β-Isocupreidine-Catalyzed Asymmetric Baylis−Hillman Reaction of Imines

Abstract

[reaction: see text] beta-Isocupreidine (beta-ICD)-catalyzed asymmetric Baylis-Hillman reactions of aromatic imines with 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) give (S)-enriched N-protected-alpha-methylene-beta-amino acid esters. In contrast to the corresponding aldehydes, imines show the opposite enantioselectivity. A mechanistic proposal governed by hydrogen bonding is presented.

Total Synthesis of Biologically Active Natural Products Based on Highly Selective Synthetic Methodologies

“…14) As can be seen in Chart 4, β-ICD-catalyzed reactions of aromatic N-(diphenylphosphinoyl) imines 10 gave N-diphenylphosphinoyl-α-methylene-β-amino acid esters 11 in moderate to good yields and enantioselectivities. Fortunately, the products were Susumi Hatakeyama crystalline and the optical purity was enriched to >93% ee by simple recrystallization.…”

Synthesis of an Enantiocomplementary Catalyst of β‐Isocupreidine (β‐ICD) from Quinine

“…To a stirred solution of 8 (13.91 g, 31.7 mmol) in THF (40 mL) at À 40 8C was added dropwise thexylborane-THF, freshly prepared from BH 3 (1 M in THF, 220 mL, 220 mmol) and 2,3-dimethyl-2-butene (26.4 mL, 269 mmol). After being stirred at 0 8C for 16 h, the mixture was concentrated.…”

“…To a solution of the oxime in pyridine (20 mL) was added acetic anhydride (6 mL, 63.5 mmol) at 0 8C and the mixture was stirred for 12 h. After removal of the pyridine, the residue was extracted with CH 2 Cl 2 , washed with 10% Na 2 CO 3 and brine, dried, and concentrated. Purification of the residue by column chromatography on silica gel (CHCl 3 (3S,8S,9R,10S)-9-(tert-Butyldimethylsilyloxy)-10,11-dihydro-10-hydroxy-6'-methoxycinchonan-5-one (15) To a solution of 14 (933 mg, 1.64 mmol) in acetone (30 mL) was added aqueous TiCl 3 (1.3 M, 2.91 mL, 3.78 mmol) at room temperature and the mixture was stirred for 3 h. After the reaction was quenched with 10% K 2 CO 3 , the reaction mixture was stirred until it became a white suspension and filtered through a pad of Celite. The filtrate was extracted with CH 2 Cl 2 , washed with brine, dried, and concentrated.…”

“…[1] Recently, we have developed a highly enantioselective asymmetric Baylis-Hillman reaction of aldehydes [2] as well as imines [3] by use of b-isocupreidine (b-ICD) [4,5] as a chiral Lewis base catalyst and 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) as an activated alkene. In addition, we have successfully demonstrated the synthetic utility of this reaction via syntheses of biologically intriguing natural products.…”

Cinchona Alkaloid Derivatives as Chiral Organocatalysts

“…b-isocupreidine, allowed the reaction between 1,1,1,3,3,3-hexafluoroisopropylacrylate and aromatic imines 5 to proceed in good yield with high enantioselectivity. 6 Interestingly, the corresponding aldehyde substrates (the Baylis-Hillman reaction) gave products with the opposite configuration. 7 (C) Gaunt and co-workers have described a novel enantioselective organocatalytic synthesis of functionalised cyclopropanes 8 via intermediate ammonium ylides.…”