Design of Y-Shaped Trimers of Chiral Phase-Transfer Catalysts for the Asymmetric Alkylation of Amino Acid Derivatives
Shengyu Yu
a
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, P. R. of China
,
Jiahao Liu
a
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, P. R. of China
,
Zhe Wang
a
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, P. R. of China
,
Terumasa Kato
a
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, P. R. of China
b
Guangdong Provincial Key Laboratory of Plant Resouces Biorefinery, Guangdong University of Technology, Guangzhou, 510006, P. R. of China
c
Laboratory of Organocatalytic Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan
,
Yan Liu∗
a
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, P. R. of China
b
Guangdong Provincial Key Laboratory of Plant Resouces Biorefinery, Guangdong University of Technology, Guangzhou, 510006, P. R. of China
,
Keiji Maruoka∗
a
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, P. R. of China
b
Guangdong Provincial Key Laboratory of Plant Resouces Biorefinery, Guangdong University of Technology, Guangzhou, 510006, P. R. of China
c
Laboratory of Organocatalytic Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan
› Author AffiliationsWe are grateful for the financial support from the National Natural Science Foundation of China (Nos. 21977019, 22101053, 22050410279, 22250710134), the Guangdong Provincial Key Laboratory of Plant Resources Biorefinery (2021B1212040011), and the Japan Society for the Promotion of Science (JSPS KAKENHI, Grant JP21H05026).
Dedicated to the 80th birthday of Prof. Hisashi Yamamoto
Abstract
A series of soluble Y-shaped trimers of chiral phase-transfer catalysts were synthesized and utilized in the asymmetric alkylation of amino acid Schiff bases. The length of the linker between the ammonium cation of the simplified Maruoka catalyst and a phloroglucinol moiety was varied and excellent yields and enantioselectivity were observed when using the Y-shaped trimer of chiral phase-transfer catalyst with an octamethylene linker. A theoretical study of the most efficient Y-shaped trimer of chiral phase-transfer catalyst suggests the chiral ammonium center of the catalyst is more exposed and thus more available in the reaction.
6General Procedure for the Asymmetric Benzylation of Glycine Schiff Base Using Chiral PTCs
To a solution of chiral PTC (1 mol%) and N-(diphenylmethylene)glycine tert-butyl ester (5, 88.6 mg, 0.30 mmol) in toluene (1.0 mL)/50% KOH aqueous solution (1.0 mL) was added benzyl bromide (61.6 mg, 0.36 mmol) at 0 °C. The reaction mixture was stirred vigorously at the same temperature for 3-9 h. The resulting mixture was poured into ice-cooled water and extracted with CH2Cl2. The organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (eluted with AcOEt/hexane = 1:50) to give product 6.
tert-Butyl (R)-2-[(Diphenylmethylene)amino]-3-phenylpropanoate (6)1H NMR (400 MHz, CDCl3): δ = 7.50-7.47 (m, 2 H), 7.25-7.13 (m, 6 H), 7.08-7.03 (m, 3 H), 6.96-6.94 (m, 2 H), 6.51 (d, J = 6.4 Hz, 2 H), 4.03 (dd, J = 9.2, 4.4 Hz, 1 H), 3.17-3.04 (m, 2 H), 1.36 (s, 9 H), 13C NMR (100 MHz, CDCl3): δ = 170.9, 170.4, 139.6, 138.4, 136.5, 130.2, 130.0, 128.8, 128.3, 128.2, 128.1, 128.0, 127.8, 126.3, 81.2, 68.0, 39.7, 28.1. The enantiomeric excess of compound 6 was determined by chiral HPLC analysis using Daicel Chiralcel OD-H, hexane/2-propanol = 99:1, flow rate 0.5 mL/min, λ = 254 nm, retention time: 13.2 min (R) and 18.9 min (S).
7a
Seibert J,
Bannwarth C,
Grimme S.
J. Am. Chem. Soc. 2017; 139: 11682