One-pot two-step oxidative cleavage of 1,2-arylalkenes to aryl ketones instead of arylaldehydes in an aqueous medium: A complementary approach to ozonolysis

Article abstract of DOI:10.1002/ejoc.201000672

A new approach has been developed for a one-pot and selective oxidative cleavage of aryl- and 1,2-diarylalkenes leading to one-carbon shorter aryl ketones; thereby, providing a complementary approach to classical ozonolysis. The methodology was applicable to diverse aromatic and polyaromaticarylalkenes bearing electron-donating or -withdrawing groups on the aromatic ring. The protocol also provided a useful one-pot oxidative cleavage-condensation sequence, which could potentially have important applications in natural product total synthesis. A one-pot, two-step approach has been achieved for the oxidative cleavage of 1,2-disubstituted arylalkenes into the corresponding aryl ketones instead of arylaldehydes (see scheme; NIS = N-iodosuccinimide; CTAB = cetyltrimethylammonium bromide; PDC/TBHP = pyridinium dichromate/tert-butyl hydroperoxide). The methodology also led to a valuable one-pot oxidative cleavage-condensation reaction that has widespread utility in the total synthesis of natural products.

Full text of DOI:10.1002/ejoc.201000672

FULL PAPER
DOI: 10.1002/ejoc.201000672
One-Pot Two-Step Oxidative Cleavage of 1,2-Arylalkenes to Aryl Ketones
Instead of Arylaldehydes in an Aqueous Medium: A Complementary Approach
to Ozonolysis[‡]
Naina Sharma,[a] Abhishek Sharma,[a] Rakesh Kumar,[a] Amit Shard,[a] and
Arun K. Sinha*[a]
Keywords: Cleavage reactions / Alkenes / Oxidation / Ketones / Microwave chemistry
A new approach has been developed for a one-pot and selec-
tive oxidative cleavage of aryl- and 1,2-diarylalkenes leading
to one-carbon shorter aryl ketones; thereby, providing a com-
arylalkenes bearing electron-donating or -withdrawing
groups on the aromatic ring. The protocol also provided a
useful one-pot oxidative cleavage–condensation sequence,
plementary approach to classical ozonolysis. The methodol- which could potentially have important applications in natu-
ogy was applicable to diverse aromatic and polyaromatic
ral product total synthesis.
quence). In spite of their immense utility, the demanding
nature of both of these strategies has spurred the explora-
tion of improved methods. For instance, the safety concerns
with ozonolysis has led to the development of some equiva-
lent reactions with OsO4/Oxone,[4a] trapping of carbonyl ox-
ides,[4b] or biocatalysis.[4c] Similarly, there have been note-
worthy attempts to explore the dihydroxylation–cleavage
route for olefinic cleavage by using RuCl nanoparticles,[5a]
RuCl3/Oxone,[5b] micro-encapsulated OsO4,[5c] H2O2/
Na2WO4,[5d] and a combination of PhI(OAc)2 and OsO4
(cat.)/2,6-lutidine.[5e]
Introduction
The oxidative scission of C=C bonds is a fundamental syn-
thetic transformation[1a–1b] and has widespread applications
in organic synthesis, including the total synthesis of natural
products.[1c] The major utility of such cleavage reactions is
due to their ability to truncate large compounds with the
simultaneous introduction of a carbonyl function. This crit-
ical transformation is usually achieved through
two principal approaches, that is, ozonolysis[2] and the
Lemieux–Johnson reaction[3] (dihydroxylation–cleavage se-
Scheme 1. Some prominent approaches for direct oxidative cleavage of 1,1- or 1,2-disubstituted arylalkenes (a, b) and the present work (c).
[‡] IHBT Communication No. 2013.
On the other hand, increased attention has recently been
placed on developing conceptually newer olefinic cleavage
approaches. For instance, the one-step C=C bond cleavage
of 1,1-diaryl-substituted alkenes into ketones has been ac-
complished by using gold(I) complex/TBHP.[6] In another
instance, Pd(OAc)2 has also been employed for the oxi-
[a] Natural Plant Products Division, Institute of Himalayan
Bioresource Technology, C.S.I.R.,
Palampur (H.P.) 176061, India
Fax: +91-1894-230433
E-mail: aksinha08@rediffmail.com
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000672.
View this journal online at
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N. Sharma, A. Sharma, R. Kumar, A. Shard, A. K. Sinha
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dation of alkenes by cleavage of a dioxo–PdII intermedi- ing aryl ketones by using N-iodosuccinimide (NIS) and pyr-
ate.[7] In spite of the utility of the above protocols, almost idinium dichromate/tert-butyl hydroperoxide (PDC/TBHP)
all of these approaches cleave 1,2-disubstituted alkenes into as co-oxidants with microwave (MW) heating under aque-
aldehydes, whereas ketone cleavage products are usually ob- ous conditions.
tained from respective 1,1-disubstituted alkenes (Scheme 1).
Thus, it is generally well recognized that the substitution
pattern around an olefinic bond largely determines the na-
ture of cleavage products. To the best of our knowledge, a
Results and Discussion
general approach for the counterintutive one-step formal
In the course of our programme towards the catalytic
scission of abundantly available aryl- and 1,2-diarylalkenes synthesis of biologically important phenolics,[9] we initially
into one-carbon shorter aryl ketones, instead of aryl- desired to achieve a one-step conversion of abundantly
aldehydes, has not been disclosed, although in a few cases available arylalkenes into the corresponding α-aryl propi-
such a transformation has been noticed as a side reaction onic acids, which are constituents of nonsteroidal anti-in-
during the oxidation of stilbenes.[8]
flammatory drugs (NSAIDs).[10] In this context, we
Such a methodology would provide a useful complemen- planned to utilize our recently developed approach[9b] com-
tary tool to the prevalent approaches[4–7] as it considerably prising direct oxidation of arylalkenes into α-arylaldehydes
enhances the flexibility for cleaving an olefinic bond into for an in situ oxidation[11] of such aldehydes into respective
either aldehydes or ketones irrespective of the substitution α-substituted arylalkanoic acids. Consequently, PDC was
pattern around a double bond. In this context, we herein chosen as the in situ oxidizing agent due to its known abil-
report a one-pot oxidative cleavage approach that splits ity to convert such α-substituted aldehydes into acids.[12]
various 1,2-disubstituted arylalkenes into the correspond- However, contrary to our expectations, the reaction[9b] of
Table 1. Optimization of conditions for cascade oxidative cleavage of 1,2-arylalkenes into aryl ketones under focused microwave irradia-
tion.[a]
[a] CEM monomode microwave. General conditions: 1a (1.35 mmol), NIS (1.75 mmol), and CTAB (0.08 mmol) in dioxane (11 mL)/water
(3.7 mL) were irradiated under MW conditions (115 °C, 250 W) for 15 min, followed by cooling, addition of an oxidant and, in some
cases, an additive (2.0 mmol), and further MW treatment for 15 min. [b] Based on GC–MS analysis. [c] Isolated yield of pure product.
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One-Pot Two-Step Oxidative Cleavage of 1,2-Arylalkenes
1a (C6–C3 unit) with NIS (1.3 equiv.) and then cetyltrimeth- under MW conditions. Interestingly, the above reaction af-
ylammonium bromide (CTAB), followed by treatment with forded only 4-methoxybenzaldehyde; thereby, clearly high-
PDC (6 equiv.)[12] in same pot under microwave conditions lighting the critical role of the cascade pathway (Figure 1)
provided a product, the detailed GC–MS and NMR investi- in providing exclusive access to ketone cleavage products.
gations of which revealed it to be one-carbon shorter aceto- Further, the role of the MW[14] was also evaluated by reac-
phenone (1b), instead of the expected α-arylpropionic tion of 1a under thermal heating at a similar temperature;
acid.[11–12] Nevertheless, the promising utility of such an ap- however, 1b was obtained in a comparatively lower yield
proach for direct oxyfunctionalization and cleavage of even (55%) with longer reaction times (6 h). It is pertinent to
1,2-arylalkenes into ketones instead of aldehydes[5–7] mention here that such a cleavage of incipient α-arylal-
prompted us to further explore its scope and mechanistic dehydes into respective one-carbon shorter ketones has ear-
[13c–13d]
pathway. Consequently, a detailed optimization study lier been observed by using reagents, such as O2
(in
(Table 1) was conducted to evaluate the effect of various combination with polyoxometalates/zeolite), oxidoruthe-
oxidizing agents and additives. Interestingly, the use of nium complexes,[13e] peroxidases,[13f] and PhI(OAc)2,[8] etc.
other well-known oxidizing agents, such as Oxone, TBHP,
The utility of the above optimized protocol for the cleav-
H2O2 etc., was not beneficial for oxidative cleavage of aryl- age of C=C double bonds was subsequently ascertained.
alkenes (Table 1, entries 6, 12–13). However, addition of a As would be evident from Table 2, various aromatic and
reduced amount of PDC (1.5 equiv.) led to a significantly polyaromatic arylalkenes bearing electron-donating/-with-
increased yield of 1b (71%) (Table 1, entry 3). Amongst the drawing groups (EDGs/EWGs) underwent facile oxidative
various acidic/basic additives, the use of acetic acid led to cleavage into the corresponding aryl ketones instead of the
a further improvement in the reaction performance besides arylaldehydes. Further, the arylalkene with an elongated
helping in the workup of the reaction mixture (Table 1, en- side chain (C6–C5 unit) was also compatible (Table 2, entry
try 14).
3) with the developed methodology. On the other hand, the
The apparently counterintuitive cleavage of even 1,2-di- olefin possessing a free phenolic group (Table 2, entry 11)
substituted arylalkenes into aryl ketones instead of arylal- provided a lower yield of the respective aryl ketone owing
dehydes implied an oxygenation–rearrangement–oxidative to probable polymerization besides formation of some side
cleavage mechanistic pathway. Thus, arylalkene (a) is ini- products. Similarly, the relatively unactivated substrates,
tially converted to the corresponding α-arylaldehyde[9b] in such as 1,1-disubstituted (Table 2, entry 14) and aliphatic
the presence of NIS/H2O (aЈ). Subsequently, the oxidation alkenes (Table 2, entry 15) also led to low reaction perform-
of this α-arylaldehyde into an one-carbon shorter ketone ance, presumably due to a reduced formation of the corre-
can proceed through a number of intermediates,[13] includ- sponding α-substituted aldehydes in the first step (Fig-
ing an α-aryl acid[8,13b–13c] and enol[12–13a] etc. Thus, the in- ure 1).
cipient α-arylaldehyde (aЈ) can undergo oxidation into the
To utilize the present approach for the simultaneous in-
corresponding α-aryl acid, which is then further converted troduction of multiple functionalities, an one-pot halogena-
into the respective ketone through oxidative decarboxyl- tion–oxidative cleavage sequence was envisaged. However,
ation (Figure 1).[8,13b–13c] To evaluate the above possibility, the in situ reaction of 2b (obtained from oxidative cleavage
the standard acids, that is, Flurbiprofen® [2-(2-fluorobi- of 2a) with NIS[15] did not afford the expected 2-iodoaceto-
phenyl-4-yl)propanoic acid] or Ibuprofen® {2-[4-(2-meth- phenone (2bЈ; Scheme 2). Surprisingly, an alternative ap-
ylpropyl)phenyl]propionic acid} were treated with PDC un- proach proved fruitful, wherein, initial treatment of 2a with
der identical conditions; however, the corresponding excess NIS[9b] provided the expected iodo derivative 2bЈ;
ketones were not detected. In another alternative pathway, thereby, demonstrating the successful incorporation of both
the incipient α-arylaldehyde undergoes acid-catalyzed enoli- oxygen and iodo groups in a single operational step
zation,[12–13a] followed by PDC-assisted oxidative cleavage (Scheme 2).
into the corresponding ketone (Figure 1; b). To further con-
The above success with 1,2-arylalkenes (Table 2) moti-
firm the above mechanistic rationale, arylalkene (1a) was vated us to explore an analogous oxidative cleavage of 1,2-
treated with PDC/acetic acid alone in dioxane/water (3:1) diarylalkenes into the corresponding benzophenones. How-
Figure 1. Plausible mechanistic pathways for one-pot oxidative cleavage of 1,2-disubstituted arylalkenes into one-carbon shorter ketones.
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Table 2. Cascade oxidative cleavage of 1,2-arylalkenes into aryl ketones instead of benzaldehydes under focussed microwave irradiation.[a]
[a] CEM monomode microwave. General conditions: substrate (0.9 mmol), NIS (1.18 mmol), and CTAB (0.08 mmol) in dioxane
(11 mL)/water (3.7 mL) were irradiated under MW conditions (115 °C, 250 W) for 15 min, followed by cooling and addition of
PDC (1.36 mmol) and CH3COOH (1.36 mmol) and further MW treatment for 15 min. [b] Yield of pure isolated product (single run).
The structure of all products was confirmed by NMR spectroscopy (1H and 13C) and HRMS analysis. [c] Based on GC–MS. [d] Not
detected.
Scheme 2. One-pot halogenation–oxidative cleavage of an arylalkene.
ever, the developed protocol did not provide the expected
result, even as parent stilbenes were selectively cleaved into such diarylalkenes towards cleavage into benzaldehydes,[5c]
benzaldehydes (Scheme 3). a reduced amount of PDC (0.8 equiv.) was also tried but to
In view of above result and the well-known tendency of
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One-Pot Two-Step Oxidative Cleavage of 1,2-Arylalkenes
Scheme 3. Selective oxidative cleavage of symmetrical and unsymmetrical 1,2-diarylalkenes into benzaldehydes.
no avail. On the other hand, the use of other oxidizing
Further, some unreacted starting 1,2-diarylalkene was
agents, such as H2O2, TBHP, and K2Cr2O7 etc., did provide also obtained by using the above reaction conditions.
the desired benzophenone 19b but in low yields.
Thereafter, detailed studies were conducted for identifying
Table 3. Cascade oxidative cleavage of 1,2-diarylalkenes into benzophenones instead of benzaldehydes under focused microwave irradia-
tion.[a]
[a] CEM monomode microwave. General conditions: substrate (0.79 mmol), NIS (1.5 mmol), CH3COOH (1.16 mmol), and CTAB
(0.08 mmol) in dioxane (11 mL)/water (3.7 mL) were irradiated under MW conditions (115 °C, 250 W) for 15 min, followed by cooling
and addition of PDC (0.04 mmol)/TBHP (4.7 mmol) and further MW treatment for 15 min. [b] Yield of the pure isolated product (single
run). The structure of all products was confirmed by NMR spectroscopy (1H and 13C) and HRMS analysis. [c] Based on GC–MS.
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Table 4. One-pot oxidative cleavage–condensation of alkenes with benzaldehydes under focused microwave irradiation.[a]
[a] CEM monomode microwave. General conditions: alkene (1.35 mmol), NIS (1.75 mmol), and CTAB (0.08 mmol) in dioxane (11 mL)/
water (3.7 mL) were irridated under MW conditions (250 W, 115 °C) for 15 min, followed by cooling and addition of PDC (2.0 mmol).
CH3COOH (2.0 mmol) was then added and MW treatment was continued for 15 min. Thereafter, 10% NaOH (5–8 mL) and a methanolic
solution (2–3 mL) of benzaldehyde (1.48 mmol) was added and the resulting mixture was stirred for 2 h. [b] Overall yield of pure isolated
product from arylalkene (single run).
an oxidation system compatible with such 1,2-diarylalkenes. of an one-pot protocol for tandem oxidative cleavage–con-
Interestingly, a combination of catalytic PDC (0.05 equiv.) densation would be beneficial as it would eliminate the iso-
along with TBHP (6 equiv.) as a co-oxidant was optimum lation of intermediates.[16] As a proof of concept, 1a was
to afford the desired 19b (Table 3, entry 19) in an enhanced subjected to the developed oxidation protocol (Table 2)
49% yield. In addition, the use of acetic acid along with till formation of 1b occured, and, thereafter, a base,
an increased amount of NIS [2 equiv. in place of 1.3 equiv. such as NaOH (10%) and 2,4,5-trimethoxybenzaldehyde
(Table 2)] at the start was required to overcome the initial (1.3 equiv.), was added to the same pot and stirred for 2 h.
sluggish conversion of such diaryl-substituted alkenes into Gratifyingly, this one-pot approach proved useful to di-
the corresponding iodohydrins (Figure 1). Subsequently, rectly obtain the condensation product 27d from the corre-
the above reaction conditions were also found to be appli- sponding arylalkenes in a 56% overall yield (Table 4, entry
cable to various unsubstituted, electron-rich and -deficient 27). Later on, the above one-pot strategy was also success-
1,2-diarylalkenes with aromatic or polyaromatic cores fully applied to various other arylalkenes (Table 4); thereby,
(Table 3). It is pertinent to mention that the oxidative cleav- providing a hitherto unknown route to the one-step oxi-
age of olefins into benzophenones has been earlier reported dation–condensation of olefinic bonds.
by using only 1,1-diaryl-substituted C=C double
bonds.[5b,6,7] In this context, the developed methodology af-
fords the first direct scission of even 1,2-disubstituted ole-
fins into the corresponding benzophenones.
Conclusions
After having developed a new approach for the oxidative
We have developed a new oxidative cleavage approach
cleavage of diverse arylalkenes, we were intrigued to evalu- that affords for the first time a selective scission of 1,2-dis-
ate further applications of this methodology. In this con- ubstitued alkenes into one-carbon shorter ketones by using
text, we were attracted by several reports of the total syn- NIS and PDC/TBHP as co-oxidants. As the classical ap-
thesis of natural products, wherein a two-step sequence of proaches like ozonolysis predominantly involve cleavage of
oxidative cleavage followed by condensation[16] has com- 1,2-disubstituted alkenes into aldehydes, the developed
prised an important strategy. Consequently, the realization methodology considerably enhances the flexibility for cleav-
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One-Pot Two-Step Oxidative Cleavage of 1,2-Arylalkenes
NMR (300 MHz, CDCl3): δ = 7.66 (t, J = 6.5 Hz, 2 H, Ar), 7.08
(s, 1 H, Ar), 4.30 (t, J = 7.1 Hz, 2 H), 4.07 (s, 3 H), 2.78 (s, 3 H),
2.12–2.04 (m, 2 H), 1.79–1.67 (m, 2 H), 1.23 (t, J = 6.7 Hz, 3 H)
ppm. 13C NMR (75.4 MHz, CDCl3): δ = 197.0, 153.1, 149.4, 130.4,
123.4, 111.2, 110.6, 68.9, 56.2, 31.1, 26.3, 19.3, 14.0 ppm. HRMS-
ESI: calcd. for C13H18O3 [M + H]+ 223.1302; found 223.1302.
ing an 1,2-disubstituted olefinic bond into either ketones or
aldehydes. Moreover, the reaction showed a wide substrate
scope as diverse 1,2-aryl and diarylalkenes bearing electron-
donating or -withdrawing groups underwent facile cleavage
into the corresponding aryl ketones. Significantly, the pro-
tocol also paved the way for a valuable one-pot oxidative
cleavage–condensation reaction, which has widespread util-
ity in the total synthesis of natural products. Further in-
vestigations to improve the scope of the developed reaction
are currently underway.
The above procedure was also used for the oxidative cleavage of all
the other arylalkenes (Table 2, entries 1–11, 13–15). The structures
of the corresponding products were confirmed by NMR spec-
troscopy (1H and 13C), HRMS, or GC–MS analysis (see Support-
ing Information).
Representative Procedure for the Cascade Oxidative Cleavage of 1,2-
Diarylalkenes into Benzophenones: Water (3.7 mL), CTAB (0.03 g,
0.08 mmol), NIS (0. 35 g, 1.5 mmol), and acetic acid (0.07 mL,
1.16 mmol) were added to a stirred mixture of trans-4Ј-methoxy-
3,4-(methylenedioxy)stilbene (Table 3, entry 22; 0.2 g, 0.79 mmol)
and dioxane (11 mL) and the reaction mixture was allowed to stir
for 3–4 h at room temperature. Subsequently, the flask was irradi-
ated under MW conditions (250 W, 115 °C) for 15 min. Thereafter,
the reaction flask was cooled, PDC (0.015 g, 0.04 mmol) and
TBHP (0.45mL, 4.7 mmol) were added and the mixture was further
irradiated under microwave conditions (250 W, 115 °C) for 15 min.
The above mixture was cooled, washed with saturated aq. Na2S2O3
solution (1ϫ10 mL), and extracted with ethyl acetate (3ϫ20 mL).
The combined organic layer was washed with brine (1ϫ10 mL),
dried with Na2SO4, and vacuum evaporated. The obtained residue
was subsequently purified by column chromatography on silica gel
(60–120 mesh size) by using hexane/ethyl acetate (9.3:0.7) to give
4Ј-methoxy-3,4-(methylenedioxy)benzophenone (22b) (0.13 g, 67%
yield) as a white solid.
Experimental Section
General: β-Asarone was obtained from natural Acorus calamus oil
by following our earlier reported procedure.[17a] The naphthyl and
stilbene derivatives were prepared through a previously reported
Grignard–dehydration[9c] or Heck approach,[17b] respectively. All of
the above synthesized alkenes were fully characterized by 1H and
13C NMR spectroscopy before further use. The rest of the arylalk-
enes were reagent grade (purchased from Merck and Aldrich). NIS
was reagent grade (Merck) and used as such without any further
purification. Glacial acetic acid (99–100% for synthesis) and PDC
(pyridinium dichromate) and other oxidants were used as supplied.
The solvents used for isolation/purification of compounds were ob-
tained from commercial sources and used without further purifica-
tion. Column chromatography was performed by using silica gel
(60–120 mesh size). 1H (300 MHz) and 13C (75.4 MHz) NMR spec-
tra were recorded on a Bruker Avance-300 spectrometer. HRMS-
ESI spectra were determined by using a micromass Q-TOF ultima
spectrometer. GC–MS analysis was carried out on Shimadzu MS-
QP-2010 system equipped with a Stationary phase DB-5MS col-
umn (Agilent Technologies, U.S.A.). A CEM Discover focused mi-
crowave (2450 MHz, 300 W) was used wherever mentioned. The
temperature of reactions in microwave heating experiments was
measured by an inbuilt IR temperature probe that determined the
temperature on the surface of reaction flask. The sensor is attached
in a feedback loop with an on-board microprocessor to control the
temperature rise rate. For the case of conventional heating in an
oil bath, the temperature of the reaction mixture was monitored by
an inner thermometer.
4Ј-Methoxy-3,4-(methylenedioxy)benzophenone (22b): See Table 3.
White solid, m.p. 96–98 °C. 1H NMR (300 MHz, CDCl3): δ = 7.80
(d, J = 9.7 Hz, 2 H, Ar), 7.33 (d, J = 9.3 Hz, 2 H, Ar), 7.00 (d, J
= 9.7 Hz, 2 H, Ar), 6.95 (d, J = 8.0 Hz, 1 H, Ar), 6.07 (s, 2 H,
OCH2O), 3.89 (s, 3 H, OCH3) ppm. 13C NMR (75.4 MHz, CDCl3):
δ = 194.4, 163.3, 151.5, 148.2, 132.9, 132.6, 131.0, 126.6, 113.9,
110.3, 108.0, 102.1, 55.9 ppm. HRMS-ESI: calcd. for C15H12O4
[M + H]+ 257.0808; found 257.0806.
The above procedure was also used for the oxidative cleavage of
all the other 1,2-diarylalkenes (Table 3, entries 19–21, 23–26). The
structures of the corresponding products were confirmed by NMR
spectroscopy (1H and 13C) and HRMS analysis (see Supporting
Information).
Representative Procedure for the One-Pot Oxidative Cleavage of Ar-
ylalkenes into One-Carbon Shorter Aryl Ketones: Water (3.7 mL),
CTAB (0.03 g, 0.08 mmol), and NIS (0.26 g, 1.18 mmol) were
added to a stirred mixture of 4-butoxy-3-(methoxyphenyl)propene
(Table 2, entry 12, 0.2 g, 0.9 mmol) and dioxane (11 mL) and the
mixture was allowed to stir for 5 min at room temperature. Sub-
sequently, the flask was irradiated under a focused microwave sys-
tem (250 W, 115 °C) for 15 min. Thereafter, the above reaction flask
was cooled and acetic acid (0.08 mL, 1.36 mmol) and PDC (0.51 g,
1.36 mmol) were added and the mixture further irradiated under
microwave conditions (250 W, 115 °C) for 15 min. The above mix-
ture was cooled, washed with saturated aq. Na2S2O3 solution
(1ϫ10 mL), and extracted with ethyl acetate (3ϫ20 mL). The
combined organic layer was washed with brine (1ϫ10 mL), dried
with Na2SO4, and vacuum evaporated. The obtained residue was
subsequently purified by column chromatography on silica gel (60–
120 mesh size) by using hexane/ethyl acetate (9.3:0.7) to give 4Ј-
butoxy-3Ј-methoxyacetophenone (12b) (0.152 g, 76% yield) as a
cream-coloured solid.
Representative Procedure for the One-Pot Oxidative Cleavage–Con-
densation of Arylalkenes with Benzaldehydes: Water (3.7 mL),
CTAB (0.03 g, 0.08 mmol), and NIS (0.395 g, 1.75 mmol) were
added to a stirred mixture of 4-(methoxyphenyl)propene (Table 4,
entry 27; 0.2 g, 1.35 mmol) and dioxane (11 mL), and the reaction
mixture was allowed to stir for 5 min at room temperature. Sub-
sequently, the flask was irradiated under MW conditions (250 W,
115 °C) for 15 min. The mixture was then cooled and acetic acid
(0.12 mL, 1.99 mmol) and PDC (2.0 mmol) were added and MW
treatment (250 W, 115 °C) was continued for 15 min. Thereafter,
the reaction mixture was filtered and 5–8 mL of 10% sodium hy-
droxide (till basic conditions) along with a methanolic solution (2–
3 mL) of 2,4,5-trimethoxybenzaldehyde (0.29 g, 1.48 mmol) were
added. The reaction mixture was allowed to stir for 2 h, after
which, it was washed with saturated aq. Na2S2O3 solution
(1ϫ10 mL) and extracted with ethyl acetate (3ϫ20 mL). The com-
bined organic layer was washed with brine (1ϫ10 mL), dried with
Na2SO4, and vacuum evaporated to give a crude mixture which
4Ј-Butoxy-3Ј-methoxyacetophenone (12b): See Table 2. Cream-col-
oured solid. IR (KBr): ν = 1674 (C=O) cm–1, m.p. 35–37 °C. 1H upon addition of methanol led to the precipitation of condensation
˜
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product 1-(4Ј-methoxyphenyl)-3-(2,4,5-trimethoxyphenyl)-2-pro-
pen-1-one (27d) (0.24 g, 56% yield) as a light-yellow solid.
1-(4Ј-Methoxyphenyl)-3-(2,4,5-trimethoxyphenyl)-2-propen-1-one
(27d): See Table 4. Light-yellow solid, m.p. 107–110°C. 1H NMR
(300 MHz, CDCl3): δ = 8.10–8.00 (m, 3 H, Ar, CH), 7.50 (d, J =
16.6 Hz, 1 H, CH), 7.12 (s, 1 H, Ar), 6.96 (d, J = 8.0 Hz, 1 H, Ar),
6.50 (s, 1 H, Ar), 3.87 (s, 3 H, OCH3), 3.85 (s, 6 H, OCH3), 3.84
(3 H, S, OCH3) ppm. 13C NMR (75.4 MHz, CDCl3): δ = 189.6,
163.5, 154.9, 151.8, 143.1, 139.6, 132.0, 130.8, 120.5, 116.5, 114.1,
112.0, 97.1, 57.3, 57.0, 56.3, 56.2 ppm. HRMS-ESI: calcd. for
C19H20O5 [M + H]+ 329.1383; found 329.1387.
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The above procedure was also used for the one-pot oxidative cleav-
age–condensation of all the other arylalkenes (Table 4, entries 28–
31). The structures of the corresponding products were confirmed
by NMR spectroscopy (1H and 13C) and HRMS analysis (see Sup-
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Received: May 10, 2010
Published Online: September 16, 2010
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