ORGANIC
LETTERS
2012
Vol. 14, No. 15
3874–3877
Efficient Aziridine Synthesis in Metastable
Crystalline Phases by Photoinduced
Denitrogenation of Crystalline Triazolines
Denisse de Loera and Miguel A. Garcia-Garibay*
Department of Chemistry, University of California, Los Angeles, California 90095-1559,
United States
Received June 7, 2012
ABSTRACT
The solid-state photodenitrogenation of crystalline triazolines proceeds with high efficiency to form the corresponding aziridines in high chemical
yields upon selection of the proper irradiation wavelength. It was shown that the solid-to-solid reactions occur by formation of the product in
metastable crystalline phases.
Aziridines (2, Scheme 1) are three-membered ring
nitrogen-containing heterocycles that are frequently used
as intermediates for selective ring-opening reactions1 and
can be found in the structure of several natural products.
Some synthetic aziridines exhibit antitumor and antibi-
otic activities.2 Among the many strategies developed to
prepare them,3 the thermal and photochemical denitro-
genation of 2-triazolines (1) provides a simple approach
to form the strained three-memberd ring by taking ad-
vantage of a highly energetic 1,3-aminyl-alkyl biradical
intermediate (BR, Scheme 1) and its propensity to form a
cycle by making a CꢀN bond.4
We have been interested in the development and ex-
ploration of synthetically promising solvent-free reactions
in crystalline solids,5 as these reactions tend to be more
selective than analogous reactions in solution.6 With that in
mind, we recognized an opportunity to explore a two-step
strategy for the stereospecific synthesis of substituted azir-
idines. As illustrated in Scheme 2, we propose the use of
diastereomerically pure (Z)- or (E)-alkenes 3 in 1,3-dipolar
cycloadditions with suitable azides 4 to form substituted
2-triazolines 5. On the basis of numerous observations by us
and others,5,6 one may expect that the photochemical
reaction of crystalline 5 (Scheme 2b) will proceed in the
crystal lattice by irreversible loss of N2 followed by a
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and Azirine Monocyclic; Padwa, A., Ed.; Comprehensive Heterocyclic
Chemistry II; Pergamon Press: Oxford, 1996. (b) Hu, X. E. Tetrahedron
2004, 60, 2701. (c) Watson, I. D. G.; Yu, L.; Yudin, A. K. Acc. Chem.
Res. 2006, 39, 194.
(2) (a) Kasai, M.; Kono, M. Synlett 1992, 10, 778. (b) Degel, B. D.;
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Rohrer, S.; Schreiber, S.; Martina, E.; Buchold, C.; Baumann, K.;
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Morschhauser, J.; Schirmeister, T. ChemMedChem 2008, 3, 302.
(5) (a) Shiraki, S.; Garcia-Garibay, M. A. Handbook of Synthetic
Photochemistry; Albini, A., Fagnini, M., Eds.; Wiley-VCH: Weinheim,
2010; pp 25ꢀ66; (b) Mortko, C. J.; Garcia-Garibay, M. A. Top.
Stereochem. 2006, 25, 205. (c) Garcia-Garibay, M. A.; Campos, L. In
Handbook for Organic Photochemistry and Photobiology; Horspool, W.,
Ed.; CRC Press: Boca Raton, FL, 2003.
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(3) (a) Cruz, A.; Padilla-Martınez, I. I.; Garcıa-Baez, E. V. Tetra-
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2010, 20, 3423. (c) Hayashi, S.; Yorimitsu, H.; Oshima, K. Angew.
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Calandriello, A.; Testaferri, L.; Tiecco, M. Tetrahedron 2010, 66, 6851.
(4) (a) Scheiner, P. In Selective Organic Transformtions; Tyagarajan,
B. S., Ed.; Wiley-Interscience: New York, 1970. (b) Hansen, P. E.; Undheim,
(6) (a) Schmidt, G. M. J. Pure Appl. Chem. 1971, 27, 647. (b) Cohen, M.
Angew. Chem., Int. Ed. 1975, 14, 386. (c) Ramamurthy, V.; Venkatesan, K.
Chem. Rev. 1987, 87, 433. (d) Gamlin, J. N.; Jones, R.; Leibovitch, M.;
Patrick, B.; Scheffer, J. R.; Trotter, J. Acc. Chem. Res. 1996, 29, 203. (e)
Zimmerman, H. E.; Nesterov, E. E. Acc. Chem. Res. 2002, 35, 77. (f)
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K. J. Chem. Soc., Perkin Trans. 1 1975, 305. (c) Perrocheau, J.; Carrie,
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R.; Fleury, J.-P. Can. J. Chem. 1994, 72, 2458. (d) Hunig, S.; Kraft, P.
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ꢁꢁ ꢀ
MacGillivray, L. R.; Papaefstathiou, G. S.; Friscic, T.; Hamilton, T. D.;
Heterocycles 1995, 40, 639. (e) Hunig, S.; Schmitt, M. Liebigs Ann. 1996,
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559. (f) Pocar, D.; Trimarco, P.; Bombieri, G. J. Heterocycl. Chem. 1998,
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Bucar, D.-K.; Chu, Q.; Varshney, D. V.; Georgiev, I. G. Acc. Chem. Res.
2008, 41, 280. (g) Garcia-Garibay, M. A. Acc. Chem. Res. 2003, 36, 491.
r
10.1021/ol301582n
Published on Web 07/13/2012
2012 American Chemical Society