Synlett, Table of Contents Synlett 2022; 33(07): 655-658DOI: 10.1055/s-0040-1719909 letter Synthesis of β-anti-Substituted α-Amino Acids through Iridium-Catalyzed Alkylation/Chelation-Controlled Nucleophilic Addition Panpan Wang a School of Petrochemical Engineering, Lanzhou Petrochemical University of Vocational Technology, Lanzhou 730060, P. R. of China b State Key Laboratory of Applied Organic Chemistry Department of Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China , Ruibo Zhao b State Key Laboratory of Applied Organic Chemistry Department of Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China , Jiaxiang Wang b State Key Laboratory of Applied Organic Chemistry Department of Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China , Xiaolei Wang∗ b State Key Laboratory of Applied Organic Chemistry Department of Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract An Ir/Ag dual-catalysis method has been developed for the synthesis of β-anti-substituted α-amino acids in high yields and with good enantioselectivities through a ligand/chelation-control strategy. By using this chiral-ligand-control strategy, a natural product for the regulation of a plant-growth hormone was synthesized on a gram scale in three steps. Key words Key wordsiridium catalysis - allylic carbonates - asymmetric catalysis - natural products - dual catalysis - amino acids Full Text References References and Notes 1a Yoshimura H, Takegami K, Doe M, Yamashita T, Shibata K, Wakabayashi K, Soga K, Kamisaka S. Phytochemistry 1999; 52: 25 1b Randazzo A, Bifulco G, Giannini C, Bucci M, Debitus C, Cirino G, Gomez-Paloma L. J. Am. Chem. 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ACS Catal. 2018; 8: 48 8 The absolute configuration of 4a was deduced from reports in the literature and confirmed through the synthesis of 6 and by comparing its optical rotation with that of the natural product. 9 When R1 = Ph, the diastereoselectivity dropped significantly. The phenyl group might have some unknown interaction with 1a. 10a Morimoto Y, Takaishi M, Kinoshita T, Sakaguchi K, Shibata K. Chem. Commun. 2002; 42 10b Spangenberg T, Schoenfelder A, Breit B, Mann A. Org. Lett. 2007; 9: 3881 11 Yu S, Pan X, Lin X, Ma D. Angew. Chem. Int. Ed. 2005; 44: 135 12 Srinivas K, Dangat Y, Kommagalla Y, Vanka K, Ramana CV. Chem. Eur. J. 2017; 23: 7570 13 tert-Butyl (2S,3S)-2-Amino-3-{[(4-methoxybenzyl)oxy] methyl}pent-4-enoate (4a); Typical Procedure [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol, 0.03 equiv), ligand (S,S,S)-L (6.4 mg, 0.012 mmol, 0.06 equiv), and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD; 2.8 mg, 0.02 mmol, 0.1 equiv) were dissolved in THF (0.5 mL) under N2, and the mixture was vigorously stirred at 50 °C for 30 min. The resulting dark-red solution was added to a mixture of 1a (88.5 mg, 0.30 mmol, 1.5 equiv), Ag2CO3 (5.5 mg, 0.02 mmol, 0.1 equiv), and DABCO (22.5 mg, 0.24 mmol, 1.2 equiv) in a screw-capped glass vial, affording a yellow solution. To this solution was added a solution of the allylic carbonate ester 2a (53 mg, 0.2 mmol, 1.0 equiv) in THF (0.5 mL). The vessel was purged with N2 and the resulting solution was stirred at r.t. for 8–12 h. The 1H NMR spectrum of the crude mixture was recorded to determine the diastereomeric ratio of the product. The mixture was then purified by flash chromatography to afford product 3a. The product diastereomers were not separable under these conditions. A 0.1 M solution of 3a (0.2 mmol) in 1:1 THF–H2O at r.t. was treated with 15% aq citric acid (5.0 mL), and the resulting mixture was stirred at r.t. until the starting material was completely consumed (TLC). The reaction was then quenched by addition of sat. aq NaHCO3, and the mixture was diluted with EtOAc. The organic phases were separated and the aqueous phase was extracted with EtOAc. The organic phases were combined, dried (Na2SO4), filtered, and concentrated under vacuum. The residue was purified by flash chromatography (silica gel, 10%~20% EtOAc/hexans) to give a colorless oil; yield: 62.9 mg (98%); ee 99%. SFC: AD-H column (5.0% i-PrOH–hexanes, 1 mL/min, λ = 200 nm, 25 °C); Rt = 11.48 min (major), 12.48 min (minor). 1H NMR (400 MHz, CDCl3): δ = 7.27 (d, J = 8.4 Hz, 2 H), 6.90–6.85 (m, 2 H), 5.73–5.61 (m, 1 H), 5.19–5.08 (m, 2 H), 4.52–4.41 (m, 2 H), 3.80 (s, 3 H), 3.65–3.57 (m, 2 H), 3.49 (dd, J = 9.3, 5.8 Hz, 1 H), 2.86 (tt, J = 8.7, 4.6 Hz, 1 H), 1.44 (s, 9 H). 13C{1H} NMR (75 MHz, CDCl3): δ = 174.3, 159.2, 133.8, 130.3, 129.3, 118.6, 113.8, 81.0, 72.8, 70.1, 55.2, 54.9, 46.9, 28.1. HRMS (ESI): m/z [M + H]+ calcd for C18H28NO4: 322.2013; found: 322.2012. Supplementary Material Supplementary Material Supporting Information
