ORGANIC
LETTERS
2011
Vol. 13, No. 20
5676–5679
Modular Approach to Saturated and r,β-
Unsaturated Ketones
ꢀ
Laurent Debien, Beatrice Quiclet-Sire, and Samir Z. Zard*
ꢁ
Laboratoire de Synthese Organique, CNRS UMR 7652 Ecole Polytechnique, 91128
Palaiseau Cedex, France
Received September 5, 2011
ABSTRACT
2-Fluoro-6-pyridinyloxy derivatives of 2-ethoxyvinyl carbinols react with radicals derived from xanthates by an additionÀfragmentation pathway
to give highly functionalized ketones after acid hydrolysis. 1,4-Diketones are readily accessible by this approach. R,β-Unsaturated ketones can be
obtained by starting with geminal acetoxy xanthates prepared by addition of a simpler xanthate to vinyl acetate.
Ketones play a central role in organic chemistry and are
key building blocks in modern synthesis. They are involved
in many fundamental transformations such as the aldol,1
the Wittig2 and the HornerÀWadsworthÀEmmons2 reac-
tions to cite a few and are the direct precursors of numer-
ous organic functionalities such as imines, amines, oximes
and alcohols.
Furthermore, 1,4-diketones and, more generally, 1,4-di-
carbonyls are substrates of paramount importance for the
synthesis of valuable five-membered carbo- and heterocycles
such as cyclopentenones,3 pyrroles,4 furans,5 or thiophenes.6
Indeed, cyclopentenones, furans, and pyrroles are found in
many biologically important natural products such as
prostaglandins,7 terpenes5 and porphyrins.8 Furans are also
versatile dienes and dienophiles for DielsÀAlder reactions.9
(1) For a review on the aldol and related addition reactions see:
Casiraghi, G.; Battistini, L.; Curti, C.; Rassu, G.; Zanardi, F. Chem.
Rev. 2011, 111, 3076.
(5) (a) Dean, F. M. Naturally Occurring Oxygen Ring Compounds;
Butterworths: London, 1963; Chapter 1, p 1. (b) Keay, B. A.; Dibble, P. W.
In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W.,
Scriven, E. F. V., Eds; Pergamon Press: Oxford, 1997; Vol. 2, pp 395À 436.
(c) Elliot, M. C. J. Chem. Soc., Perkin Trans. I 2002, 2301. (d) Harmange,
J. C.; Figadere, B. Tetrahedron: Asymmetry 1993, 4, 1711.
(6) (a) Campaigne, E. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Eds; Pergamon Press: Oxford, 1984; Vol. 4,
pp 909À934. (b) Russell, R. K. In Comprehensive Heterocyclic Chemistry
II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds; Pergamon Press:
Oxford, 1997; Vol. 2, pp 679À729.
(2) For reviews of the Wittig and the Horner-Wadsworth-Emmons
€
reactions, see: (a) Schobert, R.; Holzel, C.; Barnickel, B. In Science of
Synthesis; de Meijere, A., Ed.; Thieme: Stuttgart, 2010; Vol. 47a, pp 9À84.
(b) Vedejs, E. J. Org. Chem. 2004, 69, 5159. (c) Kelly, S. E. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, 1991; Vol. 1, pp 729À818.
(3) (a) Mussatto, M. C.; Savoia, D.; Trombini, C.; Umani-Ronchi, A.
J. Org. Chem. 1980, 45, 4002. (b) Takahashi, K.; Aihara, T.; Ogura, K.
Chem. Lett. 1987, 2359. (c) Pecuniso, A.; Menicagli, R. J. Org. Chem.
1988, 53, 2614. (d) Bergman, R.; Nilsson, B.; Wickberg, B. Tetrahedron
1990, 31, 2783.
(7) For a review on the synthesis of prostaglandins see: (a) Collins,
P. W.; Djuric, S. W. Chem. Rev. 1993, 93, 1533. (b) Suzuki, M.; Kiho, T.;
Tomokiyo, K.; Furuta, K.; Fukushima, S.; Takeuchi, Y.; Nakanishi,
M.; Noyori, R. J. Med. Chem. 1998, 41, 3084.
(4) (a) Jones, A.; Bean, G. P. The Chemistry of Pyrroles; Academic
Press: London, 1977. (b) Jones, A. Pyrroles; Wiley: New York, 1990.
(c) Sobenina, L. N.; Mikhaleva, A. I.; Trofimov, B. A. Russ. Chem. Rev.
(Engl. Transl.) 1989, 58, 163. For some more recent examples, see:
(d) Minetto, G.; Raveglia, L. F.; Sega, A.; Taddei, M. Eur. J. Org. Chem.
2005, 5277. (e) Minetto, G.; Raveglia, L. F.; Tadde, M. Org. Lett. 2004,
6, 389. (f) Veitch, G. E.; Bridgwood, K. L.; Rands-Trevor, K.; Ley, S. V.
Synlett 2008, 17, 2597.
(8) (a) The Porphyrins; Dolphin, D., Ed.; Academic Press: New York,
1978. (b) Battersby, A. R. Nat. Prod. Rep. 2000, 17, 507.
(9) (a) Sternbach, D. D.; Rossana, D. M.; Onan, K. D. J . Org. Chem.
1984, 49, 3427. (b) Wenkert, E.; Moeller, P. D. R.; Piettre, S. R. J. Am.
Chem. Soc. 1988, 110, 7188.
r
10.1021/ol202399c
Published on Web 09/28/2011
2011 American Chemical Society