Selective Tetrahydropyranylation under Non-Acidic Conditions

Abstract

We report that the tetrahydropyranylation of hydroxyl groups, exhibiting especially very low nucleophilicities, can be achieved by means of Mitsunobu reaction with 2-hydroxytetra­hydropyran. This reaction led to the protection of phenols and ­pyridinols without the use of an acidic catalyst. For instance ­hydroxypyridines could not be protected by dihydropyran under acidic conditions, whereas they underwent a smooth tetrahydro­pyranylation under Mitsunobu conditions. The method is selective for a phenol over an alcohol.

Key words

protecting groups - glycosylations - acetals - phenols - pyridines

References

• 1a Greene T. Protective Groups in Organic Synthesis   3rd ed.:  Wiley; New York: 1999. 
• 1b For a recent review listing new methods for the protection of hydroxyl groups under heterogeneous conditions, see: Sartori G. Ballini R. Bigi F. Bosica G. Maggi R. Righi P. Chem. Rev.  2004,  104:  199 
• 2 Bordwell FG. Singer DL. Satish AV. J. Am. Chem. Soc.  1993,  115:  3543 
• 3 Michelot D. Meyer M. Nat. Prod. Res.  2003,  17:  41 
• 4 Meltzer PC. Wang P. Blundell P. Madras BK. J. Med. Chem.  2003,  46:  1538 
• 5 Aakerfeldt K. Garegg PJ. Iversen T. Acta Chem. Scand., Ser. B  1979,  33:  467 
• 6 Bowles SA. Davidson AH. Miller A. Thompson TM. Whittaker M. Synlett  1993,  111 
• 7 Murphy PJ. Williams HL. Hibbs DE. Hursthouse MB. Abdul Malik KM. Tetrahedron  1996,  52:  8315