A Novel Dipeptide-Based Chiral Phosphine Organocatalyst for Asymmetric Cyclization

The dipeptide-based chiral phosphine (1), which was developed by Lu et al., is an efficient and versatile organocatalyst for the [3+2] and [4+2] asymmetric cyclizations of allenoates with unsaturated compounds.^1-3) For example, the [3+2] cyclization of allenoates with alkyl or arylimines proceeds in the presence of 5 mol% of 1, affording the reaction products in good yields and high enantioselectivities.¹⁾ Notably, 1 is stable in the air at room temperature.

Typical procedure (entry 1: R = CH₃CH₂CH₂-): To a dried round bottom flask is added N-butylidene-P,P-diphenylphosphinic amide (27.1 mg, 0.1 mmol), O-TBDPS-D-Thr-N-Boc-L-tert-Leu-diphenylphosphine (3.6 mg, 0.005 mmol) and MS5Å (60 mg) under N₂, followed by the addition of anhydrous Et₂O (1 mL). The reaction mixture is cooled to 0 ºC, tert-butyl 2,3-butadienoate (22 micro-L, 0.15 mmol) is then added, and the mixture is stirred at 0 ºC for 30 min. The reaction mixture is then filtered (to remove MS5Å) and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel (eluent: hexane/EtOAc = 10:1 to 2:1) to afford the cycloaddition product (37.9 mg, 92% yield, 96% ee) as a colorless oil.