Synthesis and sequential diastereoselective incorporation of hydroxyl groups into hexahydrofuro[3,2-f]indolizin-7(2H)-one to give mono-, di- and tetra-hydroxyfuroindolizidines

Abstract

Dihydrofuro[2,3-f]indolizidinone obtained from biosourced reagents even at multigram-scale, was used as advanced building-block with up to five points of chemical diversification. This resulted in the sequential synthesis of a series...

Diastereoselective Synthesis of Tetrahydrofurano[2,3-g]indolizidines and 8-Aminoindolizidines from l-Asparagine

“…The crude product was purified by flash chromatography (silica gel, 1:2 hexane/EtOAc) to give 3-dibenzylaminosuccinimide 10 (1.10 g, 98%) as a white crystal. : Rf (1:2 hexane/EtOAc) 0.31; 1 H NMR (300 MHz, CDCl3) δ 9.31 (brs, 1H), 7.43-7.14 (m, 10H), 3.91 (dd, J = 9.0, 6.0 Hz, 1H), 3.81 (d, J = 13.5 Hz, 2H), 3.61 (d, J = 13.5 Hz, 2H), 2.61 (dd, J = 18.0, 6.0 Hz, 1H), 2.71 (dd, J = 18.0, 9.0 Hz, 1H); 13…”

“…The product was obtained without purification as N-pentenylsuccinimide 12 (994 mg, quantitative) as a green oil. Rf (4:1 hexane/EtOAc) 0.55; 1 H NMR (300 MHz, CDCl3) δ 7.49-7.17 (m, 10H), 5.78 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H), 5.08-4.94 (m, 2H), 3.91 (dd, J=9.0, 5.3 Hz, 1H), 3.82 (d, J= 13.4 Hz, 2H), 3.63 (d, J = 13.4 Hz, 2H), 3.50 (t, J = 7.4, 2H), 2.75 (dd, J = 18.6, 9.0 Hz, 1H), 2.60 (dd, J = 18.5, 5.3 Hz, 1H), 2.10-2.00 (m, 2H), 1.65 (q, J = 7.4 Hz, 2H); 13…”

“…The crude product was purified by flash chromatography (silica gel, 4:1 hexane/EtOAc) to give N-(ethyl pentenoate)succinimide 14 (327 mg, 81%) as a yellow oil. Rf (2:1 hexane/EtOAc) 0.50; 1 H NMR (300 MHz, CDCl3) δ 7.55-7.12 (m, 10H), 6.82 (dt, J = 15.7, 7.1 Hz, 1H), 5.82 (dt, J = 15.6, 1.5 Hz, 1H), 4.05 (q, J = 7.2 Hz, 2H), 3.88 (dd, J = 8.9, 5.3 Hz, 1H), 3.77 (d, J = 13.5 Hz, 2H), 3.70-3.51 (m, 4H), 2.71 (dd, J = 18.6, 8.9 Hz, 1H), 2.58 (dd, J = 18.6, 5.4 Hz, 1H), 2.47 (q, J = 7.0 Hz, 2H), 1.18 (t, J = 7.1 Hz, 3H) ; 13 C NMR (75 MHz, CDCl3) δ 177.0, 174.9, 165.6, 143.9, 138.2 (2C), 128.8 (4C), 128.4 (4C), 127.4 (2C), 123.9, 60.…”

“…((2S)-2-(dibenzylamino)-3-oxo-1,2,3,5,8,8a-hexahydroindolizin-8-yl)methyl acetate (16): Rf (1:1 hexane/EtOAc) 0.33; 1 H NMR (300 MHz, CDCl3) δ 7.48-7.16 (m, 10H), 5.79 (ddd, J = 10.3, 5.9, 2.7 Hz, 1H), 5.60 (dd, J = 10.3, 2.2 Hz, 1H), 4.35 (ddd, J = 18.7, 5.7, 2.7 Hz, 1H), 4.10 (dd, J = 11.3, 5.6 Hz, 1H), 4.01 (dd, J = 11.2, 5.6 Hz, 1H), 3.90 (d, J = 13.7 Hz, 2H), 3.74-3.60 (m ,3H), 3.51 (ddd, J = 18.7, 4.7, 2.2 Hz, 1H), 3.37 (td, J = 9.1, 3.6 Hz, 1H), 2.33-2.14 (m, 2H), 2.11-1.98 (m, 4H); 13 To a solution of N-pentenylsuccinimide 12 (334 mg, 0.92 mmol) in CH2Cl2 (5 mL) under argon atmosphere at -78 °C was added DIBALH (1.84 mL of 1 M solution, 1.84 mmol) and the mixture was stirred for 2 hours at -78 °C. To this mixture was added dropwise MeOH (1 mL) and sat.…”

“…The product was obtained without purification to give hydroxylactam 18 (320 mg, 95%) as an orange oil. : Rf (2:1 hexane/EtOAc) 0.43; 1 H NMR (300 MHz, CDCl3) δ 7.52-7.13 (m, 10H), 5.78 (ddt, J = 16.9, 10.3, 6.6 Hz, 1H), 5.11-4.98 (m, 4H), 3.90 (d, J = 13.7 Hz, 2H), 3.71 (d, J = 13.7 Hz, 2H), 3.52 (dd, J = 9.5, 7.5 Hz, 1H), 3.43 (ddd, J = 13.7, 8.8, 6.8 Hz, 1H), 3.18 (ddd, J = 13.9, 8.7, 5.7 Hz, 1H), 2.50 (ddd, J = 14.1, 9.5, 6.8 Hz, 1H), 2.03 (q, J = 7.2, Hz, 2H), 1.74 (ddd, J = 14.1, 7.5, 4.4 Hz, 1H), 1.71-1.49 (m, 2H); 13…”