Neighbouring formyl group assisted oxidation of o-alkynylarenecarbaldehydes by an iodine/water system

Article abstract of DOI:10.1002/ejoc.201001746

The oxidation of o-alkynylarenecarbaldehydes into tricarbonyl compounds by an iodine/water system is described. The reaction takes place via isochromenol intermediates formed by intramolecular assistance of the formyl group. The procedure was applied to various o-alkynylarenecarbaldehydes to afford the corresponding products in good to excellent yields.

Full text of DOI:10.1002/ejoc.201001746

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201001746
Neighbouring Formyl Group Assisted Oxidation of
o-Alkynylarenecarbaldehydes by an Iodine/Water System
Karuppusamy Sakthivel[a] and Kannupal Srinivasan*[a]
Keywords: Alkynes / Oxidation / Iodine / Neighboring-group effects
The oxidation of o-alkynylarenecarbaldehydes into tricar-
bonyl compounds by an iodine/water system is described.
The reaction takes place via isochromenol intermediates
formed by intramolecular assistance of the formyl group. The
procedure was applied to various o-alkynylarenecarbal-
dehydes to afford the corresponding products in good to ex-
cellent yields.
[Ru(cymene)Cl2]2/I2/H2O2,[12] etc. In a similar way, the oxi-
dation of o-alkynylarenecarbaldehydes would provide ortho-
(1,2-dioxoethyl)arenecarbaldehydes, which have previously
not been reported, and these tricarbonyl compounds could
be potential precursors for the synthesis of a wide range of
bridged carbocycles and heterocycles.
Introduction
The neighbouring group participation (NGP) – in which
an intramolecular nucleophile assists in the departure of a
leaving group thereby forming a cyclic intermediate – is a
well-established concept in aliphatic nucleophilic substitu-
tion and rearrangements. This kind of assistance is also
possible in other types of organic reactions, and a few re-
ports are available on the NGP in oxidation reactions.[1a–1g]
To complement these reports, we herein report neighbour-
ing group assistance by a formyl group in the oxidation of
Results and Discussion
Recently, Larock and co-workers reported an iodine-
o-alkynylarenecarbaldehydes. These aldehydes are versatile mediated cyclization of o-alkynylbenzaldehydes A in the
precursors for the synthesis of various carbocycles and het- presence of alcohols (ROH) to form isochromenes D
erocycles, and the basis for all these syntheses is the acti- (Scheme 1).[13a,13b] The reaction was taking place through
vation of their carbon–carbon triple bond by metal cata- the isochromenium intermediate C formed by a 6-endo-dig
lysts or other electrophiles to give isochromenylium inter- cyclization.
mediates.[2a–2i]
We serendipitously found that when water is employed in
The oxidation of internal alkynes to 1,2-diketones is an the place of alcohol in the above reaction, the aldehyde A
important synthetic transformation, because the resulting is oxidized to the tricarbonyl compound F, instead of the
diketones are readily converted into various biologically expected isochromenol DЈ (Scheme 2). We envisage that the
active compounds.[3a–3c] This oxidation could be effected reaction may occur through I2-triggered ring opening of the
with a range of reagents such as KMnO4,[4] I2/DMSO,[5] initially formed isochromenol intermediate DЈ as indicated
SO3/1,4-dioxane,[6]
FeBr3/DMSO,[7]
PdI2/DMSO,[8] in Scheme 2. This may give diiodide E, which undergoes
PdBr2,CuBr2/DMSO,[9] PdCl2/CuCl2/PEG,[10] Pd/C/O2,[11] nucleophilic displacement with water to form the tricarb-
Scheme 1. Conversion of o-alkynylarenecarbaldehydes into isochromenes.
onyl compound F. In other words, the formyl group in the
[a] School of Chemistry, Bharathidasan University,
ortho position of A acts as neighbouring group during the
overall oxidation process. Due to this kind of intramolecu-
lar assistance of the formyl group, the oxidation is expected
to proceed in a facile manner. It was found to be true and
Tiruchirappalli 620024, Tamil Nadu, India
Fax: +91-431-2407043
E-mail: srinivasank@bdu.ac.in
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001746.
Eur. J. Org. Chem. 2011, 2781–2784
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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K. Sakthivel, K. Srinivasan
SHORT COMMUNICATION
Scheme 2. Oxidation of o-alkynylarenecarbaldehydes to tricarbonyl compounds.
Table 1. Oxidation of o-alkynylcarbaldehydes to tricarbonyl compounds.[a]
[a] Reaction conditions: o-alkynlbenzaldehyde (1.0 mmol), I2 (2.1 mmol), H2O (10 mmol), MeCN (10 mL), room temp. [b] Isolated yield.
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Oxidation of o-Alkynylarenecarbaldehydes by an Iodine/Water System
several o-alkynylarenecarbaldehydes underwent smooth the tricarbonyl compound 2b, the structure was also con-
oxidation with iodine and water in acetonitrile at room tem- firmed by X-ray analysis (Figure 1).
perature in a short reaction time. It may be noted that there
is only one example in the literature for the oxidation of
an internal alkyne (diphenylacetylene) to an 1,2-diketone
(benzil) by using an iodine/water system (the reaction was
carried out at 70 °C for 10 h to give the product in 19%
yield).[14]
The scope of the oxidation was investigated for various
o-alkynylarenecarbaldehydes, which were prepared by Son-
ogashira coupling of appropriate alkynes and haloarenes.
When o-alkynylbenzaldehyde 1a was treated with I2
(2.1 equiv.) and water (10 equiv.) in CH3CN at room tem-
perature, the starting material was consumed within 30 min,
and the workup and column purification afforded the
tricarbonyl compound 2a in 80% yield (Table 1, Entry 1).
Change of the solvent or the amounts of reagents did not
Figure 1. ORTEP plot of 2b in the crystal (50% probability level).
improve the yield. By using the same reaction conditions,
We extended this procedure to the bis(aldehyde) 3, which
the oxidations of o-alkynylarenecarbaldehydes 1b–j were also produced the corresponding hexacarbonyl compound
carried out to give the tricarbonyl compounds 2b–j in good 4 in 90% yield (Scheme 3).
to excellent yields (Table 1, Entries 2–10).
As outlined in Scheme 2, the oxidation proceeds by ini-
In general, the aldehydes underwent facile oxidation to tial formation of an isochromenol intermediate, which fur-
afford the tricarbonyl compounds in good to excellent ther reacts with I2 and water to give the product. An evi-
1
yields. Among these aldehydes, 1c is unique as it contains dence for this mechanism comes from H NMR spectra.
both formyl and methoxy groups in ortho position with re- The oxidation reaction of 2b was carried out in an NMR
1
spect to –CϵC– unit; however, the competitive benzofuran tube with I2 and D2O in CD3CN, and the H NMR spec-
formation[15] did not take place. All the products were thor- trum of the reaction mixture was recorded at different time
oughly characterized by spectroscopic techniques, and for intervals. The spectra clearly revealed that isochromenol (1-
Scheme 3. Oxidation of a bis(aldehyde) to the corresponding hexacarbonyl compound.
Scheme 4. Reactions of o-alkynyl ester or ketone with the I2/H2O system.
Eur. J. Org. Chem. 2011, 2781–2784
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K. Sakthivel, K. Srinivasan
SHORT COMMUNICATION
H resonance at δ = 6.29 ppm) is indeed the intermediate in
the reaction (see Supporting Information).
Acknowledgments
Another indirect evidence for the mechanism comes from
The authors thank the Department of Science and Technology
the reactions of the o-alkynyl ester 5 and the o-alkynyl (DST) and Council of Scientific and Industrial Research (CSIR),
India for financial support and Prof. P. Thomas Muthiah, Bhara-
thidasan University and Dr. K. Saminathan, Anna University of
Technology Tirunelveli for X-ray structural determination.
ketone 8 with the I2/water system (Scheme 4). Like the
–CHO group, the –CO2R group could also act as neigh-
bouring group, and this has been well proven in the case
of the Au3+-catalyzed regioselective hydration of 3-alk-
ynoates.[16a,16b] The isochromenol formed in the case of 5
may undergo either ring cleavage to give the dioxo ester 6
or elimination of the methoxy group to give isochromenone
7. The latter seems to be facile, and the isochromenone 7
was produced in 95% yield with no sign of formation of 6.
On the other hand, the o-alkynyl ketone 18 (in which the
oxo group could also act as neighbouring group, but the
methyl group is not a leaving group) formed the triketone
9 in 95% yield.
[1] a) A. S. Hirschon, J. T. Doi, W. K. Musker, J. Am. Chem. Soc.
1982, 104, 725–730; b) J. T. Doi, P. K. Bharadwaj, W. K.
Musker, J. Org. Chem. 1987, 52, 2581–2584; c) J. T. Doi, W. K.
Musker, D. L. Deleeuw, A. S. Hirschon, J. Org. Chem. 1981,
46, 1239–1243; d) J. T. Doi, M. H. Goodrow, W. K. Musker, J.
Org. Chem. 1986, 51, 1026–1029; e) R. S. Glass, G. L. Hug, C.
Schoneich, G. S. Wilson, L. Kuznetsova, T. Lee, M. Ammam,
E. Lorance, T. Nauser, G. S. Nichol, T. Yamamoto, J. Am.
Chem. Soc. 2009, 131, 13791–13805; f) K. A. Williams, J. T.
Doi, W. K. Musker, J. Org. Chem. 1985, 50, 4–10; g) J. T. Doi,
W. K. Musker, J. Am. Chem. Soc. 1984, 106, 1887–1888.
[2] a) J. Barluenga, H. Vazquez-Villa, A. Ballesteros, J. M. Gonza-
lez, Org. Lett. 2003, 5, 4121–4123; b) N. Asao, K. Takahashi,
S. Lee, T. Kasahara, Y. Yamamoto, J. Am. Chem. Soc. 2002,
124, 12650–12651; c) C. H. Oh, H. K. Yi, J. H. Lee, D. H. Lim,
Chem. Commun. 2010, 3007–3009; d) J. Zhu, A. R. Germain,
J. A. Porco Jr., Angew. Chem. Int. Ed. 2004, 43, 1239–1243; e)
D. Dyker, D. Aildebrandt, J. Org. Chem. 2005, 70, 6093–6096;
f) R. Y. Tang, J. H. Li, Chem. Eur. J. 2010, 16, 4733–4738; g)
G. Dyker, D. Hildebrandt, J. Liu, K. Merz, Angew. Chem. Int.
Ed. 2003, 42, 4399–4402; h) D. Yue, N. D. Ca, R. C. Larock,
Org. Lett. 2004, 6, 1581–1584; i) N. Ghavtadze, R. Fröhlich,
E. U. Würthwein, Eur. J. Org. Chem. 2010, 1787–1797.
[3] a) V. Zuliani, G. Cocconcelli, M. J. Fantini, C. Ghiron, M. Riv-
ara, J. Org. Chem. 2007, 72, 4551–4553; b) P. Nowak, D. Mal-
witz, D. C. Cole, Synth. Commun. 2010, 40, 2164–2169; c) S.
Yang-Lan, M. Mueller-Johnson, J. Oehldrich, D. Wichman,
J. M. Cook, U. Weiss, J. Org. Chem. 1976, 41, 4053–4058.
[4] a) X. Deng, N. S. Mani, Org. Lett. 2006, 8, 269–272; b) D. Lee,
V. S. Chang, Synthesis 1978, 462–463; c) N. S. Srinivasan, D. G.
Lee, J. Org. Chem. 1979, 44, 1574; d) C. J. Walsh, B. K. Man-
dal, J. Org. Chem. 1999, 64, 6102–6105.
Conclusions
A simple, environmentally benign, metal-free procedure
for the oxidation of o-alkynylarenecarbaldehydes to the cor-
responding tricarbonyl compounds has been developed.
The reaction proceeds via isochromenol intermediates
formed by neighbouring group participation of the formyl
group. The utility of the product tricarbonyl compounds
in the synthesis of various carbocycles and heterocycles is
currently being investigated and will be reported in due
course.
Experimental Section
General Procedure for the Oxidation of o-Alkynylarenecarbal-
dehydes: To
a
solution of an o-alkynylarenecarbaldehyde
[5] M. S. Yusybov, V. D. Filimonov, Synthesis 1991, 131–132.
[6] V. O. Rogatchov, V. D. Filimonov, M. S. Yusubov, Synthesis
2001, 1001–1003.
[7] A. Giraud, O. Provot, J. F. Peyrat, M. Alamiand, J. D. Brion,
Tetrahedron 2006, 62, 7663–7667.
[8] C. Mousset, O. Provot, A. Hamze, J. Bignon, J. Brion, M. Al-
ami, Tetrahedron 2008, 64, 4287–4294.
[9] W. Ren, Y. Xia, S. J. Ji, Y. Zhang, X. Wan, J. Zhao, Org. Lett.
2009, 11, 1841–1844.
(1.0 mmol) in acetonitrile (10 mL) were added iodine (2.1 mmol)
and water (10 mmol). The reaction mixture was stirred at room
temperature for the appropriate time, diluted with water and ex-
tracted with CH2Cl2. The organic layer was washed with satd.
Na2S2O3 solution, dried with anhydrous Na2SO4 and concentrated
under reduced pressure. The crude product was purified by column
chromatography (SiO2; EtOAc/hexane, 1:9, v/v) to afford the corre-
sponding tricarbonyl compound.
[10] S. Chandrasekhar, N. Kesava Reddy, V. Praveen Kumar, Tetra-
hedron Lett. 2010, 51, 3623–3625.
2-(2-Oxo-2-phenylacetyl)benzaldehyde (2a): Light brown semi-solid.
1H NMR (400 MHz, CDCl3): δ = 9.97 (s, 1 H, CHO), 8.12–8.10
(m, 2 H, Ar-H), 7.85–7.83 (m, 1 H, Ar-H), 7.70–7.64 (m, 3 H, Ar-
H), 7.61–7.57 (m, 1 H, Ar-H), 7.49–7.45 (m, 2 H, Ar-H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 193.4, 191.4, 188.5, 136.1, 134.9,
133.3, 133.2, 132.0, 131.4, 131.3, 129.8, 129.6, 127.6 ppm. HRMS:
calcd. for [C15H10O3 + H]+ 239.0708; found 239.0698.
[11] S. Mori, M. Takubo, T. Yanase, T. Maegawa, Y. Monguchi, H.
Sajiki, Adv. Synth. Catal. 2010, 352, 1630–1634.
[12] W. Ren, J. Liu, L. Chen, L. Wan, Adv. Synth. Catal. 2010, 352,
1424–1428.
[13] a) D. Yue, N. Della Ca, R. C. Larock, Org. Lett. 2004, 6, 1581–
1584; b) D. Yue, N. Della Ca, R. C. Larock, J. Org. Chem.
2006, 71, 3381–3388.
CCDC-819787 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
[14] M. Niu, H. Fu, Y. Jiang, Y. Zhao, Synthesis 2008, 2879–2882.
[15] T. Yao, D. Yue, R. C. Larock, J. Org. Chem. 2005, 70, 9985–
9989.
[16] a) W. Wang, B. Xu, G. B. Hammond, J. Org. Chem. 2009, 74,
1640–1643; b) W. Wang, J. Jasinski, G. B. Hammond, B. Xu,
Angew. Chem. Int. Ed. 2010, 49, 1–7.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details; spectroscopic characterization data and
Received: December 31, 2010
Published Online: April 11, 2011
1
copies of H and 13C NMR spectra of 2a–d and 2f.
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