An improved diastereoselective synthesis of spiroazoles using multicomponent domino transformations

Synlett

Volumn , Issue 14, 2010, Pages 2106-2108

  Altieri, Elisa ^a   Cordaro, Massimiliano ^a   Grassi, Giovanni ^a   Risitano, Francesco ^a   Scala, Angela ^a  

^a UNIVERSITY OF MESSINA   (Italy)

Author keywords

cyclizations; diastereoselectivity; microwave; multicomponent reactions; spirans

Indexed keywords

PYRROLE DERIVATIVE; SPIROISOXAZOLE DERIVATIVE; SPIROPYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; CHEMICAL STRUCTURE; CRYSTAL STRUCTURE; CYCLIZATION; MICROWAVE RADIATION; PROTON NUCLEAR MAGNETIC RESONANCE; STEREOCHEMISTRY; STRUCTURE ANALYSIS; SYNTHESIS;

EID: 77956049998     PISSN: 09365214     EISSN: 14372096     Source Type: Journal    
DOI: 10.1055/s-0030-1258516     Document Type: Article

References (16)

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6. Risitano F, Grassi G, Foti F, Romeo R, Synthesis 2002 116
7. (a) In contrast with previous findings, the above spirocyclization is promoted by the regiospecific gem -C-C bond formation at the 4-position of the azolone rings. See:, Tietze L F., Hippe T, Steinmetz A, Synlett 1996 1043
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9. (a) Risitano F, Grassi G, Foti F, Moraci S, Synlett 2005 1633
10. (b) Bruno G, Rotondo A, Nicolò F, Risitano F, Grassi G, Foti F, Helv. Chim. Acta 2006 89 190
11. Risitano F, Grassi G, Foti F, Bilardo C, Tetrahedron 2000 56 9669
12. Method A; Typical Procedure: To a stirred solution of isoxazol-5-one 1 (4.2 mmol) in EtOH (20 mL), containing 4 molecular sieves and an excess of AcOHAcONH4, aldehyde 4 (8.5 mmol) and phenacyl chloride 3 (4.2 mmol) were added. The solution was heated at reflux for 2 h. After cooling, the reaction mixture was filtered to remove molecular sieves and the solvent was evaporated. The resulting residue was washed with cool H2O and the aqueous suspension was then extracted with Et2O (3 30 mL). The combined organic layer was washed with H2O, dried over anhyd Na2SO4, filtered and evaporated under reduced pressure. The crude product was purified by recrystallization from MeOH or by column chromatography on SiO2 (CHCl3) to afford 5. The use of pyrazolin-5-one 2 in place of isoxazol-5-one 1 provided 6 and 7
13. Bridgehead aziridines 7 were generated from 4 and 3 in the presence of the AcOHAcONH4 mixture, as reported in ref. 4.
14. Typical Procedure: A mixture of pyrazolin-5-one 2 (4.2 mmol), aldehyde 4 (8.5 mmol) and phenacyl chloride 3 (4.2 mmol) in n-PrOH (30 mL) containing an excess of AcOH AcONH4 and 4 molecular sieves was heated by MW irradiation at 95 C for 515 min. After cooling the reaction to r.t., filtration and evaporation of the solvent afforded a solid residue which was worked up as mentioned above. The crude product was purified by recrystallization from CHCl3 MeOH or by column chromatography on neutral Al2O3 (CHCl3) to give 8 as colorless crystals.
15. Selected Data for 8ah: 8a: yield: 79%; mp 194195 C. IR (Nujol): 1716 cm1. 1H NMR (300 MHz, CDCl3): d = 5.91 (s, 1 H), 6.797.25 (m, arom., 10 H), 7.32 (s, 1 H), 7.348.24 (m, arom., 15 H). 13C NMR (75 MHz, CDCl3): d = 68.3, 119.9142.5, 156.6, 171.7, 175. Anal. Calcd for C37H27N3O: C, 83.91; H, 5.14; N, 7.93. Found: C, 84.13; H, 5.16; N, 8.02. 8b: yield: 85%; mp 108110 C. IR (Nujol): 1708 cm1. 1H NMR (300 MHz, CDCl3): d = 2.14 (s, 3 H), 2.17 (s, 3 H), 5.91 (s, 1 H), 6.737.24 (m, arom., 10 H), 7.33 (s, 1 H), 7.35 7.95 (m, arom., 13 H). 13C NMR (75 MHz, CDCl3): d = 21.0, 21.1, 68.3, 119.8141.7, 157.2, 171.4, 174.8. Anal. Calcd for C39H31N3O: C, 83.99; H, 5.60; N, 7.53. Found: C, 83.81; H, 5.51; N, 7.49. 8c: yield: 84%; mp 106108 C. IR (Nujol): 1713 cm1. 1H NMR (300 MHz, CDCl3): d = 3.65 (s, 3 H), 3.73 (s, 3 H), 5.92 (s, 1 H), 6.517.25 (m, arom., 10 H), 7.30 (s, 1 H), 7.357.95 (m, arom., 13 H). 13C NMR (75 MHz, CDCl3): d = 55.2, 55.4, 68.6, 119.5140.7, 157.4, 159.8, 160.0, 171.4, 174.6. Anal. Calcd for C39H31N3O3: C, 79.44; H, 5.30; N, 7.13. Found: C, 79.28; H, 5.20; N, 7.05. 8d: yield: 78%; mp 124125 C. IR (Nujol): 1712 cm1. 1H NMR (300 MHz, CDCl3): d = 5.93 (s, 1 H), 6.707.24 (m, arom., 10 H), 7.32 (s, 1 H), 7.357.96 (m, arom., 13 H). 13C NMR (75 MHz, CDCl3): d = 68.5, 119.3143.0, 156.5, 170.5, 174.5. Anal. Calcd for C37H25N3OCl2: C, 74.25; H, 4.21; N, 7.02. Found: C, 74.09; H, 4.16; N, 6.95. 8e: yield: 65%; mp 175177 C. IR (Nujol): 1714 cm1. 1H NMR (300 MHz, CDCl3): d = 1.64 (s, 3 H), 2.01 (s, 3 H), 6.39 (s, 1 H), 6.727.25 (m, arom., 10 H), 7.31 (s, 1 H), 7.337.95 (m, 13 H). 13C NMR (75 MHz, CDCl3): d = 19.4, 19.5, 67.2, 119.5 143.2, 157.2, 172.3, 174.2. Anal. Calcd for C39H31N3O: C, 83.99; H, 5.60; N, 7.53. Found: C, 84.21; H, 5.61; N, 7.59. 8f: yield: 63%; mp 129130 C. IR (Nujol): 1714 cm1. 1H NMR (300 MHz, CDCl3): d = 3.21 (s, 3 H), 3.31 (s, 3 H), 6.31 (s, 1 H), 6.407.24 (m, arom., 10 H), 7.33 (s, 1 H), 7.35 7.99 (m, arom., 13 H). 13C NMR (75 MHz, CDCl3): d = 55.1, 55.5, 67.2, 118.3143.2, 156.0, 157.2, 158.1, 172.5, 175.0. Anal. Calcd for C39H31N3O3: C, 79.44; H, 5.30; N, 7.13. Found: C, 79.32; H, 5.17; N, 7.03. 8g: yield: 84%; mp 140141 C. IR (Nujol): 1710 cm1. 1H NMR (300 MHz, CDCl3): d = 1.95 (s, 3 H), 2.20 (s, 3 H), 5.91 (s, 1 H), 6.617.25 (m, arom, 10 H), 7.30 (s, 1 H), 7.347.96 (m, arom., 13 H). 13C NMR (75 MHz, CDCl3): d = 20.2, 20.3, 68.3, 119.6142.4, 157.2, 171.8, 174.5. Anal. Calcd for C39H31N3O: C, 83.99; H, 5.60; N, 7.53. Found: C, 83.85; H, 5.49; N, 7.46. 8h: yield: 81%; mp 136138 C. IR (Nujol): 1709 cm1. 1H NMR (300 MHz, CDCl3): d = 3.37 (s, 3 H), 3.66 (s, 3 H), 5.89 (s, 1 H), 6.647.25 (m, arom. 10 H), 7.32 (s, 1 H), 7.36 7.95 (m, arom., 13 H). 13C NMR (75 MHz, CDCl3): d = 55.1, 55.4, 68.5, 118.9141.9, 156.7, 158.5, 159.1, 171.9, 174.8. Anal. Calcd for C39H31N3O3: C, 79.44; H, 5.30; N, 7.13. Found: C, 79.58; H, 5.31; N, 7.19
16. X-ray data to be submitted to Acta Crystallogr.