Stereospecific Cyclization Strategies for alpha,epsilon-Dihydroxy-beta-amino Esters: Asymmetric Syntheses of Imino and Amino Sugars

作者：Davies Stephen G^*; Foster Emma M; Lee James A; Roberts Paul M; Thomson James E

来源：Journal of Organic Chemistry, 2014, 79(20): 9686-9698.

DOI：10.1021/jo5018298

A range of biologically significant imino and amino sugars [1,4-dideoxy-1,4-imino-D-allitol, 3,6-dideoxy-3,6-imino-L-allonic acid, (3R,4S)-3,4-dihydroxy-L-proline, 1,5-anhydro-4-deoxy-4-amino-D-glucitol, and 1,5-anhydro-4-deoxy-4-amino-L-iditol] has been prepared via stereospecific cyclization of alpha,epsilon-dihydroxy-beta-amino esters. These substrates are readily prepared via conjugate addition of lithium (S)-N-benzyl-N-(alpha-methylbenzyl)amide to enantiopure alpha,beta-unsaturated esters (beta-substituted with cis- and trans-dioxolane units) coupled with in situ enolate oxidation with camphorsulfonyloxaziridine (CSO). Activation of the epsilon-hydroxyl group allowed cyclization to either the corresponding pyrrolidine or the tetrahydropyran scaffold, with the course of the cyclization process being dictated by the relative configuration of the dioxolane unit. When the alpha,epsilon-dihydroxy-beta-amino ester bears a cis-dioxolane unit, cyclization occurs upon attack of the beta-amino substituent to give the corresponding pyrrolidine after in situ N-debenzylation. In contrast, when the alpha,epsilon-dihydroxy-beta-amino ester bears a trans-dioxolane unit, cyclization occurs upon attack of the alpha-hydroxyl substituent to give the corresponding tetrahydropyran.

• 出版日期2014-10-17