Synlett, Inhaltsverzeichnis Synlett 2017; 28(14): 1738-1742DOI: 10.1055/s-0036-1588503 cluster © Georg Thieme Verlag Stuttgart · New YorkBase-Induced Cyclisation of ortho-Substituted 2-Phenyloxazolines to Give 3-Aminobenzofurans and Related Heterocycles Authors Institutsangaben R. Alan Aitken * EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK eMail: raa@st-and.ac.uk Andrew D Harper EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK eMail: raa@st-and.ac.uk Alexandra M. Z. Slawin EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK eMail: raa@st-and.ac.uk Artikel empfehlen Abstract Artikel einzeln kaufen(opens in new window) Alle Artikel dieser Rubrik(opens in new window) Published as part of the ISHC Conference Special Section Abstract Treatment of ortho-benzyloxyphenyloxazolines with butyllithium and potassium tert-butoxide results in cyclisation with ring opening of the oxazoline to give 2-aryl-3-aminobenzofurans. The reaction also occurs with the corresponding benzylthio and benzylamino compounds to give benzothiophenes and indoles, respectively. Use of an ortho-allyloxyphenyloxazoline gives the corresponding 2-vinylbenzofuran, while both α-methylbenzyloxy and benzylsulfonyl compounds form stable spirooxazolidine products. The X-ray structure of an aminobenzothiophene product has been determined. Key words Key wordscyclisation - oxazoline - benzofuran - benzothiophene - indole - Schlosser’s base - spiro heterocycle Volltext Referenzen References and Notes 1 Reuman M. Meyers AI. Tetrahedron 1985; 41: 837 2 Gant TG. Meyers AI. Tetrahedron 1994; 50: 2297 3 Meyers AI. J. Org. Chem. 2005; 70: 6137 4 Typical Experimental Procedures A solution of 2-(benzyloxy)benzoic acid (10.00 g, 43.8 mmol) and thionyl chloride (6.4 mL, 10.44 g, 87.7 mmol) in toluene (90 mL) was heated under reflux for 3 h and then cooled and evaporated to give 2-(benzyloxy)benzoyl chloride (10.80 g, 100%) as a pale yellow oil which was used without further purification. This was dissolved in CH2Cl2 (40 mL) and added dropwise to a solution of 2-amino-2-methylpropan-1-ol (7.81 g, 87.6 mmol) in CH2Cl2 (50 mL) stirred at 0 °C. Once the addition was complete, the reaction mixture was allowed to warm to r.t. for 18 h before being poured into water. The two layers were separated and the aqueous layer was re-extracted with CH2Cl2 (2×). The combined organic layers were washed successively with 2 M HCl, 2 M NaOH, and water before being dried and evaporated to give the amide (12.68 g, 97%) as a colourless solid, mp 115–117 °C, which was used without further purification. SOCl2 (3.7 mL, 6.03 g, 50.7 mmol) was added to a solution of 2-(benzyloxy)-N-(1-hydroxy-2-methylpropan-2-yl)benzamide (12.68 g, 42.4 mmol) in CH2Cl2 (210 mL), and the reaction mixture was stirred at r.t. for 18 h. The mixture was washed with 2 M NaOH and water before being dried and evaporated to give, after purification by Kugelrohr distillation (185 °C/9.2 Torr), 1 (10.14 g, 85%) as a colourless oil which formed a low-melting solid on standing. IR: 1718, 1645, 1038, 967, 871, 848, 751, 733, 695 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.72 (dd, J = 7.5, 2.0 Hz, 1 H), 7.52 (d, J = 7.5 Hz, 2 H), 7.38–7.35 (m, 3 H), 7.29 (t, J = 7.3 Hz, 1 H), 7.01–6.97 (m, 2 H), 5.18 (s, 2 H, OCH2Ar), 4.11 (s, 2 H, oxazoline CH2), 1.41 (s, 6 H, CH3). 13C NMR (125 MHz, CDCl3): δ = 161.2 (C=N), 157.3 (C–O), 137.0 (C), 131.9 (CH), 131.1 (CH), 128.2 (2 CH), 127.5 (CH), 126.7 (2 CH), 120.6 (CH), 118.6 (C), 113.5 (CH), 78.8 (oxazoline CH2), 70.5 (OCH2Ar), 67.5 (C), 28.4 (CH3). HRMS (ESI+): m/z calcd for C18H20NO2 [M + H]+: 282.1489; found: 282.1478. Under a nitrogen atmosphere, n-BuLi (2.5 M in hexane, 6.6 mL, 16.5 mmol) was added to a stirred mixture of 2-[2-(benzyloxy)phenyl]-4,4-dimethyl-4,5-dihydrooxazole (1, 1.41 g, 5.01 mmol) and t-BuOK (1.88 g, 16.8 mmol) in dry THF (50 mL). The reaction mixture was stirred at r.t. for 2 h before being quenched by addition of sat. aq NH4Cl and extracted with Et2O (3×). The combined organic layers were dried and evaporated to give, after purification by column chromatography (Al2O3, gradient elution, Et2O/hexane 3:2 to EtOAc), 3 (1.13 g, 80%) as orange crystals, mp 59–63 °C. IR: 3325, 2974, 2933, 1605, 1452, 1362, 1256, 1043, 1026, 739, 694 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.08–8.05 (m, 2 H), 7.64–7.62 (m, 1 H), 7.46–7.41 (m, 3 H), 7.34–7.30 (m, 1 H), 7.29–7.25 (m, 1 H), 7.24–7.20 (m, 1 H), 3.42 (s, 2 H, CH2), 2.65 (br s, 2 H, NH and OH), 1.07 (s, 6 H, CH3). 13C NMR (125 MHz, CDCl3): δ = 153.0 (C), 148.5 (C), 131.1 (C), 129.5 (C), 128.5 (2 CH), 128.0 (CH), 126.5 (2 CH), 124.4 (CH), 122.5 (CH), 122.2 (C), 119.6 (CH), 111.2 (CH), 70.3 (CH2), 58.1 (C), 24.7 (CH3). HRMS (ESI+): m/z calcd for C18H20NO2 [M + H]+: 282.1489; found: 282.1482. 5 Baker RW. Hockless DC. R. Pocock GR. Sargent MV. Skelton BW. Sobolev AN. Twiss E. White AH. J. Chem. Soc., Perkin Trans. 1 1995; 2615 6 Yalcouye B. Berthelot-Bréhier A. Augros D. Panossian A. Choppin S. Chessé M. Colobert F. Leroux FR. Eur. J. Org. Chem. 2016; 725 7 Augros D. Yalcouye B. Berthelot-Bréhier A. Chessé M. Choppin S. Panossian A. Leroux FR. Tetrahedron 2016; 72: 5208 8 Gewald K. Jänsch H.-J. J. Prakt. Chem. 1973; 315: 779 9 Sarodnick G. Kempter GE. DD 292001, 1991 ; Chem. Abstr.; 1991, 115: 232294 10 Radl S. Hezky P. Urbánková J. Váchal P. Krejcí I. Collect. Czech. Chem. Commun. 2000; 65: 280 11 Radl S. Obadalova I. ARKIVOC 2005; (xv): 4 12 Yang J. Wangweerawong A. Dudley GB. Heterocycles 2012; 85: 1603 13 Meyers AI. Hanagan MA. Trefonas LM. Baker RJ. Tetrahedron 1983; 39: 1991 14 Poindexter GS. J. Org. Chem. 1982; 47: 3787 15 Hirano K. Satoh T. Miura M. Org. Lett. 2011; 13: 2395 16 Matsuda N. Hirano K. Satoh T. Miura M. J. Org. Chem. 2012; 77: 617 17 von Auwers K. Ber. Dtsch. Chem. Ges. 1916; 49: 820 18 Feng G. Wu J. Dai W.-M. Tetrahedron Lett. 2007; 48: 401 19 Raasch MS. J. Org. Chem. 1980; 45: 856 20 Crystal Data for 16 C18H19NOS, M = 297.41, colourless prism, crystal dimensions 0.20 × 0.20 × 0.20 mm, monoclinic, space group P21/c, a = 11.976(2), b = 12.4118(15), c = 20.997(3) Å, β = 95.825(6)°, V = 3105.0(8) Å3, Z = 8, Dc = 1.272 Mg m–3, T = 173 K, R1 = 0.0345, Rw2 = 0.0801 for 4529 reflections with I > 2σ(I) and 395 variables. Data were collected using graphite monochromated Mo Kα radiation, λ = 0.71075 Å and have been deposited at the Cambridge Crystallographic Data Centre as CCDC 1540330. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures. 21 Lee TD. Keana JF. W. J. Org. Chem. 1976; 41: 3237 22 Beck JR. J. Heterocycl. Chem. 1978; 15: 513 23 Carrington DE. L. Clarke K. Scrowston RM. J. Chem. Soc. C 1971; 3903 24 Beck JR. J. Org. Chem. 1972; 37: 3224 25 Beck JR. Yahner JA. J. Org. Chem. 1974; 39: 3440 26 Markert J. Hagen H. Liebigs Ann. Chem. 1980; 768 27 Kobayashi K. Yamashita K. Heterocycles 2017; 94: 772 28 Meyers AI. Gabel R. Mihelich ED. J. Org. Chem. 1978; 43: 1372 29 Seong CM. Park CM. Choi J. Park NS. Tetrahedron Lett. 2009; 50: 1029 Zusatzmaterial Zusatzmaterial Supporting Information (PDF)
