C. Bonini, L. Chiummiento, M. Funicello, P. Lupattelli, M. Pullez
SHORT COMMUNICATION
acologica di nuove molecole organiche quali potenziali farmaci in-
novativi grant) for financial support.
All the final compounds obtained can be seen as exam-
ples of useful chiral building blocks incorporating highly
functionalised motifs including primary and secondary hy-
droxy groups and carbonyl groups.
Above all, compounds 6, 15, 16 and 20 are direct precur-
sors for the preparation of 1,3-diol frameworks with syn or
anti relative configurations, as important building blocks in
the synthesis of natural products such as macrolide or iono-
phore antibiotics.[24] The direct hydride reduction of β-hy-
droxy ketones is one of the most widely employed method-
ologies for access to this kind of compound.[25]
As an example, the reduction of the derived compound
6 with tetramethylammonium triacetoxyborohydride[26] af-
forded the desired 1,3-anti diol in excellent yield and with
good diastereoselectivity (de Ͼ 98%).[12]
However some preliminary studies on the reduction of
the prepared ketols (6, 15, 16 and 20) to the corresponding
1,3-diols still require further developments in the use of ap-
propriate reduction reagents.
[1] P. Zhou, B. C. Chen, F. A. Davis, in Asymmetric Oxidation Re-
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[3] a) R. A. Johnson, K. B. Sharpless, in Catalytic Asymmetric
Synthesis, 2nd ed., (Ed.: I. Ojima), Wiley-VCH, New York,
Weinheim, 2000, p. 231; b) T. Katsuki, in Catalytic Asymmetric
Synthesis, 2nd ed., (Ed.: I. Ojima), Wiley-VCH, New York,
Weinheim, 2000, p. 287; c) E. N. Jacobsen, M. H. Wu, in Com-
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6534; d) T. Fukuda, T. Katsuki, Tetrahedron Lett. 1996, 37,
4389–4392.
Of particular importance are the chiral synthons 17 and
19. The first compound, ketol 17, is a useful intermediate
for the preparation of 1,4-diol units, present in several natu-
ral products such as acetogenin, a promising anticancer, an-
tibiotic and pesticidal natural compound product,[27] while
the second one, 19, is a direct precursor of amino diols.
Conclusions
In conclusion, simple chiral terminal alkenes could be
utilised in a multistep synthetic strategy involving initial
oxidation of the double bond to an α-hydroxymethyl ketone
in order to access different functionalities. The overall
method is practical and quite efficient, and is compatible
with the presence of protective groups for the hydroxy func-
tions. Moreover, the environmentally friendly (with respect
to other oxidants) KMnO4 oxidation and the use of aque-
ous media as solvent make this procedure quite appealing.
[7] N. S. Srinivasan, D. G. Lee, Synthesis 1979, 520.
[8] S. Baskaran, S. J. Das, S. Chandrasekaran, J. Org. Chem. 1989,
54, 5182–5184.
[9] T. Takai, T. Yamada, T. Mukaiyama, Chem. Lett. 1991, 1499.
[10] a) B. Plietker, Eur. J. Org. Chem. 2005, 1919–1929; b) B. Pli-
etker, Org. Lett. 2004, 6, 289–291; c) B. Plietker, J. Org. Chem.
2004, 69, 8287–8296; d) B. Plietker, M. Niggemann, Org. Bi-
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2003, 68, 7123–7125.
[11] C. Bonini, L. Chiummiento, A. Evidente, M. Funicello, Tetra-
hedron Lett. 1995, 36, 7285–7286.
[12] C. Bonini, L. Chiummiento, M. Pullez, G. Solladié, F. Colob-
ert, J. Org. Chem. 2004, 69, 5015–5022.
[13] A. R. L. Cecil, R. C. D. Brown, Org. Lett. 2002, 4, 3715–3718.
[14] A. Shaabani, P. Mirzaei, D. G. Lee, Catalysis Lett. 2004, 97,
119–123 and references cited therein.
[15] K. G. Mumford, N. R. Thomson, R. M. Allen-King, Environ.
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[16] For the preparation of unprotected compound 8 see: a) K. Ku-
bota, J. L. Leighton, Angew. Chem. Int. Ed. 2003, 42, 946–948;
b) B. Patterson, S. Marumoto, S. D. Rychnovsky, Org. Lett.
2003, 5, 3163–3166; c) M. Kurosu, M. Lorca, Tetrahedron Lett.
2002, 43, 1765–1769.
[17] For the preparation of unprotected compound 9 see: a) C.-
H. A. Lee, T.-P. Loh, Tetrahedron Lett. 2004, 45, 5819–5822;
b) G. K. Packard, Y. Hu, A. Vescovi, S. D. Rychnovsky, Angew.
Chem. Int. Ed. 2004, 43, 2822–2826; c) A. Le Flohic, C. Meyer,
J. Cossy, J.-R. Desmurs, J.-C. Galland, Synlett 2003, 667–670;
d) W. R. Roush, L. K. Hong, M. A. J. Palmer, J. A. Straub,
A. D. Palkowitz, J. Org. Chem. 1990, 55, 4117–4126.
[18] For the preparation of unprotected compound 10 see: a) Y.
Sugita, Y. Kimura, I. Yokoe, Tetrahedron Lett. 1999, 40, 5877–
5880; b) J. C. Y. Wong, P. Lacombe, C. F. Sturino, Tetrahedron
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H. Heimstra, H. E. Schoemaker, Synlett 1998, 192–194.
[19] For the preparation of unprotected compound 11 see: a) H.
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Experimental Section
General Procedure for Ketohydroxylation of Olefins: The olefin
(2.1 mmol) was added to a solution of acetone (17 mL), water
(3.8 mL) and acetic acid (0.8 mL). A solution of KMnO4 (0.5 g,
3.4 mmol) in acetone (6.4 mL) and water (2.1 mL) was added drop-
wise, and the resulting mixture was stirred at room temperature
until complete disappearance on TLC. After complete conversion
(about 2 h), EtOH was added until effervescence stopped. The
crude mixture was filtered through a pad of Celite and washed
several times with hexane. The filtrate was concentrated, diluted
with Et2O and washed with saturated aqueous NaHCO3 solution
until pH = 8. The organic layer was then washed with brine and
dried with Na2SO4. The crude product was purified by column
chromatography on silica gel.
Supporting Information (see footnote on the first page of this arti-
cle): Characterisation of all new compounds.
Acknowledgments
Thanks are due to the University of Basilicata and the MIUR
(FIRB-Progettazione, preparazione e valutazione biologica e farm-
82
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 80–83