REACTIONS OF HINDERED PHENOLS WITH N-FLUORINATING REAGENTS
59
power Y, a measure of solvent polarity. The relatively
small correlation factor m obtained indicates only a small
change in the polarity of the rate-determining transition
state compared with the reactants.
The mechanism of reaction of ‘electrophilic’ fluorinat-
ing reagents with organic molecules is still open to
discussion, but it has been generally accepted that the
course of these reactions is strongly dependent on the
structure of the reagent and the target molecule, as well as
on reaction conditions. Unequivocal definition of the
reaction pathway through which the products are formed
is very difficult, but two boundary concepts were
accepted. The main postulate of the first concept is a
transfer of a fluorine atom (FT) through a classical SN2
process: an electron-rich reaction centre on the target
molecule attacks the fluorine atom on a reagent,
displacing its ligand part, which must necessarily be a
better leaving group than fluoride. The second concept
accepts electron transfer (ET) as the key process in these
reactions. It postulates the initial formation of a charge-
transfer complex between an electron-rich organic mol-
ecule and an electron-deficient fluorinating reagent,
followed by one-electron transfer, thus forming a target
molecule cation radical as the active intermediate and
precursor of fluorinated or non-fluorinated products.1 The
formation of a charge-transfer complex and cation radical
intermediates was demonstrated by UV spectroscopy in
the case of reactions of activated aromatics with N-
fluoropyridinium salts,15 and cation radicals were
monitored by electron spin resonance spectroscopy in
the case of reactions of N-halogen reagents (NBS or
NCS) with electron-rich aromatics.16
On the basis of the present results, we conclude that the
reaction pathway in the reactions of F-TEDA-BF4 or
NFTh with hindered phenols involves an electron-
transfer process. The most probable reaction pathways
leading to the products observed are shown in Schemes
2 and 3. The initial substrate–reagent complex, after
electron transfer from donor phenol 1 to acceptor F-
TEDA-BF4, gives a cation-radical (9, Scheme 2) and an
N—F radical species [(a), Scheme 2]. This species could
disproportionate by a homolytic (b) or heterolytic (c)
process, thus revealing F. or FÀ, and all three of them
could be the potential fluorine atom transfer carriers. The
transformation of cation-radical (9) to the products is
crucially affected by the reaction conditions, and we
observed the formation of three main types of product.
Under aprotic conditions (neat MeCN), the fluorination
of target molecules, resulting in 2- and 4-fluoro-
substituted cyclohexadienone derivatives (3 and 4) or
2-fluoro-substituted phenols (5), was the exclusive
process, whereas under protic conditions (MeCN and
10% ROH) regiospecific formation of para quinols or
para quinol ethers (6) took place. The third process,
Ritter-type amidation of target molecules, was found to
be the main transformation under acidic conditions
(MeCN and 10% TFA), which is usually the case in
Scheme 2
these kinds of transformation.8 TFA also plays a
significant role in the persistence of radical cations,17
which, as highly acidic species, readily release a
proton.15b Radical cation (9) thus transforms by proton
loss to a phenoxy (10) or benzyl radical (11), which,
immediately after another electron transfer, yields benzyl
cation (12) in the case of 1a or cyclohexadienone cation
(13) in the case of 1b. Ritter-type collapse of 12 with
MeCN solvent resulted in para-methylacetamido phenol
8. In the second case an ortho attack of MeCN to 13,
followed by cyclization and dealkylation of intermediate
14 to the benzooxazole derivative 7, is the driving force
of the reaction (Scheme 3). The direct attack of MeCN to
radical cation 9 is also optional in the case of the
formation of the product 7, as observed recently
elsewhere.18 Which of the reaction steps in Scheme 2 is
rate determining depends, among others factors, on the
ionisation potentials (IPs) and half-wave redox potentials
E1/2 of the target phenols. If the electron-transfer process
is rate determining, then, with increasing IP or E1/2, the
reaction rate would be expected to decrease. Although IP
and E1/2 values increase from 1b through 1a to 2,4,6-
trimethylphenol,19 and second-order rate constants in-
crease in the opposite direction, these differences are too
small to be interpreted. Therefore, we believe that the
formation of a bimolecular substrate–reagent complex
that is strongly regulated by steric factors is the rate-
Copyright 2001 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2002; 15: 56–61