ORGANIC
LETTERS
2005
Vol. 7, No. 1
155-158
Kinetic and Theoretical Study of 4-exo
Ring Closures of Carbamoyl Radicals
onto CdC and CdN Bonds
Gino A. DiLabio,† Eoin M. Scanlan,‡ and John C. Walton*,‡
School of Chemistry, UniVersity of St. Andrews, St. Andrews, Fife, UK KY16 9ST,
National Institute for Nanotechnology, National Research Council of Canada,
W6-010 ECERF, 9107 116th Street, Edmonton, AB, Canada, T6G 2V4
Received November 7, 2004
ABSTRACT
Carbamoyl radicals were generated from oxime oxalate amides, and the kinetics of their 4-exo cyclizations onto CdC and CdNO bonds,
leading to
ring closures onto C
predicted to have much higher activation energies. Experimental evidence also favored slow reverse ring opening.
â
-lactam-containing species, were studied by EPR spectroscopy. DFT computations with model carbamoyl radicals predicted 4-exo
d
NO bonds to be facile, especially when tert-butyl substituents were present. The reverse ring-opening reactions were
4-exo Cyclizations of 4-pentenyl type radicals are normally
slow1 and are opposed by the faster ring opening of the
product cyclobutylalkyl radicals.2 Cyclizations leading to
four-membered ring azetidinones seem to differ from this
norm because â-lactams have successfully been prepared via
ring closures of carbamoyl radicals,3-5 amidoalkyl radicals,6
and amidyl radicals,7 although yields were usually moderate.
We showed recently that oxime oxalate amides, PhCHd
NOC(O)C(O)NR2, release carbamoyl radicals in photolyses
sensitized with 4-methoxyacetophenone (MAP). Carbamoyl
radicals with alkene groups appropriately sited in the NR2
groups ring-closed to give pyrrolidinone or azetidinone rings,
depending on the position of the double bond.8 In a few
instances, radical intermediates in these systems could be
directly monitored by EPR spectroscopy, and this gave a
unique opportunity to study, for the first time, the kinetics
of ring closure to â-lactams.
Cyclization onto oxime ether functional groups is re-
giospecific to the C-atom of the CdN bond9 and can be
significantly faster than with analogous alkene acceptors.10
Moreover, useful N-functionality remains available for
further synthetic elaboration. We surmised that a carbamoyl
† National Institute for Nanotechnology.
(6) See for example: Fremont, S. L.; Belletire, J. L.; Ho, D. M.
Tetrahedron Lett. 1991, 32, 2335-2338. Ishibashi, H.; Nakamura, N.; Sato,
T.; Takenuchi, M.; Ikeda, M. Tetrahedron Lett. 1991, 32, 1725-1728.
Ishibashi, H.; Kameoka, C.; Kodama, K.; Ikeda, M. Tetrahedron 1996, 52,
489-502. Quiclet-Sire, B.; Saunier, J. B.; Zard, S. Z. Tetrahedron Lett.
1996, 37, 1397-1400. Cassayre, J.; Quiclet-Sire, B.; Zard, S. Z. Tetrahedron
1998, 54, 1029-1040. Bryans, J. S.; Chessum, N. E. A.; Parsons, A. F.;
Ghelfi, F. Tetrahedron Lett. 2001, 42, 2901-2905. D’Annibale, A.; Pesce,
A.; Resta, S.; Trogolo, C. Tetrahedron 1997, 53, 13129-13138.
(7) Clark, A. J.; Peacock, J. L. Tetrahedron Lett. 1998, 39, 1265-1268.
(8) (a) Scanlan, E. M.; Walton, J. C. Chem. Commun. 2002, 2086-2087.
(b) Scanlan, E. M.; Slawin, A. M. Z.; Walton, J. C. Org. Biomol. Chem.
2004, 2, 716-724.
‡ University of St. Andrews.
(1) Park, S.-U.; Varick, T. R.; Newcomb, M. Tetrahedron Lett. 1990,
31, 2975-2978.
(2) Beckwith, A. L. J.; Moad, G. J. Chem. Soc., Perkin Trans. 2 1980,
1083-1092. Ingold, K. U.; Maillard, B.; Walton, J. C. J. Chem. Soc., Perkin
Trans. 2 1981, 970-974. Walton, J. C. J. Chem. Soc., Perkin Trans. 2
1989, 173-177.
(3) Gill, G. B.; Pattenden, G.; Reynolds, S. J. Tetrahedron Lett. 1989,
30, 3229-3232. Gill, G. B.; Pattenden, G.; Reynolds, S. J. J. Chem. Soc.,
Perkin Trans. 1 1994, 369-378.
(4) Bella, A. F.; Jackson, L. V.; Walton, J. C. J. Chem. Soc., Perkin
Trans. 2 2002, 1839-1843. Bella, A. F.; Jackson, L. V.; Walton, J. C.
Org. Biomol. Chem. 2004, 2, 421-428.
(9) Tomaszewski, M. J.; Warkentin, J.; Werstiuk, N. H. Aust. J. Chem.
1995, 48, 291-321.
(5) Ryu, I.; Miyazato, H.; Kuriyama, H.; Tanaka, M.; Komatsu, M.;
Sonoda, N. J. Am. Chem. Soc. 2003, 125, 5632-5633.
(10) Fallis, A. G.; Brinza, I. M. Tetrahedron 1997, 53, 17543-17594.
10.1021/ol047716+ CCC: $30.25
© 2005 American Chemical Society
Published on Web 12/13/2004