Methylene-Bridged Bis(imidazoline)-Derived 2-Oxopyrimidinium Salts as Catalysts for Asymmetric Michael Reactions

A series of 2-oxopyrimidinium chlorides is prepared and their utility as chiral catalyst for the asymmetric Michael reaction is demonstrated.


Synthesis of diamines 8
General procedure: 1. Deprotection. Freshly distilled acetyl chloride (5 mol equiv.) was added dropwise to dry MeOH (110 mL per 35 mmol of 7) at 0-5 °C and the solution was stirred for 5 min at 5 °C. The corresponding amide 7 (1 mol equiv.) was then added in portions, the mixture was allowed to reach r.t., and stirred for 24 h. The solvent was removed under reduced pressure; the oily residue was triturated with dry ether and dried in high vacuum to afford the corresponding hydrochlorides 7' in quantitative yields as colorless viscous glasses or white hydroscopic solids which were used for reduction without further purification.

Preparation of chiral bis-imidazoline hydrochlorides 10
General procedure: A mixture of diiminoester dihydrochloride 9 (1 mol equiv.) and the corresponding diamine 8 (2.1 mol equiv.) in dry CH 2 Cl 2 (5 mL per 1 mmol of 9) was stirred for 24-120 h at r.t. or refluxed (monitored by 1 H NMR) under an atmosphere of dry Ar or N 2 . Once completed, the reaction mixture was diluted with CH 2 Cl 2 (20 mL) and the organic extract washed with brine (20 mL). The organic phase was separated, and the aqueous phase was extracted with CH 2 Cl 2 (20 mL). The combined organic phases were washed with brine (10 mL), dried over MgSO 4 and concentrated to dryness under reduced pressure to afford pure salts 10 as white or pale-yellow solids. In some cases further recrystallization of the prepared material from suitable solvents or solvents mixtures was required.
The organic phase was separated; the aqueous phase was extracted with CH 2 Cl 2 (30 mL). The combined organic phases were washed with water (20 mL), dried over MgSO 4 and concentrated to dryness under reduced pressure to provide the corresponding free bases quantitatively as white solids.
The corresponding free MBI base was then dissolved in dry CH 2 Cl 2 (10 mL per 1 mmol) followed by the addition of NEt 3 (3.0 mol equiv.) in one portion. The resulting solution was cooled down to 0 °C under the atmosphere of dry N 2 followed by dropwise addition of a solution of triphosgene (0.66 mol equiv.) in dry CH 2 Cl 2 (15 mL per 1 mmol of triphosgene). The reaction mixture was stirred for 0.5 h at 0 °C, further 2 h at r.t., and then quenched with 10% aq. NaOH (7 mol equiv.). After 10 min of vigorous stirring at r.t., the solvent was evaporated to dryness in vacuo (12 mbar), the solid residue was dissolved in CH 2 Cl 2 (2×20 mL) and the resulting solution was washed with brine (10 mL

S47
Optimization of the reaction conditions for the addition of chalcones