(S)-(-)- and (R)-(+)-4-Methyl-2-hydroxymethyl[2]paracyclo-[2](5,8)quinolinophane: Novel N,O-Planar Chiral Catalysts for the Enantioselective Addition of Diethylzinc to Aldehydes

Abstract

Novel planar chiral N,O-ligands derived from (R)-(+)- and (S)-(-)-2,4-dimethyl[2]paracyclo[2](5,8)quinolinophane were synthesized and employed as catalyst in the enantioselective addition of diethylzinc to aromatic aldehydes. On the basis of the ee values, ranging from 30% to 75%, and the configuration of the obtained 1-phenyl-1-propanols a plausible structure of the transition state for the alkylation process of the aldehydes is discussed.

Key words

amino-alcohols - cyclophanes - ligands - planar chirality - stereoselective additions - zinc

References

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11

(S)-(-)-1 [45% from (S)-(+)-2]. Mp 116-118 °C (from diethyl ether). [α]_D ²⁰ -16.0 (c 0.50, CHCl₃). ¹H NMR (CDCl₃, 400 MHz): δ = 6.93 (s, 1 H), 6.90 (d, J = 7.3 Hz, 1 H), 6.80 (d, J = 7.3 Hz, 1 H), 6.46 (s, 2 H), 5.72 (d, J = 7.8 Hz, 1 H), 5.46 (d, J = 7.8 Hz, 1 H), 4.93-4.80 (four peaks, AB system, J = 15.0 Hz, 2 H), 4.88 (br s, 1 H), 4.28-4.25 (m, 1 H), 3.84 (dd, J = 14.0 and 9.2 Hz, 1 H), 3.19-2.92 (m, 5 H), 2.68 (s, 3 H), 2.61-2.50 (m, 1 H). ¹³C NMR (CDCl₃, 100 MHz): δ = 155.0, 148.4, 144.3, 139.4, 138.8, 137.8, 137.3, 133.7, 132.8, 132.5, 131.3, 129.6, 128.2, 127.8, 119.8, 63.4, 37.6, 35.2, 34.4, 31.9, 22.8. IR: (CHCl₃) 3417 cm^-1(broad, OH). Anal. Calcd for C₂₁H₂₁NO: C, 83.13; H, 6.98; N, 4.62. Found: C, 83.20; H, 6.99; N, 4.54.

13

Typical Procedure. Diethylzinc (3.3 mL, 0.1 M in toluene, 3.3 mmol) was added by a syringe to a solution of [(S)-(-)-1] (20 mg, 0.066 mmol) in dry toluene (3 mL) under nitrogen at 20 °C and the mixture was allowed to react for 20 min. The aldehyde (0.66 mmol) was added and the mixture was made to react at 20 °C until it completely disappeared (monitored by GLC). Sat. aq NH₄Cl was added (10 mL) and the mixture was extracted with diethyl ether (3 × 20 mL). The collected organic phases were washed with water, dried over Na₂SO₄ and the solvent was evaporated. Preparative TLC on silica gel (eluent, petroleum ether/diethyl ether mixtures) allowed the corresponding 1-aryl-1-propanols to be isolated. The ee was determined by HPLC of the alcohols or their derivatives on different chiral columns depending on the structure of the alcohol by using hexane/isopropanol mixtures as the eluent.