N. Chatterjee, A. Goswami / Tetrahedron Letters xxx (2015) xxx–xxx
3
Plausible mechanistic pathways for the organo-hypervalent
iodine(III)-catalyzed hydroxylation reaction are depicted in
Scheme 4. Successful hydroxylation of the arylboronic acid under
inert environment obviates the involvement of molecular oxygen
in the oxidation procedure. It is anticipated that iodobenzene in
the presence of NaIO4 is first oxidized to iodosobenzene, an organo
iodine(III) species, which accounts for the hydroxylation.
Two catalytic cycles can be proposed for this type of hydroxyla-
tion reaction: pathways A and B. In pathway A, nucleophilic attack
of the organoboron acid to the iodosobenzene produces another
meta-stable hypervalent iodine species (I), which in the presence
of H2O leads to the tetra coordinated boron intermediate (II). The
subsequent intra-molecular [1,2] aryl shift of the species (II) results
in the formation of desired phenol. In this process, iodosobenzene
eventually gets reduced to iodobenzene, which undergoes further
oxidation to iodine(III) by NaIO4 to initiate a repetitive oxidation-
reduction cycle. Similarly, in case of organoboronic esters, in the
presence of NaIO4, they are first converted to their corresponding
boronic acids,19 which then undergo hydroxylation following the
above mentioned pathway.
PhI (10 mol%)
NaIO4 (2.0 equiv.)
R-B(OH)2
3
R-OH
CH3CN-H2O
80 °C / 8 h
4
OH
OH
Me
OH
4b (63%)
4c (61%)
4a (65%)
Scheme 3. Organic hypervalent iodine(III) catalyzed ipso-hydroxylation of alkyl-
boronic acids. Reaction conditions: 3 (2.0 mmol), PhI (0.2 mmol, 10 mol %), NaIO4
(4.0 mmol), CH3CN–H2O (8 mL, 3:1), 80 °C, 8 h, open air.
O
B
O
B
O
B
O
B
O
O
O
O
N
5d (59%)
5a (64%)
5b (58%)
5c (61%)
Figure 2. Organic hypervalent iodine(III) catalyzed ipso-hydroxylation of organo-
boronates. Reaction conditions: (1.0 mmol), PhI (0.1 mmol, 10 mol %), NaIO4
5
In pathway B, the arylboronic acid is first transformed to tetra
coordinated species (III) that undergoes iodine-boron exchange21
to produce iodonium salt (IV), which on further reaction with
water is supposed to provide phenol and expected aromatic alco-
hol along with the iodobenzene to commence a new catalytic cycle.
It should be mentioned that under no circumstance phenol was
detected along with the desired aromatic alcohol.
Two separate reactions were performed with m-tolylboronic
acid (1a) and pyridine-3-boronic acid (1q) in anhydrous acetonitrile
in the presence of H2O18 in order to establish, more accurately, the
pathway by which iodine(III)-catalyzed hydroxylation reaction is
operating (Scheme 5). No instance of formation of aromatic alcohol
containing isotopic oxygen (Ar-18OH), which would definitely be
obtained if the reaction would proceed through path B, was detect-
ed in GC–MS. Therefore, it could be inferred that the hydroxylation
reaction proceeds through the oxidation of organoiodine(I) to orga-
noiodine(III), which is followed by the nucleophilic attack of the
organoboronic species to the organoiodine(III) agent and then
intra-molecular [1,2] aryl migration (path A, Scheme 4).
(2.0 mmol), CH3CN–H2O (8 mL, 3:1), 80 °C, 8 h, open air; the reaction was
performed with 5a in a 3.0 mmol scale.
reactions developed herein works equally well with arylboronic
acids having either an electron donating or withdrawing group.
Equally stimulating was the observation that the arylboronic
acids with oxidation-sensitive functional group such as aldehydes
(2h and 2i) also endured the reaction conditions employed, with-
out undergoing over-oxidation.
The smooth transformation of halide-substituted arylboronic
acids to their corresponding halo substituted aromatic alcohols
(2j, 2k, and 2l) makes this protocol further versatile. Hydroxylation
of N-heterocyclic boronic acid to 3-hydroxy pyridine (2q) was also
performed successfully, using this method.
Next, alkylboronic acids were also employed for hydroxylation
reactions to explore the extent of this methodology (Scheme 3).
In general, aliphatic alcohols, especially primary alcohols, are diffi-
cult to access through oxidative methods, as they are prone to get
over-oxidized easily.20
To our delight, the newly developed organocatalytic method did
not reveal such difficulties, and both primary (4b and 4c) and sec-
ondary alcohols were (4a) obtained with moderate yields.
Not only the aromatic/aliphatic boronic acids but other aryl/
alkylboronates are also found to be suitable substrates for
hydroxylation reaction developed in the present work (Fig. 2).
The protocol is found to be reconcilable with the olefin moiety,
as it did not cause oxidation of C–C double bond in compound 5a.
In conclusion, we have developed a novel methodology for
organo hypervalent iodine(III) catalyzed ipso hydroxylation of aryl-
and alkylboronic acids/esters to access diversely functionalized
aromatic and aliphatic alcohols. Another notable feature of this
protocol is that among the two electron-demanding species (aryl-
boronic acid and PhIO) involved in the reaction, arylboronic acid
acts as a nucleophile22 in spite of being an electron deficient com-
pound. To the best of our knowledge, it is a unique study in the
ArB(OH)2
ArB(OH)2(IO4)
+
OH
III
NaIO4
OH
B
O
H
I
)
ron
ne-bo
iodi
2
H
IO4
O
Ph
B(
ange
exch
r
A
PhIO
R
OH
O
OH IPh
OH
Ph
B
I
Path B
NaIO4
PhI
Path A
I
R
R
IV
OH
O
HO
R
H2O
OH
H
2O
B
I
Ph
Ph-OH
+
II
O
OH
OH
H2O
B
R
OH
R
R
Scheme 4. Plausible mechanistic pathway.