New Efficient Synthesis of 1,2,4-Trisubstituted Furans by a ­Sequential Passerini/Wittig/Isomerization Reaction Starting from Baylis–Hillman β-Bromo Aldehydes

Abstract

A new and efficient synthesis of 1,2,4-trisubstituted furans from a Baylis–Hillman β-bromo aldehyde, an acid, an isocyanide, and methyl(diphenyl)phosphine, by a sequential Passerini condensation, Wittig reaction, and isomerization in the presence of triethylamine is reported.

Key words

Passerini reaction - Wittig reaction - Baylis–Hillman ­reaction - furans - isomerization

• References and Notes

• 1a Rotstein BH. Zaretsky S. Rai V. Yudin AK. Chem. Rev. 2014; 114: 8323
• 1b Dömling A. Wang W. Wang K. Chem. Rev. 2012; 112: 3083
• 2a Zhang J. Lin S.-X. Cheng D.-J. Liu X.-Y. Tan B. J. Am. Chem. Soc. 2015; 137: 14039
• 2b Ponra S. Nyadanu A. El Kaïm L. Grimaud L. Vitale MR. Org. Lett. 2016; 18: 4060
• 2c Yugandhar D. Kuriakose S. Nanubolu JB. Srivastava AK. Org. Lett. 2016; 18: 1040
• 2d Miranda LD. Hernández-Vázquez E. J. Org. Chem. 2015; 80: 10611
• 2e Wu R. Gao S. Chen X. Yang G. Pan L. Hu G. Jia P. Zhong W. Yu C. Eur. J. Org. Chem. 2014; 3379
• 3a Ma G.-H. Jiang B. Tu X.-J. Ning Y. Tu S.-J. Li G. Org. Lett. 2014; 16: 4504
• 3b De Moliner F. Bigatti M. Banfi L. Riva R. Basso A. Org. Lett. 2014; 16: 2280
• 3c Alcaide B. Almendros P. Aragoncillo C. Callejo R. Ruiz MP. J. Org. Chem. 2013; 78: 10154
• 3d Moni L. Banfi L. Basso A. Carcone L. Rasparini M. Riva R. J. Org. Chem. 2015; 80: 3411
• 3e Martinand-Lurin E. El Kaïm L. Grimaud L. Tetrahedron Lett. 2014; 55: 5144
• 3f Cordier M. Dos Santos A. El Kaïm L. Narboni N. Chem. Commun. 2015; 51: 6411
• 3g Martinand-Lurin E. Dos Santos A. El Kaïm L. Grimaud L. Retailleau P. Chem. Commun. 2014; 50: 2214
• 4 Alnabulsi S. Santina E. Russo I. Hussein B. Kadirvel M. Chadwick A. Bichenkova EV. Bryce RA. Nolan K. Demonacos C. Stratford IJ. Freeman S. Eur. J. Med. Chem. 2016; 111: 33
• 5 Ansari MF. Siddiqui SM. Ahmad K. Avecilla F. Dharavath S. Gourinath S. Azam A. Eur. J. Med. Chem. 2016; 124: 393
• 6 Yan L. Yan C. Qian K. Su H. Kofsky-Wofford SA. Lee W.-C. Zhao X. Ho M.-C. Ivanov I. Zheng YG. J. Med. Chem. 2014; 57: 2611
• 7 Vitale P. Tacconelli S. Perrone MG. Malerba P. Simone L. Scilimati A. Lavecchia A. Dovizio M. Marcantoni E. Bruno A. Patrignani P. J. Med. Chem. 2013; 56: 4277
• 8a Khaghaninejad S. Heravi MM. Adv. Heterocycl. Chem. 2014; 111: 95
• 8b Minetto G. Raveglia LF. Sega A. Taddei M. Eur. J. Org. Chem. 2005; 5277
• 9a Feist F. Ber. Dtsch. Chem. Ges. 1902; 35: 1537
• 9b Calter MA. Zhu C. Lachicotte RJ. Org. Lett. 2002; 4: 209
• 10a Zhou Q.-F. Zhang K. Cai L. Kwon O. Org. Lett. 2016; 18: 2954
• 10b Mal K. Das I. J. Org. Chem. 2016; 81: 932
• 10c Yang Y. Ni F. Shu W.-M. Wu A.-X. Tetrahedron 2014; 70: 6733
• 11a Manna S. Antonchick AP. Org. Lett. 2015; 17: 4300
• 11b Yu J.-T. Shi B. Peng H. Sun S. Chu H. Jiang Y. Cheng J. Org. Lett. 2015; 17: 3643
• 11c Lu B. Wu J. Yoshikai N. J. Am. Chem. Soc. 2014; 136: 11598
• 11d Rajesh M. Puri S. Kant R. Reddy MS. Org. Lett. 2016; 18: 4332
• 11e Shiroodi RK. Koleda O. Gevorgyan V. J. Am. Chem. Soc. 2014; 136: 13146
• 11f Hosseyni S. Su Y. Shi X. Org. Lett. 2015; 17: 6010
• 11g Lee E. Bang J. Kwon J. Yu C.-M. J. Org. Chem. 2015; 80: 10359
• 11h Li M. Kong X.-J. Wen L.-R. J. Org. Chem. 2015; 80: 11999
• 11i Matsui K. Shibuya M. Yamamoto Y. ACS Catal. 2015; 5: 6468
• 11j Lin M.-H. Kuo C.-K. Huang Y.-C. Tsai Y.-T. Tsai C.-H. Liang K.-Y. Li Y.-S. Chuang T.-H. Tetrahedron 2014; 70: 5513
• 12a Chen Z. Nieves-Quinones Y. Waas JR. Singleton DA. J. Am. Chem. Soc. 2014; 136: 13122
• 12b Ma J. Yuan Z.-Z. Kong X.-W. Wang H. Li Y.-M. Xiao H. Zhao G. Org. Lett. 2016; 18: 1450
• 12c Bruckner S. Bilitewski U. Schobert R. Org. Lett. 2016; 18: 1136
• 12d Chen L. Du Y. Zeng X.-P. Shi T.-D. Zhou F. Zhou J. Org. Lett. 2015; 17: 1557
• 13a Zhang K. Cai L. Jiang X. Garcia-Garibay MA. Kwon O. J. Am. Chem. Soc. 2015; 137: 11258
• 13b Lee C.-J. Chang T.-H. Yu J.-K. Reddy GM. Hsiao M.-Y. Lin W. Org. Lett. 2016; 18: 3758
• 13c Wang J. Yao J. Wang H. Chen H. Dong J. Zhou H. J. Org. Chem. 2016; 81: 5250
• 13d Saleh N. Voituriez A. J. Org. Chem. 2016; 81: 4371
• 14a Beck B. Magnin-Lachaux M. Herdtweck E. Dömling A. Org. Lett. 2001; 3: 2875
• 14b Beck B. Picard A. Herdtweck E. Dömling A. Org. Lett. 2004; 6: 39
• 15a Wang L. Ren Z.-L. Ding M.-W. J. Org. Chem. 2015; 80: 641
• 15b Wang L. Guan Z.-R. Ding M.-W. Org. Biomol. Chem. 2016; 14: 2413
• 15c Duan Z. Gao Y. Yuan D. Ding M.-W. Synlett 2015; 26: 2598
• 15d Yan Y.-M. Rao Y. Ding M.-W. J. Org. Chem. 2017; 82: 2772
• 16a Tang X. Zhang B. He Z. Gao R. He Z. Adv. Synth. Catal. 2007; 349: 2007
• 16b Reddy MV. R. Rudd MT. Ramachandran PV. J. Org. Chem. 2002; 67: 5382
• 17 1-(Aminocarbonyl)-3-aryl-2-(bromomethyl)prop-2-en-1-yl Esters 4; General Procedure The appropriate acid 2 (2 mmol) and isocyanide 3 (2 mmol) were added to a solution of the Baylis–Hillman β-bromo aldehyde 1 (2 mmol) in CH₂Cl₂ (4 mL), and the mixture was stirred at r.t. for 3 d until the reaction was complete (TLC). The solvent was removed under reduced pressure, and the residue was purified by flash chromatography [silica gel, EtOAc/PE (1:10)]. (2Z)-2-(Bromomethyl)-1-[(tert-butylamino)carbonyl]-3-(4-nitrophenyl)prop-2-en-1-yl Benzoate(4a) White solid; yield: 664 mg (70%); mp 118–120 °C. ¹H NMR (600 MHz, CDCl₃): δ = 8.24 (d, J = 7.2 Hz, 2 H, Ar-H), 8.13 (d, J = 5.4 Hz, 2 H, Ar-H), 7.62–7.51 (m, 5 H, Ar-H), 7.07 (s, 1 H, =CH), 6.27 (s, 1 H, NH), 6.03 (s, 1 H, CH), 4.26 (d, J = 10.8 Hz, 1 H, CH₂ ^a), 4.16 (d, J = 10.2 Hz, 1 H, CH₂ ^b), 1.41 (s, 9 H, 3CH₃). ¹³C NMR (150 MHz, CDCl₃): δ = 166.0, 164.5, 147.1, 141.5, 135.4, 133.9, 133.3, 129.8, 129.6, 128.7, 123.8, 75.8, 51.8, 28.5, 27.1. HRMS: m/z [M + H]⁺ calcd for C₂₂H₂₄BrN₂O₅: 475.0863; found: 475.0860.
• 18 CCDC 1545270 contains the supplementary crystallographic data for compound 6a. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 19 Trang TT. T. Peshkov AA. Jacobs J. Van Meervelt L. Peshkov VA. Van der Eycken EV. Tetrahedron Lett. 2015; 56: 2882
• 20 Lowry TH. Richardson KS. Mechanism and Theory in Organic Chemistry . Harper & Row; New York: 1987. 3rd ed. 486
• 21 Furans 5; General Procedure In an oven-dried flask, bromide 4 (1 mmol) and Ph₂MeP (0.20 g, 1 mmol) were dissolved in toluene (5 mL) at r.t. After two hours, the white phosphonium salt solid 11 formed. Without isolation of the phosphonium salt intermediate, NEt₃ (0.20 g, 2 mmol) was added and the mixture was stirred at reflux for 3–12 h until the reaction was complete (TLC). The solution was then concentrated under reduced pressure and the residue was purified by flash chromatography [silica gel, EtOAc/PE (1:12 to 1:1)]. N-(tert-Butyl)-3-(4-nitrobenzyl)-5-phenyl-2-furamide (5a) Light-yellow oil; yield: 309 mg (82%). ¹H NMR (600 MHz, CDCl₃): δ = 8.04 (d, J = 8.4 Hz, 2 H, Ar-H), 7.53 (d, J = 7.2 Hz, 2 H, Ar-H), 7.39–7.23 (m, 5 H, Ar-H), 6.37 (s, 1 H, furan-4-H), 6.21 (s, 1 H, NH), 4.31 (s, 2 H, CH₂), 1.43 (s, 9 H, 3CH₃). ¹³C NMR (150 MHz, CDCl₃): δ = 158.8, 153.5, 147.9, 146.4, 142.0, 130.1, 129.5, 129.2, 128.7, 128.6, 124.3, 123.6, 109.0, 51.4, 31.3, 29.0. HRMS: m/z [M + H]⁺ calcd for C₂₂H₂₃N₂O₄: 379.1652; found: 379.1653.