First Diels-Alder Cycloaddition of N′-Oxazolyl-N,N-dimethylalkylamidines with Electron-Poor Dienophiles: Characterization of a Diastereoselective Pathway

Abstract

Diels-Alder cycloaddition of N′-oxazolyl-N,N-dime­thylalkylamidines 1a,b with electron-poor dienophiles were performed, leading to new 2-phenoxymethyl-6-formyl-2,3-dihydro-5H-oxazolo[3,2-a]pyrimidines and 2-phenoxymethyl-6-nitro-2,3-dihydro-5H-oxazolo[3,2-a]pyrimidines. The regio and endo dia­stereoselectivity of one [4+2] cycloadduct 4 was established through the single-crystal X-ray structure determination of 4a. The diastereo­selectivity could be related to a potential π-stacking interaction.

Key words

Diels-Alder reaction - regioselectivity - diastereoselectivity - 1,3-diazadiene - 2-amino-2-oxazoline

References

• 1a Zupan M. Stanovnik B. Tisler M. J. Org. Chem.  1972,  37:  2960 
• 1b Stanovnik B. Urleb U. Tisler M. Heterocycles  1985,  23:  2819 
• 1c Landreau C. Deniaud D. Reliquet A. Meslin J.-C. Synthesis  2001,  2015 
• 2a Forfar I. Jarry C. Laguerre M. Léger JM. Pianet I. Tetrahedron  1999,  55:  12819 
• 2b Chaimbault C. Bosc JJ. Léger JM. Négrier P. Capelle F. Jarry C. J. Pharm. Sci.  2000,  89:  1496 
• 3 Abdulla RF. Brinkmeyer RS. Tetrahedron  1979,  35:  1675 
• 4 Jarry C. Golse R. Panconi E. Creuzet MH. Eur. J. Med. Chem.  1986,  21:  138 
• 5a Sanfilippo PJ. Urbanski M. Press JB. Dubinsky B. Moore JB. J. Med. Chem.  1988,  31:  2221 
• 5b Hirota T. Sasaki K. Yamamoto H. Nakayama T. J. Heterocycl. Chem.  1991,  28:  257 
• 6 Naulet M. Filleux ML. Martin GJ. Org. Magn. Reson.  1975,  7:  326 
• 8 Charustin VN. Van der Plas HC. Recl. Trav. Chim. Pays-Bas  1983,  102:  373 
• 9 Thakur AJ. Saikia P. Prajapati D. Sandhu JS. Synlett  2001,  1299 
• 11a Gawley RE. Aubé J. In Principles of Asymmetric Synthesis   Baldwin JE. Magnus PD. Pergamon; Oxford: 1996.  p.274 
• 11b Garner P. Anderson JT. Turske RA. Chem. Commun.  2000,  17:  1579 
• 11c Boger DL. Corbett WL. Curran TT. Kasper AM. J. Am. Chem. Soc.  1991,  113:  1713 
• 13a Diaz-Ortiz A. Carillo JR. Gomez-Escalonilla MJ. De la Hoz A. Moreno A. Prieto P. Synlett  1998,  1069 
• 13b Diaz-Ortiz A. Carillo JR. Cossio FP. Gomez-Escalonilla MJ. De la Hoz A. Moreno A. Prieto P. Tetrahedron  2000,  56:  1569 

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Experimental Procedure for Preparation of Compound 4a. A solution of 1a (1.5 g, 6.10 mmol), and β-nitrostyrene (6.10 mmol) in benzene (60 mL) was heated at reflux for 30 h. The reaction mixture was then kept at r.t. for 15 h. A yellow solid was obtained which was removed, washed with chloroform and petroleum ether repeatedly several times and dried to afford 4a as yellow crystals (51%): mp 249 °C. IR (KBr): 1615 (C=N) cm^-1. ¹H NMR (DMSO-d₆): δ = 8.25 (s, 1 H, H-7), 7.44 (m, 5 H, H-Ar.), 7.23 (t, J = 7.65 Hz, 2 H, H-3′ and H-5′), 6.95 (t, J = 7.65 Hz, 1 H, H-4′), 6.71 (d, J = 7.65 Hz, 2 H, H-2′ and H-6′), 5.97 (s, 1 H, H-5), 5.32 (m, 1 H, H-2), 4.23 (dd, J = 11.85 and 1.90 Hz, 1 H, H-3a), 3.97 (dd, J = 8.80 and 3.60 Hz, 1 H, OCH _2a), 3.93 (dd, J = 11.85 and 2.35 Hz, 1 H, H-3b), 3.22 (dd, J = 8.80 and 6.90 Hz, 1 H, OCH _2b). ¹³C NMR (DMSO-d₆): δ = 162.2 (C-8a), 157.9 (C-1′), 150.5 (C-1′′), 137.9 (C-7), 129.6 (C-3′ and C-5′), 129.1 (C-4′′), 129.0 (C-3′′ and C-5′′), 128.0 (C-2′ and C-6′), 127.0 (C-6), 121.3 (C-4′), 114.5 (C-2′′ and C-6′′), 77.6 (C-2), 67.1 (OCH₂), 58.0 (C-5), 45.9 (C-3). Anal. Calcd for C₁₉H₁₇N₃O₄: C, 64.95; H, 4.88; N, 11.96. Found: C, 65.03; H, 4.91; N, 12.07. X-ray Data: Yellow single crystal (0.40 × 0.15 × 0.10 mm³) of 4a was obtained by slow evaporation from methanol/chloroform (10/90) solution: monoclinic, space group P2₁/c, a = 15.577(5) Å, b = 5.855(1) Å, c = 18.970(3) Å, α = 90°, β = 102°, V = 1692.3(7) ų, Z = 4, δ (calcd) = 1.379 Mgm^-3, FW = 351.36 for C₁₉H₁₇N₃O₄, F(000) = 736.

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Supplementary X-ray crystallographic data of compound 4a (CCDC 177408): Cambridge Crystallographic Data Centre, University Chemical Lab, 12 Union Road, Cambridge,CB2 1EZ, UK; E-mail : [e-mail].

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