Diastereoselective One-Pot Synthesis of Succinimides Bearing a Chromone Unit

Abstract

A diastereoselective synthesis of highly substituted succinimide derivatives with chromone and carboxylic ester functionalities from 3-formylchromones, Meldrum’s acid, and alkyl isocyanides in the presence of alcohols in moderate to good yields is described.

Key words

formylchromone - isocyanide - Meldrum’s acid - succinimide

• References and Notes

• 1 Lin G.-J, Luo S.-P, Zheng X, Ye J.-L, Huang P.-Q. Tetrahedron Lett. 2008; 49: 4007
• 2 Banjac N, Trišović N, Valentic N, Ušćumlic G, Petrović S. Hem. Ind. 2011; 65: 439
• 3 Malikov VM, Yuldashev MP. Chem. Nat. Compd. 2002; 38: 358
• 4 Chan-Bacab MJ, Peña-Rodríguez LM. Nat. Prod. Rep. 2001; 18: 674
• 5 Ellis GP, Lockhart IM. The Chemistry of Heterocyclic Compounds, Chromenes, Chromanones, and Chromones . Vol. 31. Ellis GP. Wiley-VCH; Weinheim: 2007
• 6a Shaabani A, Yavari I, Teimouri MB, Bazgir A, Bijanzadeh HR. Tetrahedron 2001; 57: 1375
• 6b Shaabani A, Teimouri MB, Bijanzadeh HR. Russ. J. Org. Chem. 2004; 40: 976
• 6c Shaabani A, Teimouri MB, Bazgir A, Bijanzadeh HR. Mol. Diversity 2003; 6: 199
• 6d Teimouri MB, Akbari-Moghaddam P. Tetrahedron 2011; 67: 5928
• 7 Shaabani A, Teimouri MB. J. Chem. Res., Synop. 2003; 433
• 8 Yavari I, Sabbaghan M, Hossaini Z. Mol. Diversity 2007; 11: 1
• 9 Habibi A, Mousavifar L, Yavari I, Yazdanbakhsh MR. Monatsh. Chem. 2007; 138: 603
• 10 Yavari I, Sabbaghan M, Ghazanfarpour-Darjani M, Hossaini Z. J. Chem. Res. 2007; 392
• 11a Shaabani A, Soleimani E, Rezayan AH, Sarvary A, Khavasi HR. Org. Lett. 2008; 10: 2581
• 11b Shaabani A, Sarvary A, Soleimani E, Rezayan AH, Heidary M. Mol. Diversity 2008; 12: 197
• 12 Subba Reddy BV, Nilanjan Majumder N, Hara Gopal AV, Chatterjee D, Kunwar AC. Tetrahedron Lett. 2010; 51: 6835
• 13 Habibi A, Tarameshloo Z. J. Iran. Chem. Soc. 2011; 8: 287
• 14 Teimouri MB, Akbari-Moghaddam P, Golbaghi G. ACS Comb. Sci. 2011; 13: 659
• 15 General Procedure for the Synthesis of Alkyl-1-alkyl-4-(4-oxo-4H-chromen-3-yl)-2,5-dioxopyrrolidine-3-carboxylates 6A mixture of the appropriate 3-formylchromone 1 (1 mmol) and Meldrum’s acid (2, 1 mmol) was stirred in anhydrous CH₂Cl₂ (10 mL) for 3 h at r.t., and then alcohol 4 (1 mmol) followed by alkyl isocyanide 3 (1 mmol) was added at r.t. After complete conversion, as monitored by TLC using EtOAc–hexane (1:1) as eluent, the mixture was concentrated in vacuo, and the solid residue was washed with Et₂O and crystallized from CH₂Cl₂–hexane (1:3) to afford pure product 6. rac-2-Adamantyl (3R,4S)-1-Benzyl-4-(6-methyl-4-oxo-4H-chromen-3-yl)-2,5-dioxopyrrolidine-3-carboxylate (6i)White powder; mp 195–196 °C (melt.). IR (KBr): ν_max = 1783, 1709, 1646 (C=O), 1616 (C=C) cm^–1.¹H NMR (300.1 MHz, CDCl₃): δ = 1.49–2.06 (14 H, m, adamantyl), 2.45 (3 H, s, CH₃), 4.02 and 4.08 (2 H, AB-q system, ³ J _HH = 6.1 Hz, CHCH), 4.75 and 4.86 (2 H, AB-q system, ² J _HH = 14.4 Hz, PhCH₂ ), 5.00 (1 H, m, OCH), 7.26–7.94 (7 H, m, arom. H), 7.95 (1 H, d, ³ J _HH = 5.9 Hz, arom. H.), 7.96 (1 H, s, C=CHO). ¹³C NMR (75.5 MHz, CDCl₃): δ = 176.6, 174.9, 170.8, 166.8, 154.8, 154.6, 135.8, 135.6, 135.3, 128.6, 128.2, 127.8, 125.0, 123.4, 119.2, 118.0, 79.8, 52.0, 44.0, 43.2, 37.2, 36.3, 36.2, 31.8, 31.6, 31.5, 31.4, 27.0, 26.8, 21.0. Anal. Calcd (%) for C₃₂H₃₁NO₆ (525.59): C, 73.13; H, 5.94; N, 2.66. Found: C, 72.81; H, 5.97; N, 2.70.X-ray Data for 6iC₃₂H₃₁N₁O₆, M = 525.58 g·mol^–1, orthorhombic system, space group P212121, a =10.0889(19), b = 11.9344(19), c = 22.490(3) Å, V = 2707.9(8) ų, Z = 4, D _calcd= 1.289 g cm^–3, μ(Mo Kα)= 0.089 mm^–1, crystal dimension of 0.50 × 0.30 × 0.25 mm. The structure was solved by using SHELXS. The structure refinement and data reduction was carried out with SHELXL of the X-Step32 suite of programs.¹⁸ Crystallographic data for 6i have been deposited with the Cambridge Crystallographic Data Centre. Copies of the data can be obtained, free of charge, on application to The Director, CCDC 1019444, Union Road, Cambridge CB2 1EZ, UK. Fax: [phone] or e-mail: [e-mail]. rac-Dimethyl {1-(6-methyl-4-oxo-4H-chromen-3-yl)-2-oxo-2-[(1,1,3,3-tetramethylbutyl)amino]ethyl}malonate (5a)White powder; mp 198–201 °C (dec.). IR (KBr): ν_max = 3330 (NH), 1730, 1681, 1649 (C=O), 1621 (C=C) cm^–1. ¹H NMR (300.1 MHz, CDCl₃): δ = 0.83 (9 H, s, CMe₃), 1.29 (6 H, br s, CMe₂), 1.49 and 1.73 (2 H, AB-q system, ² J _HH = 14.8 Hz, CH₂), 2.43 (3 H, s,CH₃), 3.55 and 3.74 (6 H, 2 s, 2 OCH ₃), 4.25 (1 H, d, ³ J _HH = 12.4 Hz, CH) 4.58 (1 H, d, ³ J _HH = 12.4 Hz, CH), 6.40 (1 H, s, NH), 7.34 (1 H, d, ³ J _HH = 8.8 Hz, CH₃C=CHCH), 7.48 (1 H, dd, ³ J _HH = 8.8 Hz, ³ J _HH = 1.6 Hz, CH₃C=CHCH), 7.97 (1 H, s, C=CHO), 7.98 (1 H, s, CH₃C=CHC). ¹³C NMR (75.5 MHz, CDCl₃): δ = 177.0, 168.6, 167.9, 167.8, 154.3, 153.6, 135.5, 135.4, 125.2, 123.0, 119.6, 118.0, 55.2, 52.9, 52.9, 52.0, 51.4, 41.4, 31.4, 31.2, 29.1, 28.7, 20.9. Anal. Calcd (%) for C₂₅H₃₃NO₇ (459.53): C, 65.34; H, 7.24; N, 3.05. Found: C, 65.50; H, 7.24; N, 3.08.
• 16 Teimouri MB. Tetrahedron 2011; 67: 1837
• 17 Sato M, Ban H, Kaneko C. Tetrahedron Lett. 1997; 38: 6689
• 18 X-STEP32 Version 1.07b, X-ray Structure Evaluation Package. Stoe & Cie; Darmstadt: 2000