Abstract
(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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4663-4672 |
| Number of pages | 10 |
| Journal | Journal of Organic Chemistry |
| Volume | 72 |
| Issue number | 13 |
| DOIs | |
| State | Published - Jun 22 2007 |
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ASJC Scopus subject areas
- Organic Chemistry
Cite this
Mechanistic studies on the stereoselective formation of β-mannosides from mannosyl iodides using α-deuterium kinetic isotope effects. / El-Badri, Mohamed H.; Willenbring, Dan; Tantillo, Dean J.; Gervay-Hague, Jacquelyn.
In: Journal of Organic Chemistry, Vol. 72, No. 13, 22.06.2007, p. 4663-4672.Research output: Contribution to journal › Article
}
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.
UR - http://www.scopus.com/inward/record.url?scp=34250812517&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34250812517&partnerID=8YFLogxK
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 -