Could diastereoselectivity in the presence of O-2 chiral nonparticipating groups be an indicator of glycopyranosyl oxacarbenium ions in glycosylation reactions?

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DOIResolve DOI: http://doi.org/10.1021/jo202563f
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TypeArticle
Journal titleThe Journal of Organic Chemistry
ISSN0022-3263
1520-6904
Volume77
Issue8
Pages37243739; # of pages: 16
AbstractAlthough 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.
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedYes
NPARC number21269038
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Record identifier44699797-34c5-4ca5-98ba-e9be038ffa6c
Record created2013-12-02
Record modified2016-05-09
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