Open AccessInfluence of Configuration at the 4- and 6-Positions on the Conformation and Anomeric Reactivity and Selectivity of 7-Deoxyheptopyranosyl Donors: Discovery of a Highly Equatorially Selective l -glycero-d -gluco-Heptopyranosyl Donor
Author(s) -
Kapil Upadhyaya,
Rahul S. Bagul,
David Crich
Publication year - 2021
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.1c01535
Subject(s) - chemistry , stereochemistry , glycosyl donor , glycosyl , anomer , side chain , stereoselectivity , reactivity (psychology) , selectivity , alkane stereochemistry , ring (chemistry) , crystallography , catalysis , crystal structure , organic chemistry , medicine , alternative medicine , pathology , polymer
The preparation of four per- O -benzyl-d- or l- glycero -d- galacto and d- or l- glycero -d- gluco heptopyranosyl sulfoxides and the influence of their side-chain conformations on reactivity and stereoselectivity in glycosylation reactions are described. The side-chain conformation in these donors is determined by the relative configuration of its point of attachment to the pyranoside ring and the two flanking centers in agreement with a recent model. In the d- and l- glycero -d- galacto glycosyl donors, the d- glycero -d- galacto isomer with the more electron-withdrawing trans , gauche conformation of its side chain was the more equatorially selective isomer. In the d- and l- glycero -d- gluco glycosyl donors, the l- glycero -d- gluco isomer with the least disarming gauche , gauche side-chain conformation was the most equatorially selective donor. Variable temperature NMR studies, while supporting the formation of intermediate glycosyl triflates at -80 °C in all cases, were inconclusive owing to a change in the decomposition mechanism with the change in configuration. It is suggested that the equatorial selectivity of the l- glycero -d- gluco isomer arises from H-bonding between the glycosyl acceptor and O6 of the donor, which is poised to deliver the acceptor antiperiplanar to the glycosyl triflate, resulting in a high degree of S N 2 character in the displacement reaction.