ORGANIC
LETTERS
2006
Vol. 8, No. 19
4335-4338
Cleavage of Activated Cyclic Amines:
Unprecedented Approach toward
2-Substituted Cyclobutanones
Sivaraj Baktharaman, Sermadurai Selvakumar, and Vinod K. Singh*
Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India
Received July 7, 2006
ABSTRACT
We report, for the first time, ring opening of activated four- to six-membered cyclic amines followed by an intramolecular expansion of
cyclopropanol to cyclobutanone via carbocation intermediate. In the case of a N-tosylaziridine ester, a cyclobutanol was formed in a stereospecific
manner during the Kulinkovich reaction step.
Strained compounds such as cyclopropanol1 and cyclobu-
tanone2 are very useful in organic synthesis. The synthetic
utility of the latter is associated with the highly electrophilic
carbonyl group whose reactivity is considerably different
from that of carbonyls in larger rings due to high strain
energy (ca. 25 kcal/mol). Cyclobutanone and its derivatives
have served as useful precursors for ring expansion reac-
tions,3,4 which are widely used in organic synthesis. In
general, a four-membered ketone ring system is synthesized
either by [2+2] cycloaddition of ketenes and olefins5 or by
ring expansion of cyclopropyl precursors.6,7 While working
on the synthesis of natural products and a Lewis acid-
catalyzed cycloaddition of four-membered cyclic amines with
nitriles,8 we envisioned that cyclopropanol may undergo
rearrangement with R-substituted activated cyclic amines.
(5) Reviews: (a) Hyatt, J. A.; Raynolds, P. W. Org. React. 1994, 45,
159-646 and references therein. (b) Snider, B. B. Chem. ReV. 1988, 88,
793-811.
(1) Reviews: (a) Kulinkovich, O. G. Chem. ReV. 2003, 103, 2597-2632.
(b) Kulinkovich, O. G.; de Meijere, A. Chem. ReV. 2000, 100, 2789-2834.
(c) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C.; Tanko, J.;
Hudlicky, T. Chem. ReV. 1989, 89, 165-198. (d) Trost, B. M. Top. Curr.
Chem. 1986, 133, 3-82.
(2) Reviews: (a) Bellusˇ, D.; Ernst, B. Angew. Chem., Int. Ed. Engl. 1988,
27, 797-827. (b) Nemoto, H.; Fukumoto, K. Synlett 1997, 863-875 and
references therein.
(3) (a) Kingsbury, J. S.; Corey, E. J. J. Am. Chem. Soc. 2005, 127,
13813-13815. (b) Bernard, A. M.; Frongia, A.; Piras, P. P.; Secci, F. Org.
Lett. 2003, 5, 2923-2926. (c) Miyata, J.; Nemoto, H.; Ihara, M. J. Org.
Chem. 2000, 65, 504-512. (d) Yoshida, M.; Ismail, M. A.-H.; Nemoto,
H.; Ihara, M. J. Chem Soc., Perkin Trans. 1 2000, 2629-2635. (e) Trost,
B. M.; Bogdanowiz, M. J. J. Am. Chem. Soc. 1973, 95, 5321-5334.
(4) (a) Gadwood, R. C. J. Org. Chem. 1983, 48, 2098-2101. (b)
Danheiser, R. L.; Martinez-Davila, C.; Sard, H. Tetrahedron 1981, 37,
3943-3950. (c) Gadwood, R. C.; Lett, R. M. J. Org. Chem. 1982, 47, 2268-
2275. (d) Paquette, L. A.; Andrews, D. R.; Springer, J. P. J. Org. Chem.
1983, 48, 1147-1149.
(6) (a) Schumacher, W.; Hanack, M. Synthesis 1981, 490-492. (b)
Zhang, L.; Koreeda, M. Org. Lett. 2002, 4, 3755-3758. (c) Doyle, M. P.;
Kundu, K.; Russell, A. E. Org. Lett. 2005, 7, 5171-5174. (d) Periasamy,
M.; Jayakumar, K. N.; Bharathi, P. Chem. Commun. 2001, 1728-1729.
(e) Miller, M.; Hegedus, L. S. J. Org. Chem. 1993, 58, 6779-6785. (f)
Kim, O. K.; Wulff, W. D.; Jiang, W. J. Org. Chem. 1993, 58, 5571-5573.
(7) (a) Markham, J. P.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc.
2005, 127, 9708-9709. (b) Oh, H.-S.; Lee, H. I.; Cha, J. K. Org. Lett.
2002, 4, 3707-3709. (c) Cho, S. Y.; Cha, J. K. Org. Lett. 2000, 2, 1337-
1339. (d) Youn, J.-H.; Lee, J.; Cha, J. K. Org. Lett. 2001, 3, 2935-2938.
(e) Shevchuk, T. A.; Kulinkovich, O. G. Russ. J. Org. Chem. 2000, 36,
491-495. (f) Ollivier, J.; Salau¨n, J. Tetrahedron Lett. 1984, 25, 1269-
1272. (g) Trost, B. M.; Balkovec, J. M.; Mao, M. K.-T. J. Am. Chem. Soc.
1983, 105, 6755-6757.
(8) (a) Parasad, B. A. B.; Bisai, A.; Singh, V. K. Org. Lett. 2004, 6,
4829-4831. (b) Baktharaman, S.; Selvakumar, S.; Singh, V. K. Tetrahedron
Lett. 2005, 46, 7527-7529.
10.1021/ol0616687 CCC: $33.50
© 2006 American Chemical Society
Published on Web 08/17/2006