Preparation method of 3-substituted 2-fluoro-1, 5-diene compound
A technology for compounds and target compounds, applied in the field of preparation of 2-fluoro-1,5-diene compounds, can solve the problems of low method versatility, cumbersome reaction operation, high toxicity of reagents, etc. Highly regioselective, wide-ranging effects
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[0044] The embodiments of the present application provide a method for preparing a 3-position substituted 2-fluoro-1,5-diene compound, the method comprising:
[0045]
[0046] where R 1 One or more selected from phenyl, naphthyl, heterocyclyl, benzoheterocyclyl, and metal organic compounds;
[0047] R 2 One selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C6 alkene, C3-C8 cycloalkyl, and phenyl;
[0048] The target compound (III) is obtained by reacting the geminal difluorocyclopropane compound (I) with the coupling agent allyl boronate compound (II) under the combined action of a catalyst and a ligand.
[0049] Further, using the geminal difluorocyclopropane compound (I) as a raw material, under the joint action of the catalyst and the ligand, react with the coupling agent allyl borate compound (II) to obtain the target compound (III), include:
[0050] The solvent is placed in a dry reaction vessel, and catalyst, ligand, base and compound (I) and compou...
Embodiment 1
[0072] Synthesis of Compound (Ia):
[0073]
[0074] Under nitrogen protection, anhydrous NaI (0.3 g, 2.0 mmol), anhydrous tetrahydrofuran (20.0 mL), TMSCF 3 (3.53 g, 25.0 mmol) and compound (Aa) (1.18 g, 10.0 mmol) were charged into a flame-dried reaction tube equipped with a magnetic stir bar; the reaction tube was sealed with a Teflon septum and stirred at 65°C for 12 hours After cooling the mixture to room temperature, it was directly filtered through a pad of celite, then evaporated to dryness under reduced pressure; the crude product was extracted with ethyl acetate (20.0 mL), saturated sodium thiosulfate (20.0 mL) and brine (10.0 mL) Washed; dried over anhydrous sodium sulfate, filtered and concentrated, and purified by silica gel column chromatography to obtain 1.43 g of pure compound (Ia) with a yield of 85%.
[0075] Synthesis of target compound (IIIa):
[0076]
[0077] In an oven-dried Schlenk tube, add THF (2 mL) followed by [Pd(allyl)Cl] 2 (3.7mg, 0.01mm...
Embodiment 9
[0091] Synthesis of target compound (IIIb):
[0092]
[0093] The preparation was carried out with reference to Example 1 to obtain 31.2 mg of the target compound (IIIb) as a colorless liquid with a yield of 67%.
[0094] In this embodiment of the present invention, refer to figure 2 , the hydrogen nuclear magnetic spectrum of the target compound (IIIb) provided in the embodiment of the present invention is as follows:
[0095] 1 H NMR (400MHz, CDCl 3 )δ7.39–7.34(m,2H),7.24–7.17(m,2H),5.76(ddt,J=17.0,10.2,6.9Hz,1H),5.17–5.00(m,2H),4.63(dd, J=17.6, 2.9Hz, 1H), 4.38 (dd, J=50.1, 2.4Hz, 1H), 3.48 (dt, J=18.5, 7.8Hz, 1H), 2.79–2.63 (m, 1H), 2.59–2.46 (m, 1H), 1.33 (s, 9H).
[0096] 13 C NMR (101MHz, CDCl 3 )δ167.4(d,J=260.4Hz),149.8,137.1,135.8,127.4,125.4,116.7,90.6(d,J=20.4Hz),48.2(d,J=25.4Hz),36.9(d,J = 3.4 Hz), 34.5, 31.4.
[0097] 19 F NMR (376MHz, CDCl 3 ) delta-99.55.
[0098] IR(film): 3079,2961,1691,1512,1152,856cm -1 .
[0099] HRMS m / z(ESI): calcd for ...
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