A Mild, Highly Efficient, and Chemoselective Deprotection of Trityl Ethers of Carbohydrates and Nucleosides Using Iodine Monobromide [¹]

Abstract

Iodine monobromide in dichloromethane-methanol or acetonitrile constitutes an effective reagent for the deprotection of O-trityl and O-dimethoxytrityl ethers of carbohydrates and nucleosides. Acid-labile functionalities (acetals, O-p-methoxybenzyl ethers, etc.) as well as base-labile groups (esters and amides) are stable under these conditions; and the method has been found to be superior to the hitherto known literature methods.

Key words

interhalogen - iodine monobromide - trityl ether - carbohydrate - nucleoside - chemoselective deprotection

References and Notes

• 1 Iodine and its Interhalogen Compounds: Versatile Reagents in Carbohydrate Chemistry XXI. For part XX, see: Kärkkäinen TS. Kartha KPR. MacMillan D. Field RA. Carbohydr. Res.  2008,  343:  1830 
• 2a Helferich B. Adv. Carbohydr. Chem.  1948,  3:  79 
• 2b Smith M. Rammle DH. Goldberg IH. Khorana HG. J. Am. Chem. Soc.  1969,  84:  430 
• 3a Whistler RL. Wolfrom ML. Methods in Carbohydrate Chemistry   Vol. 2:  Academic Press; London: 1963.  p.168 
• 3b Helferich B. Adv. Carbohydr. Chem.  1948,  3:  79 
• 4 Bessodes M. Komiotis D. Antonakis K. Tetrahedron Lett.  1986,  27:  579 
• 5 MacCoss M. Cameron DJ. Carbohydr. Res.  1978,  60:  206 
• 6 Sabitha G. Reddy EV. Swapna R. Reddy NM. Yadav JS. Synlett  2004,  1276 
• 7 Khalafi-Nezhad A. Fareghi AR. Tetrahedron  2001,  57:  6805 
• 8 Jones GB. Hynd G. Wright JM. Sharma A. J. Org. Chem.  2000,  65:  263 
• 9 Yadav JS. Reddy BVS. Srinivas R. Maiti AJ.
  J. Chem. Res., Synop.  2001,  528 
• 10 Heraldsson GG. Stefansson T. Snorrason H. Acta Chem. Scand.  1998,  52:  824 
• 11 Reviewed in: Weissman SA. Zewge D. Tetrahedron  2005,  61:  7833 
• 12 Kartha KPR. Aloui M. Field RA. Tetrahedron Lett.  1996,  37:  5175 
• 13 Wahlstrom JL. Ronald RC. J. Org. Chem.  1998,  63:  6021 
• 14 Vaino AR. Szarek WA. Chem. Commun.  1996,  2351 ; and ref. 2, 4, 8-19 cited therein
• 15 Kartha KPR. Field RA. Synlett  1999,  311 
• 16 Szarek WA. Zamojski A. Tiwari KN. Ison ER. Tetrahedron Lett.  1986,  27:  3827 

17

The workup and isolation of the product are also a lot more convenient in the present case as the literature method^³ makes use of glacial AcOH as the solvent for the reaction.

18

Treatment of 5 with HBr/AcOH reagent in CH₂Cl₂ as described for 3 led to the formation of a mixture of 1,2-O- and 3,4-O-isopropylidene-d-galactoses and d-galactose as judged by TLC and ^¹H NMR spectroscopy.

19

Typical Procedure for Conversion of 3 → 4
Method A
IBr (1.2 mL of a 1 M soln in CH₂Cl₂, 1.2 mmol) was added to a soln of 3 (562 mg, 1 mmol) in MeCN (10 mL) and was stirred until TLC (EtOAc-hexanes, 2:3) showed completion of the reaction. The reaction mixture was then diluted with CH₂Cl₂ and was washed successively with dilute aq Na₂S₂O₃ and Na₂CO₃ soln, dried (Na₂SO₄), concentrated to dryness under reduced pressure and was purified by column chroma-tography (silica gel; EtOAc-hexanes, 2:3) to yield crystals (308 mg, 95%) of 4.
Alternatively, after the completion of the reaction, the workup can also be carried out by stirring the reaction mixture with Amberlite IRA-400 (hydroxide form) resin to get a colourless solution. Filtration, concentration of the filtrate under reduced pressure, and chromatography as described above afforded 4.
Method B
The reaction was carried out by the same procedure as described above but CH₂Cl₂-MeOH (9:1) was used as the solvent instead of MeCN. The product was obtained in practically the same yield.