(+)-2,2'-Methylenebis[(3aR,8aS)-3a,8a-dihydro-8H-indeno[1,2-d]oxazole]

Chemical Properties

White powder

Uses

[3aR-[2(3′aR*,8′aS*),3′aβ,8′aβ]]-(+)-2,2′-Methylenebis[3a,8a-dihydro-8H-indeno[1,2-d]oxazole] is a C₂ symmetric chiral ligand based on bis(oxazoline) moiety, which can be used in enantioselective catalysis. It easily forms bidentate coordination complexes due to the strong affinity of the oxazoline nitrogen for various metals. Copper complex of this chiral ligand can be utilized as a reusable catalyst in the cyclopropanation reaction between styrene and ethyl diazoacetate.

Synthesis

Malonylimide diethyl ester dihydrochloride (25.8 g, 0.112 mol, 1.0 eq.) and dimethylformamide (DMF) (320 mL) were added to a 3 L round bottom flask. The mixture was cooled in an ice bath. To the suspension was added (1R,2S)-1-amino-2-indanol (40 g, 0.268 mol, 2.4 eq.) in batches over 20 min. The ice bath was then removed and the reaction mixture was allowed to slowly warm up to room temperature, during which the reaction product gradually precipitated out of solution. After 4 days of continuous stirring at room temperature, a filtration operation was carried out. The resulting white solid was suspended in dichloromethane (CH2Cl2, 450 mL). Next, the mixture was washed sequentially with water (260 mL) and brine (260 mL). The organic layer was dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated to give an off-white solid. The solid was dried overnight under vacuum to give a final 23.9 g (65% yield) of the target product bis(oxazoline) (4). The product was characterized by 1H NMR (300 MHz, CDCl3): δ 7.45 (m, 2H, Ar-H); 7.27-7.21 (m, 6H, Ar-H); 5.56 (d, J = 7.9 Hz, 2H, N-CH); 5.34 (m, 2H, O-CH); 3.39 (dd, J = 7.0, 18.0 Hz, 2H, Ar- CHH); 3.26 (s, 2H, -CH2-O); 3.16 (dd, J = 18.0 Hz, 2H, Ar-CHH). The NMR data are in agreement with those reported in the literature WO 00/15599.

References

[1] Organic Letters, 2017, vol. 19, # 8, p. 2150 - 2153
[2] Journal of the American Chemical Society, 2018, vol. 140, # 1, p. 139 - 142
[3] Patent: WO2004/96764, 2004, A1. Location in patent: Page 38
[4] Organic Letters, 2006, vol. 8, # 3, p. 539 - 542