Novel Chiral C ₂-Symmetric Bisimidazole-N-Oxides as Promising Organocatalysts for Enantioselective Allylation of Aromatic Aldehydes

Abstract

A series of new, chiral Lewis bases containing imidazole-N-oxide moiety were tested for purposes of asymmetric catalysis. Bisimidazole-N-oxides derived from (1R,2R)- and (1S,2S)-trans-1,2-diaminocyclohexane were used as catalysts in the allylation reaction of aromatic aldehydes with allyltrichlorosilane, which yielded homoallyl alcohols in good yields and with enantioselectivity up to 80% ee. Screening of catalysts revealed that the type of substituents and their location in imidazole ring has a crucial influence on enantioselectivity of the addition process.

Key words

allylation - asymmetric catalysis - chiral imidazole-N-oxides - nucleophilic addition - organocatalysis

References and Notes

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8

Typical Procedure for the Preparation of Bisimidazole N -Oxides - Synthesis of (1 R ,2 R )-1d
To a stirred soln of (1R,2R)-trans-1,2-diamonocyclohexane (114.0 mg, 1.0 mmol) in MeOH (3 mL), a portion of paraformaldehyde (63.0 mg, 2.1 mmol) was added and the soln was stirred overnight at ambient temperature. After evaporation of the solvent in vacuum, the resulting, viscous oil was dissolved in glacial acid (7 mL) containing 473 mg (2.1 mmol₎ α-benzil monoxime 3d and the soln obtained thereby was stirred overnight at ambient temperature. Next day, a gentle stream of gaseous HCl was bubbled through the soln for ca. 1.5 h, and the separated colorless bisimidazole N-oxide hydrochloride was filtered off and dried in vacuum exsiccator. The crude hydrochloride was suspended in MeOH (ca 25 mL) and 1 g of the solid NaHCO₃ was added; stirring was continued for ca.1.5 h until evolution of CO₂ was complete. Precipitated solid of inorganic salts was filtered off, and the filtrate was evaporated to dryness. The colorless solid material was triturated with a little portion (ca. 5 mL) of a CHCl₃-MeOH (2:1) mixture. Suspended, solid material was separated, and the filtrate was evaporated to dryness. Crude product was washed with little amount of dry acetone to yield analytically pure sample of (1R,2R)-trans-1,1′-(cyclohexane-1,2-diyl)bis(4,5-diphenylimida-zole)-3,3′-dioxide [(R,R)-1d]; yield 342 mg (62%); colorless crystals; mp(dec) 208-210 ˚C. IR (KBr): ν = 3424-2867 (vs, br), 1635 (m), 1570 (m), 1506 (m), 1484 (m), 1446 (m), 1405 (m), 1339 (s), 1222 (m), 1193 (m), 767 (s), 711 (s), 658 (m), 636 (m) cm^-¹. ^¹H NMR (CD₃OD): δ = 8.08 [s, 2 H, HC(2), HC(2′) imidazole], 7.65-7.50 (m, 4 H, 4 arom. H), 7.38-7.23 (m, 12 H, 12 arom. H), 7.18-7.07 (m, 4 H, 4 arom. H), 4.37-4.26 (m, 2 H, 2CH, cHex), 2.38-1.40 (m, 8 H, 4CH₂, cHex). ^¹³C NMR (CD₃OD): δ = 131.8, 131.4, 131.2, 130.8, 129.9, 129.7 [6 d, 20 arom. CH, C(2), C(2′) imidazole], 131.0, 129.6, 127.3 [3 s, 4 arom. C, C(4), C(4′), C(5), C(5′) imidazole], 61.4 (d, 2 CH, cHex), 34.0, 25.3 (2 t, 4 CH₂, cHex). ESI-MS: m/z = 575 (100) [M + Na]⁺. ESI-HRMS:
m/z calcd for C₃₆H₃₂N₄O₂Na [M + Na]⁺: 575.2423; found: 575.2422. [α]_D ^²0 +6.0 (c 1.02; MeOH). For X-ray structure determination of (1R,2R)- and (1S,2S)-1d, see: Mloston G., Mucha P., Tarka R., Urbaniak K., Linden A., Heimgartner H.; Polish J. Chem.; 2009, 83, 1105.

12

General Allylation Procedure
To a stirred soln of the catalyst 1d (27.7 mg, 0.05 mmol) in dry CH₂Cl₂ (1 mL) the corresponding aldehyde 4 (0.5 mmol) and dry diisopropylethylamine (260 µL, 1.5 mmol) were added. After 5 min. magnetic stirring at 0 ˚C, allyltrichloro-silane (90-95 µL, 0.6 mmol) was added to the reaction mixture. Stirring was continued at 0 ˚C for another 20 h, and after this time the mixture was firstly diluted with Et₂O, quenched with aq NaHCO₃ (1 mL) and next shaken with H₂O. Organic layer was separated and the aqueous soln was extracted again with Et₂O (2 × 10 mL); combined ethereal soln were dried over MgSO₄, filtered, and concentrated. The residue was purified by silica gel column chromatography. Yields refer to the isolated amount of alcohol 5. The ee was determined using HPLC technique with chiral column (Chiralcel OD-H or Chiralpak AS-H); mixture of 2-PrOH-hexane was applied as an eluent.