TY - JOUR
T1 - Mechanistic studies on the stereoselective formation of β-mannosides from mannosyl iodides using α-deuterium kinetic isotope effects
AU - El-Badri, Mohamed H.
AU - Willenbring, Dan
AU - Tantillo, Dean J.
AU - Gervay-Hague, Jacquelyn
PY - 2007/6/22
Y1 - 2007/6/22
N2 - (Chemical Equation Presented) Stereoselective synthesis of β-mannosides is one of the most challenging linkages to achieve in carbohydrate chemistry. Both the anomeric effect and the C2 axial substituent favor the formation of the axial glycoside (α-product). Herein, we describe mechanistic studies on the β-selective glycosidation of trimethylene oxide (TMO) using mannosyl iodides. Density functional calculations (at the B3LYP/6-31+G(d,p):LANL2DZ level) suggest that formation of both β- and β-mannosides involve loose SN2-like transition-state structures with significant oxacarbenium character, although the transition structure for formation of the α-mannoside is significantly looser. α-Deuterium kinetic isotope effects (α-DKIEs) based upon these computed transition state geometries match reasonably well with the experimentally measured values: 1.16 ± 0.02 for the β-linkage (computed to be 1.15) and 1.19 ± 0.05, see table 2 for the α-analogue (computed to be 1.26). Since it was unclear if β-selectivity resulted from a conformational constraint induced by the anomeric iodide, a 4,6-O-benzylidine acetal was used to lock the iodide into a chairlike conformation. Both experiments and calculations on this analogue suggest that it does not mirror the behavior of mannosyl iodides lacking bridging acetal protecting groups.
AB - (Chemical Equation Presented) Stereoselective synthesis of β-mannosides is one of the most challenging linkages to achieve in carbohydrate chemistry. Both the anomeric effect and the C2 axial substituent favor the formation of the axial glycoside (α-product). Herein, we describe mechanistic studies on the β-selective glycosidation of trimethylene oxide (TMO) using mannosyl iodides. Density functional calculations (at the B3LYP/6-31+G(d,p):LANL2DZ level) suggest that formation of both β- and β-mannosides involve loose SN2-like transition-state structures with significant oxacarbenium character, although the transition structure for formation of the α-mannoside is significantly looser. α-Deuterium kinetic isotope effects (α-DKIEs) based upon these computed transition state geometries match reasonably well with the experimentally measured values: 1.16 ± 0.02 for the β-linkage (computed to be 1.15) and 1.19 ± 0.05, see table 2 for the α-analogue (computed to be 1.26). Since it was unclear if β-selectivity resulted from a conformational constraint induced by the anomeric iodide, a 4,6-O-benzylidine acetal was used to lock the iodide into a chairlike conformation. Both experiments and calculations on this analogue suggest that it does not mirror the behavior of mannosyl iodides lacking bridging acetal protecting groups.
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U2 - 10.1021/jo070229y
DO - 10.1021/jo070229y
M3 - Article
C2 - 17539683
AN - SCOPUS:34250812517
VL - 72
SP - 4663
EP - 4672
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
SN - 0022-3263
IS - 13
ER -