Communications
dichloroethane (6.1 mL) under an Ar atmosphere was added a
Gusar, M. P. Chaus, Tetrahedron, 1985, 41, 1823; b) P. Molina, M.
Alajarꢃn, C. Lꢁpez-Leonardo, I. Madrid, C. Foces-Foces, F. H.
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Yasuike, T. Tsuchiya, J. Chem. Soc. Chem. Commun. 1992, 81;
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[11] Confirmed by TLC and LC-MS analysis.
[12] In the thiolactam method, as illustrated in Scheme 1, at least four
steps are required including nonproductive protection–depro-
tection reactions because of the high reactivity of the amino
functionality (see refs. [3a], [3b], and [6c] for details).
solution of oxalyl bromide in dichloromethane (306 mL, 2.0m,
0.612mmol) dropwise at 0 8C. After the reaction mixture was stirred
at 08C for 1 h, it was warmed to room temperature and stirred for 4 h
at the same temperature. The resulting mixture was quenched with
anisole (133 mL, 1.22 mmol) and MeOH (1.2 mL) at 08C and stirred
for 30 min at room temperature. The resulting mixture was concen-
trated to half of the original volume and extracted with 1m aq HCl.
The aqueous extract was washed with CH2Cl2 and concentrated under
reduced pressure. The resulting residue was passed through Amber-
lite IRA400 (OHÀ) with MeOH as the eluent. Evaporation of the
organic solvent gave the pure amidine 2a (70.2mg, 0.565 mmol, 92%
yield).
[13] W. Mꢅller, W. Dorsch, F. Effenberger, Chem. Ber. 1987, 120, 55.
[14] For the preparation of starting material, see the Supporting
Information.
[15] When oxalyl chloride was used, formation of the chloroiminium
1
intermediate was confirmed by H and 13C NMR spectroscopy.
Received: August 29, 2003 [Z52750]
Therefore, the cyclization step would be faster when oxalyl
bromide is used.
Keywords: azides · chirality · cyclization · nitrogen heterocycles
.
[16] Synthetic procedure reported by Kotsuki et al. (in ref. [3a]) was
as follows; 1. hydrogenation of the azide, 2. Boc protection of
the resulting amine, 3. thioamide formation with Lawesson's
reagent, 4. activation of thioamide (MeI) followed by Boc
deprotection and cyclization (trifluoroacetic acid).
[17] For reviews, see: a) G. Kꢆbrich, Angew. Chem. 1973, 85, 494;
Angew. Chem. Int. Ed. Engl. 1973, 12, 464; b) K. J. Shea,
Tetrahedron 1980, 36, 1683.
[18] In situ IR spectra were recorded on a ReactIR4000 instrument
from ASI Applied Systems.
[19] The value was in good agreement with that from a similar
compound: B. A. Phillips, G. Fodor, J. Gal, F. Letourneau, J. J.
Ryan, Tetrahedron 1973, 29, 3309.
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[3] a) H. Kotsuki, A. Sugino, H. Sakai, H. Yasuoka, Heterocycles
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58, 2481; b) B. List, Tetrahedron, 2002, 58, 5573.
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[20] The IR spectra of 2a·HBr and 2a·Br2 prepared from 2a were
measured in 1,2-dichloroethane for the reference. 2a·HBr
showed n˜ = 1679 cmÀ1 and 2a·Br2 showed n˜ = 1637 cmÀ1 as a
characteristic absorption. See the Supporting Information.
[21] 2a·Br2 was also detected with an electrospray ionization mass
spectrometer by directly sampling the reaction mixture. The
peak at m/z = 203, 205 ([2a+ + Br]) derived from 2a·Br2 was
detected although its relative intensity was weak compared to
the peak at m/z = 125 ([2a+ + H]) derived from 2a·HBr.
[22] Oxalyl bromide alone did not brominate anisole.
[7] For recent selected examples of nucleophilic reactions of azides,
see: a) P. G. Reddy, B. Vahghese, S. Baskaran, Org. Lett. 2003, 5,
583; b) K. Sahasrabudhe, V. Gracias, K. Furness, B. T. Smith,
C. E. Katz, D. S. Reddy, J. Aubꢂ, J. Am. Chem. Soc. 2003, 125,
7194; c) S. Lang, A. R. Kennedy, J. A. Murphy, A. H. Payne,
Org. Lett. 2003, 5, 3655; d) D. S. Reddy, W. R. Judd, J. Aubꢂ, Org.
Lett. 2003, 5, 3899.
[8] For recent selected examples of 1,3-dipolar cycloadditions of
azides, see: a) F. Himo, Z. P. Demko, L. Noodleman, K. B.
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therein; b) S. Kamijo, T. Jin, Z. Huo, Y. Yamamoto, J. Am.
Chem. Soc. 2003, 125, 7786, and references therein; c) N.
Shangguan, S. Katukojvala, R. Greenberg, L. J. Williams, J.
Am. Chem. Soc. 2003, 125, 7754, and references therein; d) for a
related reaction of azides bearing an electron-withdrawing
functional group and a highly strained enamine to afford
amidines, see: J. K. Crandall, L. C. Crawley, J. B. Komin, J.
Org. Chem. 1975, 40, 2045.
[9] For a review, see: a) P. Molina, M. J. Vilaplana, Synthesis 1994,
1197. For an application to total synthesis, see: b) F. He, B. M.
Foxman, B. B. Snider, J. Am. Chem. Soc. 1998, 120, 6417.
[10] For examples of aza-Wittig cyclizations at an amide carbonyl,
usually suffering from low yields, see: a) Y. G. Gololobov, N. I.
482
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Angew. Chem. Int. Ed. 2004, 43, 478 –482