Catalytic-Enantioselective Methoxycarbonylation of 1,3-Dichloroarenetricarbonyl-chromium(0) Complexes: A Desymmetrization Approach to Planar Chirality

Abstract

The Pd-catalyzed mono-methoxycarbonylation of pro­chiral 1,3-dichloroarene-Cr(CO)₃ complexes was investigated. In the presence of the chiral ferrocene ligand (R,S _P )-PPF-pyrrolidine the planar-chiral products were obtained with up to 90% ee (53% yield). A strong dependence of the enantioselectivity on the reaction time was observed. A kinetic study using η⁶-(2,6-dichlorotoluene)-Cr(CO)₃ revealed that the initial enantiomeric purity of the mono-methoxycarbonylated product is further enhanced due to a kinetic resolution (S = 4.3) connected to the formation of the bis-methoxycarbonylated side-product.

Key words

arene complexes - asymmetric catalysis - chromium - kinetic resolution - palladium.

References

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• 16b

  [α]₅₈₉ ²⁶ = -100.0 in CHCl₃ for pure ent- 6.

9

1a: Mp: 123 °C. ¹H NMR (CDCl₃, 250 MHz): δ = 5.17 (d,
2 H, J = 6.3 Hz), 5.48 (t, 1 H, J = 6.3 Hz), 5.59 (br s, 1 H). ¹³C NMR (CDCl₃, 63 MHz): δ = 87.2, 90.1, 91.9 (d), 113.3, 230.3 (s). 1b: Mp: 95 °C. ¹H NMR (CDCl₃, 250 MHz): δ = 2.48 (s, 3 H); 5.29-5.37 (m, 3 H). ¹³C NMR (CDCl₃, 63 MHz): δ = 17.3 (q), 89.5, 90.4 (d), 103.2, 113.4, 230.9 (s). 1c: Mp: 82 °C. ¹H NMR (CDCl₃, 250 MHz): δ = 3.95 (s, 3 H), 5.21-5.30 (m, 3 H). ¹³C NMR (CDCl₃, 63 MHz): δ = 65.8 (q), 87.7, 89.7 (d), 109.6, 131.9, 230.5 (s).

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Typical procedure: Complex 1b (148.5 mg, 0.5 mmol) and 5-PdCl₂ (16.2 mg, 0.025 mmol) were placed under argon in a flame-dried Schlenk flask equipped with a reflux condenser. Deoxygenated anhydrous methanol (3.3 mL) and triethylamine (1.7 mL) were added via a syringe and the reaction mixture was degassed and flushed with argon four times and finally flushed with CO. After stirring at 40 °C for 1 h the reaction mixture was cooled in an ice-bath, diluted with MTBE and filtered through a pad of silica. Upon concentration of the filtrate the received orange oil was sub-jected to column chromatography (silica, CyHex/MTBE =
8/1): 1b (10.3 mg, 7%), 2b (101.9 mg, 64%, orange oil) and 3b (39.2 mg, 23%, orange crystals).

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rac- 2a: Orange crystals. Mp: 76 °C. ¹H NMR (C₆D₆, 250 MHz): δ = 3.31 (s, 3 H), 4.19 (t, 1 H, J = 6.5 Hz), 4.62 (d, 1 H, J = 6.5 Hz), 5.18 (d, 1 H, J = 6.5 Hz), 5.83 (br s, 1 H).
¹³C NMR (C₆D₆, 63 MHz): δ = 52.5 (q), 90.1, 90.3 (d), 91.0 (s), 92.3, 92.6 (d), 109.8, 165.4, 230.5 (s). 3a: Orange crystals. Mp: 90 °C. ¹H NMR (CDCl₃, 250 MHz): δ = 3.88 (s, 6 H), 5.25 (t, 1 H, J = 6.6 Hz), 6.27 (dd, 2 H, J = 6.6 Hz, 1.1 Hz), 6.82 (br s, 1 H). ¹³C NMR (CDCl₃, 63 MHz): δ = 53.0 (q), 87.2 (d), 87.7 (s), 95.5 (d), 165.1, 228.3 (s). rac-2b: Orange-reddish oil. ¹H NMR (CDCl₃, 250 MHz): δ = 2.63 (s, 3 H), 3.88 (s, 3 H), 5.21 (t, 1 H, J = 6.5 Hz), 5.78 (dd, 1 H, J = 6.5 Hz, 0.8 Hz), 5.87 (dd, 1 H, J = 6.5 Hz, 0.8 Hz). ¹³C NMR (CDCl₃, 63 MHz): δ = 17.2, 53.0 (q), 87.5 (d), 91.8 (s), 93.8, 94.9 (d), 108.0, 109.7, 166.3, 230.2 (s). 3b: Orange crystals. Mp: 93 °C. ¹H NMR (CDCl₃, 250 MHz): δ = 2.69 (s, 3 H), 3.86 (s, 6 H), 5.12 (t, 1 H, J = 6.6 Hz), 6.18 (d, 2 H, J = 6.6 Hz). ¹³C NMR (CDCl₃, 63 MHz): δ = 17.8, 52.9 (q), 85.1 (d), 91.7 (s), 97.2 (d), 111.3, 166.2, 229.3 (s). rac- 2c: Orange-reddish oil. ¹H NMR (C₆D₆, 300 MHz): δ = 3.34 (s, 3 H), 3.58 (s, 3 H), 3.97 (t, 1 H), 4.87 (d, 1 H), 5.19 (d, 1 H). ¹³C NMR (C₆D₆, 75 MHz): δ 52.8, 64.7 (q), 86.5 (d), 89.0 (s), 92.5, 94.0 (d), 105.3, 137.9, 164.8, 230.8 (s). 3c: Orange crystals. Mp: 109 °C. ¹H NMR (CDCl₃, 250 MHz): δ = 3.89 (s, 9 H), 4.94 (t, 1 H, J = 6.3 Hz), 6.19 (d, 2 H, 6.3 Hz). ¹³C NMR (CDCl3, 63 MHz): δ = 53.0, 65.1 (q), 83.8 (d), 86.2 (s), 96.2 (d), 142.1, 164.6, 228.6 (s).

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Samples were taken from the reaction mixture in intervals of 15 min. After dilution with the HPLC eluent (i-propanol/n-hexane = 10:90) and filtration through Celite®, the mixtures were analyzed by HPLC (DAICEL Chiralcel OJ, external calibration).