TY - JOUR
T1 - Conformationally armed 3,6-tethered glycosyl donors
T2 - synthesis, conformation, reactivity, and selectivity
AU - Heuckendorff, Mads
AU - Pedersen, Christian Marcus
AU - Bols, Mikael
PY - 2013/7/19
Y1 - 2013/7/19
N2 - The reactivity and selectivity of 3,6-tethered glycosyl donors have been studied using acceptors with different steric and electronic characteristics. Eight (four anomeric pairs) 3,6-bridged-glycosyl donors were synthesized in high yields from their common parent sugars. The glycosylation properties were tested using at least three different acceptors and several promoter systems. Thiophenyl 2,4-di-O-benzyl-3,6-O-(di-tert-butylsilylene)-α-d- glucopyranoside gave α/β mixtures with standard NIS/TfOH mediated activation, whereas the corresponding fluoride was found to be highly β-selective, when using SnCl2/AgB(C6F 5)4 as the promoter system. Mannosyl donors were highly α-selective despite the altered conformation. Galactosylations using NIS/TfOH were generally α-selective, but more β-selective using the galactosyl fluoride and depending on the acceptor used. Thiophenyl 2-azido-2-deoxy-4-O-benzyl-3,6-O-(di-tert-butylsilylene)-α-d- glucopyranoside was found to be α-selective. The reactivity of the donors was investigated using competition experiments, and some but not all were found to be highly reactive. Generally it was found that the α-thioglycosides were significantly more reactive than the β; this difference in reactivity was not found for 3,6-anhydro-, armed-(benzylated), or the classic super armed (silylated) donors. A mechanism supporting the unusual observations has been suggested.
AB - The reactivity and selectivity of 3,6-tethered glycosyl donors have been studied using acceptors with different steric and electronic characteristics. Eight (four anomeric pairs) 3,6-bridged-glycosyl donors were synthesized in high yields from their common parent sugars. The glycosylation properties were tested using at least three different acceptors and several promoter systems. Thiophenyl 2,4-di-O-benzyl-3,6-O-(di-tert-butylsilylene)-α-d- glucopyranoside gave α/β mixtures with standard NIS/TfOH mediated activation, whereas the corresponding fluoride was found to be highly β-selective, when using SnCl2/AgB(C6F 5)4 as the promoter system. Mannosyl donors were highly α-selective despite the altered conformation. Galactosylations using NIS/TfOH were generally α-selective, but more β-selective using the galactosyl fluoride and depending on the acceptor used. Thiophenyl 2-azido-2-deoxy-4-O-benzyl-3,6-O-(di-tert-butylsilylene)-α-d- glucopyranoside was found to be α-selective. The reactivity of the donors was investigated using competition experiments, and some but not all were found to be highly reactive. Generally it was found that the α-thioglycosides were significantly more reactive than the β; this difference in reactivity was not found for 3,6-anhydro-, armed-(benzylated), or the classic super armed (silylated) donors. A mechanism supporting the unusual observations has been suggested.
U2 - 10.1021/jo4012464
DO - 10.1021/jo4012464
M3 - Journal article
C2 - 23786671
SN - 0022-3263
VL - 78
SP - 7234
EP - 7248
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 14
ER -