Upgrading furanic platforms to α-enaminones: tunable continuous flow hydrogenation of bio-based cyclopentenones

Abstract

Continuous flow hydrogenation of trans-4,5-diamino cyclopentenones to diamino cyclopentanones and base-promoted elimination originates α-enaminones. The strategy is applied to the short synthesis of reported ATP-sensitive potassium channel agonist.

Preparation of Aminals under Continuous Flow Conditions

“…Additional experiments may be performed, such as ICP-MS to evaluate the copper leaching. Under similar conditions, a slight copper leaching was observed, which may promote discussion on what impact this may have on the long-term reuse of the system. , …”

“…Under similar conditions, a slight copper leaching was observed, which may promote discussion on what impact this may have on the longterm reuse of the system. 55,56 The student teams were able to achieve moderate to good yields (Table 1). An overall average yield of 73% was obtained, with the best yields being obtained using the silica with 40−63 μm particle size.…”

High-Pressure Promoted Nazarov-like Electrocyclization Enables Access to trans-4,5-Diamino-cyclopent-2-enones Bearing Electron-Poor Anilines

“…We have recently reported the preparation of an ATPsensitive potassium (K ATP ) channel agonist from the reduction of bis(2,2-dimethyl-6-nitro-2,3-dihydro-4H-benzo[b] [1,4]oxazin-4-yl)cyclopentenone. 23 Surprisingly, the synthesis of DCP 1 under classical conditions at atmospheric pressure, namely, 10 mol % Cu(OTf) 2 in water and 10 mol % Sc(OTf) 3 in acetonitrile, failed to afford any product. Solely increasing Sc(OTf) 3 to 60 mol % allowed the isolation of DCP 1 in only 5% yield.…”

“…1 H NMR (300 MHz, CDCl 3 ): δ 7.63 (dd, J = 6.3, 2.0 Hz, 1H), 7.39−7.35 (m, 4H), 6.71− 6.68 (m, 2H), 6.57−6.52 (m, 3H), 5.25 (dt, J = 4.1, 2.2 Hz, 1H), 4.36 (d, J = 3.8 Hz, 1H), 2.91 (s, 3H), 2.86 (s, 3H) ppm. 23 HRMS: calcd for C 21 H 18 F 6 N 2 O [M + H] + , 429.1410 m/z; found, 429.1402 m/z. FT-IR: 1705 cm −1 (C�O stretching); 1105 and 1066 cm −1 (C−F stretching).…”

“…1 H NMR (300 MHz, CDCl 3 ): δ 7.61 (dd, J = 6.3, 2.1 Hz, 1H), 7.50 (dd, J = 8.7, 2.4 Hz, 2H), 7.41 (d, J = 2.5 Hz, 1H), 7.16 (br s, 1H), 6.77 (d, J = 8.8 Hz, 2H), 6.65 (dd, J = 6.4, 2.0 Hz, 1H), 5.40 (br s, 1H), 4.50 (br s, 1H), 3.15 (m, 2H), 3.01 (dd, J = 11.3, 6.5 Hz, 2H), 1.46−1.36 (m, 12H) ppm. 23 Synthesis of DCP 1 at 900 MPa. Furfural (86 μL, 1.04 mmol, 1 equiv) was dissolved in dry MeCN (3,5 mL, 0.3 M) and placed in a Teflon vial containing Sc(OTf) 3 (51 mg, 0.1 mmol, 10 mol %).…”