Unprecedented lability of the 5'-O-tert-butyldimethylsilyl group from 3'-spiro-5''-(4''-acylamino-1'',2''-oxathiole-2'',2''-dioxide) nucleoside derivatives via neighboring group participation of the 4''-acylamino residue.
Scarce examples of exceptionally mild desilylation of tert-butyldimethylsilyl (TBDMS) ether groups by neighboring group participation have been previously described. Here, we investigate, in detail, the discovery of the unusual lability of the 5'-TBDMS group on 4' '-acylamino TSAO derivatives in DMSO solution. The synthesis and comparative chemical stability studies in different solvents of a variety of 4' '-substituted TSAO derivatives bearing different carbonyl functionalities are reported. Modifications have also been performed at the 5'-position of the TSAO molecule to gain insight into the structural requirements for the desilylation to occur. The role of the solvent has also been studied. Additionally, NMR and theoretical investigations have been carried out to get further insight into the conformational, geometric, and/or electronic parameters that may play a role in the "spontaneous" release of the 5'-TBDMS group. A silyl hydrolysis mechanism involving neighboring group participation of the 4' '-acylamino group is proposed.
Instituto de Química Médica (C.S.I.C.), Juan de la Cierva 3, E-28006 Madrid, Spain.
Sonia
S
de Castro
Angel
A
Lozano
María-Luisa
ML
Jimeno
María-Jesús
MJ
Pérez-Pérez
Ana
A
San-Félix
María-José
MJ
Camarasa
Sonsoles
S
Velázquez
D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry*; D012821:Silanes / Q000737:chemistry*; D012997:Solvents; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry*
D009705:Nucleosides; D012821:Silanes; D012997:Solvents; D013141:Spiro Compounds; C103256:tert-butyldimethylsilane