of 2-methoxy-1-naphthaldehyde
provided brominated product in 55% yield whereas 6-bromo
derivatives gave 40% of desired product(Scheme 4).
1a), which indicated formation of the red-colored vanadium-
oxo-peroxo species (Figure 1a).[6] This characteristic
absorption can be assigned as peroxo to vanadium (5+)
charge transition band, corresponding to V5+O(O2) species.
Similar UV-vis for vanadium-oxo-peroxo species has been
reported previously by J. Mayer, M. Sivak and H-J, Kruger
[6]
groups.
The same red color solution of vanadium-oxo-
peroxo species was further characterized by 51V NMR study.
Vanadium(5+)-oxo-peroxo, VO(O2)+ complex showed
a
sharp resonance at –534.68 ppm, that corroborated well
with the literature report(Figure 2a).[7]
Further the same red color solution of VO(O2)+ was used for
Raman study.
Raman spectrum of VO(O2)+, showed
characteristic Raman shift of V-Operoxo, at 550 cm-1, O-O
(side on peroxo) at 933 cm-1 and V=O bond at 979 cm -1
(Figure 3).[8]
Scheme 4. Decarbonylative bromination byV2O5
V2O5 (0.09 mmol), KBr (0.55 g, 4.62 mmol), substrate (0.5 mmol),
H2O2 (30%, 330 L, 3.25 mmol), acidic water solution (H2SO4) in
w ater (3 mL), citrate-phosphate buffer (2 mL), acetone (1 mL).
Interestingly, with bulky alkoxy groups (OR, R = allyl,
propargyl, 2-chlorobenzyl) at the ortho- position of 1-
naphthaldehyde, trace amount of halogenated products were
obtained (Scheme 5). Such observations are suggestive of
the importance of effective coordination of alkoxy moiety to
vanadium during the decarbonylative halogenation reactions.
Scheme 5. Steric effect on decarbonylative halogenations
Figure 2.
51V NMR recorded during the course of
decarbonylative halogenation reaction under standard
reaction protocol (in acidic aqueous medium), (a) at the
beginning of the reaction and in the absence of organic
substrate (red colored species), vanadium oxo-peroxo
species formed (-534.63 ppm), (b) recorded after 30 min
upon addition of 2-methoxy-1-naphthaldehyde, (c) recorded
after 3h (d) after completion of the reaction, yellowish-green
colored species
The FT-IR analysis of V5+O(O2) species showed one peak
for V=O stretching at 987 cm -1, O–OP stretching at 910 cm-1,
and V–O stretching at615 cm-1.[6a, 9]
Figure 1. UV-vis spectra recorded (a) in the absence of
organic substrate, in water after addition of H2O2 and KCl to
an acidic aqueous soluition of V2O5, maxima at 452 due to
the formation of vanadium-oxo-peroxo species (b) and after
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10.1002/cctc.201600843
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The vanadium (5+)-oxo-peroxo species can easily form
was responsible for carrying out the decarbonylative
VO(O2)(OCl) (2) in presence of H2O2 and KCl in absence of halogenation reaction, we thought to generate the similar
substrates
in order to carry out the decarbonylative
intermediate which can be obtained from simple monomeric,
V4+O(acac)2 (5) under the same reaction condition of V2O5
catalyzed decarbonylative chlorination.[6a, 12],[8c]
halogenations reactions. When 2-methoxy-1-naphthaldehyde
in acetone was added to the persistent red colored solution
(formed under reaction standard reaction protocol) with UV-
vis band at 452 nm (Figure 1), the red colored solution
turned green with formation of decarbonylated halogenated
product 1-chloro-2-methoxynaphthalene. The green colored
species displayed UV-vis bands (Figure 1) at 342 nm (sh)
and 425 nm (sh).[10] This species further showed a sharp
peak at –538.15 ppm (51V NMR), which could be attributed to
the formation of cis-dioxovanadium species (V5+O2+).[11] This
green species turned to red colored V5+O(O2) upon addition
of H2O2 that continued the catalytic cycle.
Scheme 7. Proposed mechanism based on experimental
evidences
The 51V NMR recorded after addition of the 2-methoxy-1-
naphthaldehyde in acetone to the V5+O(O2)(OH)+ solution.
The resulting solution showed some new upfield peaks
arises at ~-520,-502 ppm which might be due to the
substrates coordination to the vanadium-oxo-peroxo species.
After the reaction the green colored solution showed up field
peak at –538.15 ppm could be due to the formation of cis-
dioxovanadium species (Figure 2d).[10d],34 The 51V NMR
spectra, at the beginning of the reaction and at the end of the
reaction showed chemical shifts at –537.3 and –538.1 ppm,
respectively. These chemical shifts are particularly
characteristics
for vanadium(+5) oxidation state.[11]
Therefore, vanadium(+5) oxidation state remains unaltered
during the course ofreaction.
Interestingly, starting from V4+O(acac)2 (5), we were
successful in obtaining 1-chloro-2-methoxy naphthalene from
2-methoxy-1-naphthaldehyde under the standard reaction
condition (Scheme 8). Expectedly, we observed formation of
deep red solution after addition of KCl/H2O2 that changed to
green during the course of the reaction. These observations
were further supported by similar UV-vis maximum (at 450
nm) and 51V NMR (~-535 ppm).[8c],28 Generation of formic
acid was also confirmed during the decarbonylative
halogenation reaction with V4+O(acac)2 (5).
Scheme 8. Decarbonylative chlorination by V4+O(acac)2
Figure 3. Raman spectrum of V5+O(O2)+, showing
characteristic Raman shift of V-Operoxo, at 550 cm-1, O-O
(side on peroxo) at 933 cm-1 and V=O bond at 979 cm-1.
Experimental Section:
General Information: Isolated compounds were characterized
1
by H and 13C NMR spectroscopy, GC−MS. IR spectrum
Scheme 6. Generation of formic acid
was recorded on a Fourier transform infrared (FT-IR)
spectrophotometer with samples prepared as KBr pellets.
NMR spectra were recorded either on a Bruker 400/500 MHz
or on a Varian 300/400 MHz instrument. All 51V NMR spectra
were recorded in D2O and reported in ppm relative to
NH4VO3 (−571.5 ppm) [13]
.
In our attempt to achieve the decarbonylative halogenations,
formic acid was expected to form. Indeed generation of
formic acid was confirmed (yield, 50%) under standard
reaction condition (Scheme 6). Such an observation,
therefore, mimics the decarbonylation reactions by metal
peroxo complexes found in Nature.
Procedure for decarbonylative chlorination:
Vanadium Pentoxide (V2O5, 18 mol%, ca. 17 mg) was taken
in a 20 mL screw-capped reaction tube. A 2 mL of acidic
aqueous solution (33 mL of conc. HCl in 300 mL distilled
water) was added followed by 7.5 mmol (0.55 g) of KCl.
Subsequently, 0.5 mmol of the substrate in 1 mL of acetone
was added. Finally, 12 mmol (330 L) of 30 % H2O2 was
added to the contents of the reaction tube and the screw cap
was closed and sealed with paraffin. The reaction tube was
kept at room temperature with constant stirring. After 12 hrs,
50 mL of dichloromethane was added to the reaction mixture
and the organic component was extracted. The process was
repeated and the organic parts were combined and dried
over Na2SO4, and concentrated under reduced pressure in a
rotary evaporator. The crude product thus obtained was
Mechanistic investigations suggested that vanadium-oxo-
peroxo species 2 was coordinated with aldehyde substrate.
The peroxo moiety reacted with the carbonyl center in 3 to
produce 4, which in presence of chloride (Cl-) and hydrogen
peroxide provided halogenated product by generation of
formic acid (Scheme 7). Active catalytic species, 2 was
regenerated in presence of H2O2 and chloride (Cl-) source.
Throughout the catalytic cycle, vanadium (5+) oxidation state
2e]
was maintained similar to that of V-HPO enzymes.[1c,
Since mononuclear vanadium-oxo-peroxo, V5+O(O2)(OCl) (2)
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10.1002/cctc.201600843
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further purified by column chromatography. Yield of isolated
product was calculated with respect to starting material used
in reaction.
the focal plane was collected through 100 μm core
multimode fiber as pinhole. Spectrum was collected at an
integration time of 60s using lens based ultrahigh throughput
spectrometer (UHTS300, 1800 grooves/mm grating) coupled
Procedure B for decarbonylative bromination:
to a back illuminated CCD-camera (1024 × 128 pixels, ∼2
Vanadium Pentoxide (V2O5, 18 mol%, ca. 17 mg) was taken
in a 20 mL screw-capped reaction tube. A 3 mL acidic water
(10-15 L of conc. H2SO4 is added to 3 mL of water) solution
was added followed by 2 mL of citrate-phosphate buffer. To
this resulting solution 0.55 g (4.62 mmol) of KBr was added.
Subsequently, 0.5 mmol of substrate in 1 mL of acetone was
added. Finally, 330 µL of 30 % H2O2 was added to the
contents of the reaction tube and the screw-cap was closed
and sealed with paraffin. The reaction tube was kept at room
temperature with constant stirring. After 12 hrs, 50 mL of
dichloromethane was added to the reaction mixture and the
organic component was extracted. The process was
repeated and the organic parts were combined and dried
over Na2SO4, and concentrated under reduced pressure in a
rotary evaporator. The crude product thus obtained was
further purified by column chromatography. Yield of isolated
product was calculated with respect to starting material used
in reaction.
cm−1 per CCD pixel).
Sample preparation for Raman study:
Vanadium Pentoxide (20 mg) was taken in 20 mL glass vial
followed by addition of 2 mL water and 40 μL of H2SO4.
Subsequently 330 μL (3.25 mmol) of H2O2 (30%) and 0.55 g
(7.5 mmol) of KCl were added to the previous solution. The
solution was stirred for 5-10 minutes. The resulting solution
showed UV-vis band at 452 nm. The prepared solution was
used for Raman study.
DFT Study:
In order to understand the intricate steps in this reaction, we
carried out DFT study to probe the mechanism of this
reaction. Based on the experimental observations, the
following mechanistic scheme was adapted for DFT
calculations (Scheme 9). We have explored the energy
landscape for the interaction of aldehyde with vanadium-oxo-
peroxo hydroxo, [V5+O(O2)(OH)] species as well as with the
vanadium-oxo-peroxo hypochlorite species, [V5+O(O2)(OCl)]
(2). Our calculations reveal that the interaction of aldehyde
with hypochlorite species is exothermic by 8 kJ/mol than the
vanadium-oxo-peroxo hydroxo species. Thus we have
decided to begin our reaction with the vanadium-oxo-peroxo
hypochlorite species (2). Although vanadium hypobromites
are commly known,[1c, 14] recent reports suggest involvement
of hypochlorite as the catalytically active species particularly
for heme-iron systems.[15] This along with the computed
energetics suggest vanadium hypochlorite as the starting
species in our catalytic reaction. Besides this species bears
also high relevance to the active site of vanadium
Preparation of acidic water solution:
In a 500 mL beaker, 300 mL of distilled water was taken and
then 33 mL conc. HCl (12 M) [from Merck Chemicals] was
added in order to form dilute acid solution. Alternatively, 250
μL of H2SO4 was added in 10 mL of distilled water and
stirred properly to make it homogeneous. Both the acidic
solution was used for the decarbonylative halogenation
reactions and the characterization of reactive intermediates.
We have obtained similar observations by using both the
acidic solutions.
Sample preparation for 51V NMR analysis:
Vanadium Pentoxide (20 mg) was taken in vial and 2 mL of haloperoxidase.[16] The geometry around vanadium was
D2O was added and subsequently 40 μL of conc. H2SO4 was
added. Then 330 μL (3.25 mmol) of H2O2 (30%) and 0.55 g
(7.5 mmol) of KCl were added and stirred for 5-10 min and
then NMR was recorded. Similar solution was prepared and
2-methoxy-1-naphthaldehyde in acetone was added to the
trigonal planar and the V=O bond was calculated to be 1.580
Å, while the other two peroxo oxygen atoms were
symmetrically bonded with a distance of 1.787 Å. The V-
O(Cl) bond distance was estimated to be 1.797 Å. Owing to
the significant relevance of the species in the mechanistic
reaction solution and stirred until the green color appeared. course of the reaction.
During the course of the reaction after 30 min and 3 hour, In the next step, the ligand L (L=2-methoxy napthaldehyde,
51V NMR was recorded. After completion of the reaction
when green color appeared, 51V NMR was also recorded
from that solution.
Scheme 9) was assumed to coordinate to the vanadium-
oxo-peroxo hypochlorite species. The optimized structure
of this pre-reacting species is shown in Scheme 9.
Energetically this step was estimated to be exothermic in
nature by -34.9 kJ/mol. This species, besides having wide
literature precedents[16a],[14b], had significant relevance to
the active site of the vanadium haloperoxidase, with the
only difference being coordination of the aldehyde oxygen
atoms instead of a nitrogen atom of an imidizole ring.
Selected bond parameters of the optimized structures are
given in Table S1.[8c]
The optimized structure revealed that the oxygen atom of
the –CHO group formed a strong coordinate bond to the
vanadium (2.012Å) while the oxygen atom of the –OMe
group coordinated weakly (3.111Å) to the center. The V=O
distance was estimated to be 1.590 Å, while the peroxo
oxygen atoms were found to be asymmetrically
coordinating to the Vanadium atom (1.799 Å and 1.836 Å).
The V-O(Cl) and O-Cl distances were found to be 1.825 Å
and 1.706 Å, respectively. A significant difference in the
structure here compared to the reactant species was the
asymmetric nature of the peroxo group with one long and
one short V-O bonds. Significant σ/π-donation from the
carbonyl oxygen influenced the peroxo bonding since a
clear π donation from only one of the oxygen (possessing
shorter V-O distance) was now visible (Figure 4). Another
Sample Preparation for UV-vis study:
Vanadium Pentoxide (20 mg) was taken in 20 mL glass vial
followed by 2 mL water and 50 μL of H2SO4 was added to it.
Subsequently 330 μL (3.25 mmol) of H2O2 (30%) and 0.55 g
(7.5 mmol) of KCl were added to the previous solution. Then
2 mL of citrate-phosphate buffer was added and UV-vis was
recorded from the resulting solution, which showed UV-vis
band at 452 nm. Alternatively, Vanadium Pentoxide (20 mg)
was taken in a vial; 2 mL of H2O and 40 μL of conc. H2SO4
were added and stirred for 5 minutes. After that 330 μL (3.25
mmol) of H2O2 and KCl (0.55 g, 7.5 mmol) were added and
stirred 5 minutes. The resulting solution was used for the UV-
vis study. By using the acid solution prepared from conc. HCl
in distilled water also provides same spectra of vanadium-
oxoperoxo complex.
Raman Spectroscopy:
We recorded resonance Raman spectra of the vanadium-
oxo-peroxo species using confocal Raman microscope
(alpha 300R, WITec, Germany). Frequency doubled DPSS
Nd:YAG laser 532 nm was used at a power of 5 mW to
excite vanadium-oxo-peroxo sample in mili-Q water under
constant flow through 1 mm flow-cell. The scattered light in
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10.1002/cctc.201600843
ChemCatChem
significant distinction noticed here was on the ligand moiety,
where the aldehyde carbon atom (noted as C(1))
developed significant positive charge (Mulliken charge
analysis reveal an increase from 0.89 from free ligand to
1.22 in int2) upon coordination.
oxygen atom. The calculated barrier height for this step
was estimated to be 74.2 kJ/mol (Figure 4). Formation of
the int2 species was slightly endothermic with respect to
int1, however from the reactant energy; it was still
exothermic in nature.
Coordination of the ligand, which induced asymmetry in the
peroxo moiety, held the key to the next step where the
longer V-O bond was expected to cleave. This was
assumed to take place via ts1 (Figure 4) leading to the
formation of V-O-O- species as an intermediate (int2;
Figure 4).[8c]
Thus the next logical step expected was the attack of the
end-on peroxo species on the aldehyde carbon atom via
ts2 (Figure 4).[8c]
The nucleophilic characters of the end-on/side-on peroxo
species with various metal ions were probed in detail.
Particularly, the deformylation by the iron(III)-peroxo
species clearly indicated that these species were
nucleophilic in character (nature).[17] Thus all these
literature precedents support our mechanistic hypothesis.
The attacks of the distal oxygen at the carbon atom lead to
elongation of the O-O bond to 1.415 Å (from 1.343 Å). The
newly forming O(2)-C(1) distances were estimated to be
1.900 Åshowing significant bonding interaction even at the
transition state level. The transition state showed stronger
interaction between the methoxy oxygen atom with the
vanadium center (from 2.567 Å at int2 to 2.210 Å here,
Figure 4).[8c] The barrier height for this step was estimated
to be 91.7 kJ/mol from int2, while from the reactant scale it
was 63.3 kJ/mol (Figure 4 below).[8c]
Scheme 9. Proposed mechanism for the decarbonylative
halogenationsbased on DFT studies
In the next step, the newly forming O(2)-C(1) bond
completes (1.434Å) leading to int3 (Figure 4).[8c] This
intermediate formation was exothermic in nature by 82.6
kJ/mol from the reactant suggesting feasible formation of
this species.
The V-O bond cleavage occurred in a heterolytic fashion.
This was consistent with the mechanism proposed for the
vanadium haloperoxidases mimics.[14b, 14c, 16a]
3
2.210
2
1
3
3.028
1.417
1.900
1.793
1
2
1.589
1.439
1
2
1.250
1
1.401
2
3
2
2
2.292
1
2
1
1
1.610
1.852
3
2
2
3
1.516
1
1.444
1.531
2
1.612
1
1
1.321
1.720
1.613
3
2.567
1.594
1
2
3
2
1.439
1
1.766
2
1.249
1.590
1.825
2.500
1
1.343
2
1
1.422
1.363
3
1.709
1.398
2
1
1.434
1.420
1.580
1.806
1
1.592
2
3
1.725
1.390
2
1.592
1.755
2
1.489
3
1.556
2
1
1
1.829
1.616
1.875
Figure 4. B3LYP computed energy (in solvent; G in
kJ/mol) profile diagram
halogenations
for the decarbonylative
Incidentally, a five coordinated hypochlorite attacking the
carbon atom was ruled out based on the following
arguments (i) the OCl- group was far away from the C(2)
carbon atom (4.986Å) (ii) as per the experimental
conditions, the solution contained significant amount of
In ts1, the V-O bond elongated from 1.836 Å to 2.300 Å
while the other V-O bond of the peroxo moiety shortened.
The O-O bond distance also shortens significantly as
greater electron density was now available at the distal
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10.1002/cctc.201600843
ChemCatChem
chloride ions thus making the external attack by a Cl- ion
feasible (iii) a dissociative pathway where O-Cl bond
breaking first leading tothe generation of Cl- species was
unlikely as the bond-dissociation energy for the O-Cl bond
was found to be very large (+443.5 kJ/mol).
requirement. The large energy barrier computed also
correlates with the experimental fact that the reactions were
very slow and required long hours for completion (nearly 6-
24 hrs for completion).
At the transition state, the newly forming Cl-(C2) bond
distance was estimated to be 2.45 Å (Figure 4).
Interestingly, attack of the chloride ion at the C(2) position
via this transition state was found to be a concerted
process where the approach of chloride ion triggered two
structural changes ;
The first transition state required significant energy as
strong V-O bond of the peroxo group was needed to be
broken. Apart from strong σ-interaction, there were also
significant π-donation from the peroxo group that enhanced
the barrier height. Stronger π-interaction was correlated to
the formal oxidation state of the V(5+) ions. For other
transition metal ions possessing half-filled and more than
half-filled orbitals, breaking up of the peroxo species was a
(i) At the transition state, the O—O bond breaks away
(2.422 Å at ts3) and (ii) a new O(2)-C(3) bond was formed
(1.443 Å at ts3). Besides, there was also slight elongation
of C(1)-C(2) bond distance (1.530 Å at ts3). At the
transition state, steps (i) and (ii) were already completed,
while step (iii) showed sign of progress towards cleavage
of the C(1)-C(2) bond. The Intrinsic reaction coordinate
(IRC) calculations affirmed this point, at 2.5 Å Cl-(C2)
distance, the peroxo bonds were not broken, however at
2.45 Å Cl-(C2) distance, the O-O bond was broken and the
O(2)-C(3) bond was partially formed. Despite all these
structural changes, the barrier height computed for this
transition state was 1.2 kJ/mol from the int3, revealing
nearly a barrier less process leading to the formation of
int4 (Figure 4).[8c]
facile step leading to the formation of highly reactive end-on
17c , 21]
peroxo/superoxo species.[17a,
Although the second
transition state was electrostatically favorable as discussed
earlier, significant penalty in energy arose due to structural
distortion required to attain this transition state and
unfavorable orientation of the π*(C=O) orbital (Figure 4).[8c]
Large exothermic gain upon reaching intermediate 3, made
other steps feasible and facilitated faster reaction. The ts3
was a concerted process where several key structural
alterations were taking place as affirmed in our IRC
calculations. The approach of chloride ion was essential to
trigger a series ofstructural alterations.
Such concerted step also correlated to the experimental
observation that decarbonylative products are not detected
in the reaction mixture. Without addition of KCl, no product
formation (decarbonylation, oxidation of aldehyde etc.) was
detected thereby suggesting a necessity of external stimuli to
drive the reaction as revealed by ts3. Thus the proposed
mechanism rationalizes all the experimental observations,
suggesting that this is the likely pathway through which the
chlorination of aromatic compounds takes place. Among the
species computed, only marginal changes in the vanadium
charge was noted (1.09 to 1.27, Table S2[8c]. This suggests
that the 5+ oxidation state of vanadium was maintained
throughout the reaction. A recent 51V NMR studies on
In the next step the C(l)-(C2) bond was formed completely
(1.829Å) and the O(2)-C(3) bond strengthened further
(1.425 Å). The formation of this intermediate was found to
be excessively exothermic in nature (-150.3 kJ/mol from
the reactant). It is worthwhile to mention here that at this
intermediate (int4), a constrained four membered ring (C-
C-C-O, Figure 4) existed and in the next step, this ring was
expected to cleave via ts4 (Figure 4). Here C(1)-C(2) and
O(2)-C(3) bonds were cleaving resulting in the formation of
formic acid and decarbonylated halogenated product.
The C(1)-C(2) and O(2)-C(3) distances were found to be
2.292 Å and 1.567 Å respectively. Although there was a
significant kinetic barrier for this species from int4, from the
reactant surface, it lied at 26.5 kJ/mol, suggesting the
feasible formation of the product. The final product
formation was found to be a thermodynamic sink, with a
stabilization of -196.9 kJ/mol and this energy gain was
likely to ease the barrier heights required for the next
catalytic cycle.[18] The potential energy surface developed
for the catalytic cycle studied is shown in Figure 4. The
catalytic cycle was assumed to start from vanadium-oxo-
Vanadium
Haloperoxidases
enzyme
suggests
spectroscopically silent V(5+) during the catalytic cycle as
revealed in our biomimic models.[16b] The mechanism
proposed has high relevance to the biology particularly when
the vanadium haloperoxidase is found to halogenate
thousands of natural products. Some of the key steps are
likely to be common to both the enzymes and the bio-mimic
chemistryproposed in this work.
Conclusion:
peroxo hypochlorite species. This species
was
We have developed decarbonylative halogenation
starting with simple available vanadium pentoxide. We have
shown that insitu formed vanadium-oxo-peroxo species is
responsible for decarbonylative halogenation reaction in
presence of chloride ion via elimination of formate. The
experimentally proposed mechanism of decarbonylative
halogenation by vanadium-oxo-peroxo species is well
supported by detailed DFT studies.
characterized by spectroscopic methods. In the next step
the ligand was assumed to coordinate to this species
leading to the formation of [V(O)(O2)(OCl)(L)] species. This
step was computed to be exothermic and formation of this
species was also witnessed in the experiments by variation
in the 51V chemical shift. The 51V chemical shifts were
qualitatively associated with the HOMO-LUMO gap and
such analysis is well supported by literature reports for
several vanadyl complexes.[19] For species 2, the HOMO-
LUMO gap was computed to be 3.1 eV while that
drastically dropped to 1.2 eV for int1 suggesting significant
shiftin the 51V shift as observed in the experiments.[20]
The first transition state had a barrier height of 74.2 kJ/mol
while the second transition state had a much higher energy
barrier (91.7 kJ/mol). These two transition states formed the
key to the product formation with the second step being the
rate limiting. Although the absolute barrier height of 91.7
kJ/mol seemed high, on a relative scale to the reactant, the
peak energy was placed at 63.3 kJ/mol i.e. the energy
gained upon ligand coordination, eased the kinetic
Computational Details:
Using the Gaussian 09 suite of program carried out all the
calculations.[22] The geometry optimizations were performed
with B3LYP functional.[23] The B3LYP had a proven track
record of predicting the structures and the energetics
accurately for such metal mediated catalytic reactions.
LACVP basis set comprising LanL2DZ - Los Alamos
effective core potential for V[24] and a 6–31G*[25] basis set for
the other atoms (B-I) had been employed for geometry
optimization and the optimized geometries were then used to
perform single point energy calculations using a TZVPP
basis set (B-II) on all atoms.[26] The solvation energies had
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10.1002/cctc.201600843
ChemCatChem
been computed using PCM solvation model employing
acetonitrile as the solvent.[27] Frequency calculations were
performed on the optimized structures at B-I level to verify
that they were minima on the potential-energy surface (PES)
and also to obtain free energy corrections. The quoted DFT
energies were B3LYP solvation energies incorporating zero
point energies correction at the B-I level computed at the
temperature of 298.15 K, unless otherwise mentioned. The
transition states were characterized by single negative
frequency corresponding to the reaction coordinate and were
verified by animating the frequency using visualization
software such as Molden.[28]
[9] (a) G. J. Colpas, B. J. Hamstra, J. W. Kampf, V. L.
Pecoraro, J. Am. Chem. Soc. 1994, 116, 3627-3628; (b) G. J.
Colpas, B. J. Hamstra, J. W. Kampf, V. L. Pecoraro, J. Am.
Chem.Soc. 1996, 118, 3469-3478.
[10] (a) G. Asgedom, A. Sreedhara, C. P. Rao, E.
Kolehmainen, Polyhedron 1996, 15, 3731-3739; (b) M. R.
Maurya, S. Khurana, W. Zhang, D. Rehder, J. Chem. Soc.,
Dalton Trans. 2002, 3015-3023; (c) M. R. Maurya, S.
Khurana, W. J. Zhang, D. Rehder, Eur. J. Inorg. Chem.
2002, 1749-1760; (d) M. R. Maurya, J. Chem. Sc. 2011, 123,
215-228; (e) M. R. Maurya, N. Chaudhary, F. Avecilla,
Polyhedron 2014, 67,436-448.
[11] D. Rehder, M. Casny, R. Grosse, Mag. Res. Chem.
2004, 42, 745-749.
[12] C. D. Nunes, P. D. Vaz, V. Felix, L. F. Veiros, T. Moniz,
M. Rangel, S. Realista, A. C. Mourato, M. J. Calhorda,
Dalton Trans. 2015.
[13] (a) S. Hayashi, K. Hayamizu, Bull. Chem. Soc. Jpn.
1990, 63, 961-963; (b) H. Eckert, I. E. Wachs, J. Phys. Chem.
1989, 93, 6796-6805.
References:
[1] (a) F. H. Vaillancourt, E. Yeh, D. A. Vosburg, S. Garneau-
Tsodikova, C. T. Walsh, Chem. Rev. 2006, 106, 3364-3378;
(b) D. G. Fujimori, C. T. Walsh, Curr. Opp. Chem. Biol. 2007,
11, 553-560; cA. Butler, M. Sandy, Nature 2009, 460, 848-
854; (d) L. C. Blasiak, C. L. Drennan, Acc. Chem. Res. 2008,
42, 147-155.
[2] (a) R. Wever, H. Plat, E. de Boer, biochimica et
biophysica acta 1985, 830, 181-186; (b) J. Littlechild, E.
Garcia Rodriguez, M. Isupov, J. Inorg. Biochem. 2009, 103,
617-621; (c) A. Butler, J. N. Carter-Franklin, Nat. Prod. Rep.
2004, 21, 180-188; (d) W. Hemrika, R. Renirie, S. Macedo-
Ribeiro, A. Messerschmidt, R. Wever, J. Biol. Chem. 1999,
274, 23820-23827; (e) V. Conte, A. Coletti, B. Floris, G. Licini,
C. Zonta, Coord. Chem. Rev. 2011, 255, 2165-2177; (f) A.
Messerschmidt, R. Wever, Proc. Natl. Acad. Sci. U.S.A.
1996, 93, 392-396; (g) J. Littlechild, E. Garcia-Rodriguez,
Coord. Chem. Rev. 2003, 237, 65-76; (h) M. Weyand, H. J.
Hecht, M. Kieß, M. F. Liaud, H. Vilter, D. Schomburg, J. Mol.
Biol. 1999, 293, 595-611.
[3] (a) K. Sen, J. C. Hackett, J. Phys. Chem. B 2009, 113,
8170-8182; (b) K. Sen, J. C. Hackett, J. Am. Chem. Soc.
2010, 132, 10293-10305; cC. Krebs, J. M. Bollinger Jr, S. J.
Booker, Curr. Opp. Chem. Biol. 2011, 15, 291-303; (d) K. M.
Henry, C. A. Townsend, J. Am. Chem. Soc. 2005, 127, 3724-
3733; (e) A. Schirmer, M. A. Rude, X. Li, E. Popova, S. B.
del Cardayre, Science 2010, 329, 559-562; (f) L. J.
Rajakovich, H. Nørgaard, D. M. Warui, W.-c. Chang, N. Li, S.
J. Booker, C. Krebs, J. M. Bollinger, M.-E. Pandelia, J. Am.
Chem.Soc. 2015, 137, 11695-11709.
[4] (a) J. Annaraj, Y. Suh, M. S. Seo, S. O. Kim, W. Nam,
Chem. Comm. 2005, 4529-4531; (b) A. Shokri, L. J. Que, J.
Am. Chem.Soc. 2015, 137, 7686-7691.
[5] S. Rana, R. Haque, S. Ganji, D. Maiti, Inorg. Chem. 2013,
52, 2927-2932.
[6] (a) C. R. Waidmann, A. G. DiPasquale, J. M. Mayer, Inorg.
Chem. 2010, 49, 2383-2391; (b) M. Sivak, Chem. Pap.
Chem. Zvesti 1987, 41, 311-319; (c) M. Sivak, P. Schwendt,
Transition Met. Chem. 1989, 14, 273-276; (d) H. Kelm, H. J.
Kruger, Angew. Chem. Int. Ed. 2001, 40, 2344-2348; (e) R.
M. Totaro, P. A. M. Williams, M. C. Apella, M. A. Blesa, E. J.
Baran, J. Chem. Soc., Dalton Trans. 2000, 4403-4406; (f) A.
Shaver, J. B. Ng, D. A. Hall, B. I. Posner, Mol. Cell. Bio. 1995,
153, 5-15; (g) A. B. P. Lever, H. B. Gray, Acc. Chem. Res.
1978, 11, 348-355.
[14] (a) A. Butler, Coordination Chemistry Reviews 1999,
187, 17-35; (b) G. J. Colpas, B. J. Hamstra, J. W. Kampf, V.
L. Pecoraro, J. Am. Chem. Soc. 1996, 118, 3469-3478; (c) G.
Zampella, P. Fantucci, V. L. Pecoraro, L. De Gioia, Inorg.
Chem.2006, 45, 7133-7143.
[15] Z. Cong, S. Yanagisawa, T. Kurahashi, T. Ogura, S.
Nakashima, H. Fujii, J. Am. Chem. Soc. 2012, 134, 20617-
20620.
[16] (a) J. M. Winter, B. S. Moore, J. Biol. Chem. 2009, 284,
18577-18581; (b) R. Gupta, G. Hou, R. Renirie, R. Wever, T.
Polenova, J. Am. Chem.Soc. 2015, 137,5618-5628.
[17] (a) A. Ansari, P. Jayapal, G. Rajaraman, Angew. Chem.
Int. Ed. 2015, 54, 564-568; (b) A. Yokoyama, J. E. Han, J.
Cho, M. Kubo, T. Ogura, M. A. Siegler, K. D. Karlin, W. Nam,
J. Am. Chem. Soc. 2012, 134, 15269-15272; (c) J. Cho, S.
Jeon, S. A. Wilson, L. V. Liu, E. A. Kang, J. J. Braymer, M. H.
Lim, B. Hedman, K. O. Hodgson, J. S. Valentine, E. I.
Solomon,W. Nam, Nature 2011, 478, 502-505.
[18] (a) S. Kozuch, S. Shaik, Acc. Chem. Res. 2011, 44, 101-
110; (b) D. Usharani, D. Janardanan, C. Li, S. Shaik, Acc.
Chem.Res. 2013, 46, 471-482.
[19] (a) M. Debnath, A. Dutta, S. Biswas, K. K. Das, H. M.
Lee, J. VÃcha, R. Marek, J. Marek, M. Ali, Polyhedron 2013,
63, 189-198; (b) P. B. Chatterjee, O. Goncharov-Zapata, L. L.
Quinn, G. Hou, H. Hamaed, R. W. Schurko, T. Polenova, D.
C. Crans, Inorg. Chem. 2011, 50, 9794-9803; (c) O.
Goncharova-Zapata, P. B. Chatterjee, G. Hou, L. L. Quinn, M.
Li, J. Yehl, D. C. Crans, T. Polenova, CrystEngComm 2013,
15, 8776-8783.
[20] M. P. Waller, M. Bühl, K. R. Geethalakshmi, D. Wang, W.
Thiel, Chem.Eur. J. 2007, 13, 4723-4732.
[21] (a) M. H. Dickman, M. T. Pope, Chem. Rev. 1994, 94,
569-584; (b) D. Maiti, J. S. Woertink, A. A. Narducci Sarjeant,
E. I. Solomon, K. D. Karlin, Inorg. Chem. 2008, 47, 3787-
3800; (c) M. S. Seo, J. Y. Kim, J. Annaraj, Y. Kim, Y.-M. Lee,
S.-J. Kim, J. Kim, W. Nam, Angew. Chem. Int. Ed. 2007, 46,
377-380.
[22] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E.
Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V.
Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M.
Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G.
Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R.
Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O.
Kitao, H. Nakai, T. Vreven, J. A. Montgomery Jr., J. E.
Peralta, F. Ogliaro, M. J. Bearpark, J. Heyd, E. N. Brothers,
K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K.
Raghavachari, A. P. Rendell, J. C. Burant, S. S. Iyengar, J.
Tomasi, M. Cossi, N. Rega, N. J. Millam, M. Klene, J. E.
Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R.
[7] L. L. G. Justino, M. L. Ramos, F. Nogueira, A. Sobral, C.
Geraldes, M. Kaupp, H. D. Burrows, C. Fiolhais, V. M. S. Gil,
Inorg.Chem. 2008, 47, 7317-7326.
[8] (a) J. E. Molinari, I. E. Wachs, J. Am. Chem. Soc. 2010,
132, 12559-12561; (b) L. L. Sun, K. E. Hermann, J. Noack, O.
Timpe, D. Teschner, M. Hävecker, A. Trunschke, R. Schlögl,
J. Phys. Chem. C 2014, 118, 24611-24622; (c) Supporting
Information; (d) P. Schwendt, M. Sivak, A. E. Lapshin, Y. I.
Smolin, Y. F. Shepelev, D. Gyepesova, Transition Met.
Chem.1994, 19, 34-36.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201600843
ChemCatChem
Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R.
Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K.
Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J.
Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B.
Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian,
Inc., Wallingford,CT, USA, 2009.
[23] (a) C. T. Lee, W. T. Yang, R. G. Parr, Phys. Rev. B,
1988, 37, 785-789; (b) A. D. Becke, J. Chem. Phys. 1993, 98,
5648-5652.
[24] (a) P. J. Hay, W. R. Wadt, J. Chem. Phys 1985, 82,
270-283; (b) W. R. Wadt, P. J. Hay, J. Chem. Phys 1985, 82,
284-298.
[25] (a) P. J. Hay, W. R. Wadt, J. Chem. Phys 1985, 82,
299-310; (b) Ditchfie.R, W. J. Hehre, J. A. Pople, J. Chem.
Phys. 1971, 54, 724.
[26] (a) A. Schafer, H. Horn, R. Ahlrichs, J. Chem. Phys
1992, 97, 2571-2577; (b) A. Schafer, C. Huber, R. Ahlrichs, J.
Chem.Phys 1994, 100, 5829-5835.
[27] B. Mennucci, WIREsComputMol Sci 2012, 2, 386-404.
[28] G. Schaftenaar, J. H. Noordik, J. Comput. Aided Mol.
Des. 2000, 14, 123-134.
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10.1002/cctc.201600843
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Entry for the Table of Contents
Sujoy Rana, Bhawana Pandey,
Aniruddha Dey, Rameezul Haque,
Gopalan Rajaraman* and Debabrata
Maiti*
Page No. – Page No.
A
Doubly Biomimetic Synthetic
Transformation: Catalytic
Decarbonylation and Halogenation
at RT by Vanadium Pentoxide
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