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comparable to those obtained with IBX or species X. In fact, the
desired dehomologated product 2c was obtained in less than
20% yield with DMP and was not detected with PhI(OAc)2.
During the last decade, IBX has attracted intense interest,13
not only as a reagent for the oxidation of alcohols to aldehydes
and ketones,4b but also as a mild and selective reagent in other
surprisingly versatile transformations.13c–j Therefore, it has
been widely applied in the total synthesis of complex natural
products.13f The novel dehomologation of primary alcohols
conducted by us stands as a new member of this class of
reactions and will also be useful for the synthesis of functional
molecules.
In summary, a novel, highly selective dehomologation of
primary alcohols to their corresponding one-carbon shorter
carboxylic acids using the mild, hypervalent iodine reagent
IBX was developed. A stable hypervalent iodine species was
isolated and shown to be crucial for the dehomologation. Further
study of the reaction mechanism is currently underway.14
K. Itto thanks JSPS for a Research Fellowship for Young
Scientists. We thank Professor Yasunori Ohba and the late
Professor Seigo Yamauchi (Institute of Multidisciplinary
Research for Advanced Materials, Tohoku University) for helpful
discussions.
Fig. 1 Comparison of the 1H- and 13C-NMR spectra of X, IBX, IBA, and BA.
All spectra were recorded in D7-DMF at room temperature. (a) 1H-NMR
spectra (600 MHz, 7.3 to 8.7 ppm). (b) 13C-NMR spectra (150 MHz, 90 to
180 ppm). A a H.
Notes and references
1 (a) P. H. Washecheck, Chem. Abstr., 1972, 77, 113810; (b) C. Harald
and K. Manfred, Chem. Abstr., 1990, 112, 7044; (c) S.-B. Li, S.-M.
Zhang, K. Wu and Y.-L. Li, Huaxue Shiji, 1992, 14, 60.
2 (a) P. Bijoy and G. S. R. Subba Rao, Synth. Commun., 1993, 23,
2701–2708; (b) R. A. Fernandes and P. Kumar, Tetrahedron Lett.,
2003, 44, 1275–1278.
3 Dehomologation has been reported as a side reaction in Jones
oxidation, see: (a) G. Just, C. Luthe and H. Oh, Synth. Commun.,
1979, 9, 613–617; (b) J. T. Doi, G. W. Luehr, D. del Carmen and
B. C. Lippsmeyer, J. Org. Chem., 1989, 54, 2764–2767.
4 (a) C. Hartmann and V. Meyer, Ber. Dtsch. Chem. Ges., 1893, 26,
1727–1732; (b) M. Frigerio and M. Santagostino, Tetrahedron Lett.,
1994, 35, 8019–8022.
5 For IBX oxidation of alcohols to carboxylic acids without carbon
loss, see: A. P. Thottumkara, M. S. Bowsher and T. K. Vinod,
Org. Lett., 2005, 7, 2933–2936.
Scheme 4 Reactivity of the hypervalent iodine species X.
6 J. D. More and N. S. Finney, Org. Lett., 2002, 4, 3001–3003.
7 For examples of chromium reagent dehomologation of 2-branched
alcohols to the ketones, see ref. 2.
8 Aldehydes and alpha-iodoaldehydes were characterized as key inter-
mediates via GC-MS and NMR analyses. The characterization of
other reaction intermediates and the examination of their possible
involvement in this dehomologation are underway.
9 This result implied that our reaction conditions were also effective
for the dehomologation of aldehydes, and may be a promising
supplemental method for the Norrish I photocleavage and the
transition-metal catalyzed deformylation of aldehydes, while the
latter two methods usually could only produce the unfunctionalized
dehomologated alkanes.
10 IBA and BA have been reported as reduced species of IBX by I2 in
DMSO, see: J. N. Moorthy, K. Senapati and S. Kumar, J. Org. Chem.,
2009, 74, 6287–6290.
11 For attribution of NMR peaks of X and comparison of NMR spectra
of X at room temperature and 80 1C, see ESI†.
12 (a) J. G. Sharefkin and H. Saltzman, Anal. Chem., 1963, 35,
1428–1431; (b) W. J. Horton and D. E. Robertson, J. Org. Chem.,
1960, 25, 1016–1020.
13 For recent reviews, see: (a) V. V. Zhdankin, Chem. Rev., 2008, 108,
5299–5358; (b) M. Uyanik and K. Ishihara, Chem. Commun., 2009,
2086–2099; (c) V. Satam, A. Harad, R. Rajule and H. Pati,
are oxidized to their corresponding aldehydes and then deho-
mologated to the corresponding carboxylic acids. First, it was
determined that the addition of X to alcohol 2a did not provide
the corresponding aldehyde in the presence or absence of I2.
This implies that the aldehyde intermediate is generated via
IBX oxidation. On the other hand, aldehydes (e.g., 5b) react
smoothly with X to afford the corresponding 2-iodoaldehydes
(e.g., 5f), which are dehomologated to the corresponding
carboxylic acids at 100 1C. Notably, in the presence of a catalytic
amount of I2, the dehomologation with X is accelerated and
proceeds in higher yield. These results suggest that both X and
some inorganic iodine species may work together during the
carbon–carbon bond cleavage step. For comparison, the combi-
nation of molecular iodine with Dess–Martin periodinane
(DMP) or (diacetoxyiodo)benzene (PhI(OAc)2) was investigated
using n-heptanal (2b) as the dehomologation substrate.
Neither alternative hypervalent iodine species yielded results
2760 | Chem. Commun., 2014, 50, 2758--2761
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