Stereoselective Synthesis of 2,3-Unsaturated-aza-O-glycosides via New Diastereoisomeric N-Cbz-imino Glycal-Derived Allyl Epoxides ² Valeria Di Bussolo, Annalisa Fiasella, Maria Rosaria Romano, Lucilla Favero, Mauro Pineschi, and Paolo Crotti* Dipartimento di Chimica Bioorganica e Biofarmacia, UniVersita ` di Pisa, Via Bonanno 33, I-56126 Pisa, Italy crotti@farm.unipi.it Received July 31, 2007 ABSTRACT Diastereoisomeric D,L-N-Cbz-imino glycal-derived allyl epoxides 5 and 6 have been synthesized, and their addition reactions with alcohols examined. The reactions lead to the corresponding 2,3-unsaturated-aza-O-glycosides through a new, completely regioselective 1,4-addition process which proceeds with complete substrate-dependent stereoselectivity. Recently, we found that the reaction of the diastereoisomeric D-galactal- and D-allal-derived allyl epoxides 1 and 2 with O-nucleophiles, such as alcohols and partially protected monosaccharides, led to the corresponding O-glycosides and disaccharides through a completely stereoselective 1,4- addition process affording R-O-glycosides from 1 and -O- glycosides from 2 in a new uncatalyzed substrate-dependent stereospecific glycosylation process. 1 The strict correspon- dence found between the configuration of the glycosides obtained and that of the starting heterocycle was rationalized by the occurrence of a coordination between the O- nucleophile and the oxirane oxygen in the form of a hydrogen bond as shown in 3 and 4 (Scheme 1). Due to our interest in the synthesis of azasugars from imino glycals, 2 we wanted to verify whether the diastereo- isomeric N-Cbz-imino glycal-derived allyl epoxides 5 and 6, the aza analogues of 1 and 2 (Scheme 2), would behave similarly in their reactions with alcohols. At the outset of this work, the glycosylation of alcohols by imino glycals had not been described. 3,4 However, appropriately substituted imino glycal systems, such as tri-O-acetyl imino glucal 7, react with C-nucleophiles, under Lewis acid mediated Ferrier reaction conditions, to give the -anomers 9 with high selectivity (24-72% de). 5 The stereochemical outcome was attributed to a preferential pseudoaxial attack of the nucleophile on the favored con- ² Dedicated to Professor Franco Macchia in the occasion of his 70th anniversary. (1) (a) Di Bussolo, V.; Caselli, M.; Romano, M. R.; Pineschi, M.; Crotti, P. J. Org. Chem. 2004, 69, 7383. (b) J. Org. Chem. 2004, 69, 8702. (2) Afarinkia, K.; Bahar, A. Tetrahedron: Asymmetry 2005, 16, 1239. Scheme 1. Stereoselective Addition of O-Nucleophiles to Allyl Epoxides 1 and 2 ORGANIC LETTERS 2007 Vol. 9, No. 22 4479-4482 10.1021/ol701836a CCC: $37.00 © 2007 American Chemical Society Published on Web 09/27/2007