Synlett, Table of Contents Synlett 2017; 28(18): 2483-2488DOI: 10.1055/s-0036-1589080 letter © Georg Thieme Verlag Stuttgart · New York Chiral Phosphinyl Enamines and Their Asymmetric Reduction through Group-Assisted Purification Chemistry Leading to Enantiopure β-Amino Esters/Amides Shuo Qiao a Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA Email: guigen.li@ttu.edu , Jianbin Wu a Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA Email: guigen.li@ttu.edu b Institute of Chemistry and Biomedical Sciences (ICBMS), Nanjing University, Nanjing 210093, P. R. of China , Junming Mo a Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA Email: guigen.li@ttu.edu , Preston T. Spigener a Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA Email: guigen.li@ttu.edu , Brian Nlong Zhao c Shanghai High School International Division, No. 989, Baise Road, Shanghai 200231, P. R. of China , Bo Jiang* a Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA Email: guigen.li@ttu.edu d School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou 221116, P. R. China Email: jiangchem@jsnu.edu.cn , Guigen Li* a Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA Email: guigen.li@ttu.edu b Institute of Chemistry and Biomedical Sciences (ICBMS), Nanjing University, Nanjing 210093, P. R. of China › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract A series of new chiral N-phosphinyl β-enamino esters and amides were successfully prepared with excellent Z-stereoselectivity (Z/E > 99:1 in nearly all cases). Group-assisted purification chemistry proved to be an efficient method for the asymmetric reduction of the resulting β-enamino esters/amides to give enantiopure β-amino esters/amides. The asymmetric reduction can be controlled efficiently by using a combination of sodium cyanoborohydride and acetic acid. Key words Key wordsgroup-assisted purification - asymmetric reduction - amino esters - amino amides - phosphinyl enamines Full Text References References and Notes 1a An G. Seifert C. Li G. Org. Biomol. Chem. 2015; 13: 1600 1b Zhang HW. Bing Y. Yang Z. Lu H. Li G. J. Org. Chem. 2016; 81: 7654 1c Seifert C. Pindi S. Li G. J. Org. Chem. 2015; 80: 447 2 Wu J. An G. Lin S. Xie J. Zhou W. Sun H. Pan Y. Li G. Chem. Commun. 2014; 50: 1259 3 Kaur P. Pindi S. Wever W. Rajale T. Li G. J. Org. Chem. 2010; 75: 5144 4 Pindi S. Kaur P. Shakya G. Li G. Chem. Biol. Drug Des. 2011; 77: 20 5a Yang B. Ji X. Xue Y. Zhang H. Shen M. Jiang B. Li G. Org. Biomol. Chem. 2016; 14: 6024 5b Yang B. Shen M. Ji X. Xu Z. Sun H. Jiang B. Li G. J. Org. Chem. 2016; 81: 2488 6 Kattamuri PV. Ai T. Pindi S. Sun Y. Gu P. Shi M. Li G. J. Org. Chem. 2011; 76: 2792 7a Wang H. Liu X. Feng X. Huang Z. Shi D. Green Chem. 2013; 15: 3307 7b Chennapuram M. Emmadi NR. Bingi C. Nanubolu JB. Atmakur K. Green Chem. 2014; 16: 3237 8a Abdel-Magid AF. Cohen JH. Maryanoff CA. Curr. Med. Chem. 1999; 6: 955 8b Li G. Kim SH. Wei H.-X. Tetrahedron Lett. 2000; 41: 8699 8c Chen DJ. Timmons C. Chao C. Li G. Eur. J. Org. Chem. 2004; 3097 8d Chen DJ. Timmons C. Wei H.-X. Li G. J. Org. Chem. 2003; 68: 5742 9a Davies SG. Dordor-Hedgecoch IM. Jones RH. Prout K. Tetrahedron 1986; 42: 5123 9b Liebeskind LS. Welker ME. Fengl RW. J. Am. Chem. Soc. 1986; 108: 6328 10 Hecht SM. Acc. Chem. Res. 1986; 19: 383 11 Seebach D. Matthews JL. Chem. Commun. 1997; 2015 12 Amézquita-Valencia M. Cabrera A. J. Organomet. Chem. 2014; 768: 145 13a Hsiao Y. Rivera NR. Rosner T. Krska SW. Njolito E. Wang F. Sun Y. Armstrong III JD. Grabowski EJ. J. Tillyer RD. Spindler F. Malan C. J. Am. Chem. Soc. 2004; 126: 9918 13b Zhang YJ. Park JH. Lee S.-g. Tetrahedron: Asymmetry 2004; 15: 2209 13c Dai Q. Yang W. Zhang X. Org. Lett. 2005; 7: 5343 13d Blot J. Bardou A. Bellec C. Fargeau-Bellassoued M.-C. Célérier JP. Lhommet G. Gardette D. Gramain J.-C. Tetrahedron Lett. 1997; 38: 8511 14a Enders D. Wahl H. Bettray W. Angew. Chem. Int. Ed. Engl. 1995; 34: 455 14b Zhou Y.-G. Tang W. Wang W.-B. Li W. Zhang X. J. Am. Chem. Soc. 2002; 124: 4952 15a You J. Drexler H.-J. Zhang S. Fischer C. Heller D. Angew. Chem. Int. Ed. 2003; 42: 913 15b Tang W. Wu S. Zhang X. J. Am. Chem. Soc. 2003; 125: 9570 15c Zhu G. Chen Z. Zhang X. J. Org. Chem. 1999; 64: 6907 15d Peña D. Minnaard AJ. de Vries JG. Feringa BL. J. Am. Chem. Soc. 2002; 124: 14552 15e Wu J. Chen X. Guo R. Yeung C. Chan AS. C. J. Org. Chem. 2003; 68: 2490 16 Han JL. Ai T. Li G. Synthesis 2008; 2519 17 Xiong Y. Mei H. Wu L. Han J. Pan Y. Li G. Beilstein J. Org. Chem. 2014; 10: 653 18a Inbar Feske M. Buitrago Santanilla A. Leighton JL. Org. Lett. 2010; 12: 688 18b Pool B. Balalaie S. Kunze A. Schilling G. Bischof P. Gleiter R. Eur. J. Org. Chem. 2004; 2812 19 Bartoli G. Cimarelli C. Marcantoni E. Palmieri G. Petrini M. J. Org. Chem. 1994; 59: 5328 20 CCDC 1448298 contains the supplementary crystallographic data for compound 3e. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures. 21 Xie J.-b. Luo J. Winn TR. Cordes DB. Li G. Beilstein J. Org. Chem. 2014; 10: 746 22 Koszelewski D. Lavandera I. Clay D. Guebitz GM. Rozzell D. Kroutil W. Angew. Chem. Int. Ed. 2008; 47: 9337 23 Phosphinyl Enamines 2; General Procedure A mixture of phosphinamide P3 (200 mg, 0.74 mmol) , β-keto ester 1 (2.21mmol), 4 Å MS (50 mg), and TsOH (5.0 mg) in toluene (3.0 ml) was heated in a sealed vial for 10 h at 100 °C until the limiting reactant was consumed (TLC). The mixture was then filtered, diluted with EtOAc (5 mL), washed with sat. aq NaHCO3 and brine, and evaporated to dryness. The residue was purified by flash chromatography [silica gel, EtOAc–hexane (1:3)]. The eluting solvents were combined and evaporated under vacuum to afford the phosphinyl enamide as a yellow oil. All new compounds were characterized by spectroscopy (31P, 1H, and 13C NMR). Ethyl (2Z)-3-{[(2S,5S)-1-Oxido-2,5-diphenylphospholan-1-yl]amino}but-2-enoate (2c) Yellow oil; yield: 277 mg (98%). 1H NMR (400 MHz, CDCl3): δ = 9.78 (d, J = 16.2 Hz, 1 H), 7.37–7.25 (m, 10 H), 4.59 (s, 1 H), 4.14 (q, J = 5.7 Hz, 2 H), 3.68–3.58 (m, 1 H), 3.18–3.12 (m, 1 H), 2.51–2.32 (m, 2 H), 2.16–2.08 (m, 2 H), 1.42–1.39 (m, 3 H), 1.27 (t, J = 5 Hz, 3 H). 31P NMR (162 MHz, CDCl3): δ = 51.8. Ethyl (3S)-3-{[(2S,5S)-1-Oxido-2,5-diphenylphospholan-1-yl]amino}butanoate White solid; yield: 88 mg (76%); mp 186–198 °C , [α]25 D –55.2 (c 0.36, CH2Cl2); 1H NMR (400 MHz, CDCl3): δ = 7.44–7.08 (m, 10 H), 4.01–3.92 (m, 2 H), 3.52–3.50 (m, 1 H), 3.37–3.29 (m, 1 H), 3.06–2.95 (m, 1 H), 2.65 (t, J = 11 Hz, 1 H), 2.36–2.28 (m, 2 H), 2.55–2.42 (m, 2 H), 2.14–2.39 (m, 1 H), 2.08–2.02 (m, 1 H), 1.20 (t, J = 6.0 Hz, 3 H), 0.70 (t, J = 3.0 Hz, 3 H). 31P NMR (162 MHz, CDCl3): δ = 53.4; HRMS (TOF-ES+): m/z [M + H]+ calcd for C22H29NO3P: 386.1880; found: 386.1879. Supplementary Material Supplementary Material Supporting Information CIF File
