title: Could diastereoselectivity in the presence of O-2 chiral nonparticipating groups be an indicator of glycopyranosyl oxacarbenium ions in glycosylation reactions?
abstract: Although long postulated, the existence of glycopyranosyl oxacarbenium ions as intermediates or transition states (TS) in chemical glycosylation reactions has not been convincingly demonstrated experimentally. It is anticipated that elucidation of such reactive species will greatly assist synthetic chemists to control the α/β stereoselectivity by rational means. Previous density functional theory (DFT) calculations from our group found that the torsion potential about C-2-O-2 in protected glycopyranosyl donors changed from a conventional 3-fold rotor to a 2-fold rotor with a strong syn (CH-2-C-2-O-2-CPg) preference once the donor was ionized to its oxacarbenium ion. This suggested to us that if CPg of the protecting group was a chiral carbon, then diastereoselectivity might be observed in glycosylation reactions that proceed through oxacarbenium ions. The hypothesis to test is as follows: if a nonparticipating O-2 racemic chiral protecting group exhibits diastereoselectivity in glycosylation reactions, then the reaction probably proceeds through an oxacarbenium ion intermediate or TS. We present data for O-2 ether-protected d-glucopyranosyl donors where the racemic protecting group 1-methyl 1'-methylcyclopropylmethyl (MCPM) provides the chirality. MCPM proves to be more activating than the O-2-benzyl ether, and in cases where the donor is otherwise deactivated, several examples of moderate diastereoselectivity are found. These results can be interpreted to indicate that a continuum of reactivity exists where some glycosyl donors form oxacarbenium ions in glycosylation reactions but more reactive donors do not. The strongly activating properties of the cyclopropylmethyl ether functionality and the ability to induce diastereoselectivity with chiral derivatives strongly suggest widespread applications.
authors.affiliation: National Research Council, Institute for Biological Sciences, 100 Sussex Drive, Ottawa, Ontario, Canada K1A 0R6.
authors.forename: Rishi
authors.initials: R
authors.lastname: Kumar
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Whitfield
mesh_terms: D006027:Glycosides / Q000737:chemistry*; D006031:Glycosylation; D007202:Indicators and Reagents / Q000737:chemistry*; D007477:Ions / Q000737:chemistry*; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D013237:Stereoisomerism
chemical_list: D006027:Glycosides; D007202:Indicators and Reagents; D007477:Ions; C030011:carbene; D008697:Methane