Cl^–···H–N Interaction Assisted Addition of Sulfonamides to Enol Ethers: Synthesis of 2-Deoxy and 2,6-Dideoxy Sulfonamido Glycosides

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

N-glycosylation - catalysis - strained Brønsted pairs - stereoselectivity - 2,4,6-tri-tert-butylpyridine.

• References and Notes

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• 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. R_f = 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).
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