ORGANIC
LETTERS
2011
Vol. 13, No. 23
6296–6299
Elimination versus Ring Opening:
A Convergent Route to
Alkylidene-Cyclobutanes
ꢀ
Julien Brioche, Michal Michalak, Beatrice Quiclet-Sire, and Samir Z. Zard*
ꢁ
Laboratoire de Synthese Organique, CNRS-UMR 7652, Ecole Polytechnique,
91128 Palaiseau Cedex, France
Received October 18, 2011
ABSTRACT
Functionalized alkylidene-cyclobutanes have been prepared from 2-fluoropyridinyl-6-oxy precursors derived from vinyl cyclobutanols by a
radical additionꢀelimination process. A wide range of functional groups is tolerated, and the alkylidene-cyclobutanes can be further elaborated
into cyclopentanones. The limitation of this approach resides in the competition with opening of the cyclobutane ring.
Alkylidene-cyclobutanes are strained structures that
exhibit enhanced reactivity and a strong propensity for
undergoing various rearrangements.1 Yet, as a class, they
have not attracted the attention they deserve, and their use
in synthetic planning has been relatively limited. One likely
reason is the dearth of convenient methods for their syn-
thesis. [2 þ 2]-Cycloadditions of allenes,2 Wittig and related
reactions on cyclobutanones,3 and a few specialized transi-
tion metal catalyzed transformations4 represent the main
routes to these structures. In view of the considerable but
still latent synthetic potential of alkylidene-cyclobutanes, we
report herein an alternative approach which complements
existing routes, and which offers some advantages in terms
of convergence and functional group tolerance.
(1) (a) Boontanonda, P.; Grigg, R. J. Chem. Soc., Chem. Commun.
ꢀ
1977, 583. (b) Jiang, M.; Shi, M. Org. Lett. 2008, 10, 2239. (c) Crepin, D.;
Dawick, J; Aıssa, C. Angew. Chem., Int. Ed. 2010, 49, 620. (d) Sun, K.;
Liu, S.; Bec, P. M.; Driver, T. G. Angew. Chem., Int. Ed. 2011, 50, 1702.
(2) Recent examples of thermal [2 þ 2]-cycloaddition of allenes: (a)
Ohno, H.; Mizutani, T.; Kadoh, Y.; Miyamura, K.; Tanaka, T. Angew.
Chem., Int. Ed. 2005, 44, 5113. (b) Ohno, H.; Mizutani, T.; Kadoh, Y.;
Aso, A.; Miyamura, K.; Fujii, N.; Tanaka, T. J. Org. Chem. 2007, 72,
4378.
As a part of our ongoing exploration of the degenerative
radical addition of xanthates,5 we recently described the
use of 2-fluoropyridine derivatives to convert alcohols into
leaving groups in a radical sense.6aꢀc This approach was
(3) For recent exemple of synthesis of alkylidene-cyclobutanes from
cyclobutanones using Wittig and related approaches, see: (a) Pearson,
W. H.; Fang, W.-K. J. Org. Chem. 2000, 65, 7158. (b) Choi, S.-Y.;
Horner, J. H.; Newcomb, M. J. Org. Chem. 2000, 65, 4447. (c) Clayden,
J.; Johnson, P.; Pink, J. H. J. Chem. Soc., Perkin Trans. 1 2001, 371. (d)
Binot, G.; Zard, S. Z. Tetrahedron Lett. 2003, 44, 7703. (e) Danappe, S.;
Pal, A.; Alexandre, C.; Aubertin, A.-M.; Bourgougnon, N.; Huet, F.
Tetrahedron 2005, 61, 5782. (f) Suhrada, C. P.; Selcuki, C.; Nendel, M.;
Cannizzaro, C.; Houk, K. N.; Rissing, P.-J.; Baumann, D.; Hasselmann,
D. Angew. Chem., Int. Ed. 2005, 44, 3548. (g) Kawashima, T.; Kashima,
H.; Wakasugi, D.; Satoh, T. Tetrahedron Lett. 2005, 46, 3767. (h)
Bernard, A. M.; Frongia, A.; Ollivier, J.; Piras, P. P.; Secci, F.; Spiga,
M. Tetrahedron 2007, 63, 4968. (i) Reisman, S. E.; Ready, J. M.; Weiss,
M. M.; Hasuoka, A.; Hirata, M.; Tamaki, K.; Ovaska, T. V.; Smith,
C. J.; Wood, J. L. J. Am. Chem. Soc. 2008, 130, 2087. (j) Yu, W.;
Williams, L.; Malveaux, E.; Camp, V. M.; Olson, J. J.; Goodman, M. M.
Bioorg. Med. Chem. Lett. 2008, 18, 1264. (k) Jai, W. S.; Hee, J. K.;
Byoung, S. L.; Katzenellenbogen, J. A.; Dae, Y. C. J. Org. Chem. 2008,
73, 715. (l) Satoh, T.; Awata, Y.; Ogata, S.; Sugiyama, S.; Tanaka, M.;
Tori, M. Tetrahedron Lett. 2009, 50, 1961. (m) Felluga, F.; Pitacco, G.;
Valentin, E.; Venneri, C. D.; Ghelfi, F.; Roncaglia, F. Tetrahedron:
Asymmetry 2010, 21, 2183. (n) Patel, R. M.; Argade, N. P. Synthesis
2010, 1188. (o) Zhou, Q.; Snider, B. B. Org. Lett. 2011, 13, 526.
ꢀ
(4) (a) Gonzalez, A. Z.; Benitez, D.; Tkatchouk, E.; Goddard, W. A.,
III; Toste, F. D. J. Am. Chem. Soc. 2011, 133, 5500. (b) Gulıas, M.;
ꢀ
~
Collado, A.; Trillo, B.; Lopez, F.; Onate, E.; Esteruelas, M. A.;
~
Mascarenas, J. L. J. Am. Chem. Soc. 2011, 133, 7660. (c) Rao, W.;
Susanti, D.; Chan, P. W. H. J. Am. Chem. Soc. 2011, 133, 15248.
(5) For general review on xanthate, see: (a) Zard, S. Z. Angew. Chem.,
Int. Ed. 1997, 36, 672. (b) Zard, S. Z. In Radical in Organic Synthesis;
Renaud, P., Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 1, p 90. (c)
Quiclet-Sire, B.; Zard, S. Z. Chem.;Eur. J. 2006, 12, 602. (d) Quiclet-
Sire, B.; Zard, S. Z. Top. Curr. Chem. 2006, 264, 201. (e) Zard, S. Z. Aust.
J. Chem. 2006, 59, 663. (f) Zard, S. Z. Org. Biomol. Chem. 2007, 5, 205. (f)
Quiclet-Sire, B.; Zard, S. Z. Pure Appl. Chem. 2011, 83, 519.
(6) (a) Charrier, N.; Quiclet-Sire, B.; Zard, S. Z. J. Am. Chem. Soc.
2008, 130, 8898. (b) Debien, L.; Quiclet-Sire, B.; Zard, S. Z. Org. Lett.
2011, 13, 5676. (c) Braun, M.-G.; Quiclet-Sire, B.; Zard, S. Z. J. Am.
Chem. Soc. 2011, 133, 15954.
r
10.1021/ol202798r
Published on Web 11/09/2011
2011 American Chemical Society