Synlett, Table of Contents Synlett 2023; 34(06): 657-662DOI: 10.1055/a-1892-4608 cluster Chemical Synthesis and Catalysis in India Cl–···H–N Interaction Assisted Addition of Sulfonamides to Enol Ethers: Synthesis of 2-Deoxy and 2,6-Dideoxy Sulfonamido Glycosides Ananya Mukherji , Pavan K. Kancharla∗ Recommend Article Abstract Buy Article All articles of this category Abstract The strained/frustrated electrostatic interactions between the ion pair of TTBPy+X– increases the reactivity in both the ions, resulting in the activation of a third molecule like sulfonamides (aromatic/aliphatic) via hydrogen bonding. This intriguing weak-interactions-based reactivity has been utilized to develop an organocatalytic synthesis of 2-deoxy-sulfonamido-glycosides from glycals. The sulfonamidoglycosylation of glycals using a catalytic amount of 2,4,6-tri-tert-butylpyridinium salts proceeded stereoselectively to provide N-glycosides in good to high yields. This process was demonstrated with l-rhamnal and d-galactal. Besides, IR spectroscopic studies explain that the hindered protonated pyridine cannot behave as a cationic Brønsted acid as is generally perceived. Key words Key wordsN-glycosylation - catalysis - strained Brønsted pairs - stereoselectivity - 2,4,6-tri-tert-butylpyridine. Full Text References References and Notes 1 Dimroth K, Mach W. Angew. Chem., Int. Ed. Engl. 1968; 7: 460 2a Brown HC, Kanner B. J. Am. Chem. Soc. 1966; 88: 986 2b Deutsch E, Cheung NK. V. J. Org. Chem. 1973; 38: 1123 3 Effenberger F, Eberhard JK, Maier AH. J. Am. Chem. Soc. 1996; 118: 12572 4 Xu XH, Liu GK, Azuma A, Tokunaga E, Shibata N. Org. Lett. 2011; 13: 4854 5a Jiang C, Blacque O, Fox T, Berke H. Organometallics 2011; 30: 2117 5b Clark ER, Ingleson MJ. Organometallics 2013; 32: 6712 6 Boebel TA, Gin DY. Angew. Chem. Int. Ed. 2003; 42: 5874 7 Geng Y, Zhang LH, Ye XS. Chem. Commun. 2008; 597 8 Mukherji A, Kancharla PK. Org. Lett. 2020; 22: 2191 9 Mukherji A, Addanki RB, Halder S, Kancharla PK. J. Org. Chem. 2021; 86: 17226 10 Ghosh T, Mukherji A, Kancharla PK. Org. Lett. 2019; 21: 3490 11 Colinas PA, Núñez NA, Bravo RD. J. Carbohydr. Chem. 2008; 27: 141 12a Jordan MA, Wilson L. Nat. Rev. Cancer 2004; 4: 253 12b Yoshimatsu K, Yamaguchi A, Yoshino H, Koyagi N, Kitoh K. Cancer Res. 1997; 57: 3208 13 Abbate F, Casini A, Owa T, Scozzafava A, Supuran CT. Bioorg. Med. Chem. Lett. 2004; 14: 217 14 Supuran CT, Briganti F, Tilli S, Chegwidde WR, Scozzafava A. Bioorg. Med. Chem. 2001; 9: 703 15 Supuran CT, Scozzafava A, Menabuoni L, Mincione F, Briganti F, Mincione G. Eur. J. Pharm. Sci. 1999; 8: 317 16 Liautard V, Pillard C, Desvergnes V, Martin OR. Carbohydr. Res. 2008; 343: 2111 17 Colinas PA, Témpera CA, Rodríguez OM, Bravo RD. Synthesis 2009; 4143 18 Griffith DA, Danishefsky SJ. J. Am. Chem. Soc. 1990; 112: 5811 19 Colinas PA, Bravo RD. Org. Lett. 2003; 5: 4509 20 Colinas PA, Bravo RD. Carbohydr. Res. 2007; 342: 2297 21 Colinas PA, Bravo RD. Mol. Med. Chem. 2007; 62 22 Colinas PA, Bravo RD. Tetrahedron Lett. 2005; 46: 1687 23 Mała P, Pedersen CM. Eur. J. Org. Chem. 2021; 5685 24 General Method to Synthesize Sulfonamidoglycosides from GlycalsGlycal (0.082–0.161 mmol, 1.0 equiv) and glycosyl sulfonamide acceptor (0.123–0.240 mmol, 1.5 equiv) was taken in a round-bottomed flask (10 mL). The flask was then filled with dry DCE, and catalyst TTBPy·HCl (20 mol%) was added to it. The mixtures were stirred at 40 °C in a sealed flask until the reaction was determined to be complete by either TLC or NMR analysis of the crude material. The reaction mixture was quenched by water (20 mL for 0.082 mmol) and it was extracted with DCM (3 × 15 mL for 0.082 mmol), dried over Na2SO4, and concentrated in vacuo and purified by silica gel column chromatography (Merck 60–120 mesh, 7 gm) followed by HPLC purification (using HPLC-grade acetonitrile solvent, flow rate 5 mL/min) for some of the compounds. 25 3,4-O-(Tetraisopropyldisiloxane-1,3-diyl)-l-erythro-hexapyranosyl-2,6-dideoxy-α,β-l-rhamnopyranosyl Methanesulfonamide (4ee)According to general method, a solution of glycosyl donor 3,4-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-1,2,6-trideoxy-l-arabino-1-hexenopyranose 1e (50 mg, 0.134 mmol, 1.0 equiv) and glycosyl sulfonamide acceptor 2e (19 mg, 0.200 mmol, 1.5 equiv) in dry DCE at 40 °C was treated with 2,4,6-tri(tert-butyl)pyridinium hydrochloride catalyst (8 mg, 0.0268 mmol, 20 mol%) and stirred for 24 h to get the product 4ee as a colourless oil. Rf = 0.4 in 20% EtOAc/hexane, eluent 7% EtOAc in hexane, amount 45 mg, yield 72%. Selectivity α:β = 1:12.5. 1H NMR (400 MHz, CDCl3): δ = 5.35 (dd, J = 9.2, 3.3 Hz, 1 H), 4.79 (td, J = 11.1, 1.9 Hz, 1 H), 3.74 (ddd, J = 11.2, 8.1, 5.3 Hz, 1 H), 3.34 (dq, J = 12.3, 6.1 Hz, 1 H), 3.19 (t, J = 8.5 Hz, 1 H), 3.10 (s, 3 H), 2.22 (ddd, J = 12.8, 5.2, 1.9 Hz, 1 H), 1.58 (dd, J = 23.9, 11.3 Hz, 1 H), 1.29 (d, J = 5.8 Hz, 3 H), 1.08–0.92 (m, 28 H). 13C NMR (101 MHz, CDCl3): δ = 80.3, 79.2, 74.1, 73.9, 43.5, 39.7, 31.0, 30.4, 29.8, 18.2, 17.7, 17.5, 17.4, 17.4, 17.4, 17.3, 17.2, 17.2, 13.2, 13.0, 12.9, 12.4, 12.3. HRMS (ESI-QTOF): m/z calcd for C19H41O6NSSi2Na [M + Na] +: 490.2091; found: 490.2099. [α]D 22 –10 (c 0.40, CHCl3). 26 3,4-Di-O-tert-butyldiphenylsilyl-2,6-dideoxy-α,β-l-rhamnopyranosyl Methanesulfonamide (5he)According to general method, a solution of glycosyl donor 3,4-di-O-tert-butyldiphenylsilyl-l-rhamnal 5h (50 mg, 0.082 mmol, 1.0 equiv) and glycosyl sulfonamide acceptor 2e (12 mg, 0.126 mmol, 1.5 equiv) in dry DCE at 40 °C was treated with 2,4,6-tri(tert-butyl)pyridinium hydrochloride catalyst (5 mg, 0.0164 mmol, 20 mol%) and stirred for 24 h to get the product 5he as a colourless oil. Rf = 0.4 in 20% EtOAc/hexane, eluent 7% EtOAc in hexane, amount 41 mg, yield 70%. Selectivity α:β = 7: 1. 1H NMR (600 MHz, CDCl3): δ = 7.52 (dd, J = 11.7, 4.6 Hz, 4 H), 7.46–7.45 (m, 1 H), 7.43–7.34 (m, 8 H), 7.31–7.23 (m, 6 H), 5.38 (td, J = 10.7, 1.6 Hz, 1 H), 4.90 (d, J = 10.6 Hz, 1 H), 4.03 (d, J = 1.6 Hz, 1 H), 3.92 (q, J = 7.3 Hz, 1 H), 3.49 (d, J = 2.8 Hz, 1 H), 3.10 (s, 3 H), 1.87–1.83 (m, 1 H), 1.60 (d, J = 13.1 Hz, 1 H), 1.29 (d, J = 7.4 Hz, 3 H), 0.98 (s, 9 H), 0.93 (s, 9 H). 13C NMR (151 MHz, CDCl3): δ = 135.9, 135.8, 135.7, 135.7, 133.8, 133.2, 133.1, 133.0, 130.1, 129.9, 129.9, 128.0, 127.9, 127.8, 127.8, 127.7, 76.0, 73.1, 71.3, 70.7, 43.6, 34.3, 27.0, 26.9, 19.3, 19.1, 16.8. HRMS (ESI-QTOF): m/z calcd for C39H51O5NSSi2NH4 [M + NH4] +: 719.3370; found: 719.3374. [α]D 22 –29 (c 0.80, CHCl3). 27a Welch GC, Juan RR. S, Masuda JD, Stephan DW. Science 2006; 314: 1124 27b Stephan DW. J. Am. Chem. Soc. 2015; 137: 10018 27c Stephan DW. Acc. Chem. Res. 2015; 48: 306 Supplementary Material Supplementary Material Supporting Information
