Free-radical selective functionalization of 1,4-naphthoquinones by perfluorodiacyl peroxides

Article abstract of DOI:10.1016/j.tet.2014.05.024

Perfluoroalkyl radicals, generated by thermal decomposition of perfluorodiacyl peroxides, react selectively with quinone rings of 1,4-naphthoquinones. In the presence of a non-conjugated alkene such as 1-hexene, perfluoroalkyl radicals add to the double bonds of the olefin forming a radical adduct, which selectively adds to the naphthoquinone ring. Several perfluorodiacyl peroxides have been synthesized and used for the direct and alkene-mediated functionalization of naphthoquinones. Geometrical parameters and electron density topology of all perfluorodiacyl peroxides have been calculated by the density functional formalism and quantum theory of atoms in molecules to attempt a rationalization of the experimental reactivity.

Full text of DOI:10.1016/j.tet.2014.05.024

Accepted Manuscript
Free-radical selective functionalization of 1,4-naphthoquinones by perfluorodiacyl
peroxides
Maurizio Sansotera , Cristian Gambarotti , Antonino Famulari , Alberto Baggioli ,
Raffaella Soave , Francesco Venturini , Stefano V. Meille , Ivan Wlassics , Walter
Navarrini
PII:
S0040-4020(14)00696-6
10.1016/j.tet.2014.05.024
TET 25573
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 9 December 2013
Revised Date: 28 April 2014
Accepted Date: 12 May 2014
Please cite this article as: Sansotera M, Gambarotti C, Famulari A, Baggioli A, Soave R, Venturini F,
Meille SV, Wlassics I, Navarrini W, Free-radical selective functionalization of 1,4-naphthoquinones by
perfluorodiacyl peroxides, Tetrahedron (2014), doi: 10.1016/j.tet.2014.05.024.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Free-radical selective functionalization of 1,4-naphthoquinones by
perfluorodiacyl peroxides
Maurizio Sansotera*, Cristian Gambarotti, Antonino Famulari, Alberto Baggioli, Raffaella Soave,
Francesco Venturini, Stefano V. Meille, Ivan Wlassics, Walter Navarrini

ACCEPTED MANUSCRIPT
Free-radical selective functionalization of 1,4-naphthoquinones by
perfluorodiacyl peroxides
Maurizio Sansotera*, Cristian Gambarotti, Antonino Famulari, Alberto Baggioli, Raffaella
Soave, Francesco Venturini, Stefano V. Meille, Ivan Wlassics, Walter Navarrini
1

ACCEPTED MANUSCRIPT
Free-radical selective functionalization of 1,4-naphthoquinones by
perfluorodiacyl peroxides
,
a,b
a
a,b
a
Maurizio Sansotera* , Cristian Gambarotti , Antonino Famulari , Alberto Baggioli ,
b,c
a
a,b
d
Raffaella Soave , Francesco Venturini , Stefano V. Meille , Ivan Wlassics , Walter
a,b
Navarrini
a
b
Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta”, Politecnico di
Milano, via Mancinelli 7, 20131, Milano, Italy
Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali, Via G.
Giusti 9, 50121 Firenze, Italy
c
CNR-ISTM, Istituto di Scienze e Tecnologie Molecolari, via Golgi 19, 20133, Milano, Italy
d
Solvay Specialty Polymers, viale Lombardia 20, 20021, Bollate (MI), Italy
Abstract
Perfluoroalkyl radicals, generated by thermal decomposition of perfluorodiacyl peroxides,
react selectively with quinone rings of 1,4-naphthoquinones. In the presence of a non-
conjugated alkene such as 1-hexene, perfluoroalkyl radicals add to the double bonds of the
olefin forming a radical adduct, which selectively adds to the naphthoquinone ring. Several
perfluorodiacyl peroxides have been synthesized and used for the direct and alkene-mediated
functionalization of naphthoquinones. Geometrical parameters and electron density topology
of all perfluorodiacyl peroxides have been calculated by the density functional formalism and
quantum theory of atoms in molecules to attempt a rationalization of the experimental
reactivity.
Highlights
ꢀ
Upon mild heating perfluorodiacyl peroxides decompose forming free perfluoroalkyl
radicals.
2

ACCEPTED MANUSCRIPT
ꢀ
ꢀ
ꢀ
Perfluorodiacyl peroxides can be used for the direct free-radical functionalization of
quinones.
In presence of an alkene perfluoroalkyl groups can be attached to quinones with a
spacer.
QTAIM shows local excess of kinetic energy at O–O BCPs correlates to thermolytic
constants.
Keywords
Peroxides, quinones, fluorine, density functional calculations, radicals
1
. Introduction
Organic peroxides have attracted special interest due to their application in industrial and
laboratory synthesis as oxidants, polymerization initiators, cross-linking agents, building
blocks, intermediates in autoxidation, and substances having antimalarial and antimicrobial
1
-3
activities. In particular, diacyl peroxides, RC(O)OO(O)CR, where R can be aliphatic,
aromatic or other groups, have been applied to the functionalization of carbon-based
4
-6
7
8-10
nanomaterials, such as carbon nanotubes, fullerenes, carbon nanohorns,
and silicon-
11
based materials for quantum dots. The perfluorinated homologues of diacyl peroxides are
perfluorodiacyl (PFDA) peroxides, R C(O)OO(O)CR , where R is a perfluorinated group.
F
F
F
Upon mild heating, PDFA peroxides decompose releasing carbon dioxide and forming free
1
2
perfluoroalkyl radicals. Recently, perfluoroalkyl free radical chemistry has raised
considerable interest, as demonstrated by many reviews and articles in the specialized
1
3-21
literature.
The comparison between electronic features and chemical behaviors of the molecules
containing an oxygen-oxygen bond allowed the comprehension of some reactivity trends in
2
2
this class of highly reactive molecules. In addition, several quantum mechanics (QM)
3

ACCEPTED MANUSCRIPT
methods, including density functional theory (DFT) approaches, have been applied to obtain
2
3,24
thermodynamic data of fluorinated organic peroxides with chemical accuracy.
However,
the debate is still open to establish if PFDA peroxides decompose by a one-bond cleavage
mechanism producing a carboxylic radical pair (Scheme 1a) or by a concerted three-bond
cleavage mechanism producing an alkyl radical pair and two molecules of carbon dioxide
2
5,26
(Scheme 1b).
The absence of products from the addition of the carboxyl radical in the
reaction mixture has been frequently used to advocate the occurrence of the latter mechanism,
2
7
although a few reports providing evidence of such side products do exist in literature.
The utility of PFDA peroxides has been firstly recognized for the initiation of free radical
2
8
fluoromonomers polymerization since the early 1950s. In fact, their use as initiators allowed
the introduction of stable perfluoroalkyl end-groups that greatly improved the thermal
2
9
stability of the synthesized fluoropolymers. More recently, this class of compounds has been
used in perfluoroalkylation reactions for the introduction of perfluoroalkyl groups in aromatic
compounds, such as benzene, chlorobenzene, toluene, anisole, and in heteroaromatic
1
4
compounds, such as furans, thiophenes, benzofurans, benzothiophenes.
Scheme 1. One-bond cleavage (a) and concerted three-bond cleavage (b) mechanisms of
PFDA peroxide decomposition.
Numerous other methods have been developed for perfluoroalkyl radical production, but they
1
3
have a few drawbacks. Perfluoroalkyl iodides represent perhaps the most important and
commonly-used source of perfluoroalkyl radicals. However, iodine radicals are also generated
1
9,20,30-33
with this synthetic methodology and iodinated derivatives are normally obtained.
4

ACCEPTED MANUSCRIPT
Perfluoroalkyl sulfonyl halides are also good photochemical sources of perfluoroalkyl
radicals, but problems can be encountered because the expulsion of SO is slow and competes
2
34
with the addition of R SO ꢀ. PFDA peroxides are convenient tools for the introduction of
F
2
fluoroalkyl groups in several organic substrates by carbon-carbon bond formation, because
the thermal conditions to generate perfluoroalkyl radicals are mild and the perfluoroalkylation
3
5-38
reaction is very clean.
radicals.
In fact, carbon dioxide is the only byproduct besides perfluoroalkyl
The synthesis of a few of these peroxides, namely perfluorodipropionyl peroxide 1a,
perfluorodi-iso-butyryl peroxide 1b, perfluorodi-n-butyryl peroxide 1c, perfluorodi-2-
methoxy-propionyl peroxide 1d and perfluorodi-2-n-propoxy-propionyl peroxide 1e, is
discussed, along with their characterization. In addition, these were employed in the
functionalization of two naphthoquinone substrates: 1,4-naphthoquinone 2 and 2-methyl-1,4-
naphthoquinone 3 (also known as menadione or vitamin K3). Naphthoquinone and quinone
moieties are present in many natural products and have been widely used because of their
3
9-42
broad spectrum of biological activities.
In addition, many attempts have been spent
4
3-
recently in the tailoring of new naphthoquinone derivatives incorporating chemical groups.
4
8
In particular, the functionalization of naphthoquinones has been widely studied to overcome
the intrinsic toxicity of quinonic compounds by synthesizing derivatives that are more stable
in their reduced state and thus less likely to initiate the formation of radicals indiscriminately
4
9
harmful to cells. Thus, several examples of fluorinated derivatives of 1,4-naphthoquinones
can be found in the literature. The inductive effect of the electronegative fluorine atoms was
applied in order to reduce the tendency of these compounds to form reactive oxygen
5
0-53
species.
Recently, Nevinsky et al. even tested the cytotoxicity of these compounds against
5
4,55
cancer cells and their ability to protect bacterial cells from mutagenesis.
The perfluoroalkylation reaction of the naphthoquinones was performed according to two
different procedures: the direct perfluoroalkylation and the perfluoroalkylation in presence of
5

ACCEPTED MANUSCRIPT
a non-conjugated alkene, such as 1-hexene. In the latter case, perfluoroalkyl radicals react
faster with the aliphatic double bond than with the quinone ring, leading to the nucleophilic
radical adduct A formed by the addition of perfluoroalkyl radicals to the olefin (see Scheme
2
). As a result, the radical A reacts selectively with the naphthoquinonic molecules, also
because of the relatively low reactivity of perfluoroalkyl radicals with the electron-deficient
quinones.
Scheme 2. Addition of perfluoroalkyl radicals to olefin and formation of the nucleophilic
radical adduct A.
In order to provide useful insight into the effect of different perfluoroalkyl substrates R on
F
the decomposition mechanism of PFDA peroxides and their general reactivity, a theoretical
study of the five PFDA peroxides used during the synthetic procedure, along with the
corresponding thermal decomposition products, was carried out. Finally, the unexpected
diastereotopic behavior of the methyl hydrogen atoms of a few perfluoroalkylation products
of naphthoquinone substrate 3 led to a conformational investigation and to a possible
explanation of the uncommon phenomenon.
2
. Results and discussion
2
.1. Synthesis of PFDA peroxides
PFDA peroxides 1a-e were synthesized starting from the corresponding low molecular weight
perfluoroacyl halides with good-to-medium yields. The synthesis of PFDA peroxides utilized
hydrogen peroxide in a biphasic system with aqueous NaOH and an inert fluorinated solvent
1
4,36-38
(Scheme 3).
The hydrolysis of PFDA peroxides and of the starting perfluoroacyl halides
was minimized by choosing proper experimental conditions. The hydrolytic decomposition is
6

ACCEPTED MANUSCRIPT
a heterogeneous reaction, and its rate is also a function of the presence of co-solvents or
surfactants and of the stirring efficiency (Scheme 4). The shortness of the fluorinated chains
in the molecular structures of PFDA peroxides 1a-e and of the starting perfluoroacyl halides
5
6
avoided the formation of annoying emulsions that often cause low preparation yields. In
fact, perfluorinated carboxylic side-products may act as surfactants and auto-catalyze the
undesired peroxides hydrolysis. Thermolysis of PFDA peroxides 1a-e is a unimolecular
reaction (Scheme 1) and the thermolytic decomposition rates, k , of PFDA peroxides 1a-e,
d
were calculated at different temperatures on the basis of first-order reaction kinetic (Table 1).
Hydrolysis of PFDA peroxides 1a-e depends also on the concentration of water (Scheme 4),
but it was possible to apply a pseudo-first order approximation because water was supplied in
great excess at the beginning of the kinetic measurement. Pseudo-first-order hydrolytic rates,
kh, are reported in Table 1 and it should be pointed out that each hydrolysis kinetic constant is
inclusive of the corresponding thermal decomposition. Therefore, these data should be
considered as a computation of the thermal and hydrolytic decomposition. Hydrolysis is a
significant side reaction in the preparation of PFDA peroxides, where highly hydrolytic
conditions, like aqueous NaOH and H O (Scheme 3), are utilized and can influence the yield
2
2
of the synthesis.
O
C
O
C
H2O
2
+ H2O2 + 2 NaOH
O
RF
+ 2 NaX + H2O
RF
X
Fluorinated
Solvent
RF
O
C
O
X = F, Cl
RF = 1a. CF2CF3
1
1
1
1
b. CF(CF3)2
c. CF2CF2CF3
d. CF(CF3)OCF3
e. CF(CF3)OCF2CF2CF3
Scheme 3. Synthesis of PFDA peroxides utilized hydrogen peroxide in a biphasic system with
aqueous NaOH.
7

ACCEPTED MANUSCRIPT
Scheme 4. Hydrolysis of PFDA peroxides.
Table 1. Thermolysis and pseudo-first-order hydrolysis kinetic data of synthesized PFDA
peroxides.
a
T
Thermolysis
d
t
1/2
Hydrolysis
k (x 10 sec )
Peroxide
RF
5
–1
5
–1
(
°C) k (x 10 sec )
(h)
h
b
1
a
CF CF2
25
1.2
5.3
16.0
3.6
4.5
-
3
c
3
0
b
1
b
(CF ) CF
60
4.4
4.4
1.1
0.34
-
21.1
-
3
2
b
b
7
8
0
0
17.3
56.5
b
1
c
CF CF CF
2
15
1.5
7.8
12.8
2.5
4.5
-
3
2
d
3
0
b
b
1
d
CF (CF O)CF
20
1.8
9.9
10.7
1.9
0.47
1.5
-
-
3
3
3
4
0
0
b
40.8
b
1
e
CF (CF CF CF O)CF
20
3.4
5.7
1.4
-
-
3
3
2
2
b
3
0
13.9
a. Fluorinated residual in the structure of PFDA peroxide, accordingly to the formula
R C(O)OO(O)CR ; b. In CF ClCFCl as solvent; c. In CF OCFClCF Cl as solvent; d. In
F
F
2
2
3
2
®
Galden D100 as solvent.
The kinetic data reported in Table 1 reveal that hydrolysis is particularly relevant for non-
branched peroxides 1a and 1c, whose k are both approximately three times larger than the
h
corresponding thermolysis kinetic constants, k . On the contrary, the thermolysis of the
d
remaining branched peroxides is only slightly influenced by the hydrolysis, because the k and
d
kh are in the same range of values.
2
.2. Naphthoquinones functionalization
It was demonstrated that PFDA peroxides are useful reagents for the introduction of the
corresponding perfluoroalkyl groups into aromatic compounds such as benzene,
1
4
chlorobenzene, toluene, and anisole (Scheme 5). In 1983 C. Zhao et al. proposed a single
electron-transfer (SET) mechanism for the perfluoroalkylation reaction with electron rich
8

ACCEPTED MANUSCRIPT
3
5
aromatic substrates. More recently evidences of a free chain radical mechanism for this
3
6-38
reaction have been observed also on electron poor substrates.
Scheme 5. Perfluoroalkylation of aromatic substrates with PFDA peroxides.
Conversely, the thermal decomposition of perfluorodiacyl peroxides in the presence of 1,4-
naphthoquinonic compounds under degassed conditions revealed that the quinonic double
3
0-33
bond is more reactive toward radicals than the aromatic ring.
Thus, the
perfluoroalkylation of the corresponding quinonic derivatives occurs selectively on the
quinone ring (Scheme 6). Perfluorinated carboxylic acid and carbon dioxide are the main
byproducts generated during the reaction. Traces of several other compounds originated by
competitive side reactions include products from the recombination of two radicals, products
from double addition on substrate 2, and products of the addition of a perfluorocarboxyl
radical.
O
O
O
O
C
RF
X
O
+
CO2
O
RF
+
+
C
RF
O
C
O
RF OH
X
O
2
3
, X = H
, X = CH3
Scheme 6. Perfluoroalkylation of naphthoquinones with PFDA peroxides.
The underlying mechanism for the direct perfluoroalkylation involves the decomposition of
PFDA peroxides with generation of reactive perfluoroalkyl radicals, R ꢀ. These radicals can
F
selectively add to the quinone ring leading to a semiquinonic radical intermediate (Scheme 7).
9

ACCEPTED MANUSCRIPT
Scheme 7. Addition of a perfluoroalkyl radical to the quinonic double bond, tautomerism of
the semiquinone radical and oxidation with hydrogen abstraction.
–
1
The semiquinone radical has a bond-dissociation energy of the O–H bond (ca. 226 kJ mol )
–1
much lower than that of phenol (369 kJ mol ) and it is much more acidic (pKa = 4.1) than
5
7-60
phenol.
Thus, the equilibrium of the acid dissociation reaction of the semiquinone radical
is not negligible, suggesting two possible mechanisms: hydrogen abstraction from the
semiquinone radical or an electron transfer in a chain process. In fact, the semiquinone radical
6
1,62
has a proper persistency and may couple with a transient radical like RFꢀ.
Alternatively, a
classical electron-transfer decomposition reaction of PFDA peroxides can be induced by
6
3
easily-oxidizable semiquinone radical-anions.
Table 2. Direct perfluoroalkylation of quinones 2 and 3.
Peroxide Quinone Product Conversion (%) Selectivity (%)
a
Isolated yield (%)
1
1
a
a
2
3
2
3
2
3
2
3
2
3
2a
3a
2b
3b
2c
3c
2d
3d
2e
3e
93
95
94
82
98
95
95
87
80
88
96
98
86
87
95
98
65
67
78
72
74
90
66
62
78
67
46
43
47
48
1
1
b
b
1
1
c
c
1
1
d
d
1
1
e
e
a. The selectivity is referred to the reported product.
The direct perfluoroalkylation methodology was successively applied to the functionalization
of naphthoquinone derivatives 2 and 3, and high conversions and selectivities (Table 2) to the
desired products 2a-e and 3a-e (Figure 1) were observed in all cases.
1
0

ACCEPTED MANUSCRIPT
Figure 1. Perfluoroalkylation of naphthoquinones 2 and 3 with PFDA peroxides 1a-e.
In presence of 1-hexene, the perfluoroalkyl radicals R ꢀ react faster with the olefinic double
F
bond than with the quinone ring. In such circumstances, with reference to Scheme 2, the
radical adduct A is formed, and then added selectively to the quinone ring, leading to the
reaction product by oxidation of the semiquinone radical (Scheme 8). The overall kinetics of
radicals addition make the process particularly selective for a one-step one-pot procedure.
Products 2f-j and 3f-j were in fact obtained with rather high conversion and selectivity. The
results of the olefin-driven perfluoroalkylation of naphthoquinones 2 and 3 are reported in
Table 3, while the products obtained are graphically reported in Figure 2.
Scheme 8. Perfluoroalkylation of naphthoquinones with PFDA peroxides in presence of 1-
hexene.
1
1

ACCEPTED MANUSCRIPT
Table 3. Perfluoroalkylation of quinones 2 and 3 in presence of 1-hexene.
a
Peroxide
Quinone Product Conversion (%) Selectivity (%) Isolated yield (%)
1
1
a
a
2
3
2
3
2
3
2
3
2
3
2f
3f
2g
3g
2h
3h
2i
99
99
98
84
99
96
99
98
99
95
61
90
65
75
66
85
65
85
72
75
45
80
49
55
50
68
49
70
56
60
1
1
b
b
1
1
c
c
1
1
d
d
3i
1
1
e
e
2j
3j
a. The selectivity is referred to the reported product.
Overall, no significant difference in reactivity was observed between naphthoquinone
substrates 2 and 3. The increased steric hindrance near the functionalization site of substrate 3
due to the methyl group resulted negligible compared to the reactivity of the quinonic double
bond towards free radicals.
Figure 2. Products obtained by perfluoroalkylation of naphthoquinones 2 and 3 with PFDA
peroxides 1a-e in presence of 1-hexene.
Dichloromethane, CH Cl , was used as solvent during direct perfluoroalkylation reactions of
2
2
quinones with PFDA peroxides as well as in the presence of n-hexene. It allowed to perform
the whole experiment in a homogenous phase by dissolving the reagents and the solutions of
1
2

ACCEPTED MANUSCRIPT
PFDA peroxides in CF OCFClCF Cl. In addition, its boiling point lies within the correct
3
2
temperature range for decomposition of PFDA peroxides, with thermolytic half-life times
between 1 and 5 hours. Hydrogen abstraction from dichloromethane was also considered but,
at the experimental conditions, only traces of hydrogen abstraction side products were
observed at the end of reactions. Perfluroalkylation of quinones arose as the largely favored
synthetic pathway.
2
2
.3. Naphthoquinones characterization
1
19
.3.1. H and F NMR and steric hindrance of R
F
1
13
19
Complete GC-MS, and H, C and F NMR analysis for products 2a-j and 3a-j are reported
in the Experimental section, while NMR spectra are reported in the Supporting Information.
1
Interesting to note is the H NMR spectrum for products 3b, 3d and 3e, which shows
diastereotopic behavior in the methyl group hydrogen atoms. This uncommon occurrence is
bound to the time-scale of two different phenomena: the characteristic time of rotation of the
methyl group (actually 1/3 of that time because of the 3-fold symmetry) and the characteristic
time of acquisition of the resonance data. In the large majority of cases, methyl groups rotate
much faster than can be captured by NMR analysis, resulting in a single signal for all three
hydrogen atoms. This is in fact the case for the hydrogen atoms in the methyl group of
products 3a, 3c and 3f-j, as well as for the methyl group hydrogen atoms of quinone
derivative 3 itself. On the other hand, if for any reason the rotation about the C−CH axis is
3
significantly slower, the resonance of each hydrogen atom can be observed separately. In this
case, the particular topicity of the methyl group hydrogens of products 3b, 3d, and 3e might
be ascribed to the combined effect of R steric hindrance and of strong ‘through space’ H,F
F
coupling.
1
3

ACCEPTED MANUSCRIPT
Figure 3. Bold lines represent the potential energy curves associated with the rotation about ω
angle (against left axis) for products 3a and 3d, using the optimized value of ω as reference.
5
Thin lines represent unscaled J coupling constants computed for different values of ∆ω. In
HF
this case R’ = F for product 3a and R’ = OCF for product 3d.
F
F
3
A conformational study of products 3a and 3d (chosen as models for homotopic- and
diastereotopic-behaving methyl hydrogens respectively) was carried out. With reference to
Figure 3, absolute minimum energy conformations of both products (Boltzmann weight
factors of 0.995 and 0.810 respectively), characterized by a ω angle of about 25°, are used as
starting points for the calculation of the potential energy curves associated with the rotation
about the ω torsion angle. Bold lines in Figure 3 thus provide a quantitative insight on the
extent of the potential energy well of such stable conformations along the internal coordinate
ω, suggesting the perfluorinated substituent of product 3a to be substantially freely-oriented
compared to that of product 3d, which shows much higher torsional barriers. Indeed, although
small deviations from ∆ω=0 are allowed for product 3d, the torsion potential of product 3a
shows a nearly-flat low-energy segment in a range of ∆ω=30−150° allowing for much larger
1
4

ACCEPTED MANUSCRIPT
deviations (it should be noted that the torsion potential of product 3a is an even function in
the reference system centered in ∆ω=90°).
Indirect dipole−dipole coupling constants JHF have been computed for products 3a and 3d at
1
9
different values of ∆ω. F is known to give rise to large coupling to protons due to its high
5
nuclear magnetic moment. Thin lines in Figure 3 show that JHF coupling constants for both
products reach a maximum in the region of the minimum potential energy well (around
6
∆
ω=0). In the ∆ω=−40° region, JHF coupling constants of comparable magnitude are
obtained via CF groups, but the potential energy curves of both products possess a maximum
3
energy point in that region, making the coupling of CF fluorine atoms irrelevant.
3
The strong H,F coupling around the optimal value of ω, combined with the inability of R to
F
assume conformations characterized by large values of |∆ω| due to steric hindrance, result in
the unwarranted diastereotopic behavior of the methyl group hydrogen atoms observed
experimentally for products 3b, 3d, and 3e. No particular topicity is observed instead for all
other derivatives of 3 because of a much more forgiving ω torsion potential. It was
demonstrated in fact that products 3a and 3c possess higher conformational freedom,
opposing the preservation of the H,F coupling over time, while the hydrogenated fragment
between menadione and R in products 3f-j disrupts the coupling in the first place.
F
2
.3.2. Single crystal X-Ray diffraction (XRD)
In order to further contribute to the characterization of the obtained products, several attempts
were made at their crystallization. However, only product 3a crystallized in ordered
structures, suitable for diffractometric analysis. The bulkiness of the substituents, and the
conformational freedom of the perfluoroalkoxy moieties in particular (when present) are
thought to be the main reasons for the inability to obtain crystalline solids suitable for single-
crystal X-ray diffraction measurements from the other naphthoquinone products. Small, light
orange crystalline specimens could indeed be obtained for compound 3a. A sample of
1
5

ACCEPTED MANUSCRIPT
appropriate size and quality was selected for the structural analysis which was performed at a
temperature of 100 K, in order to prevent crystal degradation. Compound 3a crystallized in
the orthorhombic crystal system, with space group Pna21. The molecular conformation in the
solid state as oak ridge thermal ellipsoid plot (ORTEP) and the crystal packing at 100 K are
respectively reported in Figure 4.
Figure 4. ORTEP plot with 30% probability ellipsoids (left) and content of the
crystallographic unit cell aligned along the c axis (right) obtained for product 3a from single-
crystal X-Ray diffraction at 100K. Colour code: grey, carbon; white, hydrogen; red, oxygen;
yellow, fluorine.
2
.4. Theoretical investigation of PFDA peroxides reactivity
A conformational study of the PFDA peroxides 1a-e, along with all the corresponding thermal
decomposition products, was carried out in order to attempt a rationalization of their
experimental reactivity. The analysis shows that the absolute minimum energy conformation
for all the investigated peroxides is characterized by a dihedral angle θ (Figure 5) with respect
to the O−O bond (a) in the range of 84−87°, with carboxylic moieties lying on almost
orthogonal planes. The computed values of these dihedral angles and other relevant geometric
parameters are listed in Table 4. Reaction enthalpies and free energies were also computed
assuming optimum structures for all peroxides and decomposition products. The calculation
was iterated for both thermal decomposition reactions shown in Scheme 1, one-bond and
concerted three-bond cleavage mechanisms, and results are listed in Table 5. Data obtained
were however not decisive, as they did not suffice to aid in the clarification of the peroxides’
1
6

ACCEPTED MANUSCRIPT
chemical stability observed experimentally (see Table 1). The O−O bond lengths (a)
computed are only slightly influenced by R substrates as well as the other geometrical
F
evidences listed in Table 4, and the computed reaction energies and enthalpies do not
correlate well with the thermolytic half-life times measured.
Figure 5. Geometric parameters of perfluorodiacyl peroxide: O−O bond a, C−C bond b,
valence angle φ between the two oxygen atoms and dihedral angle θ. Colour code: grey,
carbon; red, oxygen.
Table 4. Selected geometric parameters calculated at the U-B3LYP/6-311G(d,p) level for
PFDA peroxides under investigation.
a
a
a
a
Peroxide
R
F
a
b
φ
θ
1
a
CF CF
1.438
1.439
1.440
1.437
1.437
1.557
1.557
1.561
1.563
1.562
127.2
126.9
127.4
127.2
127.2
84.7
86.7
86.1
85.6
85.6
3
2
1
1
b
(CF ) CF
3 2
c
CF CF CF
3 2 2
1d
CF (CF O)CF
3 3
1e
CF (C F O)CF
3 3 7
a. see Figure 4.
Table 5. U-B3LYP/6-311G(d,p) enthalpies and free energies of decomposition of PFDA
peroxides under investigation for one-bond and concerted three-bond cleavages, as from
-1
Scheme 1. All quantities are reported in kJ mol .
One-bond cleavage
Three-bond leavage
Peroxide
∆
H
∆G
∆Hd3
∆Gd3
d1
d1
1
1
a
b
-10.21
-23.99
-15.86
-24.49
-23.90
-116.50
-131.90
-120.64
-133.58
-134.41
-121.52
-142.28
-132.36
-147.72
-146.51
-270.54
-302.48
-283.22
-308.47
-309.64
1
c
1
d
1
e
2
Table 6. Electron density (ρ ), Laplacian (∇ ρ ) and relative Hamiltonian kinetic energy
b
b
density (ꢁK) at BCPs of PFDA peroxides under investigation (atomic units).
2
Peroxide
ρb
∇ ρ
ꢁK
b
1
a
0.269
0.269
0.269
0.270
0.270
0.332
0.334
0.336
0.328
0.327
1
E
E
E
E
-3
1
b
4
4
3
-3
-3
-4
1
c
1
d
1
e
0
1
7

ACCEPTED MANUSCRIPT
Further investigation of the topic led to the application of the quantum theory of atoms in
molecules (QTAIM) proposed by Bader. This methodology analyses the electron density
topology of molecular systems and reveals bonding motifs by characterizing stationary points
6
4
between two or more nuclei. When a stationary point is located between two atoms, it is
referred to as the bond critical point (BCP), and the study of several physical quantities
relative to that point can provide invaluable information about the nature of the bond itself.
BCPs associated with the O−O bridging bonds in peroxides 1a-e were determined from the
previously optimized structures’ electronic density. For each BCP, the electron density ρ , the
b
2
Laplacian of the electron density ∇ ρ , and the Hamiltonian kinetic energy density K, were
b
computed. Results are collected in Table 6. Values of electron density at BCPs (ρ ) are found
b
to be not appreciably sensitive to R , while corresponding values of the Laplacian for the
F
2
electron density (∇ ρ ) are greater than zero, thus indicating a depletion of electron density in
b
the region of contact of the two oxygen atoms. It is known that bond interactions for which
2
65
∇
ρ is greater than zero are dominated by a local excess of kinetic energy. In fact, the
b
analysis of the energy density at BCPs shows that the values of the Hamiltonian kinetic
energy density (K) decrease as the stability of PFDA peroxides increases, in accordance with
the kinetic constants of thermolysis (see Table 1).
3
. Concluding remarks
A selection of five perfluorodiacyl (PFDA) peroxides were employed in the functionalization
of 1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone (menadione). The perfluoroalkyl
groups were attached directly to the quinone, or linked to a spacer as obtained in the presence
of a non-conjugated alkene such as 1-hexene. Substituted naphthoquinones were successfully
obtained in good yields and with good selectivities, and full characterization was achieved by
1
19
1
GC-MS, H and F NMR spectroscopic analysis. As far as H NMR spectra are concerned, a
few methyl group hydrogen atoms in 2-methyl-1,4-naphthoquinone derivatives were observed
1
8

ACCEPTED MANUSCRIPT
to display a diastereotopic behavior. This uncommon phenomenon was attributed to the
conformationally-hampered structure of such products (resulting from the steric hindrance of
R ), allowing for the preservation over time of a strong H,F dipolar coupling.
F
In addition, light orange crystals of 3-(perfluoroethyl)-menadione were obtained in ordered
structures suitable for diffractometric analysis. The bulkiness of the fluorinated chains and the
mobility due to the presence of the oxygen atoms seemed to induce a high degree of disorder
in the molecular assembly of the other quinonic derivatives.
Finally, a theoretical investigation was carried out by computational means in order to clarify
the experimentally observed chemical stability of the PFDA peroxides considered.
Preliminary DFT calculations revealed that the extrapolation of a direct relationship between
geometrical parameters and thermolysis behavior is not straightforward. However, the
QTAIM approach applied to the computed electron densities showed evidences of a subtle
correlation between the local excess of kinetic energy at oxygen-oxygen bond critical points
(BCPs) and kinetic constants of thermolysis.
4
. Experimental section
4
.1 Materials and methods
Perfluoroacyl fluorides for the syntheses of peroxides 1a and 1b were provided by Solvay
Specialty Polymers; the perfluoroacyl chloride for peroxide 1c and the perfluoroacyl fluoride
for peroxide 1e were supplied by Sigma-Aldrich. Heptafluoro-2-methoxy-propionyl fluoride
was synthesized from carbonyl difluoride (Solvay Specialty Polymers) and trifluoro-2-
(trifluoromethoxy)-ethylene (Solvay Specialty Polymers) on the basis of the procedure
6
6,67
described in the literature.
The inert fluorinated solvent for the synthesis of PFDA
peroxides was CF OCFClCF Cl and it was furnished by Solvay Specialty Polymers. All other
3
2
chemical for the synthesis of PFDA peroxides were reagent grade purchased from Sigma
1
9

ACCEPTED MANUSCRIPT
Aldrich. CAUTION: Perfluoroacyl fluorides react with moisture developing HF and
perfluorocarboxylic acids.
In a typical kinetic measurement, about 1.5 ml of PFDA peroxide solution were put in a glass
test tube with screw neck; a whole set of these tubes was placed in a thermostat (±0.1°C), and
they were taken out at specified times and immediately frozen to dry ice temperature. In
kinetic measurements in the presence of water, 2.0 ml of distilled water were also added to the
glass test tube containing PFDA peroxide solution. The tubes were opened while cool, and 1.0
ml of peroxide solution was titrated by standard iodometry. First-order rate constant at
different temperatures were calculated by linear regression analysis.
1
,4-Naphthoquinone 2, 2-methyl-1,4-naphthoquinone 3 (menadione), 1-hexene and solvents
(dichloromethane, ethyl-acetate and n-hexane) were commercial reagent grade products by
Sigma-Aldrich and they were used without further purification.
The conversion was evaluated by GC analysis and calculated on the unreacted 2 or 3 referred
to an internal standard.
The reaction products were isolated by flash column chromatography (silica gel, n-hexane–
1
13
19
ethylacetate 9:1) and identified by GC-MS, H NMR, C NMR and F NMR spectroscopy.
Agilent 6890 Gas Cromatograph (GC) system equipped with a 30mt x 0.250mm HP-5MS GC
column and an Agilent 5973 Mass Selective Detector (MSD) detector were used to record the
1
13
GC-MS spectra. Bruker AV 400 ( H 400 MHz, C 100 MHz) equipped with a 5 mm
1
multinuclear probe with reverse detection was used to record H-NMR spectra. 32 scans for
1
13
19
H and 1024 scans for C were acquired with an acquiring time of 5 seconds. F NMR
1
spectra were carried out with a Bruker Avance 500 spectrometer operating at 470 MHz. H
1
9
and F NMR chemical shifts are referenced to tetramethylsilane (TMS) and CCl F,
3
respectively. Melting points were determined with a Buchi 535 apparatus. IR spectra were
collected with a Varian 640-IR IR Spectrometer equipped with a ATR-FTIR apparatus.
Elemental analyses were performed on a EA 1108 CHNS-O Fison instrument.
2
0

ACCEPTED MANUSCRIPT
4
.2 Synthesis of PFDA peroxides 1a-e
The solutions of PFDA peroxides 1a-e were prepared with good-to-medium yields from the
perfluoroacyl halides (fluoride or chloride) with H O in a biphasic alkaline system, according
2
2
3
6-38
to methods described in the literature (Scheme 4).
Solutions having peroxide
concentrations as high as 15% were prepared and stored at the appropriate temperature for
3
6-38
days.
CAUTION: PFDA peroxides may decompose very quickly through auto-induced
decomposition.
4
.3 Direct perfluoroalkylation of 1,4-naphthoquinones 2 and 3
.3.1 2-(perfluoroethyl)-1,4-naphthoquinone 2a
4
Quinone 2 (0.36 mmol) was dissolved in CH Cl (5 ml) and the resulting quinonic solution
2
2
was added to a solution of peroxide 1a (0.9 ml of 8.0% solution in CF OCFClCF Cl). The
wt
3
2
reaction mixture was heated at 40°C (reflux). After 8 hours, the solvent was evaporated in
vacuo and purification of the crude product by flash chromatography (hexane/ethyl acetate
9
:1) gave the title compound 2a (74 mg; 74%) as a yellow solid (m.p. 77-80°C). GC-MS: m/z
˗1
=
276[M]+ꢀ, 257, 248, 207, 179, 157, 129, 104, 76, 50. IR (ATR, cm ): ν
1672, 1591,
max
1
7
454, 1359, 1326, 1298, 1224, 1197, 1157, 1117, 1089, 1005, 931, 907, 859, 831, 803, 781,
1
41, 719. H NMR (500 MHz, CDCl ): δ 7.36 (s, 1 H), 7.82-7.88 (m, 2 H), 8.14 (dd, J = 2.1,
3
H
1
9
J = 5.6 Hz, 1 H), 8.19 (dd, J = 2.1, J = 5.6 Hz, 1 H) ppm. F NMR (500 MHz, CCl F): δ -
3
F
1
3
1
1
15.5 (m, 2 F, F ), -82.5 (t, 3 F, J = 1.7 Hz, F ) ppm. C NMR (100 MHz, CCl F): δ 186.4,
α β 3 C
85.2, 138.7, 136.0, 135.4, 134.0, 131.9, 130.9, 128.2, 127.5, 126.5, 125.6 ppm. C H F O
12
5
5
2
(276.16): calc. C 52.19, H 1.82; found C 52.3, H 1.8.
4
.3.2 2-(perfluoro-iso-propyl)-1,4-naphthoquinone 2b
2
1

ACCEPTED MANUSCRIPT
Quinone 2 (0.36 mmol) was dissolved in CH Cl (5 ml) and the resulting quinonic solution
2
2
was added to a solution of peroxide 1b (1.7 ml of 5.7% solution in CF OCFClCF Cl). The
wt
3
2
reaction mixture was heated at 40°C (reflux). After 72 hours, the solvent was evaporated in
vacuo and purification of the crude product by flash chromatography (hexane/ethyl acetate
9
:1) gave the title compound 2b (77 mg; 66%) as a yellow solid (m.p. 51-54°C). GC-MS: m/z
˗
1
=
326 [M]+ꢀ, 307, 298, 257, 229, 179, 157, 129, 104, 76, 50. IR (ATR, cm ): ν 1795, 1674,
max
1
1
596, 1461, 1298, 1225, 1171, 1105, 1035, 983, 920, 825, 780, 734. H NMR (500 MHz,
CDCl ): δ 7.42 (d, J = 1.4, 1 Hz), 7.82-7.88 (m, 2 H), 8.14 (dd, J = 2.6, J = 5.5 Hz, 1 H),
3
H
LR
1
9
8
7
1
.18 (dd, J = 2.6, J =5.5 Hz, 1 H) ppm. F NMR (500 MHz, CCl F): δ -177.2 (m, 1 F, F ), -
3 F α
1
3
4.1 (d, 6 F, J = 4.8 Hz, F ) ppm. C NMR (100 MHz, CCl F): δ 185.4, 138.7, 134.9, 134.1,
β
3
C
31.9, 127.1, 126.5 ppm. C H F O (326.17): calc. C 47.87, H 1.55; found C 48.0, H 1.7.
13
5
7
2
6
8
4
.3.3 2-(perfluoro-n-propyl)-1,4-naphthoquinone 2c
Quinone 2 (0.36 mmol) was dissolved in CH Cl (5 ml) and the resulting quinonic solution
2
2
was added to a solution of peroxide 1c (2.3 ml of 4.2% solution in CF OCFClCF Cl). The
wt
3
2
reaction mixture was heated at 40°C (reflux). After 8 hours, the solvent was evaporated in
vacuo and purification of the crude product by flash chromatography (hexane/ethyl acetate
9
:1) gave the title compound 2c (92 mg; 78%) as an orange solid (m.p. 55-58°C). GC-MS:
˗1
m/z = 326 [M]+ꢀ, 307, 298, 257, 229, 179, 157, 129, 104, 76, 50. IR (ATR, cm ): ν 1672,
max
1
7
5
627, 1593, 1458, 1307, 1223, 1191, 1153, 1122, 1078, 1026, 949, 918, 859, 823, 780, 743,
1
20. H NMR (500 MHz, CDCl ): δ 7.34 (s, 1 H), 7.82-7.88 (m, 2 H), 8.14 (dd, J = 1.5, J =
3
H
19
.7 Hz, 1 H), 8.19 (dd, J = 1.5, J = 5.7 Hz, 1 H) ppm. F NMR (500 MHz, CCl F): δ -112.7
3
F
13
(
m, 2 F, F ), -125.4 (m, 2 F, F ), -81.2 (t, 3 F, J = 9.8 Hz, F ) ppm. C NMR (100 MHz,
α β γ
CCl F): δ 185.3, 179.4, 138.7, 136.6, 136.0, 134.0, 131.9, 131.3, 130.9, 128.2, 127.5, 126.5,
3
C
1
25.6 ppm. C H F O (326.17): calc. C 47.87, H 1.55; found C 47.9, H 1.6.
13 5 7 2
2
2

ACCEPTED MANUSCRIPT
4
.3.4 2-(1’-trifluoromethoxy-perfluoroethyl)-1,4-naphthoquinone 2d
Quinone 2 (0.36 mmol) was dissolved in CH Cl (5 ml) and the resulting quinonic solution
2
2
was added to a solution of peroxide 1d (2.1 ml of 4.9% solution in CF OCFClCF Cl). The
wt
3
2
reaction mixture was stirred at room temperature overnight. Thereafter, the solvent was
evaporated in vacuo and purification of the crude product by flash chromatography
(hexane/ethyl acetate 9:1) gave the title compound 2d (57 mg; 46%) as a yellow solid (m.p.
5
2-54°C). GC-MS: m/z = 342 [M]+ꢀ, 314, 273, 245, 217, 179, 157, 129, 104, 69. IR (ATR,
˗1
cm ): ν 1669, 1631, 1593, 1459, 1302, 1221, 1136, 1105, 1034, 921, 890, 829, 765, 741.
max
1
19
H NMR (500 MHz, CDCl ): δ 7.46 (s, 1 H), 7.75 (m, 2 H), 8.12 (m, 2 H) ppm. F NMR
3
H
1
3
(
500 MHz, CCl F): δ -127.0 (m, 1 F, F ), -82.4 (d, 3 F, F ), -55.0 (d, 3 F, OCF ) ppm. C
3 F α β 3
NMR (100 MHz, CCl F): δ 185.1, 138.7, 135.6, 135.3, 135.0, 134.7, 134.0, 132.0, 128.1,
3
C
1
27.6, 127.4, 126.5 ppm. C H F O (342.17): calc. C 45.63, H 1.47; found C 45.5, H 1.5.
13 5 7 3
4
.3.5 2-(1’-(perfluoro-n-propoxy)-perfluoroethyl)-1,4-naphthoquinone 2e
Quinone 2 (0.36 mmol) was dissolved in CH Cl (5 ml) and the resulting quinonic solution
2
2
was added to a solution of peroxide 1e (2.2 ml of 6.8% solution in CF OCFClCF Cl). The
wt
3
2
reaction mixture was stirred at room temperature overnight. Thereafter, the solvent was
evaporated in vacuo and purification of the crude product by flash chromatography
(hexane/ethyl acetate 9:1) gave the title compound 2e (75 mg; 47%) as a yellowish oil. GC-
MS: m/z = 442 [M]+·, 423, 414, 386, 373, 345, 317, 257, 229, 179, 169, 157, 151, 129, 119,
˗
1
1
1
7
04, 76, 69, 50. IR (ATR, cm ): ν 1676, 1595, 1459, 1335, 1302, 1229, 1198, 1143, 1080,
max
1
035, 988, 925, 835, 805, 779, 752, 731. H NMR (500 MHz, CDCl ): δ 7.39 (s, 1 H), 7.80-
3
H
1
9
.88 (m, 2 H), 8.13 (dd, J = 1.9, J = 6.4 Hz, 1 H), 8.18 (dd, J = 1.9, J = 6.4 Hz, 1 H) ppm. F
2
NMR (500 MHz, CCl F): δ -125.5 (m, 1 F, F ), -81.7 (d, 3 F, F ), -80.5 (dm, 1 F, J
=
3
F
α
β
F,F
2
1
45.7 Hz, OCF*F), -84.8 (dm, 1 F, JF,F = 145.7 Hz, OCFF*), -129.3 to -130.5 (dm, 2 F, JA,B
1
3
=
283.3 Hz, CF ), -81.6 (t, 3 F, CF ). C NMR (100 MHz, CCl F): δ 186.2, 185.5, 160.8,
2 3 3 C
2
3

ACCEPTED MANUSCRIPT
1
60.5, 140 139.0, 135.9, 135.5, 135.4, 134.5, 132.1, 131.9, 127.8, 127.7, 126.9 ppm.
C H F O (442.18): calc. C 40.74, H 1.14; found C 40.6, H 1.0.
15
5
11
3
4
.3.6 2-methyl-3-(perfluoroethyl)-1,4-naphthoquinone 3a
Quinone 3 (0.36 mmol) was dissolved in CH Cl (5 ml) and the resulting quinonic solution
2
2
was added to a solution of peroxide 1b (0.9 ml of 8.0% solution in CF OCFClCF Cl). The
wt
3
2
reaction mixture was heated at 40°C (reflux). After 8 hours, the solvent was evaporated in
vacuo and purification of the crude product by flash chromatography (hexane/ethyl acetate
9
:1) gave the title compound 3a (94 mg; 90%) as a yellow solid (m.p. 75-77°C). GC-MS: m/z
˗1
=
290[M]+·, 270, 262, 242, 221, 193, 171, 163, 143, 115, 104, 89, 76, 69, 50. IR (ATR, cm ):
νmax 1670, 1592, 1438, 1384, 1323, 1283, 1198, 1175, 1142, 1103, 1064, 1031, 993, 951, 840,
1
7
85, 736, 706. H NMR (500 MHz, CDCl ): δ 2.42 (t, J = 2.42 Hz, 3 H), 7.78 (m, 2 H), 8.11
3
H
1
9
(
m, 2 H) ppm. F NMR (500 MHz, CCl F): δ -108.1 (m, 2 F, F ), -82.8 (t, 3 F, J = 2.3 Hz,
3 F α
1
3
F ) ppm. C NMR (100 MHz, CCl F): δ 183.6, 180.1, 152.5, 134.6, 134.2, 132.7, 132.0,
β
3
C
1
31.0, 126.7, 13.9 ppm. C H F O (290.19): calc. C 53.81, H 2.43; found C 53.9, H 2.3.
13 7 5 2
4
.3.7 2-methyl-3-(perfluoro-iso-propyl)-1,4-naphthoquinone 3b
Quinone 3 (0.36 mmol) was dissolved in CH Cl (5 ml) and the resulting quinonic solution
2
2
was added to a solution of peroxide 1b (1.7 ml of 5.7% solution in CF OCFClCF Cl). The
wt
3
2
reaction mixture was heated at 40°C (reflux). After 72 hours, the solvent was evaporated in
vacuo and purification of the crude product by flash chromatography (hexane/ethyl acetate
9
:1) gave the title compound 3b (83 mg; 62%) as a yellow solid (m.p. 65-68°C). GC-MS: m/z
˗1
=
340[M]+·, 321, 300, 271, 243, 223, 195, 171, 146, 115, 104, 89, 76, 69, 50. IR (ATR, cm ):
1
νmax 1791, 1677, 1595, 1460, 1378, 1279, 1225, 1164, 993, 970, 844, 758, 734. H NMR (500
MHz, CDCl ): δ 2.48 (d, J = 8.02 Hz, 2 H), 2.60 (s, 1 H), 7.79 (m, 2 H), 8.12 (m, 2 H) ppm.
3
H
1
9
13
F NMR (500 MHz, CCl F): δ -171.7 (m, 1 F, F ), -72.5 (d, 6 F, J = 1.8 Hz, F ) ppm. C
3
F
α
β
2
4

ACCEPTED MANUSCRIPT
NMR (100 MHz, CCl F): δ 184.3, 180.8, 153.5, 134.5, 134.3, 134.2, 131.5, 131.1, 126.9,
3
C
1
26.7, 14.0-13.8 ppm. C H F O (340.19): calc. C 49.43, H 2.07; found C 49.3, H 1.9.
14 7 7 2
6
8
4
.3.8 2-methyl-3-(perfluoro-n-propyl)-1,4-naphthoquinone 3c
Quinone 3 (0.36 mmol) was dissolved in CH Cl (5 ml) and the resulting quinonic solution
2
2
was added to a solution of peroxide 1c (2.3 ml of 4.2% solution in CF OCFClCF Cl). The
wt
3
2
reaction mixture was heated at 40°C (reflux). After 8 hours, the solvent was evaporated in
vacuo and purification of the crude product by flash chromatography (hexane/ethyl acetate
9
:1) gave the title compound 3c (82 mg; 67%) as an orange solid (m.p. 69-71°C). GC-MS:
˗1
m/z = 340[M]+· 320, 293, 221, 193, 171, 164, 143, 115, 104, 76, 69, 50. IR (ATR, cm ): ν
max
1
1
676, 1591, 1352, 1287, 1213, 1183, 1117, 1042, 962, 914, 837, 792, 741, 707. H NMR (500
1
9
MHz, CDCl ): δ 2.42 (t, 3.8 Hz, 3 H), 7.78 (m, 2 H), 8.11 (m, 2 H) ppm. F NMR (500
3
H
MHz, CCl F): δ -105.6 (m, 2 F, F ), -124.8 (m, 2 F, F ), -81.3 (t, 3 F, J = 10.2 Hz, F ) ppm.
3
F
α
β
γ
1
3
C NMR (100 MHz, CCl F): δ 183.6, 180.1, 152.6, 134.6, 134.1, 132.0, 131.0, 126.7, 14.0
3
C
ppm. C H F O (340.19): calc. C 49.43, H 2.07; found C 49.5, H 2.0.
14
7
7
2
4
.3.9 2-methyl-3-(1’-trifluoromethoxy-perfluoroethyl)-1,4-naphthoquinone 3d
Quinone 3 (0.36 mmol) was dissolved in CH Cl (5 ml) and the resulting quinonic solution
2
2
was added to a solution of peroxide 1d (2.1 ml of 4.9% solution in CF OCFClCF Cl). The
wt
3
2
reaction mixture was stirred at room temperature overnight. Thereafter, the solvent was
evaporated in vacuo and purification of the crude product by flash chromatography
(hexane/ethyl acetate 9:1) gave the title compound 3d (55 mg; 43%) as a yellow solid (m.p.
˗
1
9
1
7
8
0-95°C). GC-MS: m/z = 356 [M]+·, 270, 239, 201, 171, 143, 104, 69. IR (ATR, cm ): ν
max
712, 1669, 1594, 1378, 1285, 1202, 1164, 1116, 1029, 998, 974, 919, 888, 843, 787, 750,
1
05. H NMR (500 MHz, CDCl ): δ 2.43 (d, J = 6.2 Hz, 2 H), 2.60 (s, 1 H), 7.77 (m, 2 H),
3
H
1
9
.10 (m, 2 H) ppm. F NMR (500 MHz, CCl F): δ -120.1 (m, 1 F, F ), -82.2 (s, 3 F, F ), -
3
F
α
β
2
5

ACCEPTED MANUSCRIPT
1
3
5
5.1 (d, 3 F, J = 9.1 Hz, OCF ) ppm. C NMR (100 MHz, CCl F): δ 185.2, 184.8, 148.4,
3 3 C
1
35.6, 135.2, 134.8, 134.6, 134.2, 133.6, 127.6, 127.4, 126.7, 126.1, 16.3 ppm. C H F O
3
14
7
7
(356.19): calc. C 47.21, H 1.98; found C 47.1, H 2.0.
4
.3.10 2-methyl-3-(1’-(perfluoro-n-propoxy)-perfluoro-ethyl)-1,4-naphthoquinone 3e
Quinone 3 (0.36 mmol) was dissolved in CH Cl (5 ml) and the resulting quinonic solution
2
2
was added to a solution of peroxide 1e (2.2 ml of 6.8% solution in CF OCFClCF Cl). The
wt
3
2
reaction mixture was stirred at room temperature overnight. Thereafter, the solvent was
evaporated in vacuo and purification of the crude product by flash chromatography
(hexane/ethyl acetate 9:1) gave the title compound 3e (86 mg; 48%) as a yellow solid (m.p.
6
5-70°C). GC-MS: m/z = 456 [M]+·, 387, 359, 339, 270, 243, 201, 171, 143, 104, 69. IR
˗1
1
(
ATR, cm ): ν 1671, 1594, 1284, 1229, 1198, 1141, 1101, 1059, 988, 787, 751, 730. H
max
NMR (500 MHz, CDCl ): δ 2.45 (d, J = 6.8 Hz, 2 H), 2.60 (s, 1 H), 7.77 (m, 2 H), 8.11 (m, 2
3
H
19
H) ppm. F NMR (500 MHz, CCl F): δ -118.7 (m, 1 F, F ), -81.8 (s broad, 3 F, F ), -80.2
3
F
α
β
2
2
(
dm, 1 F, J = 147.9 Hz, OCF*F), -86.5 (dm, 1 F, J = 147.9 Hz, OCFF*), -129.7 to -
F,F F,F
1
3
1
1
1
1
31.0 (dm, 2 F, JA,B = 280.1 Hz, CF ), -82.2 (t, 3 F, CF ). C NMR (100 MHz, CCl F): δ
2 3 3 C
83.5, 180.8, 151.9, 148.5, 134.7, 134.3, 134.2, 134.1, 131.9, 131.8, 131.1, 131.0, 126.9,
26.8, 126.7, 14.0, 13.6 ppm. C H F O (456.21): calc. C 42.12, H 1.55; found C 41.9, H
1
6
7
11
3
.6.
4
.4 Perfluoroalkylation of 1,4-naphthoquinones 2 and 3 in presence of 1-hexene
.4.1 2-(1’-(2’2’,3’,3’,3’-pentafluoro-propyl)-pentyl)-1,4-naphthoquinone 2f
4
Quinone 2 (0.36 mmol) and n-hexene (1.08 mmol, 0.13 ml) were dissolved in CH Cl (5 ml)
2
2
and the resulting solution was added to a solution of peroxide 1a (0.9 ml of 8.0% solution in
wt
CF OCFClCF Cl). The reaction mixture was heated at 40°C (reflux). After 8 hours, the
3
2
solvent was evaporated in vacuo and purification of the crude product by flash
2
6

ACCEPTED MANUSCRIPT
chromatography (hexane/ethyl acetate 9:1) gave the title compound 2f (58 mg; 45%) as a
yellowish oil. GC-MS: m/z = 360[M]+ꢀ, 345, 331, 317, 227, 185, 157, 157, 104, 76, 41. IR
˗1
(
ATR, cm ): ν 2959, 2932, 2873, 1777, 1665, 1595, 1459, 1327, 1301, 1192, 1030, 994,
max
1
9
1
7
06, 779, 715. H NMR (500 MHz, CDCl ): δ 0.88 (t, J = 7.1 Hz, 3 H), 1.17-1.40 (m, 4 H),
3
H
.69-1.82 (m, 2 H), 2.31–2.43 (m, 1 H), 2.55–2.67 (m, 1 H), 3.29 (m, 1 H), 6.80 (s, 1 H),
.77-7.76 (m, 2 H), 8.09 (dd, J = 2.3, J = 4.5 Hz, 1 H), 8.12 (dd, J = 2.3, J = 4.5 Hz, 1 H) ppm.
F NMR (500 MHz, CCl F): δ -117.9 to -119.5 (q, J = 271 Hz, 2 F, F ), -86.8 (t, 3 F, J = 1.1
1
9
3
F
α
13
Hz, F ) ppm. C NMR (100 MHz, CCl F): δ 185.7, 184.4, 154.0, 152.8, 135.0, 134.9, 134.1,
β
3
C
1
33.9, 132.4, 131.7, 127.0, 126.2, 37.0, 34.7, 29.4, 27.2, 22.4, 13.6 ppm. C H F O
18 17 5 2
(360.33): calc. C 60.00, H 4.76; found C 60.3, H 4.8.
4
.4.2 2-(1’-(2’-trifluoromethyl-2’,3’,3’,3’-tetrafluoro-propyl)-pentyl)-1,4-naphthoquinone 2g
Quinone 2 (0.36 mmol) and n-hexene (1.08 mmol, 0.13 ml) were dissolved in CH Cl (5 ml)
2
2
and the resulting solution was added to a solution of peroxide 1b (1.7 ml of 5.7% solution in
wt
CF OCFClCF Cl). The reaction mixture was heated at 40°C (reflux). After 72 hours, the
3
2
solvent was evaporated in vacuo and purification of the crude product by flash
chromatography (hexane/ethyl acetate 9:1) gave the title compound 2g (72 mg; 49%) as a
yellowish oil. GC-MS: m/z = 410[M]+ꢀ, 395, 381, 367, 227, 213, 185, 157, 104, 76, 41. IR
˗1
(
ATR, cm ): ν
2961, 2935, 2874, 1787, 1666, 1595, 1461, 1218, 1156, 1039, 991, 943,
max
1
9
1
7
04, 780, 717. H NMR (500 MHz, CDCl ): δ 0.87 (t, J = 7.2 Hz, 3 H), 1.16-1.36 (m, 4 H),
3
H
.64-1.76 (m, 2 H), 2.34-2.43 (m, 1 H), 2.69-2.77 (m, 1 H), 3.29 (m, 1 H), 6.77 (s, 1 H), 7.75-
1
9
.77 (m, 2 H), 8.09 (dd, J = 1.7, J = 4.5 Hz, 1 H), 8.13 (dd, J = 1.7, J = 4.5 Hz, 1 H) ppm. F
NMR (500 MHz, CCl F): δ -185.3 (m, 1 F, F ), -77.1 (dm, 3 F, J = 8.2 Hz, F ’), -78.2 (dm, 3
3
F
α
β
13
F, J = 8.2 Hz, F ”) ppm. C NMR (100 MHz, CCl F): δ 186.1, 159.6, 159.3, 135.0, 134.3,
β
3
C
1
34.1, 132.4, 131.7, 127.1, 126.3, 37.4, 35.9, 29.4, 27.2, 22.3, 13.5 ppm. C H F O
19 17 7
2
(410.33): calc. C 55.62, H 4.18; found C 55.8, H 4.3.
2
7

ACCEPTED MANUSCRIPT
4
.4.3 2-(1’-(2’,2’,3’,3’,4’,4’,4’-heptafluoro-butyl)-pentyl)-1,4-naphthoquinone 2h
Quinone 2 (0.36 mmol) and n-hexene (1.08 mmol, 0.13 ml) were dissolved in CH Cl (5 ml)
2
2
and the resulting solution was added to a solution of peroxide 1c (2.3 ml of 4.2% solution in
wt
CF OCFClCF Cl). The reaction mixture was heated at 40°C (reflux). After 8 hours, the
3
2
solvent was evaporated in vacuo and purification of the crude product by flash
chromatography (hexane/ethyl acetate 9:1) gave the title compound 2h (74 mg; 50%) as a
yellowish oil. GC-MS: m/z = 410[M]+ꢀ, 395, 381, 367, 227, 185, 157, 104, 76, 41. IR (ATR,
˗1
cm ): ν
2960, 2933, 2874, 1665, 1595, 1467, 1352, 1329, 1301, 1220, 1172, 1112, 953,
max
1
9
1
7
26, 779, 716. H NMR (500 MHz, CDCl ): δ 0.61 (t, J = 7.2 Hz, 3 H), 1.20-1.40 (m, 4 H),
3
H
.69-1.81 (m, 2 H), 2.35-2.47 (m, 1 H), 2.59-2.72 (m, 1 H), 3.30 (m, 1 H), 6.80 (s, 1 H), 7.78-
1
9
.75 (m, 2 H), 8.09 (dd, J = 1.7, J = 4.5 Hz, 1 H), 8.13 (dd, J = 1.7, J = 4.5 Hz, 1 H) ppm. F
NMR (500 MHz, CCl F): δ -113.2 to -115.9 (q, J = 271 Hz, 2 F, F ), -128.7 (m, 2 F, F ), -
3
F
α
β
13
8
1.4 (t, 3 F, J = 9.8 Hz, F ) ppm. C NMR (100 MHz, CCl F): δ 185.7, 184.4, 152.8, 135.5,
γ 3 C
1
35.0, 134.9, 134.1, 133.9, 132.5, 131.8, 127.0, 126.9, 126.2, 37.0, 34.7, 29.5, 27.2, 22.4, 13.6
ppm. C H F O (410.33): calc. C 55.62, H 4.18; found C 55.8, H 4.3.
19
17
7
2
4
.4.4 2-(1’-(2’-trifluoromethoxy-2’,3’,3’,3’-tetrafluoro-propyl)-pentyl)-1,4-naphthoquinone 2i
Quinone 2 (0.36 mmol) and n-hexene (1.08 mmol, 0.13 ml) were dissolved in CH Cl (5 ml)
2
2
and the resulting solution was added to a solution of peroxide 1d (2.1 ml of 4.9% solution in
wt
CF OCFClCF Cl). The reaction mixture was stirred at room temperature overnight.
3
2
Thereafter, the solvent was evaporated in vacuo and purification of the crude product by flash
chromatography (hexane/ethyl acetate 9:1) gave the title compound 2i (75 mg; 49%) as a
yellowish oil. Mixture of diastereomeric forms. GC-MS: m/z = 426 [M]+·, 397, 371, 351,
˗
1
2
1
81, 227, 185, 157, 128, 104, 76. IR (ATR, cm ): ν 2961, 2933, 2874, 1782, 1667, 1595,
max
1
459, 1327, 1188, 1087, 1038, 898, 779, 718. H NMR (500 MHz, CDCl ): δ 0.87 (t, J = 6.3
3
H
2
8