Regioselective C(sp2)?C(sp3) Oxidative Bond Cleavage of 1-(1-Hydroxyalkyl) naphthalen-2-ols: First Synthesis of 1-Azido-halo-naphthalene-2(1H)-ones

Article abstract of DOI:10.1002/ijch.202000082

A new one-pot oxidative cleavage of C(sp²)?C(sp³) bond has been explored using two complementary protocols employing Phenylselenyl bromide (PhSeBr) as well as Phenyltrimethylammonium Tribromide (PTAB), with much greater efficiency and scope. The oxidative cleavage proceeds via a dearomatization step to afford potentially useful bromonaphthols along with corresponding aldehydes. In this course, we also described the first synthesis of synthetically important azido-halo naphthaleneones.

Full text of DOI:10.1002/ijch.202000082

Communication
DOI: 10.1002/ijch.202000082
2
3
Regioselective C(sp )À C(sp ) Oxidative Bond Cleavage
of 1-(1-hydroxyalkyl) naphthalen-2-ols: First Synthesis
of 1-azido-halo-naphthalene-2(1H)-ones
[a]
[a]
[a]
Manoj Kumar Ghosh, Barnali Roy, and Debayan Sarkar*
2
3
Abstract: A new one-pot oxidative cleavage of C(sp )À C(sp ) via a dearomatization step to afford potentially useful
bond has been explored using two complementary protocols bromonaphthols along with corresponding aldehydes. In this
employing Phenylselenyl bromide (PhSeBr) as well as course, we also described the first synthesis of synthetically
Phenyltrimethylammonium Tribromide (PTAB), with much important azido-halo naphthaleneones.
greater efficiency and scope. The oxidative cleavage proceeds
Keywords: Dearomatization · Phenyltrimethylammonium tribromide · Phenylselenyl bromide · oxidative cleavage · Azidation
CarbonÀ carbon (CÀ C) bonds resemble the central structural
unit of this large plethora of organic compounds. Thus,
carbonÀ carbon bond formation as well as selective disconnec-
tion of the CÀ C bonds have acquired a special attention in
[1]
organic synthesis
due to their inert nature and high
dissociation energy of the CÀ C bond, yet they serve as one of
the best routes to solve molecular complexity. CÀ C bond
cleavages constitute integral part of many biological
Scheme 1. Cu-mediated C(CO)-C(α) bond cleavage.
[2]
processes. The Global challenges to combat environmental
white Pollution” today generated from waste plastics also
[12]
“
particularly azidative dearomatization,
we were attracted
[3]
demand for vibrant cleavage of the stable CÀ C bonds. Such
methods have always been demanding, as they bear a
tremendous power of converting unreactive molecular motifs
into worthy substances thus saving energy, cost and human
towards the 1-azido-1-bromonaphthalen-2(1H)-one (4) mole-
cule which resembles a synthetically important molecule and
had no reports in the cited literature (Figure 1).
[13]
Regioslective Oxidative cleavage of 1,2-diols has been
one of the most promising transformations towards generation
of aldehydes. It appeared to us that less explored oxidative C
[4]
efficiency. Regioselective CÀ O, CÀ N, CÀ S bond cleavages
[5]
have been well explored. Martin’s Ni catalyzed CÀ O
[5b]
2
3
cleavage has been an inspiring observation.
Successful
(sp )À C(sp ) cleavage of 1-(1-hydroxyalkyl) naphthalen-2-ols
attempts towards regioselective cleavage of the CÀ C bonds
[6]
have been scanty due to thermodynamic stability associated
2
2
with it. Among this set, C(sp )À C(sp ) bond disconnections are
[7]
3
3
the most traced ones. The vivacious C(sp )À C(sp ) bond
cleavage challenge has also been brought under the purview of
organic synthesis, as there have been many interesting inputs
presently, albeit the thermodynamically less stable substrates
[8]
have been usually taken in most of these reactions. It was
2
3
interesting to find that C(sp )À C(sp ) bond disconnections has
[7c]
been rarely encountered. Recently, L. Gu et. al. reported a
noteworthy Cu-mediated C(CO)À C(α) bond cleavage reaction
towards generation of aryl nitriles (Scheme 1).
Figure 1. 1-azido-1-bromonaphthalen-2(1H)-one.
On the other hand, Yu group reported a selenium catalysed
[8g]
[a] M. Kumar Ghosh, B. Roy, D. Sarkar
National Institute of Technology
Rourkela, Odisha, 769008
oxidative addition of the alkenes to carbonyls. H O was
2
2
used as the key oxidant in this reaction. A way turn to it, is the
celebrated azide functionality which had given rise to an
(India)
[9]
immensely significant “Click reaction”. Recently, the azides
E-mail: sarkard@nitrkl.ac.in
[10]
have also been used as azidation agents to alkynols. With
Supporting information for this article is available on the WWW
under https://doi.org/10.1002/ijch.202000082
[11]
our continued interest on dearomatization reactions
and
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would be a worthy route towards generation of aldehydes, also
the study may lead to the targeted dearomatised azido-bromo-
naphthaleneones (4). Albeit, the opposing thermodynamic
carbonate is the best combination for this transformation. In
absence of base, the reaction proceeds with a slower rate. On
the other hand, the use of less than two equivalents of PhSeBr
did not affect the rate of reaction, although, the reaction could
not proceed to completion which clearly demanded for two
equivalents of the PhSeBr to be present in the reaction
mixture. Having established the optimal reaction conditions,
we next examined the substrate scope to test the generality of
this bond cleavage reaction. A wide range of 1-(1-hydrox-
yalkyl) naphthalen-2-ols (Table 1) delivered successful reac-
tion with moderate to good yields at room temperature. The
aldehydes were well detected in the reaction mixture from
NMR studies. Due to low boiling point as well as oxidising
reaction condition, we were unable to isolate aliphatic
aldehydes, however, we were only able to isolate and purify
some of the aromatic aldehydes for confirmation. While
investigating the substituent effects of R, the results revealed
that À Me, À Et, etc. group as well as À F atom were compatible
for the reaction. For example, the reaction with the substrate
containing a 4-methyl group on R afforded the desired
2
3
conditions of C(sp )À C(sp ) bond cleavage along with the
accompanied endergonic dearomatization was challenging.
Further, a possible metal and ligand-free one-pot trans-
formation would be synthetically important reaction. Herein,
we report the first synthesis of azido-bromo naphthaleneone
2
3
(
4) along with a metal free C(sp )À C(sp ) bond disconnection
reaction of 1-(1-hydroxyalkyl) naphthalen-2-ols.
At the outset of our study, we took 1-(1-hydroxymethyl)
2
naphthalen-2-ol as a primary substrate for a facile C(sp )À C
3
(
sp ) bond cleavage reaction. Many Known oxidants like
[14]
[15]
[16]
NaBrO3,
N-Bromosaccharin,
Pyridinium tribromide,
Tetrabromo methane were screened and in most cases, a
complex mixture was obtained. Although, with Pyridinium
tribromide, bromonaphthols were isolated in good yields but
no trace of the cleaved aldehydes was obtained (Scheme 2).
With our prior experiences on organo-selenium mediated
[
11b]
2
dearomatization reaction,
(
the desired benzylic C(sp )À C
3
sp ) bond cleavage was planned with 1-(1-hydroxymethyl)
naphthalen-2-ol and the readily available PhSeBr (Scheme 2).
The 1-(1-hydroxymethyl) naphthalen-2-ol (1b) delivered the
desired scissored products on exposure to two equivalents of
PhSeBr. Inert condition was not necessary for this reaction.
The unusual benzylic bond cleavage reaction attributed to a
dual-oxo-selenium reactive intermediate and formation of a
highly electrophilic benzylic centre which is further stabilised
due to aromaticity along with the generation of the aldehyde
2
3
Table 1. Substrates Scope of C(sp )À C(sp ) bond cleavage mediated
by PhSeBr.
(Scheme 3).
The reactions involved two equivalents of PhSeBr and 1.2
equivalents of potassium carbonate as a base. It took 8–12 h
for complete conversion at room temperature (30°C). During
optimization of the reaction, we found THF and potassium
Scheme 2. PhSeBr mediated bond cleavage reaction.
a) All reactions were performed using 0.22 mmol of 1-(1-hydro-
xyalkyl) naphthalen-2-ols 1a–l in THF (3 mL) in presence of K CO3
2
(1.2 equiv., 0.26 mmol) and PhSeBr (2 equiv., 0.44 mmol) at room
temperature under open air condition for 8–12 h. b) Conversion
measured from the isolated yield. c) Conversion was measured from
reaction mixture.
Scheme 3. Plausible mechanism for selenium mediated bond cleav-
age.
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bromonaphthol in a 67% yield, whereas the substrate having
2
3
Table 2. Substrates Scopes for C(sp )À C(sp ) bond cleavage medi-
4-fluoro substitution gave the corresponding product in a 60%
ated by PTAB.
yield (Table 1, e and j).
In light of the aforementioned results, a plausible mecha-
nism is proposed in Scheme 3. In the process, a nucleophilic
attack at the aromatic carbon by a bromide ion with the
concomitant migration of the double bond in the dual-oxo-
selenium reactive intermediate (A) and the simultaneous
benzylic bond cleavage through the formation of aldehyde
convert the dearomatized bromoketone to the corresponding
bromonaphthol (Scheme 3). An endergonic pathway is sug-
gested which is stabilized by the formation of stable organic
co-products diphenyl diselenide and the aldehyde. This
diphenyl diselenide, obtained from the reaction, was recovered
through column chromatography during isolation of the
desired products.
At this point, we were looking into more possibilities of
this CÀ C bond cleavage, as use of more than one equivalent of
organo selenium was a severe drawback of the employed
methodology. Over the past few years, our group has been
studying the oxidation capabilities of phenyltrimeth-
ylammonium tribromide (PTAB), primarily used as a bromi-
[17]
nating reagent, along with its analogues to realize dearoma-
tisation reactions. So, we decided to test the efficacy of PTAB
in this type of CÀ C bond cleavages. To our great expectation,
treatment of a series of hydroxy-alkyl naphthols, in presence
of one equivalent PTAB under the optimal reaction condition,
afforded the desired bromonaphthols and aldehydes in moder-
ate to good yields in less reaction time (about 6–10 h) under
nitrogen atmosphere (Scheme 4).
In this protocol, presence of base was also mandatory to
maintain a feasible rate of the reaction and K CO was found
2
3
to be the optimum base. To our delight, PTAB exhibited better
functional group tolerance with respect to PhSeBr. We,
similarly screened a broad range of 1-(1-hydroxyalkyl)
naphthalen-2-ols employing PTAB under the optimal reaction
condition. 1a–l substrates provided the desired products and a
similar yield (35%–70%) of bromonaphthol was observed. It
is noteworthy that the reaction using substrates 1 m–o did not
produce the desired product in presence of PhSeBr; whereas
those substrates with PTAB gave rise to 2 in moderate to good
yield (Table 2). The phenyltrimethylammonium bromide was
obtained as side product in this methodology. Furthermore, the
purification and product isolation were much easier compared
to that in PhSeBr. Simple aqueous workup followed by
extraction with ethyl acetate delivered the crude material along
with the ammonium salt.
a) All reactions were performed using 0.22 mmol of 1-(1-hydro-
xyalkyl) naphthalen-2-ols 1a–o in dry THF (3 mL) in presence of
K CO (1.2 equiv., 0.26 mmol) and PTAB (1 equiv., 0.22 mmol) at
room temperature under nitrogen atmosphere for 6–10 h. b)
Conversion measured from the isolated yield. c) Conversion was
measured from reaction mixture.
2
3
For the detection and characterisation of the aldehyde, we
set a reaction following the procedure shown in Scheme 5 and
performed NMR spectroscopic experiment taking crude reac-
tion mixture where we observed a characteristic aldehyde peak
1
13
of 3-methyl benzaldehyde [ H δ (ppm)=9.974(s, 1H), C δ
Scheme 4. PTAB mediated bond cleavage reaction.
Scheme 5. From crude sample of NMR spectroscopy.
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(
ppm)=192.68 for À CHO] (Details in Supporting Informa-
tion).
Regarding the reaction mechanism, it may be proposed
Table 3. Synthesis of bromoazido ketones.
that the potassium salt of naphthoxide is activated in the
process by the ammonium fragment of PTAB; whereas, the
À
anionic Br3 maintains an electrophilic perpendicular approach
towards the partially planar reactive intermediate with minimal
stereo-electronic interactions, followed by a concomitant
À
nucleophilic attack of the proximal Br3 ion (Scheme 6) finally
resulted in the dearomatized bromonapthol and the corre-
sponding aldehyde.
To support the proposed mechanism, we carried out one
control experiment. As expected, no bond cleavage was
observed when benzyl protected 1-(1-hydroxybutyl)
naphthalene-2-ol (z) was used as a substrate under the same
reaction condition (Scheme 7).
With our continuous interest in dearomatisation chemistry,
we now planned to execute the reaction in presence of an azide
precursor to develop the targeted azido-bromo-naphthale-
neone. Accordingly, our initial investigation was launched
with a model reaction of 1-(1-hydroxymethyl) naphthalene-2-
ol in presence of 2.0 equivalents of K CO , 8.0 equivalents of
a) All reactions were performed using 0.22 mmol of 1-(1-hydro-
xyalkyl) naphthalen-2-ols 1d–p in dry THF (2.2 mL) and dry DCM
2
3
(
0.8 mL) in presence of K CO (2 equiv., 0.44 mmol), NaN (8 equiv.,
2
3
3
NaN and 1.0 equivalent of PTAB in dry THF and dry DCM
3
1.76 mmol) and PTAB (1 equiv., 0.22 mmol) at room temperature
under nitrogen atmosphere for 6–10 h. b) Conversion measured
from the isolated yield. c) Conversion was measured from reaction
mixture.
(2.5:1) solvent under nitrogen atmosphere at room temper-
ature. The reaction proceeded smoothly to afford azido-
bromo-naphthaleneone and corresponding aldehyde in reason-
able yields. Among the examined solvents and bases, dry THF
and K CO was found to be optimal respectively. Having
2
3
found a satisfactory reaction condition, we further turned our
attention to scope of this reaction. Various 2-naphthol
derivatives were surveyed. Fortunately, both aryl as well as
alkyl substituted naphthol delivered moderate to good yields
Considering high importance of azido-bromo-naphthale-
[18]
neone (4) towards numerous useful architectures, we were
then interested to study whether this compound would be
achieved starting with bromonaphthol (2) which can be easily
synthesised from 2-naphthol. To our delight, the reaction
provided our desired product with better yield and took less
reaction time. Subsequently, we further explored the general-
ization of this dearomatisation process by involving different
halonaphthols. Gratifyingly, all these halonaphthols (2, 5a–c),
prepared from 2-naphthol, underwent the current protocol,
affording the dearomatised product (4, 6a–c) in good yield
(Table 3).
(Table 4).
In summary, an economic, metal and ligand-free protocol
2
3
for C(sp )À C(sp ) bond cleavage using PTAB and PhSeBr has
been studied under mild reaction condition. The PTAB mediated
2
3
scissoring of the C(sp )À C(sp ) bond reveals better efficacy
compared to PhSeBr. To the best of our knowledge, the
described methodology discloses the achievement of the
synthetically challenging dearomatised azido-halo-naphthale-
neones for the first time. This synthetically important bromoazi-
doketone can be utilized in development of various interesting
synthetic methodologies such as azide-alkyne coupling, click
chemistry Diels-Alder reaction. Further investigations on
synthetic applications and the gram-scale synthesis of electron-
deficient aldehydes employing this methodology are currently
in progress and will be reported in due course.
2
3
Scheme 6. Plausible mechanisim of C(sp )À C(sp ) bond cleavage by
PTAB.
Scheme 7. Controlled experiment for mechanistic evidence.
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2
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Technology (DST), Govt. of India (EEQ/2016/000518) and
INSPIRE-DST, Govt. of India (Grant No.04/2013/000751).
We acknowledge S. Tripathy for NMR studies.
4
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M. Kumar Ghosh, B. Roy, D. Sarkar*
– 6
1
2
3
Regioselective C(sp )À C(sp )
Oxidative Bond Cleavage of 1-(1-
hydroxyalkyl) naphthalen-2-ols:
First Synthesis of 1-azido-halo-
naphthalene-2(1H)-ones