Reaction of Bromo Dipoles with (Z)-4-(Arylmethylene)azol-5-ones. Substrate-Controlled Synthesis of New Bromo-Substituted Heterocyclic Spirans and Unusual N-Benzoyl α-Aminoacids

Abstract

Bromo spirans 6 and 7 and unusual α-aminoacids 8 were prepared as diastereoisomerically pure compounds from bromo ­dipoles and (Z)-4-arylmethyleneazolones.

Key words

dipolar cycloadditions - nitrile oxides - nitrile imines - bromoheterocycles

References

• 1a Foti F. Grassi G. Risitano F. Tetrahedron Lett.  1999,  40:  2605 
• 1b Foti F. Grassi G. Risitano F. Helv. Chim. Acta  2001,  84:  3313 
• 2 Caramella P. Grunanger P. In 1,3-Dipolar Cycloaddition Chemistry   Vol. 1:  Padwa A. Wiley-Interscience; New York: 1984.  Chap. 3.
• 5a Grassi G. Risitano F. Foti F. Cordaro M. Synlett  2001,  812 
• 5b Risitano F. Grassi G. Foti F. Bruno G. Rotondo A. Heterocycles  2003,  60:  857 
• 6 Maquestiau A. Van Haverbeke Y. Muller RN. Tetrahedron Lett.  1972,  1147 
• 8a Levy GC. Lichter RL. In ¹⁵N Nuclear Magnetic Resonance Spectroscopy   John Wiley and Sons; New York: 1979.  Chap. 3. p.28 
• 8b

  ¹H NMR, ¹³C NMR, and ¹⁵N NMR spectra were recorded with a Bruker ARX 300 spectrometer at 300.13, 75.47, and 30.41 MHz, respectively. The ¹H NMR spectra were calibrated against the residual proton signal of the solvent (CDCl₃: δ = 7.24 ppm), the ¹³C{¹H} NMR spectra against the triplet of the solvent (CDCl₃: δ = 77.0 ppm), and the ¹⁵N{¹H} NMR spectra against external CH₃NO₂ (1v:1v) in CDCl₃ at δ = 379.60 ppm.

• 9a Faber K. Kappe T. J. Heterocycl. Chem.  1984,  21:  1881 
• 9b

  Selected data for 9: mp 210-211 °C. IR (nujol): 3398, 3243, 3166, 1734, 1698 cm^-1. ¹H NMR (300 MHz, DMSO-d ₆): δ = 7.47 (s, HC-4), 10.83 (s, 1 H). MS (EI):
  m/z = 309/311 [M⁺].

• 11 Halling K. Thomsen I. Torssell KBG. Liebigs Ann. Chem.  1989,  985 

3

Spyrans 6a-c were synthesized from 4-arylmethylene-imidazolones 1 and bromonitrilimine 4 at r.t. by a route analogous to that previously described in ref. [1]

4

Typical procedure for bromonitrile oxide cycloaddition: To a stirred mixture of EtOAc (50 mL) and NaHCO₃ (4.2 g, 50.0 mmol) was added a solution of 2 or 3 (10 mmol) and dibromoformaldoxime [11] (2.7 g, 13.0 mmol) in THF at r.t. The reaction was stirred for ca. 24 h at r.t. After completion of the reaction, the mixture was filtered and evaporated in vacuo. EtOAc was then added to the residue. The residue was washed twice with brine, dried over Na₂SO₄, and the solvent was removed under vacuum. Column chromatography of the residue on silica gel (CHCl₃) gave the indicated products as colorless crystals.

7

Selected data. Compound 6a: mp 114-116 °C. IR (nujol): 1758 cm^-1. ¹H NMR (DMSO-d ₆): δ = 5.06 (s, HC-4). ¹³C NMR (DMSO-d ₆): δ = 67.8 (C-4), 92.3 (C-5). MS (EI):
m/z = 444/446 [M⁺]. Compound 6b: mp 119-121 °C. IR (nujol): 1755 cm^-1. ¹H NMR (DMSO-d ₆): δ = 5.05 (s, HC-4). ¹³C NMR (DMSO-d ₆): δ = 67.3 (C-4), 92.4 (C-5). MS (EI): m/z = 458/460 [M⁺]. Compound 7a: mp 190-191 °C. IR (nujol): 1801, 1747 cm^-1. ¹H NMR (DMSO-d ₆): δ = 5.10 (s, HC-4). ¹³C NMR (DMSO-d ₆): δ = 59.2 (C-4), 96.1 (C-5). MS (EI): m/z = 309/311 [M⁺]. Compound 7b: mp 240-242 °C. IR (nujol): 3336, 1796, 1752 cm^-1. ¹H NMR (DMSO-d ₆): δ = 5.01 (s, HC-4). ¹³C NMR (DMSO-d ₆):
δ = 59.0 (C-4), 95.7 (C-5). MS (EI): m/z 340/342 [M⁺]. Compound 7c: mp 264-265 °C. IR (nujol): 1746 cm^-1. ¹H NMR (DMSO-d ₆): δ = 5.11 (HC-4). ¹³C NMR (DMSO-d ₆):
δ = 59.1 (C-4), 96.2 (C-5). MS (EI): m/z = 344-346 [M⁺]. Compound 8a: mp 128-130 °C. IR (nujol): 3485,1709, 1684 cm^-1. ¹H NMR (DMSO-d ₆): δ = 5.55 (s, HC-4). MS (EI): m/z = 338/390 [M⁺]. Compound 8b: mp 164-165 °C. IR (nujol): 3438, 1713, 1698 cm^-1. ¹H NMR (DMSO-d ₆): δ = 3.61 (s, 3 H), 5.55 (s, HC-4). MS (EI): m/z = 418/420 [M⁺].

10

X-ray data to be submitted to Acta Cryst.