Short Synthesis of a Biphenyl-Based Amino Triflamide Catalyst and Its Application in Enamine Catalysis
Yuki Uwaso
a
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto, 606-8502, Japan
,
Naoki Yokoyama
b
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo, 184-8588, Japan
,
Taichi Kano∗
b
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo, 184-8588, Japan
› InstitutsangabenThis work was supported by the Japan Society for the Promotion of Science (JSPS KAKENHI, Grant Numbers JP18H01975, JP22H02073, and JP20H04815) in Hybrid Catalysis.
This paper is dedicated to Professor Hisashi Yamamoto on the occasion of his 80th birthday.
Abstract
A novel axially chiral biphenyl-based amino triflamide has been designed and successfully synthesized from 1-nitropyrene in 6 steps. This chiral amino triflamide functions as effective catalyst for asymmetric Mannich reaction through enamine intermediates.
16Typical Procedure for the Catalytic Asymmetric Mannich Reaction of N-PMP-Protected α-Iminoacetate 9
To a stirred solution of (S)-4 (0.9 mg, 0.0025 mmol) in dioxane (2.5 mL) were added an aldehyde (0.75 mmol) and ethyl (4-methoxyphenylimino)acetate 9 (48.9 μL, 0.25 mmol) in this order at room temperature. After being stirred at the same temperature, the reaction mixture was then quenched with a saturated aqueous NH4Cl solution and extracted with ethyl acetate. The combined organic extracts were dried over Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography on silica gel (hexane/ethyl acetate = 8:1 to 4:1) to give the corresponding Mannich adduct 10.
Ethyl (2S,3R)-3-Formyl-2-(p-methoxyphenylamino)heptanoate (10a)
Following the typical procedure, using hexanal (91.6 μL, 0.75 mmol) for 4 h gave the crude product. Purification by flash column chromatography gave the title compound (67 mg, 0.22 mmol, 87% yield, dr = 12:1, 91% ee).
1H NMR (500 MHz, CDCl3): δ = 9.65 (d, J = 2.5 Hz, 1 H), 6.80–6.76 (m, 2 H), 6.67–6.63 (m, 2 H), 4.26 (d, J = 6.0 Hz, 1 H), 4.18 (qd, J = 7.1, 3.0 Hz, 2 H), 3.74 (s, 3 H), 2.78–2.71 (m, 1 H), 1.79–1.68 (m, 1 H), 1.67–1.50 (m, 2 H), 1.44–1.28 (m, 3 H), 1.22 (t, J = 7.3 Hz, 3 H), 0.89 (t, J = 7.0 Hz, 3 H). HPLC analysis: Daicel CHIRALPAK IC-3, hexane/i-PrOH (19:1), 1.0 mL/min, λ = 254 nm, tmajor = 28.5 min, tminor = 39.0 min.
