The synthesis was performed according to the literature procedure:214 2,6-lutidine (114 g, 1.06 mol, 1.0 eq) was dissolved in 4 L of water and heated to 65 °C. KMnO4 (358g, 2.26 mol, 2.0 eq) was added over 6 hours and the mixture was stirred overnight at 65°C. The mixture was filtered with a Büchner apparatus and the MnO2 cake was washed with hot water (1 L). The solution was concentrated to 200 mL and it was acidified with a 6 M HCl aqueous solution. When pH approached 5 a white precipitate started to form, consistent with the protonation of the carboxylate moieties. After further acidification to pH = 3,3 toluene (200 mL) was added and a Dean Stark apparatus allowed to remove of water. KCl then precipitated. After complete water removal, the flask was disconnected from the apparatus and two portions of 100 mL boiling toluene were added (use appropriate safety conditions!) which the 6-methyl-2-picolinic acid dissolves. It was filtered with a Büchner apparatus and the KCl with the dipicolinic acid were removed this way. Cooling the filtrate lead to precipitation of the II and a complete evaporation of the volatile allowed the isolation of a pure white powder (50 g, 0.36 mol).
1H NMR (300 MHz, CDCl3): 10.21 (br, 1H) 8.03 (d, 3J = 7.62 Hz, 1H) 7.83 (t, 3J = 7.62 Hz, 1H) 7.43 (d, 3J = 7.62 Hz, 1H) 2.62 (s, 3H)
The synthesis was performed according to the literature procedure:50 6-methyl-2-picolinic acid (50 g, 0.36 mol) was dissolved in 300 mL MeOH (excess) and a dropwise addition of 50 mL of H2SO4
(95-98%) at room temperature led to formation of a white precipitate that redissolved upon heating. The solution was refluxed 12 hours. The solution was diluted with cold water (300 mL) and it was neutralized with K2CO3. Water (1 L) was added and the mixture was transferred in a separatory funnel. The compound was extracted with three portions of 300 mL methylene chloride. The fractions were collected and dried over MgSO4. After filtration the solvent was removed to afford III as a pure light-yellow oil (47 g, 0.31 mol).
1H NMR (300 MHz, CDCl3): 7.94 (d, 3J = 7.62 Hz, 1H) 7.71 (t, 3J = 7.62 Hz, 1H) 7.34 (d, 3J = 7.62 Hz, 1H) 3.99 (s, 3H) 2.65 (s, 3H)
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The synthesis was performed according to the literature procedure:50 the reaction was carried out under argon atmosphere. NaOMe (21.7 g, 0.32 mol) was suspended in a mixture of dry EtOAc (150 mL) and toluene (75 mL) and the color of the mixture was orange. A dropwise addition of methyl-6-metyl-2-picolinate (30 g, 0.20 mol) during 90 min led to dissolution of NaOMe with a colour change to red. The solution was refluxed overnight. An orange precipitate formed, and the solution was yellow-orange. The toluene was removed under vacuum and then 68.5 mL of H2SO4 (95-98 %) diluted in 335 mL of distilled water was added directly to the orange residue.
Gas started to form consistent with the elimination of CO2 from the reaction. The reaction mixture was refluxed for 12 hours. Then it was poured onto ice (200 mL) and neutralized with K2CO3. After addition of water (300 mL), the compound was extracted with three portions of methylene chloride (200 mL). The organic layers were combined and dried over MgSO4. After filtration, the solvent was removed, and IV was obtained as a brown pure oil (24 g, 0.18).
1H NMR (300 MHz, CDCl3): 7.83 (d, 3J = 7.72 Hz, 1H) 7.69 (t, 3J = 7.72 Hz, 1H) 7.31 (d, 3J = 7.72 Hz, 1H) 2.71 (s, 3H) 2.61 (s, 3H)
The synthesis was performed according to the literature procedure:50 the reaction was carried out under argon atmosphere. NaOMe (16 g, 0.24 mol) was suspended in 200 mL dry toluene and the ester III (25.8 g, 0.17 mol) was added to the suspension via syringe. The solution was orange and a slow dropwise addition at room temperature of the IV (24 g, 0.17 mol) diluted in dry toluene (200 mL) changed the colour of the solution to dark orange-red. After addition it was stirred for 12 hours at room temperature and then 18 hours at 70°C. The toluene was then removed under vacuum and 200 mL of an aqueous CH3COOH solution (100 mL CH3COOH (99.5 %) in 100 mL H2O) was added. A light orange precipitate formed. It was filtered with a Büchner apparatus, washed with portions of water and dried under vacuum overnight. NMR of the V was recorded before the next reaction step.
1H NMR (300 MHz, CDCl3): For the enol A: 16.02 (br, 1HA) 7.95 (br, 1HA) 7.73 (d, 3J = 7.75 Hz, 2HA) 7.73 (t, 3J = 7.75 Hz, 2HA) 7.29 (d, 3J = 7.75 Hz, 2HA) 2.66 (d, 6HA). For the diketone B: 7.87 (d, 3J = 7.72 Hz, 2HB) 7.68 (t, 3J = 7.72 Hz, 2HB) 7.24 (d, 3J = 7.72 Hz, 2HB) 4.83 (s, 2HB) 2.40 (s, 6HB)
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The synthesis was performed according to the literature procedure:50 the residue of the previous reaction was suspended in EtOH and 65 % NH2NH2 (25 mL, 3 eq) was added whereby the solution turned deep red. After 15 min a precipitate was formed. The mixture was refluxed for 24 hours. The solvent was removed under vacuum and the residue was suspended in water. After Büchner filtration VI was obtained as a white powder (30.16g, 0.12 mol) that slowly becomes yellowish over days.
1H NMR (300 MHz, CDCl3): {10.0 - 8.00} (br, 1H) 7.68 (d, 3J = 7.57 Hz, 2H) 7.62 (t, 3J = 7.57 Hz, 2H) 7.35 (s, 1H) 7.08 (d, 3J = 7.57 Hz, 2H) 2.60 (s, 6H)
The synthesis was performed according to literature procedure:114 the reaction was carried out under argon atmosphere. Compound VI (2 g, 8.0 mmol) was dissolved in 20 mL dry THF. Then nBuLi 2.5 M in hexanes (8 mL, 2.5 eq) was dropwise added with a plastic syringe to the light-yellow solution at -78°C. After the addition of 1.0 equivalent of nBuLi, the solution turned dark deep red. The other 1.5 equivalent of nBuLi were added faster. When the addition was finished, the solution was allowed to warm up to room temperature whereby a red and white precipitate formed. After 2 hours stirring, the mixture was cooled down again to -78°C and (tBu)2PCl (1464 mg, 1 eq) was added in one portion with a syringe. The precipitate previously formed dissolved, giving a dark red solution. After the solution was allowed to return to ambient temperature, another light red precipitate formed in the following 20 minutes. It was stirred for two hours and then, the reaction was quenched with degassed water (20 mL) whereby the dark deep red coulour turned yellowish-orange. The mixture was transferred in a dropping funnel that was conditioned with argon in order to separate the two layers. The 20 mL organic phase was recovered in a 250 mL Schlenk and the solvent was removed under vacuum where the VII was obtained as an oxygen sensitive fluffy light-yellow powder (4.089 g, 7.59 mmol).
1H NMR (300 MHz, CO(CD3)2): 12.73 (br, 1H) {7.83 - 7.68} (br, 4H) 7.43 (s, 1H) 7.22 (d, 3J = 7.38 Hz, 1H) 7.01 (d, 3J = 7.17 Hz, 1H) 3.14 (d, 3J = 2.90 Hz, 2H) 2.54 (s, 3H) 1.18 (d, 3JH-P = 10.74 Hz, 18H)
31P NMR (121 MHz, CO(CD3)2): 36.21 (br)
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The synthesis was performed according to literature procedure:114 The reaction was carried out under argon atmosphere. Compound VII (4089 mg, 7.59 mmol) was dissolved in 20 mL dry THF. tBuLi 1.9 M in pentane (10 mL, 2.5 eq) were slowly added with a 24 mL plastic syringe at
−45°C. After 1 eq tBuLi was added, the light-yellow solution turned dark deep red. After the rest of tBuLi was added, it was stirred at −45°C for 6 hours and 12 additional hours at ambient temperature, whereby a red precipitate slowly formed. (tBu)2PCl (1.390 g, 1 eq) was added at
−78°C in one portion with a plastic syringe and the red precipitate dissolved. The dark deep red solution was allowed to warm up to room temperature and was stirred for 12 hours. After that it was quenched with degassed water, whereby the dark deep red colour turned to yellowish-orange.
The mixture was transferred in a dropping funnel that was used to separate the two layers. The organic phase was recovered in a Schlenk and the volatile were removed under vacuum. An orange-red solid was obtained and was dried under vacuum for 6 hours. The orange solid was transferred in the glovebox. The solid was washed with two portions of 20 mL of dry Et2O and VIII was finally filtrated and isolated as a pure white powder (900 mg, 1.66 mmol).
1H NMR (300 MHz, CDCl3) : 11.07 (br, 1H) 7.81 (d, 3J = 7.81 Hz, 1H) 7.64 (t, 3J = 7.81 Hz, 2H) 7.46 (d, 3J = 7.81 Hz, 1H) 7.39 (d, 3J = 7.81 Hz, 1H) 7.33 (d, 3J = 7.81 Hz, 1H) 7.31 (s, 1H) 3.15 (d, 2JH-P = 3.28 Hz, 2H) 3.08 (d, 2JH-P = 3.28 Hz, 2H) 1.19 (d, 3JH-P = 11.02 Hz, 36H).
31P NMR (121 MHz, CDCl3): 37.77 (s) 36.60 (s).
ATR-IR (solid) (cm−1): 3440 (N-H), 1567 (C=N), 1551 (C=N).
ES1. ATR-IR (solid) of the ligand VIII.
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